Two cases of "cannabis acute psychosis" following the administration of oral cannabis

Directory of Open Access Journals (Sweden)

Pin Marie

2005-04-01

Full Text Available Abstract Background Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. Case presentations We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. Conclusion While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

Science.gov (United States)

Lile, Joshua A.; Stoops, William W.; Rush, Craig R.; Negus, S. Stevens; Glaser, Paul E. A.; Hatton, Kevin W.; Hays, Lon R.

2016-01-01

Background A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Methods Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30 mg/70 kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. Results The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. Conclusions These coordinated studies successfully established drug vs. non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use. PMID:27269368

Human rights, public health and medicinal cannabis use

OpenAIRE

Bone, Melissa; Seddon, Toby

2015-01-01

This paper explores the interplay between the human rights and drug control frameworks, and critiques case law on medicinal cannabis use to demonstrate that a bona fide human rights perspective allows for a broader conception of ‘health’. This broad conception, encompassing both medicalised and social constructionist definitions, can inform public health policies relating to medicinal cannabis use. The paper also demonstrates how a human rights lens can alleviate a core tension between the St...

Psycho-Social Characteristics of Cannabis Abusing Youth

Directory of Open Access Journals (Sweden)

Ifeta Ličanin

2005-02-01

Full Text Available It is a well known fact that drug abuse is most common in early adolescence. The most popular substances among youth are cannabis products (made from Cannabis sativa L., Cannaba-ceae. The majority of heroin and cocaine addicts have started with marijuana. The aim of this study is to show some psycho-social characteristics of adolescents who abuse cannabis. Research conducted during the year 2001 was epidemiological and prospective. The study group included 600 adolescents of equal gender and age distribution. Q 2000 questionnaire was used, as a comprehensive tool for all aspects of adolescent life. The results show strong peer impact on one’s behavior. Youth who use cannabis had 2-3 friends of the same behavior, compared to others who had none. We found positive correlation between life stressful events and cannabis abuse. We also noticed tendency to delinquent behavior related to cannabis abuse (35%.

The Role of Hypothalamic Insulin and Dopamine in the Anorectic Effect of Cocaine and d-amphetamine

Science.gov (United States)

1992-08-21

smoking free-base cocaine, or smoking crack, and (5) smoking coca-paste (cocaine-sulfate, usually smoked with tobacco or cannabis ). Cocaine is a...Exposure to cocaine involves a wide variety of physiological, neurochemical, behavioral, and psychological consequences. The pharmacology and toxicology ...agonists. Neuropharmacology, 21, 885-890. Asghar, K., & De Souza, E. (1989). Pharmacology and toxicology of amphetamine and related designer drugs. NIDA

Cannabis publication analysis using density-equalising mapping and research output benchmarking

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B H Vogelzang

2010-12-01

Full Text Available Background. Cannabis has been a topic of political and medical controversy in many countries over the past century. Although many publications on this topic are available, there is currently no comprehensive evaluation of global research activities in the field. Objective. This study was conducted in order to provide a quantitative and qualitative analysis of the worldwide research output on cannabis. Methods. In a quantitative approach, items concerning cannabis published between 1900 and 2008 were retrieved from the ISI Web of Science databases developed by the Thompson Institute of Scientific Information and analysed using scientometric methods. In a second step, research fields of growing interest were identified. Results. We found that publications on this topic increased during the late 1960s, as well as during the period 1990 - 2008. We noted that South Africa was one of the countries with a high research output, having published numerous articles on cannabis. A comparison of cannabis with other drugs (e.g. alcohol, tobacco, cocaine and heroin showed that in relation to the proportion of respective drug users, cocaine and heroin are overly represented in terms of research output. When analysing the main subjects of the publications, psychiatry was prominent, especially with regard to research on psychosis. Conclusion. There is increasing interest in research on cannabis. The research only partially reflects the drug’s importance with regard to number of users.

