WorldWideScience

Sample records for psychoactive drug actions

  1. Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs.

    Science.gov (United States)

    Hassan, Zurina; Bosch, Oliver G; Singh, Darshan; Narayanan, Suresh; Kasinather, B Vicknasingam; Seifritz, Erich; Kornhuber, Johannes; Quednow, Boris B; Müller, Christian P

    2017-01-01

    A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug's properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine ("Kratom"), synthetic cannabinoids (e.g., "Spice"), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications.

  2. Novel Psychoactive Substances—Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs

    Science.gov (United States)

    Hassan, Zurina; Bosch, Oliver G.; Singh, Darshan; Narayanan, Suresh; Kasinather, B. Vicknasingam; Seifritz, Erich; Kornhuber, Johannes; Quednow, Boris B.; Müller, Christian P.

    2017-01-01

    A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug’s properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine (“Kratom”), synthetic cannabinoids (e.g., “Spice”), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications. PMID:28868040

  3. Novel Psychoactive Substances—Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs

    Directory of Open Access Journals (Sweden)

    Zurina Hassan

    2017-08-01

    Full Text Available A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug’s properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine (“Kratom”, synthetic cannabinoids (e.g., “Spice”, dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications.

  4. Psychoactive drug advertising: content analysis.

    Science.gov (United States)

    Mastroianni, Patrícia C; Vaz, Amanda Cristina R; Noto, Ana Regina; Galduróz, José Carlos F

    2008-10-01

    The goal of this study was to describe the human figures portrayed in psychoactive drug advertising in terms of gender, age, ethnic group, and social context. Content analysis for 86 new pieces of printed advertisements released in 2005 was carried out. Fisher exact test was used to analyze the association between categories. There was a preponderance of women (62.8%) who were four times more present in advertisements for antidepressants and anxyolitics than men. Most of the people shown were Caucasian (98.8%) young adults (72%). These people were pictured in leisure activities (46.5%), at home (29%), or in contact with nature (16.2%). The message conveyed was that the drugs treat routinely felt subjective symptoms of discomfort, inducing in an irrational appeal that may affect drug prescription.

  5. Expression of behaviour and psychoactive drugs in the rat EEG

    OpenAIRE

    Lier, Hester van

    2004-01-01

    Brain activity and behaviour are related to each other. Psychoactive drugs can influence both brain activity and behaviour. In order to be able to understand the interplay between brain activity as measured by the electroencephalogram (EEG), behaviour, and psychoactive drugs, it is not sufficient to describe changes in either behaviour or EEG separately. Rather, changes in EEG caused by psychoactive drugs should be described in direct concurrent relation with the subject's ongoing behaviour. ...

  6. Psychoactive Drugs and Quality of Life

    OpenAIRE

    Soren Ventegodt; Joav Merrick

    2003-01-01

    This study was performed on a representative sample of the Danish population in order to investigate the connection to the use of psychoactive drugs and quality of life (QOL) by way of a questionnaire-based survey. The questionnaire was mailed in February 1993 to 2,460 persons aged between 18 and 88, randomly selected from the CPR (Danish Central Register), and 7,222 persons from the Copenhagen Perinatal Birth Cohort 1959–61.A total of 1,501 persons between the ages 18 and 88 years and 4,626 ...

  7. Expression of behaviour and psychoactive drugs in the rat EEG

    NARCIS (Netherlands)

    Lier, Hester van

    2004-01-01

    Brain activity and behaviour are related to each other. Psychoactive drugs can influence both brain activity and behaviour. In order to be able to understand the interplay between brain activity as measured by the electroencephalogram (EEG), behaviour, and psychoactive drugs, it is not sufficient to

  8. [Psychoactive drug advertising: analysis of scientific information].

    Science.gov (United States)

    Mastroianni, Patrícia C; Noto, Ana Regina; Galduróz, José Carlos F

    2008-06-01

    According to the World Health Organization, medicinal drug promotion should be reliable, accurate, truthful, informative, balanced, up-to-date and capable of substantiation. The objective of the present study was to review psychoactive drug advertisements to physicians as for information consistency with the related references and accessibility of the cited references. Data was collected in the city of Araraquara, Southeastern Brazil, in 2005. There were collected and reviewed 152 drug advertisements, a total of 304 references. References were requested directly from pharmaceutical companies' customer services and searched in UNESP (Ibict, Athenas) and BIREME (SciELO, PubMed, free-access indexed journals) library network and CAPES journals. Advertisement statements were checked against references using content analysis. Of all references cited in the advertisements studied, 66.7% were accessed. Of 639 promotional statements identified, 346 (54%) were analyzed. The analysis showed that 67.7% of promotional statements in the advertisements were consistent with their references, while the remaining was either partially consistent or inconsistent. Of the material analyzed, an average 2.5 (1-28) references was cited per advertisement. In the text body, there were identified 639 pieces of information clearly associated with at least one cited reference (average 3.5 pieces of information per advertisement). The study results evidenced difficult access to the references. Messages on efficacy, safety and cost, among others, are not always supported by scientific studies. There is a need for regulation changes and effective monitoring of drug promotional materials.

  9. The use of psychoactive prescription drugs among DUI suspects.

    Science.gov (United States)

    Karjalainen, Karoliina; Haukka, Jari; Lintonen, Tomi; Joukamaa, Matti; Lillsunde, Pirjo

    2015-10-01

    The study seeks to increase understanding of the use of psychoactive prescription drugs among persons suspected of driving under the influence (DUI). We studied whether the use of prescribed psychoactive medication was associated with DUI, and examined the difference in the use of prescription drugs between DUI recidivists and those arrested only once. In this register-based study, persons suspected of DUI (n=29470) were drawn from the Register of DUI suspects, and an age- and gender-matched reference population (n=30043) was drawn from the Finnish general population. Data on prescription drug use was obtained by linkage to the National Prescription Register. The associations of DUI arrest and use of psychoactive prescription drugs in different DUI groups (findings for alcohol only, prescription drugs, prescription drugs and alcohol, illicit drugs) were estimated by using mixed-effect logistic regression. The use of psychoactive prescription drugs and DUI appeared to be strongly associated, with DUI suspects significantly more likely to use psychoactive prescription drugs compared to the reference population. Gender differences existed, with the use of benzodiazepines being more common among female DUI suspects. Moreover, DUI recidivists were more likely to use psychoactive prescription drugs compared to those arrested only once. In addition to alcohol and/or illicit drug use, a significant proportion of DUI suspects were using psychoactive prescription drugs. When prescribing psychoactive medication, especially benzodiazepines, physicians are challenged to screen for possible substance use problems and also to monitor for patients' alcohol or illicit drug use while being medicated. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Psychoactive Drugs and Quality of Life

    Directory of Open Access Journals (Sweden)

    Soren Ventegodt

    2003-01-01

    Full Text Available This study was performed on a representative sample of the Danish population in order to investigate the connection to the use of psychoactive drugs and quality of life (QOL by way of a questionnaire-based survey. The questionnaire was mailed in February 1993 to 2,460 persons aged between 18 and 88, randomly selected from the CPR (Danish Central Register, and 7,222 persons from the Copenhagen Perinatal Birth Cohort 1959–61.A total of 1,501 persons between the ages 18 and 88 years and 4,626 persons between the ages 31 and 33 years returned the questionnaire (response rates of 61.0% and 64.1%, respectively. Variables investigated in this study were ten different psychotropic drugs and quality of life.Our study showed that over half the Danish population had used illegal psychotropic drugs. The most commonly used was cannabis (marijuana though experience of this drug appeared not to co-vary with QOL to any significant extent. Cocaine, amphetamine, and psilocybin had been used by 1.2 to 3.3% of the population and this varied with QOL to a clear albeit small extent. LSD has been used by 1.2% of the population and the users had a QOL score 10% lower than those who had never used psychotropic drugs. The group with the lowest quality of life was found to be persons who had used heroin, morphine, methadone, and a mixture of alcohol and tranquilizers (10–20% below the group with the highest quality of life.

  11. Psychoactive drugs and quality of life.

    Science.gov (United States)

    Ventegodt, Søren; Merrick, Joav

    2003-08-18

    This study was performed on a representative sample of the Danish population in order to investigate the connection to the use of psychoactive drugs and quality of life (QOL) by way of a questionnaire-based survey. The questionnaire was mailed in February 1993 to 2,460 persons aged between 18 and 88, randomly selected from the CPR (Danish Central Register), and 7,222 persons from the Copenhagen Perinatal Birth Cohort 1959-61. A total of 1,501 persons between the ages 18 and 88 years and 4,626 persons between the ages 31 and 33 years returned the questionnaire (response rates of 61.0% and 64.1%, respectively). Variables investigated in this study were ten different psychotropic drugs and quality of life. Our study showed that over half the Danish population had used illegal psychotropic drugs. The most commonly used was cannabis (marijuana) though experience of this drug appeared not to co-vary with QOL to any significant extent. Cocaine, amphetamine, and psilocybin had been used by 1.2 to 3.3% of the population and this varied with QOL to a clear albeit small extent. LSD has been used by 1.2% of the population and the users had a QOL score 10% lower than those who had never used psychotropic drugs. The group with the lowest quality of life was found to be persons who had used heroin, morphine, methadone, and a mixture of alcohol and tranquilizers (10-20% below the group with the highest quality of life).

  12. Adulteration Practices of Psychoactive Illicit Drugs: An Updated Review.

    Science.gov (United States)

    Solimini, Renata; Rotolo, Maria C; Pellegrini, Manuela; Minutillo, Adele; Pacifici, Roberta; Busardò, Francesco P; Zaami, Simona

    2017-01-01

    Powdery drugs such as cocaine and heroin are frequently adulterated or diluted predominantly to obtain more doses and to increase the drug dealer's profits, but also to enhance, to modify or to oppose drug effects. The aim of this report is to provide an overview of the recent scientific literature on medicines as well as on new psychoactive substances, used as cutting agents (i.e. pharmacologically active adulterants) and on the related adverse health effects on consumers, possibly due to the synergistic effect of the adulterants laced with substances of abuse. A literature search up to January 2017 was performed on MEDLINE, Scopus and Web of Science and reports and documents of international agencies or institutions were also searched. Pharmacologically active substances such as: paracetamol, caffeine, dextromethorphan, clenbuterol for heroin; levamisole, phenacetine, lidocaine, hydroxyzine and diltiazem for cocaine; caffeine and phentermine for amphetamine, have been identified over the years. Furthermore, since cocaine and morphine (this latter as a precursor of heroin) are both extracted from natural products, some impurities and minor alkaloids can be present in the final preparation. In this context, it is worth considering that new psychoactive substances are also used as cutting agents. The wide availability of illicit psychotropic drugs is the most serious hazard threatening consumers. Indeed emergency departments are often responsible in evaluating damages caused not only by the base substance, but also by other eventual compounds added to mimic or antagonize drug effects or simply dilute the drug amount, with a possible harmful synergic toxic action. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Worldwide legislative challenges related to psychoactive drugs.

    Science.gov (United States)

    Negrei, Carolina; Galateanu, Bianca; Stan, Miriana; Balalau, Cristian; Dumitru, Mircea Lucian Bogdan; Ozcagli, Eren; Fenga, Concettina; Kovatsi, Leda; Fragou, Domniki; Tsatsakis, Aristidis

    2017-06-02

    The discovery of a "new" psychoactive substance is a relatively exceptional event, while the regulatory response usually involved the assessment of risks to public health and inclusion of the novel substance in the national list of controlled substances. However, in recent years we have witnessed the rapid emergence of new chemical substances, which elude international control and pose a challenge to existing processes and a threat to the credibility of control systems. We currently review and present characteristics of these legal and illegal new substances and issues regarding their global monitoring and regulatory measures already taken, or in the process of being taken, for their control. The concept of prohibition applied in active substance-related legislation is rather hazard ridden as balance is required between the ban on substances of potential therapeutic use and the access on the market of high-risk substances. Current and future laws regarding psychoactive compounds.

  14. A formal framework of knowledge to support rational psychoactive drug selection.

    NARCIS (Netherlands)

    Hyfte, D. van; Maas, A.A.F. van der; Tjandra-Maga, T.B.; Vries Robbé, P.F. de

    2001-01-01

    Rational psychoactive drug selection is a data and knowledge intensive task which requires true expertise from clinical, pathophysiological and pharmacotherapeutic knowledge. This paper presents a framework of knowledge, which relates concepts from several disciplines required for psychoactive drug

  15. Prevalence of Psychoactive Drug Use by Taxi Drivers in Nigeria ...

    African Journals Online (AJOL)

    Aim: To ascertain the prevalence and nature of psychoactive drug use amongst taxi drivers in Nigeria. Materials and Method: A total of 192 taxi drivers in Enugu, South East Nigeria was studied using a questionnaire. Information obtained from the questionnaire included socio-demographic characteristics of the drivers, ...

  16. Non-addictive psychoactive drug use: Implications for behavioral addiction.

    Science.gov (United States)

    Griffiths, Mark D

    2011-12-01

    The newly proposed framework for non-addictive psychoactive substances postulated by Müller & Schumann (M&S) provides an interesting and plausible explanation for non-addictive drug use. However, with specific reference to the relevant behavioral addiction literature, this commentary argues that the model may unexpectedly hold utility not only for non-addictive use of drugs, but also for non-addictive use of other potentially addictive behaviors.

  17. The prevalence of psychoactive drug intake in a metropolitan population.

    Science.gov (United States)

    Pakesch, G; Loimer, N; Rasinger, E; Tutsch, G; Katschnig, H

    1989-03-01

    Together with a survey conducted among the population of Vienna on the prevalence of hypertension, the consumption of psychotropic substances was investigated. In cooperation with a polling institute a quota-sample of 1,470 Viennese over 15 were visited in their homes by 50 physicians trained in interview techniques. The quota-sample comprised 1,470 people (0.959(0/00) of the population of 1,531,346 inhabitants) and was representative in terms of age, sex, social status, and area of residence. The overall prevalence of psychoactive drug consumption among the inhibitants of Vienna investigated was found to be 6.8%. The female to male ratio was 3.5 to 1. Furthermore, psychoactive drug use increased with age and was influenced by social status, with the highest consumption rate found among divorced women and widows. Using the Goldberg "General Health Questionnaire", data were collected on the presence of psychopathologic symptoms and the responders' subjective feeling of being under stress was elicited. A significant correlation could be shown between these two factors and the use of psychoactive drugs. The type of drugs most frequently used were tranquilizers (4.96%), followed by antidepressants (0.95%) and hypnotics (0.88%).

  18. Drugs as instruments: a new framework for non-addictive psychoactive drug use.

    Science.gov (United States)

    Müller, Christian P; Schumann, Gunter

    2011-12-01

    Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a "necessary" prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of "drug instrumentalization." Psychoactive drugs are consumed for their effects on mental states. Humans are able to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific "instrumentalization goals" and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future.

  19. Medicating the mind: a Kantian analysis of overprescribing psychoactive drugs.

    Science.gov (United States)

    Manninen, B A

    2006-02-01

    Psychoactive drugs are being prescribed to millions of Americans at an increasing rate. In many cases these drugs are necessary in order to overcome debilitating emotional problems. Yet in other instances, these drugs are used to supplant, not supplement, interpersonal therapy. The process of overcoming emotional obstacles by introspection and the attainment of self knowledge is gradually being eroded via the gratuitous use of psychoactive medication in order to rapidly attain a release from the common problems that life inevitably presents us with. In this paper, I argue that Kant's formula of humanity, which maintains that persons ought never to treat others or themselves soley as a means to an end, proscribes this. Moreover, Kant argues that we have an imperfect duty of self development, and I argue that we fail to adhere to such a duty whenever we seek to evade the process of introspection and self knowledge in favour of the expedient results that drugs may provide us with as we attempt to overcome the emotional hurdles in our lives.

  20. Dysregulated Translational Control: From Brain Disorders to Psychoactive Drugs

    Directory of Open Access Journals (Sweden)

    Emanuela eSantini

    2011-11-01

    Full Text Available In the last decade, a plethora of studies utilizing pharmacological, biochemical, and genetic approaches have shown that precise translational control is required for long-lasting synaptic plasticity and the formation of long-term memory. Moreover, more recent studies indicate that alterations in translational control are a common pathophysiological feature of human neurological disorders, including developmental disorders, neuropsychiatric disorders, and neurodegenerative diseases. Finally, translational control mechanisms are susceptible to modification by psychoactive drugs. Taken together, these findings point to a central role for translational control in the regulation of synaptic function and behavior.

  1. Use Of Psychoactive Drugs Among Medical Undergraduates In Abbottabad.

    Science.gov (United States)

    Nawaz, Haq; Khan, Aftab Alam; Bukhari, Saima

    2017-01-01

    Psychoactive substance abuse is prevalent among medical undergraduates of Pakistan, India & Western countries which can adversely affect the physical & psychological grooming of a medical undergraduate thus threatening to compromise their role as future physicians & health-care providers in the society. The objective of the present cross-sectional study was to explore the prevalence and patterns of psychoactive substance/drug consumption among undergraduate students of a public sector medical college in Abbottabad. Seven hundred and eighty participants after informed consent were requested to fill a questionnaire seeking information about their demographics, patterns & behaviours regarding ten common psychoactive substances of abuse including (Cigarettes, Benzodiazepines, naswar, cannabis, alcohol, amphetamine, opium, cocaine, heroin & organic solvents). Overall students who responded were 698 (89.48%). One hundred and fifty (21.49%) admitted to the use of a psychoactive substance in past or at present. Majority users (71.33%) were males. Overall (81.33%) users were living in hostel or a rented apartment. Substance abuse was more prevalent among senior students, i.e., 30.06% & 24.24% in 4th year & final year MBBS respectively. Majority of the consumers, i.e., 93 (62%) were falling in an age group between 15-20 years. Main reasons behind substance abuse were: psychological stress (49.33%) and pleasure seeking (42.67%). Substances/drugs used by students in order of preference were Cigarettes 115 (76.67%), Benzodiazepines 48 (32%), naswar 42 (28%), Cannabis 41 (27.33%), Alcohol 24 (16%), Amphetamine 22 (14.67%), Opium 15 (10%), Cocaine 14 (9.33%), Heroin 11 (7.33%) & Organic solvents 05 (3.33%). Use of more than one substance was observed in 70 (46.67%) students. It is concluded that prevalence of cigarette smoking, naswar, benzodiazepines, cannabis & alcohol is high among medical undergraduates in Abbottabad which is a matter of concern. Efforts are needed to create

  2. Segmental hair testing to disclose chronic exposure to psychoactive drugs.

    Science.gov (United States)

    Marchei, Emilia; Palmi, Ilaria; Pichini, Simona; Pacifici, Roberta; Anton Airaldi, Ileana-Rita; Costa Orvay, Juan Antonio; García Serra, Joan; Bonet Serra, Bartolomé; García-Algar, Óscar

    2016-06-15

    This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg ± 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 ± 0.94 ng/mg and 1.50 ± 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother.

  3. Increase in Psychoactive Drug Prescriptions in the Years Following Autism Spectrum Diagnosis: A Population-Based Cohort Study.

    Science.gov (United States)

    Croteau, Caroline; Mottron, Laurent; Presse, Nancy; Tarride, Jean-Eric; Dorais, Marc; Perreault, Sylvie

    2017-08-18

    Psychoactive medications are commonly prescribed to autistic individuals, but little is known about how their use changes after diagnosis. This study describes the use of psychoactive drugs in children and young adults newly diagnosed with autism spectrum, between the year before and up to 5 years after diagnosis. Multivariable logistic regression was used to examine the relationship between the use psychoactive drugs before the first diagnosis of autism spectrum condition (from 1998 to 2010), and the clinical and demographic characteristics, identified from public health care databases in Quebec. The types of drugs prescribed and psychoactive polypharmacy were evaluated over 5 years of follow-up. Generalized estimating equations (GEE) were used to examine the association of age and time with the use of psychoactive drugs. In our cohort of 2,989 individuals, diagnosis of another psychiatric disorder before autism spectrum strongly predicted psychoactive drug use. We observed that the proportion of users of psychoactive drugs increased from 35.6% the year before, to 53.2% 5 years after the autism spectrum diagnosis. Psychoactive polypharmacy (≥2 psychoactive drug classes) also increased from 9% to 22% in that time. Age and time since diagnosis strongly associated with the types and combinations of psychoactive drugs prescribed. Psychoactive drug use and polypharmacy increases substantially over time after autism spectrum disorder diagnosis in children.

  4. Psychoactive drugs and false memory: comparison of dextroamphetamine and delta-9-tetrahydrocannabinol on false recognition

    OpenAIRE

    Ballard, Michael E.; Gallo, David A.; de Wit, Harriet

    2011-01-01

    Rationale Several psychoactive drugs are known to influence episodic memory. However, these drugs’ effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood. Objectives Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ9-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger–McDermott (DRM) illu...

  5. Understanding drugs and behaviour

    National Research Council Canada - National Science Library

    Parrott, Andrew

    2004-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix xi Part I Drugs and Their Actions . . . . . . . . . . . . . . . . . . . . . . 1 Psychoactive drugs: introduction and overview . . . . . . . . 2 The brain...

  6. Permissive Attitude Towards Drug Use, Life Satisfaction, and Continuous Drug Use Among Psychoactive Drug Users in Hong Kong.

    Science.gov (United States)

    Cheung, N Wt; Cheung, Y W; Chen, X

    2016-06-01

    To examine the effects of a permissive attitude towards regular and occasional drug use, life satisfaction, self-esteem, depression, and other psychosocial variables in the drug use of psychoactive drug users. Psychosocial factors that might affect a permissive attitude towards regular / occasional drug use and life satisfaction were further explored. We analysed data of a sample of psychoactive drug users from a longitudinal survey of psychoactive drug abusers in Hong Kong who were interviewed at 6 time points at 6-month intervals between January 2009 and December 2011. Data of the second to the sixth time points were stacked into an individual time point structure. Random-effects probit regression analysis was performed to estimate the relative contribution of the independent variables to the binary dependent variable of drug use in the last 30 days. A permissive attitude towards drug use, life satisfaction, and depression at the concurrent time point, and self-esteem at the previous time point had direct effects on drug use in the last 30 days. Interestingly, permissiveness to occasional drug use was a stronger predictor of drug use than permissiveness to regular drug use. These 2 permissive attitude variables were affected by the belief that doing extreme things shows the vitality of young people (at concurrent time point), life satisfaction (at concurrent time point), and self-esteem (at concurrent and previous time points). Life satisfaction was affected by sense of uncertainty about the future (at concurrent time point), self-esteem (at concurrent time point), depression (at both concurrent and previous time points), and being stricken by stressful events (at previous time point). A number of psychosocial factors could affect the continuation or discontinuation of drug use, as well as the permissive attitude towards regular and occasional drug use, and life satisfaction. Implications of the findings for prevention and intervention work targeted at

  7. Prevalence of tobacco, alcohol and psychoactive drug use among the college students in Chitwan

    Directory of Open Access Journals (Sweden)

    Manohar Pradhan

    2017-10-01

    Full Text Available Background & Objectives:Students of colleges may be vulnerable to consume tobacco, alcohol and psychoactive drugs due to various factors. This study was conducted with objectives of determining the prevalence of smoking, alcohol and psychoactive drug use among the bachelor level college students of Chitwan.Materials & Methods:This is a descriptive cross sectional study among the 132 bachelor level students at various colleges of Bharatpur, Chitwan district of Nepal. The students were chosen by purposive sampling. A standard pre tested questionnaire was used to collect the data.Results:A total of 90 (68.2% were males and 42 (31.8% were females. The mean age was 22.2 ± 1.7 years. Seventy four (56.06% responded that they had never consumed tobacco in any form.The number of cigarette smoked ranged from one to 20, with a mean of 7.85± 4.94 years. Forty eight (36.36% never consumed alcohol and (87.87% had never used psychoactive drugs.The most common motivator of the use of smoking, tobacco and psychoactive drugs was curiosity.Conclusion:The prevalence of smoking among the bachelor level students participating in our study was 43.94%, alcohol consumption was 63.63% and psychoactive drugs use was 12.12%. 

  8. Episodic memories and their relevance for psychoactive drug use and addiction

    Directory of Open Access Journals (Sweden)

    Christian P. Müller

    2013-05-01

    Full Text Available The majority of adult people in western societies regularly consume psychoactive drugs. While this consumption is integrated in everyday life activities and controlled in most consumers, it may escalate and result in drug addiction. Non-addicted drug use requires the systematic establishment of highly organized behaviours, such as drug seeking and -taking. While a significant role for classical and instrumental learning processes is well established in drug use and abuse, declarative drug memories have largely been neglected in research. Episodic memories are an important part of the declarative memories. Here a role of episodic drug memories in the establishment of non-addicted drug use and its transition to addiction is suggested. In relation to psychoactive drug consumption, episodic drug memories are formed when a person prepares for consumption, when the drug is consumed and, most important, when acute effects, withdrawal, craving, and relapse are experienced. Episodic drug memories are one-trial memories with emotional components that can be much stronger than ‘normal’ episodic memories. Their establishment coincides with drug-induced neuronal activation and plasticity. These memories may be highly extinction resistant and influence psychoactive drug consumption, in particular during initial establishment and at the transition to ‘drug instrumentalization’. In that, understanding how addictive drugs interact with episodic memory circuits in the brain may provide crucial information for how drug use and addiction are established.

  9. Exploring the Attractiveness of New Psychoactive Substances (NPS) among Experienced Drug Users

    NARCIS (Netherlands)

    van Amsterdam, J.G.C.; Nabben, T.; Keiman, D.; Haanschoten, G.; Korf, D.

    2015-01-01

    A growing number of New Psychoactive Substances (NPS) appear yearly on the European market (81 for the first time in 2013, adding to a total of over 350 NPS). Using semi-structured interviews with 25 Dutch experienced recreational drug users, the role of the Internet and friends in gathering and

  10. Off-target effects of psychoactive drugs revealed by genome-wide assays in yeast.

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    Elke Ericson

    2008-08-01

    Full Text Available To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac interfered with establishment of cell polarity, cyproheptadine (Periactin targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol and pimozide (Orap. Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes.

  11. Psychoactive drugs and false memory: comparison of dextroamphetamine and δ-9-tetrahydrocannabinol on false recognition.

    Science.gov (United States)

    Ballard, Michael E; Gallo, David A; de Wit, Harriet

    2012-01-01

    Several psychoactive drugs are known to influence episodic memory. However, these drugs' effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood. Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ(9)-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger-McDermott (DRM) illusion. Two parallel studies were conducted in which healthy volunteers received either AMP (0, 10, and 20 mg) or THC (0, 7.5, and 15 mg) in within-subjects, randomized, double-blind designs. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions. As expected, AMP increased memory of studied words relative to placebo, and THC reduced memory of studied words. Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Across participants, both drugs' effects on true memory were positively correlated with their effects on false memory. Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories.

  12. Use of psychoactive drugs and related falls among older people living in a community in Brazil

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    Chaimowicz Flávio

    2000-01-01

    Full Text Available INTRODUCTION: Population aging in Brazil has increased the prevalence of neurodegenerative diseases (Parkinson's and Alzheimer's disease and affective disorders (anxiety, depression, all common in old age. A retrospective study was carried out with the purpose of ascertaining if there is an association between falls and psychoactive medication use among older residents of a community in Brazil. METHODS: All residents aged 65+ (n=161 of one neighborhood of Campo Belo, Brazil (population of 48,000 were evaluated regarding the use of psychoactive drugs and the occurrence of falls in the 12 months preceding the study. Vision and hearing screenings were also performed. RESULTS: From the study population, 9.3% were taking prolonged half-life benzodiazepines, 4.4% anticonvulsants (mostly barbiturates, 2.5% antidepressants (all cyclics and 8.1% alpha-methyldopa. No subject reported use of hypnotics, neuroleptics or drugs to treat Alzheimer's or Parkinson's diseases (except biperiden. As a whole, drugs that increase the risk of falls were used by 1/5 of this population. In the 12-month period preceding the study, 27 residents (16.8% experienced falls and, of those, 4 (14.8% had fracture(s. There was an independent association between psychoactive drug use and falls when variables such as age, gender, vision and hearing were controlled (p=0.02. CONCLUSIONS: Although the population of this neighborhood must be considered young (only 4% are 65 years old or more, there are already problems related to the use of psychoactive drugs among people. Prescribed anxiolytics, anticonvulsants, antidepressants and antihypertensives are not appropriate for this age group and their use is associated with falls.

  13. Fingerprinting of Psychoactive Drugs in Zebrafish Anxiety-Like Behaviors

    Science.gov (United States)

    Maximino, Caio; da Silva, Annanda Waneza Batista; Araújo, Juliana; Lima, Monica Gomes; Miranda, Vanessa; Puty, Bruna; Benzecry, Rancés; Picanço-Diniz, Domingos Luiz Wanderley; Gouveia, Amauri; Oliveira, Karen Renata Matos; Herculano, Anderson Manoel

    2014-01-01

    A major hindrance for the development of psychiatric drugs is the prediction of how treatments can alter complex behaviors in assays which have good throughput and physiological complexity. Here we report the development of a medium-throughput screen for drugs which alter anxiety-like behavior in adult zebrafish. The observed phenotypes were clustered according to shared behavioral effects. This barcoding procedure revealed conserved functions of anxiolytic, anxiogenic and psychomotor stimulating drugs and predicted effects of poorly characterized compounds on anxiety. Moreover, anxiolytic drugs all decreased, while anxiogenic drugs increased, serotonin turnover. These results underscore the power of behavioral profiling in adult zebrafish as an approach which combines throughput and physiological complexity in the pharmacological dissection of complex behaviors. PMID:25079766

  14. Non-medical use of psychoactive drugs in relation to suicide tendencies among Chinese adolescents.

    Science.gov (United States)

    Juan, Wang; Jian-Xiong, Deng; Lan, Guo; Yuan, He; Xue, Gao; Jing-Hui, Huang; Guo-Liang, Huang; Ci-Yong, Lu

    2015-12-01

    To investigate the prevalence of non-medical use of psychoactive prescription drug (NMUPD) among adolescents and to explore the associations between non-medical psychoactive prescription drug use and depressive symptoms, poor sleep quality, deliberate self-harm, and suicide. A two-stage stratified cluster sample design produced a representative sample of 12-19-year-old students in grades 1-6 who attended public middle schools in Guangdong province. Prevalence estimates (SE) of non-medical psychoactive prescription drug use were calculated, and logistic regression was used to examine its association with depressive symptoms, poor sleep quality, deliberate self-harm, and suicide. Overall, 7.5% of adolescents reported non-medical use of opioids, and 4.8% of adolescents reported non-medical use of sedatives. Lifetime, last-year, and last-month non-medical use of opioids and sedatives were positively associated with depressive symptoms, poor sleep quality, deliberate self-harm, suicidal ideation, and suicidal attempts among different gender and age-group adolescents. Those who reported last month non-medical use of opioids and sedatives had the greatest odds of reporting depressive symptoms, poor sleep quality, deliberate self-harm, suicidal ideation, and suicidal attempts. Males who were last month non-medical users of opioids or sedative had 8.9 or 10.7 times greater odds of reporting a suicidal attempt, and 8.8 or 9.8 times greater odds of reporting a suicidal attempt were observed among adolescents aged 16-19 who were last-month non-medical users of opioids or sedatives. These findings provide evidence for improving adolescents' suicide prevention strategy by targeting supervision on high risk current non-medical users of psychoactive drug. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Non-medical use of psychoactive prescription drugs is associated with fatal poisoning.

    Science.gov (United States)

    Haukka, Jari; Kriikku, Pirkko; Mariottini, Claudia; Partonen, Timo; Ojanperä, Ilkka

    2017-08-25

    The aims of this study were to estimate the prevalence and predictors of non-medical substance use, and to assess the association between non-medical substance use and fatal poisoning or history of drug abuse in Finland. Retrospective cohort study of all medico-legally investigated death cases in Finland. The postmortem toxicology database was linked together with the register on reimbursed prescription medicines. All postmortem cases between 2011 and 2013 positive for one or more of the following drugs: oxycodone, fentanyl, tramadol, clonazepam, gabapentin, pregabalin, tizanidine, olanzapine, quetiapine, risperidone, alprazolam, zolpidem, mirtazapine and bupropion, n = 2974. Non-medical use of substance was the outcome variable. Predictors were the following: gender, residence at the time of death, place of death, blood alcohol concentration, age, drug abuse, number of prescriptions of any psychoactive drugs in last year and proportion of prescriptions issued by psychiatrist in last year. In 50.4% of the studied cases, at least one drug was detected without a prescription. Clonazepam, alprazolam and tramadol were the most prevalent non-medical findings in these cases (6.6, 6.1 and 5.6%, respectively). The risk of non-medical use of prescription drugs was especially high in cases with history of drug abuse (88.5%) and in fatal poisonings (71.0%). The proportion of non-medical use of the studied substances varied between 5.9% [95% confidence interval (CI) = 3.1-10.1%)] for risperidone and 55.7% for fentanyl (95% CI = 44.1-66.9%). Valid prescription for one or more of any psychoactive drug was associated with lower odds for non-medical use of the studied substances. Additionally, the higher the proportion of psychoactive drugs prescribed by a psychiatrist, the lower the probability of non-medical use. Non-prescribed psychoactive drugs are found commonly at postmortem in drug poisoning deaths in Finland, with history of drug abuse being a major contributing

  16. Avanços em psicofarmacologia - mecanismos de ação de psicofármacos hoje Advances in psychopharmacology: mechanism of action of psychoactive drugs today

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    Clarice Gorenstein

    1999-03-01

    Full Text Available Desde o início da história da psicofarmacologia moderna, na década de 40, vários avanços foram obtidos na elucidação do mecanismo de ação dos compostos psicoativos. O artigo aborda tais avanços enfocando as principais técnicas utilizadas, desde o desenvolvimento das técnicas de mensuração de aminas por emissão de fluorescência e da técnica de ligação fármaco-receptor, até a incorporação de técnicas sofisticadas, tais como as moleculares, para o estudo das alterações pós-receptor, o uso de marcadores genéticos e técnicas de imagem (PET, SPECT. Espera-se que tais progressos levem à elucidação dos mecanismos de ação dos psicofármacos, permitindo o desenvolvimento de novas moléculas terapêuticas específicas para regular as alterações subjacentes aos transtornos psiquiátricos.Since the beginning of the history of modern psychopharmacology on the 40's, many advances were obtained on the understanding of the mechanism of action of psychotropic drugs. This article gives an overview of such advances, since the introduction of the early techniques, such as the measurement of amines by fluorescence and the receptor-binding studies up to the incorporation of sophisticated techniques such as the molecular, to study the post-receptor alterations, the genetic and the neuroimage techniques. These kind of studies might help to better understand the mechanisms of action of psychotropics, allowing the development of new therapeutic substances to regulate the alterations which underlie the psychiatric disorders.

  17. [Post-marketing surveillance systems for psychoactive prescription drug abuse].

    Science.gov (United States)

    Nordmann, Sandra; Frauger, Elisabeth; Pauly, Vanessa; Rouby, Frank; Mallaret, Michel; Micallef, Joëlle; Thirion, Xavier

    2011-01-01

    Drugs affecting the central nervous system form a unique group of products for surveillance because they could be misused, abused or diverted. Considering the characteristics of this behaviour that is often concealed, specific post-marketing surveillance systems have been developed to monitor abuse of prescription drugs in some countries. The purpose of this review is to list and to describe post-marketing surveillance systems, according their methodology, in France and in foreign countries. These programs are based on adverse effect notifications, medical or legal consequences of abuse, general or specific population-based survey, professional networks or medication databases. Some programs use simultaneously several information sources. In conclusion, the multifaceted nature, the diversity and the inventiveness of post-marketing surveillance systems reflects the complexity of the abuse issue. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  18. Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?

    Science.gov (United States)

    Cappelletti, Simone; Daria, Piacentino; Sani, Gabriele; Aromatario, Mariarosaria

    2015-01-01

    Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine’s mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine’s interaction with other substances or to the individuals' preexisting metabolism alterations or diseases. PMID:26074744

  19. Caffeine: cognitive and physical performance enhancer or psychoactive drug?

    Science.gov (United States)

    Cappelletti, Simone; Piacentino, Daria; Daria, Piacentino; Sani, Gabriele; Aromatario, Mariarosaria

    2015-01-01

    Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine's mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine's interaction with other substances or to the individuals' preexisting metabolism alterations or diseases.

  20. Do psychoactive drugs have a therapeutic role in compulsivity? Studies on schedule-induced polydipsia.

    Science.gov (United States)

    Martín-González, Elena; Prados-Pardo, Ángeles; Mora, Santiago; Flores, Pilar; Moreno, Margarita

    2018-02-01

    Clinical studies have shown that some psychoactive recreational drugs have therapeutic applications in anxiety, depression, and schizophrenia. However, to date, there are few studies on the therapeutic potential efficacy of recreational drugs in compulsive neuropsychiatric disorders. We explored the therapeutic potential of different psychoactive and psychedelic drugs in a preclinical model of compulsive behavior. Outbred male Wistar rats were selected as either high (HD) or low (LD) drinkers according to their behavior in schedule-induced polydipsia (SIP). Subsequently, we assessed the effects of acute administration of scopolamine (0.125, 0.25, and 0.5 mg/kg), methamphetamine (0.25, 0.5, 1.25, and 2.5 mg/kg), ketamine (1.25, 2.5, 5, and 10 mg/kg), cannabidiol (1 and 3 mg/kg), WIN21255-2 (0.5, 075, and 1 mg/kg), and AM404 (0.25 and 0.5 mg/kg) on compulsive drinking in SIP. Scopolamine reduced dose-dependent compulsive drinking in HD compared with LD rats in SIP. Methamphetamine induced a dose-dependent inverted U-curve effect in both groups, in which lower doses increased and higher doses reduced compulsive drinking in SIP. Ketamine, cannabidiol, WIN21255-2, and AM404 did not have any relevant effects in SIP. These data provide new evidence that low doses of scopolamine and intermediate doses of methamphetamine might therapeutically reduce compulsive behaviors and suggest that there is not a direct participation of the endocannabinoid system in compulsive behavior on SIP. The research in the underlying neurochemical mechanisms of these psychoactive drugs might provide an additional insight on new therapeutic targets in compulsive neuropsychiatric disorders.

  1. 'Designer drugs': update on the management of novel psychoactive substance misuse in the acute care setting.

    Science.gov (United States)

    Smith, Christopher D; Robert, Stefanie

    2014-08-01

    The use of novel psychoactive substances ('legal highs' or 'designer drugs') is increasing worldwide. Patients misusing such substances have been reported to experience severe or prolonged side effects requiring admission to acute or critical care wards. These complications can be life threatening if misdiagnosed or mismanaged. As physicians have traditionally had less involvement with the management of such patients compared with their colleagues in emergency departments an update in the management of such patients is indicated. Here we present a summary of the management of those novel substances with the potential for serious complications based on a review of current literature. © 2014 Royal College of Physicians.

  2. Risk Factors of Narcotic and Psychoactive Drugs Use among University and High School Student

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    Ali Kashi

    2010-05-01

    Full Text Available Aim: Today use of different banned substances such as narcotic, psychoactive and energetic drugs are social problem that has created worry in different levels of human societies. The aim of present study was examined the prevalence of use of narcotic and psychoactive drugs among high school and university students also identifying of risk factors associated with the use of this materials. Method: The population of this descriptive survey study was all students of high school and university of Khodabandeh city. By cluster random sampling 580 students of high school and university selected and questionnaires distributed among them. After eliminating incomplete questionnaires 480 students remained as research sample. Results: In consideration of selected sample the most important reasons of using of narcotics are: enjoying and curiosity, exposed to bad environment like addicted friends and families, joblessness, economic problems, lack of information and loss of affection. Conclusion: The analysis of the results indicated the high prevalence of narcotic and drugs use and necessity of codification of preventive programs for these people.

  3. Drugs of Abuse and Novel Psychoactive Substances at Outdoor Music Festivals in Colorado.

    Science.gov (United States)

    Fox, Jacob; Smith, Alexis; Yale, Alexander; Chow, Christopher; Alaswad, Elsa; Cushing, Tracy; Monte, Andrew A

    2017-11-17

    Drugs of abuse (DOA) are widely used in the United States and are ubiquitous at outdoor music festivals. Attendees at music festivals are at high-risk for novel psychoactive substance (NPS) use, which is becoming more prevalent worldwide. No U.S. studies have employed an qualitative approach to investigate the etiologies of both traditional DOA and NPS use amongst music festival attendees. The objective of this study was to improve understanding of the knowledge, attitudes, beliefs, and practices of festival attendees using NPS and DOA. We conducted semi-structured interviews of 171 attendees during the Sonic Bloom and Arise music festivals in Colorado in 2015 and 2016. Discrete variables were summarized with descriptive statistics. The anonymous, multi-domain interview documented the knowledge, attitudes beliefs, and practices underlying DOA use, which were analyzed with qualitative methods. We enrolled 171 participants that endorsed DOA use at the festivals. Most were experienced DOA users, who perceived minimal risks associated with DOA and NPS use. Nearly all unanimously reported normalization of DOA at music festivals. Participants popularly cited empathogenic, entactogenic, and entheogenic effects of DOA as their primary motivations for use. NPS use was endorsed by 39.8% (n = 68) of respondents, all of whom identified as being experienced DOA users. This population of novel psychoactive substance users is primarily composed of experienced drug users that endorsed use because of low cost, minimal perceived risk, accessibility, and normalization of drug use at music festivals.

  4. Awareness survey of so-called Dappou drugs or Kiken drugs (New Psychoactive Substances) among University Students in Japan.

    Science.gov (United States)

    Fuse-Nagase, Yasuko; Saito, Fukumi; Hirohara, Toshie; Miyakawa, Happei

    2015-10-09

    Spread of new psychoactive substances (NPS) is a worldwide problem. In Japan, NPSs with psychoactive ingredients are called as "dappou drugs" or "kiken drugs." Their potential effect on the Japanese society cannot be ignored. We conducted an awareness survey of So-called Dappou Drugs or Kiken Drugs among the students of Ibaraki University, a national university in Japan, in April 2014. 3976 students (2425 men, 1406 women and 145 unspecified) participated in this study. 2813 (70.7 %) respondents were aware of dappou drugs. Only 39.5 % of the respondents selected the option of "ingredients that cause delusions and/or hallucinations may be included" in dappou drugs. 23.4 % of the respondents selected "the number of (dappou drug) users requiring emergency hospitalization due to acute intoxication is increasing". Of the respondents, 19 (0.5 %) reported that they had been invited to use dappou drugs previously, and 40 (1.0 %) had witnessed and/or heard of somebody close to them using the drugs. Those who drank alcohol every day and those who smoked had a higher chance of witnessing and/or hearing of somebody close to them using dappou drugs than those who did not drink or smoke, respectively. Japanese university students do not have sufficient knowledge about dappou drugs or kiken drugs to protect themselves from potential drug misuse. It is both important and urgent to educate Japanese university students about the harmful effects of dappou drugs; in addition, it is important to provide such knowledge before the students are allowed to legally drink and smoke.

  5. Report on psychoactive drug use among adolescents using ayahuasca within a religious context.

    Science.gov (United States)

    Doering-Silveira, Evelyn; Grob, Charles S; de Rios, Marlene Dobkin; Lopez, Enrique; Alonso, Luisa K; Tacla, Cristiane; Da Silveira, Dartiu Xavier

    2005-06-01

    Ritual use of ayahuasca within the context of the Brazilian ayahuasca churches often starts during late childhood or early adolescence. Premature access to psychoactive drugs may represent a risk factor for drug misuse. Conversely, religious affiliation seems to play a protective role in terms of substance abuse. The objective of this study was to describe patterns of drug use in a sample of adolescents using ayahuasca within a religious setting. Forty-one adolescents from a Brazilian ayahuasca sect were compared with 43 adolescents who never drank ayahuasca. No significant differences were identified in terms of lifetime substance consumption. Throughout the previous year period, ayahuasca adolescents used less alcohol (46.31%) than the comparison group (74.4%). Recent use of alcohol was also more frequent among the latter group (65.1%) than among ayahuasca drinkers (32.5%). Although not statistically significant, slight differences in terms of patterns of drug use were definitely observed among groups. Despite their early exposure to a hallucinogenic substance, adolescents using ayahuasca in a controlled setting were mostly comparable to controls except for a considerably smaller proportion of alcohol users. Religious affiliation may have played a central role as a possible protective factor for alcohol use. Thus, ayahuasca seems to be a relatively safe substance as far as drug misuse is concerned.

  6. Lysozyme binding ability toward psychoactive stimulant drugs: Modulatory effect of colloidal metal nanoparticles.

    Science.gov (United States)

    Sonu, Vikash K; Islam, Mullah Muhaiminul; Rohman, Mostofa Ataur; Mitra, Sivaprasad

    2016-10-01

    The interaction and binding behavior of the well-known psychoactive stimulant drugs theophylline (THP) and theobromine (THB) with lysozyme (LYS) was monitored by in-vitro fluorescence titration and molecular docking calculations under physiological condition. The quenching of protein fluorescence on addition of the drugs is due to the formation of protein-drug complex in the ground state in both the cases. However, the binding interaction is almost three orders of magnitude stronger in THP, which involves mostly hydrogen bonding interaction in comparison with THB where hydrophobic binding plays the predominant role. The mechanism of fluorescence quenching (static type) remains same also in presence of gold and silver nanoparticles (NPs); however, the binding capacity of LYS with the drugs changes drastically in comparison with that in aqueous buffer medium. While the binding affinity of LYS to THB increases ca. 100 times in presence of both the NPs, it is seen to decrease drastically (by almost 1000 fold) for THP. This significant modulation in binding behavior indicates that the drug transportation capacity of LYS can be controlled significantly with the formation protein-NP noncovalent assembly system as an efficient delivery channel. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Alcohol, psychoactive drugs and fatal road traffic accidents in Norway: a case-control study.

    Science.gov (United States)

    Gjerde, Hallvard; Normann, Per T; Christophersen, Asbjørg S; Samuelsen, Sven Ove; Mørland, Jørg

    2011-05-01

    A case-control study was conducted on 204 drivers fatally injured in road traffic accidents in south-eastern Norway during the period 2003-2008. Cases from single vehicle accidents (N = 68) were assessed separately. As controls, 10540 drivers selected in a roadside survey in the same geographical area during 2005-2006 were used. Blood samples were collected from the cases and oral fluid (saliva) samples from the controls. Samples were analysed for alcohol, amphetamines, cannabis, cocaine, opioid analgesics, hypnotics, sedatives and a muscle relaxant; altogether 22 psychoactive substances. Equivalent cutoff concentrations for blood and oral fluid were used. The risk for fatal injury in a road traffic accident was estimated using logistic regression adjusting for gender, age, season of the year, and time of the week. The odds for involvement in fatal road traffic accidents for different substances or combination of substances were in increasing order: single drug < multiple drugs < alcohol only < alcohol+drugs. For single substance use: medicinal drug or THC < amphetamine/methamphetamine < alcohol. For most substances, higher ORs were found when studying drivers involved in single vehicle accidents than for those involved in multiple vehicle accidents, but confidence intervals were wider. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Simultaneous identification of abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Hei-Hwa Lee

    2016-03-01

    Full Text Available A literature search reveals no studies concerning simultaneous identification of commonly abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry (LC–MS/MS. We developed and validated an LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine from suspected drug abusers. The instrument was operated in multiple-reaction monitoring using an electrospray ionization mode. Chromatograms were separated using an ACE5 C18 column on a gradient of acetonitrile. After liquid–liquid extraction, samples were passed through a 0.22-μm polyvinylidene difluoride filter before injection into the LC–MS/MS. The limits of quantitation ranged from 0.5 ng/mL to 31.3 ng/mL. The linearity ranged from 0.5 ng/mL to 200 ng/mL. The precision results were below 15.4% (intraday and 18.7% (interday. The intraday accuracy ranged from 85.9% to 121.0%; interday accuracy ranged from 66.1% to 128.7%. The proposed method was applied to 769 urine samples. The most common three drugs identified were ketamine, amphetamine, and opiates. The drug positive rate for one or more drugs was 79.6%. Our results demonstrate the suitability of the LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine.

  9. Prevalence of psychoactive substances, alcohol, illicit drugs, and medicines, in Spanish drivers: a roadside study.

    Science.gov (United States)

    Gómez-Talegón, Trinidad; Fierro, Inmaculada; González-Luque, Juan Carlos; Colás, Monica; López-Rivadulla, Manuel; Javier Álvarez, F

    2012-11-30

    Following population, geographic, road type and time criteria, Spain has carried out random, roadside controls of 3302 representative sample of Spanish drivers, including saliva analysis for 24 psychoactive substances and alcohol breath tests. The 81.4% of the drivers were male, with an average age of 34.8±11.8 (mean±SD). The 17% of the drivers were found to be positive to any of the substances analysed. The 6.6% of the drivers found positive to alcohol (>0.05 mg/l in breath), 11% were found positive to any illicit drug, and 2% were positive to one of the medicines analysed. Some drivers were positive in more than one substance. The most common illicit drugs among Spanish drivers were cannabis (7.7%), or cocaine (3.5%), either alone or combined with other substances. The most prevalent medicines were the benzodiazepines (1.6%). As a tendency, higher figures for positive cases were observed among males than in females (being statistically significant the differences for alcohol, cannabis and cocaine). Alcohol and cocaine positive cases were more frequently found among drivers of urban roads. Alcohol positive cases (alone, >0.05 mg/l), were more likely found as age increase (OR=1.02), those driving in urban roads (OR=2.13), and driving at any period than weekdays, while alcohol+drugs cases were more likely found among males (OR=2.819), those driving on urban road (OR=2.17) and driving at night periods. Finding a medicines positive case was more likely as elder the driver was (OR=1.05). There have been differences in the prevalence of positive cases of alcohol, cannabis and cocaine, in relation to the period of the week: in three cases the highest prevalence seen in night time. This study shows the high prevalence of psychoactive substances and alcohol in Spanish drivers, mainly illicit drugs (cannabis). This question requires a response from the authorities and from society, with an integral and multi-disciplinary approach that can heighten the population

  10. Epidemiology of psychoactive drug use amongst adolescents in metropolitan Lagos, Nigeria.

    Science.gov (United States)

    Famuyiwa, Oluwole; Aina, Olatunji F; Bankole-Oki, Olufunlayo M

    2011-07-01

    The study was conducted in response to the lack of epidemiological data in recent time on the use of psychoactive substances by adolescents in metropolitan Lagos-a city unique for its socio-economic profile. We considered some methodological issues omitted in several previous studies. A total of 4,286 school pupils (mean age 15.2) were anonymously administered a Self-Report Questionnaire to ascertain a range of key drug use factors in lifetime and 1-year periods. The rate of use of most of the 14 substances investigated was much higher than reported in any other study on comparable population sample. We found that 61.8 and 32.1% of respondents have used one or more substances in their lifetime and in the past 1 year, respectively. High lifetime rates of use were found for common stimulants: coffee, kolanut, and prescription drugs (barbiturates and minor tranquilisers). The rate of use of proscribed addictive substances, cannabis, heroin, and cocaine, ranged between 4.0 and 4.8%. Missing data and non-response rates were few; however, social acquiescence, under and over reporting, could be mitigant to estimation of rates and patterns of use. We advocate properly articulated school-based educative programmes that can facilitate drug demand reduction.

  11. Psychoactive natural products: overview of recent developments

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    István Ujváry

    2014-03-01

    Full Text Available Natural psychoactive substances have fascinated the curious mind of shamans, artists, scholars and laymen since antiquity. During the twentieth century, the chemical composition of the most important psychoactive drugs, that is opium, cannabis, coca and "magic mushrooms", has been fully elucidated. The mode of action of the principal ingredients has also been deciphered at the molecular level. In the past two decades, the use of herbal drugs, such as kava, kratom and Salvia divinorum, began to spread beyond their traditional geographical and cultural boundaries. The aim of the present paper is to briefly summarize recent findings on the psychopharmacology of the most prominent psychoactive natural products. Current knowledge on a few lesser-known drugs, including bufotenine, glaucine, kava, betel, pituri, lettuce opium and kanna is also reviewed. In addition, selected cases of alleged natural (or semi-natural products are also mentioned.

  12. Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions

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    Débora González

    2015-01-01

    Full Text Available Background. 2C-B (Nexus is one of the most widespread novel psychoactive substances. There is limited information about its pharmacological properties, and few studies in humans concern its acute and chronic effects. 2C-B has been classified as a stimulant, hallucinogen, entactogen, and/or empathogen. Objectives. To evaluate the emotional, subjective, and cardiovascular effects of 2C-B. Methods. Twenty healthy recreational 2C-B users (12 women self-administered a 20 mg dose of 2C-B. Evaluations included emotional (IAPS, FERT, and speech, subjective (visual analog scales, ARCI, VESSPA, HRS, and POMS questionnaires, and cardiovascular effects (blood pressure and heart rate. Results. Positive subjective effects predominated with a reduction of anger under the influence of 2C-B. It did, however, increase reactivity to negative emotional stimuli and decrease the ability to recognize expressions of happiness. Augmented emotionality in speech could be appreciated by others. 2C-B induced euphoria and well-being, changes in perceptions, and slight hallucinogenic states. Mild sympathetic actions were observed. Conclusions. The specific profile that 2C-B exerts on emotions suggests its classification as an entactogen with psychedelic properties.

  13. Expecting innovation: psychoactive drug primes and the generation of creative solutions.

    Science.gov (United States)

    Hicks, Joshua A; Pedersen, Sarah L; Pederson, Sarah L; Friedman, Ronald S; McCarthy, Denis M

    2011-08-01

    Many individuals expect that alcohol and drug consumption will enhance creativity. The present studies tested whether substance related primes would influence creative performance for individuals who possessed creativity-related substance expectancies. Participants (n = 566) were briefly exposed to stimuli related to psychoactive substances (alcohol, for Study 1, Sample 1, and Study 2; and marijuana, for Study 1, Sample 2) or neutral stimuli. Participants in Study 1 then completed a creative problem-solving task, while participants in Study 2 completed a divergent thinking task or a task unrelated to creative problem solving. The results of Study 1 revealed that exposure to the experimental stimuli enhanced performance on the creative problem-solving task for those who expected the corresponding substance would trigger creative functioning. In a conceptual replication, Study 2 showed that participants exposed to alcohol cues performed better on a divergent thinking task if they expected alcohol to enhance creativity. It is important to note that this same interaction did not influence performance on measures unrelated to creative problem solving, suggesting that the activation of creativity-related expectancies influenced creative performance, specifically. These findings highlight the importance of assessing expectancies when examining pharmacological effects of alcohol and marijuana. Future directions and implications for substance-related interventions are discussed. (c) 2011 APA, all rights reserved.

  14. QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

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    Piccinelli Marco

    2005-01-01

    Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

  15. Simultaneous identification of abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Lee, Hei-Hwa; Lee, Jong-Feng; Lin, Shin-Yu; Chen, Bai-Hsiun

    2016-03-01

    A literature search reveals no studies concerning simultaneous identification of commonly abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry (LC-MS/MS). We developed and validated an LC-MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine from suspected drug abusers. The instrument was operated in multiple-reaction monitoring using an electrospray ionization mode. Chromatograms were separated using an ACE5 C18 column on a gradient of acetonitrile. After liquid-liquid extraction, samples were passed through a 0.22-μm polyvinylidene difluoride filter before injection into the LC-MS/MS. The limits of quantitation ranged from 0.5 ng/mL to 31.3 ng/mL. The linearity ranged from 0.5 ng/mL to 200 ng/mL. The precision results were below 15.4% (intraday) and 18.7% (interday). The intraday accuracy ranged from 85.9% to 121.0%; interday accuracy ranged from 66.1% to 128.7%. The proposed method was applied to 769 urine samples. The most common three drugs identified were ketamine, amphetamine, and opiates. The drug positive rate for one or more drugs was 79.6%. Our results demonstrate the suitability of the LC-MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine. Copyright © 2016. Published by Elsevier Taiwan.

  16. [Consumption of psychoactive drugs and exposure to bacterial toxins carried by food: a dangerous association].

    Science.gov (United States)

    Corma-Gómez, Anaïs; López-Sepúlveda, Rocío; Capitán-Del Río, Inés; Sánchez Mariscal, María Dolores; López-Hernández, Begoña

    2017-11-01

    To describe and analyse from a clinical and epidemiological point of view, a food borne outbreak in a psychiatric institution in Granada, in 2015, and to examine whether treatment with psychoactive drugs constitutes a risk factor for the development of a food borne disease, analysing the degree of susceptibility according to the therapeutic group consumed. Ambispective cohort study. Residents were the unit of analysis. Our group carried out an active case search and a food survey. A search for other risks was developed as well as a food inspection. Location, time and individual variables were studied. A descriptive analysis was conducted (absolute and relative frequencies). Calculation of attack rates by building and by menu was made. Bi-variant analysis (Chi-square test, t-Student test) and relative risk were used as a measure of strength of association. For risk analysis of medication, a multivariate analysis using logistic regression was carried out. 18 cases with diarrhoea without fever were found (incubation period from 6 to 16hours). Cases were mild and self-limiting. The clinical manifestations, the temporal grouping of cases and the characteristics of the ingested foods, focussed suspicion on a bacterial toxin. Being equal in the rest of variables, the N03AF, and N03AG therapeutic groups confer greater risk of disease (odds ratio [OR]: 8.626; 95% confidence interval [95%CI]: 2.050-36.308; p=0.003; and OR: 14.516; 95%CI: 3.155-66.784; p=0.001, respectively). Decreased intestinal transit, caused by the administration of anticonvulsants, may increase exposure time of the intestinal mucosa to the toxin, increasing the risk of disease and suffering from complications. An additional hygienic effort should be made in this type of institution to prevent these pathologies. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Psychoactive drug advertising: a comparison of technical information from three countries: Brazil, United States and United Kingdom.

    Science.gov (United States)

    Mastroianni, Patricia de Carvalho; Galduróz, José Carlos Fernandes; Carlini, Elisaldo Araujo

    2005-09-01

    Studies carried out in the 1970s and 1980s showed that there were country-dependent disparities in the information given for the same drug in medical advertisements. National and international regulations have been published to do away with such disparities and to foster the rational use of drugs. The purpose of this study was to compare the information contained in psychoactive drug advertisements published in psychiatric journals in Brazil, the United States and the United Kingdom, before and subsequent to the publication of the United States Export Act, in 1986, the WHO criteria, in 1988, and the Brazilian Sanitary Surveillance Agency Resolution no. 102, in 2000. TYPE OF STUDY AND SETTING: Content analysis, at Centro Brasileiro de Informações sobre Drogas Psicotrópicas (Cebrid). We gathered advertisements from Brazilian, American and British psychiatry periodicals published before and after each ruling. We analyzed a total of twenty-four Brazilian advertisements that were for the same psychoactive drugs as advertised in American and/or British publications from the same period. We observed that Brazilian advertisements omitted information on usage restrictions, such as contraindications, adverse reactions, interactions, warnings and precautions, and that such information was present in American and British advertisements. The data suggest that disparities in the information given for the same drug still persist. The information depends on the country in which each drug is marketed. The legislation is insufficient for eradicating such disparities.

  18. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain.

    Science.gov (United States)

    Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako

    2007-03-22

    We developed a reproducible, simple, and small-scale method for determining the re-uptake and release of monoamines (dopamine, serotonin (5-HT) and norepinephrine) using rat brain synaptosomes. These assays were then applied to study the effects of different kinds of non-medically used psychoactive drugs on monoamine re-uptake and release. The phenethylamine derivatives, 4-fluoroamphetamine, 2-methylamino-3,4-methylene-dioxy-propiophenone (methylone), 1-(1,3-benzodioxol-5-yl)-2-butanamine (BDB), and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), had strong inhibitory effects on the re-uptake of dopamine, 5-HT and norepinephrine. 4-Fluoroamphetamine, methylone and BDB also strongly increased the release of the three monoamines, but MBDB increased 5-HT and norepinephrine release, but had little effect on dopamine release. However, 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,4,5-trimethoxyamphetamine (TMA-2) and 2,4,6-trimethoxyamphetamine (TMA-6), which are methoxylated phenethylamine derivatives, slightly influenced the re-uptake and release of monoamines. Alpha-metyltryptamine (AMT), a tryptamine derivative, was one of the strongest re-uptake inhibitors and releasers of the three monoamines. The tryptamine derivative, 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), also strongly inhibited re-uptake and increased the release of the three monoamines. N,N-dipropyltryptamine (DPT), 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), 5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) inhibited monoamine re-uptake, but had a few effects on monoamine release. 1-(3-Chlorophenyl)piperazine (3CPP) and 1-(methoxyphenyl)piperazine (4MPP), which are piperazine derivatives, inhibited monoamine re-uptake and accelerated their release. The results suggest that some designer drugs strongly act on the central nerve system to the same

  19. Consumo de drogas psicoativas por adolescentes escolares de Assis, SP Psychoactive drug use in school age adolescents, Brazil

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    José Luiz Guimarães

    2004-02-01

    Full Text Available Com o objetivo de quantificar o consumo das diferentes drogas psicoativas entre os estudantes da cidade de Assis, SP, e investigar as variáveis relacionadas com seu uso, foi aplicado um questionário que identificava dados sociodemográficos e padrão de uso não-médico de psicotrópicos em 20% dos estudantes das escolas públicas e privadas da cidade. Os maiores índices de consumo para o uso na vida foram os do álcool com 68,9% e o tabaco com 22,7%. As drogas mais utilizadas foram: solventes (10,0%; maconha (6,6%; ansiolíticos (3,8%; anfetamínicos (2,6%; cocaína (1,6% e anticolinérgicos (1,0%.To quantify psychoactive drug use and investigate use-related variables among students of Assis, Brazil, a questionnaire was administered to collect sociodemographic data and identify the pattern of non-medical use of psychoactive drugs in 20% of public and private school students. The largest consumption indexes for lifetime use were seen for alcohol (68.9% and tobacco (22.7%. Drugs most often used were: solvents (10.0%; marijuana (6.6%; benzodiazepines (3.8%; amphetamines (2.6%; cocaine (1.6%; and anticholinergics (1.0%.

  20. [Pharmacological influences on the brain level and transport of GABA. II) Effect of various psychoactive drugs on brain level and uptake of GABA].

    Science.gov (United States)

    Gabana, M A; Varotto, M; Saladini, M; Zanchin, G; Battistin, L

    1981-04-30

    The effects of some psychoactive drugs on the level and uptake of GABA in the mouse brain was studied using well standardized procedures, mainely the silica-gel cromatography for determining the GABA content and the brain slices for measuring GABA uptake. It was found that levomepromazine, sulpiride, haloperidol and amytryptiline were without effects on the cerebral level of GABA; it was also found that these drugs do not influence the rates of uptake of GABA by mouse brain slices. Such results do indicate that the psychoactive drugs studied are without effects on the level and uptake of GABA in the brain.

  1. Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products.

    Science.gov (United States)

    Baumann, Michael H; Partilla, John S; Lehner, Kurt R; Thorndike, Eric B; Hoffman, Alexander F; Holy, Marion; Rothman, Richard B; Goldberg, Steven R; Lupica, Carl R; Sitte, Harald H; Brandt, Simon D; Tella, Srihari R; Cozzi, Nicholas V; Schindler, Charles W

    2013-03-01

    The abuse of psychoactive 'bath salts' containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [(3)H]dopamine (IC(50)=4.1 nM) and [(3)H]norepinephrine (IC(50)=26 nM) with high potency but has weak effects on uptake of [(3)H]serotonin (IC(50)=3349 nM). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1-0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1-3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of 'bath salts' preparations.

  2. In vitro screening of psychoactive drugs by [(35)S]GTPgammaS binding in rat brain membranes.

    Science.gov (United States)

    Nonaka, Ryouichi; Nagai, Fumiko; Ogata, Akio; Satoh, Kanako

    2007-12-01

    We constructed a reproducible, simple, and small-scale determination method of the psychoactive drugs that acted directly on the monoamine receptor by measuring the activation of [(35)S]guanosine-5'-O-(3-thio)-triphosphate binding to guanine nucleotide-binding proteins (G proteins). This method can simultaneously measure the effects of three monoamines, namely dopamine (DA), serotonin (5-HT), and norepinephrine (NE), in rat brain membranes using a 96-well microplate. Activation of D(1) and D(2) receptors in striatal membranes by DA as well as 5-HT and NEalpha(2) receptors in cortical membranes could be measured. Of 12 tested phenethylamines, 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), and 2,5-dimethoxy-4-iodophenethylamine (2C-I) stimulated G protein binding. The other phenethylamines did not affect G protein binding. All 7 tryptamines tested stimulated G protein binding with the following rank order of potency; 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)>5-methoxy-N,N-diallyltryptamine (5-MeO-DALT)>5-methoxy-alpha-methyltryptamine (5-MeO-AMT)>or=5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT)>5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT)>N,N-dipropyltryptamine (DPT)>or=alpha-methyltryptamine (AMT). This assay system was able to designate psychoactive drugs as prohibited substances in accordance with criteria set forth by the Tokyo Metropolitan government.

  3. [Psychoactive Drug Abuse in Adolescent Addicts of a Colombian Rehabilitation Foundation. Descriptive Study].

    Science.gov (United States)

    Medina-Pérez, Óscar Adolfo; Rubio, Luz Adriana

    2012-09-01

    To describe the use of psychoactive substances (PAS) in addict population between 14 and 18 years of a foundation devoted to rehabilitation in the Department of Quindío, Colombia. Quantitative-descriptive research. The VESPA (Epidemiological surveillance for psychoactive substance abuse) Forms of the people admitted to the institution between 2006 and 2009. During the study, 333 adolescents between 14 and 18 were attended. 75.4% were men, only 31.2% had primary education, 56% reported being unemployed, and 34.5% stated they were admitted at the foundation after legal indication. Upon admission, the PAS was: 44.2%, tobacco; 25.8%, marijuana; 18.0%, alcohol and 5.7% cocaine. The average starting age for men was 12.33, while for women was 11.96; reported substances showed the following starting averages: alcohol, 12.26 ys old; tobacco, 12.49 ys old; marijuana, 13.39 ys old; inhalants, 13.98 ys old; cocaine, 14.01 ys old; crack, 14.27 ys old; and heroin, 15 ys old. The average admission age to the institution was 15.7 ys old. Figures found highlight the need for greater and better prevention programs regarding PAS abuse in adolescents and children. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  4. Fatal injuries while under the influence of psychoactive drugs: a cross-sectional exploratory study in England

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    Dryden Ruth

    2006-06-01

    Full Text Available Abstract Background Studies of drug-related mortality rarely describe fatal injuries due to psychoactive drug intoxication (FIUI. The main aim of this study was to determine the nature, extent and pattern of FIUI. Methods This observational study covered the period January 1999 to December 2001. Data were provided by members of a study panel of coroners in England using a standard protocol. Sources of data for this study included autopsy protocols, death certificates, hospital records, police reports, toxicology reports and inquest transcripts. Inclusion criteria for this were (i the mention of one or more psychoactive substances as contributing to fatality; and (ii the presence of a Controlled Drug at post mortem. Results A total of 3,803 drug-related deaths of persons aged 16–64 years were reported by the study panel during the three-year period. The study panel accounted for 86% of drug-related deaths in England in this period. There were 147 FIUI cases (119 males, 28 females, giving a proportionate mortality ratio of approximately 4%. The majority of FIUI cases (84% were aged 16–44 years, with a median age at death of 33 years (Quartile deviation = 7. Fifty-six percent of FIUI occurred in urban areas of England. The population of the study jurisdictions aged 16–64 years contributed 49,545,766 person-years (py to the study, giving an annual crude rate of 3/1,000,000 person-years (py. Rates for male and females were 4.9 and 1.1/1,000,000 py respectively, giving a male/female rate ratio of 4.5 (95%CI = 2.9–6.8. The rates of intentional and unintentional FIUI were 2 and 1/1,000,000 py respectively. The leading mechanism for intentional FIUI was suffocation while the predominant mechanisms in unintentional FIUI were road traffic accidents and falls. There is a significant difference in the pattern of drug-specific risk between FIUI and fatal poisoning. Risks of intentional FIUI are elevated among Black and Minority Ethnic groups

  5. [Psychoactive Drug Use by Youth in a Post Armed-Conflict Region].

    Science.gov (United States)

    Díaz, Carlos Gantiva; Ramírez, Nohelia Hewitt; Maldonado, Anderssen Vera; Varela, Adriana Angarita; Baños, Arturo Parado; Puerto, Angélica Guillén

    2012-06-01

    There are no studies in Colombia on the use of psychoactive substances (PAS) by post armed-conflict population to serve as guide for prevention programs and to account for the potential impact armed conflict may have upon this area. To describe the use of PAS in young students in a post-conflict region. A quantitative-descriptive study involving the totality of students of the township of Viotá, Department of Cundinamarca, Colombia (1,304 participants). The World Health Survey for Schoolchildren was applied. Alcohol is the substance with the highest percentage of lifetime prevalence; during the last month, it was observed that the highest percentage of people start PAS use between the age of 8 and 13, while 42% of youngsters have experienced at least one drunkenness episode. It was found that 43.4% have been exposed to alcohol in their families while 35.1% were exposed to tobacco at school or in their neighborhoods. 84.5% stated their intention to continue consuming tobacco during the next year. Results show lower consumption percentages in comparison to school youngsters in Bogotá, Colombia, which may indicate that the armed conflict has not increased consumption levels in this population. Based on the results, certain elements to be taken into account are proposed for the implementation of prevention programs with this population. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  6. Prediction of Smoking, Alcohol, Drugs, and Psychoactive Drugs Abuse Based on Emotional Dysregulation and Child Abuse Experience in People with Borderline Personality Traits

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    M GannadiFarnood

    2014-12-01

    Full Text Available Objective: This research was an attempt to predict the tendency of people having borderline personality traits to smoking, drinking alcohol, and taking psychoactive drugs based on emotional dysregulation and child abuse. Method: This study employed a correlation method which is categorized in descriptive category. A sample including 600 male and female bachelor students of Tabriz University was selected by cluster sampling. Then, high risk behaviors scale, Emotional dysregulation Scale, Child abuse scale, and borderline personality scale (STB were distributed among this group. Findings: Stepwise multiple regression analysis suggested that emotional dysregulation and child abuse significantly predicted varying degrees of smoking, drug, and alcohol usage. Conclusion: The research findings suggest the basic role of initial biological vulnerability in terms of emotional regulation (dysregulation and invalidating family environment (child abuse in the prediction of catching the disorder of borderline personality traits and producing high riskbehaviorssuch as alcohol drink and drug usage.

  7. The effects of psychoactive drugs and neuroleptics on language in normal subjects and schizophrenic patients: a review.

    Science.gov (United States)

    Salomé, F; Boyer, P; Fayol, M

    2000-12-01

    The aim of this survey is to present an overview of research into psychopharmacology as regards the effects of different psychoactive drugs and neuroleptics (NL) on language in normal subjects and schizophrenic patients. Eighteen studies that have investigated the effects of different drugs (alcohol, amphetamines, secobarbital, L-dopa, psilocybin, ketamine, fenfluramine) and neuroleptics (conventional and atypical) on language are reviewed. There are no studies concerning the effects of neuroleptics on language in healthy subjects. The results of the effects of other molecules indicate that language production can be increased (alcohol, amphetamine, secobarbital), rendered more complex (d-amphetamine), more focused (L-dopa) or more unfocused (psilocybin) and clearly impaired (ketamine). For schizophrenic patients, most studies show that conventional neuroleptic treatments, at a therapeutic dosage and in acute or chronic mode, reduce language disorders at all levels (clinic, linguistic, psycholinguistic). In conjunction with other molecules, the classical NL, when administered at a moderate dosage and in chronic mode, modify language in schizophrenia, either by improving the verbal flow and reducing pauses and positive thought disorder (NL + amphetamine) or by inducing an impairment in the language measurements (NL + fenfluramine). Clinical, methodological and theoretical considerations of results are debated in the framework of schizophrenic language disorders.

  8. [Initiation and consumption of psychoactive substances among adolescents and young adults in an Anti-Drug Psychosocial Care Center].

    Science.gov (United States)

    Silva, Carolina Carvalho; Costa, Maria Conceição Oliveira; de Carvalho, Rosely Cabral; Amaral, Magali Teresópolis Reis; Cruz, Nilma Lázara de Almeida; da Silva, Mariana Rocha

    2014-03-01

    The study seeks to characterize the initiation and consumption pattern of psychoactive substances among adolescents and young adults enrolled in an Alcohol and Drug Psychosocial Care Center (CAPS-AD). This study was conducted with records of attendance and the consumption pattern was classified in accordance with WHO: infrequent use (lifetime use, per year or up to five days per month); frequent use (6 to 19 times in the past 30 days); heavy use (≥ 20 times in the last 30 days). In the age group comparison, the test for proportion and association analysis was used and the prevalence and prevalence ratio was calculated with a significance level of 5% and 95% confidence interval. Of the total of adolescents and young adults treated between 2003 and 2008 (475), most were male, single, poorly educated, live with relations and have psychic symptoms. Statistical significance was found for age at initiation of use: adolescents compared to young adults started earlier (≤ 14 years): tobacco, marijuana, cocaine, crack and other SPA consumption. Among adolescents, significant results were found for the less frequent consumption of tobacco, more frequent use of alcohol, and heavy consumption of marijuana. These findings may contribute to the preventive and therapeutic CAPS-AD programs.

  9. 25C-NBOMe: Preliminary Data on Pharmacology, Psychoactive Effects, and Toxicity of a New Potent and Dangerous Hallucinogenic Drug

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    Francesco Saverio Bersani

    2014-01-01

    Full Text Available Introduction. The use of novel psychoactive substances (NPSs has rapidly increased as well as their online availability. The aim of this paper is to provide a comprehensive review of the nature and the risks associated with 25C-NBOMe, which has recently appeared in the drug market. Methods. A systematic analysis of the scientific literature and a qualitative assessment of online and media resources (e.g., e-newsgroups, chat-rooms, and e-newsletters in 10 languages were carried out. Results. 25C-NBOMe is sold online as legal LSD or as research chemical with different designations such as “Boom,” “Pandora,” “Holland film,” or “N-bomb.” It is a partial agonist of 5-HT2A receptors. It is usually ingested orally/sublingually and, less commonly, nasally, through injection, vaginally, rectally, and smoked. Its effects include sublingual numbing, stimulation, “body high,” hallucinations, dissociation, and anxiety. 25C-NBOMe presents high risk of overdoses; acute toxicity and fatalities have been reported. Conclusions. 25C-NBOMe consumption represents an emerging phenomenon with potential harmful effects. Its use is increased by its online availability at low costs. Health and other professionals should be informed about this new trend of substance use.

  10. Concept and Use of Psychoactive Drugs Among University Students in the Sao Paulo Area

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    Zanini, Antonio C.; And Others

    1977-01-01

    This paper presents the results of a medical-social questionnaire made by members of the Scientific Commission of the First International Congress of Drug Addiction Among University Students, Sao Paulo, Brazil, 1974. (Author)

  11. DrugBank: a knowledgebase for drugs, drug actions and drug targets

    OpenAIRE

    Wishart, David S.; Knox, Craig; Guo, An Chi; Cheng, Dean; Shrivastava, Savita; Tzur, Dan; Gautam, Bijaya; Hassanali, Murtaza

    2007-01-01

    DrugBank is a richly annotated resource that combines detailed drug data with comprehensive drug target and drug action information. Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release. With ∼4900 drug ...

  12. Psychoactive Medication and Traffic Safety

    Directory of Open Access Journals (Sweden)

    Joris C. Verster

    2009-03-01

    Full Text Available Driving a car is important to maintain independence and participate in society. Many of those who use psychoactive medication are outpatients and are thus likely to drive a vehicle. Most common adverse effects that impair driving are reduced alertness, affected psychomotor functioning and impaired vision. This review discusses the effects on driving ability of most commonly prescribed psychoactive drugs, including hypnotics, antidepressants, antihistamines, analgesics and stimulant drugs. Within these categories of medicines significant differences concerning their impact on driving ability are evident. The International Council on Alcohol, Drugs and Traffic Safety (ICADTS categorization can help physicians to make a choice between treatments when patients want to drive a car.

  13. Psychoactive drug use by medical students: a review of the national and international literature

    Directory of Open Access Journals (Sweden)

    Ana Maria Mesquita

    Full Text Available Non-medical drug use among medical students is a major concern among researchers and policy makers in several countries, not only because of the personal harmful consequences that may arise from this behavior, but also for the social consequences. This article aims to evaluate national and international data available on non-medical drug-use among medical students and risk factors associated with these problems, as well as social and institutional implications. Prevalence rates, in Brazilian and international samples, of alcohol and drug use, abuse and dependence, reasons for onset, methodological issues, and the role of medical education are presented, compared and discussed. The authors suggest some issues that should be a addressed in order to deal with this complex situation.

  14. [Cartography of psychoactive heterotopias: a look at the medical, legal and social discourses regarding drug use].

    Science.gov (United States)

    Massó, Paloma

    2015-09-01

    This article traces a map of the social control of drugs through the politics of space, according to the Foucaultian concept of "heterotopia." Firstly, a brief genealogy of the use of psychotropic substances in different times and cultures is described, up to the introduction of the prohibitionist paradigm. Attention is paid to the way in which power has marked, separated and enclosed certain rituals and uses of pleasure in physical and symbolic sites. The itinerary is focused on the Spanish context to establish a dialogue between the various policies of space that have come into being and have overlapped in the construction and management of a problem which has been rendered an object to the gazes, mechanics and discourses of the medical, legal, and social fields. In this way, the intersections between the liminal spaces of drug use and the harm reduction paradigm are analyzed, including therapeutic strategies with prescribed drugs, from methadone programs to the new heroin programs.

  15. Novel psychoactive substances of interest for psychiatry

    OpenAIRE

    Schifano, Fabrizio; Orsolini, Laura; Duccio Papanti, G; John M. Corkery

    2015-01-01

    Novel psychoactive substances include synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine-like dissociatives, piperazines, GABA-A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of performance and image enhancing drugs. Users are typically attracted by these substances due to their intense psychoactive effects and likely lack of detection in ...

  16. Use of psychoactive medicines and drugs as a cause of road trauma.

    NARCIS (Netherlands)

    Mathijssen, M.P.M. Movig, K.L.L. Degier, J.J. Nagel, P.H.A. Egmond, T. van & Egberts, A.C.G.

    2004-01-01

    This article deals with the feasibility of a case-control design for determining the relative injury risk of motorists who have used alcohol, and/or illicit drugs, and/or medicines. Methods of data collection are presented, as well as analytical and statistical methods. Preliminary study results

  17. Can the use of psychoactive drugs in the general adult population be estimated based on data from a roadside survey of drugs and driving?

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    Hallvard Gjerde

    2011-12-01

    Full Text Available A roadside survey of drugs and driving was performed in south-eastern Norway in 2005-6. Samples of saliva from a total of 10,503 drivers above 20 years of age were analysed, and the results were weighted for under- and over-sampling compared to the population distribution in the study area. Weighted results were compared with data on dispensed prescriptions of zopiclone, codeine and diazepam at Norwegian pharmacies in the same area and with self-reported use of cannabis. When using roadside data to estimate drug use, the use of medicinal drugs was under-estimated by 17-59% compared to amounts dispensed. One of the main reasons for the under-estimation may be that a large proportion of the users of psychoactive medicinal drugs are not frequent drivers. For cannabis, self-reported data corresponded approximately to the estimated prevalence range. The results indicate that roadside surveys cannot be used for accurate estima tions of drug use in the population, but may provide minimum figures.

  18. The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity.

    Science.gov (United States)

    Colon-Perez, Luis M; Tran, Kelvin; Thompson, Khalil; Pace, Michael C; Blum, Kenneth; Goldberger, Bruce A; Gold, Mark S; Bruijnzeel, Adriaan W; Setlow, Barry; Febo, Marcelo

    2016-08-01

    The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks

  19. Drug addiction and diabetes: South Asian action.

    Science.gov (United States)

    Singh Balhara, Yatan Pal; Kalra, Sanjay

    2017-06-01

    Both diabetes and drug addiction are common phenomena across the world. Drug abuse impacts glycaemic control in multiple ways. It becomes imperative, therefore, to share guidance on drug deaddiction in persons with diabetes. The South Asian subcontinent is home to specific forms and patterns of drug abuse. Detailed study is needed to ensure good clinical practice regarding the same. This communication provides a simple and pragmatic framework to address this issue, while calling for concerted action on drug deaddiction in South Asia.

  20. Toxicokinetics of novel psychoactive substances: characterization of N-acetyltransferase (NAT) isoenzymes involved in the phase II metabolism of 2C designer drugs.

    Science.gov (United States)

    Meyer, Markus R; Robert, Anja; Maurer, Hans H

    2014-06-05

    The 2,5-dimethoxyphenethylamine-derived designer drugs (so-called "2Cs") recently became of great importance on the illicit drug market as stimulating hallucinogens. They are distributed and consumed as "novel psychoactive substances" (NPS) without any safety testing at the forefront. As previous studies have shown, the 2Cs are mainly metabolized by O-demethylation, N-acetylation, or deamination. Therefore, the aim of this study was to elucidate the role of the recombinant human N-acetyltransferase (NAT) isoforms 1 and 2 in the phase II metabolism of 2Cs. For these studies, cDNA-expressed recombinant human NATs were used and formation of metabolites after incubation was measured using GC-MS. NAT2 could be shown to be the only isoform catalyzing the reaction in vitro, hence it should be the only relevant enzyme for in vivo acetylation. In general, all metabolite formation reactions followed classic Michaelis-Menten kinetics and the affinity to human NAT2 was increasing with the volume of the 4-substituent. In consequence, a slow acetylator phenotype or inhibition of NAT2 could lead to decreased N-acetylation and might lead to an increased risk of side effects caused by these novel psychoactive substances. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts' Products

    Science.gov (United States)

    Baumann, Michael H; Partilla, John S; Lehner, Kurt R; Thorndike, Eric B; Hoffman, Alexander F; Holy, Marion; Rothman, Richard B; Goldberg, Steven R; Lupica, Carl R; Sitte, Harald H; Brandt, Simon D; Tella, Srihari R; Cozzi, Nicholas V; Schindler, Charles W

    2013-01-01

    The abuse of psychoactive ‘bath salts' containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [3H]dopamine (IC50=4.1 nℳ) and [3H]norepinephrine (IC50=26 nℳ) with high potency but has weak effects on uptake of [3H]serotonin (IC50=3349 nℳ). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1–0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1–3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of ‘bath salts' preparations. PMID:23072836

  2. Fatores associados ao uso de psicofármacos em idosos asilados Factors associated with the use of psychoactive drugs in institutionalized elderly

    Directory of Open Access Journals (Sweden)

    Giancarlo Lucchetti

    2010-01-01

    psychoactive drugs for the control of behavioral disorders. Few Brazilian studies have so far focused on this aspect of elderly care. OBJECTIVE: To evaluate the factors associated with use of psychoactive drugs in institutionalized elderly patients. METHODS: A cross-sectional, retrospective study was carried out based on medical charts of all elderly patients (60 years and over treated in a nursing home, independently of their diseases. Logistic regression analysis was performed to assess factors associated with the use of psychoactive drugs in the institution. RESULTS: Two hundred and nine patients were evaluated (73.2% females, suffering predominantly of dementia syndromes, sequelae of stroke or cranial trauma, and hypertension. Of these, 123 patients (58.9% were using some type of psychoactive drug, mainly antipsychotics and antidepressants. Logistic regression analysis revealed an association between antipsychotic drug use and dementia (p = 0.000, whereas antidepressant drug use was associated with a higher number of drugs (p = 0.004 and depression (p = 0.000. In general, the use of psychoactive drugs was strongly associated with depression (p = 0.000, dementia (p = 0.006, and psychiatric disorders (p = 0.02. There were no associations with sex, functional status or age. CONCLUSION: There is a high consumption of psychoactive drugs in nursing homes. The association between polypharmacy and depression is evident, and patients with dementia were shown to receive more antipsychotics than other patients. Factors such as age or sex, usually relevant among outpatients, did not present association with psychoactive drug use in nursing home patients.

  3. Standard additions-dilution method for absolute quantification in voltammetry of microparticles. Application for determining psychoactive 1,4-benzodiazepine and antidepressants drugs as adulterants in phytotherapeutic formulations.

    Science.gov (United States)

    Doménech-Carbó, Antonio; Martini, Mariele; de Carvalho, Leandro Machado; Viana, Carine; Doménech-Carbó, María Teresa; Silva, Miguel

    2013-06-01

    A standard additions-dilution solid-state electrochemical method for the determination of psychoactive 1,4-benzodiazepine and antidepressants drugs used as adulterants in commercial slimming herbal formulations is described and compared with conventional standard addition method. The proposed method, based on the voltammetry of microparticles approach, permits quantify, via standard additions methodology, 1,4-benzodiazepine and antidepressants drugs in phytotherapeutic formulations with no need of sample dissolution using dilution with a reference electroactive compound. The method was used to measure 1,4-benzobenzodiazepines (clonazepam, flurazepam, alprazolam, midazolam, bromazepam, chlordiazepoxide, lorazepam and diazepam) and antidepressants (bupropion, sertraline, paroxetine and fluoxetine) in slimming formulations that have been commercialized in Brazil. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. DrugBank: a knowledgebase for drugs, drug actions and drug targets.

    Science.gov (United States)

    Wishart, David S; Knox, Craig; Guo, An Chi; Cheng, Dean; Shrivastava, Savita; Tzur, Dan; Gautam, Bijaya; Hassanali, Murtaza

    2008-01-01

    DrugBank is a richly annotated resource that combines detailed drug data with comprehensive drug target and drug action information. Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release. With approximately 4900 drug entries, it now contains 60% more FDA-approved small molecule and biotech drugs including 10% more 'experimental' drugs. Significantly, more protein target data has also been added to the database, with the latest version of DrugBank containing three times as many non-redundant protein or drug target sequences as before (1565 versus 524). Each DrugCard entry now contains more than 100 data fields with half of the information being devoted to drug/chemical data and the other half devoted to pharmacological, pharmacogenomic and molecular biological data. A number of new data fields, including food-drug interactions, drug-drug interactions and experimental ADME data have been added in response to numerous user requests. DrugBank has also significantly improved the power and simplicity of its structure query and text query searches. DrugBank is available at http://www.drugbank.ca.

  5. DrugBank: a knowledgebase for drugs, drug actions and drug targets

    Science.gov (United States)

    Wishart, David S.; Knox, Craig; Guo, An Chi; Cheng, Dean; Shrivastava, Savita; Tzur, Dan; Gautam, Bijaya; Hassanali, Murtaza

    2008-01-01

    DrugBank is a richly annotated resource that combines detailed drug data with comprehensive drug target and drug action information. Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release. With ∼4900 drug entries, it now contains 60% more FDA-approved small molecule and biotech drugs including 10% more ‘experimental’ drugs. Significantly, more protein target data has also been added to the database, with the latest version of DrugBank containing three times as many non-redundant protein or drug target sequences as before (1565 versus 524). Each DrugCard entry now contains more than 100 data fields with half of the information being devoted to drug/chemical data and the other half devoted to pharmacological, pharmacogenomic and molecular biological data. A number of new data fields, including food–drug interactions, drug–drug interactions and experimental ADME data have been added in response to numerous user requests. DrugBank has also significantly improved the power and simplicity of its structure query and text query searches. DrugBank is available at http://www.drugbank.ca PMID:18048412

  6. Preclinical models of antipsychotic drug action

    Science.gov (United States)

    Moreno, José L.; González-Maeso, Javier

    2016-01-01

    One of the main obstacles faced by translational neuroscience is the development of animal models of psychiatric disorders. Behavioural pharmacology studies indicate that psychedelic drugs, such as lysergic acid diethylamide (LSD) and dissociative drugs, such as phencyclidine (PCP), induce in healthy human volunteers psychotic and cognitive symptoms that resemble some of those observed in schizophrenia patients. Serotonin 5-HT2A and metabotropic glutamate 2 receptors have been involved in the mechanism of action of psychedelic and dissociative drugs. Here we review recent advances using LSD-like and PCP-like drugs in rodent models that implicate these receptors in the neurobiology of schizophrenia and its treatment. PMID:23745738

  7. A cloud on the horizon-a survey into the use of electronic vaping devices for recreational drug and new psychoactive substance (NPS) administration.

    Science.gov (United States)

    Blundell, M; Dargan, P; Wood, D

    2018-01-01

    There is limited published scientific data on vaping recreational drugs other than cannabis. A recent review suggested that 15% of people vaping cannabis have also vaped a synthetic cannabinoid receptor agonist (SCRA) and identified over 300 Internet reports of e-liquid manufacture of recreational drugs and/or new psychoactive substances (NPS). To determine the prevalence of use of electronic vaping devices for recreational drug and NPS delivery in the UK. A voluntary online survey using a convenience sample of UK adult participants (aged 16 years old and over) identified by a market research company. Data was collected regarding demographics, smoking history, electronic vaping device history and recreational drug/NPS use and route of administration. There were 2501 respondents. The mean (±SD) age was 46.2 ± 16.8 years old. The commonest lifetime recreational drug used was Cannabis (818, 32.7%). The majority of respondents had smoked (1545, 61.8%) with 731 (29.2%) being current smokers. The most commonly used SCRA product was 'Spice Gold' (173, 6.9%) and SCRA compound was ADB-CHMICA (48, 1.9%). 861 (34.4%) had used an electronic vaping device; 340 (13.6%) having used them for recreational drug administration; 236 (9.4%) reporting current use. The commonest lifetime recreational drug to be vaped was cannabis (155, 65.7%), with electronic cigarettes (230, 48.2%) being the commonest reported route of SCRA compound administration. 9.4% of respondents currently use electronic vaping devices for recreational drug administration with 6.2% reporting lifetime cannabis vaping use. Further larger scale studies are required to help inform the appropriate treatment and primary prevention strategies.

  8. Assessment of Lemna minor (duckweed) and Corbicula fluminea (freshwater clam) as potential indicators of contaminated aquatic ecosystems: responses to presence of psychoactive drug mixtures.

    Science.gov (United States)

    Mohamed, Bourioug; Jean-Yves, Mazzitelli; Pierre, Marty; Hélène, Budzinski; Aleya, Lotfi; Elsa, Bonnafé; Florence, Geret

    2017-01-31

    The pharmaceutical products are emerging pollutants continuously released into the environment, because they cannot be effectively removed by the wastewater treatment plants. In recent years, questions have been raised concerning the environmental risks related to these pollutants. The goal of this research was to evaluate the responses in Lemna minor after 7 days and in Corbicula fluminea after differing durations (1, 3, 7, and 19 days) of exposure to the psychoactive drug mixture (valproic acid, citalopram, carbamazepine, cyamemazine, hydroxyzine, oxazepam, norfluoxetine, lorazepam, fluoxetine, and sertraline) in different concentrations (0, 0 + ethanol, drug concentration (DC) 1 = river water concentration, DC2 = effluent concentration, and DC3 = 10× effluent concentration). In this aim, growth parameters of L. minor, gluthathione S-transferase (GSTs), catalase (CAT), ethoxyresorufin-O-deethylase (EROD) and/or gene expressions (pi-gst, cat, cytochrome P450 4 (cyp4), multidrug resistant 1 (mdr1), and superoxide dismutase (sod)) were measured. GST activities increased significantly in L. minor exposed to DC3, but no changes were found in CAT activity. In C. fluminea, EROD activity was induced significantly in both gill and digestive gland tissues after 3 days' exposure to DC3, while a GST increase was observed only in digestive gland tissues, suggesting that these pharmaceuticals induced an oxidative effect. Gene expression analysis revealed transient transcriptomic responses of cyp4, sod, and mdr1 under drug concentrations 2 or 3 and no change of expression for the other genes (cat and pi-gst) or condition (environmental drug concentration) tested. Finally, the data reported in this study represent important ecotoxicological information, confirming that this enzyme family (cyp4, sod, and mdr1) may be considered as a sensible and early indicator of exposure to drugs and emphasizing the involvement of selected genes in detoxification pathways.

  9. New psychoactive substances as part of polydrug abuse within opioid maintenance treatment revealed by comprehensive high-resolution mass spectrometric urine drug screening.

    Science.gov (United States)

    Heikman, Pertti; Sundström, Mira; Pelander, Anna; Ojanperä, Ilkka

    2016-01-01

    At present, polydrug abuse comprises, besides traditional illicit drugs, new psychoactive substances (NPS) and non-prescribed psychotropic medicines (N-PPM). Polydrug abuse was comprehensively evaluated among opioid-dependent patients undergoing opioid maintenance treatment (OMT). Two hundred consecutively collected urine samples from 82 OMT patients (52 male) treated with methadone or buprenorphine-naloxone medication were studied using a liquid chromatography/time-of-flight mass spectrometry screening method. The method enables simultaneous detection of hundreds of abused substances covering the traditional drugs of abuse and many NPS as well as N-PPM. Ninety-two (45.8%) samples were positive for the abused substances. Benzodiazepines (29.0%), amphetamines (19.5%), cannabinoids (17.0%), NPS (13.0%), N-PPM (9.0%), and opioids (9.0%) were detected in different combinations. The simultaneous occurrence of up to three groups of abused substances was common (40.0%), and in one sample, all six groups were found. The stimulant NPS alpha-pyrrolidinovalerophenone was found in 10.0% and the sedative N-PPM pregabalin in 4.0% of the samples. The patients were seldom aware of what particular NPS they had abused. A widespread occurrence of abused substances beyond the ordinary was revealed. Identifying these patients is essential as polydrug abuse is a safety risk to the patient and may cause attrition from OMT. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Analysis of projects developed by teachers: the challenge of preventing psychoactive drug use and violence among young people in Medellín

    Directory of Open Access Journals (Sweden)

    Ana C. Jaramillo M

    2012-02-01

    Full Text Available Objective: to analyze the development of projects formulated by professional teachers who are students of the certified course named “Red Formemos Educadores 2008-2010”. The projects were formulated in order to prevent violence and psychoactive drug use among the young students of Medellín, Colombia. Methodology: the Methodological elements proposed by grounded theory were used. Data collection was carried out in three stages: 1 one group interview, 2 four individual in-depth interviews, and 3 two individual in-depth interviews with two teachers and two interviews of the same nature with two members from the SURGIR NGO. No theories were formulated. Results: an important reason to develop prevention projects is the well-being of the young individuals living in communities where violence and drug use are common. Teacher motivation allowed for the successful development of the projects. Conversely, a lack of motivation led to withdrawal from the certified course. Discussion: the various problems of the teachers’ social environment have a direct effect on their motivations. For some teachers, the lack of time is an obstacle to carry out the academic activities proposed during the certified course. A motivated teacher can successfully face the difficulties encountered during the project development process

  11. Use of psychoactive drugs and related falls among older people living in a community in Brazil Uso de medicamentos psicoativos e seu relacionamento com quedas entre idosos

    Directory of Open Access Journals (Sweden)

    Flávio Chaimowicz

    2000-12-01

    Full Text Available INTRODUCTION: Population aging in Brazil has increased the prevalence of neurodegenerative diseases (Parkinson's and Alzheimer's disease and affective disorders (anxiety, depression, all common in old age. A retrospective study was carried out with the purpose of ascertaining if there is an association between falls and psychoactive medication use among older residents of a community in Brazil. METHODS: All residents aged 65+ (n=161 of one neighborhood of Campo Belo, Brazil (population of 48,000 were evaluated regarding the use of psychoactive drugs and the occurrence of falls in the 12 months preceding the study. Vision and hearing screenings were also performed. RESULTS: From the study population, 9.3% were taking prolonged half-life benzodiazepines, 4.4% anticonvulsants (mostly barbiturates, 2.5% antidepressants (all cyclics and 8.1% alpha-methyldopa. No subject reported use of hypnotics, neuroleptics or drugs to treat Alzheimer's or Parkinson's diseases (except biperiden. As a whole, drugs that increase the risk of falls were used by 1/5 of this population. In the 12-month period preceding the study, 27 residents (16.8% experienced falls and, of those, 4 (14.8% had fracture(s. There was an independent association between psychoactive drug use and falls when variables such as age, gender, vision and hearing were controlled (p=0.02. CONCLUSIONS: Although the population of this neighborhood must be considered young (only 4% are 65 years old or more, there are already problems related to the use of psychoactive drugs among people. Prescribed anxiolytics, anticonvulsants, antidepressants and antihypertensives are not appropriate for this age group and their use is associated with falls.INTRODUÇÃO: O envelhecimento populacional no Brasil tem aumentado a prevalência de doenças neurodegenerativas (Parkinson, Alzheimer e psiquiátricas (depressão, ansiedade, comuns em idosos. Realizou-se estudo retrospectivo com o objetivo de determinar se h

  12. Rapid detection by direct analysis in real time-mass spectrometry (DART-MS) of psychoactive plant drugs of abuse: the case of Mitragyna speciosa aka "Kratom".

    Science.gov (United States)

    Lesiak, Ashton D; Cody, Robert B; Dane, A John; Musah, Rabi A

    2014-09-01

    Mitragyna speciosa, also known commonly as "Kratom" or "Ketum", is a plant with psychoactive properties that have been attributed to the presence of various indole alkaloids such as mitragynine and 7-hydroxymitragynine. M. speciosa use is gaining popularity internationally as a natural and legal alternative to narcotics. As a drug of abuse, its detection and identification are not straightforward, since M. speciosa plant material is not particularly distinctive. Here, we show that direct analysis in real time-mass spectrometry (DART-MS) can be used not only to rapidly identify M. speciosa plant material and distinguish it from other plants, but also to distinguish between M. speciosa plant varieties, based on differences between their chemical profiles. The method is rapid and the analysis expeditious. Plant material such as that found at a crime scene can be analyzed directly with no sample pre-preparation steps. Furthermore, we show that the basis set of principal components that permit characterization of the plant material can be used to positively identify M. speciosa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Modes of action of anthelmintic drugs.

    Science.gov (United States)

    Martin, R J

    1997-07-01

    Modes of action of anthelmintic drugs are described. Some anthelmintic drugs act rapidly and selectively on neuromuscular transmission of nematodes. Levamisole, pyrantel and morantel are agonists at nicotinic acetylcholine receptors of nematode muscle and cause spastic paralysis. Dichlorvos and haloxon are organophosphorus cholinesterase antagonists. Piperazine is a GABA (gamma-amino-butyric acid) agonist at receptors on nematode muscles and causes flaccid paralysis. The avermectins increase the opening of glutamate-gated chloride (GluCl) channels and produce paralysis of pharyngeal pumping. Praziquantel has a selective effect on the tegument of trematodes and increases permeability of calcium. Other anthelmintics have a biochemical mode of action. The benzimidazole drugs bind selectively to beta-tubulin of nematodes, cestodes and fluke, and inhibit microtubule formation. The salicylanilides: rafoxanide, oxyclozanide, brotianide and closantel and the substituted phenol, nitroxynil, are proton ionophores. Clorsulon is a selective antagonist of fluke phosphoglycerate kinase and mutase. Diethylcarbamazine blocks host, and possibly parasite, enzymes involved in arachidonic acid metabolism, and enhances the innate, nonspecific immune system.

  14. Characteristics of the use of 3-MMC and other new psychoactive drugs in Slovenia, and the perceived problems experienced by users.

    Science.gov (United States)

    Sande, Matej

    2016-01-01

    The study presents the characteristics of the use of new psychoactive substances (NPS), the perceived problems experienced by users, and the reasons for cessation or cutting down. The research focused mainly on synthetic cathinones and the use of 3-MMC in Slovenia. In order to research the characteristics of NPS use, we used a questionnaire which had been developed to determine the characteristics of the use of ATS and cocaine in the context of nightlife and was elaborated in our study on the use of mephedrone. The final non-representative sample included 249 users of NPS from Slovenia, who had completed an on-line survey over a period of 5 months in 2014. Part of the sampling was conducted on the ground and with the help of peer-groups. DrogArt's outreach workers and correspondents visited open public places, clubs, and discotheques to encourage users to participate in the survey. Most users of NPS in Slovenia have tried NPS from the groups of synthetic cathinones and amphetamines. Most respondents included in the sample (67.9%) have tried 3-MMC, while 43.0% have tried methylone and 37.3% have tried mephedrone (4-MMC). Users attributed greater risks to the use of new drugs and preferred the effects of traditional drugs to those of new drugs. The most frequently reported problems were depression (55.2% of users), concentration difficulties (44.0%), damage to the mucous membrane of the nose and to the throat (39.8%), feelings of fear and anxiety (39.4%), and tingling in the arms or legs (34.4%). The main reasons for cutting down or discontinuing the use of NPS were 'fear of the health consequences', 'actual health consequences', and 'growing weary of using'. Among users of NPS, 7% have sought help, while 9.1% have considered doing so. The results also highlight differences between the NPS drug markets in Slovenia and the United Kingdom. In 2014, the most frequently used NPS in Slovenia were synthetic cathinones such as 3-MMC. Users experienced various problems

  15. Self-admitted behavior and perceived use of performance-enhancing vs psychoactive drugs among competitive athletes.

    Science.gov (United States)

    Uvacsek, M; Nepusz, T; Naughton, D P; Mazanov, J; Ránky, M Zs; Petróczi, A

    2011-04-01

    The relationships between projected use, self-reported behavior and attitudes to performance-enhancing (PED) and recreational (RD) drugs were investigated among 82 competitive Hungarian athletes, with 14.6% admitting using PED and 31.7% using RD. Both the observed doping estimations (even those made by non-users) and self-admitted use were considerably higher than the average rate of positive doping tests (2% of all tests). The notable overestimation by PED users (34.6% vs 16.9%) was in keeping with the false consensus effect. A prediction model with attitude and projection to the likelihood of PED use suggested at least a 70% chance of self-involvement of athletes, with responses at or above the median scores (Performance Enhancement Attitude Scale ≥ 60 and estimation ≥ 50%) on the two independent measures. Users overestimated the prevalence of doping in their sport (P=0.007) but not RD use, with the converse holding for RD users' views of doping (P=0.029). PED users also showed a significantly more lenient attitude toward doping (P<0.001). This domain-specific characteristic adds new information to the ongoing research effort in understanding drug-doping co-morbidity. The reasons for elevated in-group projection are discussed, along with the potential application of this phenomenon in doping epidemiology studies. © 2009 John Wiley & Sons A/S.

  16. Chiral resolution and absolute configuration of the enantiomers of the psychoactive "designer drug" 3,4-methylenedioxypyrovalerone.

    Science.gov (United States)

    Suzuki, Masaki; Deschamps, Jeffrey R; Jacobson, Arthur E; Rice, Kenner C

    2015-04-01

    Illicit rac-MDPV (3,4-methylenedioxypyrovalerone), manufactured in clandestine labs, has become widely abused for its cocaine-like stimulant properties. It has recently been found as one of the toxic materials in the so-called "bath salts," producing, among other effects, psychosis and tachycardia in humans when introduced by any of the several routes of administration (e.g., intravenous, oral, etc.). The considerable toxicity of this "designer drug" probably resides in one of the enantiomers of the racemate. In order to obtain a sufficient amount of the enantiomers of rac-MDPV to determine their activity, we improved the known synthesis of rac-MDPV and found chemical resolving agents, (+)- and (-)-2'-bromotetranilic acid, that gave the MDPV enantiomers in >96% enantiomeric excess as determined by (1) H nuclear magnetic resonance and chiral high-performance liquid chromatography. The absolute stereochemistry of these enantiomers was determined by single-crystal X-ray diffraction studies. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  17. Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions.

    Science.gov (United States)

    Shen, Hong-Wu; Jiang, Xi-Ling; Winter, Jerrold C; Yu, Ai-Ming

    2010-10-01

    5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination pathway mediated by monoamine oxidase A (MAO-A). 5-MeO-DMT is often used with MAO-A inhibitors such as harmaline. Concurrent use of harmaline reduces 5-MeO-DMT deamination metabolism and leads to a prolonged and increased exposure to the parent drug 5-MeO-DMT, as well as the active metabolite bufotenine. Harmaline, 5-MeO-DMT and bufotenine act agonistically on serotonergic systems and may result in hyperserotonergic effects or serotonin toxicity. Interestingly, CYP2D6 also has important contribution to harmaline metabolism, and CYP2D6 genetic polymorphism may cause considerable variability in the metabolism, pharmacokinetics and dynamics of harmaline and its interaction with 5-MeO-DMT. Therefore, this review summarizes recent findings on biotransformation, pharmacokinetics, and pharmacological actions of 5-MeO-DMT. In addition, the pharmacokinetic and pharmacodynamic drug-drug interactions between harmaline and 5-MeO-DMT, potential involvement of CYP2D6 pharmacogenetics, and risks of 5-MeO-DMT intoxication are discussed.

  18. La vivencia de la dependencia en un consumidor de drogas psicoactivas The experience of the dependence to a psychoactive drug in a consumer drug

    Directory of Open Access Journals (Sweden)

    Liliana Basso Musso

    2011-06-01

    Full Text Available Investigación cualitativa, de trayectoria fenomenológica, siguiendo el referencial sociológico de Schutz, cuyo objetivo es conocer la vivencia del fenómeno de la dependencia o adicción, en un consumidor de drogas psicoactivas en tratamiento en un Centro Abierto, teniendo como base las siguientes preguntas orientadoras: ¿Cómo se inició la experiencia de consumo de drogas? ¿Cuáles fueron los motivos para consumir drogas? ¿Cómo se va instalando la dependencia a ellas? ¿Cómo se dio cuenta que se había hecho dependiente a la droga? En el discurso de los consumidores se identificaron siete categorías del referencial de Shutz, que muestran aspectos significativos de la vivencia. Al analizarlas se pudo comprender al tipo vivido del consumidor de drogas psicoactivas que presenta adicción y el entendimiento de los motivos existenciales que influyeron en la instalación de esta dependencia, profundizándose así el conocimiento del fenómeno, lo que permitirá otorgarles un mejor cuidado.Qualitative, phenomenological research following Schutz, referential sociological, whose objective is to know the experience of the phenomenon of dependence or addiction to a consumer of drugs in treatment in an open centre, based on the following questions guide path: How do you start drug experience? What were the reasons for drug use? You how is it installing dependence to them? How gave account which had become dependent drug? The speech of consumers identified seven categories Schutz, referential, that showing significant aspects of the experience. To analyze them lived type drugs featuring addiction and understanding of the existential reasons that influenced the installation of this dependency, deepening the understanding of the phenomenon, thereby granting consumer could understand better care.

  19. Propagandas de medicamentos psicoativos: análise das informações científicas Psychoactive drug advertising: analysis of scientific information

    Directory of Open Access Journals (Sweden)

    Patrícia C Mastroianni

    2008-06-01

    , medicinal drug promotion should be reliable, accurate, truthful, informative, balanced, up-to-date and capable of substantiation. The objective of the present study was to review psychoactive drug advertisements to physicians as for information consistency with the related references and accessibility of the cited references. METHODS: Data was collected in the city of Araraquara, Southeastern Brazil, in 2005. There were collected and reviewed 152 drug advertisements, a total of 304 references. References were requested directly from pharmaceutical companies' customer services and searched in UNESP (Ibict, Athenas and BIREME (SciELO, PubMed, free-access indexed journals library network and CAPES journals. Advertisement statements were checked against references using content analysis. RESULTS: Of all references cited in the advertisements studied, 66.7% were accessed. Of 639 promotional statements identified, 346 (54% were analyzed. The analysis showed that 67.7% of promotional statements in the advertisements were consistent with their references, while the remaining was either partially consistent or inconsistent. Of the material analyzed, an average 2.5 (1-28 references was cited per advertisement. In the text body, there were identified 639 pieces of information clearly associated with at least one cited reference (average 3.5 pieces of information per advertisement. CONCLUSIONS: The study results evidenced difficult access to the references. Messages on efficacy, safety and cost, among others, are not always supported by scientific studies. There is a need for regulation changes and effective monitoring of drug promotional materials.

  20. Psychoactive substance use and the risk of motor vehicle accidents

    NARCIS (Netherlands)

    Movig, K.L.; Mathijssen, M.P.; Nagel, P.H.; van Egmond, T.; de Gier, J.J.; Leufkens, H.G.; Egberts, A.C.

    The driving performance is easily impaired as a consequence of the use of alcohol and/or licit and illicit drugs. However, the role of drugs other than alcohol in motor vehicle accidents has not been well established. The objective of this study was to estimate the association between psychoactive

  1. Basic Mechanisms of Action of the Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    Kuzmanova R.

    2017-10-01

    Full Text Available Available antiepileptic drugs interact with a variety of different molecular targets. The mechanism of action of most anticonvulsants is most often complex with a number of affected regions. The combination of mechanisms of action of drugs in particular proportions can possibly determine the showcase of its antiepileptic activity. The common factor between the different supposed mechanisms for a number of drugs includes the possibility for modulating the excitatory and inhibitory neurotransmission through effects upon the voltage-gated ion channels, synaptic plasticity, heterogeneous receptors, and metabolism of neurotransmitters. There are controversial data on the extent to which a specific action can be the reason for the wholesome anticonvulsive characteristics of various medications, as well as the relation with the presence of undesired drug effects. The complexity of the action of some antiepileptic drugs creates conditions for optimal choice during therapy. In many cases, the insufficient familiarity with individual genetic differences and the disease related receptor damages can hinder defining a particular drug action. Characterizing the mechanisms of action of the present antiepileptic medications would increase the understanding for the pathophysiological mechanisms of epileptic seizures, as well as the development of new therapeutic strategies. The development of novel antiepileptic drugs and the ongoing research regarding the mechanism of action of established antiepileptic drugs, are continuously increasing the level of complexity in the spectrum of molecular targets relevant for epilepsy therapy. The current state of knowledge as well as the limitations in our understanding should guide future research aiming for a more detailed elucidation of the impact of genetics and pathophysiological mechanisms on interindividual differences in expression and function of antiepileptic drug targets.

  2. Is dried paw-paw leaf a psychoactive substance | Olley | IFE ...

    African Journals Online (AJOL)

    While many studies have looked at the prevalence and pattern as well as effects of drug abuse and dependence among Nigerians, the use of dried paw-paw leaf as a psychoactive substance has not been investigated. This study examines the attitude and perception towards dried paw-paw leaf as a psychoactive ...

  3. Use of psychoactive substances in students at a public university

    Directory of Open Access Journals (Sweden)

    Meire Luci da Silva

    2014-11-01

    Full Text Available Introduction: The use of psychoactive substances by the student population has been the object of various studies in Brazil. Objective: To determine the prevalence of substance use among students. Methods: Quantitative study with a closed questionnaire based on standardized assessment instruments was developed. It consists of questions related to types of psychoactive substance use, abuse, frequency and duration of use, self-criticism regarding the use, consequences of use in relation to health, and misdemeanors committed under the influence of psychoactive substances. The sample included the participation of 268 students. A total of 183 (68.3% questionnaires were analyzed, and only those with positive result for substance abuse at some point in life, the remainder, 85 (31% questionnaires, had negative responses to psychoactive substances. Results: Students’ responses to the two years surveyed indicated that the first psychoactive substance used was alcohol (77.9%, followed by tobacco use (10.9%, and marijuana (7.6%. Of the students surveyed, 145 (79.2% answered that still make use of psychoactive substances, and the current frequency of use varies from one or more times per week. When asked about the possibility of being or becoming drug addicts, 169 (92.3% responded that they are not or will not become dependent. Conclusion: The results indicate the high rate of substance use among college students surveyed, and point to their contradiction to consider such psychoactive substances harmful to their health.

  4. Use of psychoactive substances among commercial motorcyclists in ...

    African Journals Online (AJOL)

    Commonly identified psychoactive substance/drugs used were: marijuana [Indian hemp] 25.8%, solution 24.5%, caffeine (Kola) 15.8%, and coffee 4.8%. ... It is further recommended that law enforcement agencies (NAFDAC, NDLEA and FRSC) need to work in tandem so as to curb the problem of substance abuse in our ...

  5. Pattern and practice of psychoactive substance abuse and risky ...

    African Journals Online (AJOL)

    education, shelter, food, hygiene, healthcare and a loving family has been violated.[1] Street children ... drugs to minors is a crime punishable by law in most countries, implementation of the law is ... psychoactive substance abuse and the related behaviours among street children in Cameroon. The information is critical to ...

  6. Psychoactive pharmaceutical residues in the watersheds of Galicia (Spain).

    Science.gov (United States)

    Esteban, Sara; Valcárcel, Yolanda; Catalá, Myriam; Castromil, Miguel González

    2012-01-01

    To monitor the presence of pharmaceutical residues of 14 psychoactive drugs belonging to three therapeutic groups in the watersheds of Galicia (Spain). Five sewage treatment plants were selected in the main cities of Galicia. Thirteen psychoactive pharmaceutical compounds and one metabolite were chosen. In addition, tap water samples were taken from public places and private residences in the selected cities. In all the water samples analyzed, the highest concentrations corresponded to the group of anxiolytics. In particular, high concentrations of lorazepam were found in river and tap water samples. This investigation demonstrates the presence of psychoactive pharmaceuticals in the watersheds of the autonomous region of Galicia and the conversion of metabolites to parent compounds. This work also shows the need to increase environmental monitoring of watersheds and to improve sewage and drinking water treatment processes to remove these pharmaceuticals. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.

  7. Application of Conformational Space Search in Drug Action | Adikwu ...

    African Journals Online (AJOL)

    The role of conformational space in drug action is presented. Two examples of molecules in different therapeutic groups are presented. Conformational space search will lead to isolating the exact conformation with the desired medicinal properties. Many conformations of a plant isolate may exist which are active, weakly ...

  8. Determinants of knowledge and use of psychoactive substance among commercial motorcyclist in Sokoto metropolis, Northwest Nigeria

    Directory of Open Access Journals (Sweden)

    M.O.Raji

    2017-01-01

    Full Text Available Background Substance abuse, also known as drug abuse, is a patterned use of a drug in which the user consumes the substance in amounts or with methods which are harmful to themselves or others, and is a form of substance related disorder. Riding commercial motorcycle entails lot of risk, compounded by abuse of drugs, the scenario can only be worse. This study aimed to assess the determinants of knowledge and use of psychoactive substances among commercial motorcyclist in Sokoto metropolis. Methods The study was a cross sectional descriptive study conducted in Sokoto metropolis, among Commercial motorcyclist, 253 respondents were recruited using multi stage sampling technique. Data was obtained using interviewer administered structured questionnaire containing 47‐item structured questions. Data was analysed using IBM statistical software package version 21, 5% was set as level of significance Result Majority of respondent believed that use of alcohol 214 (84.6, cannabis 147 (58.1 and codeine 171 (67.6 can lead to mental problems. Thirty percent of the respondents reported ever use of psychoactive substances. Most of the respondents (49.3% initiated use of Psychoactive substances between 16‐20 years of age. Respondents who had some formal education had less odds of ever using psychoactive substances (p=0.001, OR= 0.337. Respondents who had ever encouraged fellow commercial motorcyclist to use psychoactive substances had 22 times odds of ever having used psychoactive substances (p=0.000 Conclusion Substance abuse is prevalent among commercial motorcyclist. Despite good knowledge of psychoactive substances and the consequences associated with it, the use was still relatively high. The main predictor of ever use of psychoactive substances was willingness to be friends with someone who use psychoactive substance. There is need for continuous counselling and education of commercial motorcyclist, by road safety workers, on the dangers associated

  9. ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS

    Science.gov (United States)

    Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.

    2014-01-01

    Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. PMID:24656971

  10. Injection of new psychoactive substance snow blow associated with recently acquired HIV infections among homeless people who inject drugs in Dublin, Ireland, 2015.

    LENUS (Irish Health Repository)

    Giese, Coralie

    2015-10-08

    In February 2015, an outbreak of recently acquired HIV infections among people who inject drugs (PWID) was identified in Dublin, following similar outbreaks in Greece and Romania in 2011. We compared drug and risk behaviours among 15 HIV cases and 39 controls. Injecting a synthetic cathinone, snow blow, was associated with recent HIV infection (AOR: 49; p = 0.003). Prevention and control efforts are underway among PWID in Dublin, but may also be needed elsewhere in Europe.

  11. Evidence for an inhibitory presynaptic component of neuroleptic drug action.

    OpenAIRE

    de Belleroche, J. S.; Bradford, H. F.

    1981-01-01

    1 The action of five neuroleptic drugs (haloperidol, cis-flupenthixol, chlorpromazine, fluphenazine and thioridazine) was studied on the synthesis and release of dopamine from rat striatal synaptosomes. 2. In vitro application of the drugs induced an inhibition of synthesis of [14C]-dopamine from L-[U-14C]-tyrosine and a decrease in the tissue content of [14-C]-dopamine, with IC50 values for the latter effect ranging from 3.6 x 10(-7) to 5.9 x 10(-5) M. The rank of their potency was similar t...

  12. A study of nootropic drugs for anti-anxiety action.

    Science.gov (United States)

    Petkov, V D; Getova, D; Mosharrof, A H

    1987-01-01

    The effects of adafenoxate (100 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg), piracetam (250 mg/kg), and standardized ginseng extract-G115 (100 mg/kg) applied for five days were studied with Vogel's conflict procedure in which thirsty naive rats were periodically administered shocks for licking water. The results showed a significant anti-anxiety effect (increases in licking) with adafenoxate and meclofenoxate. Piracetam significantly suppressed licking behaviour and this effect was evaluated as anxiogenic (resulting from the non-specific stimulant action of the drug). Adafenoxate was found to increase also the number of entries into and escapes from the dark compartment without punishment responding. This effect of adafenoxate was considered to be an expression of facilitated conditioned-reflex activity. A beneficial role for the observed anti-anxiety effects of adafenoxate and meclofenoxate in the nootropic action of these drugs is suggested.

  13. What products are considered psychoactive under New Zealand's legal market for new psychoactive substances (NPS, 'legal highs')? Implications for law enforcement and penalties.

    Science.gov (United States)

    Rychert, Marta; Wilkins, Chris

    2016-08-01

    The problem of defining what psychoactive products and substances should be covered by legislation aimed at controlling new psychoactive substances (NPS; 'legal highs') is central to the current debate on designing new legislative responses to NPS. In New Zealand, implementation of the Psychoactive Substances Act 2013 (PSA) revealed uncertainties about which psychoactive products are covered by the new regime, with important implications for legal penalties. We reviewed five pieces of legislation which can cover substances with psychoactive properties: PSA, Misuse of Drugs Act (MODA), Food Act, Dietary Supplements Regulations and Medicines Act. Our analysis revealed that a number of psychoactive substances which are not MODA-scheduled may potentially fall under more than one regulatory regime, including kava, Salvia divinorum, nitrous oxide, 25I-NBOMe, and 1,3-dimethylbutylamine (DMBA). For example, kava may be classified as a food, a dietary supplement, a herbal remedy, or a psychoactive substance, depending on how it is presented (including advertising and labelling). There are considerable differences in penalties and regulatory requirements between the different legislative regimes and these may result in unnecessary prosecutions or 'gaming' of the system. We discuss a number of ways to more clearly categorize products, including a public schedule of psychoactive substances and products, demarcation criteria based on the quantity of the active ingredient, and demarcation based on 'discernible intoxication'. Routine use of forensic testing is essential to ensure appropriate prosecutions and penalties. Robust safety standards are also required in legislative regimes exempted from psychoactive substances regime to prevent 'creative compliance'. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Psychedelic 5-Methoxy-N,N-dimethyltryptamine: Metabolism, Pharmacokinetics, Drug Interactions, and Pharmacological Actions

    OpenAIRE

    Shen, Hong-Wu; Jiang, Xi-Ling; Winter, Jerrold C.; Yu, Ai-Ming

    2010-01-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination pathway mediated by monoamine oxidase A (MAO-A). 5-MeO-DMT is often used with MAO-A inhibitors such as h...

  15. Psychoactive "bath salts" intoxication with methylenedioxypyrovalerone.

    Science.gov (United States)

    Ross, Edward A; Reisfield, Gary M; Watson, Mary C; Chronister, Chris W; Goldberger, Bruce A

    2012-09-01

    Abuse of the psychoactive "designer drug" methylenedioxypyrovalerone (MDPV) has become a serious international public health concern because of the severity of its physical and behavioral toxicities. MDPV is the primary ingredient in so-called "bath salts," labeled as such to avoid criminal prosecution and has only been classified recently as a controlled substance in the United States and some other countries. However, it remains a danger because of illegal sources, including the Internet. MDPV is a synthetic, cathinone-derivative, central nervous system stimulant and is taken to produce a cocaine- or methamphetamine-like high. Administered via oral ingestion, nasal insufflation, smoking, intravenous or intramuscular methods, or the rectum, the intoxication lasts 6 to 8 hours and has high addictive potential. Overdoses are characterized by profound toxicities, causing increased attention by emergency department and law enforcement personnel. Physical manifestations range from tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, and seizures to those as severe as stroke, cerebral edema, cardiorespiratory collapse, myocardial infarction, and death. Behavioral effects include panic attacks, anxiety, agitation, severe paranoia, hallucinations, psychosis, suicidal ideation, self-mutilation, and behavior that is aggressive, violent, and self-destructive. Treatment is principally supportive and focuses on counteracting the sympathetic overstimulation, including sedation with intravenous benzodiazepines, seizure-prevention measures, intravenous fluids, close (eg, intensive care unit) monitoring, and restraints to prevent harm to self or others. Clinical presentation is often complicated by coingestion of other psychoactive substances that may alter the treatment approach. Clinicians need to be especially vigilant in that MDPV is not detected by routine drug screens and overdoses can be life-threatening. Copyright © 2012 Elsevier Inc. All rights

  16. Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

    Science.gov (United States)

    Wenthur, Cody J.; Zhou, Bin; Janda, Kim D.

    2017-08-01

    Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and ‘pharmacoterrorism’ in the Middle East. Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it also incorporates a covalently linked xanthine moiety into its parent structure. These independently active pharmacophores are liberated during metabolism, resulting in the release of a structurally diverse chemical mixture into the central nervous system. Although the psychoactive properties of fenethylline have been reported to differ from those of other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects. Here we develop a ‘dissection through vaccination’ approach, called DISSECTIV, to mitigate the psychoactive effects of fenethylline and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against a single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacological activity. We anticipate that DISSECTIV will be used to expose unidentified active chemical species and resolve pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples and natural product extracts.

  17. Neuropharmacological Targets for Drug Action in Vestibular Sensory Pathways.

    Science.gov (United States)

    Lee, Choongheon; Jones, Timothy A

    2017-09-01

    The use of pharmacological agents is often the preferred approach to the management of vestibular dysfunction. In the vestibular sensory pathways, the sensory neuroepithelia are thought to be influenced by a diverse number of neuroactive substances that may act to enhance or inhibit the effect of the primary neurotransmitters [i.e., glutamate (Glu) and acetylcholine (ACh)] or alter their patterns of release. This review summarizes various efforts to identify drug targets including neurotransmitter and neuromodulator receptors in the vestibular sensory pathways. Identifying these receptor targets provides a strategic basis to use specific pharmacological tools to modify receptor function in the treatment and management of debilitating balance disorders. A review of the literature reveals that most investigations of the neuropharmacology of peripheral vestibular function have been performed using in vitro or ex vivo animal preparations rather than studying drug action on the normal intact vestibular system in situ. Such noninvasive approaches could aid the development of more accurate and effective intervention strategies for the treatment of dizziness and vertigo. The current review explores the major neuropharmacological targets for drug action in the vestibular system.

  18. A "parliamentary inquiry" into alcohol and drugs: a survey of psychoactive substance use and gambling among members of the Dutch parliament.

    Science.gov (United States)

    Hendriks, V M; Garretsen, H F; van de Goor, L A

    1997-05-01

    In the fall of 1994 a survey was conducted on the use of alcohol and drugs and on gambling among members of the Dutch parliament. The survey indicated that almost two-thirds of the representatives sampled supported legalization of marijuana. A smaller majority (57%) was in favor of reducing the number of coffee shops selling marijuana. At least a quarter of the members of parliament had used marijuana themselves at one time or other. Alcohol consumption could be said to be "excessive" or "very excessive" for nearly 10% of the members of parliament. In general, the nature and extent of the parliamentarians' substance use was comparable to that in the Dutch general population.

  19. Progress in antihypertensive therapy with a multiple-action drug.

    Science.gov (United States)

    Prichard, B N; Tomlinson, B

    1988-01-01

    The beta-blockers in clinical use have been classified into 2 major divisions, nonselective or selective agents, and those with or without intrinsic sympathomimetic activity (ISA). These properties confer differing pharmacological properties with some relevance to the treatment of hypertension. A beta-blocker with significant beta 2-ISA can be regarded as a multiple-action drug. A third division of beta-blockers is a newer development; these agents, besides blocking the beta-receptor, possess important peripheral vasodilator activity. Labetalol was the first drug of this group and prizidolol followed, but has been withdrawn because of toxicity. Several other agents now under evaluation include bucindolol and medroxolol, and carvedilol and dilevalol (1 of the isomers of labetalol), which have been the most widely studied in hypertension. Combined action results in important haemodynamic differences compared with pure beta-blockade. Notably, peripheral resistance is reduced, and there is less reduction in, or no effect on, cardiac output. The 3 following mechanisms have been described as responsible for peripheral vasodilatation: alpha-receptor blockade, beta 2-agonism, and a dilator action independent of either the alpha- or beta-receptors. Evidence for these various mechanisms is more readily obtainable from animal experiments, but some confirmatory evidence has been obtained in man. Inhibition of alpha-stimulation has been found with labetalol and to a small degree with medroxalol and carvedilol. beta 2-Mediated vasodilatation has been shown by dilevalol and medroxolol, and evidence of vasodilatation independent of alpha- or beta-receptors has been obtained with carvedilol. More evidence is required to confirm the exact contribution of each of these mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Effects of Schedule I drug laws on neuroscience research and treatment innovation.

    Science.gov (United States)

    Nutt, David J; King, Leslie A; Nichols, David E

    2013-08-01

    Many psychoactive drugs are used recreationally, particularly by young people. This use and its perceived dangers have led to many different classes of drugs being banned under national laws and international conventions. Indeed, the possession of cannabis, 3,4-methylenedioxy-N-methylamphetamine (MDMA; also known as ecstasy) and psychedelics is stringently regulated. An important and unfortunate outcome of the controls placed on these and other psychoactive drugs is that they make research into their mechanisms of action and potential therapeutic uses - for example, in depression and post-traumatic stress disorder - difficult and in many cases almost impossible.

  1. Controlling thought and action : a perspective from khat users and cocaine users

    NARCIS (Netherlands)

    Ruiz Muñoz, Manuel Jesús

    2015-01-01

    The mechanisms that control thought and action vary with the fluctuating and dynamic nature of both internal physiological states and external environmental constraints. Psychoactive drugs have the ability to alter mood state or behavior by acting directly on these mechanisms. The alteration of

  2. [Prevalence and predictors of psychoactive substance use among men in prisons].

    Science.gov (United States)

    Caravaca-Sánchez, Francisco; Falcón Romero, María; Luna, Aurelio

    2015-01-01

    The use of psychoactive substances among the prison population is an important public health issue because of its magnitude and health consequences. The aim of this study was to estimate the prevalence of psychoactive substance use among the prison population and to analyse its association with sociodemographic and penitentiary factors, particularly the size of the prison. Data were gathered using a self-administered questionnaire among 2,484 random male inmates in eight prisons of different sizes in Spain. The prevalence of psychoactive substance use with 95% confidence intervals (95% CI) during the last 6 months in prison were estimated. Prevalence ratios were used to estimate the association between psychoactive substance use and sociodemographic and penitentiary characteristics. The prevalence of psychoactive substance use in the past 6 months in prison was 59.9% (95% CI: 57.9-62.0). Notable among the sociodemographic variables associated with substance use were drug consumption prior to imprisonment (6.90; 95% CI: 5.51-8.65) and recidivism in prison (2.41; 95% CI: 2.04-2.85). The largest prisons showed a higher frequency of drug use than other prisons. A high prevalence of psychoactive substance use was found in prisons and significant differences were found according to delinquent profile and the size of the prison. Copyright © 2015 SESPAS. Published by Elsevier Espana. All rights reserved.

  3. A rede de comércio popular de drogas psicoativas na cidade de Diadema e o seu interesse para a Saúde Pública The trade network of psychoactive drugs in the city of Diadema and its interest for Public Health, São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Julino A. R. Soares Neto

    2010-06-01

    , origin were recorded, and also how they were obtained, manipulated, stocked, packaged and used. The study registered 63, herbs, which were categorized according to their possible psychoactive actions. The stimulants (67% and the depressants (27% predominated. Shortcomings were observed in the stock, manipulation and packaging of the drugs, exposing their customers to health risks. These findings aid in the understanding of aspects related to the quality and safety of herbs that are informally traded in Diadema, and show the need to promote a dialogue between this system and the formal health system.

  4. Assessment of the prevalence of taking psychoactive substances in secondary school students from the Silesia region

    Directory of Open Access Journals (Sweden)

    Mateusz Patyk

    2013-12-01

    Full Text Available Background: The aim of the study was to scrutinize the scale of a current problem of psychoactive substances taking by adolescents aged 13–16, including the level of their knowledge of that subject. The results obtained can help to create an educational program targeted at decreasing the number of students using drugs. Material and methods: The study was performed on a group of 197 secondary school students in 2013 with the use of selfdeveloped query based on ESPAD (The European School Survey Project on Alcohol and Other Drugs questionnaire. Results: 25% of the students showed their curiosity in trying some psychoactive substances, if those were legal. 19% declared that they already have had a contact with drugs. Teenagers are worried about the possible reaction of their parents and legal consequences of the use of psychoactive substances. At least every tenth of the respondents have had an opportunity to try marihuana. Conclusions: Despite the low average age the group of respondents has had contact with psychoactive substances. Every third person has been offered psychoactive substances. At least 40% of teenagers know about the possible ways where to take the drugs from. The outcome of the study is quite alarming because it shows a considerable interest in common drugs, as well as in some OTC medicaments.

  5. A influência da comorbidade com transtornos alimentares na apresentação de mulheres dependentes de substâncias psicoativas The impact of eating disorders as a comorbidity on psychoactive drug-dependent women seeking care

    Directory of Open Access Journals (Sweden)

    Silvia Brasiliano

    2006-01-01

    DSM-IV Disorders, The Addiction Severity Index and a standardized questionnaire for demographics and psychoactive substance use variables. The 27 (33.75% patients who had current eating disorders (ED group were compared to the 53 (66.25% patients who did not have such comorbidity (WED group. Results showed that the ED group had drug related problems earlier in life, was significantly younger and had higher drug related severity than the WED group. The differences observed between the groups and the higher prevalence of eating disorders not otherwise specified underscore the importance of a through evaluation of eating disorders in patients with substance use disorders seeking treatment. In order to plan effective therapeutic approaches these differences and moreover the comorbidity between eating disorders and substance use disorders in the course of substance abuse treatment need to be further investigated.

  6. Análise do conteúdo de propagandas de medicamentos psicoativos Análisis del contenido de propagandas de medicamentos psicoactivos Psychoactive drug advertising: content analysis

    Directory of Open Access Journals (Sweden)

    Patrícia C Mastroianni

    2008-10-01

    Full Text Available O objetivo do estudo foi descrever as figuras humanas retratadas nas propagandas de medicamentos psicoativos quanto ao gênero, a idade, a etnia e o contexto social. Foi realizada análise de conteúdo de 86 impressos publicitários inéditos divulgados em Araraquara (SP no ano de 2005. A associação entre as categorias foi analisada usando o teste exato de Fisher. Houve predomínio de mulheres (62,8%, sendo quatro vezes mais freqüentes que os homens em propagandas de antidepressivos e ansiolíticos. A maioria era constituída de jovens adultos (72%, de etnia branca (98,8%. As pessoas estavam em lazer (46,5%, em suas casas (29% ou em contato com a natureza (16,2%. A mensagem transmitida foi que os medicamentos tratam sintomatologias subjetivas de desconforto do dia-a-dia, induzindo a um apelo irracional que pode refletir na prescrição medicamentosa.El objetivo del estudio fue describir las figuras humanas retratadas en las propagandas de medicamentos psicoactivos con relación al género, la edad, la etnia y el contexto social. Se realizó un análisis del contenido de 86 anuncios publicitarios inéditos divulgados en Araraquara (sureste de Brasil, en el año 2005. La asociación entre las categorías fue analizada usando la prueba exacta de Fisher. Se detectó un predominio de mujeres (62,8%, siendo cuatro veces mas frecuentes que los hombres en propagandas de antidepresivos y ansiolíticos. La mayoría estaba constituida por jóvenes adultos (72%, de etnia blanca (98,8%. Las personas estaban en tiempo de ocio (46,5%, en sus casas (29% o en contacto con la naturaleza (16,2%. El mensaje transmitido fue que los medicamentos tratan sintomatologías subjetivas de incomodidad del día a día, induciendo un reclamo irracional que puede reflejarse en la prescripción medicamentosaThe goal of this study was to describe the human figures portrayed in psychoactive drug advertising in terms of gender, age, ethnic group, and social context. Content

  7. Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand.