Characterization of a cocaine binding protein in human placenta

International Nuclear Information System (INIS)

Ahmed, M.S.; Zhou, D.H.; Maulik, D.; Eldefrawi, M.E.

1990-01-01

[ 3 H]-Cocaine binding sites are identified in human placental villus tissue plasma membranes. These binding sites are associated with a protein and show saturable and specific binding of [ 3 H]-cocaine with a high affinity site of 170 fmole/mg protein. The binding is lost with pretreatment with trypsin or heat. The membrane bound protein is solubilized with the detergent 3-(3-cholamidopropyl)dimethyl-ammonio-1-propane sulphonate (CHAPS) with retention of its saturable and specific binding of [ 3 H]-cocaine. The detergent-protein complex migrates on a sepharose CL-6B gel chromatography column as a protein with an apparent molecular weight of 75,900. The protein has an S 20,w value of 5.1. The binding of this protein to norcocaine, pseudococaine, nomifensine, imipramine, desipramine, amphetamine and dopamine indicates that it shares some, but not all, the properties of the brain cocaine receptor. The physiologic significance of this protein in human placenta is currently unclear

Functional consequences of cocaine expectation: findings in a non-human primate model of cocaine self-administration.

Science.gov (United States)

Porrino, Linda J; Beveridge, Thomas J R; Smith, Hilary R; Nader, Michael A

2016-05-01

Exposure to stimuli and environments associated with drug use is considered one of the most important contributors to relapse among substance abusers. Neuroimaging studies have identified neural circuits underlying these responses in cocaine-dependent subjects. But these studies are often difficult to interpret because of the heterogeneity of the participants, substances abused, and differences in drug histories and social variables. Therefore, the goal of this study was to assess the functional effects of exposure to cocaine-associated stimuli in a non-human primate model of cocaine self-administration, providing precise control over these variables, with the 2-[(14) C]deoxyglucose method. Rhesus monkeys self-administered 0.3 mg/kg/injection cocaine (n = 4) under a fixed-interval 3-minute (FI 3-min) schedule of reinforcement (30 injections/session) for 100 sessions. Control animals (n = 4) underwent identical schedules of food reinforcement. Sessions were then discontinued for 30 days, after which time, monkeys were exposed to cocaine- or food-paired cues, and the 2-[(14) C]deoxyglucose experiment was conducted. The presentation of the cocaine-paired cues resulted in significant increases in functional activity within highly restricted circuits that included portions of the pre-commissural striatum, medial prefrontal cortex, rostral temporal cortex and limbic thalamus when compared with control animals presented with the food-paired cues. The presentation of cocaine-associated cues increased brain functional activity in contrast to the decreases observed after cocaine consumption. Furthermore, the topography of brain circuits engaged by the expectation of cocaine is similar to the distribution of effects during the earliest phases of cocaine self-administration, prior to the onset of neuroadaptations that accompany chronic cocaine exposure. © 2015 Society for the Study of Addiction.

Prenatal and postnatal cocaine exposure predict teen cocaine use

Science.gov (United States)

Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

2015-01-01

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

Peripheral benzodiazepine receptors are decreased during cocaine withdrawal in humans.

Science.gov (United States)