    Science.gov (United States)

    Rychert, Marta; Wilkins, Chris; Witten, Karen

    2017-09-01

    New Zealand's Psychoactive Substances Act (2013) established the world's first regulated market for 'low risk' psychoactive products ('legal highs'). Under an interim PSA regime, 47 existing products were permitted to be continued to be sold. To explore issues with the implementation of regulatory systems to monitor the safety of products on the legal market under the interim Psychoactive Substances Act regime. Semi-structured interviews with 30 key stakeholders, including industry, government agency, health and drug service professionals were conducted, transcribed and analysed thematically. In retrospect stakeholders questioned the decision to approve strong synthetic cannabinoid smoking products, noting their health risks because of product formulation, inconsistent manufacturing practices and smoking as the means of administration. Industry actors claimed the decision to approve synthetic cannabinoid smokeable products prevented potentially safer products from gaining market share. The system for withdrawing approved products which were subsequently found to be harmful was criticised for the poor quality of data available, limited engagement with health professionals and the slowness of product withdrawal. Many of the problems with the regime were attributed to the urgency under which the legal market under the interim Psychoactive Substances Act was established and implemented. The selection of 'safer' products, implementation of the product monitoring system, and engagement with health professionals may have benefited from more time and resources. An incremental approach to establishing the new market may have made the regulatory management of the new regime more workable. [Rychert M, Wilkins C, Witten K. Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  8. NIH study uncovers new mechanism of action for class of chemotherapy drugs

    Science.gov (United States)

    NIH researchers have discovered a significant new mechanism of action for a class of chemotherapy drugs known as poly (ADP-ribose) polymerase inhibitors, or PARP inhibitors. They have also identified differences in the toxic capabilities of three drugs in

  9. Intravenous self-administration of benzydamine, a non-steroidal anti-inflammatory drug with a central cannabinoidergic mechanism of action.

    Science.gov (United States)

    Avvisati, Riccardo; Meringolo, Maria; Stendardo, Emiliana; Malavasi, Elisa; Marinelli, Silvia; Badiani, Aldo

    2018-03-01

    Benzydamine (BZY) is a non-steroidal anti-inflammatory drug used for the topical treatment of inflammations of the oral and vaginal mucosae. Virtually nothing is known about the central pharmacological actions of BZY. Yet there are reports of voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric, hallucinatory state. In the present study, we investigated the reinforcing properties of BZY in a rat self-administration paradigm. We found that BZY has a powerful reinforcing effect and that this effect is greatly facilitated in animals that already had substance experience, having previously self-administered heroin and cocaine, indicating cross sensitization between BZY and other common drugs of abuse. We then assessed the effect of BZY on prelimbic cortex-to-nucleus accumbens glutamatergic transmission, using field recordings in rat parasagittal brain slices. BZY dose-dependently reduced both field excitatory post synaptic potential amplitude and paired pulse ratio, suggesting a presynaptic mechanism of action. Similarly to the in vivo paradigm, also the electrophysiological effects of BZY were potentiated in slices from animals that had undergone cocaine and heroin self-administration. Furthermore, BZY-induced Long Term Depression (LTD)-like responses in the prelimbic cortex-to-nucleus accumbens circuitry were significantly reduced in the presence of the CB1 receptor antagonist AM251. These findings provide firm evidence of the abuse liability of BZY and suggest a possible cannabinoidergic mechanism of action. Further research is needed in order to give insights into the molecular mechanism underlying BZY psychoactive and reinforcing effects, to better understand its abuse potential. © 2017 Society for the Study of Addiction.

  10. Modern representations about differential diagnosis of schizophrenia-like psychosis disorders due to psychoactive substance use

    OpenAIRE

    V. V. Chugunov; I. F. Pirogov

    2014-01-01

    In recent years in the world there is a tendency of quantity of persons who use drugs increase. Free availability of drugs of different groups for population is the main cause. Another trend associated with the consumption of drugs. All these factors led to the increased frequency of psychosis occurrence among consumers of psychoactive substances. In structure of such psychosis there are a variety of symptoms and syndromes. And since the number of drug users is quite broad in its structur...

  11. Leptin signaling molecular actions and drug target in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Jiang N

    2014-11-01

    Full Text Available Nan Jiang,1,* Rongtong Sun,2,* Qing Sun3 1Shandong University School of Medicine, Jinan, Shandong Province, People’s Republic of China; 2Weihai Municipal Hospital, Weihai, Shandong Province, People’s Republic of China; 3Department of Pathology, QianFoShan Hospital Affiliated to Shandong University, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Abstract: Previous reports indicate that over 13 different tumors, including hepatocellular carcinoma (HCC, are related to obesity. Obesity-associated inflammatory, metabolic, and endocrine mediators, as well as the functioning of the gut microbiota, are suspected to contribute to tumorigenesis. In obese people, proinflammatory cytokines/chemokines including tumor necrosis factor-alpha, interleukin (IL-1 and IL-6, insulin and insulin-like growth factors, adipokines, plasminogen activator inhibitor-1, adiponectin, and leptin are found to play crucial roles in the initiation and development of cancer. The cytokines induced by leptin in adipose tissue or tumor cells have been intensely studied. Leptin-induced signaling pathways are critical for biological functions such as adiposity, energy balance, endocrine function, immune reaction, and angiogenesis as well as oncogenesis. Leptin is an activator of cell proliferation and anti-apoptosis in several cell types, and an inducer of cancer stem cells; its critical roles in tumorigenesis are based on its oncogenic, mitogenic, proinflammatory, and pro-angiogenic actions. This review provides an update of the pathological effects of leptin signaling with special emphasis on potential molecular mechanisms and therapeutic targeting, which could potentially be used in future clinical settings. In addition, leptin-induced angiogenic ability and molecular mechanisms in HCC are discussed. The stringent binding affinity of leptin and its receptor Ob-R, as well as the highly upregulated expression of both

  12. What a clinician needs to know about the mechanisms of action of antiarrhythmic drugs

    NARCIS (Netherlands)

    Janse, M. J.

    1991-01-01

    Vaughan Williams' classifications of antiarrhythmic drugs are briefly discussed, including the fact that these drugs are classified based upon their effects on normal cardiac cells; that more and more subclassifications need to be introduced; that many drugs have actions belonging to different

  13. Can Google Searches Predict the Popularity and Harm of Psychoactive Agents?

    Science.gov (United States)

    Jankowski, Wojciech; Hoffmann, Marcin

    2016-02-25

    Predicting the popularity of and harm caused by psychoactive agents is a serious problem that would be difficult to do by a single simple method. However, because of the growing number of drugs it is very important to provide a simple and fast tool for predicting some characteristics of these substances. We were inspired by the Google Flu Trends study on the activity of the influenza virus, which showed that influenza virus activity worldwide can be monitored based on queries entered into the Google search engine. Our aim was to propose a fast method for ranking the most popular and most harmful drugs based on easily available data gathered from the Internet. We used the Google search engine to acquire data for the ranking lists. Subsequently, using the resulting list and the frequency of hits for the respective psychoactive drugs combined with the word "harm" or "harmful", we estimated quickly how much harm is associated with each drug. We ranked the most popular and harmful psychoactive drugs. As we conducted the research over a period of several months, we noted that the relative popularity indexes tended to change depending on when we obtained them. This suggests that the data may be useful in monitoring changes over time in the use of each of these psychoactive agents. Our data correlate well with the results from a multicriteria decision analysis of drug harms in the United Kingdom. We showed that Google search data can be a valuable source of information to assess the popularity of and harm caused by psychoactive agents and may help in monitoring drug use trends.

  14. Biological Evidence for Paradoxical Improvement of Psychiatric Disorder Symptoms by Addictive Drugs.

    Science.gov (United States)

    Müller, Christian P; Kornhuber, Johannes

    2017-06-01

    Addiction biology has focused on the mechanisms of the positive and negative reinforcing actions of addictive drugs but neglected potential benefits. Two new studies provide the first insights into a neurobiology of psychoactive drug instrumentalization. This may help us design better models for addiction neuroscience and opens a new dimension for the development of personalized pharmacotherapy of drug addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Population based models of cortical drug response: insights from anaesthesia.

    NARCIS (Netherlands)

    Foster, B.L.; Bojak, I.; Liley, D.T.

    2008-01-01

    A great explanatory gap lies between the molecular pharmacology of psychoactive agents and the neurophysiological changes they induce, as recorded by neuroimaging modalities. Causally relating the cellular actions of psychoactive compounds to their influence on population activity is experimentally

  16. Prevalence of alcohol and other psychoactive substances in drivers in general traffic. Part II: Country reports

    DEFF Research Database (Denmark)

    Houwing, Sjoerd; Hagenzieker, Marjan; Mathijssen, René

    2011-01-01

    DRUID (Driving under the Influence of Drugs, Alcohol and Medicines) aimed to combat the problem of driving under the influence of psychoactive substances by providing a solid scientific base for European policy makers. It brought together experienced organisations in Europe to assemble a coordina...

  17. Prevalence of alcohol and other psychoactive substances in drivers in general traffic. Part I: General results

    DEFF Research Database (Denmark)

    Houwing, Sjoerd; Hagenzieker, Marjan; Mathijssen, René

    2011-01-01

    DRUID (Driving under the Influence of Drugs, Alcohol and Medicines) aimed to combat the problem of driving under the influence of psychoactive substances by providing a solid scientific base for European policy makers. It brought together experienced organisations in Europe to assemble a coordina...

  18. New psychoactive substances of natural origin: A brief review

    Directory of Open Access Journals (Sweden)

    Ling-Yi Feng

    2017-07-01

    Full Text Available Plant-based drugs of abuse are as old as recorded human history. Although traditional addictive substances, such as opium, cannabis and coca, have been controlled by the United Nations anti-drug conventions, many, if not most, natural plants with addictive or abuse liability remain elusive. Therefore, the United Nations Office on Drugs and Crime (UNODC has warned the emerging threat from new psychoactive substances (NPS, which are mostly derived or modified from the constituents of natural origin. For example, synthetic cannabinoids and synthetic cathinones are derived from the cannabis and khat plant, respectively. In this review, we briefly discussed the chemistry, pharmacology and toxicology of five common NPS of natural origin, i.e., khat, kratom, salvia, magic mushroom and mandrake. Through the review, we hope that professionals and general public alike can pay more attention to the potential problems caused by natural NPS, and suitable control measures will be taken.

  19. New psychoactive substances of natural origin: A brief review.

    Science.gov (United States)

    Feng, Ling-Yi; Battulga, Altansuvd; Han, Eunyoung; Chung, Heesun; Li, Jih-Heng

    2017-07-01

    Plant-based drugs of abuse are as old as recorded human history. Although traditional addictive substances, such as opium, cannabis and coca, have been controlled by the United Nations anti-drug conventions, many, if not most, natural plants with addictive or abuse liability remain elusive. Therefore, the United Nations Office on Drugs and Crime (UNODC) has warned the emerging threat from new psychoactive substances (NPS), which are mostly derived or modified from the constituents of natural origin. For example, synthetic cannabinoids and synthetic cathinones are derived from the cannabis and khat plant, respectively. In this review, we briefly discussed the chemistry, pharmacology and toxicology of five common NPS of natural origin, i.e., khat, kratom, salvia, magic mushroom and mandrake. Through the review, we hope that professionals and general public alike can pay more attention to the potential problems caused by natural NPS, and suitable control measures will be taken. Copyright © 2017. Published by Elsevier B.V.

  20. Psychoactive Substance Use among Medical/Health Faculty Undergraduate Students

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    P Whitehorne-Smith

    2015-03-01

    Full Text Available Objective: This study sought to explore the drug use practices of undergraduate students within the Faculty of Medical Sciences, The University of the West Indies, Mona, Jamaica. Method: This study was a multicentre study carried out in Jamaica and six Latin American countries. The study utilized a cross-sectional design using a survey method of data collection. A list of compulsory classes for first- and second-year undergraduate students in the Faculty of Medical Sciences was retrieved by researchers and then cluster sampling was used to choose lectures to carry out data collection. The instrument utilized for the study was a self-report questionnaire which consisted of 58 questions which enquired about sociodemographic information, psychoactive substance use and associated consequences. Results: A total of 380 students (78 males, 302 females participated in the study; 115 (30.3% reported a past year prevalence of psychoactive substance use. Roughly half (50.8% reported that they first used substances when they were 15−19 years old. Students also reported a past month prevalence of alcohol use (16.6%, prescription drugs without a prescription (4.5%, tobacco (2.4% and cannabis (2.1% use. Conclusion: These preliminary results on substance use patterns among students in the Faculty of Medical Sciences indicate urgent need for further research among this population. Such research should be used to inform prevention and treatment programmes that will directly target this student population.

  1. On some mechanisms of antihypoxic actions of nootropic drugs.

    Science.gov (United States)

    Fischer, H D; Schmidt, J; Wustmann, C

    1984-01-01

    The antihypoxic effect of meclofenoxate hydrochloride seen in the accelerated restitution of posthypoxic dopamine release inhibition originates in the alcoholic component of the drug. Via choline dimethylaminoethanol might run, like orotic acid, into a CDP-choline pool, the generation of which is able to be facilitated by piracetam which in turn increases the phosphorylation potential. All these nootropic drugs will in this way increase the biosynthesis of hypoxically vulnerable phospholipids by different mechanisms. Indeed, a combined treatment with piracetam, meclofenoxate hydrochloride and methylglucamineorotate leads to a more rapid restitution of posthypoxic dopamine release inhibition than the drugs are active when applied separately.

  2. Experimentation with psychoactive substances by public school students

    Directory of Open Access Journals (Sweden)

    Maria Eliane de Andrade

    2017-09-01

    Full Text Available ABSTRACT OBJECTIVE To analyze the prevalence of exposure to psychoactive substances in public students of basic education and its association with sociodemographic characteristics. METHODS This is a cross-sectional survey conducted from March to September 2015, involving 1,009 students of the basic and high school education in 20 public schools in the municipality of Aracaju, State of Sergipe, Brazil. The data have been compiled using questionnaires previously applied in national studies of the Brazilian Center for Psychotropic Drugs. The variables have been dichotomized for later logistic regression using the Chi-square test to analyze associations between experimentation with psychoactive substances and other sociodemographic variables; odds ratio and confidence intervals have also been calculated. The level of significance adopted was 5%. RESULTS We have identified that 69.6% of the students have experimented alcohol and 12.4% cigarettes. Age (≥ 15 years has shown a significant association with experimentation with alcohol (p < 0.001 and cigarettes (p = 0.02, acting as risk factor in both cases (OR = 2.34 and 1, 78, respectively, but it acted as a protective factor for the use of inhalants (p = 0.03 and OR = 0.58 and weight loss medication (p = 0.006 and OR = 0.44. Religious practice had a significant association with experimentation with alcohol (p = 0.01, functioning as a protective factor (OR = 0.56. CONCLUSIONS We have concluded that the psychoactive substance most experienced by students was alcohol, followed by cigarettes, and chance for experimentation increases after the age of 15. Religious practice, in turn, acts as a protective factor for experimentation with alcohol.

  3. FDA safety actions for antidiabetic drugs marketed in the US, 1980-2015.

    Science.gov (United States)

    Kwon, Christina S; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa

    2016-01-01

    Concerns about safety and complexity of diabetes treatments have increased overtime. We assessed secular trends in the FDA approvals, market discontinuations, and safety actions of all antidiabetic drugs marketed in the US in the period 1980-2015. Regulatory and safety related information about FDA-approved pharmaceuticals for diabetes treatment was collected from the FDA databases, the Orange Book, and Drugs@FDA. Descriptive statistics were performed to describe trends in approvals, discontinuations, and safety actions. The number of insulins and analogue approvals declined after the 1980s; whereas, the approvals of non-insulin antidiabetic drugs increased after 1995. The number of antidiabetic drugs with FDA safety actions significantly increased overtime. Overall, 59.0% of insulins and analogues and 5.7% of non-insulin antidiabetic drugs were discontinued from the market. The FDA released at least one safety action for 7.7% of insulins and analogues and 88.7% of non-insulin antidiabetic drugs. Newly approved antidiabetic drugs have raised safety concerns and led to FDA safety regulatory actions including boxed warnings, risk evaluation and mitigation strategies, medication guides, and safety communications to health care providers. There is a need for systematic post-marketing studies assessing the long-term safety of antidiabetic drugs to improve patient safety and health outcomes.

  4. Determinants of psychoactive substance use among incarcerated ...

    African Journals Online (AJOL)

    Determinants of psychoactive substance use among incarcerated delinquents in Nigeria. ... substance use prevalence is high among incarcerated delinquents, the incorporation of substance abuse screening and treatment as part of their programmeme is advocated. Key Words: Substance use, delinquents, incarceration, ...

  5. prevalence of psychoactive substance use among commercial ...

    African Journals Online (AJOL)

    Emmanuel Ameh

    Conclusion: Road traffic accidents among commercial motorcyclists are a frequent occurrence in this part of the country. There is need for public awareness campaigns on road safety education and health consequences of psychoactive substance use among commercial motorcyclists. It is further recommended that law ...

  6. The antimalarial drug quinine interferes with serotonin biosynthesis and action

    DEFF Research Database (Denmark)

    Islahudin, Farida; Tindall, Sarah M.; Mellor, Ian R.

    2014-01-01

    The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmit......The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor...

  7. Food-drug interactions: Careful drug selection and patient counseling can reduce the risk in older patients.

    Science.gov (United States)

    Leibovitch, Eric R; Deamer, Robert L; Sanderson, Leslie A

    2004-03-01

    Older patients are at high risk for food-drug Interactions. These patients are commonly on multiple medications for chronic medical conditions. Age-related physiologic changes affecting drug absorption, distribution, metabolism and excretion, as well as drug action occur in these patients, and this variability in drug action may be further potentiated by interactions with foods. The most prominent interactions involve drug absorption from the GI tract; however alterations in drug metabolism are also highly significant. Food-drug interactions have been reported amongst a wide range of therapeutic drug classes, including, but not limited to, cardiovascular, psychoactive, anti-infective, endocrinologic, gastrointestinal, and respiratory agents. Health care providers can prevent significant drug therapy-related morbidity by carefully selecting drugs for geriatric patients and thoroughly counseling these patients about drug interactions with the foods they eat.

  8. Prevalence of psychoactive substances use in a Lithuanian women's prison revisited after 5 years.

    Science.gov (United States)

    Narkauskaitė, Laura; Juozulynas, Algirdas; Mackiewicz, Zygmunt; Venalis, Algirdas; Utkuvienė, Janina

    2010-11-01

    This paper re-examines the prevalence of psychoactive substances (tobacco, alcohol, narcotic drugs) use among inmates in a Lithuanian women's prison. The main goal of this study was to determinate the changes in the use of the psychoactive substances in a women's prison in Lithuania. We accomplished the retesting of the first ever investigation of this kind, carried out in 2004, using the same questionnaire, in the only women's prison in Lithuania. In June 2009, 71 (27.8%) women of 255 inmates of the prison were given questionnaires with information about the aim of the study, stating that the study was voluntary and anonymous, and obtaining permission for release of information. The results were compared with the previous investigation. A statistical analysis was carried out using SPSS 17.0. Tobacco smokers comprised 85.3% of respondents.; the average age at which respondents started to smoke was 14±7.3 years; 57.7% of respondents had tried narcotic drugs at least once; 22.5% of respondents used drugs (in 2004 we had found no drug use in this women's prison); 18.3% of respondents indicated that they narcotic drugs were tried for the first time away, 4.2% - in a custodial establishment. Psychoactive substances are often used due to their psychological effect. inmates constitute a high-risk group of drug users and distributors of narcotic drugs. Intravenous narcotics stimulating dangerous behavior prevail in Lithuanian prisons. Women in prison are especially prone to smoking.

  9. Activated Carbon-Based System for the Disposal of Psychoactive Medications

    Directory of Open Access Journals (Sweden)

    Yang Song

    2016-11-01

    Full Text Available The misuse and improper disposal of psychoactive medications is a major safety and environmental concern. Hence, the proper disposal of these medications is critically important. A drug deactivation system which contains activated carbon offers a unique disposal method. In the present study, deactivation efficiency of this system was tested by using three model psychoactive drugs. HPLC validation was performed for each drug to ensure that the analytical method employed was suitable for its intended use. The method was found to be specific, accurate and precise for analyzing the drugs. The extent and rate of deactivation of the drugs was determined at several time points. After 28 days in the presence of activated carbon, the extent of leaching out of the drugs was evaluated. Deactivation started immediately after addition of the medications into the disposal pouches. Within 8 h, around 47%, 70% and 97% of diazepam, lorazepam and buprenorphine were adsorbed by the activated carbon, respectively. By the end of 28 days, over 99% of all drugs were deactivated. The desorption/leaching study showed that less than 1% of the active ingredients leached out from the activated carbon. Thus, this deactivation system can be successfully used for the disposal of psychoactive medications.

  10. Frequency and risk factors of the use of psychoactive substances among the young

    Directory of Open Access Journals (Sweden)

    Pavlović Zorana

    2008-01-01

    Full Text Available Background/Aim. Socio-economic changes that occurred in the wake of dismemberment of former Yugoslavia resulted in the appearance of social pathology, one of which was the increase in the use of psychoactive substances. The over whole epidemiological research in the use of psychoactive substances has not been conducted so far. The aim of this study was to establish the type and form of the use of psychoactive substances considering sex and age, as well as risk factors for the use of psychoactive substances among the children and adolescents. Methods. The research was carried out among 1011 elementary school children (seventh and eighth grades and secondary school children (all four grades in the area of Belgrade from October 2003 to January 2004. Out of the total number 457 (45.2% were elementary school pupils and 554 (54.8% secondary school pupils. There were 524 (51.8% boys and 487 (48.2% girls, aged from 12 to 18 years (the average age being 15.3 years. The method used was the European School Survey Project on Alcohol and Other Drugs Questionnaire. Chisquare test, Mann-Whitney, Student's t test and Logistic Regression test were used in statistical processing of the data. Results. Totally 14.2% examinees tried psychoactive substances. The most frequent drug used at the first contact was marijuana (10.8% at the age of 15 tried by 12.7% examinees, inhalants (4.4%, amphetamines (4.1%, sedatives (3.7%, alcohol combined with marijuana (3.9%, then cocaine (2.8%, heroine (2.3%, alcohol combined with sedatives (2.2%, and ecstasy (1.6%, followed by anabolic steroids, heroin, diethilamid lisergic acid (LSD and magic mushrooms. It was determined that going out in the evening, smoking and binge form drinking were directly connected with the use of psychoactive substances. Conclusion. Totally 14.2% of the examiners used psychoactive substances, mostly marijuana, followed by amphetamines and others. New tendencies of use characterized by the increase in the

  11. Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet.

    Science.gov (United States)

    Rogawski, Michael A; Löscher, Wolfgang; Rho, Jong M

    2016-05-02

    Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement of γ-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and α2δ; or by blockade of ionotropic glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, such as adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion from glycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  12. [Stereochemical aspects of narcotic and psychotropic drug action].

    Science.gov (United States)

    Noszál, B; Schiller, Z

    1999-01-01

    Medicinal drugs are predominantly, whereas narcotic and psychotropic drugs are exclusively exogenous compounds. Three further fundamental properties of the narcotic/psychotropic compounds of significant abuse potential is that they all are of natural (plant or microbial) origin, they contain a large number of chiral atoms, and they influence the neurotransmission processes in the central nervous system. For some of them, the existence of corresponding endogenous ligands have recently been reported. Since exogenous compounds and their endogenous ligands are assumed to bind the same target moiety of the receptor, several fundamental questions arise: To what extent can stereochemical relationships be established between the exogenous compound and its endogenous counterpart? Do they have superimposable moieties? Are the corresponding chiral atoms of the same configuration? Is there a chiral-genetic relationship between the exogenous and endogenous compound? Theoretical aspects and answers to all these questions are sought for morphine, cocaine, LSD, tetrahydrocannabinol, amphetamine and related molecules.

  13. The action of Pseudomonas aeruginosa biofilms in intrinsic drug resistance.

    Science.gov (United States)

    Xie, Yi; Jia, Wen-xiang; Zeng, Wei; Yang, Wei-qing; Cheng, Xi; Li, Xue-ru; Wang, Lan-lan; Kang, Mei; Zhang, Zai-rong

    2005-10-05

    There is a growing interest in studying the relationship between intrinsic resistance and biofilms resistance to drugs. However, the relationship still remains unclear in the macroscopic bacterial growth. Our study is to illuminate the change of bacterial drug resistance of gyrA mutant and active efflux pump during the development of Pseudomonas aeruginosa (P. aeruginosa) biofilms. The strains of type II topoisomerase gene mutant (gyrA mutant) and multidrug resistance (MDR) efflux pump were clinical isolates and detected by polymerase chain reaction (PCR). The process of bacterial biofilms development was observed by scanning electron microscope. Triparental mating experiments were performed to transfer report gene of green fluorescent protein (GFP) into P. aeruginosa biofilms strains and followed by analysis of bacterial survival rate between intrinsic resistance and biofilms resistance. The fluorescent strains with pGFPuv could develop mature biofilms on Teflon surface. Before a period of 72 hours, the survival rate of biofilms bacteria and intrinsic resistance strains in ciprofloxacin solution was significantly different (P 0.05). The carbonyl cyanide m-chlorophenylhydrazone and azithromycin could significantly reduce the drug resistance of biofilm strains and efflux pump strains. In the development of P. aeruginosa biofilms, the strains of gyrA mutation and MDR efflux could be conferred with new level of drug resistance. When co-cultured mutated strains with biofilm strains, biofilms may play a major role in bacterial resistance. But after 72 hours incubation (a mature biofilms had been developed), there was no clearly difference between the number of mutant strains and biofilm strains.

  14. Visualizing the site of drug action in living human brain

    Energy Technology Data Exchange (ETDEWEB)

    Suhara, Tetsuya [National Inst. of Radiological Sciences, Chiba (Japan)

    1997-03-01

    PET is the only technique available to date to measure molecular interactions in vivo, but the basic mechanism of molecular interaction in vivo is not yet fully understood. However, PET can allow visualization of various phenomena which we can not observe with in vitro techniques. Progress in PET study will provide a new viewpoint for drug development and the study of molecular mechanism in the brain. (J.P.N.)

  15. Neuropharmacological Targets for Drug Action in Vestibular Sensory Pathways

    OpenAIRE

    Lee, Choongheon; Jones, Timothy A

    2017-01-01

    The use of pharmacological agents is often the preferred approach to the management of vestibular dysfunction. In the vestibular sensory pathways, the sensory neuroepithelia are thought to be influenced by a diverse number of neuroactive substances that may act to enhance or inhibit the effect of the primary neurotransmitters [i.e., glutamate (Glu) and acetylcholine (ACh)] or alter their patterns of release. This review summarizes various efforts to identify drug targets including neurotransm...

  16. Cellular Mechanisms of Action of Drug Abuse on Olfactory Neurons

    Directory of Open Access Journals (Sweden)

    Thomas Heinbockel

    2015-12-01

    Full Text Available Cannabinoids (Δ9-tetrahydrocannabinol are the active ingredient of marijuana (cannabis which is the most commonly abused illicit drug in the USA. In addition to being known and used as recreational drugs, cannabinoids are produced endogenously by neurons in the brain (endocannabinoids and serve as important signaling molecules in the nervous system and the rest of the body. Cannabinoids have been implicated in bodily processes both in health and disease. Recent pharmacological and physiological experiments have described novel aspects of classic brain signaling mechanisms or revealed unknown mechanisms of cellular communication involving the endocannabinoid system. While several forms of signaling have been described for endocannabinoids, the most distinguishing feature of endocannabinoids is their ability to act as retrograde messengers in neural circuits. Neurons in the main olfactory bulb express high levels of cannabinoid receptors. Here, we describe the cellular mechanisms and function of this novel brain signaling system in regulating neural activity at synapses in olfactory circuits. Results from basic research have the potential to provide the groundwork for translating the neurobiology of drug abuse to the realm of the pharmacotherapeutic treatment of addiction, specifically marijuana substance use disorder.

  17. Safety-related regulatory actions for orphan drugs in the US and EU: a cohort study.

    Science.gov (United States)

    Heemstra, Harald E; Giezen, Thijs J; Mantel-Teeuwisse, Aukje K; de Vrueh, Remco L A; Leufkens, Hubert G M

    2010-02-01

    Drugs for rare diseases, so-called orphan drugs, are often intended for serious or chronically debilitating diseases. Safety information is more limited at the time of approval for orphan drugs as a result of various factors, such as the limited number of patients in clinical trials, quality of the clinical trials and special approval procedures. Several studies have been conducted on safety-related regulatory actions for drugs, but none of these have specifically focused on orphan drugs. To determine the frequency and nature of safety-related regulatory actions for orphan drugs in the US and EU. This cohort study examined publicly available data from the websites of US and EU regulatory authorities on orphan drugs approved in the US and/or the EU between January 2000 and December 2007. The main outcome measures were the nature, frequency and timing of safety-related regulatory actions, defined as (i) safety withdrawals; (ii) 'black-box' warnings; and (iii) written communications to healthcare professionals issued by the US FDA or the European Medicines Agency between January 2000 and June 2008. Ninety-five orphan drugs were approved during the study period (75 in the US, 44 in the EU, and 24 in both regions). Ten products (10.5%) received a safety-related regulatory action. No safety withdrawals, four black-box warnings and 12 written communications were identified. The probability of a first safety-related regulatory action for orphan drugs was 20.3% after 8 years of follow-up. Orphan drugs approved by accelerated approval (relative risk [RR] 3.32; 95% CI 1.06, 10.42), oncological products (RR 7.83; 95% CI 0.96, 63.82) and products for gastrointestinal and metabolism indications (RR 10.44; 95% CI 1.25, 87.27) may have a higher risk for a safety-related regulatory action. The probability of a first safety-related regulatory action for an orphan drug was slightly lower than that reported in the literature for biologicals in one study and new molecular entities in

  18. Following “the Roots” of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries

    Science.gov (United States)

    Cinosi, Eduardo; Martinotti, Giovanni; Simonato, Pierluigi; Singh, Darshan; Demetrovics, Zsolt; Roman-Urrestarazu, Andres; Bersani, Francesco Saverio; Vicknasingam, Balasingam; Piazzon, Giulia; Li, Jih-Heng; Yu, Wen-Jing; Kapitány-Fövény, Máté; Farkas, Judit; Di Giannantonio, Massimo; Corazza, Ornella

    2015-01-01

    The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon. PMID:26640804

  19. Following “the Roots” of Kratom (Mitragyna speciosa: The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries

    Directory of Open Access Journals (Sweden)

    Eduardo Cinosi

    2015-01-01

    Full Text Available The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom, a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i reviews the state of the art on kratom pharmacology and identification; (ii provides a comprehensive overview of kratom use cross-culturally; (iii explores the subjective experiences of users; (iv identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.

  20. Following "the Roots" of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries.

    Science.gov (United States)

    Cinosi, Eduardo; Martinotti, Giovanni; Simonato, Pierluigi; Singh, Darshan; Demetrovics, Zsolt; Roman-Urrestarazu, Andres; Bersani, Francesco Saverio; Vicknasingam, Balasingam; Piazzon, Giulia; Li, Jih-Heng; Yu, Wen-Jing; Kapitány-Fövény, Máté; Farkas, Judit; Di Giannantonio, Massimo; Corazza, Ornella

    2015-01-01

    The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.

  1. Emerging psychoactive substance use among regular ecstasy users in Australia.

    Science.gov (United States)

    Bruno, Raimondo; Matthews, Allison J; Dunn, Matthew; Alati, Rosa; McIlwraith, Fairlie; Hickey, Sophie; Burns, Lucy; Sindicich, Natasha

    2012-07-01

    The past decade has seen the development of an array of emerging psychoactive substances (EPS), however, there is minimal information on the extent of their use outside Europe. This study aimed to determine the extent of use of EPS from stimulant (such as mephedrone) and psychedelic classes (such as 5-methoxy-dimethyltryptamine [5-MeO-DMT]) among an Australian sample of regular ecstasy users (REU). Further, to determine if consumers of these drugs represent a distinct subgroup of REU. Australian national cross-sectional surveys of 693 regular (at least monthly) ecstasy users conducted during 2010. More than one quarter (28%) of REU had used an EPS in the past six months, most commonly from the stimulant class (20%, typically mephedrone, 17%) rather than the psychedelic class (13%). Demographics and risk behaviours of REU that used stimulant EPS were largely no different from non-EPS consuming REU. Those using psychedelic EPS were distinct, initiating ecstasy use earlier, more frequently using multiple substances (cannabis, inhalants, GHB, ketamine) and more commonly experiencing legal, psychological and social problems. Psychedelic EPS use appears largely restricted to a distinct subset of REU with high-level non-injecting polydrug use, but use appears generally limited. The demographic similarity of stimulant EPS consumers with 'mainstream' REU, in conjunction with positive responses to the psychoactive effects of these drugs and declining ecstasy purity, suggests strong potential for stimulant EPS to expand further into ecstasy markets. Such drugs may have a greater public health impact than ecstasy, and merit careful monitoring into the future. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Vulnerabilidade à Doenças Sexualmente Transmissíveis/AIDS e uso de drogas psicoativas por caminhoneiros Vulnerabilidad a las Enfermedades de Transmisión Sexual/SIDA y uso de drogas psicoativas por conductores de camiones Vulnerability to Sexually Transmitted Diseases/AIDS and use of psychoactive drugs by truck drivers

    Directory of Open Access Journals (Sweden)

    Valéria Aparecida Masson

    2010-02-01

    .A cross-sectional epidemiological descriptive study with the purpose of identify the demographic characteristics, health aspects and life style, vulnerability to Sexually Transmitted Diseases/AIDS amongst long distance truck drivers were applied to 50 drivers from supply center of Campinas (fruit, vegetable, product wholesale market. The outcomes showed that almost all drivers interviewed were men, the majority were married, had kids, low study level and fewer than 40 years old. 70% reported abuse psychoactive drugs. The majority was aware of the importance of using condoms with casual partners; 94% reported relationship with casual partners and just 6% never used condoms. Although the small sample analyzed, the results suggests that must be implemented health promotion actions and illness prevention public politics, including the development of customized educational interventions with in this professional group.

  3. Nanoscale monitoring of drug actions on cell membrane using atomic force microscopy

    Science.gov (United States)

    Li, Mi; Liu, Lian-qing; Xi, Ning; Wang, Yue-chao

    2015-01-01

    Knowledge of the nanoscale changes that take place in individual cells in response to a drug is useful for understanding the drug action. However, due to the lack of adequate techniques, such knowledge was scarce until the advent of atomic force microscopy (AFM), which is a multifunctional tool for investigating cellular behavior with nanometer resolution under near-physiological conditions. In the past decade, researchers have applied AFM to monitor the morphological and mechanical dynamics of individual cells following drug stimulation, yielding considerable novel insight into how the drug molecules affect an individual cell at the nanoscale. In this article we summarize the representative applications of AFM in characterization of drug actions on cell membrane, including topographic imaging, elasticity measurements, molecular interaction quantification, native membrane protein imaging and manipulation, etc. The challenges that are hampering the further development of AFM for studies of cellular activities are aslo discussed. PMID:26027658

  4. Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance.

    Science.gov (United States)

    Zeng, Daina; Debabov, Dmitri; Hartsell, Theresa L; Cano, Raul J; Adams, Stacy; Schuyler, Jessica A; McMillan, Ronald; Pace, John L

    2016-12-01

    The glycopeptide antimicrobials are a group of natural product and semisynthetic glycosylated peptides that show antibacterial activity against Gram-positive organisms through inhibition of cell-wall synthesis. This is achieved primarily through binding to the d-alanyl-d-alanine terminus of the lipid II bacterial cell-wall precursor, preventing cross-linking of the peptidoglycan layer. Vancomycin is the foundational member of the class, showing both clinical longevity and a still preferential role in the therapy of methicillin-resistant Staphylococcus aureus and of susceptible Enterococcus spp. Newer lipoglycopeptide derivatives (telavancin, dalbavancin, and oritavancin) were designed in a targeted fashion to increase antibacterial activity, in some cases through secondary mechanisms of action. Resistance to the glycopeptides emerged in delayed fashion and occurs via a spectrum of chromosome- and plasmid-associated elements that lead to structural alteration of the bacterial cell-wall precursor substrates. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. Challenges Posed by Novel Psychoactive Substances – Middle East Perspective

    Directory of Open Access Journals (Sweden)

    Maciej J. Bogusz

    2017-04-01

    Full Text Available New psychoactive substances (NPS are defined as substances of abuse, either in a pure form or a preparation, that are not controlled by the 1961 Single Convention on Narcotic Drugs or the 1971 Convention on Psychotropic Substances, but which may pose a public health threat. In this context, the term “new” does not necessarily refer to new inventions but to substances that have recently become available or popular in a given society or country. This definition indicates that the problem of NPS is not new; however, the availability of any information via new communication technologies in the 21st century has enabled the spread of unwanted and socially harmful information, like information on the commercial availability of various NPS, offered in rising amounts and brands.

  6. New psychoactive substances: catalysing a shift in forensic science practice?

    Science.gov (United States)

    Tettey, Justice; Crean, Conor

    2015-08-05

    The analysis of substances of abuse remains one of the most matured areas in forensic science with a strong scientific basis, namely analytical chemistry. The current evolving drug markets, characterized by the global emergence of new psychoactive substances (NPS) and the need for forensic scientists to identify an unprecedented and ever-increasing number of NPS, presents a unique challenge to this discipline. This article looks at the current situation with NPS at the global level, and the challenges posed to the otherwise technically robust forensic science discipline of analysis of substances of abuse. It discusses the preparedness of forensic science to deal with the current situation and identifies the need for a shift in forensic science practice, especially one which embraces research and looks beyond normal casework in order to provide the much needed data for developing effective policy responses to the NPS problem. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  7. A medicalização como estratégia biopolítica: um estudo sobre o consumo de psicofármacos no contexto de um pequeno município do Rio Grande do Sul Medicalization as a biopolitical strategy: a study about the consuming of psychoactive prescribed drugs in a small town in state of Rio Grande do Sul

    Directory of Open Access Journals (Sweden)

    Vivian Tatiana Galvão Ignácio

    2007-12-01

    Full Text Available Este estudo teve como objetivo compreender como o consumo de psicofármacos se legitimou como uma tecnologia de si no interior do dispositivo de medicalização. Concluímos que esta é uma tecnologia que incide sobre os corpos por estar acoplada aos modos de subjetivação contemporâneos. A análise aqui apresentada trata do contexto social de Boa Vista das Missões, um pequeno município do Rio Grande do Sul. Realizamos uma pesquisa de campo com seis meses de duração e entrevistamos uma amostra de 400 pessoas. A análise dos relatos e das informações construídas buscou dar visibilidade aos enunciados presentes nas formações discursivas e que definem e explicam o consumo de psicofármacos por 53% da população da cidade. Utilizamos a perspectiva genealógica de Michel Foucault para refletir sobre este campo de pesquisa e problematizar a produção de modos de vida marcados por formas de controle individualizantes e totalizantes ao mesmo tempo. Neste sentido, partimos do histórico da inserção dos psicofármacos em nossa cultura para entender as dimensões que ocupam neste contexto. A análise identificou as redes enunciativas no interior do dispositivo de medicalização que fundamentam uma apresentação do biopoder que se sustenta no tripé "dependência, assistencialismo, individualismo".The goal of this research was to comprehend how the consumption of psychoactive prescribed drugs was legitimated as a technology of the self inside the medicalization device (dispositf. We concluded that this is a technology that incurs on the body because it's attached to contemporary modes of subjectification. The analysis presented here refers to Boa Vista das Missões, a small town in the state of Rio Grande do Sul. We conducted a six months field research and interviewed a sample of 400 inhabitants. The speech and data analysis intended to give visibility to the statements present in the discursive formations and which define and explain the

  8. Using evolutionary tools to search for novel psychoactive plants

    DEFF Research Database (Denmark)

    Halse-Gramkow, Morten; Ernst, Madeleine; Rønsted, Nina

    2016-01-01

    Bioprospecting is the search for valuable products from natural sources. Given that most species are poorly known, a key question is where to search. Ethnodirected bioprospecting approaches use traditional knowledge in the process of selecting plants to screen for desired properties...... and phylogenetic distribution of psychoactive plants. We compiled a database of 501 psychoactive plant species and their properties from published sources. We mapped these plant attributes on a phylogenetic tree of all land plant genera and showed that psychoactive properties are not randomly distributed...... on the phylogeny of land plants; instead certain plant lineages show overabundance of psychoactive properties. Furthermore, employing a "hot nodes" approach to identify these lineages, we can narrow down our search for novel psychoactive plants to 8.5% of all plant genera for psychoactivity in general and 1...

  9. The drug discrimination assay: Interpretative value of partial generalization for drug schedule control actions.

    Science.gov (United States)

    Gauvin, David V; Zimmermann, Zachary J; Code, Robert; Baird, Theodore J

    2017-12-11

    The U.S. Food & Drug Administration (FDA) has issued a final guidance document on the preclinical determination of abuse potential that must be conducted in animals for all new molecular entities (NMEs) submitted for a new drug application (NDA). Under statutory restrictions government guidance documents serve only as a guide or an expression of the agency's current thinking on the topic. Guidelines do not legally bind the agency or its registrants to any content in the guidance. There are no statutory (legal) descriptions of what study designs or methodology must be submitted to the Drug Enforcement Administration with respect to drug scheduling review. This paper describes the utility of an alternate method used, worldwide, to assess the internal subjective effects of drugs to predict the abuse liability that provides additional information to address the relative aspects of that liability. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The ethnobotany of psychoactive plant use: a phylogenetic perspective

    National Research Council Canada - National Science Library

    Alrashedy, Nashmiah Aid; Molina, Jeanmaire

    2016-01-01

    ... alternate uses for plants containing psychoactive phytochemicals that have purportedly evolved to ward off plant predators. However, the affinity of these phytochemicals within the hominid nervou...

  11. Epidemiological aspects of illicit psychoactive substance dependents the interned in psychiatric institution of Criciúma-SC

    Directory of Open Access Journals (Sweden)

    Zunei Votri

    2009-01-01

    Full Text Available The research is about a descriptive study of quantitative boarding, developed in October of 2008 in the Psychiatric Hospital of the city of Criciúma-SC, with the objective to identify to the aspects epidemiologists of the illicit psychoactive substance dependents. The specific objectives of the study had been: to identify illicit psychoactive substance dependents interned through handbooks of the institution; to inquire the number of psychiatric readmissions in the studied population; to identify the types of more common illicit psychoactive substances, To identify to aspects epidemiologists of the psychoactive substance dependents from dependent 0 variable: sex, age, age group, level of instruction, race, civil state, number of children, religion, profession and origin; e changeable independent: type of used substance, time of use, number of internments and clinical patology associates. The interest for the research subject appeared from the comment in field of work for presenting great number of patients interned for abuse or dependence of psychoactive substances and its social repercussion. 193 handbooks had been inquired, being that 13 had been identified with illicit psychoactive substance diagnosis in the period of the collection of data, having the prevalence in the masculine sex (9, of the white race (11, the majority single (7, with a young age group, on average 35 years. The majority interned involuntarily (8 and the number of readmissions was equivalent 50% of patients and others 50% having its first internment. How much to the types of used illicit psychoactive substances more, the most cited they had been marijuana (20%, crack (17% and cocaine (17%. The half of the sample almost possess clinical illnesses associates, as cardiopathy, diabetes, hepatitis C, arterial hypertension and HIV (Virus of the Immunodeficiency Human being. From these results one sees it importance of clarification and organization of preventive programs in

  12. The prevalence of psychoactive substances use among secondary school students from selected cities of Upper Silesia

    Directory of Open Access Journals (Sweden)

    Maja Muszyńska-Graca

    2012-09-01

    Full Text Available Background: The prevalence of psychoactive substances among teenagers in Poland has grown for several years. Statistics maintain at a lower level than in the western Europe, however it is necessary to conduct its permanent monitoring. The work presents results of the questionnaire study carried out in IOMEH in years 2010–11. Objective: The aim of this paper is to present the scale of psychoactive substances prevalence among teenagers from Silesian cities. Materials and methods: The programme was carried out by use of modified questionnaire of the ESPAD study. Questions related to characteristics of the examined person, dissemination, accessibility, awareness of risk and problems associated with the use of psychoactive substances. 928 teenagers: students of IIIrd grade of secondary schools and Ist and IInd grades of high schools from Sosnowiec and Chorzów (62% boys and 38% girls participated in the study. Results: 86,9% girls and 89,8% boys confirmed contact with the alcohol at least once in the lifetime and it is the most widespread psychoactive substance in the study group. Out of the other substances, cannabis use was confirmed by 40,7% of students (34,7% girls and 44,3% boys, designer drugs use - by of 21,8% pupils (17,5% girls and 24,5% boys. The distribution within the limits of 10% has been observed in the case of soothing/sleeping pills (also together with alcohol, and amphetamine. The prevalence of contact with other substances was at the level *10%. Boys more often than girls used the respective psychoactive substances (statistically significant differences. Conclusions: Results of the study confirm observation concerning the entire country that drinking alcohol by the young adolescents is becoming the statistical norm. The frequency of other psychoactive substances use demonstrates also concerning levels. There is a need of systematic education among teenagers at school, with particular emphasis on issues related to addiction and

  13. From molecular signatures to predictive biomarkers: Modeling disease pathophysiology and drug mechanism of action

    Directory of Open Access Journals (Sweden)

    Andreas eHeinzel

    2014-08-01

    Full Text Available Omics profiling significantly expanded the molecular landscape describing clinical phenotypes. Association analysis resulted in first diagnostic and prognostic biomarker signatures entering clinical utility. However, utilizing Omics for deepening our understanding of disease pathophysiology, and further including specific interference with drug mechanism of action on a molecular process level still sees limited added value in the clinical setting.We exemplify a computational workflow for expanding from statistics-based association analysis towards deriving molecular pathway and process models for characterizing phenotypes and drug mechanism of action. Interference analysis on the molecular model level allows identification of predictive biomarker candidates for testing drug response. We discuss this strategy on diabetic nephropathy, a complex clinical phenotype triggered by diabetes and presenting with renal as well as cardiovascular endpoints. A molecular pathway map indicates involvement of multiple molecular mechanisms, and selected biomarker candidates reported as associated with disease progression are identified for specific molecular processes. Selective interference of drug mechanism of action and disease-associated processes is identified for drug classes in clinical use, in turn providing precision medicine hypotheses utilizing predictive biomarkers.

  14. Cannabidiol, a non-psychoactive cannabinoid compound, inhibits proliferation and invasion in U87-MG and T98G glioma cells through a multitarget effect.

    Directory of Open Access Journals (Sweden)

    Marta Solinas

    Full Text Available In the present study, we found that CBD inhibited U87-MG and T98G cell proliferation and invasiveness in vitro and caused a decrease in the expression of a set of proteins specifically involved in growth, invasion and angiogenesis. In addition, CBD treatment caused a dose-related down-regulation of ERK and Akt prosurvival signaling pathways in U87-MG and T98G cells and decreased hypoxia inducible factor HIF-1α expression in U87-MG cells. Taken together, these results provide new insights into the antitumor action of CBD, showing that this cannabinoid affects multiple tumoral features and molecular pathways. As CBD is a non-psychoactive phytocannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anti-cancer drug in the management of gliomas.

  15. Prevalence and Behaviour Effects of Psychoactive Substance Use ...

    African Journals Online (AJOL)

    Background: Psychoactive substances can alter consciousness, mood and behaviour of an individual user. Objectives: To determine the pattern of psychoactive substance use and its mental and behavioural effects on university students in Enugu, Nigeria. Methods: A descriptive study was conducted among 422 ...

  16. Psychoactive substance and road traffic accident among commercial ...

    African Journals Online (AJOL)

    Family support influence behaviour such as alcohol use and other psychoactive substances. However, few studies have reported on the relationship between family support and road traffic accidents. The present study was to examine whether perceived family support influence the prevalence of psychoactive substances ...

  17. Prevalence of Self-Medication of Psychoactive Stimulants and ...

    African Journals Online (AJOL)

    Purpose: To evaluate the prevalence of self-medication of psychoactive stimulants and antidepressants among pharmacy students of Pakistan. Methods: A cross-sectional survey on self-medication of psychoactive stimulants and antidepressants among pharmacy students was conducted with a structured and validated ...

  18. 40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise explicitly...

  19. The ethnobotany of psychoactive plant use: a phylogenetic perspective

    Science.gov (United States)

    2016-01-01

    Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane) have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants suggests

  20. The ethnobotany of psychoactive plant use: a phylogenetic perspective.

    Science.gov (United States)

    Alrashedy, Nashmiah Aid; Molina, Jeanmaire

    2016-01-01

    Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane) have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants suggests

  1. The ethnobotany of psychoactive plant use: a phylogenetic perspective

    Directory of Open Access Journals (Sweden)

    Nashmiah Aid Alrashedy

    2016-10-01

    Full Text Available Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives. The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg, Papaveraceae (opium poppy, Cactaceae (peyote, Convolvulaceae (morning glory, Solanaceae (tobacco, Lamiaceae (mints, Apocynaceae (dogbane have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence. However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants

  2. [Sex differences in drug action: the role of multidrug-resistance proteins (MRPs)].

    Science.gov (United States)

    Smirnova, O V

    2012-01-01

    The mechanisms of participation of multidrug-resistance proteins (MRPs) in sex difference pattern of drug efficiency and side effects have been analyzed. MRPs structure, their tissue and cellular localization, substrate specificity, and functions have been considered. Regulation of expression and activity of MRPs by endogenous metabolites, signal compounds, including sex hormones, as well as by drug agents have been represented. The role of nuclear receptors in the regulation of MRPs expression has been demonstrated. The data on sex differences in hepatic and renal MRPs expression and expression of nuclear receptors, participating in their induction, have been shown. The participation of MRPs in the formation of sex differences of drug pharmacokinetics has been discussed. Sex differences in representation and functional activity of MRPs in such excretory organs as liver and kidney was concluded would play the essential role in sex dependence of pharmacokinetics and efficiency of drug action.

  3. Isothermal microcalorimetry, a new tool to monitor drug action against Trypanosoma brucei and Plasmodium falciparum.

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    Tanja Wenzler

    Full Text Available Isothermal microcalorimetry is an established tool to measure heat flow of physical, chemical or biological processes. The metabolism of viable cells produces heat, and if sufficient cells are present, their heat production can be assessed by this method. In this study, we investigated the heat flow of two medically important protozoans, Trypanosoma brucei rhodesiense and Plasmodium falciparum. Heat flow signals obtained for these pathogens allowed us to monitor parasite growth on a real-time basis as the signals correlated with the number of viable cells. To showcase the potential of microcalorimetry for measuring drug action on pathogenic organisms, we tested the method with three antitrypanosomal drugs, melarsoprol, suramin and pentamidine and three antiplasmodial drugs, chloroquine, artemether and dihydroartemisinin, each at two concentrations on the respective parasite. With the real time measurement, inhibition was observed immediately by a reduced heat flow compared to that in untreated control samples. The onset of drug action, the degree of inhibition and the time to death of the parasite culture could conveniently be monitored over several days. Microcalorimetry is a valuable element to be added to the toolbox for drug discovery for protozoal diseases such as human African trypanosomiasis and malaria. The method could probably be adapted to other protozoan parasites, especially those growing extracellularly.

  4. Bufotenine: toward an understanding of possible psychoactive mechanisms.

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    McBride, M C

    2000-01-01

    A review of the neuropharmacology of the alleged hallucinogen bufotenine is presented, including recent experimental results showing activity similar to LSD and other known hallucinogens (psilocin and 5-MeO-DMT) at the purported hallucinogenic serotonin (5-HT) receptors, 5-HT2A and 5-HT2C. In addition, current reports of computer modeling of the receptors and ligand binding sites give evidence of bufotenine's ability to bind and activate these receptors. While binding and activation of the purported hallucinogenic receptors are not the full extent of the hallucinogenic signature, this evidence shows support for the rationale that the reported lack of the drug's classic hallucinogenic response in human experiments is due to poor ability to cross the blood brain barrier (BBB), not lack of activation of the appropriate brain receptors. Further evidence is reviewed that in some physiological states, some drugs with characteristics similar to bufotenine which do not normally cross the BBB, cross it and enter the brain. While direct human experimental evidence of bufotenine's hallucinogenic activity seems lacking, the above combined factors are considered, and possible explanations of bufotenine's reported psychoactivity are suggested. Additionally, updated experimental models testing the possible nature of bufotenine's hallucinogenic potential are proposed.

  5. MULTIFACTORINESS OF THE MECHANISMS OF ACTION OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN OSTEOARTHROSIS

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    Vladimir Vasilyevich Badokin

    2009-12-01

    Full Text Available The paper presents the current views of the effects of nonsteroidal anti-inflammatory drugs on the mechanisms of development of inflammation in osteoarthrosis and their action on the metabolism of chondrocytes and extracellular substance of the articular cartilage. It also gives the results of numerous studies of the efficacy and safety of meloxicam in osteoarthrosis and the data supporting its chondroprotective properties

  6. MULTIFACTORINESS OF THE MECHANISMS OF ACTION OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN OSTEOARTHROSIS

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2009-01-01

    Full Text Available The paper presents the current views of the effects of nonsteroidal anti-inflammatory drugs on the mechanisms of development of inflammation in osteoarthrosis and their action on the metabolism of chondrocytes and extracellular substance of the articular cartilage. It also gives the results of numerous studies of the efficacy and safety of meloxicam in osteoarthrosis and the data supporting its chondroprotective properties

  7. Kinetics of drug action in disease states: towards physiology-based pharmacodynamic (PBPD) models.

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    Danhof, Meindert

    2015-10-01

    Gerhard Levy started his investigations on the "Kinetics of Drug Action in Disease States" in the fall of 1980. The objective of his research was to study inter-individual variation in pharmacodynamics. To this end, theoretical concepts and experimental approaches were introduced, which enabled assessment of the changes in pharmacodynamics per se, while excluding or accounting for the cofounding effects of concomitant changes in pharmacokinetics. These concepts were applied in several studies. The results, which were published in 45 papers in the years 1984-1994, showed considerable variation in pharmacodynamics. These initial studies on kinetics of drug action in disease states triggered further experimental research on the relations between pharmacokinetics and pharmacodynamics. Together with the concepts in Levy's earlier publications "Kinetics of Pharmacologic Effects" (Clin Pharmacol Ther 7(3): 362-372, 1966) and "Kinetics of pharmacologic effects in man: the anticoagulant action of warfarin" (Clin Pharmacol Ther 10(1): 22-35, 1969), they form a significant impulse to the development of physiology-based pharmacodynamic (PBPD) modeling as novel discipline in the pharmaceutical sciences. This paper reviews Levy's research on the "Kinetics of Drug Action in Disease States". Next it addresses the significance of his research for the evolution of PBPD modeling as a scientific discipline. PBPD models contain specific expressions to characterize in a strictly quantitative manner processes on the causal path between exposure (in terms of concentration at the target site) and the drug effect (in terms of the change in biological function). Pertinent processes on the causal path are: (1) target site distribution, (2) target binding and activation and (3) transduction and homeostatic feedback.

  8. Preclinical platform for the translational research of the abuse potential of novel drug candidates

    OpenAIRE

    Teuns, Greet

    2014-01-01

    To determine the abuse potential of new CNS-active molecular entities with a novel mechanism of action, considerable knowledge of the pharmacology, toxicity and kinetics is needed to enable the choice of the correct tests, the selection of an appropriate dose range of the test compound and the proper choice of the psycho-active reference compound(s) or a scheduled comparator. In addition, one must have a thorough expertise of the current overall Drug Development process and subsequent require...

  9. Baths Salts, Spice, and Related Designer Drugs: The Science Behind the Headlines

    Science.gov (United States)

    Solis, Ernesto; Watterson, Lucas R.; Marusich, Julie A.; Fantegrossi, William E.; Wiley, Jenny L.

    2014-01-01

    The abuse of synthetic psychoactive substances known as “designer drugs,” or “new psychoactive substances” (NPS), is increasing at an alarming rate. NPS are purchased as alternatives to traditional illicit drugs of abuse and are manufactured to circumvent laws regulating the sale and use of controlled substances. Synthetic cathinones (i.e., “bath salts”) and synthetic cannabinoids (i.e., “spice”) are two types of NPS that have received substantial media attention. Although low recreational doses of bath salts or spice compounds can produce desirable effects, high doses or chronic exposure often leads to dangerous medical consequences, including psychosis, violent behaviors, tachycardia, hyperthermia, and even death. Despite the popularity of NPS, there is a paucity of scientific data about these drugs. Here we provide a brief up-to-date review describing the mechanisms of action and neurobiological effects of synthetic cathinones and cannabinoids. PMID:25392483

  10. [Psychoactive substance use among Espírito Santo Federal University odontology students].

    Science.gov (United States)

    Teixeira, Renata Frossard; Souza, Renata Santos de; Buaiz, Vitor; Siqueira, Marluce Miguel de

    2010-05-01

    The objective of this article is to trace the psychoactive substance use profile among odontology college students from the Espírito Santo Federal University Health Sciences Center. It is an explorative, descriptive, transversal and quantitative study developed with first to last year college students of the odontology course. The instrument used for data collection was an adaptation of one proposed by WHO and developed by WHO - Research and Reporting Project on the Epidemiology of Drug Dependence. Data were listed and analyzed through the Statistical Package Program for the Social Science. The results showed that 60.3% colleges student are female, 48.9% age between 20 and 22 years, 41.3% and 43.7% belong to A and B social class, respectively. The prevalence of psychoactive drugs use reported at least once in lifetime was 72.4% except for alcohol and tobacco; 25.9% used inhaled drugs, 13.2% marijuana, 10.9% amphetamines , 27% tobacco and 87.9% alcohol. It could be concluded that is necessary to prevent improper drug use among college students by inserting this subject on the college curriculum as well as establishing drug use prevention programs for students.

  11. New psychoactive substances legislation in Ireland - Perspectives from academia.

    Science.gov (United States)

    Kavanagh, Pierce V; Power, John D

    2014-01-01

    The emergence of 'legal highs' or 'new psychoactive substances' (NPS) on the Irish market is reflective of their appearance in many countries, with some notable exceptions. The official response to the situation is examined here by looking at Irish controlled drugs legislation and drug enforcement policies as enacted in recent years and their effects on academic research on NPS. The philosophy and practice of outright bans of scheduled substances has not been effective in delivering the stated aims of illicit drug control, namely harm reduction. With these legislative changes, we have witnessed the removal of the 'legitimate' sale and open marketing of a number of NPS to the general public in commercial retail premises. However, as legislation was enacted, suppliers and vendors rapidly changed the contents of their legal high products from now controlled to non-controlled substances. We have found that it is administratively challenging to perform scientific research on controlled substances at academic institutions. It is desirable to gather analytical, pharmacological, and toxicological data on these substances as they emerge on the market but due to the restrictive nature of licensing requirements, once a substance or generic class of substances is controlled, this becomes more difficult. The facts that any quantity of substance, no matter how small, is controlled, the nomenclature used to describe compounds is not consistent within the enacted legislation and the use of catch-all classes of compounds with the intention of controlling many similar molecular structures, all create problematic issues for academic researchers. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Implementation of mechanism of action biology-driven early drug development for children with cancer.

    Science.gov (United States)

    Pearson, Andrew D J; Herold, Ralf; Rousseau, Raphaël; Copland, Chris; Bradley-Garelik, Brigid; Binner, Debbie; Capdeville, Renaud; Caron, Hubert; Carleer, Jacqueline; Chesler, Louis; Geoerger, Birgit; Kearns, Pamela; Marshall, Lynley V; Pfister, Stefan M; Schleiermacher, Gudrun; Skolnik, Jeffrey; Spadoni, Cesare; Sterba, Jaroslav; van den Berg, Hendrick; Uttenreuther-Fischer, Martina; Witt, Olaf; Norga, Koen; Vassal, Gilles

    2016-07-01

    An urgent need remains for new paediatric oncology drugs to cure children who die from cancer and to reduce drug-related sequelae in survivors. In 2007, the European Paediatric Regulation came into law requiring industry to create paediatric drug (all types of medicinal products) development programmes alongside those for adults. Unfortunately, paediatric drug development is still largely centred on adult conditions and not a mechanism of action (MoA)-based model, even though this would be more logical for childhood tumours as these have much fewer non-synonymous coding mutations than adult malignancies. Recent large-scale sequencing by International Genome Consortium and Paediatric Cancer Genome Project has further shown that the genetic and epigenetic repertoire of driver mutations in specific childhood malignancies differs from more common adult-type malignancies. To bring about much needed change, a Paediatric Platform, ACCELERATE, was proposed in 2013 by the Cancer Drug Development Forum, Innovative Therapies for Children with Cancer, the European Network for Cancer Research in Children and Adolescents and the European Society for Paediatric Oncology. The Platform, comprising multiple stakeholders in paediatric oncology, has three working groups, one with responsibility for promoting and developing high-quality MoA-informed paediatric drug development programmes, including specific measures for adolescents. Key is the establishment of a freely accessible aggregated database of paediatric biological tumour drug targets to be aligned with an aggregated pipeline of drugs. This will enable prioritisation and conduct of early phase clinical paediatric trials to evaluate these drugs against promising therapeutic targets and to generate clinical paediatric efficacy and safety data in an accelerated time frame. Through this work, the Platform seeks to ensure that potentially effective drugs, where the MoA is known and thought to be relevant to paediatric

  13. Mid-Term Assessment of the EU Drugs Strategy 2013–2020 and Final Evaluation of the Action Plan on Drugs 2013–2016

    Science.gov (United States)

    Emilie, Balbirnie; Matthew, Davies; Emma, Disley; Cristina Gonzalez, Monsalve; Stephen, Hartka; Stijn, Hoorens; Kristy, Kruithof; Martin, Sacher; Jirka, Taylor

    2018-01-01

    Abstract The aim of the EU Drugs Strategy 2013–2020 is to contribute to a reduction in drug demand and drug supply within the EU. The Strategy has so far been implemented by an Action Plan covering the period 2013–2016. This article sets out the findings of an evaluation that assesses the degree of implementation of the Strategy and the Action Plan in terms of outputs and, where possible, impacts. It looks at the extent to which the objectives of the Strategy have been achieved. The evaluation aims to provide evidence to support the European Commission's decision about whether to propose a new Action Plan for the period 2017–2020 and, if so, what changes would be needed compared to the current plan. Through applying a mixed-methods approach, the evaluation examined the effectiveness, efficiency, relevance and coherence of the actions undertaken on the basis of the EU Drugs Strategy and the Action Plan, as well as their EU added value. The evaluation makes 20 recommendations, addressed to the European Commission, Member States, the European Council and other stakeholders. The key recommendation for the Commission is that a new Action Plan should be implemented for the period 2017–2020. This should be an updated version of the current Action Plan, rather than taking a new approach or introducing more new actions.

  14. Target and suspect screening of psychoactive substances in sewage-based samples by UHPLC-QTOF.

    Science.gov (United States)

    Baz-Lomba, J A; Reid, Malcolm J; Thomas, Kevin V

    2016-03-31

    The quantification of illicit drug and pharmaceutical residues in sewage has been shown to be a valuable tool that complements existing approaches in monitoring the patterns and trends of drug use. The present work delineates the development of a novel analytical tool and dynamic workflow for the analysis of a wide range of substances in sewage-based samples. The validated method can simultaneously quantify 51 target psychoactive substances and pharmaceuticals in sewage-based samples using an off-line automated solid phase extraction (SPE-DEX) method, using Oasis HLB disks, followed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) in MS(e). Quantification and matrix effect corrections were overcome with the use of 25 isotopic labeled internal standards (ILIS). Recoveries were generally greater than 60% and the limits of quantification were in the low nanogram-per-liter range (0.4-187 ng L(-1)). The emergence of new psychoactive substances (NPS) on the drug scene poses a specific analytical challenge since their market is highly dynamic with new compounds continuously entering the market. Suspect screening using high-resolution mass spectrometry (HRMS) simultaneously allowed the unequivocal identification of NPS based on a mass accuracy criteria of 5 ppm (of the molecular ion and at least two fragments) and retention time (2.5% tolerance) using the UNIFI screening platform. Applying MS(e) data against a suspect screening database of over 1000 drugs and metabolites, this method becomes a broad and reliable tool to detect and confirm NPS occurrence. This was demonstrated through the HRMS analysis of three different sewage-based sample types; influent wastewater, passive sampler extracts and pooled urine samples resulting in the concurrent quantification of known psychoactive substances and the identification of NPS and pharmaceuticals. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. In vitro action of antiparasitic drugs, especially artesunate, against Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Thaís Cobellis Gomes

    2012-08-01

    Full Text Available INTRODUCTION: Toxoplasmosis is usually a benign infection, except in the event of ocular, central nervous system (CNS, or congenital disease and particularly when the patient is immunocompromised. Treatment consists of drugs that frequently cause adverse effects; thus, newer, more effective drugs are needed. In this study, the possible activity of artesunate, a drug successfully being used for the treatment of malaria, on Toxoplasma gondii growth in cell culture is evaluated and compared with the action of drugs that are already being used against this parasite. METHODS: LLC-MK2 cells were cultivated in RPMI medium, kept in disposable plastic bottles, and incubated at 36ºC with 5% CO2. Tachyzoites of the RH strain were used. The following drugs were tested: artesunate, cotrimoxazole, pentamidine, pyrimethamine, quinine, and trimethoprim. The effects of these drugs on tachyzoites and LLC-MK2 cells were analyzed using nonlinear regression analysis with Prism 3.0 software. RESULTS: Artesunate showed a mean tachyzoite inhibitory concentration (IC50 of 0.075µM and an LLC MK2 toxicity of 2.003µM. Pyrimethamine was effective at an IC50 of 0.482µM and a toxicity of 11.178µM. Trimethoprim alone was effective against the in vitro parasite. Cotrimoxazole also was effective against the parasite but at higher concentrations than those observed for artesunate and pyrimethamine. Pentamidine and quinine had no inhibitory effect over tachyzoites. CONCLUSIONS: Artesunate is proven in vitro to be a useful alternative for the treatment of toxoplasmosis, implying a subsequent in vivo effect and suggesting the mechanism of this drug against the parasite.

  16. Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

    Science.gov (United States)

    Swedberg, Michael D B

    2016-01-01

    Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

  17. Preclinical models for interrogating drug action in human cancers using Stable Isotope Resolved Metabolomics (SIRM).

    Science.gov (United States)

    Lane, Andrew N; Higashi, Richard M; Fan, Teresa W-M

    2016-07-01

    In this review we compare the advantages and disadvantages of different model biological systems for determining the metabolic functions of cells in complex environments, how they may change in different disease states, and respond to therapeutic interventions. All preclinical drug-testing models have advantages and drawbacks. We compare and contrast established cell, organoid and animal models with ex vivo organ or tissue culture and in vivo human experiments in the context of metabolic readout of drug efficacy. As metabolism reports directly on the biochemical state of cells and tissues, it can be very sensitive to drugs and/or other environmental changes. This is especially so when metabolic activities are probed by stable isotope tracing methods, which can also provide detailed mechanistic information on drug action. We have developed and been applying Stable Isotope-Resolved Metabolomics (SIRM) to examine metabolic reprogramming of human lung cancer cells in monoculture, in mouse xenograft/explant models, and in lung cancer patients in situ (Lane et al. 2011; T. W. Fan et al. 2011; T. W-M. Fan et al. 2012; T. W. Fan et al. 2012; Xie et al. 2014b; Ren et al. 2014a; Sellers et al. 2015b). We are able to determine the influence of the tumor microenvironment using these models. We have now extended the range of models to fresh human tissue slices, similar to those originally described by O. Warburg (Warburg 1923), which retain the native tissue architecture and heterogeneity with a paired benign versus cancer design under defined cell culture conditions. This platform offers an unprecedented human tissue model for preclinical studies on metabolic reprogramming of human cancer cells in their tissue context, and response to drug treatment (Xie et al. 2014a). As the microenvironment of the target human tissue is retained and individual patient's response to drugs is obtained, this platform promises to transcend current limitations of drug selection for clinical

  18. Preclinical models for interrogating drug action in human cancers using Stable Isotope Resolved Metabolomics (SIRM)

    Science.gov (United States)

    Lane, Andrew N.; Higashi, Richard M.; Fan, Teresa W-M.

    2016-01-01

    Aims In this review we compare the advantages and disadvantages of different model biological systems for determining the metabolic functions of cells in complex environments, how they may change in different disease states, and respond to therapeutic interventions. Background All preclinical drug-testing models have advantages and drawbacks. We compare and contrast established cell, organoid and animal models with ex vivo organ or tissue culture and in vivo human experiments in the context of metabolic readout of drug efficacy. As metabolism reports directly on the biochemical state of cells and tissues, it can be very sensitive to drugs and/or other environmental changes. This is especially so when metabolic activities are probed by stable isotope tracing methods, which can also provide detailed mechanistic information on drug action. We have developed and been applying Stable Isotope-Resolved Metabolomics (SIRM) to examine metabolic reprogramming of human lung cancer cells in monoculture, in mouse xenograft/explant models, and in lung cancer patients in situ (Lane et al. 2011; T. W. Fan et al. 2011; T. W-M. Fan et al. 2012; T. W. Fan et al. 2012; Xie et al. 2014b; Ren et al. 2014a; Sellers et al. 2015b). We are able to determine the influence of the tumor microenvironment using these models. We have now extended the range of models to fresh human tissue slices, similar to those originally described by O. Warburg (Warburg 1923), which retain the native tissue architecture and heterogeneity with a paired benign versus cancer design under defined cell culture conditions. This platform offers an unprecedented human tissue model for preclinical studies on metabolic reprogramming of human cancer cells in their tissue context, and response to drug treatment (Xie et al. 2014a). As the microenvironment of the target human tissue is retained and individual patient's response to drugs is obtained, this platform promises to transcend current limitations of drug selection

  19. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Juan P de Macêdo

    2015-05-01

    Full Text Available Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug

  20. Sex-related differences in cadmium-induced alteration of drug action in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Schnell, R.C.; Pence, D.H.; Prosser, T.D.; Miya, T.S.

    1976-01-01

    Three days after pretreatment of rats of both sexes with cadmium (2 mg/kg, i.p.), the duration of hypnosis induced by hexobarbital (75 mg/kg, i.p.) was potentiated in males but not females. Likewise, similar treatment with cadmium leads to significant inhibition of the metabolism of hexobarbital by hepatic microsomal enzymes obtained from male but not female animals. These data suggest that there is a sex-related difference in the ability of cadmium to alter drug action in rats.

  1. Novel Strategies to Improve the Anticancer Action of 5-Fluorouracil by Using Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    José L. Arias

    2008-10-01

    Full Text Available Because of the fundamental importance of new therapeutic routes for cancer treatment, a number of systems based on colloidal particles as vehicles for the delivery of the anticancer drug 5-fluorouracil have been devised. The target is always to provide the proper dose of the antitumor agent only at the desired locus of action, thus reducing the unwanted side effects. In this review, the main strategies and the more significant results in the development of 5-fluorouracil carriers for cancer treatment are discussed.

  2. [Letter: Influence of certain drugs on the action of contraceptive pills].

    Science.gov (United States)

    Belaisch, J; Driguez, P; Janaud, A

    1976-06-26

    4 cases from the authors' experiences are added to the list of women who became pregnant during oral contraception while taking other drugs. 2 were 24- and 28-year-old epileptics taking Stediril and Mysoline, or primidone, a deoxybarbiturate. The 3rd was a 32-year-old woman who had forgotten 1 Stediril pill and taken 2 the next day, while taking 75 mg phenobarbital for a homeopathic regime. The 4th had been using Stediril for 5 years and had stopped for 2 months, and conceived during her 1st cycle after resuming the pill. She was taking drugs for migraine headaches, Nivaprine to prevent malaria, tetracyclines and trisulfazine for diarrhea. It is emphasized that when the usual pill side effects or regular withdrawal bleeding are absent in women on other medications, physicians should be alerted that the contraceptive action of the pill may be compromised.

  3. Pharmacological receptors of nematoda as target points for action of antiparasitic drugs

    Directory of Open Access Journals (Sweden)

    Trailović Saša M.

    2010-01-01

    Full Text Available Cholinergic receptors of parasitic nematodes are one of the most important possible sites of action of antiparasitic drugs. This paper presents some of our own results of electrophysiological and pharamcological examinations of nicotinic and muscarinic receptors of nematodes, as well as data from literature on a new class of anthelmintics that act precisely on cholinergic receptors. The nicotinic acetylcholine receptor (nAChR is located on somatic muscle cells of nematodes and it is responsible for the coordination of parasite movement. Cholinomimetic anthelmintics act on this receptor, as well as acetylcholine, an endogenic neurotransmitter, but they are not sensitive to enzyme acetylcholineesterase which dissolves acetylcholine. As opposed to the nicotinic receptor of vertebra, whose structure has been examined thoroughly, the stoichiometry of the nicotinic receptor of nematodes is not completely known. However, on the grounds of knowledge acquired so far, a model has been constructed recently of the potential composition of a type of nematodes nicotinic receptor, as the site of action of anthelmintics. Based on earlier investigations, it is supposed that a conventional muscarinic receptor exists in nematodes as well, so that it can also be a new pharamocological target for the development of antinematode drugs. The latest class of synthesized anthelmintics, named aminoacetonitriles (AAD, act via the nicotinic receptor. Monepantel is the first drug from the AAD group as a most significant candidate for registration in veterinary medicine. Even though several groups of cholinomimetic anthelmintics (imiodazothiazoles, tetrahydropyrimidines, organophosphat anthelmintics have been in use in veterinary practice for many years now, it is evident that cholinergic receptors of nematodes still present an attractive place in the examinations and development of new antinematode drugs. .

  4. Action sequencing in the spontaneous swimming behavior of zebrafish larvae - implications for drug development.

    Science.gov (United States)

    Palmér, Tobias; Ek, Fredrik; Enqvist, Olof; Olsson, Roger; Åström, Kalle; Petersson, Per

    2017-06-09

    All motile organisms need to organize their motor output to obtain functional goals. In vertebrates, natural behaviors are generally composed of a relatively large set of motor components which in turn are combined into a rich repertoire of complex actions. It is therefore an experimental challenge to investigate the organizational principles of natural behaviors. Using the relatively simple locomotion pattern of 10 days old zebrafish larvae we have here characterized the basic organizational principles governing the swimming behavior. Our results show that transitions between different behavioral states can be described by a model combining a stochastic component with a control signal. By dividing swimming bouts into a limited number of categories, we show that similar types of swimming behavior as well as stand-stills between bouts were temporally clustered, indicating a basic level of action sequencing. Finally, we show that pharmacological manipulations known to induce alterations in the organization of motor behavior in mammals, mainly through basal ganglia interactions, have related effects in zebrafish larvae. This latter finding may be of specific relevance to the field of drug development given the growing importance of zebrafish larvae in phenotypic screening for novel drug candidates acting on central nervous system targets.

  5. Test of a model of antiarrhythmic drug action. Effects of quinidine and lidocaine on myocardial conduction.

    Science.gov (United States)

    Hondeghem, L; Katzung, B G

    1980-06-01

    The effects of quinidine and lidocaine on the maximum upstroke velocity (Vmax) of the ventricular myocardial action potential were compared with the effects predicted by a model over a wide range of driving rates, rhythm disturbances and holding potentials. These rate-, rhythm- and voltage-dependent effects were accurately predicted by the proposed model. The model was also able to predict several previously undocumented properties of the drugs: 1) If lidocaine decreases Vmax of a pulse train, the steady state is reached within a few action potentials. 2) The poststimulation recovery of Vmax in the presence of lidocaine or quinidine can occur in a multiexponential fashion, if the membrane potential is kept at the potential where both the fast (operating mainly at more negative membrane potentials) and the slow (operating at more positive potentials) recovery processes are operative. 3) Hyperpolarization markedly attenuates the rate-dependent drug effects. 4) Combinations of lidocaine and quinidine have a superadditive effect on the Vmax of early extrasystoles.

  6. Unique Mechanism of Action of the Thiourea Drug Isoxyl on Mycobacterium tuberculosis*

    Science.gov (United States)

    Phetsuksiri, Benjawan; Jackson, Mary; Scherman, Hataichanok; McNeil, Michael; Besra, Gurdyal S.; Baulard, Alain R.; Slayden, Richard A.; DeBarber, Andrea E.; Barry, Clifton E.; Baird, Mark S.; Crick, Dean C.; Brennan, Patrick J.

    2016-01-01

    The thiourea isoxyl (thiocarlide; 4,4′-diisoamyloxydiphenylthiourea) is known to be an effective anti-tuberculosis drug, active against a range of multidrug-resistant strains of Mycobacterium tuberculosis and has been used clinically. Little was known of its mode of action. We now demonstrate that isoxyl results in a dose-dependent decrease in the synthesis of oleic and, consequently, tuberculostearic acid in M. tuberculosis with complete inhibition at 3 μg/ml. Synthesis of mycolic acid was also affected. The anti-bacterial effect of isoxyl was partially reversed by supplementing growth medium with oleic acid. The specificity of this inhibition pointed to a Δ9-stearoyl desaturase as the drug target. Development of a cell-free assay for Δ9-desaturase activity allowed direct demonstration of the inhibition of oleic acid synthesis by isoxyl. Interestingly, sterculic acid, a known inhibitor of Δ9-desaturases, emulated the effect of isoxyl on oleic acid synthesis but did not affect mycolic acid synthesis, demonstrating the lack of a relationship between the two effects of the drug. The three putative fatty acid desaturases in the M. tuberculosis genome, desA1, desA2, and desA3, were cloned and expressed in Mycobacterium bovis BCG. Cell-free assays and whole cell labeling demonstrated increased Δ9-desaturase activity and oleic acid synthesis only in the desA3-overexpressing strain and an increase in the minimal inhibitory concentration for isoxyl, indicating that DesA3 is the target of the drug. These results validate membrane-bound Δ9-desaturase, DesA3, as a new therapeutic target, and the thioureas as anti-tuberculosis drugs worthy of further development. PMID:14559907

  7. Modern representations about differential diagnosis of schizophrenia-like psychosis disorders due to psychoactive substance use

    Directory of Open Access Journals (Sweden)

    V. V. Chugunov

    2014-08-01

    Full Text Available In recent years in the world there is a tendency of quantity of persons who use drugs increase. Free availability of drugs of different groups for population is the main cause. Another trend associated with the consumption of drugs. All these factors led to the increased frequency of psychosis occurrence among consumers of psychoactive substances. In structure of such psychosis there are a variety of symptoms and syndromes. And since the number of drug users is quite broad in its structure - there are also persons with mental illness. This gives number of diagnostic difficulties. In this regard, the aim of the study was to trace the modern ideas of differential diagnosis of schizophrenia-like psychosis disorders due to the drug use. Materials and methods of research. In this work the content analysis of the modern representations of differential diagnosis of schizophrenia-like psychosis disorders as a result of the use of psychoactive substances was made. The problem of determination of primary and secondary nature of drug addiction in patients with psychotic disorders was indicated. Etiology and psychopathogenesis hypotheses of the addiction from psychoactive substances in the context of their correlation with endogenous mental pathology were defined. In the literature there is no clear diagnostic criteria that would allow distinguishing psychosis due to the use of drugs and endogenous psychosis, which is combined with the admission medicines. However, the attention of clinicians should be concentrated on the premorbid condition: the presence of hereditary family history, pathological behavior in childhood and adolescence. It was found that the majority of substances may cause one or more syndromes - delirium, dementia, and amnestic syndrome, delusional syndrome, hallucinatory syndrome, depressive syndrome, anxiety, and personality disorder, such disorders as schizophrenia-like psychosis disorders are not rare. Special attention was paid to the

  8. Proficiency testing for psychoactive substances in Italy.

    Science.gov (United States)

    Ferrara, S D; Brusini, G; Maietti, S; Frison, G; Castagna, F; Allevi, S; Menegus, A M; Tedeschi, L

    1999-01-01

    This paper describes the general design and main results of the Italian proficiency testing program for the analysis of psychoactive substances in urine, a long-term initiative created in 1995 on an educational basis and characterized by an innovative internet-based service for data exchange between laboratories and the organizing body. Batches of six urine samples, validated by reference laboratories, are sent every 3 months to participating laboratories, which may choose which classes of substances to test from those planned by the program panel and, within those classes, which type of analytical commitment to work on: identification of just one class (Option 1), identification of single substances (Option 2), or identification and quantification of single substances (Option 3). Comprehensive periodical reports and annual reports are provided to participants with evaluation of their performance and an annual workshop is organized to discuss technical-scientific topics related to clinical, forensic and analytical toxicology. About 200 laboratories currently participate in the program and a total of 67,059 analyses have been carried out since 1995. The mean percentage of correct results was 96.8%, with a yearly improvement of about 0.4%. The best average false positive and false negative rates were obtained for methadone (0.2% and 2.1% respectively) and cocaine (0.3% and 2.2%). The worst average false positive rates were obtained for amphetamines and opiates (3.2% and 5.0%) and worst average false negative rates for amphetamines, barbiturates and cannabinoids (17.4%, 30.7% and 19.9%).

  9. The noradrenaline transporter as site of action for the anti-Parkinson drug amantadine.

    Science.gov (United States)

    Sommerauer, Christian; Rebernik, Patrick; Reither, Harald; Nanoff, Christian; Pifl, Christian

    2012-03-01

    Amantadine is an established antiparkinsonian drug with a still unclear molecular site of action. In vivo studies on rodents, in vitro studies on tissue of rodents as well as binding studies on post mortem human tissue implicate monoamine transporters and NMDA receptors. In order to re-examine its action at human variants of these proteins on intact cells we established cells stably expressing the human NR1/2A NMDA-receptor, noradrenaline transporter (NAT) or dopamine transporter (DAT) and tested the activity of amantadine in patch-clamp, uptake, release, and cytotoxicity experiments. Amantadine was less potent in blockade of NMDA-induced inward currents than in blockade of noradrenaline uptake and in induction of inward currents in NAT expressing cells. It was 30 times more potent in blocking uptake in NAT- than in DAT cells. Amantadine induced NAT-mediated release at concentrations of 10-100 μM in superfusion experiments and blocked NAT-mediated cytotoxicity of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl-pyridinium (MPP(+)) at concentrations of 30-300 μM, whereas 300-1000 μM amantadine was necessary to block NMDA-receptor mediated cytotoxicity. Similar to amphetamine, amantadine was inactive at α(2A)-adrenergic receptors and induced reverse noradrenaline transport by NAT albeit with smaller effect size. Thus, amantadine acted as "amphetamine-like releaser" with selectivity for the noradrenergic system. These findings and differences with memantine, which had been reported as less efficient antiparkinsonian drug than amantadine but in our hands was significantly more potent at the NMDA-receptor, suggest contributions from a noradrenergic mechanism in the antiparkinsonian action of amantadine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Drug insight: Mechanisms and sites of action of ursodeoxycholic acid in cholestasis.

    Science.gov (United States)

    Beuers, Ulrich

    2006-06-01

    Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in various cholestatic disorders. Several potential mechanisms and sites of action of UDCA have been unraveled in clinical and experimental studies, which could explain its beneficial effects. The relative contribution of these mechanisms to the anticholestatic action of UDCA depends on the type and stage of the cholestatic injury. In early-stage primary biliary cirrhosis and primary sclerosing cholangitis, protection of injured cholangiocytes against the toxic effects of bile acids might prevail. Stimulation of impaired hepatocellular secretion by mainly post-transcriptional mechanisms, including stimulation of synthesis, targeting and apical membrane insertion of key transporters, seems to be relevant in more advanced cholestasis. In intrahepatic cholestasis of pregnancy, stimulation of impaired hepatocellular secretion could be crucial for rapid relief of pruritus and improvement of serum liver tests, as it is in some forms of drug-induced cholestasis. In cystic fibrosis, stimulation of cholangiocellular calcium-dependent secretion of chloride and bicarbonate ions could have a major impact. Inhibition of bile-acid-induced hepatocyte apoptosis can have a role in all states of cholestasis that are characterized by hepatocellular bile-acid retention. Different mechanisms of action could, therefore, contribute to the beneficial effect of UDCA under various cholestatic conditions.

  11. Vegetables as new psychoactive drugs: a narrative review

    Directory of Open Access Journals (Sweden)

    Beatriz Rodríguez Salgado

    2016-03-01

    Full Text Available Existe un interés creciente en los vegetales con efectos psicoactivos por parte de consumidores, con diferentes niveles de experiencia. Esto ha generado una necesidad de actualización de conocimientos del lado de los profesionales médicos y de otros responsables de la salud pública. Se trata, por lo general, de plantas de uso en ceremonias chamánicas con intención curativa, en rituales o simplemente de uso tradicional que han dado el salto al mundo occidental como nuevas drogas psicoactivas, en gran medida gracias a la facilidad de compra, venta, cultivo e intercambio de información que ofrece Internet. Recopilamos en este texto los vegetales con propiedades psicoactivas más relevantes, tanto por su frecuente mención en foros de usuarios o en portales destinados a la reducción de daños en el consumo de drogas, como por su aparición en textos científicos.

  12. Use of psychoactive and antiepileptic drugs: guidelines for pediatricians

    OpenAIRE

    Rocha, Gibsi P.; Batista, Bianca H.; Nunes, Magda L.

    2004-01-01

    OBJETIVO: Revisar as indicações e o manejo clínico das drogas psicoativas e antiepilépticas na infância e adolescência. FONTES DE DADOS: Estudo baseado em revisão de literatura. Os autores organizam, de acordo com os quadros patológicos, uma rotina para o manejo dos psicofármacos e das drogas antiepilépticas na infância e na adolescência. SÍNTESE DOS DADOS: Indicação clínica, dosagem terapêutica e efeitos colaterais dos psicofármacos e drogas antiepilépticas são descritos. O uso de psicofárma...

  13. Deconstructing Designer Drugs.

    Science.gov (United States)

    Sellers, E M

    2017-02-01

    The concepts behind current "designer drugs" are not new. For several centuries, chemical synthesis has made drugs more specific and more selective. However, headline designer drugs now are different and a serious public health problem because they are illicit unregulated chemical knockoffs of approved psychoactive stimulant, sedative, or perception-altering controlled substances. © 2016 ASCPT.

  14. Correlates of psychoactive substance use among Nigerian adolescents

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    Oluyemi O Akanni

    2015-01-01

    Full Text Available Context: The abuse of psychoactive substances which is one of the most important global public health problems begins in adolescence. Adolescents usually start by abusing the gateway substances. They suffer social, economic, physical, and legal consequences on account of use of substances, and this is very worrisome because of the increasing prevalence of use. Aims: The aim was to identify the characteristics of adolescents that use gateway substances. This knowledge shall be utilized in preventive programs. Settings and Design: Cross-sectional study with secondary school adolescents as participants. Subjects and Methods: Multistage sampling technique was used to select 492 respondents and the questionnaire consisted of characteristics of the adolescents, their families and schools and the alcohol, tobacco, cannabis, and stimulant use sections of the World Health Organisation questionnaire for student drug use surveys. Statistical Analysis Used: The data were analyzed using the Statistical Package for Social Sciences, and Chi-square statistics was used. Results: Having a friend who uses substance was significantly associated with tobacco, alcohol, cannabis, and caffeine use while being a male, having a family member that uses substance were significantly associated with tobacco, alcohol, and caffeine use. Older age, lack of satisfaction with the relationship with the teacher and polygamous family background were significantly associated with tobacco use. And finally, lack of satisfaction with the relationship with parents/guardians and having parents or guardians who are not religious were significantly associated with alcohol use. Conclusion: A comprehensive approach is needed to prevent the use of substances; this should target individuals, schools, families, and religious institutions.

  15. Transtornos mentais comuns e uso de psicofármacos: impacto das condições socioeconômicas Trastornos mentales comunes y uso de psicofármacos: impacto de las condiciones socioeconómicas Common mental disorders and the use of psychoactive drugs: the impact of socioeconomic conditions

    Directory of Open Access Journals (Sweden)

    Maria Cristina Pereira Lima

    2008-08-01

    probabilístico, estratificado y por conglomerados. Fueron realizadas entrevistas domiciliares con 1.023 sujetos de 15 años o mas de edad, entre 2001 y 2002. Trastorno mental común fue evaluado utilizando el Self Reporting Questionnaire (SRQ-20. El uso de servicios fue investigado con relación a la quincena anterior a la entrevista y uso de psicotrópicos, en los tres días anteriores. Se utilizó regresión logística para análisis multivariable, considerando el efecto del diseño. RESULTADOS: En el total de la muestra, 13.4% (IC 95%: 10.7;16.0 buscaron servicios de salud en la quincena anterior a la entrevista. La búsqueda de servicios de salud se asoció al sexo femenino (OR=2.0 y la presencia de trastorno mental común (OR=2.2. En la muestra 13.3% (IC 95%: 9.2; 17.5 se refirieron a haber usado al menos un psicotrópico, destacándose los antidepresivos (5.0% y los benzodiazepínicos (3.1%. En el análisis multivariable, sexo femenino y presencia de trastorno mental común se mantuvieron asociados al uso de benzodiazepínicos. Renta per capita se mostró directa e independientemente asociada al uso de psicofármacos, de acuerdo al aumento de la renta. CONCLUSIONES: Menor renta se asoció a la presencia de trastorno mental común, pero no al uso de psicotrópicos. La asociación entre trastorno mental común y uso de psicotrópicos y mayor renta refuerza la hipótesis de la existencia de injusticias en el acceso a la asistencia médica en la población estudiada.OBJECTIVE: To evaluate the influence of socioeconomic conditions on the association between common mental disorders and the use of health services and psychoactive drugs. METHODS: This was a population-based cross-sectional study conducted in the city of Botucatu, Southeastern Brazil. The sample was probabilistic, stratified and cluster-based. Interviews with 1,023 subjects aged 15 years or over were held in their homes between 2001 and 2002. Common mental disorders were evaluated using the Self

  16. Nurses' perception of the quality of care they provide to hospitalized drug addicts: testing the theory of reasoned action.

    Science.gov (United States)

    Natan, Merav Ben; Beyil, Valery; Neta, Okev

    2009-12-01

    A correlational design was used to examine nursing staff attitudes and subjective norms manifested in intended and actual care of drug users based on the Theory of Reasoned Action. One hundred and thirty-five nursing staff from three central Israeli hospitals completed a questionnaire examining theory-based variables as well as sociodemographic and professional characteristics. Most respondents reported a high to very high level of actual or intended care of drug users. Nurses' stronger intentions to provide quality care to drug users were associated with more positive attitudes. Nursing staff members had moderately negative attitudes towards drug users. Nurses were found to hold negative stereotypes of drug addict patients and most considered the management of this group difficult. Positive attitudes towards drug users, perceived expectations of others and perceived correctness of the behaviour are important in their effect on the intention of nurses to provide high-quality care to hospitalized patients addicted to drugs.

  17. Familial Risk Analysis of the Association between Attention-Deficit/Hyperactivity Disorder and Psychoactive Substance Use Disorder in Female Adolescents: A Controlled Study

    Science.gov (United States)

    Biederman, Joseph; Petty, Carter R.; Monuteaux, Michael C.; Mick, Eric; Clarke, Allison; Ten Haagen, Kristina; Faraone, Stephen V.

    2009-01-01

    Background: A robust and bi-directional comorbidity between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD, alcohol or drug abuse, or dependence) has been consistently reported in the literature. However, this literature has been based almost exclusively on male only samples and, therefore, the…

  18. Experimental Clinical Medicine and Drug Action in Mid-Seventeenth-Century Leiden.

    Science.gov (United States)

    Ragland, Evan R

    2017-01-01

    Leiden University boasted one of the most popular and influential medical schools of the mid-seventeenth century, drawing hundreds of students from across Europe. These students participated in the revival of frequent clinical instruction, anatomical and chymical experiments, and even tests of supposed disease-causing substances and remedies on living animals and humans. Comparing records of cases from the hospital clinic with the professors' treatises and student-authored disputations shows that old and new theories of disease and drug action were hotly contested and often tested, including the claims of the leading professors at the school. Though notable exemplars of their work received sharp criticism and rejection from contemporaries and subsequent generations, Leiden students and professors united chymistry, postmortem autopsy, anatomical experiments, and clinical tests, often aiming at discovery. They enacted one, perhaps ephemeral, instance of experimental, clinical medicine well before its putative modern birth.

  19. Towards the use of non-psychoactive cannabinoids for prostate cancer.

    Science.gov (United States)

    Pacher, Pál

    2013-01-01

    The palliative effects of Cannabis sativa (marijuana), and its putative main active ingredient, Δ(9) -tetrahydrocannabinol (THC), which include appetite stimulation, attenuation of nausea and emesis associated with chemo- or radiotherapy, pain relief, mood elevation, and relief from insomnia in cancer patients, are well-known. Because of the adverse psychoactive effects of THC, numerous recent preclinical studies have been focused on investigating other non-psychoactive constituents of C. sativa, such as cannabidiol, for potential therapeutic use. In this issue of the British Journal of Pharmacology, De Petrocellis and colleagues present comprehensive evidence that plant-derived cannabinoids, especially cannabidiol, are potent inhibitors of prostate carcinoma viability in vitro. They also showed that the extract was active in vivo, either alone or when administered with drugs commonly used to treat prostate cancer (the anti-mitotic chemotherapeutic drug docetaxel (Taxotere) or the anti-androgen bicalutamide (Casodex)) and explored the potential mechanisms behind these antineoplastic effects. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  20. Psychoactive substance misuse among Nigerian adolescents ...

    African Journals Online (AJOL)

    Results: Surveys suggest that in both in-and out-of-school adolescents, the socially acceptable drugs like alcohol and cigarettes are commonly used. The patients interviewed illustrate the important 'gateway\\' theory of drug progression. Psychological dynamics identified include peer pressure, experimentation and conduct ...

  1. Evaluation of problematic psychoactive substances use in people placed in police custody.

    Science.gov (United States)

    Gérardin, Marie; Guigand, Gabriel; Wainstein, Laura; Jolliet, Pascale; Victorri-Vigneau, Caroline; Clément, Renaud

    2017-07-01

    In France, the law states that any person held in custody could be examined by a doctor. The main objective of the medical examination is to give medical evidence of health compatibility with custody. This review identifies health risks such as addictive behaviour. We wanted to know which psychoactive substances are used in this particular population, and how problematic these uses are. A prospective, monocentric, open-ended study conducted via a structured questionnaire was carried out on detainees who reported having taken drugs or illegal substances. Practitioners investigated desired effects for each substance, and characteristics of use, by means of the dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric Association, 1994). Problematic use was assessed when at least 3 items of the DSM IV were positive. 604 questionnaires were examined. 90.7% of questionnaires reported tobacco use, 76.2% cannabis, 57.3% alcohol, 12.5% psychostimulants, 10.0% opiates and 0.7% benzodiazepines or Z-drugs. The frequency of problematic use was 74.6% for opiates, 44.9% for cocaine and 25.3% for cannabis. Compared to non-problematic users, problematic users were older, more likely to be jobless without financial means, more likely to have a medical history, including a greater likelihood of mental illness, and more chance of undergoing prescribed medical treatment. They included more women and more homeless people. These results show characteristics of psychoactive substance use in a sample of people in custody. Psychoactive substances mentioned by respondents are not different from those observed in the general population, but for certain users, the desired effects are far from the pharmacologically expected ones. For some, taking substances seems to be part of their way of life, for others it is a means to compensate for an underlying feeling of uneasiness. Furthermore, problematic users present severity criteria which

  2. Chromatography as Method for Analytical Confirmation of Paracetamol in Postmortem Material Together with Psychoactive Substances

    Science.gov (United States)

    Biscevic-Tokic, Jasmina; Tokic, Nedim; Ibrahimpasic, Elma

    2015-01-01

    Introduction: Paracetamol (Acetaminophen) in addition to aspirin is the most commonly used analgesic and antipyretic medication by millions of patients worldwide. It is an example that paracetamol as medicine that in the world is provided without a doctor’s prescription, can lead to death. Today paracetamol became an integral part of a heroin mixture and is very popular at the street market. The main reason for this is that it can be obtained without a prescription, it is cheap, and by most people well tolerated without side effects. It is probably used for “cutting” the pure heroin, as it says in the jargon, and in that manner from small amount of pure drug is obtained greater amount, which is then sold on the street. The goal is to identify presence of paracetamol, by analytical method of gas chromatography mass spectrometer (GC-MS) in postmortem material together with psychoactive substances. Material and methods: For chemical-toxicological analysis is used biological material collected trough autopsy of 20 deceased people, suspected to have died due to psychoactive substance overdose. All received samples are stored at -20 ° C until analysis at our laboratory. From processed 47 samples that were analyzed in the period from 2014 to 2015, 19 are blood samples, urine 19, 3 samples of stomach contents, and 6 samples of bile content. Deceased were middle-aged, of which only 7 were female. The tested samples were processed according to two methods of extraction. Extraction by XAD-2 resin, and the extraction by the method of salting out with sodium tungstate. Extracts of the samples were then dissolved in chloroform and continued analysis at the analytical instrument. Identification of the paracetamol presence, in the test biological samples is demonstrated by the technique of gas chromatography with mass spectometry (hereinafter referred to as GC-MS). The technique of GC-MS is a selective, sensitive and reliable, and is therefore considered a “gold standard

  3. Recent advances in the pathogenesis and drug actions in periodic paralyses and related channelophaties

    Directory of Open Access Journals (Sweden)

    Domenico eTricarico

    2011-02-01

    Full Text Available The periodic paralysis(PP are rare autosomal-dominant disorders associated to mutations in the skeletal muscle sodium, calcium and potassium channel genes characterized by muscle fiber depolarization with un-excitability, episodes of weakness with variations in serum potassium concentrations. Recent advances in thyrotoxic-PP(TPP and hypokalemic-PP(hypoPP confirm the involvement of the muscle potassium channels in the pathogenesis of the diseases and their role as target of action for drugs of therapeutic interest. The novelty in the gating pore currents theory help to explain the disease symptoms, and open the possibility to more specifically target the disease. It is now known that the fiber depolarization in the hypoPP is due to an unbalance between the novel identified depolarizing gating pore currents(Igp carried by protons or Na+ ions flowing through aberrant alternative pathways of the mutant subunits and repolarizing inwardly rectifying potassium channel(Kir currents which also includes the ATP-sensitive subtype. Abnormal activation of the Igp or deficiency in the Kir channels predispose to fiber depolarization. One pharmacological strategy is based on blocking the Igp without affecting normal channel gating. It remains safe and effective the proposal of targeting the KATP, Kir channels or BK channels by drugs capable to specifically open at nanomolar concentrations the skeletal muscle subtypes with less side effects.

  4. Recent advances in the pathogenesis and drug action in periodic paralyses and related channelopathies.

    Science.gov (United States)

    Tricarico, Domenico; Camerino, Diana Conte

    2011-01-01

    The periodic paralysis (PP) are rare autosomal-dominant disorders associated to mutations in the skeletal muscle sodium, calcium, and potassium channel genes characterized by muscle fiber depolarization with un-excitability, episodes of weakness with variations in serum potassium concentrations. Recent advances in thyrotoxic PP and hypokalemic PP (hypoPP) confirm the involvement of the muscle potassium channels in the pathogenesis of the diseases and their role as target of action for drugs of therapeutic interest. The novelty in the gating pore currents theory help to explain the disease symptoms, and open the possibility to more specifically target the disease. It is now known that the fiber depolarization in the hypoPP is due to an unbalance between the novel identified depolarizing gating pore currents (I(gp)) carried by protons or Na(+) ions flowing through aberrant alternative pathways of the mutant subunits and repolarizing inwardly rectifying potassium channel (Kir) currents which also includes the ATP-sensitive subtype. Abnormal activation of the I(gp) or deficiency in the Kir channels predispose to fiber depolarization. One pharmacological strategy is based on blocking the I(gp) without affecting normal channel gating. It remains safe and effective the proposal of targeting the K(ATP), Kir channels, or BK channels by drugs capable to specifically open at nanomolar concentrations the skeletal muscle subtypes with less side effects.

  5. Target and suspect screening of psychoactive substances in sewage-based samples by UHPLC-QTOF

    Energy Technology Data Exchange (ETDEWEB)

    Baz-Lomba, J.A., E-mail: jba@niva.no [Norwegian Institute for Water Research, Gaustadalléen 21, NO-0349, Oslo (Norway); Faculty of Medicine, University of Oslo, PO box 1078 Blindern, 0316, Oslo (Norway); Reid, Malcolm J.; Thomas, Kevin V. [Norwegian Institute for Water Research, Gaustadalléen 21, NO-0349, Oslo (Norway)

    2016-03-31

    The quantification of illicit drug and pharmaceutical residues in sewage has been shown to be a valuable tool that complements existing approaches in monitoring the patterns and trends of drug use. The present work delineates the development of a novel analytical tool and dynamic workflow for the analysis of a wide range of substances in sewage-based samples. The validated method can simultaneously quantify 51 target psychoactive substances and pharmaceuticals in sewage-based samples using an off-line automated solid phase extraction (SPE-DEX) method, using Oasis HLB disks, followed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) in MS{sup e}. Quantification and matrix effect corrections were overcome with the use of 25 isotopic labeled internal standards (ILIS). Recoveries were generally greater than 60% and the limits of quantification were in the low nanogram-per-liter range (0.4–187 ng L{sup −1}). The emergence of new psychoactive substances (NPS) on the drug scene poses a specific analytical challenge since their market is highly dynamic with new compounds continuously entering the market. Suspect screening using high-resolution mass spectrometry (HRMS) simultaneously allowed the unequivocal identification of NPS based on a mass accuracy criteria of 5 ppm (of the molecular ion and at least two fragments) and retention time (2.5% tolerance) using the UNIFI screening platform. Applying MS{sup e} data against a suspect screening database of over 1000 drugs and metabolites, this method becomes a broad and reliable tool to detect and confirm NPS occurrence. This was demonstrated through the HRMS analysis of three different sewage-based sample types; influent wastewater, passive sampler extracts and pooled urine samples resulting in the concurrent quantification of known psychoactive substances and the identification of NPS and pharmaceuticals. - Highlights: • A novel reiterative workflow

  6. Psychoactive substance use, family context and mental health among Brazilian adolescents, National Adolescent School-based Health Survey (PeNSE 2012

    Directory of Open Access Journals (Sweden)

    Deborah Carvalho Malta

    2014-01-01

    Full Text Available OBJECTIVE: To evaluate the association between the consumption of psychoactive substances (tobacco, alcohol and illicit drugs and demographic variables, mental health and family context among school-aged children. METHODS: The National Adolescent School-based Health Survey was held with a national sample of 109,104 students. Data regarding demographic variables, family background and mental health were collected. Logistic regression was used to evaluate the associations of interest. RESULTS: Multivariate analyses showed that alcohol consumption was higher among girls, drug experimentation was more frequent among boys and that there was no difference between sexes for smoking. Being younger and mulatto were negatively associated with the use of tobacco, alcohol and illicit drugs. Also negatively associated with such risk behaviors were characteristics of the family context represented by: living with parents, having meals together and parental supervision (when parents know what the child does in their free time. Moreover, characteristics of mental health such as loneliness and insomnia were positively associated with use of tobacco, alcohol and illicit drugs. Not having friends was positively associated with use of tobacco and illicit drugs and negatively associated with alcohol use. CONCLUSIONS: The study shows the protective effect of family supervision in the use of tobacco, alcohol and drugs and, on the contrary, the increasing use of substances according to aspects of mental health, such as loneliness, insomnia and the fact of not having friends. The study's findings may support actions from health and education professionals, as well as from the government and families in order to prevent the use of these substances by adolescents.

  7. Experimentation with psychoactive substances by public school students.

    Science.gov (United States)

    Andrade, Maria Eliane de; Santos, Igor Henrique Farias; Souza, Antônio Araújo Menezes de; Silva, Aliane Caroline Santos; Leite, Tatiane Dos Santos; Oliveira, Cristiane Costa da Cunha; Albuquerque, Ricardo Luiz Cavalcanti de

    2017-09-04

    To analyze the prevalence of exposure to psychoactive substances in public students of basic education and its association with sociodemographic characteristics. This is a cross-sectional survey conducted from March to September 2015, involving 1,009 students of the basic and high school education in 20 public schools in the municipality of Aracaju, State of Sergipe, Brazil. The data have been compiled using questionnaires previously applied in national studies of the Brazilian Center for Psychotropic Drugs. The variables have been dichotomized for later logistic regression using the Chi-square test to analyze associations between experimentation with psychoactive substances and other sociodemographic variables; odds ratio and confidence intervals have also been calculated. The level of significance adopted was 5%. We have identified that 69.6% of the students have experimented alcohol and 12.4% cigarettes. Age (≥ 15 years) has shown a significant association with experimentation with alcohol (p Drogas Psicotrópicas. As variáveis foram dicotomizadas para posterior regressão logística com aplicação do teste Qui-quadrado para analisar associações entre a experimentação de substâncias psicoativas e outras variáveis sociodemográficas, e calculada a razão de chances e seus intervalos de confiança. O nível de significância adotado foi de 5%. Identificamos que 69,6% dos estudantes têm experimentado álcool e 12,4% cigarro. A idade dos alunos (≥ 15 anos) mostrou associação significativa com a experimentação de álcool (p < 0,001) e cigarros (p = 0,02), atuando como fator de risco em ambos os casos (OR = 2,34 e 1,78, respectivamente), mas atuando como fator de proteção para o uso de inalantes (p = 0,03 e OR = 0,58) e remédios para emagrecer (p = 0,006 e OR = 0,44). A prática religiosa apresentou associação significativa com a experimentação de álcool (p = 0,01), funcionando como um fator de proteção (OR = 0,56). Conclui-se que a subst

  8. Quality of life of users of psychoactive substances, relatives, and non-users assessed using the WHOQOL-BREF

    Directory of Open Access Journals (Sweden)

    Taís de Campos Moreira

    2013-07-01

    Full Text Available Quality of life is related to one of the basic human desires, which is to live well and feel good. The scope of this study was to evaluate the quality of life of psychoactive substance users and relatives, compared to non-users, analyzed by socioeconomic strata. A cross-sectional study with users of psychoactive substances, relatives, and other individuals who called the Information and Orientation Service regarding drug abuse. Data collection took place between November 2009 and December 2010. Data was collected from users, relatives, and non-users, including socioeconomic characteristics and data regarding substance consumption when appropriate. In addition to this the abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF questionnaire was given to 347 individuals. Among the 138 users (70% used alcohol, 76 (39%, marijuana, 111 (57% tobacco, 78 (40% cocaine and 70 (36% crack. Control subjects had higher, scores than the relatives of users and users in all areas of the questionnaire (p < 0.05. Psychoactive substance users scored lower in almost all domains and overall score in the WHOQOL-BREF questionnaire in comparison with the sample of non-drug users. These findings reflect poor quality of life of patients and their relatives.

  9. Fate of psychoactive compounds in wastewater treatment plant and the possibility of their degradation using aquatic plants.

    Science.gov (United States)

    Mackuľak, Tomáš; Mosný, Michal; Škubák, Jaroslav; Grabic, Roman; Birošová, Lucia

    2015-03-01

    In this study we analyzed and characterized 29 psychoactive remedies, illicit drugs and their metabolites in single stages of wastewater treatment plants in the capital city of Slovakia. Psychoactive compounds were present within all stages, and tramadol was detected at a very high concentration (706 ng/L). Significant decreases of codeine, THC-COOH, cocaine and buprenorphine concentration were observed in the biological stage. Consequently, we were interested in the possibility of alternative tertiary post-treatment of effluent water with the following aquatic plants: Cabomba caroliniana, Limnophila sessiliflora, Egeria najas and Iris pseudacorus. The most effective plant for tertiary cleansing was I. pseudacorus which demonstrated the best pharmaceutical removal capacity. After 48 h codeine and citalopram was removed with 87% efficiency. After 96 h were all analyzed compounds were eliminated with efficiencies above 58%. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Pattern and practice of psychoactive substance abuse and risky ...

    African Journals Online (AJOL)

    This study was an analytical cross-sectional survey conducted by the administration of questionnaires to 399 street children who had been homeless for at least a month in three cities of Cameroon during 2015. Results. All 399 participants reported that they were using some psychoactive substance at the time of the survey.

  11. Parental Guidance about Drinking: Relationship with Teenage Psychoactive Substance Use

    Science.gov (United States)

    Miller, Patrick; Plant, Martin

    2010-01-01

    Parental guidance concerning alcohol was explored using data from a 2007 survey of 2179 UK school students aged 15 and 16 years. Cluster analysis based on questions about parental advice was used to establish seven student groups. Associations between groups, other family background and psychoactive substance use variables were explored. Substance…

  12. Prevalence of Psychoactive Substances in Dutch and Belgian Traffic

    NARCIS (Netherlands)

    Houwing, Sjoerd; Legrand, Sara-Ann; Mathijssen, Rene; Hagenzieker, Marjan; Verstraete, Alain G.; Brookhuis, Karel

    2012-01-01

    Objective: The purpose of this study was to compare the prevalence of psychoactive substances in general traffic in The Netherlands and Belgium. Method: Randomly selected car drivers and drivers of small vans in six police regions in The Netherlands and five police regions in Belgium were included

  13. Psychoactive substance intake and gender on crime | okediji ...

    African Journals Online (AJOL)

    This study investigated the influence of psychoactive substance (alcohol, marijuana, and cocaine) intake and gender on crime. Three hundred and eighty participants (380) were randomly selected from inmates as models of prisons in Uyo, Akwa Ibom State. The participants comprised 314 males (82.63%) and 66 females ...

  14. A Comparative study of use of psychoactive substances amongst ...

    African Journals Online (AJOL)

    Similarly, parents\\' marital status (p=0.05) was statistically significant in the use of Indian hemp, while family type (P=0.00), upbringing (P=0.03)was significant in cocaine. The findings of this study confirm the presence and use of psychoactive substances in varying proportions among students. Therefore, there is need to ...

  15. Psychoactive substance intake and gender on crime | Okediji ...

    African Journals Online (AJOL)

    This study investigated the influence of psychoactive substance (alcohol, marijuana, and cocaine) intake and gender on crime. Three hundred and eighty participants (380) were randomly selected from inmates as models of prisons in Uyo, Akwa Ibom State. The participants comprised 314 males (82.63%) and 66 females ...

  16. Effect of selected anti-inflammatory drugs on the lethal actions of Leiurus quinquestriatus venom

    Directory of Open Access Journals (Sweden)

    N. A. Abdoon

    2006-01-01

    Full Text Available The cumulative actions of scorpion neurotoxins are complex and may be traced to activation of different ion channels with subsequent release of various transmitters and modulators including inflammatory mediators. This could lead to various pathological manifestations such as acute respiratory distress syndrome (ARDS, systemic inflammatory response syndrome (SIRS, and multiple organ failure (MOF. Several approaches have been advocated to treat the multitude of scorpion-venom-elicited pathological changes. However, few have tried to combat the venom-induced effects on the inflammatory process, which manifest as ARDS, SIDS and MOF. Thus, the aim of this study was to determine the capability of inhibitors of different steps of the inflammatory sequence of events in scorpion envenomation to ameliorate the detrimental action of the venom and prolong survival of mice injected with Leiurus quinquestriatus quinquestriatus (LQQ venom. Animals were divided into groups (n = 10 and given montelukast (10 or 20 mg.kg-1, orally, hydrocortisone (5 or 10 mg.kg-1, intravenously or indomethacin (10 or 20 mg kg-1, intravenously. Then, all animals were subcutaneously injected with either 0.25 or 0.3 mg.kg-1 LQQ venom. Signs and symptoms of envenomation were recorded and survival percentages after 24 hours as well as survival time were determined in each group. To analyze data, we utilized Covariance Wilcoxon survival statistics and survival distribution curves. In general, when compared to venom alone, administration of montelukast (p<0.001, hydrocortisone (p<0.05 and indomethacin (p<0.05 prolonged survival time and increased the percentage of surviving animals per group, with montelukast exhibiting the greatest protecting power. Thus, anti-inflammatory drugs may play an important role in protection against the lethal effects of scorpion venoms.

  17. Psychoactive herb use and youth: a closer look at salvia divinorum.

    Science.gov (United States)

    Ahern, Nancy R; Greenberg, Cindy S

    2011-08-01

    Salvia divinorum is a psychoactive herb and an increasingly popular recreational drug used by young people in our country and abroad. Much of its increased popularity stems from its easy accessibility and affordability; its effects produce an intense and potent "high" and concomitant disorientation and hallucinations. The risks associated with Salvia are poorly defined due to a lack of scientific evidence, leaving Salvia users with false assurances about its safety. Although its safety profile is ill defined, its intense effects are well known and can put young people at risk for injuries and serious errors in judgment. Psychiatric nurses and health care practitioners are in key positions to influence practice, education, and policy regarding the use and abuse of this drug by youth. Copyright 2011, SLACK Incorporated.

  18. [Soluble guanylate cyclase in the molecular mechanism underlying the therapeutic action of drugs].

    Science.gov (United States)

    Piatakova, N V; Severina, I S

    2012-01-01

    The influence of ambroxol--a mucolytic drug--on the activity of human platelet soluble guanylate cyclase and rat lung soluble guanylate cyclase and activation of both enzymes by NO-donors (sodium nitroprusside and Sin-1) were investigated. Ambroxol in the concentration range from 0.1 to 10 microM had no effect on the basal activity of both enzymes. Ambroxol inhibited in a concentration-dependent manner the sodium nitroprusside-induced human platelet soluble guanylate cyclase and rat lung soluble guanylate cyclase with the IC50 values 3.9 and 2.1 microM, respectively. Ambroxol did not influence the stimulation of both enzymes by protoporphyrin IX. The influence of artemisinin--an antimalarial drug--on human platelet soluble guanylate cyclase activity and the enzyme activation by NO-donors were investigated. Artemisinin (0.1-100 microM) had no effect on the basal activity of the enzyme. Artemisinin inhibited in a concentration-dependent manner the sodium nitroprusside-induced activation of human platelet guanylate cyclase with an IC50 value 5.6 microM. Artemisinin (10 microM) also inhibited (by 71 +/- 4.0%) the activation of the enzyme by thiol-dependent NO-donor the derivative of furoxan, 3,4-dicyano-1,2,5-oxadiazolo-2-oxide (10 microM), but did not influence the stimulation of soluble guanylate cyclase by protoporphyrin IX. It was concluded that the sygnalling system NO-soluble guanylate cyclase-cGMP is involved in the molecular mechanism of the therapeutic action of ambroxol and artemisinin.

  19. New challenges and innovation in forensic toxicology: focus on the "New Psychoactive Substances".

    Science.gov (United States)

    Favretto, Donata; Pascali, Jennifer P; Tagliaro, Franco

    2013-04-26

    In the recent years, new molecules have appeared in the illicit market, claimed to contain "non-illegal" compounds, although exhibiting important psychoactive effects; this heterogeneous and rapidly evolving class of compounds are commonly known as "New Psychoactive Substances" or, less properly, "Smart Drugs" and are easily distributed through the e-commerce or in the so-called "Smart Shops". They include, among other, synthetic cannabinoids, cathinones and tryptamine analogs of psylocin. Whereas cases of intoxication and death have been reported, the phenomenon appears to be largely underestimated and is a matter of concern for Public Health. One of the major points of concern depends on the substantial ineffectiveness of the current methods of toxicological screening of biological samples to identify the new compounds entering the market. These limitations emphasize an urgent need to increase the screening capabilities of the toxicology laboratories, and to develop rapid, versatile yet specific assays able to identify new molecules. The most recent advances in mass spectrometry technology, introducing instruments capable of detecting hundreds of compounds at nanomolar concentrations, are expected to give a fundamental contribution to broaden the diagnostic spectrum of the toxicological screening to include not only all these continuously changing molecules but also their metabolites. In the present paper a critical overview of the opportunities, strengths and limitations of some of the newest analytical approaches is provided, with a particular attention to liquid phase separation techniques coupled to high accuracy, high resolution mass spectrometry. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Analysis of pharmaceutical safety-related regulatory actions in Japan: do tradeoffs exist between safer drugs and launch delay?

    Science.gov (United States)

    Yamada, Toru; Kusama, Makiko; Hirai, Yuka; Arnold, Frank; Sugiyama, Yuichi; Ono, Shunsuke

    2010-12-01

    Prediction and management of drug safety is a global regulatory issue. Safety-related regulatory actions (SRRAs) are taken mostly when unexpected adverse drug reactions occur. Currently, Japan is reconciled to delayed access to new drugs (ie, launch delay compared to Western countries), but may have been benefiting by free-riding on safety data accumulated in other countries prior to Japanese launch. To identify factors that are significantly associated with SRRAs, and to discuss the challenges that Japan might have to face with increasing access to new drugs. The SRRAs of 135 new drugs approved from January 2000 to December 2005 were analyzed to investigate association with launch lag, company and drug characteristics, market size, submission data, and regulatory status. SRRAs were measured in terms of the number of emergency safety information notifications and official safety instructions issued by the Japanese regulatory agency within 3 years after approval. A negative binomial distribution model was used for regression analysis. Longer launch lags and presence of drugs with similar modes of action were associated with fewer SRRAs. Bridging strategy showed increased SRRAs. No significant association was observed between SRRAs and the subject number in clinical data packages. Occurrence of SRRAs was varied among development strategy, preceding products, and regional regulations. The occurrence of SRRAs was associated with the accumulation of both foreign and domestic postmarketing evidence rather than with clinical trial data upon launch. Considering the paradigm shift to simultaneous global drug development and filing for regulatory approval, this study indicates the importance of intensive data collection in the early postmarketing phase and use of safety information in early markets. However, even if we would be sufficiently cautious about safety risks of new drugs, a population that enjoys first-in-class drugs probably has to bear the risks.

  1. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

    Directory of Open Access Journals (Sweden)

    Varsha Agarwal

    2008-06-01

    Full Text Available Cytochrome P450 (P450 is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

  2. Conflicting perspectives on neurobehavioral theories of the depressive disorders and drug actions.

    Science.gov (United States)

    Katz, Martin M

    2016-12-01

    A prominent theory of depression focusses on neural plasticity and stress as central issues in seeking to develop a pattern of identifiable biological markers for the depressive disorders. Relative neglect, however, of clinical factors in that theory limits the uncovering of markers and opens to question their methodological approach. A conflicting theory, the 'opposed neurobehavioral states', based on dimensional analysis of monoamine neurotransmitter systems and behavioural factors is presented. This perspectives paper contrasts the two approaches viewing the biomarkers theory as premature at this point in the progress of depression research. Studies developed to support the biomarkers theory and the opposed neurobehavioral states theory are examined for their strengths and limitations in explaining the nature of the disorder and the actions of therapeutic drugs. Reference is made to reviews of the many studies on biomarkers and the recent work that supports the opposed neurobehavioral states theory. Discussion Main issue: the biomarkers theory sets important goals, but despite the many advances in the neural investigations of factors underlying depression, is still not successful in specifying markers. Thus, it is believed to be applying the wrong methodologic approach and premature in its claims. the 'opposed neurobehavioral' theory is limited in its breadth of research. It applies, however, the dimensional approach to the clinical side of the problem, a methodological approach more likely to be effective in selecting the best clinical treatment and open to a more productive path to understanding of the nature of the disorder in future research.

  3. PROSPECTS FOR DEVELOPMENT OF ANTIDIABETIC POLYPHENOL-BASED DRUGS: MECHANISMS OF HYPOGLYCEMIC ACTION AND PHARMACOKINETICS

    Directory of Open Access Journals (Sweden)

    Ruban E. A.

    2015-12-01

    Full Text Available Introduction. Diabetes mellitus is one of the most serious chronic diseases and considered to be non-infectious epidemic worldwide. Persistent hyperglycemia is a major hallmark of diabetes and risk factor for the development of its complications. Therefore, the main therapeutic goal in the treatment of diabetes is to reduce the elevated blood glucose level. Unfortunately, management of diabetes without any side effects is still a challenge to the modern medicine and pharmacy. Among potential alternatives to synthetic antidiabetic drugs plant polyphenols are very promising. However, polyphenol efficiency in diabetes is determined by their chemical structure and hence the affinity to a certain molecular targets in body tissues. Moreover, the bioavailability and other pharmacokinetic parameters of different individual substances may also vary significantly. In this context the present paper is devoted to the analysis of the available data on the hypoglycemic mechanisms and pharmacokinetics of various individual polyphenolic compounds in order to provide the necessary biopharmaceutical requirements in the development of a new blood glucose-lowering drug. Materials and methods. A systematic literature search of Pubmed, EMBASE and other databases with no language restrictions was performed until to the end of August 2015. The following terms were used: polyphenols, diabetes mellitus, hypoglycemic action, pharmacokinetics and bioavailability of polyphenols. Results and discussion. According to available experimental data various polyphenols may influence carbohydrate metabolism at many levels. The mechanisms by which plant polyphenols exert their hypoglycemic action are mediated primarily by their ability to directly bind to target proteins (or peptides and include inhibition of carbohydrate digestion and glucose absorption in the intestine, stimulation of insulin secretion from the pancreatic β-cells, modulation of glucose release from the liver

  4. Psychoactive substances belonging to the amphetamine class potently activate brain carbonic anhydrase isoforms VA, VB, VII, and XII.

    Science.gov (United States)

    Angeli, Andrea; Vaiano, Fabio; Mari, Francesco; Bertol, Elisabetta; Supuran, Claudiu T

    2017-12-01

    Identifying possible new biological activities of psychoactive substances belonging to various chemical classes may lead to a better understanding of their mode of action and side effects. We report here that amines structurally related to amphetamine, a widely used psychoactive substance, such as amphetamine, methamphetamine, phentermine, mephentermine, and chlorphenteramine, potently activate several carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in important physiological functions. Of the 11 investigated human (h) isoforms, the widespread hCA I and II, the secreted hCA VI, as well as the cytosolic hCA XIII, and membrane-bound hCA IX and XIV were poorly activated by these amines, whereas the extracellular hCA IV, the mitochondrial enzymes hCA VA/VB, the cytosolic hCA VII, and the transmembrane isoform hCA XII were potently activated. Some of these enzymes are abundant in the brain, raising the possibility that some of the cognitive effects of such psychoactive substances might be related to their activation of these enzymes.

  5. A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects.

    Science.gov (United States)

    Ignatowska-Jankowska, Bogna M; Baillie, Gemma L; Kinsey, Steven; Crowe, Molly; Ghosh, Sudeshna; Owens, Robert A; Damaj, Imad M; Poklis, Justin; Wiley, Jenny L; Zanda, Matteo; Zanato, Chiara; Greig, Iain R; Lichtman, Aron H; Ross, Ruth A

    2015-12-01

    The CB1 receptor represents a promising target for the treatment of several disorders including pain-related disease states. However, therapeutic applications of Δ(9)-tetrahydrocannabinol and other CB1 orthosteric receptor agonists remain limited because of psychoactive side effects. Positive allosteric modulators (PAMs) offer an alternative approach to enhance CB1 receptor function for therapeutic gain with the promise of reduced side effects. Here we describe the development of the novel synthetic CB1 PAM, 6-methyl-3-(2-nitro-1-(thiophen-2-yl)ethyl)-2-phenyl-1H-indole (ZCZ011), which augments the in vitro and in vivo pharmacological actions of the CB1 orthosteric agonists CP55,940 and N-arachidonoylethanolamine (AEA). ZCZ011 potentiated binding of [(3)H]CP55,940 to the CB1 receptor as well as enhancing AEA-stimulated [(35)S]GTPγS binding in mouse brain membranes and β-arrestin recruitment and ERK phosphorylation in hCB1 cells. In the whole animal, ZCZ011 is brain penetrant, increased the potency of these orthosteric agonists in mouse behavioral assays indicative of cannabimimetic activity, including antinociception, hypothermia, catalepsy, locomotor activity, and in the drug discrimination paradigm. Administration of ZCZ011 alone was devoid of activity in these assays and did not produce a conditioned place preference or aversion, but elicited CB1 receptor-mediated antinociceptive effects in the chronic constriction nerve injury model of neuropathic pain and carrageenan model of inflammatory pain. These data suggest that ZCZ011 acts as a CB1 PAM and provide the first proof of principle that CB1 PAMs offer a promising strategy to treat neuropathic and inflammatory pain with minimal or no cannabimimetic side effects.

  6. Crisis intervention related to the use of psychoactive substances in recreational settings--evaluating the Kosmicare Project at Boom Festival.

    Science.gov (United States)

    Carvalho, Maria Carmo; de Sousa, Mariana Pinto; Frango, Paula; Dias, Pedro; Carvalho, Joana; Rodrigues, Marta; Rodrigues, Tania

    2014-01-01

    Kosmicare project implements crisis intervention in situations related to the use of psychoactive substances at Boom Festival (Portugal). We present evaluation research that aims to contribute to the transformation of the project into an evidence-based intervention model. It relies on harm reduction and risk minimization principles, crisis intervention models, and Grof's psychedelic psychotherapy approach for crisis intervention in situations related to unsupervised use of psychedelics. Intervention was expected to produce knowledge about the relation between substance use and mental health impact in reducing potential risk related to the use of psychoactive substances and mental illness, as well as an impact upon target population's views of themselves, their relationship to substance use, and to life events in general. Research includes data on process and outcome indicators through a mixed methods approach, collected next to a sample of n=176 participants. Sample size varied considerably, however, among different research measures. 52% of Kosmicare visitors reported LSD use. Over 40% also presented multiple drug use. Pre-post mental state evaluation showed statistically significant difference (pcrisis resolution. Crisis episodes that presented no resolution were more often related with mental health outburst episodes, with psychoactive substance use or not. Visitors showed high satisfaction with intervention (n=58) and according to follow-up (n=18) this perception was stable over time. Crisis intervention was experienced as very significant. We discuss limitations and implications of evaluating natural setting based interventions, and the relation between psychoactive substance use and psychopathology. Other data on visitor's profile and vulnerability to crisis showed inconclusive.

  7. Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?

    Science.gov (United States)

    Seely, Kathryn A; Prather, Paul L; James, Laura P; Moran, Jeffery H

    2011-02-01

    The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.

  8. Risk of severe driver injury by driving with psychoactive substances

    DEFF Research Database (Denmark)

    Hels, Tove; Lyckegaard, Allan; Bernhoft, Inger Marie

    2013-01-01

    Driving with alcohol and other psychoactive substances imposes an increased risk of severe injury accidents. In a population-based case-control design, the relative risks of severe driver injury (MAIS ≥ 2) by driving with ten substance groups were approximated by odds ratios (alcohol, amphetamines...... (N = 2490) were collected from severely injured drivers of passenger cars or vans in selected hospitals in various regions of the countries. Control samples (N = 15,832) were sampled in a uniform sampling scheme stratified according to country, time, road type and season. Relative risks were...... driver injury with increasing age. It is concluded that among psychoactive substances alcohol still poses the largest problem in terms of driver risk of getting injured. © 2013 Elsevier Ltd. All rights reserved....

  9. Molecular mechanisms of parthenolide’s action: Old drug with a new face

    Directory of Open Access Journals (Sweden)

    Kamila Koprowska

    2010-03-01

    Full Text Available Parthenolide, a sesquiterpene lactone derived from the leaves of feverfew ([i]Tanacetum parthenium[/i], is considered a main bioactive component of this herb. Feverfew has been used orally or as an infusion for the treatment of migraine, arthritis, fever, and stomachache. Besides its anti-inflammatory and anti-migraine properties, parthenolide also shows anticancer activities in a variety of cell lines. It contains an α-methylene-γ-lactone ring and an epoxide moiety which are able to interact with nucleophilic sites of biologically important molecules. Parthenolide modulates multiple targets, thereby contributing to its various [i]in vitro[/i] and [i]in vivo[/i] effects. Inhibition of NF-κB activity, constitutive in many types of cancers, via either interaction with IKK or more directly with the p65 subunit of NF-κB, is considered one of the main mechanisms of its action. In addition, inhibition of STAT and MAP kinase activities and the induction of sustained JNK activity as well as p53 activity via influencing MDM2 and HDAC1 levels lead to an increased susceptibility of cancer cells to chemo- and radiotherapy. At the epigenetic level, parthenolide reduces HDAC1 level and, by inhibiting DNMT2 activity, induces global hypomethylation of DNA, which can restore the expressions of some suppressor genes. Moreover, this compound reduces the cellular level of GSH in cancer cells, followed by ROS accumulation and apoptosis. A unique property of parthenolide is its ability to induce cell death mainly in cancer cells, while sparing healthy ones and it also protects normal cells from UVB and oxidative stress. More remarkably, it seems to have the potential to target some cancer stem cells. Its wide array of biological activity and low toxicity make parthenolide a very promising drug with multi-pharmacological potential, largely dependent on the cellular context.

  10. Pleuromutilins: Potent Drugs for Resistant Bugs-Mode of Action and Resistance.

    Science.gov (United States)

    Paukner, Susanne; Riedl, Rosemarie

    2017-01-03

    Pleuromutilins are antibiotics that selectively inhibit bacterial translation and are semisynthetic derivatives of the naturally occurring tricyclic diterpenoid pleuromutilin, which received its name from the pleuromutilin-producing fungus Pleurotus mutilus Tiamulin and valnemulin are two established derivatives in veterinary medicine for oral and intramuscular administration. As these early pleuromutilin drugs were developed at a time when companies focused on major antibacterial classes, such as the β-lactams, and resistance was not regarded as an issue, interest in antibiotic research including pleuromutilins was limited. Over the last decade or so, there has been a resurgence in interest to develop this class for human use. This has resulted in a topical derivative, retapamulin, and additional derivatives in clinical development. The most advanced compound is lefamulin, which is in late-stage development for the intravenous and oral treatment of community-acquired bacterial pneumonia and acute bacterial skin infections. Overall, pleuromutilins and, in particular, lefamulin are characterized by potent activity against Gram-positive and fastidious Gram-negative pathogens as well as against mycoplasmas and intracellular organisms, such as Chlamydia spp. and Legionella pneumophila Pleuromutilins are unaffected by resistance to other major antibiotic classes, such as macrolides, fluoroquinolones, tetracyclines, β-lactam antibiotics, and others. Furthermore, pleuromutilins display very low spontaneous mutation frequencies and slow, stepwise resistance development at sub-MIC in vitro. The potential for resistance development in clinic is predicted to be slow as confirmed by extremely low resistance rates to this class despite the use of pleuromutilins in veterinary medicine for >30 years. Although rare, resistant strains have been identified in human- and livestock-associated environments and as with any antibiotic class, require close monitoring as well as prudent

  11. Psychoactive substance use by truck drivers: a systematic review

    Science.gov (United States)

    Girotto, Edmarlon; Mesas, Arthur Eumann; de Andrade, Selma Maffei; Birolim, Marcela Maria

    2014-01-01

    The aim of this study was to summarise the scientific evidence on the prevalence of psychoactive substance use and on the factors associated with their intake among truck drivers. A systematic review was performed in the databases PubMed, Scientific Electronic Library Online, Latin American and Caribbean Health Sciences, and Cochrane and 36 cross-sectional studies were identified with quantitative results about the use of psychoactive substances by truck drivers. Out of these, 28 were carried out in countries with large land areas and 23 obtained their information through self-reporting. The most frequently studied substances were alcohol (n=25), amphetamines (n=17), marijuana (n=16) and cocaine (n=13). The prevalence of the use of these substances greatly varied: alcohol (0.1–91.0%); amphetamines (0.2–82.5%), marijuana (0.2–29.9%), cocaine (0.1–8.3%). The frequency of substance use was lower in studies that investigated the presence of these substances in biological samples than in those based on self-reported use. In 12 studies that evaluated factors associated with the intake of psychoactive substances, the following stood out: younger age, higher income, longer trips, alcohol consumption, driving in the night shift, travelling interstate routes, long or short sleep, fewer hours of rest, little experience of the driver, connection with small and medium sized companies, income below levels determined by labour agreements, productivity-based earnings and prior involvement in accidents. The frequency of psychoactive substance use by truck drivers seems to be high, although that greatly varies according to the type of substance and the method of collecting the information. The use of these substances was mainly associated with indicators of poor working conditions. PMID:24145953

  12. The use of conferencing technologies to support drug policy group knowledge exchange processes: an action case approach.