Javaid, J I; Notorangelo, M P; Pandey, S C; Reddy, P L; Pandey, G N; Davis, J M

1994-07-01

In the present study, homovanillic acid in plasma (pHVA) and benzodiazepine receptors (3H-PK11195 binding) in neutrophil membranes were determined in blood obtained from cocaine-dependent (DSM-III-R) adult male inpatients at baseline-(within 72 hr of last cocaine use) and after 3 weeks of cocaine abstinence, and normal controls. The mean (+/- SEM) pHVA at baseline (10.3 ng/ml +/- 1.1) was similar to normals and did not change after 3 weeks of cocaine abstinence. Similarly, the binding indices of benzodiazepine receptors in cocaine-dependent subjects as a group were not significantly different than in normal controls. In 10 cocaine-dependent subjects, however, where both blood samples were available, the number of 3H-PK11195 binding sites was significantly (p < 0.05) decreased after 3 weeks of cocaine abstinence (mean +/- sem: Bmax = 6371 +/- 657 fmol/mg protein) compared with baseline (Bmax = 7553 +/- 925 fmol/mg protein), although there were no differences in the binding affinity (mean +/- sem: KD = 8.6 +/- 1.2 nmol/L after 3 weeks of abstinence compared with 8.1 +/- 1.0 nmol/L at baseline). These preliminary results suggest that peripheral benzodiazepine receptors may play an important role in the pathophysiology of cocaine withdrawal in cocaine-dependent human subjects.

A mathematical model of a recombinant humanized anti-cocaine monoclonal antibody's effects on cocaine pharmacokinetics in mice.

Science.gov (United States)

Wetzel, Hanna N; Zhang, Tongli; Norman, Andrew B

2017-09-01

A recombinant humanized anti-cocaine monoclonal antibody (mAb), h2E2, is at an advanced stage of pre-clinical development as an immunotherapy for cocaine abuse. It is hypothesized that h2E2 binds to and sequesters cocaine in the blood. A three-compartment model of the effects of h2E2 on cocaine's distribution was constructed. The model assumes that h2E2 binds to cocaine and that the h2E2-cocaine complex does not enter the brain but distributes between the central and peripheral compartments. Free cocaine is eliminated from both the central and peripheral compartments, and h2E2 and the h2E2-cocaine complex are eliminated from the central compartment only. This model was tested against a new dataset measuring cocaine concentrations in the brain and plasma over 1h in the presence and absence of h2E2. The mAb significantly increased plasma cocaine concentrations with a concomitant significant decrease in brain concentration. Plasma concentrations declined over the 1-hour sampling period in both groups. With a set of parameters within reasonable physiological ranges, the three-compartment model was able to qualitatively and quantitatively simulate the increased plasma concentration in the presence of the antibody and the decreased peak brain concentration in the presence of antibody. Importantly, the model explained the decline in plasma concentrations over time as distribution of the cocaine-h2E2 complex into a peripheral compartment. This model will facilitate the targeting of ideal mAb PK/PD properties thus accelerating the identification of lead candidate anti-drug mAbs. Copyright © 2017 Elsevier Inc. All rights reserved.

Prenatal and postnatal cocaine exposure predict teen cocaine use.

Science.gov (United States)

Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

2011-01-01

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity

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Schindler, Charles W; Goldberg, Steven R

2012-01-01

One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans. PMID:22300096

The use of tobacco and cannabis at an international music festival

DEFF Research Database (Denmark)

Hesse, Morten; Tutenges, Sébastien; Schliewe, Sanna

2010-01-01

users who had not used a substance in the past 12 months. Results: New onset of tobacco use was reported by 9.2% of never-smokers, and new onset of cannabis use was reported by 9.3% of never-smokers of cannabis. Resumption of tobacco use was reported by 24% of past year abstainers, and resumption...... of cannabis use was reported by 30% of past year abstainers. New onset of other types of substances was reported by less than 0.5% of subjects, but among past year abstainers, 5–10% reported resumption of amphetamine, ketamine, MDMA and cocaine use. New onset smokers of cannabis were significantly younger...... than never-smokers. Conclusion: Music festivals such as the Roskilde Festival may be important arenas for the prevention of onset of tobacco and cannabis use and for a return to substance use....