    Science.gov (United States)

    Househ, Mowafa Said; Kushniruk, Andre; Maclure, Malcolm; Carleton, Bruce; Cloutier-Fisher, Denise

    2011-04-01

    To describe experiences, lessons and the implications related to the use of conferencing technology to support three drug policy research groups within a three-year period, using the action case research method. An action case research field study was executed. Three different drug policy groups participated: research, educator, and decision-maker task groups. There were a total of 61 participants in the study. The study was conducted between 2004 and 2007. Each group used audio-teleconferencing, web-conferencing or both to support their knowledge exchange activities. Data were collected over three years and consisted of observation notes, interviews, and meeting transcripts. Content analysis was used to analyze the data using NIVIO qualitative data analysis software. The study found six key lessons regarding the impact of conferencing technologies on knowledge exchange within drug policy groups. We found that 1) groups adapt to technology to facilitate group communication, 2) web-conferencing communication is optimal under certain conditions, 3) audio conferencing is convenient, 4) web-conferencing forces group interactions to be "within text", 5) facilitation contributes to successful knowledge exchange, and 6) technology impacts information sharing. This study highlights lessons related to the use of conferencing technologies to support distant knowledge exchange within drug policy groups. Key lessons from this study can be used by drug policy groups to support successful knowledge exchange activities using conferencing technologies. 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Impact of Safety-Related Regulatory Action on Drug Use in Ambulatory Care in the Netherlands

    NARCIS (Netherlands)

    Piening, S.; Reber, K. C.; Wieringa, J. E.; Straus, S. M. J. M.; de Graeff, P. A.; Haaijer-Ruskamp, F. M.; Mol, P. G. M.

    The effect of Direct Healthcare Professional Communications (DHPCs) informing health-care providers of serious drug safety issues has been questioned. The aim of this study was to evaluate the impact of DHPCs on drug use. Nationwide dispensing data for the period 2000-2008 for new users of 46 drugs

  14. Teens in Action. Creating a Drug-Free Future for America's Youth.

    Science.gov (United States)

    Adams, Tom; Resnik, Hank

    This book on drug abuse prevention is addressed to teenagers and covers five main areas where drug use can be prevented: schools, communities, media, the social scene, and the family. The first chapter on school programs briefly discusses peer-led alcohol and drug education, peer counseling, creating a positive school climate, and developing…

  15. Detection of new psychoactive substance use among emergency room patients: results from the Swedish STRIDA project.

    Science.gov (United States)

    Helander, Anders; Bäckberg, Matilda; Hultén, Peter; Al-Saffar, Yasir; Beck, Olof

    2014-10-01

    The "STRIDA" project monitors the occurrence and trends of new psychoactive substances (NPS; "Internet drugs/designer drugs/legal highs") in Sweden, and collects information about their clinical symptoms, toxicity and associated health hazards. The initial results of the project documented a widespread use of many different NPS by mainly adolescents and young (age range 13-63 years, median 20), male (79%) adults, among cases of drug intoxications presenting at emergency departments and intensive care units across the country. The new substances were identified in samples of urine and blood by a multi-component LC-MS/MS method, and the severity of clinical symptoms were graded by the Poisoning Severity Score (PSS). Of the initial 189 samples submitted for laboratory investigation, 156 (83%) tested positive for at least one drug. Besides classical substances such as ethanol, cannabis and amphetamines, many NPS were detected comprising synthetic cannabinoid receptor agonists ("Spice"), piperazines, substituted phenethylamines, synthetic cathinones, hallucinogenic tryptamines, piperidines, opioid related substances, ketamine and related substances, and GABA analogues (in total more than 50 substances). About half of the cases were demonstrated to be multiple drug intoxications, sometimes making it hard to associate the clinical presentations with one specific substance. In conclusion, the STRIDA project has documented use of a broad variety of NPS among mainly young people all over Sweden. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. The interaction of public-school teachers with student users of psychoactive substances

    Directory of Open Access Journals (Sweden)

    De Castro Rossi L.C.

    2010-12-01

    Full Text Available The increasing and early use of psychoactive substances by children and adolescents represents a challenge to public-health practice. To understand teachers' interactions with student users of drugs and develop a representative theoretical model of such experience this study was conducted. Qualitative study conducted in Sro Paulo, Brazil, with 32 teachers from public schools by means of focal groups and based on the Grounded Theory as its methodological framework. Progressively comprehensive categories converged to three phenomena: Identifying student's users; Feeling powerless in face the challenges of drugs use; Silencing to preserve oneself from a threatening scenario. These phenomena constructed the core category of the experience: Silencing to preserve oneself from a threatening scenario in face of the fragility of rescuing student's users of drugs. The clash between inducing and protective factors in the concrete situations of drugs use was revealed, thus pointing out that the lack of State and social support associated with the user's relation with drug trafficking and violence leads teachers to silence as they feel unprotected in face of a situation surrounded by stigma and prejudice. Coping strategies should include the educators, relatives, health care professionals and government institutions, thus providing ways to prevent and treat use, orientate and reconstruct lives in a process of active participation for all students

  17. Preclinical assessment of CNS drug action using eye movements in mice

    Science.gov (United States)

    Cahill, Hugh; Rattner, Amir; Nathans, Jeremy

    2011-01-01

    The drug development process for CNS indications is hampered by a paucity of preclinical tests that accurately predict drug efficacy in humans. Here, we show that a wide variety of CNS-active drugs induce characteristic alterations in visual stimulus–induced and/or spontaneous eye movements in mice. Active compounds included sedatives and antipsychotic, antidepressant, and antiseizure drugs as well as drugs of abuse, such as cocaine, morphine, and phencyclidine. The use of quantitative eye-movement analysis was demonstrated by comparing it with the commonly used rotarod test of motor coordination and by using eye movements to monitor pharmacokinetics, blood-brain barrier penetration, drug-receptor interactions, heavy metal toxicity, pharmacologic treatment in a model of schizophrenia, and degenerative CNS disease. We conclude that eye-movement analysis could complement existing animal tests to improve preclinical drug development. PMID:21821912

  18. Relationship of alexithymia to personality styles in people dependent on psychoactive substance

    Directory of Open Access Journals (Sweden)

    Roman Procházka

    2014-12-01

    Full Text Available The addiction to psychoactive drugs still remains among the relevant research topics. The research herein focuses on the study and analysis of the relations among the alexithymia, and personality styles. The analyses of such psychological constructs may represent valuable views beneficial for the progress in the up-to-date addictology. The article deals with a number of topics, such as, definition of alexithymia, the issue of addictology and personality aspects.. The applied statistical methods are descriptive statistics, factor analysis, non-parametric Spearman's correlation analysis and Mann-Whitney U Test. The reason for choosing the non-parametric statistics has been the conclusion of the normality test pointing at the fact that the acquired data had not complied with the normal distribution assumption. The data collection methods were questionnaires TAS-20 (Toronto Alexithymia Scale to measure alexithymia, and PSSI (Personality Style and Disorder Inventory. The gross sample under research was represented by 55 probands, namely 14 women and 41 men. The data were collected in the Psychiatric Hospital of Marianna Oranžská in Bílá Voda. The obtained results enabled us to answer the postulated research questions, which were evaluated and the following conclusions were reached: In people addicted to alcohol alexithymia occurs in 41.83 %. In subjects addicted to psychoactive drugs with alexithymia there is a substantial difference in the personality styles of a schizoid, obsessive-compulsive, avoidant, negativistic, borderline, histrionic, and self-defeating type. We believe that in this field of research there is still a huge gap to be filled, and we hope that the research may help to do so by enriching the knowledge with concrete results.

  19. Oral lesions of 500 habitual psychoactive substance users in Chennai, India.

    Science.gov (United States)

    Thavarajah, Rooban; Rao, Anita; Raman, Uma; Rajasekaran, Saraswathi T; Joshua, Elizabeth; R, Hemalatha; Kannan, Ranganathan

    2006-06-01

    The aim of this study was to ascertain the prevalence of oral lesions among 500 psychoactive substance users in a hospital-based population. The study group consisted of 500 consecutive patients attending TTK Hospital, a non-governmental organisation involved in rehabilitation of substance users. Patient history was recorded in a pre-determined format and clinical findings were recorded by a trained physician and dental surgeons. Psychoactive substances used by the patients were alcohol (97%), tobacco (72%), arecanut (57.2%), narcotics (6.8%), cannabis (3.2%) and benzodiazipines (1.8%). Ninety-one percent of patients had one or more oral lesions: dental caries (39%), gingivitis (37.6%), extrinsic stains (24%), oral submucous fibrosis (OSF) (8%), periodontitis (7.4%), leukoplakia (6.6%), melanosis (5.2%), nicotina palatini (2.2%) and erythroplakia (0.6%). For OSF, those using arecanut and alcohol had an odds ratio (OR) of 2.4 [95% confidence intervals (CI) 1.23-4.69, P=0.009], smokers using arecanut products and alcohol had an OR of 3.07 (95% CI 1.59-5.91, P=0.000), and smokers who chewed arecanut products and used drugs had an OR of 23.1 (95% CI 2.05-260, P=0.001) compared with the general population. Those who smoked and used alcohol, arecanut and drugs had a 20.67-fold higher risk of developing leukoplakia compared with those who did not engage in these habits. In conclusion, 91% of patients had one or more oral lesions that needed dental treatment, and most patients were not aware of their oral lesions. The high prevalence of OSF and leukoplakia in substance abusers compared with the general population emphasises the need for regular dental assessments in these patients.

  20. [Factors Related With Psychoactive Substance Use in an Educational Institution in Jamundí Valle, Colombia].

    Science.gov (United States)

    Espinosa Soto, Katalina; Hernández Carrillo, Mauricio; Cassiani, Carlos Arturo; Cubides Munevar, Ángela M; Martínez Cardona, María del Carmen

    2016-01-01

    To estimate the prevalence of psychoactive substances (SPA) use in young people in an educational institution in Jamundí and possible related factors. Cross-sectional study, analytical approach that simulates cases and controls, was conducted in an educational institution in Jamundí-Valley. The sample was composed of 146 students selected through simple random probability sampling without replacement. Participants individually and anonymously completed a questionnaire to identify SPA consumption and associated factors, including APGAR scale to measure family functioning. The data extracted from the questionnaires were entered into a matrix in Microsoft Excel and processed in EpiInfo version 5.0 and Stata. Descriptive analysis was performed, and a multivariate analysis was performed using unconditional logistic regression. Current consumption of SPA, 35%; age of first use was 10 to 13 years; the prevalence of drug misuse by gender was 34% for girls and 37% in boys. The most consumed legal substance was alcohol 34%, and illegal 3%. The most significant associations with the use of psychoactive substances was; having severe family dysfunction (OR=7.32; 95%CI, 1.74-30.76), being enrolled in the 11th grade (OR=14.6; 95%CI, 2.37-89.74), and having friends who use (OR=3.12; 95%CI, 2.49-10.38). The results obtained in this study show a high percentage of SPA consumption, with a higher prevalence in males. In this population, the most commonly used legal substance is alcohol. Family dysfunction and school grade were significantly associated with drug misuse. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  1. Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

    2017-04-01

    Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

  2. An ethnomycological review of psychoactive agarics in Australia and New Zealand.

    Science.gov (United States)

    Allen, J W; Merlin, M D; Jansen, K L

    1991-01-01

    A comprehensive review is presented of the recreational and accidental ingestion of psychoactive mushrooms in Australia and New Zealand; 15 recognized species are considered from Australia and eight from New Zealand. Common epithets, potency levels, and methods of ingestion are discussed. Legal aspects involving the use of these psychoactive fungi are noted. In addition, medical and psychoactive effects of these mushrooms and treatment for psilocybian mushroom poisoning are described. Numerous case reports, with commentary, are also presented.

  3. Critical role of peripheral drug actions in experience-dependent changes in nucleus accumbens glutamate release induced by intravenous cocaine

    Science.gov (United States)

    Wakabayashi, Ken T.; Kiyatkin, Eugene A.

    2015-01-01

    Recent studies reveal that cocaine experience results in persistent neuroadaptive changes within glutamate (Glu) synapses in brain areas associated with drug reward. However, it remains unclear whether cocaine affects Glu release in drug-naive animals and how it is altered by drug experience. By using high-speed amperometry with enzyme-based and enzyme-free biosensors in freely moving rats, we show that an initial intravenous cocaine injection at a low self-administering dose (1 mg/kg) induces rapid, small and transient Glu release in the nucleus accumbens shell (NAc), which with subsequent injections rapidly becomes a much stronger, two-component increase. Using cocaine-methiodide, cocaine’s analogue that does not cross the blood-brain barrier, we confirm that the initial cocaine-induced Glu release in the NAc has a peripheral neural origin. Unlike cocaine, Glu responses induced by cocaine-methiodide rapidly habituate following repeated exposure. However, after cocaine experience this drug induces cocaine-like Glu responses. Hence, the interoceptive actions of cocaine, which essentially precede its direct actions in the brain, play a critical role in experience-dependent alterations in Glu release, cocaine-induced neural sensitization and may contribute to cocaine addiction. PMID:24111505

  4. Antitumor-active cobalt-alkyne complexes derived from acetylsalicylic acid: studies on the mode of drug action.

    Science.gov (United States)

    Ott, Ingo; Schmidt, Kathrin; Kircher, Brigitte; Schumacher, Petra; Wiglenda, Thomas; Gust, Ronald

    2005-01-27

    Cobalt-alkyne complexes are drugs with remarkable cytotoxicity. From the complexes tested up to now we selected the aspirin derivative [2-acetoxy-(2-propynyl)benzoate]hexacarbonyldicobalt (Co-ASS) as the lead compound. To get more insight into the mode of action, we systematically modified the alkyne ligand and determined the cytotoxic properties of the resulting cobalt complexes. Further investigations were performed on the drug lipophilicity, the cellular uptake into MCF-7 and MDA-MB 231 breast cancer cells, the DNA-binding efficacy, and the nuclear drug content. The ability to inhibit glutathione reductase and cyclooxygenase (COX) enzymes, the binding to the estrogen receptor, and the induction of apoptotic processes were examined for selected compounds. Interestingly, the most antitumor active compounds were potent COX inhibitors (COX-1 and COX-2). The presented results indicate that cobalt-alkyne complexes of the Co-ASS type, represent a new class of organometallic cytostatics with a mode of drug action in which COX inhibition probably plays a major role.

  5. Bioinformatics and rational drug design: tools for discovery and better understanding of biological targets and mode of action of drugs.

    Science.gov (United States)

    Thibaut, U

    2002-01-01

    With the advent of modern high throughput technologies in both genomics and biological screening, and at the same time the enormous advances in computer technology, it is now feasible to use these tools in rational approaches in the search for new medicines. The role of bioinformatics in the search for new medicines is discussed. Discussion of the author's own work on bioinformatics in drug research in future perspective. The emerging discipline of Bioinformatics plays a central role in the concert of technologies of the 'biological revolution' because it allows for handling of the enormous data load that comes with sequencing efforts and subsequent analyses of whole genomes, with mRNA profiling techniques and, last but not least, at a later stage of drug discovery the up-to-date application of rational drug design techniques to 3D structures of target proteins. This article covers and explains parts of the steps used in modern pharmaceutical research by means of a small number of examples. Bioinformatics is likely to play a pivotal role in the rational approaches for the search of new medicines.

  6. Sitamaquine as a putative antileishmanial drug candidate: from the mechanism of action to the risk of drug resistance

    Directory of Open Access Journals (Sweden)

    Loiseau P.M.

    2011-05-01

    Full Text Available Sitamaquine is a 8-aminoquinoline in development for the treatment of visceral leishmaniasis by oral route, no activity being observed on the experimental cutaneous leishmaniasis experimental models. Recent data explain how sitamaquine accumulate in Leishmania parasites, however its molecular targets remain to be identified. An advantage of sitamaquine is its short elimination half-life, preventing a rapid resistance emergence. The antileishmanial action of its metabolites is not known. The selection of a sitamaquine-resistant clone of L. donovani in laboratory and the phase II clinical trials pointing out some adverse effects such as methemoglobinemia and nephrotoxicity are considered for a further development decision.

  7. "Someone Else's Problem": New Psychoactive Substances in the Online Hungarian Media.

    Science.gov (United States)

    Kassai, Szilvia; Rácz, József; Nagy, Alexandra; Bíbók, Tamás; Galambvári, Éva; Kilián, Csillag; Gyarmathy, V Anna

    2017-01-01

    Media monitoring is an important method to inform public health and prevention services about emerging health issues, such as new psychoactive substances (NPS). This study assessed the portrayal of NPS in online Hungarian media in 2015 using qualitative content analysis. Hungarian online media considers the dealer to be the main cause of drug use, which is portrayed as a problem for youth, poor people, minorities, and rural populations. The point of view of the articles is externalized, and so is the solution offered by them. From the perspective of the police or using a biomedical approach, the articles suggest that drug use is an individual (someone else's) problem, and the perspectives of insiders (such as users or addiction treatment professionals) are absent. The media portrays low socioeconomic background and the hopelessness of disadvantaged rural and mostly minority populations as the roots of NPS use, and misses the pressing incapability of health care emergency and drug treatment services to cope with the problem. The dominant portrayal of police raids is rarely counterbalanced by voices of active or recovering drug users or professionals in addiction treatment and harm reduction, who could offer a systematic solution to the apparent rapid spread of NPS use.

  8. [Use and abuse of alcohol and other psychoactive substances among Polish university students].

    Science.gov (United States)

    Mellibruda, Jerzy; Nikodemska, Sabina; Fronczyk, Krzysztof

    2003-01-01

    The results of country-wide research on alcohol and psychoactive substances use among Polish students are presented. The survey was carried out in the year 2000 and included 9446 students from 8 major academic centres in Poland. Negative events linked with the use of alcohol and drugs were discovered - 40% of students (42% of men and 37% of women) during the last two weeks exceeded the limit of dangerous drinking. Large range of harmful consequences of binge drinking has been found - one in three men and one in four women committed acts under the influence of alcohol, which they regretted after. One in four men under influence of alcohol was involved in aggressive fights with peers and one in six has had serious trouble with studying and bad assessments. The scope of drug use was much smaller but also alarming. During the last 30 days 7% of the studied population reported use of marijuana and 1.5% amphetamine. Abuse of alcohol was correlated with use of drugs. This creates a serious risk of cross addiction and shows an important role of alcohol drinking as a gateway to drug use.

  9. Forfeiture of the profits and proceeds derived from drug trafficking: thoughts on future action in Malaysia.

    Science.gov (United States)

    Vohrah, K C

    1984-01-01

    While the Dangerous Drugs Act 1952 of Malaysia has been amended to take into account changing patterns of drug abuse and trafficking, it lacks provisions for the mandatory forfeiture of proceeds derived from drug trafficking. Nor do the general powers of forfeiture in the Criminal Procedure Code of the country extend to such proceeds. To meet further changing patterns of drug trafficking involving criminal syndicate leaders, who rarely incriminate themselves through overt and detectable acts, Malaysia has a bill in Parliament the purpose of which, when it becomes law, is to detain without trial, upon cogent evidence, persons who have been associated with any activity relating to or involving drug trafficking, and to prevent them from further committing drug crimes. In addition, serious thinking has been given to the possibility of adopting, within the constraints of the Malaysian Constitution, a law on forfeiture of the proceeds derived from drug trafficking. There are, in this respect, several problems to be resolved, such as the secrecy of bank accounts and taxpayers' returns, which might make it difficult to trace proceeds and to keep track of tainted money being remitted abroad, although it is believed that such problems could be overcome by domestic measures. A more serious problem is the lack of international co-operation for investigations to be carried out outside national borders to trace, seize, freeze and secure the forfeiture of the proceeds of drug crimes located abroad.

  10. Drug insight: Mechanisms and sites of action of ursodeoxycholic acid in cholestasis

    NARCIS (Netherlands)

    Beuers, Ulrich

    2006-01-01

    Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in various cholestatic disorders. Several potential mechanisms and sites of action of UDCA have been unraveled in clinical and experimental studies, which could explain its beneficial effects. The relative contribution of these mechanisms to

  11. Cognitive and value parameters of students’ perceptions of the effects of psychoactive substances

    Directory of Open Access Journals (Sweden)

    Dontsov, Aleksander I.

    2016-09-01

    Full Text Available This article sets forth the main results of a study analyzing attitudes toward psychoactivesubstance (PAS effects. These findings demonstrate the conditionality of social, historic, and cultural views of PAS effects. Despite the threat posed by increasing high school and university students’ drug involvement, exploration of this phenomenon in the format of scientific discourse has been limited so far. In 2014–2015, in Yekaterinburg, Moscow, and Krasnoyarsk a survey to evaluate perceptions of high school and university students about PAS effects was conducted (289 respondents, aged 16–22.The methods used included the semantic differential (Peabody Picture Vocabulary Test modified by A.G. Shmelyov, a modified version of the Rokeach Value Survey, word associations, and content analysis. The use of psychoactive substances is a specific social practice emerging in a certain social context that includes both drug-addicted and PAS-free young people. Examination of the factors affecting the formation of views about PAS effects and the dynamics of youth values is possible by using a bio-psycho-socio paradigm for performing a complex analysis of cognitive, behavioral, and value parameters. As documented in the respondents’ perceptions, distinctive features that are characteristic of drug addicts and that are seen in their behavior area loss of control over behavior, emotions, and volition; changes in value systems; and a tendency to develop a manipulative communication style. Within the system of their social perceptions the respondents endowed drug-addicted persons with pronounced negative characteristics (“aggressiveness,” “addiction,” “stupidity,” “light-mindedness”. Still, they stated that drug abusers are capable of being active, decisive, cheerful, generous, and flexible. The value analysis demonstrated that terminal values appreciated by the school and university students included health, true friends, love, happy family

  12. Action of β-endorphin and nonsteroidal anti-inflammatory drugs, and the possible effects of nonsteroidal anti-inflammatory drugs on β-endorphin.

    Science.gov (United States)

    Luan, Yuan-Hang; Wang, Di; Yu, Qi; Chai, Xiao-Qing

    2017-02-01

    This study aimed to review research on the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on β-endorphin. NSAIDs are commonly used as anti-inflammatory and analgesic drugs. They are well known for inducing peripheral analgesia by inhibiting cyclooxygenase (COX). However, an increasing number of studies have shown that NSAIDs have an analgesic effect not only in the periphery but also at the center. It means that a central analgesic mechanism of the action of NSAIDs exists besides the peripheral mechanism, and the central mechanism likely involves β-endorphin. β-Endorphin is one of the most prominent endogenous peptides, existing in the hypophysis cerebri and hypothalamus. It plays an irreplaceable role in the central and peripheral analgesia in the human body mainly through three mechanisms including three parts, the spinal cord, the supraspinal cord, and peripheries. β-Endorphin plays an important role in the development of hyperalgesia. However, the specific signal transduction pathways between prostaglandin E 2 or NSAIDs and β-endorphin are still not quite clear. Whether NSAIDs can lead to the increased content of β-endorphin in all patients after any operation needs further investigation. Further studies should determine the optimal dose when NSAIDs and opioid drugs are used together, and also explore the existence of one NSAID that has the potential to replace the traditional opioid drugs and can achieve adequate analgesia. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. FitSearch: a robust way to interpret a yeast fitness profile in terms of drug's mode-of-action.

    Science.gov (United States)

    Lee, Minho; Han, Sangjo; Chang, Hyeshik; Kwak, Youn-Sig; Weller, David M; Kim, Dongsup

    2013-01-01

    Yeast deletion-mutant collections have been successfully used to infer the mode-of-action of drugs especially by profiling chemical-genetic and genetic-genetic interactions on a genome-wide scale. Although tens of thousands of those profiles are publicly available, a lack of an accurate method for mining such data has been a major bottleneck for more widespread use of these useful resources. For general usage of those public resources, we designed FitRankDB as a general repository of fitness profiles, and developed a new search algorithm, FitSearch, for identifying the profiles that have a high similarity score with statistical significance for a given fitness profile. We demonstrated that our new repository and algorithm are highly beneficial to researchers who attempting to make hypotheses based on unknown modes-of-action of bioactive compounds, regardless of the types of experiments that have been performed using yeast deletion-mutant collection in various types of different measurement platforms, especially non-chip-based platforms. We showed that our new database and algorithm are useful when attempting to construct a hypothesis regarding the unknown function of a bioactive compound through small-scale experiments with a yeast deletion collection in a platform independent manner. The FitRankDB and FitSearch enhance the ease of searching public yeast fitness profiles and obtaining insights into unknown mechanisms of action of drugs. FitSearch is freely available at http://fitsearch.kaist.ac.kr.

  14. Prevalence and factors determining psychoactive substance (PAS) use among Hawassa University (HU) undergraduate students, Hawassa Ethiopia.

    Science.gov (United States)

    Kassa, Andargachew; Taddesse, Fiker; Yilma, Aweke

    2014-10-07

    Use of psychoactive substances (PAS) early in school age implies drug dependence in later life. Although no studies have been conducted on undergraduate students of Hawassa University, a few studies in Ethiopia have reported that alcohol, khat, and cigarette are the commonly abused PASs among young high school/undergraduate university students. Therefore, this study was designed to establish the prevalence of and predictors for PAS use among undergraduate HU Students. An institution-based quantitative cross-sectional study using the self-administered WHO Model Core Questionnaire to collect information on use of various Psychoactive Substances (PASs) was conducted from June to July 2011. A multistage stratified sampling method was employed to select a total of 586 undergraduate HU students as study participants. Bivariate and multivariate logistic regression analysis were done to determine factors affecting PAS use. Lifetime, past 12 months, and current prevalence rate for overall PAS were 53.6%, 45.7%, and 35.5% respectively. The study depicted that in the past 12 months of the study period 40.8% used alcohol, 20.3% chewed khat, 11.9% smoked cigarettes, and 0.9% used marijuana. The prevalence of other illicit PASs such as Ecstasy, lysergic diethylamide (LSD), cocaine, crack, heroin, solvents or inhalants and un-prescribed psycho active medications was found zero percent (0%). Having family members who used PAS, peer influence, being male, and living alone during school age were found to be positively associated with overall PAS use in the past 12 months. The prevalence of PAS use among undergraduate HU students is high. Designing effective strategies to reduce PAS use should be everyone's priority.

  15. Graph Theory Enables Drug Repurposing – How a Mathematical Model Can Drive the Discovery of Hidden Mechanisms of Action

    Science.gov (United States)

    Gramatica, Ruggero; Di Matteo, T.; Giorgetti, Stefano; Barbiani, Massimo; Bevec, Dorian; Aste, Tomaso

    2014-01-01

    We introduce a methodology to efficiently exploit natural-language expressed biomedical knowledge for repurposing existing drugs towards diseases for which they were not initially intended. Leveraging on developments in Computational Linguistics and Graph Theory, a methodology is defined to build a graph representation of knowledge, which is automatically analysed to discover hidden relations between any drug and any disease: these relations are specific paths among the biomedical entities of the graph, representing possible Modes of Action for any given pharmacological compound. We propose a measure for the likeliness of these paths based on a stochastic process on the graph. This measure depends on the abundance of indirect paths between a peptide and a disease, rather than solely on the strength of the shortest path connecting them. We provide real-world examples, showing how the method successfully retrieves known pathophysiological Mode of Action and finds new ones by meaningfully selecting and aggregating contributions from known bio-molecular interactions. Applications of this methodology are presented, and prove the efficacy of the method for selecting drugs as treatment options for rare diseases. PMID:24416311

  16. Graph theory enables drug repurposing--how a mathematical model can drive the discovery of hidden mechanisms of action.

    Directory of Open Access Journals (Sweden)

    Ruggero Gramatica

    Full Text Available We introduce a methodology to efficiently exploit natural-language expressed biomedical knowledge for repurposing existing drugs towards diseases for which they were not initially intended. Leveraging on developments in Computational Linguistics and Graph Theory, a methodology is defined to build a graph representation of knowledge, which is automatically analysed to discover hidden relations between any drug and any disease: these relations are specific paths among the biomedical entities of the graph, representing possible Modes of Action for any given pharmacological compound. We propose a measure for the likeliness of these paths based on a stochastic process on the graph. This measure depends on the abundance of indirect paths between a peptide and a disease, rather than solely on the strength of the shortest path connecting them. We provide real-world examples, showing how the method successfully retrieves known pathophysiological Mode of Action and finds new ones by meaningfully selecting and aggregating contributions from known bio-molecular interactions. Applications of this methodology are presented, and prove the efficacy of the method for selecting drugs as treatment options for rare diseases.

  17. Graph theory enables drug repurposing--how a mathematical model can drive the discovery of hidden mechanisms of action.

    Science.gov (United States)

    Gramatica, Ruggero; Di Matteo, T; Giorgetti, Stefano; Barbiani, Massimo; Bevec, Dorian; Aste, Tomaso

    2014-01-01

    We introduce a methodology to efficiently exploit natural-language expressed biomedical knowledge for repurposing existing drugs towards diseases for which they were not initially intended. Leveraging on developments in Computational Linguistics and Graph Theory, a methodology is defined to build a graph representation of knowledge, which is automatically analysed to discover hidden relations between any drug and any disease: these relations are specific paths among the biomedical entities of the graph, representing possible Modes of Action for any given pharmacological compound. We propose a measure for the likeliness of these paths based on a stochastic process on the graph. This measure depends on the abundance of indirect paths between a peptide and a disease, rather than solely on the strength of the shortest path connecting them. We provide real-world examples, showing how the method successfully retrieves known pathophysiological Mode of Action and finds new ones by meaningfully selecting and aggregating contributions from known bio-molecular interactions. Applications of this methodology are presented, and prove the efficacy of the method for selecting drugs as treatment options for rare diseases.

  18. Unique Mechanism of Action of the Thiourea Drug Isoxyl on Mycobacterium tuberculosis

    National Research Council Canada - National Science Library

    Benjawan Phetsuksiri; Mary Jackson; Hataichanok Scherman; Michael McNeil; Gurdyal S. Besra; Alain R. Baulard; Richard A. Slayden; Andrea E. DeBarber; Clifton E. Barry III; Mark S. Baird; Dean C. Crick; Patrick J. Brennan

    2003-01-01

    The thiourea isoxyl (thiocarlide; 4,4′-diisoamyloxydiphenylthiourea) is known to be an effective anti-tuberculosis drug, active against a range of multidrug-resistant strains of Mycobacterium tuberculosis and has been used clinically...

  19. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs

    Science.gov (United States)

    SOARES, Geisla Mary Silva; FIGUEIREDO, Luciene Cristina; FAVERI, Marcelo; CORTELLI, Sheila Cavalca; DUARTE, Poliana Mendes; FERES, Magda

    2012-01-01

    Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole) and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections. PMID:22858695

  20. Pilot experiments on the actions of drugs injected into the human corpus cavernosum penis.

    OpenAIRE

    Brindley, G. S.

    1986-01-01

    Seven drugs that are known to relax smooth muscle (phenoxybenzamine, phentolamine, thymoxamine, imipramine, verapamil, papaverine, naftidrofuryl) caused erection when injected intracavernosally. Salbutamol, hydralazine, lignocaine and bupivacaine caused tumidity but not erection. Metaraminol and guanethidine caused shrinkage followed by tumidity. Neostigmine, atropine, propranolol and idazoxan had no effect in the doses tried. It is argued that the seven drugs that cause erection do so by rel...

  1. Analysis of Safety-Related Regulatory Actions for New Drugs in Japan by Nature of Identified Risks.

    Science.gov (United States)

    Fujikawa, Makoto; Ono, Shunsuke

    2017-01-01

    Mechanisms underlying safety events may be heterogeneous and depend on conditions of development and marketing, including the populations studied in clinical trials and the amount of data required for approval, especially under pathways for accelerated access. This study was conducted to investigate possible factors affecting the first post-marketing safety-related regulatory actions (SRRAs) after launch of new drugs in Japan. We studied 338 new molecular entities (NMEs) approved in Japan between 2004 and 2014. We focused on three different types of SRRAs: (1) all-SRRAs (i.e. SRRAs from domestic cases and other countries), (2) domestic-SRRAs (i.e. SRRAs from domestic cases) and (3) domestic unknown-SRRAs (i.e. SRRAs of unknown risks from domestic cases). Occurrences of the three types of SRRAs were analyzed using Kaplan-Meier analysis and Cox-regression. SRRAs tended to occur sooner for NMEs launched in recent years versus those launched towards the beginning of the study period. Risk of SRRA was high for antineoplastics. Drugs for cardiovascular diseases, central nervous system, and diabetes had positive associations with all-SRRAs, but the associations were weaker with domestic-SRRAs. Domestic-SRRAs were more likely for drugs with relatively novel modes of action (MOAs). Longer lag to Japanese launch after first global launch significantly lowered SRRA risks. While most of the variables showed similar associations across the three types of SRRAs, adoption of bridging strategies showed higher risks only for domestic-SRRAs, not for all-SRRAs. FDA safety labeling changes and non-orphan priority review drugs presented higher domestic-SRRA risks. The number of adverse drug reactions (ADRs) from spontaneous reports had positive correlations with the three types of SRRAs, whereas the number from company-led surveillance showed no association. Our results indicated that global clinical development pathways and marketing status should be considered more seriously in

  2. [The use of psychoactive substances among street teenagers in Ouagadougou].

    Science.gov (United States)

    Garanet, Franck; Bogono, Etienne; Ouédraogo, Ousmane; Mésenge, Christian

    2016-01-01

    Objectives: To study the determinants of psychoactive substance use among street teenagers living in Ouagadougou.Methods: Qualitative and quantitative cross-sectional study with street teenagers living on the Zogona campus in Ouagadougou, in September 2012. A focus group was then formed with eight members of the group.Results: The median age was 16 years (range: 12 to 20 years). The various psychotropic agents were tobacco, alcohol, gasoline, glue sniffing and cannabis. Seventeen of the 31 teenagers had already been admitted to a rehabilitation centre and none of them attended school at the time of data collection. However, 12 street teenagers had previously attended school. The main reasons for the presence of these teenagers in the street were “poverty in the family”, “death of the parents”, “Koranic school”. The main reasons reported by the teenagers for substance use were “to give oneself courage”, “to relieve hunger”, “to be like the others”, “to be accepted by the group”, “to protect oneself from the cold”. The main determinants of substance abuse were social exclusion, group membership, and group identification.Conclusion: Psychoactive substance use is an integral part of the life of street teenagers and is a major obstacle to social integration.

  3. Readiness to Use Psychoactive Substances Among Second-Generation Adolescent Immigrants and Perceptions of Parental Immigration-Related Trauma.

    Science.gov (United States)

    Aviad-Wilchek, Yael; Levy, Inna; Ben-David, Sarah

    2017-10-15

    This research explores the relationship between parental immigration-related trauma and second-generation adolescent substance abuse. To examine this relationship, we focused on Ethiopian adolescents in Israel who are at risk for substance abuse. Many immigrants from Ethiopia experienced severe immigration trauma and research indicates the existence of transgenerational trauma transmission. The current research focuses on the connection between Ethiopian adolescents' perceptions of their parents' immigration trauma and their readiness to use psychoactive substances. Five hundred and ten second-generation Ethiopian adolescents (Israeli-born children of Ethiopian immigrants) filled out questionnaires examining socio-demographic characteristics, immigration impact and readiness to consume alcoholic beverages and use illegal drugs. Our findings show that readiness levels among Ethiopian adolescents to use psychoactive substances are relatively low, and that parental trauma only affects the readiness to consume alcohol. The levels of readiness to consume drugs were partially related to parental trauma. Conclusions/Importance: Transgenerational trauma transmission should be considered when implementing alcohol and substance abuse treatment and prevention policies among second generation immigrants. This should be done on all levels including personal, interpersonal and community levels.

  4. Knowledge of actions of inhaled corticosteroids in patients who did not persist drug treatment early

    NARCIS (Netherlands)

    Menckeberg, T.T.; Hugtenburg, J.G.; Lammers, J.W.; Raaijmakers, J.A.; Bouvy, M.L.

    2012-01-01

    Objective To evaluate, among new users of inhaled corticosteroids that did not persist treatment, knowledge of inhaled corticosteroids' actions and whether they were instructed on the use of their inhaler. Setting Fifteen community pharmacies in The Netherlands. Methods Patients were interviewed by

  5. Action at a Distance: Functional Drug Delivery Using Electromagnetic-Field-Responsive Polypyrrole Nanowires

    Science.gov (United States)

    2015-01-01

    In this work, we introduce a free-standing, vertically aligned conductive polypyrrole (Ppy) architecture that can serve as a high-capacity drug reservoir. This novel geometric organization of Ppy provides a new platform for improving the drug-loading efficiency. Most importantly, we present the first formal evidence that an impregnated drug (dexamethasone, DEX) can be released on demand by a focal, pulsatile electromagnetic field (EMF). This remotely controlled, on–off switchable polymer system provides a framework for implantable constructs that can be placed in critical areas of the body without any physical contact (such as percutaneous electrodes) with the Ppy, contributing to a low “foreign body” footprint. We demonstrate this possibility by using a BV-2 microglia culture model in which reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) expression was attenuated in response to DEX released from EMF-stimulated Ppy. PMID:24961510

  6. In Silico Screening of Nonsteroidal Anti-Inflammatory Drugs and Their Combined Action on Prostaglandin H Synthase-1

    Directory of Open Access Journals (Sweden)

    Alexey Goltsov

    2010-07-01

    Full Text Available The detailed kinetic model of Prostaglandin H Synthase-1 (PGHS-1 was applied to in silico screening of dose-dependencies for the different types of nonsteroidal anti-inflammatory drugs (NSAIDs, such as: reversible/irreversible, nonselective/selective to PGHS-1/PGHS-2 and time dependent/independent inhibitors (aspirin, ibuprofen, celecoxib, etc. The computational screening has shown a significant variability in the IC50s of the same drug, depending on different in vitro and in vivo experimental conditions. To study this high heterogeneity in the inhibitory effects of NSAIDs, we have developed an in silico approach to evaluate NSAID action on targets under different PGHS-1 microenvironmental conditions, such as arachidonic acid, reducing cofactor, and peroxide concentrations. The designed technique permits translating the drug IC50, obtained in one experimental setting to another, and predicts in vivo inhibitory effects based on the relevant in vitro data. For the aspirin case, we elucidated the mechanism underlying the enhancement and reduction (aspirin resistance of its efficacy, depending on PGHS-1 microenvironment in in vitro/in vivo experimental settings. We also present the results of the in silico screening of the combined action of sets of two NSAIDs (aspirin with ibuprofen, aspirin with celecoxib, and study the mechanism of the experimentally observed effect of the suppression of aspirin-mediated PGHS-1 inhibition by selective and nonselective NSAIDs. Furthermore, we discuss the applications of the obtained results to the problems of standardization of NSAID test assay, dependence of the NSAID efficacy on cellular environment of PGHS-1, drug resistance, and NSAID combination therapy.

  7. The motor way: Clinical implications of understanding and shaping actions with the motor system in autism and drug addiction.

    Science.gov (United States)

    Casartelli, Luca; Chiamulera, Cristiano

    2016-04-01

    To understand others' minds is crucial for survival; however, it is quite puzzling how access to others' minds can be--to some extent--direct and not necessarily mediated by conceptual reasoning. Recent advances in neuroscience have led to hypothesize a role for motor circuits not only in controlling the elementary physical features of movement (e.g., force, direction, and amplitude), but also in understanding and shaping human behavior. The concept of "motor cognition" refers to these aspects, and neurophysiological, neuroimaging, and behavioral studies in human and nonhuman primates support this view. From a clinical perspective, motor cognition represents a challenge in several domains. A thorough investigation of the neural mechanisms mediating motor action/intention understanding and automatized/compulsive behaviors seems to be a promising way to tackle a range of neurodevelopmental and drug-related disorders. On the one hand, anomalies in motor cognition may have cascade effects on social functioning in individuals with autism spectrum disorder (ASD); on the other, motor cognition may help explain the pathophysiology of drug-seeking and drug-taking behaviors in the most severe phase of drug addiction (i.e., see drug dependence, motor low-order cue reactivity). This may represent a promising approach that could improve the efficacy of rehabilitative interventions. The only way to shed light on multifactorial disorders such as ASD and drug addiction is through the investigation of their multiple factors. This motor way can promote new theoretical and experimental perspectives that would help bridge the gap between the basic neuroscience approach and clinical practice.

  8. Gene duplication and divergence affecting drug content in Cannabis sativa

    National Research Council Canada - National Science Library

    Weiblen, George D; Wenger, Jonathan P; Craft, Kathleen J; ElSohly, Mahmoud A; Mehmedic, Zlatko; Treiber, Erin L; Marks, M. David

    2015-01-01

    ..., and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid ( THCA...

  9. GLATIRAMER ACETATE IS A FIRST-LINE DUAL-ACTION DRUG FOR THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    T. E. Shmidt

    2016-01-01

    Full Text Available Multiple sclerosis (MS is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs  has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis.The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs. To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

  10. Internalization, Trafficking, Intracellular Processing and Actions of Antibody-Drug Conjugates.

    Science.gov (United States)

    Xu, Shi

    2015-11-01

    This review discusses the molecular mechanism involved in the targeting and delivery of antibody-drug conjugates (ADCs), the new class of biopharmaceuticals mainly designed for targeted cancer therapy. this review goes over major progress in preclinical and clinical studies of ADCs, in the past 5 years. The pharmacokinetics and pharmacodynamics of ADCs involve multiple mechanisms, including internalization of ADCs by target cells, intracellular trafficking, release of conjugated drugs, and payload. These mechanisms actually jointly determine the efficacy of ADCs. Therefore, the optimization of ADCs should take them as necessary rationales.

  11. Nrf2/ARE-mediated antioxidant actions of pro-electrophilic drugs.

    Science.gov (United States)

    Satoh, Takumi; McKercher, Scott R; Lipton, Stuart A

    2013-12-01

    Living cells maintain a balance between oxidation and reduction, and perturbations of this redox balance are thought to contribute to various diseases. Recent attempts to regulate redox state have focused on electrophiles (EPs), which activate potent cellular defense systems against oxidative stress. One example of this approach is exemplified by carnosic acid (CA) and carnosol (CS), compounds that are found in the herb rosemary (Rosmarinus officinalis). Importantly, CA and CS themselves are not electrophilic, but in response to oxidation, become electrophilic, and then activate the Keap1/Nrf2/ARE (antioxidant-response element) transcription pathway to synthesize endogenous antioxidant "phase 2" enzymes. As a result of our efforts to develop these compounds as therapeutics for brain health, we have formulated two innovative criteria for drug development: the first concept is the use of pro-electrophilic drugs (PEDs) that are innocuous in and of themselves; and the second concept involves the use of compounds that are pathologically activated therapeutics (PATs);i.e., these small molecules are chemically converted to their active form by the very oxidative stress that they are designed to then combat. The chemical basis for PED and PAT drugs is embodied in the ortho- and para-hydroquinone electrophilic cores of the molecules, which are oxidized by the Cu(2+)/Cu(+) cycling system (or potentially by other transition metals). Importantly, this cycling pathway is under stringent regulation by the cell redox state. We propose that redox-dependent quinone formation is the predominant mechanism for formation of PED and PAT drugs from their precursor compounds. In fact, redox-dependent generation of the active form of drug from the "pro-form" distinguishes this therapeutic approach from traditional EPs such as curcumin, and results in a decrease in clinical side effects at therapeutic concentrations, e.g., lack of reaction with other thiols such as glutathione (GSH), which

  12. Reprint of: Nrf2/ARE-mediated antioxidant actions of pro-electrophilic drugs.

    Science.gov (United States)

    Satoh, Takumi; McKercher, Scott R; Lipton, Stuart A

    2014-01-01

    Living cells maintain a balance between oxidation and reduction, and perturbations of this redox balance are thought to contribute to various diseases. Recent attempts to regulate redox state have focused on electrophiles (EPs), which activate potent cellular defense systems against oxidative stress. One example of this approach is exemplified by carnosic acid (CA) and carnosol (CS), compounds that are found in the herb rosemary (Rosmarinus officinalis). Importantly, CA and CS themselves are not electrophilic, but in response to oxidation, become electrophilic, and then activate the Keap1/Nrf2/ARE (antioxidant-response element) transcription pathway to synthesize endogenous antioxidant "phase 2"enzymes. As a result of our efforts to develop these compounds as therapeutics for brain health, we have formulated two innovative criteria for drug development: the first concept is the use of pro-electrophilic drugs (PEDs) that are innocuous in and of themselves; and the second concept involves the use of compounds that are pathologically activated therapeutics (PATs); i.e., these small molecules are chemically converted to their active form by the very oxidative stress that they are designed to then combat. The chemical basis for PED and PAT drugs is embodied in the ortho- and para-hydroquinone electrophilic cores of the molecules, which are oxidized by the Cu(2+)/Cu(+) cycling system (or potentially by other transition metals). Importantly, this cycling pathway is under stringent regulation by the cell redox state. We propose that redox-dependent quinone formation is the predominant mechanism for formation of PED and PAT drugs from their precursor compounds. In fact, redox-dependent generation of the active form of drug from the "pro-form" distinguishes this therapeutic approach from traditional EPs such as curcumin, and results in a decrease in clinical side effects at therapeutic concentrations, e.g., lack of reaction with other thiols such as glutathione (GSH), which

  13. The role of serotonin in drug use and addiction

    NARCIS (Netherlands)

    Muller, C.P.; Homberg, J.R.

    2015-01-01

    The use of psychoactive drugs is a wide spread behaviour in human societies. The systematic use of a drug requires the establishment of different drug use-associated behaviours which need to be learned and controlled. However, controlled drug use may develop into compulsive drug use and addiction, a

  14. Voluntary Action and Illegal Drugs: Health and Society in Britain Since the 1960s

    OpenAIRE

    Mold, A; Berridge, V

    2010-01-01

    Through a study of the voluntary activity around illegal drug use since the 1960s, this book explores wider issues in the changing relationship between the state and the individual in the making, provision and delivery of public services, and addresses the history of key issues in the development of contemporary health and social policy.

  15. The mechanism of action of the oral anti-diabetic drugs: A review of ...

    African Journals Online (AJOL)

    Type 2 diabetes mellitus (DM) is a disorder that is placing an increasing burden on health service delivery worldwide. Consequently, it has become increasingly important that physicians who treat such patients have a good knowledge of antidiabetic drugs that are currently available or will come onto the market. This article ...

  16. Effects of formulation design on niacin therapeutics: mechanism of action, metabolism, and drug delivery.

    Science.gov (United States)

    Cooper, Dustin L; Murrell, Derek E; Roane, David S; Harirforoosh, Sam

    2015-07-25

    Niacin is a highly effective, lipid regulating drug associated with a number of metabolically induced side effects such as prostaglandin (PG) mediated flushing and hepatic toxicity. In an attempt to reduce the development of these adverse effects, scientists have investigated differing methods of niacin delivery designed to control drug release and alter metabolism. However, despite successful formulation of various orally based capsule and tablet delivery systems, patient adherence to niacin therapy is still compromised by adverse events such as PG-induced flushing. While the primary advantage of orally dosed formulations is ease of use, alternative delivery options such as transdermal delivery or polymeric micro/nanoparticle encapsulation for oral administration have shown promise in niacin reformulation. However, the effectiveness of these alternative delivery options in reducing inimical effects of niacin and maintaining drug efficacy is still largely unknown and requires more in-depth investigation. In this paper, we present an overview of niacin applications, its metabolic pathways, and current drug delivery formulations. Focus is placed on oral immediate, sustained, and extended release niacin delivery as well as combined statin and/or prostaglandin antagonist niacin formulation. We also examine and discuss current findings involving transdermal niacin formulations and polymeric micro/nanoparticle encapsulated niacin delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. 29 CFR 1472.225 - What actions must I take concerning employees who are convicted of drug violations in the workplace?

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false What actions must I take concerning employees who are convicted of drug violations in the workplace? 1472.225 Section 1472.225 Labor Regulations Relating to Labor... in a drug abuse assistance or rehabilitation program approved for these purposes by a Federal, State...

  18. Psychoactive pharmaceutical residues in the watersheds of Galicia (Spain Fármacos psicoactivos en las cuencas de Galicia

    Directory of Open Access Journals (Sweden)

    Sara Esteban

    2012-10-01

    Full Text Available Objective: To monitor the presence of pharmaceutical residues of 14 psychoactive drugs belonging to three therapeutic groups in the watersheds of Galicia (Spain. Method: Five sewage treatment plants were selected in the main cities of Galicia. Thirteen psychoactive pharmaceutical compounds and one metabolite were chosen. In addition, tap water samples were taken from public places and private residences in the selected cities. Results: In all the water samples analyzed, the highest concentrations corresponded to the group of anxiolytics. In particular, high concentrations of lorazepam were found in river and tap water samples. Conclusions: This investigation demonstrates the presence of psychoactive pharmaceuticals in the watersheds of the autonomous region of Galicia and the conversion of metabolites to parent compounds. This work also shows the need to increase environmental monitoring of watersheds and to improve sewage and drinking water treatment processes to remove these pharmaceuticals.Objetivo: Monitorizar la presencia de 14 fármacos psicoactivos pertenecientes a tres grupos terapéuticos en la cuenca de Galicia. Método: Se seleccionaron cinco estaciones depuradoras de aguas residuales en las principales ciudades de Galicia. Se escogieron trece compuestos farmacéuticos psicoactivos y un metabolito. Asimismo, se tomaron muestras de aguas del grifo de espacios públicos y privados en las ciudades seleccionadas. Resultados: En todas las muestras de agua analizadas, las mayores concentraciones han correspondido al grupo de los ansiolíticos, y especialmente el lorazepam ha aparecido en altas concentraciones en las muestras de aguas de río y del grifo. Conclusiones: Esta investigación demuestra la presencia de fármacos psicoactivos en las cuencas de Galicia y la reversión de los metabolitos a sus compuestos parentales. Asimismo, muestra la necesidad de incrementar la monitorización ambiental de las cuencas y de mejorar los procesos de

  19. Antithrombotic and fibrinolytic drugs for retinal vein occlusion: a systematic review and a call for action.

    Science.gov (United States)

    Squizzato, A; Manfredi, E; Bozzato, S; Dentali, F; Ageno, W

    2010-02-01

    Optimal management of retinal vein occlusion (RVO) is still a matter of debate. Antithrombotic and fibrinolytic drugs have been investigated after demonstration of a role of thrombosis in the complex pathogenesis of the disease. Aim of our study was to systematically summarise best available evidence on the acute treatment and on the secondary prevention of RVO with antithrombotic and fibrinolytic drugs. A computer-assisted search of the MEDLINE and EMBASE electronic databases up to January 2009 was performed. Two review authors selected all published randomised controlled trials (RCTs) from the search, assessed study quality and extracted data. Based on Jadad's score, RCTs were stratified into three quality categories. A total of six RCTs were included. Only one RCT of high quality was identified. A total of 384 patients were investigated, 234 with central retinal vein occlusion and 150 with branch retinal vein occlusion. No study enrolled more than 100 patients. Three studies compared therapeutic doses of low-molecular-weight heparin (LMWH) with low-dose aspirin, one study compared ticlopidine with placebo and two studies compared intravenous fibrinolytic therapy followed by warfarin or aspirin with either haemodilution or no treatment. A partial improvement of visual acuity was reported in every study, independently of the study drug. No long-term secondary prevention study was published. The present systematic review suggests that antithrombotic therapy, in particular LMWH, may be part of the therapeutic armamentarium for patients with recent onset RVO. No firm recommendation can be provided given the limited available evidence.

  20. The age of anxiety: role of animal models of anxiolytic action in drug discovery

    Science.gov (United States)

    Cryan, John F; Sweeney, Fabian F

    2011-01-01

    Anxiety disorders are common, serious and a growing health problem worldwide. However, the causative factors, aetiology and underlying mechanisms of anxiety disorders, as for most psychiatric disorders, remain relatively poorly understood. Animal models are an important aid in giving insight into the aetiology, neurobiology and, ultimately, the therapy of human anxiety disorders. The approach, however, is challenged with a number of complexities. In particular, the heterogeneous nature of anxiety disorders in humans coupled with the associated multifaceted and descriptive diagnostic criteria, creates challenges in both animal modelling and in clinical research. In this paper, we describe some of the more widely used approaches for assessing the anxiolytic activity of known and potential therapeutic agents. These include ethological, conflict-based, hyponeophagia, vocalization-based, physiological and cognitive-based paradigms. Developments in the characterization of translational models are also summarized, as are the challenges facing researchers in their drug discovery efforts in developing new anxiolytic drugs, not least the ever-shifting clinical conceptualization of anxiety disorders. In conclusion, to date, although animal models of anxiety have relatively good validity, anxiolytic drugs with novel mechanisms have been slow to emerge. It is clear that a better alignment of the interactions between basic and clinical scientists is needed if this is to change. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21545412

  1. Serious and actionable risks, plus disclosure: Investigating an alternative approach for presenting risk information in prescription drug television advertisements.

    Science.gov (United States)

    Betts, Kevin R; Boudewyns, Vanessa; Aikin, Kathryn J; Squire, Claudia; Dolina, Suzanne; Hayes, Jennifer J; Southwell, Brian G

    2017-08-02

    Broadcast direct-to-consumer (DTC) prescription drug ads that present product claims are required to also present the product's major risks. Debate exists regarding how much information should be included in these major risk statements. Some argue that such statements expose people to unnecessary amounts of information, while others argue that they leave out important information. Examine the impact of type of risk statement (unedited versus serious and actionable risks only) and a disclosure indicating that not all risks are presented on consumers' ability to remember the important risks and benefits of a drug following exposure to a DTC television advertisement (ad). Risk and benefit perceptions, ad-prompted actions, recognition of the disclosure statement, and evaluations of both the disclosure and risk statement were also examined. A web-based experiment was conducted in which US adults who self-reported as having depression (N = 500), insomnia (N = 500), or high cholesterol (N = 500) were randomly assigned to view one of four versions of the television ad, and then complete a questionnaire. The type of risk statement had a significant effect on risk recall and recognition, benefit recognition, perceived risk severity (depression condition only), and perceived benefit magnitude (high cholesterol condition only). Disclosure recognition (using bias-corrected scores) ranged from 63% to 70% across the three illness samples. The revised risk statement improved overall processing of the television ad, as evidenced by improved risk recall and recognition and improved benefit recognition. Further, the presence of the disclosure did not adversely affect consumers' processing of drug risk and benefit information. Therefore, limiting the risks presented in DTC television ads and including a disclosure alerting consumers that not all risks are presented may be an effective strategy for communicating product risks. Published by Elsevier Inc.

  2. Extending the capability of forensic electrochemistry to the novel psychoactive substance benzylpiperazine

    Directory of Open Access Journals (Sweden)

    S.A. Waddell

    2017-04-01

    Full Text Available Benzylpiperazine (BZP is a novel psychoactive substance that is commonly abused in tablet form as an “ecstasy-type” drug. Electroanalysis offers genuine potential for field testing of bulk drug samples. This research is the first to investigate the viability of voltammetric analysis of BZP. Initial cyclic voltammetry in 0.1 M KCl showed an oxidative peak at a glassy carbon electrode for BZP at approximately 0.8 V (scan rate 205 mV s−1. Next an optimised electrode/electrolyte combination (viz. 80:20 W:W glassy carbon beads:nujol and pH 9.5, 40 mM, Britton-Robinson buffer was developed using K3Fe(CN6 to test the electrode material. The oxidation of BZP involves two electrons and two protons and a mechanism has been proposed. An anodic stripping square wave voltammetric method was optimised by factorial design with the conditions of deposition: −0.8 V for 135 s, and stripping: step height 10 mV, amplitude 50 mV and frequency 13 Hz. A limit of detection of 6 μM was achieved. The resolution against 3,4-methylenedioxymethylamphetamine (MDMA was also verified.

  3. Práticas culturais familiares e o uso de drogas psicoativas pelos adolescentes: reflexão teórica Las prácticas culturales familiares y el uso de drogas por los adolescentes: reflexión teórica Family culture practices and psychoactive drug abuse by adolescents: theoretical reflection

    Directory of Open Access Journals (Sweden)

    Hellen Roehrs

    2008-06-01

    drogas, lo cual corresponde a un problema familiar y social que afecta no solamente la salud física y mental de la persona que la utiliza, pero de toda la sociedad. Se apuntan posibilidades de aculturación de creencias y hábitos más saludables por medio del trabajo individual, realizado con las familias.This article objectifies to reflect on teenage drug abuse as well as the influence of cultural family practices. Identity build-up takes on meaningful outlines in adolescence, when an array of factors is at stake which brings new outlook to life with unique meanings. Family in our society takes up a basic system, with a broad value diversity, organizational ways of living and functioning such as teenagers’ health care. The existence of a set of family values, beliefs and practices take up the cultural background which guides family actions. These actions entail some "bad family habits" such as drug abuse, a social and family problem affecting not only an individual’s physical and mental health but also society as a whole. Possibilities of introduction of healthier beliefs and habits are pointed out by means of individual work carried out with families.

  4. Capgras Syndrome associated with the use of psychoactive substances.

    Science.gov (United States)

    Mercurio, Ezequiel N

    2011-04-01

    Capgras syndrome has originally been described as psychiatric syndrome. However, in the last few years reports of patients with this syndrome has significantly increased in patients with neurological, metabolic, and infectious diseases and those who consume alcohol. Different hypotheses have been proposed to explain the neurobiology of this very unusual symptom, such as changes in the dopamine circuit and specific dysfunctions in facial processing. In this work we present a new case of Capgras syndrome, associated with an acute cocaine overdose, which was transient and reversible. The neurobiological bases of this syndrome are analysed, along with their relationship with the changes induced by cocaine use. Thus, Capgras syndrome could be the expression of functional changes at frontal-temporal level, and the paralimbic region secondary to the consumption of psychoactive substances such as cocaine. Copyright © 2010 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  5. Teotlaqualli: the psychoactive food of the Aztec gods.

    Science.gov (United States)

    Elferink, J G

    1999-01-01

    The Aztecs in pre-Columbian Mexico used not only a large number of single hallucinogens, they also used some combinations. The present article describes reports of the use of teotlaqualli, an unction prepared from ololiuhqui and picietl, with a large number of additions. The work of the chroniclers of pre-Columbian Mexico served as a source of information. The teotlaqualli was offered to the gods, for whom it served as food. The Aztec priests smeared themselves with this unction, to lose fear and to get the appropriate state of mind to serve the Aztec gods. A few cases are reported in which the Aztec emperor or soldiers were smeared with teotlaqualli. It is suggested that the black color of some Aztec deities, as depicted in the codices, was due to anointment with teotlaqualli. In addition to its use for psychoactive purposes, teotlaqualli was used in medicine under the name teopatli.

  6. Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA)

    DEFF Research Database (Denmark)

    Kos, Bor; Vasquez, Juan Luis; Miklavčič, D

    2016-01-01

    Objective. Bladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy......A delivered through a catheter electrode for 30 min. For numerical electric field computation we built a 3-D nonhomogeneous patient specific model based on CT images and used finite element method simulations to determine the electric fields in the whole body. Results. Results indicate that highest electric...

  7. Psychoactive substances and the political ecology of mental distress.

    Science.gov (United States)

    Aggarwal, Sunil K; Carter, Gregory T; Zumbrunnen, Craig; Morrill, Richard; Sullivan, Mark; Mayer, Jonathan D

    2012-01-18

    The goal of this paper is to both understand and depathologize clinically significant mental distress related to criminalized contact with psychoactive biotic substances by employing a framework known as critical political ecology of health and disease from the subdiscipline of medical geography. The political ecology of disease framework joins disease ecology with the power-calculus of political economy and calls for situating health-related phenomena in their broad social and economic context, demonstrating how large-scale global processes are at work at the local level, and giving due attention to historical analysis in understanding the relevant human-environment relations. Critical approaches to the political ecology of health and disease have the potential to incorporate ever-broadening social, political, economic, and cultural factors to challenge traditional causes, definitions, and sociomedical understandings of disease. Inspired by the patient-centered medical diagnosis critiques in medical geography, this paper will use a critical political ecology of disease approach to challenge certain prevailing sociomedical interpretations of disease, or more specifically, mental disorder, found in the field of substance abuse diagnostics and the related American punitive public policy regimes of substance abuse prevention and control, with regards to the use of biotic substances. It will do this by first critically interrogating the concept of "substances" and grounding them in an ecological context, reviewing the history of both the development of modern substance control laws and modern substance abuse diagnostics, and understanding the biogeographic dimensions of such approaches. It closes with proposing a non-criminalizing public health approach for regulating human close contact with psychoactive substances using the example of cannabis use.

  8. Psychoactive constituents of cannabis and their clinical implications: a systematic review.

    Science.gov (United States)

    Casajuana, Cristina; López-Pelayo, Hugo; Balcells, Mª Mercedes; Colom, Joan; Gual, Antoni

    2017-07-14

    Objective This systematic review aims to summarize current evidence on which naturally present cannabinoids contribute to cannabis psychoactivity, considering their reported concentrations and pharmacodynamics in humans. Design Following PRISMA guidelines, papers published before March 2016 in Medline, Scopus-Elsevier, Scopus, ISI-Web of Knowledge and COCHRANE, and fulfilling established a-priori selection criteria have been included. Results In 40 original papers, three naturally present cannabinoids (∆-9-Tetrahydrocannabinol, ∆-8-Tetrahydrocannabinol and Cannabinol) and one human metabolite (11-OH-THC) had clinical relevance. Of these, the metabolite produces the greatest psychoactive effects. Cannabidiol (CBD) is not psychoactive but plays a modulating role on cannabis psychoactive effects. The proportion of 9-THC in plant material is higher (up to 40%) than in other cannabinoids (up to 9%). Pharmacodynamic reports vary due to differences in methodological aspects (doses, administration route and volunteers’ previous experience with cannabis). Conclusions Findings reveal that 9-THC contributes the most to cannabis psychoactivity. Due to lower psychoactive potency and smaller proportions in plant material, other psychoactive cannabinoids have a weak influence on cannabis final effects. Current lack of standard methodology hinders homogenized research on cannabis health effects. Working on a standard cannabis unit considering 9-THC is recommended.

  9. Knowledge regarding antibiotic drug action and prescription practices among dentist in Jaipur city, Rajasthan

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    Dushyant Pal Singh

    2015-01-01

    Full Text Available Introduction: Dentists prescribe antibiotics routinely to manage oral and dental infections. Unscrupulous antibiotic prescriptions can be associated with unfavorable side effects and the development of resistance. Thus, the aim of this study was to assess the level of knowledge regarding antibiotic prescription use among dentists in Jaipur City, Rajasthan. Materials and Methods: A questionnaire survey was conducted among 300 dentists in Jaipur city. A validated, self-designed, 21-item, closed-ended questionnaire was used to collect data on knowledge regarding antibiotic prescription. Descriptive statistics were calculated. Results: A total of 300 dental practitioners were included in the study. The majority of the respondents seem to prescribe antibiotics that are broad spectrum or the ones that are commonly used. A considerable percentage of the respondents were not aware of the pregnancy drug risk categories by Food and Drug Administration. The most of the respondents said that they prescribe antibiotics on the basis of the diagnosis, whereas more than two-thirds of the respondents said that they never advise culture sensitivity test before prescribing the antibiotics. Conclusion: Our findings suggest the knowledge of dentists regarding antibiotic prescription is inadequate and more focus should be given to the ongoing training regarding the pharmacological aspects, pertinent medical conditions, and prophylactic use of antibiotics in dentistry.

  10. Action of Natural Products on P2 Receptors: A Reinvented Era for Drug Discovery

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    Luiz Alves

    2012-11-01

    Full Text Available Natural products contribute significantly to available drug therapies and have been a rich source for scientific investigation. In general, due to their low cost and traditional use in some cultures, they are an object of growing interest as alternatives to synthetic drugs. With several diseases such as cancer, and inflammatory and neuropathic diseases having been linked to the participation of purinergic (P2 receptors, there has been a flurry of investigations on ligands within natural products. Thirty-four different sources of these compounds have been found so far, that have shown either agonistic or antagonistic effects on P2 receptors. Of those, nine different plant sources demonstrated effects on P2X2, P2X3, P2X7, and possibly P2Y12 receptor subtypes. Microorganisms, which represent the largest group, with 26 different sources, showed effects on both receptor subtypes, ranging from P2X1 to P2X4 and P2X7, and P2Y1, P2Y2, P2Y4, and P2Y6. In addition, there were seventeen animal sources that affected P2X7 and P2Y1 and P2Y12 receptors. Natural products have provided some fascinating new mechanisms and sources to better understand the P2 receptor antagonism. Moreover, current investigations should clarify further pharmacological mechanisms in order to consider these products as potential new medicines.

  11. Headspace analysis of new psychoactive substances using a Selective Reagent Ionisation-Time of Flight-Mass Spectrometer

    Science.gov (United States)

    Acton, W. Joe; Lanza, Matteo; Agarwal, Bishu; Jürschik, Simone; Sulzer, Philipp; Breiev, Kostiantyn; Jordan, Alfons; Hartungen, Eugen; Hanel, Gernot; Märk, Lukas; Mayhew, Chris A.; Märk, Tilmann D.

    2014-01-01

    The rapid expansion in the number and use of new psychoactive substances presents a significant analytical challenge because highly sensitive instrumentation capable of detecting a broad range of chemical compounds in real-time with a low rate of false positives is required. A Selective Reagent Ionisation-Time of Flight-Mass Spectrometry (SRI-ToF-MS) instrument is capable of meeting all of these requirements. With its high mass resolution (up to m/Δm of 8000), the application of variations in reduced electric field strength (E/N) and use of different reagent ions, the ambiguity of a nominal (monoisotopic) m/z is reduced and hence the identification of chemicals in a complex chemical environment with a high level of confidence is enabled. In this study we report the use of a SRI-ToF-MS instrument to investigate the reactions of H3O+, O2+, NO+ and Kr+ with 10 readily available (at the time of purchase) new psychoactive substances, namely 4-fluoroamphetamine, methiopropamine, ethcathinone, 4-methylethcathinone, N-ethylbuphedrone, ethylphenidate, 5-MeO-DALT, dimethocaine, 5-(2-aminopropyl)benzofuran and nitracaine. In particular, the dependence of product ion branching ratios on the reduced electric field strength for all reagent ions was investigated and is reported here. The results reported represent a significant amount of new data which will be of use for the development of drug detection techniques suitable for real world scenarios. PMID:25844048

  12. Attitudes and Beliefs About New Psychoactive Substance Use Among Electronic Dance Music Party Attendees.

    Science.gov (United States)

    Palamar, Joseph J; Acosta, Patricia; Cleland, Charles M

    2018-02-23

    Attitudes and beliefs about drug use have been shown to be robust correlates of use of drugs such as alcohol, marijuana, and cocaine; however, little is known regarding attitudes or beliefs about new psychoactive substances (NPS). We sought to examine attitudes and beliefs about NPS and how they relate to self-reported use in a high-risk population-electronic dance music (EDM) party attendees. 1,048 individuals (age 18-40) were surveyed entering EDM parties in New York City in 2016. We queried lifetime use and attitudes and beliefs specific to NBOMe, 2C series drugs, "bath salts" (synthetic cathinones), tryptamines, dissociative NPS, and synthetic cannabinoids. More than half the sample reported being unfamiliar with NPS other than "bath salts" and synthetic cannabinoids. "Bath salts" received the highest ratings of strong disapproval (34.3%), followed by synthetic cannabinoids (23.3%), compared to other NPS (10-14%). "Bath salts" were perceived to be a great risk by 43.1% of the sample, followed by synthetic cannabinoids (27.0%), and other NPS (12-16%). "Bath salts" were reportedly least likely to be used if offered (2.9%). In multivariable models, reporting no disapproval towards use was associated with increased odds of reporting use of 2C drugs, "bath salts", and tryptamines. Having friends who use and reporting intent to use or willingness to use if offered were also associated with use of various NPS classes. This study delineated attitudinal and belief-related correlates of use of various NPS classes. Results can inform prevention effects as NPS continue to emerge.

  13. The diverse reasons for using Novel Psychoactive Substances - A qualitative study of the users' own perspectives.

    Science.gov (United States)

    Soussan, Christophe; Andersson, Martin; Kjellgren, Anette

    2017-12-11

    The increasing number of legally ambiguous and precarious Novel Psychoactive Substances (NPS) constitutes a challenge for policy makers and public health. Scientific and more in-depth knowledge about the motivations for using NPS is scarce and often consist of predetermined, non-systematic, or poorly described reasons deduced from top-down approaches. Therefore, the aim of the present study was to explore and characterize the users' self-reported reasons for NPS use inductively and more comprehensively. The self-reported reasons of a self-selected sample of 613 international NPS users were collected via an online survey promoted at the international drug discussion forum bluelight.org and later analyzed qualitatively using inductive thematic analysis. The analysis showed that the participants used NPS because these compounds reportedly: 1) enabled safer and more convenient drug use, 2) satisfied a curiosity and interest about the effects, 3) facilitated a novel and exciting adventure, 4) promoted self-exploration and personal growth, 5) functioned as coping agents, 6) enhanced abilities and performance, 7) fostered social bonding and belonging, and 8) acted as a means for recreation and pleasure. The consumption of NPS was also driven by 9) problematic and unintentional use. The present study contributed to a more comprehensive understanding of the users' own and self-reported reasons for using NPS, which needs to be acknowledged not only in order to minimize drug related harm and drug user alienation but also to improve prevention efforts and reduce the potentially counter-intuitive effects of strictly prohibitive policies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. The contamination of young people’s notions about narcotics and psychoactive substances as a threat to psychological security

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    Zinchenko, Yury P.

    2016-06-01

    Full Text Available The study described in this article investigated contemporary young people’s perceptions of drugs and psychoactive substances (PAS. In the course of the research the following hypothesis was tested: in young people’s perceptions about drugs and PAS there are differences in emotional coloring, coherence, and tolerance. J.-C. Abric’s structural approach was used as the basic methodology. The free-associations method provided the bulk of the empirical material. The results obtained were processed via prototypic analysis (by P. Vergès’s method, indexing of emotional associations (by E.E. Pronina’s method, and frequency and content analysis. As a result the core and the periphery of the perceptions of youth about drugs and PAS were described, and generalized notional categories that synthesize the structural elements of the perceptions were identified. The study revealed that the perceptions of young people about drugs and PAS do differ in coherence, tolerance, and emotional coloring. Perceptions of drugs are firm, consistent, and negative, while perceptions of PAS are less coherent but dynamic and have an ambivalent emotional coloration. The results are of prognostic importance for understanding young people’s attitudes toward drugs and PAS and can be used to design programs and measures directed to the prevention of PAS and drug abuse.

  15. Action of anti-TNF-α drugs on the progression of Alzheimer's disease: A case report

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    Carlos Henrique Ferreira Camargo

    Full Text Available The aim of this study was to describe a clinical case of a patient with Alzheimer's disease (AD in use of an anti-TNF-α agent for rheumatoid arthritis (RA. The patient reported is an 81-year-old Caucasian man and retired teacher, diagnosed with RA in 2008 and AD in 2011. Treatment with donepezil was started in 2011 and the use of etanercept introduced in 2012. He was previously treated with adalimumab in 2010 for 18 months. In 2013, the subject was engaged in a clinical trial to assess a complementary non-pharmacological approach for AD, presenting significant cognitive improvement during the follow-up period. We propose the hypothesis of a synergistic effect of anti-TNF-α medication used for the treatment of RA as the cause of the improvement in cognitive response observed. These findings could suggest a possible use of this drug class in the therapeutic management of AD.

  16. Mecanismos moleculares de acción de algunas drogas inmunosupresoras Molecular mechanisms of action of some immunosuppresive drugs

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    Ana C. Liberman

    2008-12-01

    action of mononuclear cells, being T cells the main targets. Immunosuppressive agents have different molecular targets, and an important drawback in their use is that they also inhibit the normal immune system response. Depending on their mode of action, immunosuppressive drugs can be classified in four different groups: antinflammatory drugs of the corticosteroid family, inhibitors of the calcineurin pathway, cytototoxic or antiproliferative drugs and specific antibodies. In this article, we focus on the molecular action of immunosuppressive drugs such as steroids, cyclosporine, tacrolimus, azathioprine, cyclophosphamide, sirolimus, mycophenolate mofetil, leflunomide and specific antibodies, providing data to characterize and improve the use of these agents.

  17. Modeling of miRNA and drug action in the EGFR signaling pathway.

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    Jian Li

    Full Text Available MicroRNAs have gained significant interest due to their widespread occurrence and diverse functions as regulatory molecules, which are essential for cell division, growth, development and apoptosis in eukaryotes. The epidermal growth factor receptor (EGFR signaling pathway is one of the best investigated cellular signaling pathways regulating important cellular processes and its deregulation is associated with severe diseases, such as cancer. In this study, we introduce a systems biological model of the EGFR signaling pathway integrating validated miRNA-target information according to diverse studies, in order to demonstrate essential roles of miRNA within this pathway. The model consists of 1241 reactions and contains 241 miRNAs. We analyze the impact of 100 specific miRNA inhibitors (anit-miRNAs on this pathway and propose that the embedded miRNA-network can help to identify new drug targets of the EGFR signaling pathway and thereby support the development of new therapeutic strategies against cancer.

  18. Optimizing therapeutics in the management of patients with multiple sclerosis: a review of drug efficacy, dosing, and mechanisms of action

    Directory of Open Access Journals (Sweden)

    Damal K

    2013-11-01

    Full Text Available Kavitha Damal, Emily Stoker, John F FoleyRocky Mountain Multiple Sclerosis Research Group, Salt Lake City, UT, USAAbstract: Multiple sclerosis (MS is a debilitating neurological disorder that affects nearly 2 million adults, mostly in their prime of youth. An environmental trigger, such as a viral infection, is hypothesized to initiate the abnormal behavior of host immune cells: to attack and damage the myelin sheath surrounding the neurons of the central nervous system. While several other pathways and disease triggers are still being investigated, it is nonetheless clear that MS is a heterogeneous disease with multifactorial etiologies that works independently or synergistically to initiate the aberrant immune responses to myelin. Although there are still no definitive markers to diagnose the disease or to cure the disease per se, research on management of MS has improved many fold over the past decade. New disease-modifying therapeutics are poised to decrease immune inflammatory responses and consequently decelerate the progression of MS disease activity, reduce the exacerbations of MS symptoms, and stabilize the physical and mental status of individuals. In this review, we describe the mechanism of action, optimal dosing, drug administration, safety, and efficacy of the disease-modifying therapeutics that are currently approved for MS therapy. We also briefly touch upon the new drugs currently under investigation, and discuss the future of MS therapeutics.Keywords: multiple sclerosis, immunomodulation, interferons, glatiramer acetate, monoclonal antibodies, dimethyl fumarate

  19. Tuberculosis and HIV in people who inject drugs: evidence for action for tuberculosis, HIV, prison and harm reduction services.

    Science.gov (United States)

    Getahun, Haileyesus; Gunneberg, Christian; Sculier, Delphine; Verster, Annette; Raviglione, Mario

    2012-07-01

    To provide a comprehensive summary of the prevention, diagnosis and treatment of HIV-related tuberculosis (TB) in people who inject drugs (PWIDs), and recommend actions to enhance the clinical and programmatic responses to the epidemic. People who live with HIV and inject drugs have a 2-6-fold increased risk of developing TB compared with noninjectors, and commonly have comorbidities with hepatitis B (HBV) and C viral (HCV) infection. Among PWIDs who develop TB, at least one in three will also have HIV and two out of three will have HCV antibodies. They are also at increased risk of criminalization and incarceration. The risk of TB disease in prisons is on average 23 times higher than the level in the general population. Key recent developments to address HIV-related TB among PWIDs include the use of simplified symptom-based algorithm to provide isoniazid-preventive therapy, molecular DNA detection methods for Mycobacterium tuberculosis and the immediate provision of antiretroviral therapy within the first 2 weeks of initiation of anti-TB treatment. Addressing the challenge posed by HIV-associated TB among PWIDs requires a systematic and integrated response to viral hepatitis and incarceration-related health issues, in addition to ensuring HIV and TB prevention, diagnosis and treatment as core components of harm reduction services. Regionally tailored measures, taking into consideration the epidemiology of these comorbidities, the policy and programmatic environment, and the infrastructure of the health system are needed.

  20. Legal high industry business and lobbying strategies under a legal market for new psychoactive substances (NPS, 'legal highs') in New Zealand.

    Science.gov (United States)

    Rychert, Marta; Wilkins, Chris

    2016-11-01

    The establishment of a regulated legal market for new psychoactive substances (NPS, 'legal highs') under New Zealand's Psychoactive Substances Act (PSA) 2013 created a new commercial sector for psychoactive products, previously limited to alcohol and tobacco. To explore how the newly-recognised 'legal high' industry (LHI) viewed and responded to the changing regulatory and market environment. In-depth interviews with six key informants (KI) from the LHI: a leading entrepreneur, chemist, industry spokesperson, retailer, product buyer and a researcher commissioned by the LHI - were conducted, transcribed and analysed thematically. Formative work for the study included review of official LHI documents (websites, public submissions, self-regulation documents). The LHI stakeholders espoused an idealistic mission of shifting recreational users of alcohol, tobacco and illegal drugs towards "safer alternatives". Passage of the PSA was viewed as a success after years of lobbying led by pioneering LHI actors. The growth and professionalisation of the LHI resulted in an increasingly commercial market which challenged idealistic views of the original operators. LHI KI reported the targeting of young and low income customers, price cutting and increasing the strength of products as business strategies. Attempts by the LHI to self-regulate did not prevent escalation in the strength of products and fall in retail prices. The LHI reported outsourcing of manufacturing and exporting of their products to other countries, demonstrating an international business model. There was a tension between profit and idealistic motivations within the LHI and this increased as the sector became more commercialised. While the LHI distanced itself from both alcohol and tobacco, they reported the use of similar marketing, business and political lobbying strategies. Rules for engagement with new 'addictive consumption industries' are required to clarify the role they are permitted to play in the

  1. [Visits to the doctor because of illness or injury of the students of vocational schools who consume or do not consume psychoactive substances (comparative aspects)].

    Science.gov (United States)

    Iurgaĭtene, D P; Shopagene, D S; Andreev, V A

    2012-01-01

    To elucidate what impact has the use of different narcotic drugs, alcohol and tobacco on the health of students and the risk of injuries. We carried out a questionnaire survey of the first year students from all six vocational schools of Klaipeda (Lithuania) in 2004, 2006 and 2008. A total of 912 students (507 boys and 405 girls, mean age 17.5 years) were surveyed with an anonymous questionnaire. The findings were analysed with computer soft SPSS (SPSS 16.0 for Windows). The results showed that the use of any psychoactive substances is damaging to health, especially injection and club narcotic drugs. Adolescents addicted to any psychoactive substances more often than non-addicts visited doctor due to illness or injury during the last 12 months. Adolescents on illegal drugs, especially boys on injectable narcotic drugs and girls on club drugs were at twice higher risk for disease or injury (odds ratio--OR--3.39, 95% confidence interval--CI--1.25 to 9.19, p = 0.016 and OR--2.38, CI--1.35 to 4.20, p = 0.003, respectively). Tobacco and alcohol consumption did not significantly increase this risk with the exception of tobacco smoking girls. We think it happened because these two addictions are widely spread among large part of the boys from the vocational schools.

  2. Drug-mediated shortening of action potentials in LQTS2 human induced pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Duncan, Gary; Firth, Karl; George, Vinoj; Hoang, Minh Duc; Staniforth, Andrew; Smith, Godfrey; Denning, Chris

    2017-10-09

    Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are now a well-established modality for modelling genetic disorders of the heart. This is especially so for long QT syndrome (LQTS), which is caused by perturbation of ion channel function, and can lead to fainting, malignant arrhythmias and sudden cardiac death. LQTS2 is caused by mutations in KCNH2, a gene whose protein product contributes to IKr (also known as HERG), which is the predominant repolarising potassium current in CMs. b-blockers are the mainstay treatment for patients with LQTS, functioning by reducing heart rate and arrhythmogenesis. However, they are not effective in around a quarter of LQTS2 patients, in part because they do not correct the defining feature of the condition, which is excessively prolonged QT interval. Since new therapeutics are needed, in this report, we biopsied skin fibroblasts from a patient who was both genetically and clinically diagnosed with LQTS2. By producing LQTS-hiPSC-CMs, we assessed the impact of different drugs on action potential duration (APD), which is used as an in vitro surrogate for QT interval. Not surprisingly, the patient's own b-blocker medication, propranolol, had a marginal effect on APD in the LQTS-hiPSC-CMs. However, APD could be significantly reduced by up to 19% with compounds that enhanced the IKr current by direct channel binding or by indirect mediation via the PPARd/protein 14-3-3 epsilon/HERG pathway. Drug-induced enhancement of an alternative potassium current, IKATP, also reduced APD by up to 21%. This study demonstrates the utility of LQTS-hiPSC-CMs is evaluating whether drugs can shorten APD and, importantly, shows that PPARd agonists may form a new class of therapeutics for this condition.

  3. A SINGLE MECHANISM OF ACTION OF HYPOLIPIDEMIC DRUGS. BASIC PRINCIPLES OF PRIMARY PREVENTION OF ATHEROSCLEROSIS, ATHEROMATOSIS AND CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    V. N. Titov

    2014-01-01

    Full Text Available Irrespective of differences in mechanism of action, hypolipidemic drugs develop their effects according to a single algorithm. They normalize receptor-mediated uptake of polyenic fatty acids (PFA by cells, thus restoring their functional, regulatory and structural state. Atherosclerosis is an in vivo pathology of each individual cell that cannot actively internalize PFA. Atherosclerosis is a syndrome of intracellular deficiency of ω-3 and ω-6 PFA. Compensatory production of humoral mediators (eicosanoids from endogenous ω-9 С20:3 digomo-ү-linolenic unsaturated fatty acids (FA renders them aphysiological and capable of impairing all functional processes in vivo, which results in a multilevel clinical manifestations of atherosclerosis and development of atheromatosis. Although atherosclerosis and atheromatosis are related to each other, they are different processes. Neither statins, nor other hypolipidemic drugs have any pleiotropic activity. They normalize cellular uptake of PFA which produce their intrinsic pleiotropic effects. As peroxisomal prolilferators, ω-3 eicosanoids oxidize excessive exogenous palmitic acid. Hypolipidemic effect of insulin is realized in conversion of entire palmitic FA synthesized in vivo from glucose into oleic FA. Hypolipidemic drugs are not the means of primary prevention of hyperlipidemia and atherosclerosis. This prevention should be based on normalization of the biological function of trophology and biological reaction of exotrophy and correction of quality and quantity of food according to real, quite limited functional possibilities ofHomo sapiens. The biological function of intellect plays an important role in primary prevention of hyperlipidemias and atherosclerosis.

  4. EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS

    Directory of Open Access Journals (Sweden)

    A. B. Dzheliya

    2015-01-01

    Full Text Available This article presents the results of immunotoxicity study of a novel slow-release drug for multiple sclerosis treatment based on recombinant human interferon beta-1а. The test article is polyethylene glycol (PEG-conjugated interferon beta-1a. Performed modification allows to improve pharmacokinetic parameters, decrease immunogenicity and elevate tolerance that significantly increases safety of the test article. The study is performed in nonhuman primates – rhesus monkeys (Macaca mulatta. The species, used in this study, is susceptible to human interferon beta-1a that has previously been shown in specific activity studies. Dynamics of peripheral blood lymphocyte subsets composition, activated lymphocyte count (based on the presence of early activation marker, serum antibodies (IgM, IgG, IgA and IgE level and ratio were assessed within in vivo experiments. The effect of interferon beta-1a on CD69 expression was examined in mononuclear cells culture. It was shown that the test article causes changes in lymphocyte subsets ratio (decrease of NK-cells relative count with T-lymphocytes relative count elevation in primates’ peripheral blood. Revealed changes were reversible and dose-independent. It was not shown that the test article have reliable effect on CD69 expression rate. There was no evidence of test article effect on level and ratio of serum antibodies and polymorphonucleocytes phagocytic rate in the absence of additional antigenic exposure. The results obtained during the experiment indicate the absence of pathological effect of the test article on the nonhuman primates’ immune system.

  5. Antiplasmodial activity of chloroquine analogs against chloroquine-resistant parasites, docking studies and mechanisms of drug action.

    Science.gov (United States)

    de Souza, Nicolli B; Carmo, Arturene M L; da Silva, Adilson D; França, Tanos C C; Krettli, Antoniana U

    2014-12-02

    Given the threat of resistance of human malaria parasites, including to artemisinin derivatives, new agents are needed. Chloroquine (CQ) has been the most widely used anti-malarial, and new analogs (CQAns) presenting alkynes and side chain variations with high antiplasmodial activity were evaluated. Six diaminealkyne and diaminedialkyne CQAns were evaluated against CQ-resistant (CQ-R) (W2) and CQ-sensitive (CQ-S) (3D7) Plasmodium falciparum parasites in culture. Drug cytotoxicity to a human hepatoma cell line (HepG2) evaluated, allowed to calculate the drug selectivity index (SI), a ratio of drug toxicity to activity in vitro. The CQAns were re-evaluated against CQ-resistant and -sensitive P. berghei parasites in mice using the suppressive test. Docking studies with the CQAns and the human (HssLDH) or plasmodial lactate dehydrogenase (PfLDH) enzymes, and, a β-haematin formation assay were performed using a lipid as a catalyst to promote crystallization in vitro. All tested CQAns were highly active against CQ-R P. falciparum parasites, exhibiting half-maximal inhibitory concentration (IC(50)) values below 1 μΜ. CQAn33 and CQAn37 had the highest SIs. Docking studies revealed the best conformation of CQAn33 inside the binding pocket of PfLDH; specificity between the residues involved in H-bonds of the PfLDH with CQAn37. CQAn33 and CQAn37 were also shown to be weak inhibitors of PfLDH. CQAn33 and CQAn37 inhibited β-haematin formation with either a similar or a 2-fold higher IC(50) value, respectively, compared with CQ. CQAn37 was active in mice with P. berghei, reducing parasitaemia by 100%. CQAn33, -39 and -45 also inhibited CQ-resistant P. berghei parasites in mice, whereas high doses of CQ were inactive. The presence of an alkyne group and the size of the side chain affected anti-P. falciparum activity in vitro. Docking studies suggested a mechanism of action other than PfLDH inhibition. The β-haematin assay suggested the presence of an additional mechanism of

  6. No349 - Consommation de substances psychoactives pendant la grossesse.

    Science.gov (United States)

    Ordean, Alice; Wong, Suzanne; Graves, Lisa

    2017-10-01

    Accroître la sensibilisation à la consommation problématique de substances psychoactives pendant la grossesse et les connaissances à ce sujet, et formuler des recommandations factuelles relatives à la prise en charge de cet épineux problème clinique à l'intention de l'ensemble des fournisseurs de soins. La présente directive clinique analyse l'utilisation d'outils de dépistage, l'approche générale de soins et les recommandations pour la prise en charge clinique de la consommation problématique de substances psychoactives pendant la grossesse. Recommandations factuelles pour le dépistage et la prise en charge de la consommation problématique de substances psychoactives pendant la grossesse et l'allaitement. La littérature à jour a été obtenue au moyen de recherches dans Medline, PubMed et la Bibliothèque Cochrane visant les articles publiés entre 1996 et 2016, avec les mots clés suivants : « pregnancy », « electronic cigarettes », « tobacco use cessation products », « buprenorphine » et « methadone ». Les résultats ont d'abord été restreints aux analyses systématiques, aux ECR et aux essais cliniques contrôlés. Ensuite, en raison de la rareté des ECR sur le sujet, des recherches d'études observationnelles ont également été menées. Les articles sélectionnés ont été limités aux études chez l'humain publiées en anglais, puis d'autres articles ont été trouvés manuellement, par l'analyse des listes de références. La qualité des données a été évaluée au moyen des critères énoncés dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs. Les recommandations visant la pratique ont été classées conformément à la méthode décrite dans ce rapport. AVANTAGES, DéSAVANTAGES ET COûTS: La présente directive clinique a pour but d'améliorer les connaissances et le degré d'aisance des fournisseurs qui dispensent des soins aux femmes enceintes ayant un trouble de l'usage d'une substance

  7. Influence of the legislation on the advertisement of psychoactive medications in Brazil

    Directory of Open Access Journals (Sweden)

    Mastroianni Patrícia de Carvalho

    2003-01-01

    Full Text Available OBJECTIVE: The regulations on the advertisement of medications aim to encourage and promote an improved health care and the rational use of medications. The objective of this paper is to evaluate the influence of three regulations on the advertisement of medications: the "Export act", published in the United States in 1986; the "WHO's Criteria", published in 1988, and the Resolution 102/2000 of the Collegiate Board of Directors of the ANVISA (Agência Nacional de Vigilância Sanitária- Brazilian Sanitary Surveillance Agency, on the advertisement of psychoactive medications. METHOD: We collected advertisements that were published in Brazilian psychiatric journals before and after the regulations were established. The contents of the advertisements were analyzed according to a program created based on the regulation's demands. RESULTS: In the 118 analyzed issues there were 199 different advertisements on 85 psychotropic drugs. We observed that, regardless the studied medication, the information about restrictions of use, such as adverse drug reactions, interactions, contraindications, warnings and precautions, does not appear very often, and when it does, its print sizes were smaller than that of the information favoring the use, such as indication, presentation and dosage. After the publication of the regulations, only 38.2% of the advertisements had all the essential technical information, and 35.3% were irregular in some way. CONCLUSION: The data suggest that there was very little influence of the regulations on the advertisement of psychotropic drugs in Brazil. Consequently, other control measures are necessary in addition to the regulations.

  8. I like the old stuff better than the new stuff? Subjective experiences of new psychoactive substances.

    Science.gov (United States)

    Matthews, Allison; Sutherland, Rachel; Peacock, Amy; Van Buskirk, Joe; Whittaker, Elizabeth; Burns, Lucinda; Bruno, Raimondo

    2017-02-01

    Over the past decade, monitoring systems have identified the rapid emergence of new psychoactive substances (NPS). While the use of many NPS is minimal and transitory, little is known about which products have potential for capturing the attention of significant proportions of the drug consuming market. The aim of this study was to explore self-reported experiences of three commonly used NPS classes within the Australian context (synthetic cathinones, hallucinogenic phenethylamines and hallucinogenic tryptamines) relative to traditional illicit drug counterparts. Frequent psychostimulant consumers interviewed for the Australian Ecstasy and related Drugs Reporting System (EDRS) (n=1208) provided subjective ratings of the pleasurable and negative (acute and longer-term) effects of substances used in the last six months on the last occasion of use, and the likelihood of future use. Stimulant-type NPS (e.g., mephedrone, methylone) were rated less favourably than ecstasy and cocaine in terms of pleasurable effects and likelihood of future use. DMT (a hallucinogenic tryptamine) showed a similar profile to LSD in terms of pleasurable effects and the likelihood of future use, but negative effects (acute and comedown) were rated lower. Hallucinogenic phenethylamines (e.g., 2C-B) showed a similar negative profile to LSD, but were rated as less pleasurable and less likely to be used again. The potential for expanded use of stimulant-type NPS may be lower compared to commonly used stimulants such as ecstasy and cocaine. In contrast, the potential of DMT may be higher relative to LSD given the comparative absence of negative effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Characterizing users of new psychoactive substances using psychometric scales for risk-related behavior.

    Science.gov (United States)

    Vreeker, Annabel; van der Burg, Babette G; van Laar, Margriet; Brunt, Tibor M

    2017-07-01

    Studies investigating risk-related behavior in relation to new psychoactive substance (NPS) use are sparse. The current study investigated characteristics of NPS users by comparing risk-related behavior of NPS users to that of illicit drugs (ID) users and licit substances users and non-users (NLC) users. In this cross-sectional study we included 528 individuals across an age range of 18-72years. Using a web-based questionnaire we collected self-report data on substance use, sensation seeking, impulsivity, peer substance use and risk perception of substance use. NPS and ID users had a higher level of sensation seeking compared to NLC users (NPS users: pusers: pusers (pusers (p=0.16), had increased levels of impulsivity compared to NLC users. NPS users had significantly higher scores for sensation seeking (F1,423=51.52, pusers. Additionally, NPS users had significantly more peers who use substances compared to ID and NLC users. Also, NPS and ID users had lower risk perception for most substances than NLC users. NPS users had lower risk perception for most substances than ID users. The findings highlight that NPS users show substantial more risk-related behavior than both ID and NLC users. Therefore, NPS users might be considered as a distinctive group of substance users that need another approach in terms of prevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Analysis of the psychoactive terpenoid salvinorin A content in five Salvia divinorum herbal products.

    Science.gov (United States)

    Wolowich, William R; Perkins, Alisha M; Cienki, John J

    2006-09-01

    To determine the content of the hallucinogen salvinorin A in a variety of Salvia divinorum herbal products and to compare the content with the label claims of potency and purity. Laboratory analysis. University-affiliated laboratory. Five herbal products containing Salvia divinorum. The samples were purchased from the Internet and local drug paraphernalia shops ("head shops"). Highperformance liquid chromatography and thin-layer chromatography-gas chromatography-mass spectroscopy were used for the analysis. All five samples contained salvinorin A, a psychoactive compound found in Salvia divinorum; however, the salvinorin A concentrations we measured were much lower than those claimed on the product label. Vitamin E was also found in two samples and caffeine in one sample. The five salvinorin A herbal products were found to be subpotent, and three products contained adulterants. Any discrepancy between the advertised salvinorin A concentration and their actual concentration may pose a potential risk of both misuse and overdose. These concerns, and the recently reported teenage suicide that could have been related to salvia consumption, underscore the need for practitioners to become familiar with the signs and symptoms of salvia use.

  11. Uso de substâncias psicoativas entre estudantes de Medicina de Salvador (BA Psychoactive substance use by medical students from Salvador (BA

    Directory of Open Access Journals (Sweden)

    Kleuber Moreira Lemos

    2007-01-01

    Full Text Available CONTEXTO: Estudos indicam que estudantes de Medicina, apesar do seu dedutível conhecimento sobre os efeitos das substâncias psicoativas, consomem-nas em proporção semelhante à dos jovens de mesma idade na população geral. OBJETIVO: Analisar o padrão local do consumo dessas substâncias entre graduandos de Medicina e contribuir na formulação de atividades preventivas. MÉTODOS: Aplicação de questionário semi-estruturado no qual foi avaliada a freqüência de uso das substâncias psicoativas entre os estudantes, assim como as principais razões apontadas para o consumo. Foram analisados 404 questionários obtidos entre alunos dos seis anos de curso das duas maiores escolas médicas de Salvador. RESULTADOS: As drogas mais utilizadas no critério uso na vida foram álcool (92,8% e lança-perfume (46,2%. O uso de álcool apresentou-se constante nos seis anos de curso. Entretanto, o uso de tabaco, lança-perfume e tranqüilizantes aumentou significativamente para os alunos dos últimos anos (p BACKGROUND: Studies have shown that medical students consume psychoactive substances at the same rates as the same age youth on general population, despite their predictable knowledge about drugs effects. OBJECTIVE: To analyze the local pattern of psychoactive substances use among medical students and contribute for the formulation of preventive activities. METHODS: The frequency of psychoactive substances use was evaluated by a self-administered anonymous questionnaire that also asked the main reasons for that use. Four hundred and four students in the first to sixth year from the two biggest medical schools in Salvador answered the questionnaire. RESULTS: The lifetime use was bigger for alcohol (92.8% and inhalant (46.2%. Alcohol use was constant for the students from first to sixth year of course, but it was not statistically significant (p > 0.05. However, tobacco, inhalants and tranquilizers use had a significant increase at the last two years

  12. The Use and Abuse of Psychoactive substances by Students of A ...

    African Journals Online (AJOL)

    Conclusion: It is pertinent to mention the observation of the absence of the use of Amphetamine, Cocaine, Opiodis and Hallucinogens in our study population. However, the need for immediate action to check this level of drug is highlighted and the need for health education in all schools is stressed. Key words: Drug abuse, ...

  13. Cytotoxicity and modes of action of five Cameroonian medicinal plants against multi-factorial drug resistance of tumor cells.

    Science.gov (United States)

    Kuete, Victor; Tankeo, Simplice B; Saeed, Mohamed E M; Wiench, Benjamin; Tane, Pierre; Efferth, Thomas

    2014-04-11

    Beilschmiedia acuta Kosterm, Clausena anisata (Willd) Hook, Fagara tessmannii Engl., Newbouldia laevis Seem., and Polyscias fulva (Hiern) Harms. are medicinal plants used in Cameroonian traditional medicine in the treatment of various types of cancers. The present study aims at investigating 11 methanolic extracts from the above Cameroonian medicinal plants on a panel of human cancer cell lines, including various drug-resistant phenotypes. Possible modes of action were analyzed for two extracts from Beilschmiedia acuta and Polyscia fulva and alpha-hederin, the representative constituent of Polyscia fulva. Cytotoxicity was determined using a resazurin assay. Cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were measured by flow cytometry. Cellular response to alpha-hederin was investigated by a mRNA microarray approach. Prescreening of extracts (40µg/mL) showed that three of eleven plant extracts inhibited proliferation of CCRF-CEM cells by more than 50%, i.e. BAL (73.65%), the bark extract of Beilschmiedia acuta (78.67%) and PFR (68.72%). Subsequent investigations revealed IC50 values below or around 30µg/mL of BAL and PFR in 10 cell lines, including drug-resistant models, i.e. P-glycoprotein-overexpressing CEM/ADR5000, breast cancer resistance protein-transfected MDA-MB-231-BCRP, TP53 knockout cells (HCT116 p53(-/-)), and mutation-activated epidermal growth factor receptor-transfected U87MG.ΔEGFR cells. IC50 values below 5µg/mL of BAL were obtained for HCT116 (p53(-/-)) cells. IC50 values below 10µM of alpha-hederin were found for sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 cells. The BAL and PFR extracts induced cell cycle arrest between G0/G1 and S phases. PFR-induced apoptosis was associated with increased ROS generation and MMP breakdown. Microarray-based cluster analysis revealed a gene expression profile that predicted cellular response to alpha-hederin. BAL, PFL and alpha-hederin, an

  14. Drugs en geneesmiddelen in het verkeer.

    NARCIS (Netherlands)

    Meesmann, U. Houwing, S. & Opdenakker, E.

    2015-01-01

    Drugs and certain medicines influence the behaviour and perception of the user. Therefore driving under the influence of drugs and psychoactive medicines is generally seen as a danger to traffic safety. Not only does the quantity or type of substance influence driving behaviour, but also the way or

  15. Suicidal thoughts related to psychoactive substance abuse among adolescents.

    Science.gov (United States)

    Licanin, Ifeta; Music, Emina; Laslo, Erdes; Berg-Kelly, Kristina; Masic, Izet; Redzic, Amira; Vejzagic, Anesa; Krosnjar, Sanja

    2003-01-01

    The enquiry of suicide is of particular importance. According to WHO statistics suicide in people aged from 15 to 24 years has shown the greatest increase of relative mortality. In the group of suicidal adolescents, depression, behavioural disorders, abuse of different substances and personality deviations are frequent factors in presence. The aim of our investigation was to determine the correlation between psychoactive substance abuse and the occurrence of suicidal thoughts in adolescents. The specific "Q 2000" test was used to question 600 adolescents, from Tuzla and Sarajevo Cantons, with the same gender and age distribution and rural-urban ambient. The more prevailing suicidal idea occurrence was observed in cannabis abusers (50.0%) and alcohol abusers (36.6%) in comparison to non-abusers regardless gender and/or living ambient (settlement types) (19.5% and 17.6% per each, x2 = 17.184 p = 0.00001). The augmentation in number of suicidal ideas was not observed in tobacco smokers.

  16. Combination Chemistry: Structure-Activity Relationships of Novel Psychoactive Cannabinoids.

    Science.gov (United States)

    Wiley, Jenny L; Marusich, Julie A; Thomas, Brian F

    2017-01-01

    Originally developed as research tools for use in structure-activity relationship studies, synthetic cannabinoids contributed to significant scientific advances in the cannabinoid field. Unfortunately, a subset of these compounds was diverted for recreational use beginning in the early 2000s. As these compounds were banned, they were replaced with additional synthetic cannabinoids with increasingly diverse chemical structures. This chapter focuses on integration of recent results with those covered in previous reviews. Whereas most of the early compounds were derived from the prototypic naphthoylindole JWH-018, currently popular synthetic cannabinoids include tetramethylcyclopropyl ketones and indazole-derived cannabinoids (e.g., AB-PINACA, AB-CHMINACA). Despite their structural differences, psychoactive synthetic cannabinoids bind with high affinity to CB1 receptors in the brain and, when tested, have been shown to activate these receptors and to produce a characteristic profile of effects, including suppression of locomotor activity, antinociception, hypothermia, and catalepsy, as well as Δ9-tetrahydrocannabinol (THC)-like discriminative stimulus effects in mice. When they have been tested, synthetic cannabinoids are often found to be more efficacious at activation of the CB1 receptor and more potent in vivo. Further, their chemical alteration by thermolysis during use and their uncertain stability and purity may result in exposure to degradants that differ from the parent compound contained in the original product. Consequently, while their intoxicant effects may be similar to those of THC, use of synthetic cannabinoids may be accompanied by unpredicted, and sometimes harmful, effects.

  17. Prevalence of alcohol and other psychoactive substances in injured drivers: comparison between Belgium and The Netherlands.

    Science.gov (United States)

    Legrand, Sara-Ann; Houwing, Sjoerd; Hagenzieker, Marjan; Verstraete, Alain G

    2012-07-10

    To compare the prevalence of alcohol and (il)licit drugs in seriously injured drivers in Belgium (BE) and the Netherlands (NL). Injured car and van drivers admitted to the emergency departments of five hospitals in Belgium and three in the Netherlands from January 2008 to May 2010 were included. Blood samples were taken and analysed for ethanol (with an enzymatic method) and 22 other psychoactive substances (UPLC-MS/MS or GC-MS). In total 535 injured drivers were included in the study (BE: 348; NL: 187). More drivers were found positive for alcohol and drugs in Belgium (52.6%) than in the Netherlands (33.9%). Alcohol (≥0.1 g/L) was the most prevalent substance in both countries (BE: 42.5%; NL: 29.6%). A similar prevalence was found for amphetamine (BE: 2.6%; NL: 2.2%) and cocaine (BE: 2.3%; NL: 2.1%). In the Netherlands almost no positive findings for cannabis were recorded (0.5%). No driver tested positive for benzodiazepines in the Netherlands compared to 7.3% in Belgium. More injured drivers tested positive for Z-drugs (BE: 1.8%; NL: 0.5%) and medicinal opioids (BE: 3.3%; NL: 0.5%) in Belgium. The prevalence of alcohol in seriously injured drivers was 12% higher found in Belgium than in the Netherlands. The prevalence of drugs was similar in both countries except for THC and medicinal drugs, particularly benzodiazepines, with a much higher prevalence in Belgium. In comparison to previous survey there were differences in the prevalence of THC, benzodiazepines and combinations of drugs. Possible explanations are the different matrix used, a bias in study population, or in case of illicit opiates and benzodiazepines a different consumption pattern in the two countries. Alcohol is still the most prevalent substance among the injured driver population and this increased the last 15 years. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Hiemke Christoph

    2011-01-01

    Full Text Available Abstract Background In Major Depressive Disorder (MDD, treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement of antidepressant treatment. The identical time course of symptom amelioration after early improvement in patients treated with antidepressants of all classes or with placebo strongly suggests a common biological mechanism, which is not specific for a particular antidepressant medication. However, the biology underlying early improvement and final treatment response is not understood and there is no established biological marker as yet, which can predict treatment response for the individual patient before initiation or during the course of antidepressant treatment. Peripheral blood markers and executive functions are particularly promising candidates as markers for the onset of action and thus the prediction of final treatment outcome in MDD. Methods/Design The present paper presents the rationales, objectives and methods of a multi-centre study applying close-meshed repetitive measurements of peripheral blood and neuropsychological parameters in patients with MDD and healthy controls during a study period of eight weeks for the identification of biomarkers for the onset of antidepressants' action in patients with MDD. Peripheral blood parameters and depression severity are assessed in weekly intervals from baseline to week 8, executive performance in bi-weekly intervals. Patients are participating in a randomized controlled multi-level clinical trial, healthy controls are matched according to mean age, sex and general intelligence. Discussion This investigation will help to identify a biomarker or a set of biomarkers with decision-making quality in the treatment of MDD in order to increase the currently

  19. Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder.

    Science.gov (United States)

    Tadić, André; Wagner, Stefanie; Gorbulev, Stanislav; Dahmen, Norbert; Hiemke, Christoph; Braus, Dieter F; Lieb, Klaus

    2011-01-26

    In Major Depressive Disorder (MDD), treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement) of antidepressant treatment. The identical time course of symptom amelioration after early improvement in patients treated with antidepressants of all classes or with placebo strongly suggests a common biological mechanism, which is not specific for a particular antidepressant medication. However, the biology underlying early improvement and final treatment response is not understood and there is no established biological marker as yet, which can predict treatment response for the individual patient before initiation or during the course of antidepressant treatment. Peripheral blood markers and executive functions are particularly promising candidates as markers for the onset of action and thus the prediction of final treatment outcome in MDD. The present paper presents the rationales, objectives and methods of a multi-centre study applying close-meshed repetitive measurements of peripheral blood and neuropsychological parameters in patients with MDD and healthy controls during a study period of eight weeks for the identification of biomarkers for the onset of antidepressants' action in patients with MDD. Peripheral blood parameters and depression severity are assessed in weekly intervals from baseline to week 8, executive performance in bi-weekly intervals. Patients are participating in a randomized controlled multi-level clinical trial, healthy controls are matched according to mean age, sex and general intelligence. This investigation will help to identify a biomarker or a set of biomarkers with decision-making quality in the treatment of MDD in order to increase the currently disappointing remission rates of antidepressant treatment.

  20. Actions in response to drug safety signals arising from a spontaneous reporting system : Retrospective study in The Netherlands

    NARCIS (Netherlands)

    Rolfes, Leàn; Kolfschoten, Judith; van Hunsel, Florence; Kooijman, Michel; van Puijenbroek, Eugène

    2016-01-01

    BACKGROUND: There is limited information on actions taken in response to drug safety signals originating from a spontaneous reporting system (SRS) in pharmacovigilance. In The Netherlands the Pharmacovigilance Centre Lareb is an independent organization that works in close collaboration with the

  1. Designer Drugs 2.0.

    Science.gov (United States)

    Huestis, M A; Tyndale, R F

    2017-02-01

    This "Designer Drugs 2.0" issue of Clinical Pharmacology & Therapeutics focuses on novel psychoactive substances, primarily cannabinoids and cathinones, and the repurposing of established psychoactive compounds (e.g., modafinil, psilocybin, lysergic acid diethylamide, and 3,4-methylenedioxymethamphetamine) that simultaneously offer new pharmacotherapies and pose serious health problems. Novel psychoactive substances were initially used as potent tools to investigate endogenous neurotransmitter systems; for example, synthetic cannabinoids have much higher potency than Δ9-tetrahydrocannabinol at the cannabinoid receptors. However, they are now being used illicitly as well as being tested for their efficacy in numerous clinical indications. Likewise, previously established psychoactive drugs are being repurposed as treatments for a wide variety of indications where currently approved medications are ineffective. This set of papers examines the arising problems associated with designer drugs (e.g., adverse events, psychosis, rapid new synthesis, abuse liability testing, internet sales, scheduling) as well as the potential therapeutic promises in areas as diverse as cognition enhancement, exercise-mimetics, epilepsy, multiple sclerosis, and posttraumatic stress disorder. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  2. Effectiveness of action in India to reduce exposure of Gyps vultures to the toxic veterinary drug diclofenac.

    Directory of Open Access Journals (Sweden)

    Richard Cuthbert

    Full Text Available Contamination of their carrion food supply with the non-steroidal anti-inflammatory drug diclofenac has caused rapid population declines across the Indian subcontinent of three species of Gyps vultures endemic to South Asia. The governments of India, Pakistan and Nepal took action in 2006 to prevent the veterinary use of diclofenac on domesticated livestock, the route by which contamination occurs. We analyse data from three surveys of the prevalence and concentration of diclofenac residues in carcasses of domesticated ungulates in India, carried out before and after the implementation of a ban on veterinary use. There was little change in the prevalence and concentration of diclofenac between a survey before the ban and one conducted soon after its implementation, with the percentage of carcasses containing diclofenac in these surveys estimated at 10.8 and 10.7%, respectively. However, both the prevalence and concentration of diclofenac had fallen markedly 7-31 months after the implementation of the ban, with the true prevalence in this third survey estimated at 6.5%. Modelling of the impact of this reduction in diclofenac on the expected rate of decline of the oriental white-backed vulture (Gyps bengalensis in India indicates that the decline rate has decreased to 40% of the rate before the ban, but is still likely to be rapid (about 18% year(-1. Hence, further efforts to remove diclofenac from vulture food are still needed if the future recovery or successful reintroduction of vultures is to be feasible.

  3. Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle.

    Science.gov (United States)

    Meisel, Christian; Schulze-Bonhage, Andreas; Freestone, Dean; Cook, Mark James; Achermann, Peter; Plenz, Dietmar

    2015-11-24

    Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability.

  4. Tetrahydrocannabinolic acid synthase, the enzyme controlling marijuana psychoactivity, is secreted into the storage cavity of the glandular trichomes

    National Research Council Canada - National Science Library

    Sirikantaramas, Supaart; Taura, Futoshi; Tanaka, Yumi; Ishikawa, Yu; Morimoto, Satoshi; Shoyama, Yukihiro

    2005-01-01

    ...), the psychoactive component of marijuana (Cannabis sativa L.). We suggest herein that THCA is biosynthesized in the storage cavity of the glandular trichomes based on the following observations...

  5. New psychoactive substances: Purchasing and supply patterns in Australia.

    Science.gov (United States)

    Sutherland, Rachel; Bruno, Raimondo; Peacock, Amy; Dietze, Paul; Breen, Courtney; Burns, Lucinda; Barratt, Monica J

    2017-05-01

    To examine the purchasing and supply patterns of new psychoactive substance (NPS) consumers in Australia. Data were obtained from a self-selected sample of 296 past-year NPS consumers, with comparisons made across dimethyltryptamine (n = 104), 2C-x (n = 59), NBOMe (n = 27), and synthetic cannabinoid (n = 22) users. Most consumers (58%) nominated a friend as their main NPS source, and almost half (46%) reported that they had supplied NPS to others in the past year (predominantly "social supply"). However, when comparisons were made across NPS, NBOMe users were more likely to nominate a dealer (30%) or online marketplace (22%) as their main source and to report: supplying NPS to others (63%); supplying to strangers (29%) and acquaintances (24%); and supplying NPS for cash profit (29%). Similarly, NPS consumers who nominated online markets as their main NPS source (9%; n = 26) were more likely to have supplied NPS to others (risk ratio [RR] 1.57); supplied to strangers (RR 6.05) and acquaintances (RR 12.11); sold NPS for cash profit (RR 4.36); and to have exchanged NPS for something else (RR 3.27) than those who reported alternative primary sources. NBOMe consumers and those who nominated online markets as their main NPS source reported greater engagement with for-profit supply; it is unclear if these individuals have "drifted" into dealing or if they were already engaged in such activities. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Systematic analytical characterization of new psychoactive substances: A case study.

    Science.gov (United States)

    Lobo Vicente, Joana; Chassaigne, Hubert; Holland, Margaret V; Reniero, Fabiano; Kolář, Kamil; Tirendi, Salvatore; Vandecasteele, Ine; Vinckier, Inge; Guillou, Claude

    2016-08-01

    New psychoactive substances (NPS) are synthesized compounds that are not usually covered by European and/or international laws. With a slight alteration in the chemical structure of existing illegal substances registered in the European Union (EU), these NPS circumvent existing controls and are thus referred to as "legal highs". They are becoming increasingly available and can easily be purchased through both the internet and other means (smart shops). Thus, it is essential that the identification of NPS keeps up with this rapidly evolving market. In this case study, the Belgian Customs authorities apprehended a parcel, originating from China, containing two samples, declared as being "white pigments". For routine identification, the Belgian Customs Laboratory first analysed both samples by gas-chromatography mass-spectrometry and Fourier-Transform Infrared spectroscopy. The information obtained by these techniques is essential and can give an indication of the chemical structure of an unknown substance but not the complete identification of its structure. To bridge this gap, scientific and technical support is ensured by the Joint Research Centre (JRC) to the European Commission Directorate General for Taxation and Customs Unions (DG TAXUD) and the Customs Laboratory European Network (CLEN) through an Administrative Arrangement for fast recognition of NPS and identification of unknown chemicals. The samples were sent to the JRC for a complete characterization using advanced techniques and chemoinformatic tools. The aim of this study was also to encourage the development of a science-based policy driven approach on NPS. These samples were fully characterized and identified as 5F-AMB and PX-3 using (1)H and (13)C nuclear magnetic resonance (NMR), high-resolution tandem mass-spectrometry (HR-MS/MS) and Raman spectroscopy. A chemoinformatic platform was used to manage, unify analytical data from multiple techniques and instruments, and combine it with chemical and

  7. Diverted medications and new psychoactive substances-A chemical network analysis of discarded injecting paraphernalia in Hungary.

    Science.gov (United States)

    Gyarmathy, Valéria Anna; Péterfi, Anna; Figeczki, Tamás; Kiss, József; Medgyesi-Frank, Katalin; Posta, János; Csorba, József

    2017-08-01

    Until about 2010, people who inject drugs (PWIDs) injected almost exclusively heroin and amphetamines in Hungary. After 2010, self-reported studies have indicated a dominance of new psychoactive substances on the drug market for injectable drugs. Between March 2015 and February 2016, we collected used and discarded injecting paraphernalia. We utilized chemical analysis to assess and UCINet to visualize the connections between the most prevalent main substances and their respective co-occurring additional components at 7 locations in Hungary. The samples (n=2977) contained a mean of 4.5 components (SD=3.1, range: 1-18); 422 contained only one component. We found that the most common main components were the diverted substitution medication methadone (32%) and cathinones: pentedrone (18%), mephedrone (13%), alpha-PHP (8%), and alpha-PEP (5%). While these main substances also occurred among the top co-occurring additional components, caffeine and benzoic acid (a preservative) also frequently co-occurred. A large number of co-occurring additional components indicate either common reuse of injecting paraphernalia or the common addition of additives or both. While caffeine may indeed be an adulterant, the high prevalence of benzoic acid may be difficult to explain. The preference of methadone despite the availability of a wide array of drugs may indicate a preference for opioids during the current heroin drought and/or a true demand for opioid substitution therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Psychoactive substances in seriously injured drivers in Denmark

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Steentoft, Anni; Bernhoft, IM

    2013-01-01

    , which is 0.53 g/l in Denmark. The percentage of seriously injured drivers testing positive for medicinal drugs at levels above the Danish legal limit was 6.8%. Benzodiazepines and Z-drugs (6.4%) comprised the majority of this group. One or more illegal drugs (primarily amphetamines and cannabis) were...

  9. Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain.

    Science.gov (United States)

    Valjent, Emmanuel; Pagès, Christiane; Hervé, Denis; Girault, Jean-Antoine; Caboche, Jocelyne

    2004-04-01

    A major goal of research on addiction is to identify the molecular mechanisms of long-lasting behavioural alterations induced by drugs of abuse. Cocaine and delta-9-tetrahydrocannabinol (THC) activate extracellular signal-regulated kinase (ERK) in the striatum and blockade of the ERK pathway prevents establishment of conditioned place preference to these drugs. However, it is not known whether activation of ERK in the striatum is specific for these two drugs and/or this brain region. We studied the appearance of phospho-ERK immunoreactive neurons in CD-1 mouse brain following acute administration of drugs commonly abused by humans, cocaine, morphine, nicotine and THC, or of other psychoactive compounds including caffeine, scopolamine, antidepressants and antipsychotics. Each drug generated a distinct regional pattern of ERK activation. All drugs of abuse increased ERK phosphorylation in nucleus accumbens, lateral bed nucleus of the stria terminalis, central amygdala and deep layers of prefrontal cortex, through a dopamine D1 receptor-dependent mechanism. Although some non-addictive drugs moderately activated ERK in a few of these areas, they never induced this combined pattern of strong activation. Antidepressants and caffeine activated ERK in hippocampus and cerebral cortex. Typical antipsychotics mildly activated ERK in dorsal striatum and superficial prefrontal cortex, whereas clozapine had no effect in the striatum, but more widespread effects in cortex and amygdala. Our results outline a subset of structures in which ERK activation might specifically contribute to the long-term effects of drugs of abuse, and suggest mapping ERK activation in brain as a way to identify potential sites of action of psychoactive drugs.

  10. Nejat Briefcase: A tool for drug education.

    Science.gov (United States)

    Najafi, Mostafa; Mollabashi, Roya; Mollabashi, Zahra; Mousavi, Arefeh

    2015-01-01

    On account of the prevalence of psychoactive substances and drug abuse and its diversity of forms and methods of use, along with the reduction in the age of drug abuse, a continuing medical educationof physicians with these issues is necessary. Although it is legally forbidden, most physicians have no close contact to these drugs, and this is not effective for training, prevention and treatment of drug addiction. In this regard, offering an educational tool is needed, if in close contact to these drugs. The 'Nejat Briefcase' is a tool designed for the purpose of training and familiarization of psychoactive substances and drugs. The aim of this study is to investigate the points of view of the participants in the continuing medical education program, 'Introduction to types of psychoactive substances and drugs' and about the Nejat Briefcase, in the Isfahan University of Medical Sciences (IUMS). In this descriptive, cross-sectional study, all the general physicians (108 people) who participated in the continuing medical education program, 'Introducing types of psychoactive substances and drugs,' in the Isfahan University of Medical Sciences (IUMS), in 2012 - 2013, were considered. In this program, in order to introduce various types of psychoactive substances and drugs to the physicians, as well as acquaint them with their forms, methods of use, and prices, the new educational tool (Nejat Briefcase), containing various types of psychoactive substances and drugs and the related educational packages, such as, booklets and brochures, was used. A researcher-made, valid and reliable questionnaire was distributed at the end of program to gather the participants' points of view about the educational program. Data was analyzed by the SPSS and t-test and descriptive statistical tests. The response rate to the questionnaire was 83%. Forty-four people (41%) were women and 64 (59%) were men. The mean total score of the participants' points of view was 4/58 ± 0/45 (out of 5

  11. Reproductive effects of the psychoactive beverage ayahuasca in male Wistar rats after chronic exposure

    Directory of Open Access Journals (Sweden)

    Alana de Fátima Andrade Santos

    Full Text Available Abstract Ayahuasca is a psychoactive beverage used ancestrally by indigenous Amazonian tribes and, more recently, by Christian religions in Brazil and other countries. This study aimed to investigate the reproductive effects of this beverage in male Wistar rats after chronic exposure. The rats were treated by gavage every other day for 70 days at 0 (control, 1×, 2×, 4× and 8× the dose used in a religious ritual (12 animals per group, and animals euthanized on the 71st day. Compared to controls, there was a significant decrease in food consumption and body weight gain in rats from the 4× and 8× groups, and a significant increase in the brain and stomach relative weight at the 8× group. There was a significant increase in total serum testosterone, and a decrease in spermatic transit time and spermatic reserves in the epididymis caudae in the 4× group, but not in the highest dose group. No significant changes were found in the other reproductive endpoints (spermatozoid motility and morphology, total spermatozoid count and daily sperm production, and histology of testis and epididymis. This study identified a no-observed-adverse-effect-level for chronic and reproductive effects of ayahuasca in male Wistar rats at 2× the ritualistic dose, which corresponds in this study to 0.62 mg/kg bw N, N-dimethyltryptamine, 6.6 mg/kg bw harmine and 0.52 mg/kg bw harmaline. A potential toxic effect of ayahuasca in male rats was observed at the 4× dose, with a non-monotonic dose–response. Studies investigating the role of ayahuasca components in regulating testosterone levels are needed to better understand this action.

  12. A pooled analysis of lacosamide clinical trial data grouped by mechanism of action of concomitant antiepileptic drugs.

    Science.gov (United States)

    Sake, John-Kenneth; Hebert, David; Isojärvi, Jouko; Doty, Pamela; De Backer, Marc; Davies, Kendra; Eggert-Formella, Andrea; Zackheim, James

    2010-12-01

    Lacosamide, a new antiepileptic drug (AED) with a different pharmacological action that enhances sodium channel slow inactivation, is approved for the adjunctive treatment of partial-onset seizures in adults. Previous analyses of pooled phase II/III trials have demonstrated that lacosamide provides additional efficacy when added to a broad range of AEDs. To further evaluate the efficacy and safety of lacosamide by grouping patients based upon the sodium channel-blocking properties of their concomitant AEDs. Post hoc exploratory analyses were performed on pooled data in which patients were grouped based upon inclusion or non-inclusion of at least one 'traditional' sodium channel-blocking AED (defined as carbamazepine, lamotrigine, oxcarbazepine and phenytoin derivatives) as part of their concomitant AED regimen. Data pooled from previously conducted phase II/III clinical trials of lacosamide. Adult patients with partial-onset seizures with or without secondary generalization (N = 1308). Four- to six-week Titration Phase followed by 12-week maintenance treatment with adjunctive lacosamide (Vimpat®) [200, 400 or 600 mg/day] or placebo. Efficacy variables included change in seizure frequency per 28 days and the proportion of patients experiencing a ≥50% reduction in seizure frequency (50% responder rate) from Baseline to the Maintenance Phase. The proportion of patients experiencing a ≥75% reduction in seizure frequency from Baseline to the Maintenance Phase (75% responder rate) was also assessed. Safety parameters assessed were treatment-emergent adverse events (TEAEs) and discontinuation due to TEAEs. Additional safety assessments were changes in ECG and laboratory parameters as well as vital signs (including bodyweight). Of 1308 patients in the pooled phase II/III population, the majority (82%) were using at least one 'traditional' sodium channel-blocking concomitant AED. In this subgroup of patients, adjunctive lacosamide showed significant reductions in

  13. Turning Awareness into Action: What Your Community Can Do about Drug Use in America = De La Toma de Conciencia a la Accion: Que Puede Hacer la Comunidad Respecto al Consumo de Drogas en America.

    Science.gov (United States)

    Alcohol, Drug Abuse, and Mental Health Administration (DHHS/PHS), Rockville, MD. Office for Substance Abuse Prevention.

    This booklet gives examples of successful community drug abuse prevention programs, as well as guidelines for finding out more about a community's prevention needs and taking action. The first section discusses taking action against drug abuse. It presents examples which illustrate the different approaches communities have taken. Ten steps to help…

  14. The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

    Directory of Open Access Journals (Sweden)

    Camila Sanz

    2018-01-01

    Full Text Available Ever since the modern rediscovery of psychedelic substances by Western society, several authors have independently proposed that their effects bear a high resemblance to the dreams and dreamlike experiences occurring naturally during the sleep-wake cycle. Recent studies in humans have provided neurophysiological evidence supporting this hypothesis. However, a rigorous comparative analysis of the phenomenology (“what it feels like” to experience these states is currently lacking. We investigated the semantic similarity between a large number of subjective reports of psychoactive substances and reports of high/low lucidity dreams, and found that the highest-ranking substance in terms of the similarity to high lucidity dreams was the serotonergic psychedelic lysergic acid diethylamide (LSD, whereas the highest-ranking in terms of the similarity to dreams of low lucidity were plants of the Datura genus, rich in deliriant tropane alkaloids. Conversely, sedatives, stimulants, antipsychotics, and antidepressants comprised most of the lowest-ranking substances. An analysis of the most frequent words in the subjective reports of dreams and hallucinogens revealed that terms associated with perception (“see,” “visual,” “face,” “reality,” “color”, emotion (“fear”, setting (“outside,” “inside,” “street,” “front,” “behind” and relatives (“mom,” “dad,” “brother,” “parent,” “family” were the most prevalent across both experiences. In summary, we applied novel quantitative analyses to a large volume of empirical data to confirm the hypothesis that, among all psychoactive substances, hallucinogen drugs elicit experiences with the highest semantic similarity to those of dreams. Our results and the associated methodological developments open the way to study the comparative phenomenology of different altered states of consciousness and its relationship with non-invasive measurements of brain

  15. Anticancer drug mithramycin interacts with core histones: An additional mode of action of the DNA groove binder

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    Amrita Banerjee

    2014-01-01

    Full Text Available Mithramycin (MTR is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin – histone proteins – as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode or both histones and chromosomal DNA (dual binding mode. The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR–DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg2+. As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies.

  16. Melatonin-sulforaphane hybrid ITH12674 induces neuroprotection in oxidative stress conditions by a 'drug-prodrug' mechanism of action.

    Science.gov (United States)

    Egea, Javier; Buendia, Izaskun; Parada, Esther; Navarro, Elisa; Rada, Patricia; Cuadrado, Antonio; López, Manuela G; García, Antonio G; León, Rafael

    2015-04-01

    Neurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with Nrf2 induction properties, with the idea of achieving improved neuroprotective properties. Compound ITH12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug-prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia. ITH12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH12674 (i) mediated a concentration-dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the Nrf2-antioxidant response element transcriptional response in transfected HEK293T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re-oxygenation from stress by increasing the expression of haem oxygenase-1 and reducing free radical production. ITH12674 combines the signalling pathways of the parent compounds to improve its neuroprotective properties. This opens a new line of research for such hybrid compounds to treat neurodegenerative diseases. © 2014 The British Pharmacological Society.

  17. Self-reported use of novel psychoactive substances among attendees of electronic dance music venues.

    Science.gov (United States)

    Palamar, Joseph J; Acosta, Patricia; Sherman, Scott; Ompad, Danielle C; Cleland, Charles M

    2016-11-01

    Novel psychoactive substances (NPSs) continue to emerge in the United States and worldwide. Few epidemiological studies have examined the prevalence and correlates of use. We examined the extent of NPS use in a high-risk population-attendees of electronic dance music (EDM) parties at nightclubs and festivals. We surveyed 682 adults (age 18-25) entering EDM events at nightclubs and festivals in New York City (NYC) in 2015. A variation of time-space sampling was used. We examined the prevalence of self-reported use of 196 NPS and correlates of any NPS use. Over a third (35.1%) of participants reported lifetime use of any NPS. Self-reported use of synthetic cannabinoids was most prevalent (16.3%), followed by psychedelic phenethylamines (14.7%; 2C series: 10.3%, 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine [NBOMe] series: 9.0%, Dox series: 3.5%), synthetic cathinones ("bath salts", 6.9%), other psychedelics (6.6%), tryptamines (5.1%), and dissociatives (4.3%). 2C-I was the most prevalent 2C series drug (5.1%); methylone was the most prevalent synthetic cathinone (3.3%), 2-MeO-ketamine was the most prevalent dissociative (3.7%), and 1P-lysergic acid diethylamide (LSD) (2.9%) was the most prevalent non-phenethylamine psychedelic. Risk factors for NPS use included Ecstasy/MDMA/Molly, LSD, and ketamine use; identifying as bisexual (compared to heterosexual), reporting higher frequency of nightclub/festival attendance, and being surveyed outside of a festival (compared to those surveyed outside of nightclubs). NPS use is prevalent in the nightclub and festival scenes in NYC. Since individuals in these scenes-especially frequent attendees-are at high risk for use, prevention and harm reduction services need to be geared toward this population.

  18. Pollution by psychoactive pharmaceuticals in the Rivers of Madrid metropolitan area (Spain).

    Science.gov (United States)

    González Alonso, Silvia; Catalá, Myriam; Maroto, Raúl Romo; Gil, José Luis Rodríguez; de Miguel, Angel Gil; Valcárcel, Yolanda

    2010-02-01

    There are a number of reports in the literature which describe the occurrence of so-called emerging pollutants, such as pharmaceuticals, in surface water. Few of these studies have reported values from large cities in relatively arid areas, such as in Spain. The persistence of some pharmaceuticals to usual wastewater treatments allows their discharge into surface waters. It is increasingly evident that mental health problems are of special concern for public health since psychiatric drugs are used in large amounts. Compared to other countries, Spain has a high pharmaceutical consumption rate, and Madrid metropolitan area is one of the most densely populated areas in Europe. The aim of the present study was to determine the presence of different psychoactive pharmaceuticals and metabolites in the main rivers of Madrid metropolitan area: Jarama, Manzanares, Guadarrama, Henares and Tajo. Sampling was done downstream of ten sewage treatment plants (STP) discharging into these rivers. Control points upstream of STPs discharge points were also sampled. Pharmaceutical compounds and metabolites for analysis were selected according to human consumption and prescription rates in Madrid, and the availability of valid techniques for detection. We observed residues of the antidepressants fluoxetine (80% of the sampling sites), citalopram (60%) and venlafaxine (100%), the anxiolytics nordiazepam (90%), oxazepam (80%) and 7-aminoflunitrazepam (10%) and the anticonvulsant carabamazepine (70%). Measured concentrations equalled or exceeded those reported for other geographical areas, although there is a pronounced lack of information for the anxiolytics and venlafaxine. This is of special concern given that Wyeth-Ayerst's venlafaxine, Effexor, was the 10th greatest selling pharmaceutical worldwide in 2006. We conclude that the origin of pharmaceutical pollution in the rivers of Madrid is mainly the discharge of sewage treatment plants in Madrid's metropolitan area and a

  19. The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover.

    Science.gov (United States)

    Costa, M A; Fonseca, B M; Marques, F; Teixeira, N A; Correia-da-Silva, G

    2015-08-06

    The noxious effects of cannabis consumption for fertility and pregnancy outcome are recognized for years. Its consumption during gestation is associated with alterations in foetal growth, low birth weight and preterm labor. The main psychoactive molecule of cannabis, Δ(9)-tetrahydrocannabinol (THC) impairs the production of reproductive hormones and is also able to cross the placenta barrier. However, its effect on the main placental cells, the trophoblasts, are unknown. Actually, the role of THC in cell survival/death of primary human cytotrophoblasts (CTs) and syncytiotrophoblasts (STs) and in the syncytialization process remains to be explored. Here, we show that THC has a dual effect, enhancing MTT metabolism at low concentrations, whereas higher doses decreased cell viability, on both trophoblast phenotypes, though the effects on STs were more evident. THC also diminished the generation of oxidative and nitrative stress and the oxidized form of glutathione, whereas the reduced form of this tripeptide was increased, suggesting that THC prevents ST cell death due to an antioxidant effect. Moreover, this compound enhanced the mitochondrial function of STs, as observed by the increased MTT metabolism and intracellular ATP levels. These effects were independent of cannabinoid receptors activation. Besides, THC impaired CT differentiation into STs, since it decreased the expression of biochemical and morphological biomarkers of syncytialization, through a cannabinoid receptor-dependent mechanism. Together, these results suggest that THC interferes with trophoblast turnover, preventing trophoblast cell death and differentiation, and contribute to disclose the cellular mechanisms that lead to pregnancy complications in women that consume cannabis-derived drugs during gestation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Mental health professional perception of the embracement towards psychoactive substance user in CAPSad

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    Daiane Bernardoni Salles

    2017-06-01

    Full Text Available Introduction: Adherence to chemical dependency treatment is still a great challenge for both, users and health care professionals. Currently, public healthcare policy is a tool to assist in the development of a humanized care model, which advocates for the practice of user inclusion. Objective: Investigate the perception of professionals who work in the mental health field, to understand the inclusion offered to users of psychoactive substances in Psychosocial Care Centers for alcohol and drug users (CAPSad. Method: A descriptive and exploratory study conducted at the CAPSad in São Paulo. Active professionals in the mental health field working at the CAPSad participated in the present study. For data collection a semi-structured questionnaire was used with 27 self-report questions, 15 closed questions, analyzed through statistics and 12 open questions, with speech analysis. Results: The questionnaires of six professionals with a mean of 14.3 years working at the CAPSad, revealed that they had no prior training about inclusion. Five participants responded that they carried out inclusion in the presence of the family, four responded without the presence of family and just one responded according to user choice (each participant could choose more than one option. The results show ambiguity regarding the concept of user inclusion, as all reported that inclusion hampers user reception, qualified listening, guidance and making necessary referrals. Conclusion: The need to create formal spaces for knowledge exchange, case discussion, and encourage professional training, promoting the identity of the service and improving user adherence to treatment was highlighted.