Snow Control - An RCT protocol for a web-based self-help therapy to reduce cocaine consumption in problematic cocaine users

Directory of Open Access Journals (Sweden)

Sullivan Robin

2011-09-01

Full Text Available Abstract Background Cocaine use has increased in most European countries, including Switzerland, and many states worldwide. The international literature has described treatment models that target the general population. In addition to supplying informative measures at the level of primary and secondary prevention, the literature also offers web-based self-help tools for problematic substance users, which is in line with tertiary prevention. Such programs, however, have been primarily tested on individuals with problematic alcohol and cannabis consumption, but not on cocaine-dependent individuals. Methods/Design This paper presents the protocol of a randomised clinical trial to test the effectiveness of a web-based self-help therapy to reduce cocaine use in problematic cocaine users. The primary outcome is severity of cocaine dependence. Secondary outcome measures include cocaine craving, consumption of cocaine and other substances of abuse in the past month, and changes in depression characteristics. The therapy group will receive a 6-week self-help therapy to reduce cocaine consumption based on methods of Cognitive Behavioural Therapy, principles of Motivational Interviewing and self-control practices. The control group will be presented weekly psycho-educative information with a quiz. The predictive validity of participant characteristics on treatment retention and outcome will be explored. Discussion To the best of our knowledge, this will be the first randomised clinical trial to test the effectiveness of online self-help therapy to reduce or abstain from cocaine use. It will also investigate predictors of outcome and retention. This trial is registered at Current Controlled Trials and is traceable as NTR-ISRCTN93702927.

Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

OpenAIRE

Siciliano, Cody A.; Fordahl, Steve C.; Jones, Sara R.

2016-01-01

Cocaine addiction is a debilitating neuropsychiatric disorder characterized by uncontrolled cocaine intake, which is thought to be driven, at least in part, by cocaine-induced deficits in dopamine system function. A decreased ability of cocaine to elevate dopamine levels has been repeatedly observed as a consequence of cocaine use in humans, and preclinical work has highlighted tolerance to cocaine's effects as a primary determinant in the development of aberrant cocaine taking behaviors. Her...

Magnetic dispersive solid-phase extraction based on modified magnetic nanoparticles for the detection of cocaine and cocaine metabolites in human urine by high-performance liquid chromatography-mass spectrometry.

Science.gov (United States)

Yang, Feiyu; Zou, Yun; Ni, Chunfang; Wang, Rong; Wu, Min; Liang, Chen; Zhang, Jiabin; Yuan, Xiaoliang; Liu, Wenbin

2017-11-01

An easy-to-handle magnetic dispersive solid-phase extraction procedure was developed for preconcentration and extraction of cocaine and cocaine metabolites in human urine. Divinyl benzene and vinyl pyrrolidone functionalized silanized Fe 3 O 4 nanoparticles were synthesized and used as adsorbents in this procedure. Scanning electron microscopy, vibrating sample magnetometry, and infrared spectroscopy were employed to characterize the modified adsorbents. A high-performance liquid chromatography with mass spectrometry method for determination of cocaine and its metabolites in human urine sample has been developed with pretreatment of the samples by magnetic dispersive solid-phase extraction. The obtained results demonstrated the higher extraction capacity of the prepared nanoparticles with recoveries between 75.1 to 105.7% and correlation coefficients higher than 0.9971. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.10 ng/mL. The proposed magnetic dispersive solid-phase extraction method provided a rapid, environmentally friendly and magnetic stuff recyclable approach and it was confirmed that the prepared adsorbents material was a kind of highly effective extraction materials for the trace cocaine and cocaine metabolites analyses in human urine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

What can we learn from the Dutch cannabis coffeeshop system?