  1. Correlation between depressive symptoms and quality of life in users of psychoactive substances

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    Samira Reschetti Marcon

    2014-08-01

    Full Text Available Objectives: To evaluate the correlation between the presence of depressive symptoms and quality of life in users of psychoactive substances from Psychosocial Attention Centers in Mato Grosso. Method: A cross-sectional analytical study, conducted in Psychosocial Attention Centers, with 109 users. The instruments used were: Medical Outcomes Study 36, Beck Depression Inventory, socio-demographic variables and the use of psychoactive substances. A Tukey analysis and a Spearman correlation were conducted with a significance level of α<0,05. Results: The most affected domains of quality of life were emotional, social and mental health aspects, besides the strong correlation between depressive symptoms and quality of life. Conclusion: The use of psychoactive substances and the presence of symptoms significantly interfere in the life of users, which can compromise the motivation to the treatment, negatively affecting the quality of life in this population.

  2. Running away experience and psychoactive substance use among adolescents in Taiwan: multi-city street outreach survey

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    Lew-Ting Chih-Yin

    2010-01-01

    Full Text Available Abstract Background This study aimed to examine: 1 the relationship between being a runaway and the time since the first absconding event and adolescent substance use; 2 whether different kinds of psychoactive substances have a different temporal relationship to the first absconding event; and 3 whether the various reasons for the first absconding event are associated with different risks of substance use. Methods Participants were drawn from the 2004-2006 nationwide outreach programs across 26 cities/towns in Taiwan. A total of 17,133 participants, age 12-18 years, who completed an anonymous questionnaire on their experience of running away and substances use and who were now living with their families, were included in the analysis. Results The lifetime risk of tobacco, alcohol, betel nut, and illegal drug/inhalant use increased steadily from adolescents who had experienced a trial runaway episode (one time lasting ≤ 1 day, to those with extended runaway experience (≥ 2 times or lasting > 1 day, when compared to those who had never ran away. Adolescents who had their first running away experience > 6 months previously had a greater risk of betel nut or illegal drug/inhalant use over the past 6-months than those with a similar experience within the last 6 months. Both alcohol and tobacco use were most frequently initiated before the first running away, whereas both betel nut and illegal drug/inhalant use were most frequently initiated after this event. When adolescents who were fleeing an unsatisfactory home life were compared to those who ran away for excitement, the risk of alcohol use was similar but the former tended to have a higher risk of tobacco, betel nut, and illegal drug/inhalant use. Conclusions More significant running away and a longer time since the first absconding experience were associated with more advanced substance involvement among adolescents now living in a family setting. Once adolescents had left home, they

  3. HighResNPS.com – an Internet Database for Liquid Chromatography - High Resolution Mass Spectrometry Screening for New Psychoactive Substances

    DEFF Research Database (Denmark)

    Dalsgaard, Petur Weihe; Mollerup, Christian Brinch; Mardal, Marie

    Background/Introduction: The number of new psychoactive substances (NPS) is constantly increasing which makes it challenging to keep the screening libraries updated with the relevant analytical targets. Liquid chromatography coupled High Resolution Mass Spectrometry (LC-HRMS) screening methods...... frequently utilize accurate mass of fragment ions for identification, in addition to retention time and accurate mass of precursor ions. The fragment ion information is obtained with data independent acquisition or data dependent acquisition. Both tend to generate similar fragment ions, when acquired...... cannabinoids and their metabolites constitute more than 60% of the database and opioids and their metabolites account for around 15% of the entries. 74% of the entries in HighResNPS are present in the European Database on New Drugs (EDND) governed by the European Monitoring Centre for Drugs and Drug Addiction...

  4. Alcohol, psychoactive substances and non-fatal road traffic accidents - a case-control study

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    Bogstrand Stig

    2012-09-01

    Full Text Available Abstract Background The prevalence of alcohol and other psychoactive substances is high in biological specimens from injured drivers, while the prevalence of these psychoactive substances in samples from drivers in normal traffic is low. The aim of this study was to compare the prevalence of alcohol and psychoactive substances in drivers admitted to hospital for treatment of injuries after road traffic accidents with that in drivers in normal traffic, and calculate risk estimates for the substances, and combinations of substances found in both groups. Methods Injured drivers were recruited in the hospital emergency department and drivers in normal conditions were taken from the hospital catchment area in roadside tests of moving traffic. Substances found in blood samples from injured drivers and oral fluid samples from drivers in moving traffic were compared using equivalent cut off concentrations, and risk estimates were calculated using logistic regression analyses. Results In 21.9% of the injured drivers, substances were found: most commonly alcohol (11.5% and stimulants eg. cocaine or amphetamines (9.4%. This compares to 3.2% of drivers in normal traffic where the most commonly found substances were z-hypnotics (0.9% and benzodiazepines (0.8%. The greatest increase in risk of being injured was for alcohol combined with any other substance (OR: 231.9, 95% CI: 33.3- 1615.4, p  Conclusion The prevalence of psychoactive substances was higher among injured drivers than drivers in normal moving traffic. The risk of accident is greatly increased among drivers who tested positive for alcohol, in particular, those who had also ingested one or more psychoactive substances. Various preventive measures should be considered to curb the prevalence of driving under the influence of psychoactive substances as these drivers constitute a significant risk for other road users as well as themselves.

  5. A network-based classification model for deriving novel drug-disease associations and assessing their molecular actions.

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    Min Oh

    Full Text Available The growing number and variety of genetic network datasets increases the feasibility of understanding how drugs and diseases are associated at the molecular level. Properly selected features of the network representations of existing drug-disease associations can be used to infer novel indications of existing drugs. To find new drug-disease associations, we generated an integrative genetic network using combinations of interactions, including protein-protein interactions and gene regulatory network datasets. Within this network, network adjacencies of drug-drug and disease-disease were quantified using a scored path between target sets of them. Furthermore, the common topological module of drugs or diseases was extracted, and thereby the distance between topological drug-module and disease (or disease-module and drug was quantified. These quantified scores were used as features for the prediction of novel drug-disease associations. Our classifiers using Random Forest, Multilayer Perceptron and C4.5 showed a high specificity and sensitivity (AUC score of 0.855, 0.828 and 0.797 respectively in predicting novel drug indications, and displayed a better performance than other methods with limited drug and disease properties. Our predictions and current clinical trials overlap significantly across the different phases of drug development. We also identified and visualized the topological modules of predicted drug indications for certain types of cancers, and for Alzheimer's disease. Within the network, those modules show potential pathways that illustrate the mechanisms of new drug indications, including propranolol as a potential anticancer agent and telmisartan as treatment for Alzheimer's disease.

  6. A market on both "sides" of the law: The use of the hidden web for the sale of new psychoactive substances.

    Science.gov (United States)

    Wadsworth, Elle; Drummond, Colin; Kimergård, Andreas; Deluca, Paolo

    2017-05-01

    The hidden Web is used for the anonymous sale of drugs, and with the UK Psychoactive Substances Act, 2016, implemented on May 26th 2016; it could increase as a platform for obtaining new psychoactive substances (NPS). This study aims to describe the NPS market on the visible and hidden Web preban, and assess whether the hidden Web is a likely place for the sale of NPS postban. Data collection of 113 online shops took place in October 2015. Data collection of 22 cryptomarkets took place every 2 months from October 2015 to 2016 as part of the CASSANDRA project. All online shops with a UK domain location sold NPS that were uncontrolled by the UK Misuse of Drugs Act, 1971, and closed after the ban. Of the cryptomarkets analysed, the total number of vendors selling NPS, number of substances, and listings advertised, all increased over the year. The majority of the NPS advertised on the hidden Web were phenethylamines and cathinones, yet the majority of uncontrolled NPS were synthetic cannabinoids. Vendors selling and availability of NPS increased over the 12 months of data collection. Potential displacement from the visible Web to hidden Web should be taken into consideration. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Psychoactive substances in seriously injured drivers in Denmark

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Steentoft, Anni; Bernhoft, Inger Marie

    2013-01-01

    found to be above the Danish legal limit in 4.9% of injured drivers. Young men (median age 31 years) were over-represented among injured drivers who violated Danish law for alcohol and drugs. Diazepam (4.4%), tramadol (3.2%), and clonazepam (3.0%) were the medicinal drugs most frequently detected...

  8. The Prevalence and Factors affecting Psychoactive Substance Use ...

    African Journals Online (AJOL)

    UNIBEN

    Health and Population. Perspectives and Issues. 2008; 31(3):. 212-219. 47. Bahls FRC, Ingbermann YK. Desenvolvimento escolar e abuso de drogas na adolescência / School development and adolescents' drug abuse. Estudos de psicologia. (Campinas). 2005; 22(4): 395-402. 48. Oliha JA. Adolescent and Drug Abuse.

  9. Risk of driving when positive for psychoactive substances

    DEFF Research Database (Denmark)

    Lyckegaard, Allan; Hels, Tove; Bernhoft, Inger Marie

    2013-01-01

    Background Driving with alcohol imposes an increased risk of injury, but the knowledge about other drugs is limited. Aims This paper aims to assess the risk of driving with alcohol, illicit drugs and medicines in various European countries. Method The risk of getting seriously injured or killed...

  10. A Profile Of Adolescents' Psychoactive Substance Users' Socio ...

    African Journals Online (AJOL)

    This is against the backdrop of numerous surveys globally, without the consequent impact on the education of a volatile sample of the population – adolescents. ... students is alcohol, and the significant source of push to use and stay on drugs is the peer group or friends, family type like divorce does determine drug use.

  11. Thioridazine: A Non-Antibiotic Drug Highly Effective, in Combination with First Line Anti-Tuberculosis Drugs, against Any Form of Antibiotic Resistance of Mycobacterium tuberculosis Due to Its Multi-Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Leonard Amaral

    2017-01-01

    Full Text Available This review presents the evidence that supports the use of thioridazine (TZ for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infected with extensively drug resistant (XDR Mtb. The mechanisms of action by which TZ brings about successful therapeutic outcomes are presented in detail.

  12. Thioridazine: A Non-Antibiotic Drug Highly Effective, in Combination with First Line Anti-Tuberculosis Drugs, against Any Form of Antibiotic Resistance of Mycobacterium tuberculosis Due to Its Multi-Mechanisms of Action.

    Science.gov (United States)

    Amaral, Leonard; Viveiros, Miguel

    2017-01-14

    This review presents the evidence that supports the use of thioridazine (TZ) for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb) regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infected with extensively drug resistant (XDR) Mtb. The mechanisms of action by which TZ brings about successful therapeutic outcomes are presented in detail.

  13. A tale of two citizens: a State Attorney General and a hematologist facilitate translation of research into US Food and Drug Administration actions--a SONAR report.

    Science.gov (United States)

    Chen, Brian; Restaino, John; Norris, LeAnn; Xirasagar, Sudha; Qureshi, Zaina P; McKoy, June M; Lopez, Isaac S; Trenery, Alyssa; Murday, Alanna; Kahn, Adam; Mattison, Donald R; Ray, Paul; Sartor, Oliver; Bennett, Charles L

    2012-11-01

    Pharmaceutical safety is a public health issue. In 2005, the Connecticut Attorney General (AG) raised concerns over adverse drug reactions in off-label settings, noting that thalidomide was approved to treat a rare illness, but more than 90% of its use was off label. A hematologist had reported thalidomide with doxorubicin or dexamethasone was associated with venous thromboembolism (VTE) rates of 25%. We review US Food and Drug Administration (FDA) and manufacturer responses to a citizen petition filed to address these thalidomide safety issues. Case study. The AG petitioned the FDA requesting thalidomide-related safety actions. Coincidentally, the manufacturer submitted a supplemental New Drug Approval (sNDA), requesting approval to treat multiple myeloma with thalidomide-dexamethasone. FDA safety officers reviewed the petition and the literature and noted that VTE risks with thalidomide were not appropriately addressed in the existing package insert. In the sNDA application, the manufacturer reported thalidomide-associated toxicities for multiple myeloma were primarily somnolence and neurotoxicity, and a proposed package insert did not focus on VTE risks. In October, the FDA informed the Oncology Drug Division that VTE risks with thalidomide were poorly addressed in the existing label. After reviewing this memorandum, an Oncology Drug Division reviewer informed the manufacturer that approval of the sNDA would be delayed until several thalidomide-associated VTE safety actions, including revisions of the package insert, were implemented. The manufacturer and FDA agreed on these actions, and the sNDA was approved. New approaches addressing off-label safety are needed. The conditions that facilitated the successful response to this citizen petition are uncommon.

  14. Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits.

    Science.gov (United States)

    Odening, Katja E; Jung, Bernd A; Lang, Corinna N; Cabrera Lozoya, Rocio; Ziupa, David; Menza, Marius; Relan, Jatin; Franke, Gerlind; Perez Feliz, Stefanie; Koren, Gideon; Zehender, Manfred; Bode, Christoph; Brunner, Michael; Sermesant, Maxime; Föll, Daniela

    2013-10-01

    Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias. To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS. Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments. In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P < .01) and APD dispersion was greater than that in LMC rabbits (P < .01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P < .01; E4031-treated: -3.24 ± 0.6 cm/s, P < .0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P < .05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P < .001; E4031-treated: 199.5 ± 2.2 ms, P < .0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P < .01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data. The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an

  15. The determinants of physician attitudes and subjective norms toward drug information sources: modification and test of the theory of reasoned action.

    Science.gov (United States)

    Gaither, C A; Bagozzi, R P; Ascione, F J; Kirking, D M

    1997-10-01

    To improve upon the theory of reasoned action and apply it to pharmaceutical research, we investigated the effects of relevant appraisals attributes, and past behavior of physicians on the use of drug information sources. We also examined the moderating effects of practice characteristics. A mail questionnaire asked HMO physicians to evaluate seven common sources of drug information on general appraisals (degree of usefulness and ease of use), specific attributes (availability, quality of information on harmful effects and on drug efficacy), and past behavior when searching for information on a new, simulated H2 antagonist agent. Semantic differential scales were used to measure each appraisal, attribute and past behavior. Information was also collected on practice characteristics. Findings from 108/200 respondents indicated that appraisals and attributes were useful determinants of attitudes and subjective norms toward use. Degree of usefulness and quality of information on harmful effects were important predictors of attitudes toward use for several sources of information. Ease of use and degree of usefulness were important predictors of subjective norms toward use. In many cases, moderating effects of practice characteristics were in opposing directions. Past behavior had significant direct effects on attitudes toward the PDR. The findings suggest ways to improve the usefulness of the theory of reasoned action as a model of decision-making. We also propose practical guidelines that can be used to improve the types of drug information sources used by physicians.

  16. From Words to Action: Comparing the Disparities Between National Drug Policy and Local Implementation in Tijuana, Mexico and Vancouver, Canada

    OpenAIRE

    Smith, Danielle; Werb, D.; Strathdee, S. A.

    2016-01-01

    In 2009, Mexico passed a national drug policy reform decriminalizing the possession of small amounts of certain drugs for personal use with the aim of diverting drug-dependent individuals from prison and towards addiction treatment. However, the public health approach codified by the reform has not yet led to a meaningful change in local police practices nor contributed to the meaningful scale-up of harm reduction and addiction treatment services in many Mexican cities. Specifically, in Tijua...

  17. DRUGS – “WAY” OF LIFE

    Directory of Open Access Journals (Sweden)

    Anna Nowacka

    2010-12-01

    Full Text Available This article refers to the phenomenon of an increasing number of people abusing drugs in the 20th century. In addition to the natural types of narcotics there are many other semi-synthetic and fully synthetic substances made available to the market by chemical and pharmaceutical industries. The use of narcotics and psychoactive substances usually causes adverse and often irreversible health effects. In Department of Laboratory Diagnostics of the Institute of Occupational Medicine and Environmental Health in Sosnowiec tests for presence of drugs are among routinely conducted analyses. The presence of drugs has been revealed in 898 cases between the years 2004 and 2008. On top of the list of the most frequently detected narcotics were: amphetamine, cannabis, opiates, methamphetamine and cocaine. At the same time the most popular psychoactive substances are atropine, scopolamine and psilocybin. Additionally, the laboratory analyses indicated in many cases the presence of derivatives of benzodiazepines, trycyclic antidepressants and alcohol. Regional Centre of Acute Intoxication in Sosnowiec, Poland, hospitalized 78 patients due to overdose of drugs, narcotics or psychoactive substances as a result of experimenting with such substances. Half of the hospitalized cases patients have tried to commit suicide; one of the attempts has led to death. According to patients’ history their problems with reaching out for the use of psychoactive substances and narcotics were mainly caused by socio-psychological disorders.

  18. Mixing drink and drugs: 'Underclass' politics, the recovery agenda and the partial convergence of English alcohol and drugs policy.

    Science.gov (United States)

    Monaghan, Mark; Yeomans, Henry

    2016-11-01

    Alcohol policy and illicit drugs policy are typically presented as separate and different in academic discussion. This is understandable, to a degree, as the criminal law upholds a 'great regulatory divide' (Seddon, 2010: 56) separating the licit trade in alcohol from the illicit trade in substances classified as either class A, B or C under the Misuse of Drugs Act 1971. This paper takes a different stance. In doing so, it draws upon Berridge's (2013) argument that policies governing various psychoactive substances have been converging since the mid-twentieth century and seeks to elaborate it using recent developments relating to the control and regulation of drugs and alcohol in the broader areas of criminal justice and welfare reform. Significantly, the article examines how recent policy directions relating to both drugs and alcohol in England have, under the aegis of the 'recovery agenda', been connected to a broader behavioural politics oriented towards the actions and lifestyles of an apparently problematic subgroup of the population or 'underclass'. The paper thus concludes that, although the great regulatory divide remains intact, an underclass politics is contributing towards the greater alignment of illicit drugs and alcohol policies, especially in regards to the respective significance of abstinence (or abstinence-based 'recovery'). Copyright © 2016 Elsevier B.V. All rights reserved.

  19. EFFEKCTIVENESS OF TREATMENT OF DRUG ADDICTS AND THEIR SOCIAL INTEGRATION.

    OpenAIRE

    DONNEROVÁ, Dominika

    2009-01-01

    The Effectiveness of Therpay for Drug Addicts and Their Integration within Society The purpose of my thesis "The Effectiveness of Therapy for Drug Addicts and Their Integration in Society" is to elucidate the lifestyles of addicts during different stages of therapy and to help people to understand the problems of drug addicts. The function of the brain can be altered by a number of psycho-active drugs that can influence a person's behavior, conscience, morals and mood. Drug addiction results ...

  20. Formação do acadêmico de enfermagem: vivência na atenção a usuários de drogas psicoativas La formación del estudiante de enfermería: vivencia en la atención de los usuarios de drogas Nursing student's education: experience in the care to users of psychoactive drugs

    Directory of Open Access Journals (Sweden)

    Andiara Araújo Cunegundes de Brito

    2012-06-01

    , crítica y reflexiva del enfermero profesional.This article intended to report the experience lived by nursery nursing academics in Fundação Belo Amor, located in Caicó/RN, a psycho-social rehabilitation service for alcohol and drug users, aiming to recognize the town's mental health network. This living was prompted by the subject of Mental Health Public Policies, offered during the sixth semester of the nursing graduation course, and included two moments: getting to the reality and performing two group techniques. Through the activities performed, it was possible to approach to the users' life-story, to understand their feelings which led them to drugs consumption or recurrences, current rehabilitation process living and future perspectives. This experience promoted the academics to understand the importance of this service to mental health network, and also for generalist, critic, and reflexive training of nursing professionals.

  1. Prescrição, dispensação e regulação do consumo de psicotrópicos anorexígenos em Belo Horizonte, Minas Gerais, Brasil Prescription, dispensing, and regulation of psychoactive anorexigenic drugs in Belo Horizonte, Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Mônica de Fátima Gontijo Carneiro

    2008-08-01

    Full Text Available Estudo retrospectivo, realizado na cidade de Belo Horizonte, Minas Gerais, Brasil, para avaliar indicadores de dispensação e consumo de substâncias anorexígenas. Ocorreu em duas etapas: na primeira, foram analisadas 2.906 das 168.237 notificações de receitas aviadas por estabelecimentos farmacêuticos da cidade, em 2003. Observou-se uma baixa qualidade nas notificações. O consumo projetado foi de 19,75 DDD/mil habitantes/dia. A substância mais consumida foi o fenproporex (59,8%. Uma farmácia foi responsável por 39,8% das dispensações. Na segunda etapa, foram analisados 14.554 registros do livro de receituário geral da farmácia que mais dispensou tais produtos, no período de abril a agosto de 2005. Os anorexígenos responderam por 9,2% das manipulações e 91,8% deles foram prescritos para uso concomitante com outra substância: 43% com clordiazepóxido, 50,6% com fluoxetina, 7,5% com outro anorexígeno e 28,2% com bromazepam. Os resultados observados sugerem um uso indiscriminado e irracional de anorexígenos neste município, sendo fundamental aprimorar a regulação do mercado de produtos manipulados. Para tanto, é necessário uma melhor compreensão do papel da farmácia nessa regulação e o papel dos prescritores no uso racional dessas substâncias.This retrospective study in Belo Horizonte, Minas Gerais, Brazil, aimed to provide indicators on the sale and consumption of anorexigenic substances. During the first stage, 2,906 of 168,237 prescriptions received by pharmacies in 2003 were analyzed, showing low quality of prescriptions. Projected consumption in defined daily doses was 19.75 DDD/1,000 inhabitants/day in 2003. Fenproporex (59.8% was the most widely consumed drug. One pharmacy was responsible for 39.8% of the pharmaceutical sales. During the second stage, 14,554 sales records from this "blockbuster" pharmacy were analyzed, from April to August 2005; 9.2% of sales were for anorexigenic products, 91.8% of which

  2. The antitumor activity of plant-derived non-psychoactive cannabinoids

    Science.gov (United States)

    McAllister, Sean D.; Soroceanu, Liliana; Desprez, Pierre-Yves

    2015-01-01

    As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer stem cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment. PMID:25916739

  3. The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.

    Science.gov (United States)

    McAllister, Sean D; Soroceanu, Liliana; Desprez, Pierre-Yves

    2015-06-01

    As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ(9)-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.

  4. Psychoactive Substance use among People living with HIV/AIDS in ...

    African Journals Online (AJOL)

    The life time uses of psychoactive substances among the participants were: alcohol (84.8%), oral sedatives (21.03%), cannabis (3.64%), cocaine, inhalants and solvents (0.26%) while polysubstance use (alcohol, cannabis and nonprescription use of sedatives) was 0.8%. However, a combination of alcohol, cocaine and ...

  5. Psychoactive Substance Use and School Performance among Adolescents in Public Secondary Schools in Uganda

    Science.gov (United States)

    Rukundo, Aloysius; Kibanja, Grace; Steffens, Karl

    2014-01-01

    Introduction: Psychoactive substance use among adolescents influences behavioral and cognitive processes and is associated with adolescents' performance in school. We therefore sought to investigate association of PASU with adolescents' school performance. Methods: We employed quantitative methods of data collection and analysis. To test the…

  6. The prevalence of novel psychoactive substances (NPS use in non-clinical populations: a systematic review protocol

    Directory of Open Access Journals (Sweden)

    Salma M. Khaled

    2016-11-01

    Full Text Available Abstract Background Novel psychoactive substances (NPS are new narcotic or psychotropic drugs that are not controlled by the United Nations drug convention that may pose a serious public health threat due to their wide availability for purchase on the internet and in so called “head shops.” Yet, the extent of their global use remains largely unknown. The aim of this study is to conduct a systematic review of the prevalence of NPS use in non-clinical populations. Methods This is a systematic review of observational studies. Embase, MEDLINE, PubMed, Cumulative Index to Nursing and Allied Health (CINAHL, Cochrane Library, Lilacs, Scopus, Global Health, PsychINFO, Web of Science, and the World Health Organization (WHO regional databases will be searched for eligible prevalence studies published between 2010 and 2016. Data from cross-sectional studies that report the prevalence of NPS use (one or more types in participants (of any age from censuses or probabilistic or convenience samples will be included. Data will be extracted from eligible publications, using a data extraction tool developed for this study. Visual and statistical approaches will be adopted instead of traditional meta-analytic approaches. Discussion This review will describe the distributions of various types of prevalence estimates of NPS use and explore the impact of different population groups and study-related and tempo-geographical variables on characteristics of these distributions over the period of 2010 to 2016. Systematic review registration PROSPERO CRD42016037020

  7. Reinforcing the membrane-mediated mechanism of action of the anti-tuberculosis candidate drug thioridazine with molecular simulations

    DEFF Research Database (Denmark)

    Kopec, Wojciech; Khandelia, Himanshu

    2014-01-01

    Thioridazine is a well-known dopamine-antagonist drug with a wide range of pharmacological properties ranging from neuroleptic to antimicrobial and even anticancer activity. Thioridazine is a critical component of a promising multi-drug therapy against M. tuberculosis. Amongst the various propose...

  8. Synergistic Effect of Eicosapentaenoic Acid on Antiproliferative Action of Anticancer Drugs in a Cancer Cell Line Model.

    Science.gov (United States)

    Ogo, Ayako; Miyake, Sachi; Kubota, Hisako; Higashida, Masaharu; Matsumoto, Hideo; Teramoto, Fusako; Hirai, Toshihiro

    2017-11-14

    It has been found experimentally and clinically that eicosapentaenoic acid (EPA) exerts an anticancer effect and that it has a minimal adverse event profile relative to other anticancer drugs. Any synergy between EPA and other anticancer drugs could be of therapeutic relevance, especially in elderly or high-risk patients. Therefore, we investigated the synergism between anticancer drugs and EPA experimentally. EPA was coadministered in vitro with various anticancer drugs (paclitaxel, docetaxel, 5-fluorouracil and cis-diamminedichloridoplatinum[II]) to TE-1 cells, which were derived from human esophageal cancer tumors. Cell proliferation was measured by the water soluble tetrazolium-1 method. Sub-threshold concentrations of EPA, which alone produced no anticancer effect, caused a synergistic suppressive effect on TE-1 cell proliferation when combined with other anticancer agents. Coadministration of EPA with other anticancer drugs may represent a new therapeutic paradigm offering a reduced side effect profile. © 2017 S. Karger AG, Basel.

  9. Development of a Questionnaire to Assess Drug Abuse among High School Students of Isfahan Province, Iran: An Action Research.

    Science.gov (United States)

    Geramian, Nahid; Gharaat, Leila; Taheri, Shohreh Akhavan; Mohebpour, Fatemeh; Nahvizadeh, Mahmonir; Farajzadegan, Ziba; Heidari, Kamal

    2014-12-01

    Considering the problem of drug abuse in Iran especially in adolescents and the youth, recent alterations in drug abuse rate and its trend, the necessity to have local information about this problem, applied research has a determining role in management of this problem and making proper decisions. Therefore, the current study was conducted to develop a questionnaire to assess the status of drug abuse among high school students of Isfahan Province, Iran. This cross-sectional study was conducted out in 2009 in 20 cities of Isfahan Province. A researcher-made questionnaire was developed to determine knowledge, attitude, and practice of high school students regarding addictive drugs and their associated causes. This was accomplished by recruiting 7137 students who were selected by multistage random cluster sampling. The designed questionnaire identified the status quo of drug abuse according to age, gender, and different cities of Isfahan Province. We also accessed information about the type of abused drug, the most common causes of drug abuse for the first time, the most important causes of drug abuse, mean age of abusers and mean age at the first abuse, common time and locations of drug abuse, and the most common routes of drug abuse according to gender as well as urban and rural areas of Isfahan Province. Reliability of the questionnaire, based on the calculated Cronbach's alpha coefficient, was 77% considering a cut-off point of 0.07. According to the obtained results, the designed questionnaire is capable to assess the drug abuse status among high school students of Isfahan Province. Regarding the importance of teenage years in forming the future behaviors of adolescents and the opportunities provided at schools, it is prudent to pay more attention to interventions in this age group in order to increase their knowledge and correct their attitude toward illegal drugs and strengthening their confidence in this regard. These interventions can have an important role

  10. Influence of Matrices on 3D-Cultured Prostate Cancer Cells' Drug Response and Expression of Drug-Action Associated Proteins

    Science.gov (United States)

    Edmondson, Rasheena; Adcock, Audrey F.; Yang, Liju

    2016-01-01

    This study investigated the effects of matrix on the behaviors of 3D-cultured cells of two prostate cancer cell lines, LNCaP and DU145. Two biologically-derived matrices, Matrigel and Cultrex BME, and one synthetic matrix, the Alvetex scaffold, were used to culture the cells. The cell proliferation rate, cellular response to anti-cancer drugs, and expression levels of proteins associated with drug sensitivity/resistance were examined and compared amongst the 3D-cultured cells on the three matrices and 2D-cultured cells. The cellular responses upon treatment with two common anti-cancer drugs, Docetaxel and Rapamycin, were examined. The expressions of epidermal growth factor receptor (EGFR) and β-III tubulin in DU145 cells and p53 in LNCaP cells were examined. The results showed that the proliferation rates of cells cultured on the three matrices varied, especially between the synthetic matrix and the biologically-derived matrices. The drug responses and the expressions of drug sensitivity-associated proteins differed between cells on various matrices as well. Among the 3D cultures on the three matrices, increased expression of β-III tubulin in DU145 cells was correlated with increased resistance to Docetaxel, and decreased expression of EGFR in DU145 cells was correlated with increased sensitivity to Rapamycin. Increased expression of a p53 dimer in 3D-cultured LNCaP cells was correlated with increased resistance to Docetaxel. Collectively, the results showed that the matrix of 3D cell culture models strongly influences cellular behaviors, which highlights the imperative need to achieve standardization of 3D cell culture technology in order to be used in drug screening and cell biology studies. PMID:27352049

  11. Influence of Matrices on 3D-Cultured Prostate Cancer Cells' Drug Response and Expression of Drug-Action Associated Proteins.

    Science.gov (United States)

    Edmondson, Rasheena; Adcock, Audrey F; Yang, Liju

    2016-01-01

    This study investigated the effects of matrix on the behaviors of 3D-cultured cells of two prostate cancer cell lines, LNCaP and DU145. Two biologically-derived matrices, Matrigel and Cultrex BME, and one synthetic matrix, the Alvetex scaffold, were used to culture the cells. The cell proliferation rate, cellular response to anti-cancer drugs, and expression levels of proteins associated with drug sensitivity/resistance were examined and compared amongst the 3D-cultured cells on the three matrices and 2D-cultured cells. The cellular responses upon treatment with two common anti-cancer drugs, Docetaxel and Rapamycin, were examined. The expressions of epidermal growth factor receptor (EGFR) and β-III tubulin in DU145 cells and p53 in LNCaP cells were examined. The results showed that the proliferation rates of cells cultured on the three matrices varied, especially between the synthetic matrix and the biologically-derived matrices. The drug responses and the expressions of drug sensitivity-associated proteins differed between cells on various matrices as well. Among the 3D cultures on the three matrices, increased expression of β-III tubulin in DU145 cells was correlated with increased resistance to Docetaxel, and decreased expression of EGFR in DU145 cells was correlated with increased sensitivity to Rapamycin. Increased expression of a p53 dimer in 3D-cultured LNCaP cells was correlated with increased resistance to Docetaxel. Collectively, the results showed that the matrix of 3D cell culture models strongly influences cellular behaviors, which highlights the imperative need to achieve standardization of 3D cell culture technology in order to be used in drug screening and cell biology studies.

  12. Development of a questionnaire to assess drug abuse among high school students of Isfahan province, Iran: An action research

    Directory of Open Access Journals (Sweden)

    Nahid Geramian

    2014-01-01

    Conclusions: According to the obtained results, the designed questionnaire is capable to assess the drug abuse status among high school students of Isfahan Province. Regarding the importance of teenage years in forming the future behaviors of adolescents and the opportunities provided at schools, it is prudent to pay more attention to interventions in this age group in order to increase their knowledge and correct their attitude toward illegal drugs and strengthening their confidence in this regard. These interventions can have an important role in decreasing the rate of drug abuse in this age group and consequently in the whole community.

  13. Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

    Science.gov (United States)

    Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

    2017-09-01

    Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Promoting innovation and excellence to face the rapid diffusion of novel psychoactive substances in the EU: the outcomes of the ReDNet project.

    Science.gov (United States)

    Corazza, Ornella; Assi, Sulaf; Simonato, Pierluigi; Corkery, John; Bersani, Francesco Saverio; Demetrovics, Zsolt; Stair, Jacqueline; Fergus, Suzanne; Pezzolesi, Cinzia; Pasinetti, Manuela; Deluca, Paolo; Drummond, Colin; Davey, Zoe; Blaszko, Ursula; Moskalewicz, Jacek; Mervo, Barbara; Furia, Lucia Di; Farre, Maggi; Flesland, Liv; Pisarska, Agnieszka; Shapiro, Harry; Siemann, Holger; Skutle, Arvid; Sferrazza, Elias; Torrens, Marta; Sambola, F; van der Kreeft, Peer; Scherbaum, Norbert; Schifano, Fabrizio

    2013-07-01

    The recent emergence of new psychoactive compounds (novel psychoactive substances (NPS)) has raised prominent challenges in the fields of drug policy, substance use research, public health and service provision. The Recreational Drugs European Network project, funded by the European Commission, was implemented to improve the information stream to young people and professionals about effects/risks of NPS by identifying online products and disseminating relevant information through technological tools. Regular multilingual qualitative assessments of websites, drugs fora and other online resources were carried out using the Google search engine in eight languages from collaborating countries. These included the following: the UK, Norway, Belgium, Germany, Hungary, Poland, Italy and Spain. Products were tested and prevention messages were developed and disseminated via technological tools such as interactive websites, SMS alert, social networking (Facebook, Twitter), Multimedia (You Tube), Smartphone applications (iPhone) and virtual learning environments (Second Life). The Recreational Drugs European Network project established itself as the first Europe-wide prevention programme designed for NPS based on the efficacy of novel information and communication technology-based forms of intervention. More than 650 NPS products and combinations were identified; relevant information was disseminated to target population and advice was given to both European Union/international agencies and national policy makers. Web-monitoring activities are essential for mapping the diffusion of NPS and the use of technological tools can be successfully incorporated in specific prevention programmes. Furthermore, the involvement of multi-disciplinary international partnerships was and continues to be fundamental for responding to such a prominent challenge. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Spontaneous and evoked pain-associated behaviors in a rat model of neuropathic pain respond differently to drugs with different mechanisms of action.

    Science.gov (United States)

    Murai, Nobuhito; Sekizawa, Toshihiro; Gotoh, Takayasu; Watabiki, Tomonari; Takahashi, Masayasu; Kakimoto, Shuichiro; Takahashi, Yuko; Iino, Masanobu; Nagakura, Yukinori

    2016-02-01

    Given that patients with neuropathic pain suffer a mixture of spontaneous and evoked pain symptoms, we assessed the effects of drugs with different mechanism of action on spontaneous and evoked pain-associated behaviors in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Frequent aberrant limb movement on the operated side was measured to assess spontaneous pain-associated behavior, and mechanical allodynia and thermal hyperalgesia were evaluated to assess evoked pain-associated behaviors. These three types of behavior were assessed after administration of the following drugs: pregabalin (α2δ-subunit ligand), morphine (μ-opioid receptor agonist), perampanel (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] receptor antagonist), clonidine, dexmedetomidine (α2-adrenoceptor agonists), and diclofenac (non-steroidal anti-inflammatory drug [NSAID]). Pregabalin at an oral dose of 10 or 30mg/kg significantly alleviated frequent aberrant limb movement and mechanical allodynia, but not thermal hyperalgesia. Morphine at a subcutaneous dose of 1 or 3mg/kg significantly improved all three types of behavior. Perampanel at an oral dose of 1mg/kg attenuated only frequent aberrant limb movement. Intraperitoneal administration of clonidine (0.01 or 0.03mg/kg) and dexmedetomidine (0.03mg/kg) significantly improved all three types of behavior, while diclofenac did not relieve any of the behaviors. Pregabalin, clonidine, and dexmedetomidine significantly decreased motor performance at doses close to analgesic doses in the rotarod test. The present study demonstrates that responses to spontaneous and evoked pain symptoms in neuropathic pain condition differ depending on a drug's mechanism of action. The selection and application of drugs according to the specific symptoms would be considered for the medication of patients with neuropathic pain. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Perception of health risks among adolescents due to consumption of cigarettes, alcohol and psychoactive substances in the Federation of Bosnia and Herzegovina.

    Science.gov (United States)

    Pilav, A; Rudić, A; Branković, S; Djido, V

    2015-07-01

    This article describes the perception of health risks in adolescents due to the consumption of cigarettes, alcohol and psychoactive substances in the Federation of Bosnia and Herzegovina (FBIH), as well as their observation of the behavior of their peers related to addictive behaviors. For the analysis was used a database from the European School Survey Project on Alcohol and Other Drugs (ESPAD) survey which was conducted in FBIH in 2011. The target population were students in the second grade of secondary schools in FBIH born in 1995 according to the ESPAD protocol. The total number of respondents from the cohort born in 1995 was 3813 students. The research results showed that the prevalence of risk perception due to the consumption of cigarettes, alcohol and psychoactive substances among adolescents in the FBIH is lower than the mean prevalence in countries which have implemented the ESPAD survey of 2011. PPreventive activities should be aimed at adolescent risk behaviours and empower them to make the right decisions that can have far reaching significance. Attention has to be paid to selective prevention that is directed towards individuals or subgroup of population where the risk of developing disorder is much higher than average. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  17. Psychoactive Substance Use Among Long Distance Vehicle Drivers ...

    African Journals Online (AJOL)

    15.9%). Except for cigrattes, the other substances were used mainly for instrumental purposes. Only about 50% of the respondents had ever attended a health talk on drug abuse. High level of religiousity was less likely to be associated with ...

  18. Homicide and Psychoactive Substance use among Offenders in a ...

    African Journals Online (AJOL)

    , cannabis and stimulants with rates of 34.6%, 15.2% and 1.5% respectively. During imprisonment, lower rates of use were reported for these substances. These were 6.1% 1.5% and 6.1% respectively. The consolidated drug use rate among ...

  19. Current challenges and problems in the field of new psychoactive substances in Germany from a law enforcement perspective.

    Science.gov (United States)

    Duffert, Anna

    2014-01-01

    Over the last few years, a range of so-called new psychoactive substances (NPS) have established themselves on the German recreational drug scene, causing increased concern. At the same time, a great number of Internet shops have come into existence offering these substances for sale online, ensuring a high level of availability. A number of these substances derived from pharmaceutical research which did not result in marketing authorization, presumably due to unfavourable properties. There are hardly any reliable data on long-term health damage, addictive potential, and other aspects of these scientifically unexplored substances. A number of fatal intoxications have also become known. As a rule, the mostly young consumers do not know what substance they are taking and in what concentration, thus exposing themselves to incalculable health risks and consequences. The punishability of the handling of NPS depends on the actual content: the Narcotic Drugs Act (BtMG) is applicable if a product contains narcotic drugs. If similarly effective substances are contained, which are not classified as narcotic drugs, the (penal) provisions of the Medicinal Products Act might be applicable, if the product has a pharmaceutical effect. Experience gained so far has shown that manufacturers of these intoxicating substances react immediately to inclusions in the German BtMG and put new substances on the market which are chemically similar to the known substances thus circumventing legislation. In view of the immense variety of NPS and the enormous profits derived from their sale, an end to this development is not in sight. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Medicinal Chemistry and Molecular Modeling: An Integration to Teach Drug Structure-Activity Relationship and the Molecular Basis of Drug Action

    Science.gov (United States)

    Carvalho, Ivone; Borges, Aurea D. L.; Bernardes, Lilian S. C.

    2005-01-01

    The use of computational chemistry and the protein data bank (PDB) to understand and predict the chemical and molecular basis involved in the drug-receptor interactions is discussed. A geometrical and chemical overview of the great structural similarity in the substrate and inhibitor is provided.

  1. Nanomedicines Eradicating Cancer Stem-like Cells in Vivo by pH-Triggered Intracellular Cooperative Action of Loaded Drugs.

    Science.gov (United States)

    Kinoh, Hiroaki; Miura, Yutaka; Chida, Tsukasa; Liu, Xueying; Mizuno, Kazue; Fukushima, Shigeto; Morodomi, Yosuke; Nishiyama, Nobuhiro; Cabral, Horacio; Kataoka, Kazunori

    2016-06-28

    Nanomedicines capable of control over drug functions have potential for developing resilient therapies, even against tumors harboring recalcitrant cancer stem cells (CSCs). By coordinating drug interactions within the confined inner compartment of core-shell nanomedicines, we conceived multicomponent nanomedicines directed to achieve synchronized and synergistic drug cooperation within tumor cells as a strategy for enhancing efficacy, overcoming drug resistance, and eradicating CSCs. The approach was validated by using polymeric micellar nanomedicines co-incorporating the pan-kinase inhibitor staurosporine (STS), which was identified as the most potent CSC inhibitor from a panel of signaling-pathway inhibitors, and the cytotoxic agent epirubicin (Epi), through rationally contriving the affinity between the drugs. The micelles released both drugs simultaneously, triggered by acidic endosomal pH, attaining concurrent intracellular delivery, with STS working as a companion for Epi, down-regulating efflux transporters and resistance mechanisms induced by Epi. These features prompted the nanomedicines to eradicate orthotopic xenografts of Epi-resistant mesothelioma bearing a CSC subpopulation.

  2. Catalysis and Sulfa Drug Resistance in Dihydropteroate Synthase: Crystal structures reveal the catalytic mechanism of DHPS and the structural basis of sulfa drug action and resistance

    OpenAIRE

    Yun, Mi-Kyung; Wu, Yinan; Li, Zhenmei; Zhao, Ying; Waddell, M. Brett; Ferreira, Antonio M.; Lee, Richard E.; Bashford, Donald; White, Stephen W

    2012-01-01

    The sulfonamide antibiotics inhibit dihydropteroate synthase (DHPS), a key enzyme in the folate pathway of bacteria and primitive eukaryotes. However, resistance mutations have severely compromised the usefulness of these drugs. Here, we report structural, computational and mutagenesis studies on the catalytic and resistance mechanisms of DHPS. By performing the enzyme-catalyzed reaction in crystalline DHPS, we have structurally characterized key intermediates along the reaction pathway. Resu...

  3. Ready for Retirement: The Gateway Drug Hypothesis.

    Science.gov (United States)

    Kleinig, John

    2015-01-01

    The psycho-social observation that the use of some psychoactive substances ("drugs") is often followed by the use of other and more problematic drugs has given rise to a cluster of so-called "gateway drug hypotheses," and such hypotheses have often played an important role in developing drug use policy. The current essay suggests that drug use policies that have drawn on versions of the hypothesis have involved an unjustified oversimplification of the dynamics of drug use, reflecting the interests of certain stakeholders rather than wise social policy. The hypothesis should be retired.

  4. INFLUENCE OF ADVERTISING ON THE WAY OF ACTION IN THE ACQUISITION OF OVER-THE-COUNTER DRUGS

    Directory of Open Access Journals (Sweden)

    Stefan-Dragoş CÎRSTEA

    2016-12-01

    Full Text Available Advertising of the Over-the-counter drugs is a growing segment. Our research aims to identify the main factors involved in making decisions for the purchase of OTC drugs and to identify what are the ways of informing consumers for this process. To test the hypotheses, a number of statistical tools such as factor analysis, Shapiro-Wilk and Mann-Whitney U tests have been used. The analyzed factors were: (A doctor’s choice , (b former own experience, (c pharmacist’s advice, (d information stated on the prospectus, (e opinion of people who bought that drug, (f opinion of colleagues, friends, relatives, (g price, (h brand, manufacturer, (i information from advertising, (j quality of advertising. For our analysis, we focused on two main populations: students and employed educated people. The main conclusion of this paper is that recent exposure to OTC advertising is likely to change both related behaviors and decision grids.

  5. Best Practices of Computer-Aided Drug Discovery: Lessons Learned from the Development of a Preclinical Candidate for Prostate Cancer with a New Mechanism of Action.

    Science.gov (United States)

    Ban, Fuqiang; Dalal, Kush; Li, Huifang; LeBlanc, Eric; Rennie, Paul S; Cherkasov, Artem

    2017-05-22

    Small-molecule drug design is a complex and iterative decision-making process relying on pre-existing knowledge and driven by experimental data. Low-molecular-weight chemicals represent an attractive therapeutic option, as they are readily accessible to organic synthesis and can easily be characterized.1 Their potency as well as pharmacokinetic and pharmacodynamic properties can be systematically and rationally investigated and ultimately optimized via expert science behind medicinal chemistry and methods of computer-aided drug design (CADD). In recent years, significant advances in molecular modeling techniques have afforded a variety of tools to effectively identify potential binding pockets on prospective targets, to map key interactions between ligands and their binding sites, to construct and assess energetics of the resulting complexes, to predict ADMET properties of candidate compounds, and to systematically analyze experimental and computational data to derive meaningful structure-activity relationships leading to the creation of a drug candidate. This Perspective describes a real case of a drug discovery campaign accomplished in a relatively short time with limited resources. The study integrated an arsenal of available molecular modeling techniques with an array of experimental tools to successfully develop a novel class of potent and selective androgen receptor inhibitors with a novel mode of action. It resulted in the largest academic licensing deal in Canadian history, totaling $142M. This project exemplifies the importance of team science, an integrative approach to drug discovery, and the use of best practices in CADD. We posit that the lessons learned and best practices for executing an effective CADD project can be applied, with similar success, to many drug discovery projects in both academia and industry.

  6. Network-based discovery through mechanistic systems biology. Implications for applications--SMEs and drug discovery: where the action is.

    Science.gov (United States)

    Benson, Neil

    2015-08-01

    Phase II attrition remains the most important challenge for drug discovery. Tackling the problem requires improved understanding of the complexity of disease biology. Systems biology approaches to this problem can, in principle, deliver this. This article reviews the reports of the application of mechanistic systems models to drug discovery questions and discusses the added value. Although we are on the journey to the virtual human, the length, path and rate of learning from this remain an open question. Success will be dependent on the will to invest and make the most of the insight generated along the way. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Correlates for psycho-active substance use among boarding secondary school adolescents in Enugu, South East, Nigeria

    National Research Council Canada - National Science Library

    Manyike, Pius C; Chinawa, Josephat M; Chinawa, Awoere T; Obu, Herbert A; Nwokocha, Ada R C; Odetunde, Odutola I

    2016-01-01

    ...; the substances involved and the extent of the problem in this locale. This is a cross-sectional study that assesses the pattern of psychoactive substance use among secondary school adolescents in Enugu, south East, Nigeria...

  8. Determination of the psychoactive drugs carbamazepine and diazepam in hospital effluent and identification of their metabolites.

    Science.gov (United States)

    de Almeida, Carlos A A; Oliveira, Maurício S; Mallmann, Carlos A; Martins, Ayrton F

    2015-11-01

    This study addresses the occurrence of carbamazepine and diazepam and their metabolites in the wastewater of the University Hospital (HUSM) of the Federal University of Santa Maria, RS-Brazil. Samples were collected from three sampling points of the sewage treatment system: point A ('emergency effluent'), point B ('general effluent') and point C ('water course-receptor'). Eight metabolites were identified: carbamazepine-10-11-epoxide, 10-dihydro-carbamazepine, 2-OH-carbamazepine, iminoquinone, acridone, nordiazepam, oxazepam and temazepam. The mean concentrations in the emergency, general effluent and water course-receptor were as follows: 433.0 ± 4.7, 349.0 ± 5.0 and 485.0 ± 5.6 ng L(-1), for carbamazepine and 550.0 ± 4.3, 441.0 ± 7.9 and 586.6 ± 9.3 ng L(-1), for diazepam, respectively. Liquid chromatography with electrospray ionization tandem mass spectrometry (LC-QqLIT-MS) proved to be a method fit-to-purpose. The determination of carbamazepine and diazepam, and the identification of active metabolites showing environmental persistence (carbamazepine-10-11-epoxide, nordiazepam and oxazepam) revealed the need for a more effective treatment of the HUSM effluent. As far as we know, no similar study has been carried out on the wastewater of Brazilian hospitals.

  9. Implications of neuroscience Psychoactive drugs and identity: between history and culture

    Directory of Open Access Journals (Sweden)

    Lydia Feito Grande

    2016-02-01

    Full Text Available Neuroscientifical advances open the possibility to modify capacities in human beings, aimed to enhance them. An example is neurodrugs. Altering memory, attention or mood can make a difference in personal identity. This question about identity is analyzed and its implications on modification of human nature. This raises again the nature/culture debate, also from the contemporary neuroscience. The conclusion is that dynamism in human narrative identity is the result of an interaction between nature and culture.

  10. The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

    OpenAIRE

    Colon-Perez, Luis M; Tran, Kelvin; Thompson, Khalil; Pace, Michael C; Blum, Kenneth; Goldberger, Bruce A; Gold, Mark S; Bruijnzeel, Adriaan W; Setlow, Barry; Febo, Marcelo

    2016-01-01

    The abuse of ‘bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on br...

  11. Alcohol, Tobacco, and Other Psychoactive Drug Use among High School Students in Bogota, Colombia.

    Science.gov (United States)

    Perez, Miguel A.; Pinzon-Perez, Helda

    2000-01-01

    Investigated health behaviors practiced by 10th graders in Bogota, Colombia. Data from a modified version of the Youth Risk Behavior Survey indicated that there was a high use of gateway substances (tobacco and alcohol) among respondents, but lower usage, when compared to U.S. students, of other mind-altering substances such as marijuana,…

  12. Acute renal failure by ingestion of Cortinarius species confounded with psychoactive mushrooms: a case series and literature survey.

    Science.gov (United States)

    Frank, H; Zilker, T; Kirchmair, M; Eyer, F; Haberl, B; Tuerkoglu-Raach, G; Wessely, M; Gröne, H-J; Heemann, U

    2009-05-01

    Mushrooms of the Cortinarius species are nephrotoxic and can cause severe acute renal failure. The toxic effect is due to orellanine. It is suspected that the cytotoxic damage is caused by the production of oxygen-free radicals. Renal pathology shows tubular necrosis with interstitial nephritis. In addition to accidental intoxications as a consequence of mushroom meals, recent cases are often due to voluntary abuse of natural drugs like magic mushrooms. We report 4 current cases of acute renal failure from intoxication by Cortinarius species by confusing it with psychoactive fungi. Typical for the Cortinarius poisoning is the long latency period from ingestion until the onset of clinical symptoms (3 - 20 days). Diagnosis is based on microscopical identification of the mushroom spores, and detection of the orellanine toxin in leftover mushrooms. In renal biopsy tissue, orellanine is detectable by thin-layer chromaography technique up to 6 months after poisoning. There is no causative therapy, and treatment is symptomatic with adequate hemodialysis. In cases of otherwise unexplained acute renal failure, intoxication with nephrotoxic mushrooms should be considered.

  13. "Spice," "kryptonite," "black mamba": an overview of brand names and marketing strategies of novel psychoactive substances on the web.

    Science.gov (United States)

    Corazza, Ornella; Valeriani, Giuseppe; Bersani, Francesco Saverio; Corkery, John; Martinotti, Giovanni; Bersani, Giuseppe; Schifano, Fabrizio

    2014-01-01

    Abstract Introduction: Novel Psychoactive Substances (NPSs) are often sold online as "legal" and "safer" alternatives to International Controlled Drugs (ICDs) with captivating marketing strategies. Our aim was to review and summarize such strategies in terms of the appearance of the products, the brand names, and the latest trends in the illicit online marketplaces. Scientific data were searched in PsychInfo and Pubmed databases; results were integrated with an extensive monitoring of Internet (websites, online shops, chat rooms, fora, social networks) and media sources in nine languages (English, French, Farsi, Portuguese, Arabic, Russian, Spanish, and Chinese simplified/traditional) available from secure databases of the Global Public Health Intelligence Network. Evolving strategies for the online diffusion and the retail of NPSs have been identified, including discounts and periodic offers on chosen products. Advertisements and new brand names have been designed to attract customers, especially young people. An increased number of retailers have been recorded as well as new Web platforms and privacy systems. NPSs represent an unprecedented challenge in the field of public health with social, cultural, legal, and political implications. Web monitoring activities are essential for mapping the diffusion of NPSs and for supporting innovative Web-based prevention programmes.

  14. 76 FR 24901 - Request for Input To Inform a Possible Surgeon General Action on Prescription Drug Abuse in Youth

    Science.gov (United States)

    2011-05-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Request for Input To Inform a Possible Surgeon General... work group has received expert input on the state of the science for addressing prescription drug abuse...

  15. 78 FR 54469 - Solicitation of Written Comments on Draft National Action Plan for Adverse Drug Event Prevention

    Science.gov (United States)

    2013-09-04

    ... and can include, but are not limited to, medication errors, adverse drug reactions, allergic reactions..., aware, and knowledgeable of issues regarding the safe use of prescribed medications to prevent ADEs... materials to demonstrate or exhibit concepts of their written responses, however, we request that comments...

  16. Neuropharmacology of new psychoactive substances (NPS: focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants

    Directory of Open Access Journals (Sweden)

    Cristina eMiliano

    2016-04-01

    Full Text Available New psychoactive substances (NPS are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, dark net as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society (UNODC, World Drug Report, 2014; EMCDDA, European Drug Report 2014: Trends and developments. The chemical structure (phenethylamines, piperazine, cathinones, tryptamines, synthetic cannabinoids of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%(WDR, 2014. Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone and MDMA analogues. Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ9-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of

  17. Social representations as a subjective production on the use of psychoactive substances in four young people

    Directory of Open Access Journals (Sweden)

    Leandro Caicedo-Castaño

    2017-09-01

    Full Text Available This study is approached from a historical-cultural perspective, which places as central axis the representations as subjective productions from Fernando González Rey's Theory of subjectivity. The objective is centered on investigating social representations as a subjective production about the consumption of psychoactive substances in four young people. In this, identify the emotional and symbolic dimensions that have four young people regarding the consumption of substances. Method: Comprehensive, interpretive, constructive, interpretive, qualitative study, completing phrases, compositions and inducers not written as films in a group of four young people. Results: The social representations constructed by young people who have used psychoactive substances are involved both symbolic and emotional dimensions that converge as elements of subjective senses in social and individual instances.

  18. [Psychoactive substance abuse, behavioral disorder and depression during adolescence.].

    Science.gov (United States)

    Vitaro, F; Rorive, M; Zoccolillo, M; Romano, E; Tremblay, R E

    2001-01-01

    This article examines coocurrence of three types of problems of adaptation during adolescence : abuse of psychotropic drugs, behavioral disorder (oppositional and behavioral disorders) and feelings of depression (depression and dysthymia). The study also examines behavioral, social as well as family characteristics which, during childhood, distinguish youths with many adaptation problems from those with only one or no problem. More than 1600 youths from all regions of Quebec participated in the study. These youths were around 15,7 years old when they completed an interview aiming at determining the possible presence of abusive use of psychotropic drugs, behavioral problems and feelings of depression. Their behavioral and sociofamilial characteristics had been previously evaluated (between the ages of 6 and 12) with questionnaires answered by parents and teachers. Results reveal that almost 10 % of youths experience two or three adaptation problems. These youths distinguish themselves from those with only one problem on various personal and sociofamilial dimensions in the course of childhood. Those with one problem represent a little more than 25 % of the sample. They also distinguish themselves from the group of youth with no problem on several variables. However, the group of youths with a problem of substance abuse only, is an exception. The discussion underlines the importance of knowing if there is simultaneous presence of several problems and proposes to intervene in a preventive fashion with youths who risk experiencing many problems.

  19. Quantifying reinforcement value and demand for psychoactive substances in humans.

    Science.gov (United States)

    Heinz, Adrienne J; Lilje, Todd C; Kassel, Jon D; de Wit, Harriet

    2012-12-01

    Behavioral economics is an emerging cross-disciplinary field that is providing an exciting new contextual framework for researchers to study addictive processes. New initiatives to study addiction under a behavioral economic rubric have yielded variable terminology and differing methods and theoretical approaches that are consistent with the multidimensional nature of addiction. The present article is intended to provide an integrative overview of the behavioral economic nomenclature and to describe relevant theoretical models, principles and concepts. Additionally, we present measures derived from behavioral economic theories that quantify demand for substances and assess decision making processes surrounding substance use. The sensitivity of these measures to different contextual elements (e.g., drug use status, acute drug effects, deprivation) is also addressed. The review concludes with discussion of the validity of these approaches and their potential for clinical application and highlights areas that warrant further research. Overall, behavioral economics offers a compelling framework to help explicate complex addictive processes and it is likely to provide a translational platform for clinical intervention.

  20. Toward a comparative overview of dependence potential and acute toxicity of psychoactive substances used nonmedically.

    Science.gov (United States)

    Gable, R S

    1993-01-01

    A procedure is outlined for comparing dependence potential and acute toxicity across a broad range of abused psychoactive substances. Tentative results, based on an extensive literature review of 20 substances, suggested that the margin of safety ("therapeutic index") varied dramatically between substances. Intravenous heroin appeared to have the greatest risk of dependence and acute lethality; oral psilocybin appeared to have the least. Hazards due to behavioral deficits, perceptual distortion, or chronic illness were not factored into the assessments.

  1. Localization of Salvinorin A and Related Compounds in Glandular Trichomes of the Psychoactive Sage, Salvia divinorum

    OpenAIRE

    SIEBERT, DANIEL J.

    2004-01-01

    • Background and Aims Salvia divinorum produces several closely related neoclerodane diterpenes. The most abundant of these, salvinorin A, is responsible for the psychoactive properties of the plant. To determine where these compounds occur in the plant, various organs, tissues and glandular secretions were chemically analysed. A microscopic survey of the S. divinorum plant was performed to examine the various types of trichomes present and to determine their distribution.

  2. Modafinil and its metabolites enhance the anticonvulsant action of classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model.

    Science.gov (United States)

    Zolkowska, Dorota; Andres-Mach, Marta; Prisinzano, Thomas E; Baumann, Michael H; Luszczki, Jarogniew J

    2015-07-01

    Seizures occur when the excitability of brain circuits is not sufficiently restrained by inhibitory mechanisms. Although modafinil is reported to reduce GABA-activated currents and extracellular GABA levels in the brain, the drug exerts anticonvulsant effects in animal studies. The aim of this study was to determine the effects of modafinil and its metabolites (sulfone and carboxylic acid) on the anticonvulsant action of four classical antiepileptic drugs (AEDs)-carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA). Anticonvulsant activity was assessed with the maximal electroshock seizure threshold (MEST) test and MES test in mice. Brain concentrations of AEDs were measured to ascertain any pharmacokinetic contribution to the observed anticonvulsant effects. Intraperitoneal injection of 75 mg kg(-1) of modafinil or its metabolites significantly elevated the threshold for electroconvulsions in mice, whereas 50 mg kg(-1) of each compound enhanced the anticonvulsant activity of CBZ, PHT, and VPA, but not that of PB. A 25-mg kg(-1) dose of modafinil or its sulfone metabolite enhanced anticonvulsant activity of VPA. Modafinil and its metabolites (50 mg kg(-1)) did not alter total brain concentrations of PB and VPA but did elevate CBZ and PHT. Enhancement of anticonvulsant actions of VPA by modafinil in the mouse MES model is a pharmacodynamic effect. Collectively, our data suggest that modafinil may be a safe and beneficial adjunct to the therapeutic effects of AEDs in human patients.

  3. Attenuating action of taurine and labetalol on cardiovascular alterations by pyridoxal-isoproterenol, a vitamin-drug interaction with cardiopathologic significance.

    Science.gov (United States)

    Acharya, Miteshkumar; Lau-Cam, Cesar A

    2009-01-01

    Taking into account the ability of vitamin B6 vitamers (i.e., pyridoxal, pyridoxine, pyridoxamine) to stimulate adrenomedullary catecholamine outflow and biochemical and cardiovascular changes consistent with adrenoceptor stimulation, this study was undertaken in mice to verify the possibility that pyridoxal (PL), the most potent of the B6 vitamers, could enter into an adverse vitamin-drug interaction when coadministered with a cardioactive drug, and that compounds like taurine (TAU) and labetalol (LAB) could be protective. To this end, mice were treated with PL (200 mg/kg) and isoproterenol (ISO 200 mg/kg), with and without a pretreatment with TAU (300 mg/kg), LAB (30 mg/kg), or TAU plus LAB, and monitored for heart rate, electrocardiographic (ECG) and myocardial electrolyte changes. PL plus ISO lowered the LD50 of ISO and magnified the changes in heart rate, ECG and myocardial electrolytes seen with ISO alone. Pretreating rats with TAU or TAU plus LAB attenuated the cardiovascular changes induced by PL plus ISO to a greater extent than LAB alone. The attenuating actions of TAU and LAB probably reflect independent and complementary mechanisms of action.

  4. Cannabinoid-induced alterations in brain disposition of drugs of abuse.

    Science.gov (United States)

    Reid, M J; Bornheim, L M

    2001-06-01

    Marijuana contains a complex mixture of compounds including tetrahydrocannabinol (THC), the major psychoactive constituent, and cannabidiol (CBD), a nonpsychoactive constituent. We have shown previously that CBD pretreatment of mice increases brain levels of THC and have now further characterized this effect and determined whether the brain pharmacokinetics of other drugs are also affected. CBD pretreatment of mice (30-60 min) increased brain levels of THC nearly 3-fold, whereas CBD co-administration did not. Because marijuana is often consumed with other drugs, the influence of cannabinoids on the brain levels of several other drugs of abuse was also determined. CBD pretreatment of mice increased brain levels (2- to 4-fold) of subsequently administered cocaine as well as phencyclidine (PCP). Although CBD pretreatment increased blood and brain levels of cocaine comparably, blood levels of PCP were only modestly elevated (up to 50%). Behavioral tests indicated that the CBD-mediated increases in the brain levels of THC, cocaine, and PCP correlated with increased pharmacological responses. Pretreatment with THC instead of CBD could similarly increase brain levels of cocaine, PCP, and CBD, although with a lower potency than CBD. On the other hand, pretreatment of mice with CBD had no effect on the brain levels of several other drugs of abuse including morphine, methadone, or methylenedioxyphenyl-methamphetamine. These findings demonstrate that cannabinoids can increase the brain concentrations and pharmacological actions of several other drugs of abuse, thereby providing a biochemical basis for the common practice of using marijuana concurrently with such drugs.

  5. Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens.

    Science.gov (United States)

    Rickli, Anna; Moning, Olivier D; Hoener, Marius C; Liechti, Matthias E

    2016-08-01

    The present study investigated interactions between the novel psychoactive tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline. We investigated binding affinities at human monoamine receptors and determined functional serotonin (5-hydroxytryptamine [5-HT]) 5-HT2A and 5-HT2B receptor activation. Binding at and the inhibition of human monoamine uptake transporters and transporter-mediated monoamine release were also determined. All of the novel tryptamines interacted with 5-HT2A receptors and were partial or full 5-HT2A agonists. Binding affinity to the 5-HT2A receptor was lower for all of the tryptamines, including psilocin and DMT, compared with LSD and correlated with the reported psychoactive doses in humans. Several tryptamines, including psilocin, DMT, DiPT, 4-OH-DiPT, and 4-OH-MET, interacted with the serotonin transporter and partially the norepinephrine transporter, similar to 3,4-methylenedioxymethamphetamine but in contrast to LSD and mescaline. LSD but not the tryptamines interacted with adrenergic and dopaminergic receptors. In conclusion, the receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also MDMA-like psychoactive properties. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  6. Novel Psychoactive Substances in Young Adults with and without Psychiatric Comorbidities

    Directory of Open Access Journals (Sweden)

    Giovanni Martinotti

    2014-01-01

    Full Text Available Objective. Comorbidities between psychiatric diseases and consumption of traditional substances of abuse (alcohol, cannabis, opioids, and cocaine are common. Nevertheless, there is no data regarding the use of novel psychoactive substances (NPS in the psychiatric population. The purpose of this multicentre survey is to investigate the consumption of a wide variety of psychoactive substances in a young psychiatric sample and in a paired sample of healthy subjects. Methods. A questionnaire has been administered, in different Italian cities, to 206 psychiatric patients aged 18 to 26 years and to a sample of 2615 healthy subjects matched for sex, gender, and living status. Results. Alcohol consumption was more frequent in the healthy young population compared to age-matched subjects suffering from mental illness (79.5% versus 70.7%; P<0.003. Conversely, cocaine and NPS use was significantly more common in the psychiatric population (cocaine 8.7% versus 4.6%; P=0.002 (NPS 9.8% versus 3%; P<0.001. Conclusions. The use of novel psychoactive substances in a young psychiatric population appears to be a frequent phenomenon, probably still underestimated. Therefore, careful and constant monitoring and accurate evaluations of possible clinical effects related to their use are necessary.

  7. Antiplasmodial activity of chloroquine analogs against chloroquine-resistant parasites, docking studies and mechanisms of drug action

    OpenAIRE

    de Souza, Nicolli B; Carmo, Arturene ML; da Silva, Adilson D; França, Tanos CC; Krettli, Antoniana U

    2014-01-01

    Background Given the threat of resistance of human malaria parasites, including to artemisinin derivatives, new agents are needed. Chloroquine (CQ) has been the most widely used anti-malarial, and new analogs (CQAns) presenting alkynes and side chain variations with high antiplasmodial activity were evaluated. Methods Six diaminealkyne and diaminedialkyne CQAns were evaluated against CQ-resistant (CQ-R) (W2) and CQ-sensitive (CQ-S) (3D7) Plasmodium falciparum parasites in culture. Drug cytoto...

  8. N-Acetylcysteine enhances the action of anti-inflammatory drugs as suppressors of prostaglandin production in monocytes

    Directory of Open Access Journals (Sweden)

    Erica Hoffer

    2002-01-01

    Full Text Available The anti-inflammatory effect of non-steroidal anti-inflammatory drugs (NSAIDs is associated with inhibition of cyclooxygenase (COX, the rate-limiting enzyme responsible for the synthesis of prostaglandins. Since oxygen free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract, it seems plausible that antioxidants might affect the production of prostaglandin by activated cells. This research is focused on the effect of the antioxidant N-acetylcysteine (NAC on the inhibition of prostaglandin E2 formation in activated monocytes by specific and non-specific COX inhibitors. We found that lipopolysaccharide-induced prostaglandin E2 formation was significantly reduced by rofecoxib and by diclofenac, two NSAIDs. Addition of NAC to each of these drugs enhanced the effect of the NSAIDs. These results suggest that one might expect either a potentiation of the anti-inflammatory effect of COX inhibitors by their simultaneous administration with NAC, or obtaining the same anti-inflammatory at lower drug levels.

  9. Arrhythmogenic drugs can amplify spatial heterogeneities in the electrical restitution in perfused guinea-pig heart: An evidence from assessments of monophasic action potential durations and JT intervals.

    Directory of Open Access Journals (Sweden)

    Oleg E Osadchii

    Full Text Available Non-uniform shortening of the action potential duration (APD90 in different myocardial regions upon heart rate acceleration can set abnormal repolarization gradients and promote arrhythmia. This study examined whether spatial heterogeneities in APD90 restitution can be amplified by drugs with clinically proved proarrhythmic potential (dofetilide, quinidine, procainamide, and flecainide and, if so, whether these effects can translate to the appropriate changes of the ECG metrics of ventricular repolarization, such as JT intervals. In isolated, perfused guinea-pig heart preparations, monophasic action potentials and volume-conducted ECG were recorded at progressively increased pacing rates. The APD90 measured at distinct ventricular sites, as well as the JTpeak and JTend values were plotted as a function of preceding diastolic interval, and the maximum slopes of the restitution curves were determined at baseline and upon drug administration. Dofetilide, quinidine, and procainamide reverse rate-dependently prolonged APD90 and steepened the restitution curve, with effects being greater at the endocardium than epicardium, and in the right ventricular (RV vs. the left ventricular (LV chamber. The restitution slope was increased to a greater extent for the JTend vs. the JTpeak interval. In contrast, flecainide reduced the APD90 restitution slope at LV epicardium without producing effect at LV endocardium and RV epicardium, and reduced the JTpeak restitution slope without changing the JTend restitution. Nevertheless, with all agents, these effects translated to the amplified epicardial-to-endocardial and the LV-to-RV non-uniformities in APD90 restitution, paralleled by the increased JTend vs. JTpeak difference in the restitution slope. In summary, these findings suggest that arrhythmic drug profiles are partly attributable to the accentuated regional heterogeneities in APD90 restitution, which can be indirectly determined through ECG assessments of the

  10. Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures.

    Directory of Open Access Journals (Sweden)

    Alessandro Furlan

    Full Text Available The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by "RTK swapping" by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in

  11. [Ethanol and other psychoactive substances in fatal road traffic accidents in the Czech Republic in 2008].

    Science.gov (United States)

    Mravcík, Viktor; Zábranský, Tomás; Vorel, Frantisek

    2010-01-01

    To map the recent prevalence of alcohol and other psychoactive substances in deceased victims of traffic accidents in the Czech Republic. The studied sample consisted of individuals autopsied in the departments of forensic medicine who died during traffic accidents in 2008 and were toxicologically tested for one or more of the following substances: ethanol, volatile substances, cannabis, opiates, stimulants, cocaine, benzodiazepines, and barbiturates. Case definition involved alcohol cases with blood alcohol concentration (BAC) 0.2 g/kg and higher; with cannabis, detections of active THC metabolites only were taken into account; from cases where volatile substances (solvents) were detected we included into the positive cases only those where substances were not produced post mortem or in some physiological or pathological statuses. The sample consisted of 1,040 persons deceased in traffic accidents, of whom 582 (56.0%) were toxicologically tested for one or more of the substances listed above. The sample has been divided into two subsamples--one of 778 (74.8%) active participants of road traffic accidents (pedestrians, bicyclists, and drivers) and other subsample consisting of 262 (25.4%) non-active participants. Ethanol was found in 38.3% of 381 tested and at least one of other psychoactive substances was found in 11.7% of 384 tested active participants--of those, stimulants (mostly methamphetamine) were found most frequently (6.5% of 337 tested), cannabis (5.9% of 203 tested) and benzodiazepines (3.9% of 363 tested active participants). Drivers were positive for ethanol in 29.2% cases, for one or more of other psychoactive substances except ethanol in 12.7% cases, most frequently for stimulants (9.2%) and cannabis (6.2%). Professional drivers were found negative for ethanol and other psychoactive substance except of one case of methamphetamine (6.7%). The study confirms high prevalence of alcohol and other psychoactive substances, especially stimulants

  12. APPLICATION OF CHEMOMETRICS FOR IDENTIFICATION OF PSYCHOACTIVE PLANTS.

    Science.gov (United States)

    Kowalczuk, Anna Paulina; Łozak, Anna; Kiljan, Monika; Mętrak, Krystyna; Zjawiony, Jordan Kordian

    2015-01-01

    Drug market changes dynamically causing many analytical challenges for police experts. Among illicit substances there are synthetic designer products but also herbal material. Plant material is usually in fine-cut or powdered form, thus difficult to identify. For such fragmented material classic taxonomical identification methods using anatomical and morphological features of the plant cannot be employed. The aim of the study was to develop an identification method of the powdered material with employment of multidimensional data analysis techniques. Principal Component Analysis (PCA) was chosen as a method of data exploration. The study was conducted on four plants controlled in Poland: Salvia divinorum, Mitragyna speciosa, Psychotria viridis and Calea zacatechichi. The compatibility of grouping features of selected species was compared in two variants: chemical and elemental composition. In a first variant, GC-MS chromatograms of extracts were analyzed and in the second, elements composition with the AAS and the ICP-MS techniques. The GC-MS method, based on the qualitative interpretation of results, allows for clear differentiation of samples with regard to their species affiliation. Even the plants belonging to the same family Rubiaceae, P. viridis and M. speciosa formed homogeneous and clearly separated clusters. Additionally, the cluster analysis was performed, as a method confirming sample grouping.

  13. Pharmacological profile of methylphenidate-based designer drugs.

    Science.gov (United States)

    Luethi, Dino; Kaeser, Philine J; Brandt, Simon D; Krähenbühl, Stephan; Hoener, Marius C; Liechti, Matthias E

    2017-08-18

    Methylphenidate-based designer drugs are new psychoactive substances (NPS) that are used outside medical settings and their pharmacology is largely unexplored. The aim of the present study was to characterize the pharmacology of methylphenidate-based substances in vitro. We determined the potencies of the methylphenidate-based NPS N-benzylethylphenidate, 3,4-dichloroethylphenidate, 3,4-dichloromethylphenidate, ethylnaphthidate, ethylphenidate, 4-fluoromethylphenidate, isopropylphenidate, 4-methylmethylphenidate, methylmorphenate, and propylphenidate and the potencies of the related compounds cocaine and modafinil with respect to norepinephrine, dopamine, and serotonin transporter inhibition in transporter-transfected human embryonic kidney 293 cells. We also investigated monoamine efflux and monoamine receptor and transporter binding affinities. Furthermore, we assessed the cell integrity under assay conditions. All methylphenidate-based substances inhibited the norepinephrine and dopamine transporters 4 to >1000-fold more potently than the serotonin transporter. Similar to methylphenidate and cocaine, methylphenidate-based NPS did not elicit transporter-mediated efflux of monoamines. Besides binding to monoamine transporters, several test drugs had affinity for adrenergic, serotonergic, and rat trace amine-associated receptors but not for dopaminergic or mouse trace amine-associated receptors. No cytotoxicity was observed after drug treatment at assay concentrations. Methylphenidate-based substances had pharmacological profiles similar to methylphenidate and cocaine. The predominant actions on dopamine transporters vs. serotonin transporters may be relevant when considering abuse liability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Alcohol and drugs in seriously injured drivers in six European countries

    DEFF Research Database (Denmark)

    Legrand, Sara-Ann; Isalberti, Cristina; Van der Linden, Trudy

    2013-01-01

    therapeutic. Cannabis (0.5–7.6%) was the most prevailing illicit drug. Alcohol was found in combination with drugs in 2.3-13.2% of the drivers. Drug combinations were found in 0.5–4.3% of the drivers. This study confirms the high prevalence of psychoactive substances in injured drivers, but we observed large...... differences between the participating countries. Alcohol was the most common finding, followed by cannabis and benzodiazepines. Notable are the many drivers having a BAC = 1.3 g/L. The majority of the substances were found in combination with another psychoactive substance, mostly alcohol. The high prevalence...

  15. New psychoactive substances (NPS) on cryptomarket fora: An exploratory study of characteristics of forum activity between NPS buyers and vendors.

    Science.gov (United States)

    Van Hout, Marie Claire; Hearne, Evelyn

    2017-02-01

    The continual diversification of new psychoactive substances (NPS) circumventing legislation creates a public health and law enforcement challenge, and one particularly challenged by availability on Hidden Web cryptomarkets. This is the first study of its kind which aimed to explore and characterise cryptomarket forum members' views and perspectives on NPS vendors and products within the context of Hidden Web community dynamics. An internal site search was conducted on two cryptomarkets popular with NPS vendors and hosting fora; Alphabay and Valhalla, using the search terms of 40 popular NPS in the seven categories of stimulant/cathinone; GABA activating; hallucinogen, dissociative, cannabinoid, opioid and other/unspecified/uncategorised NPS. 852 identified threads relating to the discussion of these NPS were generated. Following exclusion of duplicates, 138 threads remained. The Empirical Phenomenological Psychological method of data analysis was applied. Four themes and 32 categories emerged. 120 vendors selling NPS were visible on Alphabay, and 21 on Valhalla. Themes were 'NPS Cryptomarkets and Crypto-community interest in NPS'; 'Motives for NPS use'; 'Indigenous Crypto Community Harm Reduction'; and 'Cryptomarket Characteristics underpinning NPS trafficking', with two higher levels of abstraction centring on 'NPS vendor reputation' and 'NPS transactioning for personal use'. NPS cryptomarket characteristics centred on generation of trust, honesty and excellent service. Users appeared well informed, with harm reduction and vendor information exchange central to NPS market dynamics. GABA activating substances appeared most popular in terms of buyer interest on cryptomarkets. Interest in sourcing 'old favorite' stimulant and dissociative NPS was evident, alongside the sequential and concurrent poly use of NPS, and use of NPS with illicit drugs such as MDMA. Continued monitoring of new trends in NPS within Surface Web and cryptomarkets are warranted. A particular

  16. Polysubstance use profiles among electronic dance music party attendees in New York City and their relation to use of new psychoactive substances.

    Science.gov (United States)

    Fernández-Calderón, Fermín; Cleland, Charles M; Palamar, Joseph J

    2018-03-01

    Electronic Dance Music (EDM) party attendees are often polysubstance users and are at high risk for use of new psychoactive substances (NPS). We sought to identify patterns of use of common illegal drugs among EDM party attendees, sociodemographic correlates, and use of NPS as a function of patterns of use of more common drugs to inform prevention and harm reduction. Using time-space-sampling, 1045 individuals aged 18-40 were surveyed entering EDM parties in New York City. We queried past-year use of common illegal drugs and 98 NPS. We conducted latent class analysis to identify polysubstance use profiles of use of eight common drugs (i.e., ecstasy, ketamine, LSD, mushrooms, powder cocaine, marijuana, amphetamine, benzodiazepines). Relationships between drug classification membership and sociodemographics and use of drugs within six NPS categories were examined. We identified four profiles of use of common drugs: non-polysubstance use (61.1%), extensive polysubstance use (19.2%), moderate polysubstance use/stimulants (12.8%), and moderate polysubstance use/psychedelics (6.7%). Those in the moderate/psychedelic group were at higher odds of using NPS with psychedelic-type effects (2C, tryptamines, and other "new" psychedelics; Ps<0.05). Extensive polysubstance users were at increased odds of reporting use of 2C drugs, synthetic cathinones ("bath salts"), tryptamines, other new (non-phenethylamine) psychedelics, new dissociatives, and synthetic cannabinoids (Ps<0.05). NPS preference is linked to the profile of use of common drugs among individuals in the EDM scene. Most participants were identified as non-polysubstance users, but findings may help inform preventive and harm reduction interventions among those at risk in this scene. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Protein-Free Efavirenz Concentrations in Cerebrospinal Fluid and Blood Plasma Are Equivalent: Applying the Law of Mass Action To Predict Protein-Free Drug Concentration

    Science.gov (United States)

    Avery, L. B.; Sacktor, N.; McArthur, J. C.

    2013-01-01

    Efavirenz (EFV) is one of the most commonly prescribed antiretroviral drugs (ARVs) for the treatment of HIV. Highly protein-bound drugs, like EFV, have limited central nervous system (CNS) penetration when measured using total drug concentration gradients between blood plasma (BP) and cerebrospinal fluid (CSF). However, the more relevant pharmacologically active protein-free drug concentrations are rarely assessed directly in clinical studies. Using paired BP and CSF samples obtained from 13 subjects on an EFV-containing regimen, both the protein-free and total concentrations of EFV were determined. Despite a median (interquartile range [IQR]) total EFV BP/CSF concentration ratio of 134 (116 to 198), the protein-free EFV BP/CSF concentration ratio was 1.20 (0.97 to 2.12). EFV median (IQR) protein binding was 99.78% (99.74 to 99.80%) in BP and 76.19% (74.47 to 77.15%) in CSF. In addition, using the law of mass action and an in vitro-derived EFV-human serum albumin dissociation constant, we have demonstrated that the predicted median (IQR) protein-free concentration in BP, 4.59 ng/ml (4.02 to 9.44 ng/ml), compared well to that observed in BP, 4.77 ng/ml (3.68 to 6.75 ng/ml). Similar results were also observed in CSF and seminal plasma. This method provides a useful predictive tool for estimating protein binding in varied anatomic compartments. Our results of equivalent protein-free EFV concentrations in BP and CSF do not support prior concerns of the CNS as a pharmacological sanctuary from EFV. As CSF penetration of ARVs may increase our understanding of HIV-associated neurological dysfunction and antiretroviral effect, assessment of protein-free CSF concentrations of other highly protein-bound ARVs is warranted. PMID:23295919

  18. Effectiveness of brief interventions as part of the screening, brief intervention and referral to treatment (SBIRT model for reducing the non-medical use of psychoactive substances: a systematic review protocol

    Directory of Open Access Journals (Sweden)

    Young Matthew M

    2012-05-01

    Full Text Available Abstract Background There is a significant public health burden associated with substance use in Canada. The early detection and/or treatment of risky substance use has the potential to dramatically improve outcomes for those who experience harms from the non-medical use of psychoactive substances, particularly adolescents whose brains are still undergoing development. The Screening, Brief Intervention, and Referral to Treatment model is a comprehensive, integrated approach for the delivery of early intervention and treatment services for individuals experiencing substance use-related harms, as well as those who are at risk of experiencing such harm. Methods This article describes the protocol for a systematic review of the effectiveness of brief interventions as part of the Screening, Brief Intervention, and Referral to Treatment model for reducing the non-medical use of psychoactive substances. Studies will be selected in which brief interventions target non-medical psychoactive substance use (excluding alcohol, nicotine, or caffeine among those 12 years and older who are opportunistically screened and deemed at risk of harms related to psychoactive substance use. We will include one-on-one verbal interventions and exclude non-verbal brief interventions (for example, the provision of information such as a pamphlet or online interventions and group interventions. Primary, secondary and adverse outcomes of interest are prespecified. Randomized controlled trials will be included; non-randomized controlled trials, controlled before-after studies and interrupted time series designs will be considered in the absence of randomized controlled trials. We will search several bibliographic databases (for example, MEDLINE, EMBASE, CINAHL, PsycINFO, CORK and search sources for grey literature. We will meta-analyze studies where possible. We will conduct subgroup analyses, if possible, according to drug class and intervention setting. Discussion This

  19. Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.

    Science.gov (United States)

    Villain, Jonathan; Minguez, Laetitia; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2016-02-01

    The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water). Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Evidence for involvement of the astrocytic benzodiazepine receptor in the mechanism of action of convulsant and anticonvulsant drugs

    Energy Technology Data Exchange (ETDEWEB)

    Bender, A.S.; Hertz, L.

    1988-01-01

    The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit (/sup 3/H)diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel.

  1. Theophylline action on primary human bronchial epithelial cells under proinflammatory stimuli and steroidal drugs: a therapeutic rationale approach.

    Science.gov (United States)

    Gallelli, Luca; Falcone, Daniela; Cannataro, Roberto; Perri, Mariarita; Serra, Raffaele; Pelaia, Girolamo; Maselli, Rosario; Savino, Rocco; Spaziano, Giuseppe; D'Agostino, Bruno

    2017-01-01

    Theophylline is a natural compound present in tea. Because of its property to relax smooth muscle it is used in pharmacology for the treatment of airway diseases (ie, chronic obstructive pulmonary disease, asthma). However, this effect on smooth muscle is dose dependent and it is related to the development of side effects. Recently, an increasing body of evidence suggests that theophylline, at low concentrations, also has anti-inflammatory effects related to the activation of histone deacetylases. In this study, we evaluated the effects of theophylline alone and in combination with corticosteroids on human bronchial epithelial cells under inflammatory stimuli. Theophylline administrated alone was not able to reduce growth-stimulating signaling via extracellular signal-regulated kinases activation and matrix metalloproteases release, whereas it strongly counteracts this biochemical behavior when administered in the presence of corticosteroids. These data provide scientific evidence for supporting the rationale for the pharmacological use of theophylline and corticosteroid combined drug.

  2. Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers.

    Science.gov (United States)

    Riba, Jordi; Anderer, Peter; Morte, Adelaida; Urbano, Gloria; Jané, Francesc; Saletu, Bernd; Barbanoj, Manel J

    2002-06-01

    Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism, and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries. This tea contains measurable amounts of the psychotropic indole N,N-dimethyltryptamine (DMT), and beta-carboline alkaloids with MAO-inhibiting properties. In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self-assessment instruments. In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography (q-EEG), a noninvasive method measuring drug-induced variations in brain electrical activity. Two doses (one low and one high) of encapsulated freeze-dried ayahuasca, equivalent to 0.6 and 0.85 mg DMT kg(-1) body weight, were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial. Nineteen-lead recordings were undertaken from baseline to 8 h after administration. Subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Ayahuasca induced a pattern of psychoactive effects which resulted in significant dose-dependent increases in all subscales of the HRS, and in significant and dose-dependent modifications of brain electrical activity. Absolute power decreased in all frequency bands, most prominently in the theta band. Mean absolute power decreases (95% CI) at a representative lead (P3) 90 min after the high dose were -20.20+/-15.23 microV2 and -2.70+/-2.21 microV2 for total power and theta power, respectively. Relative power decreased in the delta (-1.20+/-1.31% after 120 min at P3) and theta (-3.30+/-2.59% after 120 min at P3) bands, and increased in the beta band, most prominently in the faster beta-3 (1.00+/-0.88% after 90 min at P3) and beta-4 (0

  3. New Evidence for the Mechanism of Action of a Type-2 Diabetes Drug Using a Magnetic Bead-Based Automated Biosensing Platform

    DEFF Research Database (Denmark)

    Uddin, Rokon; Nur-E-Habiba; Rena, Graham

    2017-01-01

    platform for investigating the MOA of metformin using a magnetic microbead-based agglutination assay which has allowed us to demonstrate for the first time the interaction between Cu and metformin at clinically relevant low micromolar concentrations of the drug, thus suggesting a potential pathway...... of metformin's blood-glucose lowering action. In this assay, cysteine-functionalized magnetic beadswere agglutinated in the presence of Cu due to cysteine's Cu-chelation property. Addition of clinically relevant doses of metformin resulted in disaggregation of Cu-bridged bead-clusters, whereas the effect......'s distinctive Cu-binding properties may be required for its effect on glucose homeostasis. The novel automated platform demonstrating this novel investigation thus holds the potential to be utilized for investigating significant and sensitive molecular interactions via magnetic bead-based agglutination assay....

  4. Risk of injury by driving with alcohol and other drugs

    DEFF Research Database (Denmark)

    Hels, Tove; Bernhoft, Inger Marie; Lyckegaard, Allan

    2011-01-01

    The objective of this deliverable is to assess the risk of driving with alcohol, illicit drugs and medicines in various European countries. In total nine countries participated in the study on relative risk of serious injury/fatality while positive for psychoactive substances. Six countries contr...

  5. Effects of Thyrotropin-Releasing Hormone (TRH) on the Actions of Pentobarbital and Other Centrally Acting Drugs1

    Science.gov (United States)

    Breese, George R.; Cott, Jerry M.; Cooper, Barrett R.; Prange, Arthur J.; Lipton, Morris A.; Plotnikoff, Nicholas P.

    2010-01-01

    Thyrotropin-releasing hormone (TRH) was found to antagonize pentobarbital-induced sleeping time and hypothermia. While 3 to 100 mg/kg of TRH reduced pentobarbital sleeping time when administered prior to the barbiturate, a dose-response relationship to TRH could not be established. However, doses of 10 to 100 mg/kg of TRH enhanced the lethality of pentobarbital when these compounds were administered simultaneously. Thyrotropin or l-triiodothyronine did not imitate and hypophysectomy did not reduce the effects of TRH, indicating that the pituitary is not essential for its antagonism of pentobarbital Studies of TRH analogs provided further support of this view In addition TRH reduced the sleep and hypothermia produced by thiopental amobarbital, seco-barbital and phenobarbital, and it antagonized the hypothermia and reduced motor activity produced by chloral hydrate, reserpine, chlorpromazine and diazepam Intracisternally administered TRH also reduced pentobarbital sleeping time and hypothermia but melanocyte-stimulating hormone release-inhibiting factor and somatostatin administered by this route did not While reduction of pentobarbital sleeping time by TRH could not be attributed to an affect on monoamine systems or to deamidated TRH, this action was reduced by intracisternally administered atropine suggesting that cholinergic mechanisms may contribute to the effects of TRH. Thus the results provide evidence that TRH acts on brain independent of an effect on the pituitary. PMID:805836

  6. ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.

    Science.gov (United States)

    Mahoney, Emilia; Lucas, David M; Gupta, Sneha V; Wagner, Amy J; Herman, Sarah E M; Smith, Lisa L; Yeh, Yuh-Ying; Andritsos, Leslie; Jones, Jeffrey A; Flynn, Joseph M; Blum, Kristie A; Zhang, Xiaoli; Lehman, Amy; Kong, Hui; Gurcan, Metin; Grever, Michael R; Johnson, Amy J; Byrd, John C

    2012-08-09

    Cyclin dependent kinase (CDK) inhibitors, such as flavopiridol, demonstrate significant single-agent activity in chronic lymphocytic leukemia (CLL), but the mechanism of action in these nonproliferating cells is unclear. Here we demonstrate that CLL cells undergo autophagy after treatment with therapeutic agents, including fludarabine, CAL-101, and flavopiridol as well as the endoplasmic reticulum (ER) stress-inducing agent thapsigargin. The addition of chloroquine or siRNA against autophagy components enhanced the cytotoxic effects of flavopiridol and thapsigargin, but not the other agents. Similar to thapsigargin, flavopiridol robustly induces a distinct pattern of ER stress in CLL cells that contributes to cell death through IRE1-mediated activation of ASK1 and possibly downstream caspases. Both autophagy and ER stress were documented in tumor cells from CLL patients receiving flavopiridol. Thus, CLL cells undergo autophagy after multiple stimuli, including therapeutic agents, but only with ER stress mediators and CDK inhibitors is autophagy a mechanism of resistance to cell death. These findings collectively demonstrate, for the first time, a novel mechanism of action (ER stress) and drug resistance (autophagy) for CDK inhibitors, such as flavopiridol in CLL, and provide avenues for new therapeutic combination approaches in this disease.

  7. Apoptosis induction by the dual-action DNA- and protein-reactive antitumor drug irofulven is largely Bcl-2-independent.

    Science.gov (United States)

    Herzig, Maryanne C S; Trevino, Alex V; Liang, Huiyun; Salinas, Richard; Waters, Stephen J; MacDonald, John R; Woynarowska, Barbara A; Woynarowski, Jan M

    2003-02-15

    The overexpression of Bcl-2 is implicated in the resistance of cancer cells to apoptosis. This study explored the potential of irofulven (hydroxymethylacylfulvene, HMAF, MGI 114, NSC 683863), a novel DNA- and protein-reactive anticancer drug, to overcome the anti-apoptotic properties of Bcl-2 in HeLa cells with controlled Bcl-2 overexpression. Irofulven treatment resulted in rapid (12hr) dissipation of the mitochondrial membrane potential, phosphatidylserine externalization, and apoptotic DNA fragmentation, with progressive changes after 24hr. Bcl-2 overexpression caused marginal or partial inhibition of these effects after treatment times ranging from 12 to 48hr. Both Bcl-2-dependent and -independent responses to irofulven were abrogated by a broad-spectrum caspase inhibitor. Despite the somewhat decreased apoptotic indices, cell growth inhibition by irofulven was unaffected by Bcl-2 status. In comparison, Bcl-2 overexpression drastically reduced apoptotic DNA fragmentation by etoposide, acting via topoisomerase II-mediated DNA damage, but had no effect on apoptotic DNA fragmentation by helenalin A, which reacts with proteins but not DNA. Irofulven retains its pro-apoptotic and growth inhibitory potential in cell lines that have naturally high Bcl-2 expression. Collectively, the results implicate multiple mechanisms of apoptosis induction by irofulven, which may differ in time course and Bcl-2 dependence. It is possible that the sustained ability of irofulven to induce profound apoptosis and to block cell growth despite Bcl-2 overexpression may be related to its dual reactivity with both DNA and proteins.

  8. Tobacco regulatory science: research to inform regulatory action at the Food and Drug Administration's Center for Tobacco Products.

    Science.gov (United States)

    Ashley, David L; Backinger, Cathy L; van Bemmel, Dana M; Neveleff, Deborah J

    2014-08-01

    The U.S. Food and Drug Administration (FDA) promotes the development of regulatory science to ensure that a strong evidence base informs all of its regulatory activities related to the manufacture, marketing, and distribution of tobacco products as well as public education about tobacco product constituents and effects. Toward that end, the FDA's Center for Tobacco Products (CTP) provides funding for research studies with scientific aims that fall within its defined regulatory authority. However, given their traditional biomedical focus on basic and applied research, some researchers may not understand the principles of regulatory science or the types of studies CTP funds. The purpose of this paper is (1) to clarify the definition of regulatory science as a distinct scientific discipline, (2) to explore the role of tobacco regulatory science in order to help researchers understand the parameters and types of research that can be funded by CTP, and (3) to describe the types of research efforts that will inform the FDA's public health framework for tobacco product regulation. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  9. Psychometric properties of the Internalized Stigma of Mental Illness scale adapted for people who use psychoactive substances.

    Science.gov (United States)

    Gallo, Verónica Del Valle; Burrone, María Soledad; Fernandez, Alicia Ruth; Boyd, Jennifer E; Abeldaño, Roberto Ariel

    2017-01-01

    People who consume psychoactive substances may experience situations of social stigma on the part of the society in general, and also situations of internalized-stigma derived from their own consumption of substances. The Internalized Stigma of Mental Illness (ISMI) scale has been shown to be valid and reliable to evaluate the internalized-stigma in people with severe mental disorders, but in Argentina there is no a Spanish version of this scale for use with people who use psychoactive substances. The objective of this work was to evaluate the psychometric properties of the Spanish version of the Internalized Stigma of Mental Illness instrument adapted for people who use psychoactive substances. The work was carried out on a sample of 200 patients older than 18 years under treatment of rehabilitation by consumption of psychoactive substances in a public institution of the city of Córdoba (Argentina) between the years 2014 and 2016. The instrument used was the Internalized Stigma of Mental Illness (ISMI) previously adapted for use in these groups of patients. It was determined the reliability of the scale through Cronbach's coefficients α and factorial structure was analyzed through an exploratory factor analysis. The obtained coefficients showed a high reliability, while in the factorial structure emerged the 4 theoretical dimensions described by Ritsher, namely: social isolation, perceived discrimination, alienation and stereotyping. It is concluded that the scale adapted for people who use psychoactive substances is reliable and with an adequate factorial structure.

  10. Psychoactive medications and disengagement from office based opioid treatment (obot) with buprenorphine.

    Science.gov (United States)

    Weinstein, Zoe M; Cheng, Debbie M; Quinn, Emily; Hui, David; Kim, Hyunjoong; Gryczynski, Gabriela; Samet, Jeffrey H

    2017-01-01

    The prevalence of psychoactive medications (PAMs) use in patients enrolled in Office Based Opioid Treatment (OBOT) and its association with engagement in this care is largely unknown. To describe the use of PAMs, including those medications with emerging evidence of misuse ("emerging PAMs" - gabapentin, clonidine and promethazine) among patients on buprenorphine, and its association with disengagement from OBOT. This is a retrospective cohort study of adults on buprenorphine from January 2002 to February 2014. The association between use of PAMs and 6-month disengagement from OBOT was examined using multivariable logistic regression models. A secondary analysis exploring time-to-disengagement was conducted using Cox regression models. At OBOT entry, 43% of patients (562/1308) were prescribed any PAM; including 17% (223/1308) on an emerging PAM. In separate adjusted analyses, neither the presence of any PAM (adjusted odds ratio [AOR] 1.07, 95% CI [0.78, 1.46]) nor an emerging PAM (AOR 1.28 [0.95, 1.74]) was significantly associated with 6-month disengagement. The results were similar for the Cox model (any PAM (adjusted hazard ratio [AHR] 1.16, 95% CI [1.00, 1.36]), emerging PAM (AHR 1.18 [0.98, 1.41])). Exploratory analyses suggested gabapentin (AHR 1.30 [1.05-1.62]) and clonidine (AHR 1.33 [1.01-1.73]) specifically, may be associated with an overall shorter time to disengagement. Psychoactive medication use is common among patients in buprenorphine treatment. No significant association was found between the presence of any psychoactive medications, including medications with emerging evidence of misuse, and 6-month disengagement from buprenorphine treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Psychoactive plants described in a Brazilian literary work and their chemical compounds.

    Science.gov (United States)

    Otsuka, Rafaela Denise; Lago, João Henrique Ghilardi; Rossi, Lucia; Galduróz, José Carlos Fernandes; Rodrigues, Eliana

    2010-09-01

    Ethnopharmacological research investigates the plants and other medicinal and toxic substances utilized by different traditional populations. One approach in this field is a literature search of the available publications on medicinal plants. The purpose of the current study was to select plants with psychoactive effects described in a Brazilian literary work written by Pio Correa in 1926. Those mentioned plants were classified in accordance with their indications for use as stimulants and depressors of the central nervous system. For the phytochemical study herein, we researched these species via a database search, and all the obtained information was compiled into a new database to analyze possible correlations between the chemical compounds and the psychoactive categories. Of the 813 plants searched in the literary work, 104 presented chemical data in the scientific periodicals consulted. Seventy-five of them belong to the stimulant category, while 31 are depressors and two of them belong to both categories. Phenols and flavonoids were the main compounds observed in plants of both categories, though at different frequencies. Monoterpenes (29.9%) and sesquiterpenes (28.6%) were also observed in plants from the stimulant category, while 25.8% of plants from the depressor category were comprised of carotenoids and 22.6% of steroids. The main specific compounds were identified as ferulic acid, α-pinene, limonene, α-humulene and kaempferol among the stimulant plants. Otherwise, in depressor plants were characterized caffeic acid, kaempferol, quercetin, β-carotene, physalins and withanolides as specific compounds. The association between ethnopharmacological and chemotaxonomic data, as presented in this study, could support plant selection in further investigations by research groups whose studies focus on psychoactive plants as potential therapeutics.

  12. Poly(ADP-ribose) polymerase, a potential target for drugs: Cellular regulatory role of the polymer and the polymerase protein mediated by catalytic and macromolecular colligative actions (Review).

    Science.gov (United States)

    Kun

    1998-08-01

    The cellular coenzymatic role of NAD, being a pleiotropic cofactor for diverse cellular reactions, is extended to poly(ADP-ribose) and to the highly abundant nuclear protein, poly(ADP-ribose) polymerase, with special focus on the pharmacological action of ligands on the latter. The polymer is defined to possess a helical configuration. From direct analyses of the polymer under physiological conditions, it is concluded that the polymerase is dormant in normal tissues, but is activated under certain pathological conditions: malignancy, retroviral integrate containing cells, and in a variety of inflammatory states. The interaction of poly(ADP-ribose) polymerase ligands with the DNA component of the active poly (ADP-ribose) polymerase - DNA complex is shown. A major cellular function of the poly(ADP-ribose) polymerase protein is its binding capacity to a large number of nuclear proteins and DNA sites, an effect which is induced by drugs that inhibit the polymerase activity. The malignancy-reverting effect of poly(ADP-ribose) polymerase ligand drugs is illustrated in chemically and oncovirally transformed cancer cells. The poly(ADP-ribose) polymerase ligand-induced cessation of HIV replication is analyzed. Peroxynitrite-induced DNA damage-initiated pathological responses are shown to be inhibited by a specific poly(ADP-ribose) polymerase ligand. The irreversibly acting C-NO drugs oxidize asymmetric zinc fingers [poly(ADP-ribose) polymerase, HIV gag-precursor protein] and act as anti-cancer and anti-HIV agents, an effect that is regulated by cellular concentration of GSH.

  13. Subtype-specific promoter-driven action potential imaging for precise disease modelling and drug testing in hiPSC-derived cardiomyocytes

    Science.gov (United States)

    Chen, Zhifen; Xian, Wenying; Bellin, Milena; Dorn, Tatjana; Tian, Qinghai; Goedel, Alexander; Dreizehnter, Lisa; Schneider, Christine M.; Ward-van Oostwaard, Dorien; Ng, Judy King Man; Hinkel, Rabea; Pane, Luna Simona; Mummery, Christine L.; Lipp, Peter

    2017-01-01

    Aims Cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) are increasingly used in disease modelling and drug evaluation. However, they are typically a heterogeneous mix of ventricular-, atrial-, and nodal-like cells based on action potentials (APs) and gene expression. This heterogeneity and the paucity of methods for high-throughput functional phenotyping hinder the full exploitation of their potential. We aimed at developing a method for rapid, sequential, and subtype-specific phenotyping of hiPSC-CMs with respect to AP morphology and single-cell arrhythmias. Methods and results We used cardiac lineage-specific promoters to drive the expression of a voltage-sensitive fluorescent protein (VSFP-CR) in hiPSC-CMs, enabling subtype-specific optical AP recordings. In a patient-specific hiPSC model of long-QT syndrome type 1, AP prolongation and frequent early afterdepolarizations were evident in mutant ventricular- and atrial like, but not in nodal-like hiPSC-CMs compared with their isogenic controls, consistent with the selective expression of the disease-causing gene. Furthermore, we demonstrate the feasibility of sequentially probing a cell over several days to investigate genetic rescue of the disease phenotype and to discern CM subtype-specific drug effects. Conclusion By combining a genetically encoded membrane voltage sensor with promoters that drive its expression in the major subtypes of hiPSC-CMs, we developed a convenient system for disease modelling and drug evaluation in the relevant cell type, which has the potential to advance the emerging utility of hiPSCs in cardiovascular medicine. PMID:28182242

  14. New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG).

    Science.gov (United States)

    Ocio, E M; Richardson, P G; Rajkumar, S V; Palumbo, A; Mateos, M V; Orlowski, R; Kumar, S; Usmani, S; Roodman, D; Niesvizky, R; Einsele, H; Anderson, K C; Dimopoulos, M A; Avet-Loiseau, H; Mellqvist, U-H; Turesson, I; Merlini, G; Schots, R; McCarthy, P; Bergsagel, L; Chim, C S; Lahuerta, J J; Shah, J; Reiman, A; Mikhael, J; Zweegman, S; Lonial, S; Comenzo, R; Chng, W J; Moreau, P; Sonneveld, P; Ludwig, H; Durie, B G M; Miguel, J F S

    2014-03-01

    Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data from already approved and active agents (including second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents and alkylators). Next, we focus on agents with novel mechanisms of action, such as monoclonal antibodies (MoAbs), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Among this plethora of new agents or mechanisms, some are specially promising: anti-CD38 MoAb, such as daratumumab, are the first antibodies with clinical activity as single agents in MM. Moreover, the kinesin spindle protein inhibitor Arry-520 is effective in monotherapy as well as in combination with dexamethasone in heavily pretreated patients. Immunotherapy against MM is also being explored, and probably the most attractive example of this approach is the combination of the anti-CS1 MoAb elotuzumab with lenalidomide and dexamethasone, which has produced exciting results in the relapsed/refractory setting.

  15. Presynaptic and postsynaptic regulation of muscle contractions in the ascarid nematode Ascaris suum: a target for drug action.

    Science.gov (United States)

    Trailović, S M; Zurovac, Z; Gruborović, S; Marjanović, D S; Nedeljković-Trailović, J

    2016-11-01

    The aim of this study was to determine the role in contractions of postsynaptic nicotinic acetylcholine (nACh) and γ-aminobutyric acid (GABA) receptors, in the bag region of Ascaris suum muscle cells, as well as the role of synaptic receptors between interneurons and motor neurons in the dorsal and ventral nerve cord. We have measured the isometric contractions of isolated segments of A. suum, with or without the nerve cord (dorsal or ventral). Contractions were caused by increasing concentrations of ACh or by electrical field stimulation (EFS). Based on our results, the presence of the nerve cord is essential for the contractile effects of ACh. The EC50 value of ACh for innervated muscle strips was 10.88 μm. Unlike intact (innervated) preparations, there was no contraction of the muscle flaps when the nerve cord was mechanically removed. Furthermore, continuous EFS produced stable contractions of innervated muscle strips, but they are not sensitive to mecamylamine (100 μm). However, GABA (30 μm) significantly inhibited the EFS-induced contractions. EFS with the same characteristics did not cause muscle contractions of denervated muscle strips, but EFS with a wider pulse induced the increasing of tone and irregular contractions. These contractions were completely insensitive to the effect of GABA. The EC50 for ACh did not differ between the dorsal and ventral segments (9.83 μm and 9.45 μm), while GABA exhibited features of competitive and non-competitive antagonists, regardless of whether it acted on the dorsal or ventral segments of A. suum. It is obvious that drugs will be more effective if they act on both the synaptic and extrasynaptic nACh and GABA receptors.

  16. Monitoring drug markets in the Internet age and the evolution of drug monitoring systems in Australia.

    Science.gov (United States)

    Burns, Lucy; Roxburgh, Amanda; Bruno, Raimondo; Van Buskirk, Joe

    2014-01-01

    In Australia, drug monitoring systems have been in place for more than a decade allowing for the measurement of ongoing trends in drug use and the detection of new drugs. The Drug Trends Unit at the National Drug and Alcohol Research Centre monitors drugs through four separate systems. The Illicit Drug Reporting System (IDRS) measures the price, purity, and availability of drugs that are primarily injected. The Ecstasy and Related Drugs Reporting System (EDRS) monitors psychostimulants that are used recreationally. The National Illicit Drugs Indicator Project (NIDIP) analyzes indicator data including drug-related hospitalizations and deaths. Finally, the Drugs and Emerging Technologies Project (DNeT) analyzes the role of the Internet in the procurement and use of novel psychoactive substances. This paper provides an overview of each component of the system, demonstrating how the system has evolved over time. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Young drug addicts and the drug scene.

    Science.gov (United States)

    Lucchini, R

    1985-01-01

    The drug scene generally comprises the following four distinct categories of young people: neophytes, addicts who enjoy a high status vis-à-vis other addicts, multiple drug addicts, and non-addicted drug dealers. It has its own evolution, hierarchy, structure and criteria of success and failure. The members are required to conform to the established criteria. The integration of the young addict into the drug scene is not voluntary in the real sense of the word, for he is caught between the culture that he rejects and the pseudo-culture of the drug scene. To be accepted into the drug scene, the neophyte must furnish proof of his reliability, which often includes certain forms of criminal activities. The addict who has achieved a position of importance in the drug world serves as a role model for behaviour to the neophyte. In a more advanced phase of addiction, the personality of the addict and the social functions of the drug scene are overwhelmed by the psychoactive effects of the drug, and this process results in the social withdrawal of the addict. The life-style of addicts and the subculture they develop are largely influenced by the type of drug consumed. For example, it is possible to speak of a heroin subculture and a cocaine subculture. In time, every drug scene deteriorates so that it becomes fragmented into small groups, which is often caused by legal interventions or a massive influx of new addicts. The fragmentation of the drug scene is followed by an increase in multiple drug abuse, which often aggravates the medical and social problems of drug addicts.

  18. Mechanism of action of antiplatelet drugs on decompression sickness in rats: a protective effect of anti-GPIIbIIIa therapy.

    Science.gov (United States)

    Lambrechts, Kate; Pontier, Jean-Michel; Mazur, Aleksandra; Theron, Michaël; Buzzacott, Peter; Wang, Qiong; Belhomme, Marc; Guerrero, François

    2015-05-15

    Literature highlights the involvement of disseminated thrombosis in the pathophysiology of decompression sickness (DCS). We examined the effect of several antithrombotic treatments targeting various pathways on DCS outcome: acetyl salicylate, prasugrel, abciximab, and enoxaparin. Rats were randomly assigned to six groups. Groups 1 and 2 were a control nondiving group (C; n = 10) and a control diving group (CD; n = 30). Animals in Groups 3 to 6 were treated before hyperbaric exposure (HBE) with either prasugrel (n = 10), acetyl salicylate (n = 10), enoxaparin (n = 10), or abciximab (n = 10). Blood samples were taken for platelet factor 4 (PF4), thiobarbituric acid reactive substances (TBARS), and von Willebrand factor analysis. Onset of DCS symptoms and death were recorded during a 60-min observation period after HBE. Although we observed fewer outcomes of DCS in all treated groups compared with the CD, statistical significance was reached in abciximab only (20% vs. 73%, respectively, P = 0.007). We also observed significantly higher levels of plasmatic PF4 in abciximab (8.14 ± 1.40 ng/ml; P = 0.004) and enoxaparin groups (8.01 ± 0.80 ng/ml; P = 0.021) compared with the C group (6.45 ± 1.90 ng/ml) but not CD group (8.14 ± 1.40 ng/ml). Plasmatic levels of TBARS were significantly higher in the CD group than the C group (49.04 ± 11.20 μM vs. 34.44 ± 5.70 μM, P = 0.002). This effect was prevented by all treatments. Our results suggest that abciximab pretreatment, a powerful glycoprotein IIb/IIIa receptor antagonist, has a strong protective effect on decompression risk by significantly improving DCS outcome. Besides its powerful inhibitory action on platelet aggregation, we suggest that abciximab could also act through its effects on vascular function, oxidative stress, and/or inflammation. Copyright © 2015 the American Physiological Society.

  19. A quick method for determination of psychoactive agents in serum and hair by using capillary electrophoresis and mass spectrometry.

    Science.gov (United States)

    Woźniakiewicz, Aneta; Wietecha-Posłuszny, Renata; Woźniakiewicz, Michał; Bryczek, Ewelina; Kościelniak, Paweł

    2015-01-01

    The aim of the research was to develop a new sensitive method for simultaneously the determination of psychoactive drugs: 1-benzylpiperazine, 7-aminoclonazepam, alprazolam, clonazepam, diazepam, estazolam, lorazepam and tetrazepam in human serum and hair samples. In the preparation step, microwave-assisted extraction (MAE) was used. Extracts were analyzed by means of capillary electrophoresis with mass spectrometry time-of-flight detection (CE-TOF-MS). In the validation study of the MAE/CE-TOF-MS analytical method, three concentration levels of analytes (10, 100 and 250 ng/mL for serum and 0.2, 2.2 and 5.6 ng/mL for hair) were taken into account. Such parameters as limit of detection (0.4-1.2 ng/mL for serum, 6.0-23.0 pg/mg for hair), limit of quantification (1.3-4.1 ng/mL for serum, 20.0-77.0 pg/mg for hair), precision (3.0-11.3% for serum, 2.4-14.2% for hair), accuracy of the assay (RE) (-8.0 to 12.0% for serum, -8.0 to 11.0% for hair), recovery (88.6-113.4% for serum, 86.1-107.4% for hair) and matrix effects (87.9-110.7% for serum, 85.1-108.4% for hair) were calculated for the studied compounds. Then, the MAE/CE-TOF-MS method was successfully applied to the analysis of hair samples taken from patients treated with benzodiazepines. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Medical complications of psychoactive substances with abuse risks: Detection and assessment by the network of French addictovigilance centres.

    Science.gov (United States)

    Peyrière, Hélène; Eiden, Céline; Mallaret, Michel; Victorri-Vigneau, Caroline

    2016-12-01

    The use of psychoactive substances, whether occasional or regular, can induce a large number of clinical and/or biological complications. These complications may be related to the effects of the active substance itself and/or adulterants, but also to the modalities for use (administrations route, contexts of use). The detection and evaluation of these potentially severe complications are a public health issue. Beyond the assessment of the potential for abuse of and dependence on psychoactive substances, the collection and evaluation of complications related to the use of the substances are one of the roles of addictovigilance centres. In this article, the expertise of the French addictovigilance centres in the detection and assessment of medical complications related to psychoactive substances, adulterants or route of administration of substances is advanced through a few recent examples. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  1. [Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges].

    Science.gov (United States)

    Majić, Tomislav; Jungaberle, Henrik; Schmidt, Timo T; Zeuch, Andrea; Hermle, Leo; Gallinat, Jürgen

    2017-07-01

    Background Recently, scientific interest in the therapeutic potential of serotonergic and psilocybin hallucinogens (psychedelics) such as lysergic acid diethylamide (LSD) and entactogens like 3,4-methylendioxymethamphetamine (MDMA) within the framework of psychotherapy has resumed. The present article provides an overview on the current evidence on substance-assisted psychotherapy with these substances. Method A selective search was carried out in the PubMed and Cochrane Library including studies investigating the clinical use of serotonergic psychoactive substances since 2000. Results Studies were found investigating the following indications: alcohol (LSD and psilocybin) and tobacco addiction (psilocybin), anxiety and depression in patients suffering from life-threatening somatic illness (LSD and psilocybin), obsessive-compulsive disorder (OCD) (psilocybin), treatment-resistant major depression (psilocybin), and posttraumatic stress disorder (PTSD) (MDMA). Discussion Substance use disorders, PTSD and anxiety and depression in patients suffering from life-threatening somatic illness belong to the indications with the best evidence for substance-assisted psychotherapy with serotonergic psychoactive agents. To date, studies indicate efficacy and relatively good tolerability. Further studies are needed to determine whether these substances may represent suitable and effective treatment options for some treatment-resistant psychiatric disorders in the future. © Georg Thieme Verlag KG Stuttgart · New York.

  2. [Self-Reported consumption of illegal psychoactive substances in a street inhabitant population from Cali, Colombia].

    Science.gov (United States)

    Hernández-Carrillo, Mauricio; Álvarez-Claros, Katherine E; Osorio-Sabogal, Iván Alberto

    2015-04-01

    Objective To determine the prevalence of self-reported use of illegal psychoactive substances in a homeless population of the city of Cali. Method Descriptive study of prevalence of period. The target population was 763 homeless people registered during 2010 in the database provided by a temporary shelter facility in the city of Cali. Statistical analysis was performed using R version 3.2.0. Research safe according to the resolution 8430 of 1993. Results 76.9 % of the homeless population recognizes that they consume some type of illegal psychoactive substance (IPAS). The substances with a higher prevalence of use in this population were: marijuana (51.2 %), the crack cocaine (44.6 %) and cocaine (11.3 %). 28.6 % of homeless people were found to consume IPAS more than three times a day and that the main route of administration is smoke (54.7 %). 50% of respondents reported having been hospitalized at some time in a rehabilitation center. Discussion The results in this study show that the problem of PASI consumption significantly affects the population of homeless people, with marijuana and crack cocaine being the most commonly used, which is a complex situation if the easy access of these substances and the severe physical and mental degenerative effects the cause in those who consume them are taken into account. Therefore it is necessary to support initiatives aimed at intervening in this social phenomenon.

  3. Reappraisal of the clinical pharmacology of low-dose aspirin by comparing novel direct and traditional indirect biomarkers of drug action.

    Science.gov (United States)

    Patrignani, P; Tacconelli, S; Piazuelo, E; Di Francesco, L; Dovizio, M; Sostres, C; Marcantoni, E; Guillem-Llobat, P; Del Boccio, P; Zucchelli, M; Patrono, C; Lanas, A

    2014-08-01

    Even though the acetylation of platelet cyclooxygenase (COX)-1 at serine-529 is the direct mechanism of action of low-dose aspirin, its antiplatelet effect has been characterized using indirect indexes of COX-1 activity. We performed a clinical study with enteric-coated low-dose aspirin (EC-aspirin), in healthy subjects, to evaluate the effects on the extent and duration of platelet COX-1 acetylation, using a novel proteomic strategy for absolute protein quantification (termed AQUA), as compared with traditional pharmacokinetic and pharmacodynamic parameters. In a phase I, single-arm, open-label study of EC aspirin (100 mg day(-1) ) administered to 24 healthy subjects, we compared, over a 24 h-period on day 1 and 7, % platelet acetylated COX-1 (AceCOX-1) with traditional pharmacokinetic and pharmacodynamics [i.e. serum thromboxane (TX) B2 , platelet function by monitoring CEPI(collagen/epinephrine) closure time (CT) using whole-blood PFA-100 and urinary excretion of 11-dehydro-TXB2 ] parameters. Acetylation of platelet COX-1 was measurable before detection of aspirin levels in the systemic circulation and increased in a cumulative fashion upon repeated dosing. After the last dose of EC-aspirin, %AceCOX-1, serum TXB2 and CEPI-CT values were maximally and persistently modified throughout 24 h; they averaged 76 ± 2%, 99.0 ± 0.4% and 271 ± 5 s, respectively. EC-aspirin caused 75% reduction in urinary 11-dehydro-TXB2 excretion. After chronic dosing with aspirin, the pharmacokinetics of acetylsalicylic acid was completely dissociated from pharmacodynamics. The demonstrated feasibility of quantifying the extent and duration of platelet COX-1 acetylation will allow characterizing the genetic, pharmacokinetic and pharmacodynamic determinants of the inter-individual variability in the antiplatelet response to low-dose aspirin as well as identifying extra-platelet sites of drug action. © 2014 International Society on Thrombosis and Haemostasis.

  4. ViscumTT induces apoptosis and alters IAP expression in osteosarcoma in vitro and has synergistic action when combined with different chemotherapeutic drugs.

    Science.gov (United States)

    Kleinsimon, Susann; Kauczor, Gwenda; Jaeger, Sebastian; Eggert, Angelika; Seifert, Georg; Delebinski, Catharina

    2017-01-07

    Osteosarcoma is the most common bone tumor and is associated with a poor prognosis. Conventional therapies, surgery and chemotherapy, are still the standard but soon reach their limits. New therapeutic approaches are therefore needed. Conventional aqueous mistletoe extracts from the European mistletoe (Viscum album L.) are used in complementary cancer treatment. These commercial extracts are water-based and do not include water-insoluble compounds such as triterpenic acids. However, both hydrophilic and hydrophobic triterpenic acids possess anti-cancer properties. In this study, a whole mistletoe extract viscumTT re-created by combining an aqueous extract (viscum) and a triterpene extract (TT) was tested for its anti-cancer potential in osteosarcoma. Two osteosarcoma cell lines were treated with three different mistletoe extracts viscum, TT and viscumTT to compare their apoptotic potential. For this purpose, annexin/PI staining and caspase-3, -8 and -9 activity were investigated by flow cytometry. To determine the mechanism of action, alterations in expression of inhibitors of apoptosis (IAPs) were detected by western blot. Apoptosis induction by co-treatment of viscum, TT and viscumTT with doxorubicin, etoposide and ifosfamide was examined by flow cytometry. In vitro as well as ex vivo, the whole mistletoe extract viscumTT led to strong inhibition of proliferation and synergistic apoptosis induction in osteosarcoma cells. In the investigations of mechanism of action, inhibitors of apoptosis such as XIAP, BIRC5 and CLSPN showed a clear down-regulation after viscumTT treatment. In addition, co-treatment with doxorubicin, etoposide and ifosfamide further enhanced apoptosis induction, also synergistically. ViscumTT treatment results in synergistic apoptosis induction in osteosarcoma cells in vitro and ex vivo. Additionally, conventional standard chemotherapeutic drugs such as doxorubicin, etoposide and ifosfamide were able to dramatically enhance apoptosis induction

  5. DRUGS – “WAY” OF LIFE

    OpenAIRE

    Anna Nowacka; Zofia Olszowy; Małgorzata Kapala; Edmund Anczyk; Łukasz Miśkiewicz

    2010-01-01

    This article refers to the phenomenon of an increasing number of people abusing drugs in the 20th century. In addition to the natural types of narcotics there are many other semi-synthetic and fully synthetic substances made available to the market by chemical and pharmaceutical industries. The use of narcotics and psychoactive substances usually causes adverse and often irreversible health effects. In Department of Laboratory Diagnostics of the Institute of Occupat...

  6. The frequency of drugs in randomly selected drivers in Denmark

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Steentoft, Anni; Hels, Tove

    Introduction Driving under the influence of alcohol and drugs is a global problem. In Denmark as well as in other countries there is an increasing focus on impaired driving. Little is known about the occurrence of psychoactive drugs in the general traffic. Therefore the European commission...... initiated the DRUID project. This roadside study is the Danish part of the EU-project DRUID (Driving under the Influence of Drugs, Alcohol, and Medicines) and included three representative regions in Denmark. Methods Oral fluid samples (n = 3002) were collected randomly from drivers using a sampling scheme...... stratified by time, season, and road type. The oral fluid samples were screened for 29 illegal and legal psychoactive substances and metabolites as well as ethanol. Results Fourteen (0.5%) drivers were positive for ethanol (alone or in combination with drugs) at concentrations above 0.53 g/l, which...

  7. HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions

    Directory of Open Access Journals (Sweden)

    Francesca Esposito

    2012-01-01

    Full Text Available During the retrotranscription process, characteristic of all retroviruses, the viral ssRNA genome is converted into integration-competent dsDNA. This process is accomplished by the virus-coded reverse transcriptase (RT protein, which is a primary target in the current treatments for HIV-1 infection. In particular, in the approved therapeutic regimens two classes of drugs target RT, namely, nucleoside RT inhibitors (NRTIs and nonnucleoside RT inhibitors (NNRTIs. Both classes inhibit the RT-associated polymerase activity: the NRTIs compete with the natural dNTP substrate and act as chain terminators, while the NNRTIs bind to an allosteric pocket and inhibit polymerization noncompetitively. In addition to these two classes, other RT inhibitors (RTIs that target RT by distinct mechanisms have been identified and are currently under development. These include translocation-defective RTIs, delayed chain terminators RTIs, lethal mutagenesis RTIs, dinucleotide tetraphosphates, nucleotide-competing RTIs, pyrophosphate analogs, RT-associated RNase H function inhibitors, and dual activities inhibitors. This paper describes the HIV-1 RT function and molecular structure, illustrates the currently approved RTIs, and focuses on the mechanisms of action of the newer classes of RTIs.

  8. Use of psychoactive substances in prison: Results of a study in the Lyon-Corbas prison, France.

    Science.gov (United States)

    Sahajian, F; Berger-Vergiat, A; Pot, E

    2017-09-01

    In prison, in 2012, according to various sources, from 4 to 56% of the European inmate population used psychoactive substances (PAS). The aim of our study was to describe PAS consumption during incarceration in the prison of Lyon-Corbas, France. A transversal descriptive study was conducted between September 23rd and September 27th 2013 among all inmates of this prison. We used an anonymous self-administered questionnaire, distributed at lunchtime and collected, the same day, at dinnertime, by the mental health service personnel. Among 785 inmates present at the time of the study in the prison of Lyon-Corbas, 710 were included and the response rate was 64.4% (95% CI [60.8-67.8]). Among 457 responding inmates, 16.4% (95% CI [13.2-20.0]) reported no PAS consumption. Among 382 consumers, 74.4% (95% CI [69.8-78.5]) used tobacco, 36.8% (95% CI [32.2-41.8]) cannabis, 30.4% (95% CI [25.9-35.1]) alcohol, 7.7% (95% CI [5.2-10.6]) heroin and 10.3% (95% CI [7.5-13.6]) cocaine. Furthermore, 15% of consumers had started PAS consumption during their incarceration. Among consumers of at least one PAS other than tobacco, cannabis and alcohol, the way of consumption was sniff for 60.0% (95% CI [48.5-70.2]) and injection for 31.0% (95% CI [21.6-42.1]). Use of several PAS at the same time and sharing sniffing and/or injection paraphernalia were other risky behaviors observed; 12% (95% CI [5.8-20.4]) of drug injectors declared using chlorine to sterilize their injection paraphernalia. Our study provides worrying data about PAS consumption in prison. The measures of prohibition do not prevent this consumption. There is even an initiation of consumption of PAS for 15% of the first-time incarcerated inmates. This finding should encourage public authorities to facilitate access of inmates to the care structures in prisons, to improve drug use prevention and care programs and to develop activities (sports, cultural, educational and vocational). Copyright © 2017 Elsevier Masson SAS

  9. Therapeutic drug monitoring: antiarrhythmic drugs

    OpenAIRE

    Campbell, T. J.; Williams, K. M.(Virginia Polytechnic Institute and State University, 24061, Blacksburg, VA, USA)

    1998-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class ...

  10. Designer drugs: a medicinal chemistry perspective.

    Science.gov (United States)

    Carroll, F Ivy; Lewin, Anita H; Mascarella, S Wayne; Seltzman, Herbert H; Reddy, P Anantha

    2012-02-01

    There are numerous medicinal chemistry reports in the literature describing the pharmacological properties of thousands of narcotics, stimulants, hallucinogens, sedative-hypnotic drugs, cannabinoids, and other psychoactive substances as well as synthetic methods for their preparations. This information, while essential for the advancement of science, has been used by clandestine chemists to manufacture and market an endless variety of analogs of so-called designer drugs. In this review, we describe how clandestine chemists used the principles of medicinal chemistry to design molecules, referred to as designer drugs, that elicit the effects of opioids, amphetamine and analogs, cannabinoids, and phencyclidine analogs while circumventing the law. © 2012 New York Academy of Sciences.

  11. [Comorbidity in adolescence: simultaneous declaration of depressive, eating, obsessive-compulsive symptoms and use of psychoactive substances in the general population of 17 year old students in a big city].

    Science.gov (United States)

    Modrzejewska, Renata

    2010-01-01

    To determine whether the following symptoms: depressive symptoms, eating disorder symptoms and obsessive-compulsive symptoms among adolescents in Kraków secondary schools are associated with an increased risk of psychoactive substance use. A representative sample of the population of Kraków secondary school pupils was tested. A two-stage draw method identified a group of 2034 2nd form pupils of all types of secondary schools: grammar schools, technical schools and vocational schools (17-year olds). They were tested using the following screening questionnaires: Beck Depression Scale, EAT-26 eating disorders scale, Obsessive-compulsive disorder (Leyton) scale and the author's drug questionnaire. The incidence of depressive symptoms among boys and girls is associated with an increased risk of alcohol use (74.8% among depressive boys versus 65.8% in the depressive group of girls), cigarette smoking (42.7% vs. 46.7%) and drug use (29.0% vs. 18.6%). All of the relationships are statistically significant in both sexes. 41.7% depressive boys admit to smoking, vs. only 32.6% in the non-depressive group. In the girls' group, these relationships are as follows: 46.7% versus 32.1%. The relationships are statistically significant in both sexes. The incidence of eating disorder symptoms among boys and girls is associated with a higher risk of alcohol use (respectively: 73.5% vs. 61.9%), cigarette smoking (42.1% vs. 46.9%), and drug use (31.6% versus 21.5%). Compared with a group of young people without eating disorder symptoms, the relationships are of statistical significance. Comorbidity of the following symptoms was found: depressive symptoms, eating disorder symptoms, obsessive-compulsive symptoms and symptoms of psychoactive substance use. The presence of depressive symptoms increases the risk of the use of psychoactive substances, especially alcohol and tobacco, to a lesser extent--drugs, both in the boys and in the girls. The presence of eating disorder symptoms

  12. An Assessment of Drug Education-Prevention Programs in the U. S. Army. Army Research Institute Technical Paper 261.

    Science.gov (United States)

    Cook, Royer F.; Morton, Anton S.

    In recent years the Army has been concerned about the widespread use of psychoactive drugs by all classes of young people and the effects of this use on the Army. In order to curb this use among soldiers the Army initiated a comprehensive program to prevent and control the abuse of alcohol and drugs. Prevention was considered to include education,…

  13. Self-reported use of novel psychoactive substances in a US nationally representative survey: Prevalence, correlates, and a call for new survey methods to prevent underreporting.

    Science.gov (United States)

    Palamar, Joseph J; Martins, Silvia S; Su, Mark K; Ompad, Danielle C

    2015-11-01

    In recent years, there has been an increase in emergence and use of novel psychoactive substances (NPS) in the US and worldwide. However, there is little published epidemiological survey data estimating the prevalence of use in the US. Data on self-reported NPS use came from the National Survey of Drug Use and Health (2009-2013), a national representative sample of non-institutionalized individuals in the US. Subjects were asked to provide names of (non-traditional) drugs they used that they were not specifically asked about. We examined lifetime prevalence and sociodemographic correlates of self-reported use of new and uncommon synthetic drugs (NPS) among subjects ages 12-34-years-old. 1.2% of subjects self-reported any use of the 57 NPS we examined. Use of psychedelic tryptamines (primarily DMT) was most common, followed by psychedelic phenethylamines (e.g., 2C series) and synthetic cannabinoids. Prevalence of self-reported use of NPS increased from 2009 to 2013 and use was most common among males, whites, older subjects, those of lower income, and among those residing in cities. Lifetime use of various other illicit drugs (e.g., LSD, cocaine, ecstasy/MDMA) was highly prevalent among NPS users. This the first study reporting on use of a variety of NPS in a nationally representative US sample; however, use appears to be underreported as other national data suggest higher rates of NPS (e.g., synthetic cannabinoid) use. Developing more adaptable survey tools and systematically assessing NPS use would allow researchers to ask about hundreds of NPS and improve reporting as new drugs continue to rapidly emerge. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Population Screening for Coronary Artery Calcification Does Not Increase Mental Distress and the Use of Psychoactive Medication

    DEFF Research Database (Denmark)

    Nielsen, Anders Daldorph; Videbech, Poul; Gerke, Oke

    2012-01-01

    as a result of the observations were at the discretion of the individual general practitioner. Before screening and at 6-month follow-up a depression test (Major Depression Inventory) was conducted, and the use of psychoactive medication was recorded. RESULTS:: A total of 1257 (69%) subjects agreed...

  15. [Workplace and psychoactive substances dependence: certificate of eligibility for work and perspectives of prevention in the light of recent innovative regulations].

    Science.gov (United States)

    Spigno, F; Debarbieri, N; Traversa, F

    2007-01-01

    The Authors consider a present widespread social problem i.e. the abuse and/or addiction to alcohol and drugs (psychoactive substances) with regard to the interferences and consequences it can have on one's working environment. In particular they look into the hardest problem an occupational physician has to face when required to pass judgement on a worker's specific duty fitness, which rightfully falls within the so-called "knotty qualifications". In addition the authors go over the rather complicated Italian laws regulating drugs, alcohol and their relevant problems, underlining how, despite the great number of regulations in force, it's still unclear what an occupational physician is allowed or not allowed to do in such cases. Although even the latest provisions fail to give a clue for correctly running such phenomena, the Authors suggest a diagnostic and rehabilitation/reinstating programme that, by involving the main operators in charge of prevention both at work and inside health territorial services, can set reasonable aims and feasible operating plans granting all due respect for the workers' dignity and self determination.

  16. [Impact of internet on poisoning with psychoactive substances in young people].

    Science.gov (United States)

    Radoniewicz-Chagowska, Anna; Tchórz, Michał; Kujawa, Anna; Szponar, Jarosław; Drelich, Grzegorz

    2012-01-01

    These days young people use internet as a source of information. Internet offers knowledge that can be used not only for school education but also to obtain information about usage and effects of psychoactive substances. Recent research shows that young people more often use internet websites and chat rooms to exchange knowledge and experience with chemicals and everyday products used as intoxicants, for example: nutmeg, nonprescription medications, metal cleaning liquid or feminine hygiene products. This article shows the extend of knowledge young people can gain from popular internet websites. Information on the web is presented as appealing, attractive and encouraging. From a toxicologist point of view it is extremely important to be familiar with those new threats because more and more often we have to treat young patients with a serious poisoning from usage of experimental intoxicating substances.

  17. Psychiatric diagnoses and psychoactive medication use among nonsurgical critically ill patients receiving mechanical ventilation

    DEFF Research Database (Denmark)

    Wunsch, Hannah; Christiansen, Christian Fynbo; Johansen, Martin B

    2014-01-01

    , the absolute risk of new psychiatric diagnoses was low but higher than hospitalized patients: 0.5% vs 0.2% over the first 3 months (adjusted HR, 3.42; 95% CI, 1.96-5.99; P general population cohort (0.02%; adjusted HR, 21.77; 95% CI, 9.23-51.36; Pmedication....... CONCLUSIONS AND RELEVANCE: Prior psychiatric diagnoses are more common in critically ill patients than in hospital and general population cohorts. Among survivors of critical illness, new psychiatric diagnoses and psychoactive medication use is increased in the months after discharge. Our data suggest both......IMPORTANCE: The relationship between critical illness and psychiatric illness is unclear. OBJECTIVE: To assess psychiatric diagnoses and medication prescriptions before and after critical illness. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study in Denmark of critically ill patients...

  18. [Psychiatric emergencies in drug addiction].

    Science.gov (United States)

    Benyamina, Amine; Bouchez, Jacques; Rahioui, Hassan; Reynaud, Michel

    2003-06-01

    The practitioner is very frequently confronted by emergencies in drug-addicted patients also having psychiatric symptomatology. In this article the authors will address emergencies related to alcohol (notably intoxication, pre-DTs and the encephalopathies); emergencies related to cannabis (notably intoxication, psychotic states and panic attacks); and emergencies related to other psycho-active substances (overdoses, drug-withdrawal, psychiatric complications related to cocaine or amphetamines). In the domain of drug addiction, as in psychiatry, the practitioner must give as much importance to the organisation of the long-term healthcare plan for the drug addict, ulterior to the management of the immediate emergency. For example, whereas 90% of subjects presenting to the emergency department for acute alcoholic intoxication have a pathological consumption of alcohol (abuse or dependance), management of the alcoholism is proposed in only 2% of them.

  19. Illicit drugs and the rise of epidemiology during the 1960s.

    Science.gov (United States)

    Mold, Alex

    2007-04-01

    Epidemiology has been crucial to the understanding of both tobacco smoking and illicit drug taking as public health issues in Britain since the 1960s. There were, however, significant differences in the way in which epidemiology was used between the two psychoactive substances.

  20. Illicit drugs and the rise of epidemiology during the 1960s

    OpenAIRE

    Mold, Alex

    2007-01-01

    Epidemiology has been crucial to the understanding of both tobacco smoking and illicit drug taking as public health issues in Britain since the 1960s. There were, however, siginificant differences in the way in which epidemiology was used between the two psychoactive substances.