Science.gov (United States)

MacCoun, Robert J

2011-11-01

To examine the empirical consequences of officially tolerated retail sales of cannabis in the Netherlands, and possible implications for the legalization debate. Available Dutch data on the prevalence and patterns of use, treatment, sanctioning, prices and purity for cannabis dating back to the 1970s are compared to similar indicators in Europe and the United States. The available evidence suggests that the prevalence of cannabis use among Dutch citizens rose and fell as the number of coffeeshops increased and later declined, but only modestly. The coffeeshops do not appear to encourage escalation into heavier use or lengthier using careers, although treatment rates for cannabis are higher than elsewhere in Europe. Scatterplot analyses suggest that Dutch patterns of use are very typical for Europe, and that the 'separation of markets' may indeed have somewhat weakened the link between cannabis use and the use of cocaine or amphetamines. Cannabis consumption in the Netherlands is lower than would be expected in an unrestricted market, perhaps because cannabis prices have remained high due to production-level prohibitions. The Dutch system serves as a nuanced alternative to both full prohibition and full legalization. © 2011 The Author, Addiction © 2011 Society for the Study of Addiction.

[MEDICAL CANNABIS].

Science.gov (United States)

Naftali, Timna

2016-02-01

The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation. Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and:pain and diarrhea in Crohn's disease. Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse. Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing. Currently, as long as cannabis is classified as an illicit drug and until further controlled studies are performed, the use of medical cannabis should be limited to patients who failed conventional better established treatment.

Cross-national differences in clinically significant cannabis problems: epidemiologic evidence from 'cannabis-only' smokers in the United States, Mexico, and Colombia

Directory of Open Access Journals (Sweden)

Posada-Villa Jose

2010-03-01

Full Text Available Abstract Background Epidemiological studies show wide variability in the occurrence of cannabis smoking and related disorders across countries. This study aims to estimate cross-national variation in cannabis users' experience of clinically significant cannabis-related problems in three countries of the Americas, with a focus on cannabis users who may have tried alcohol or tobacco, but who have not used cocaine, heroin, LSD, or other internationally regulated drugs. Methods Data are from the World Mental Health Surveys Initiative and the National Latino and Asian American Study, with probability samples in Mexico (n = 4426, Colombia (n = 5,782 and the United States (USA; n = 8,228. The samples included 212 'cannabis only' users in Mexico, 260 in Colombia and 1,724 in the USA. Conditional GLM with GEE and 'exact' methods were used to estimate variation in the occurrence of clinically significant problems in cannabis only (CO users across these surveyed populations. Results The experience of cannabis-related problems was quite infrequent among CO users in these countries, with weighted frequencies ranging from 1% to 5% across survey populations, and with no appreciable cross-national variation in general. CO users in Colombia proved to be an exception. As compared to CO users in the USA, the Colombia smokers were more likely to have experienced cannabis-associated 'social problems' (odds ratio, OR = 3.0; 95% CI = 1.4, 6.3; p = 0.004 and 'legal problems' (OR = 9.7; 95% CI = 2.7, 35.2; p = 0.001. Conclusions This study's most remarkable finding may be the similarity in occurrence of cannabis-related problems in this cross-national comparison within the Americas. Wide cross-national variations in estimated population-level cumulative incidence of cannabis use disorders may be traced to large differences in cannabis smoking prevalence, rather than qualitative differences in cannabis experiences. More research is needed to identify conditions that

Cocaine abuse or dependency and other pyschiatric disorders. Madrid study on dual pathology.

Science.gov (United States)

Arias, Francisco; Szerman, Nestor; Vega, Pablo; Mesias, Beatriz; Basurte, Ignacio; Morant, Consuelo; Ochoa, Enriqueta; Poyo, Félix; Babin, Francisco

2013-01-01

The main objective of this study was to analyse the cocaine addict subgroup from the Madrid study of prevalence of dual disorders in community mental health and substance misuse services. The sample consisted of 837 outpatients from Madrid, Spain. We compared 488 subjects who had a lifetime diagnosis of cocaine abuse or dependence, and 222 subjects who did not have a cocaine substance use disorder. We used the Mini International Neuropsychiatric Interview to evaluate axis I mental disorders, and the Personality Disorder Questionnaire to evaluate personality disorders. Almost three-quarters (73.4%) of cocaine addicts had a current dual disorder. Most prevalent were mood and anxiety disorders. Almost half (49.6%) had a personality disorder. Most of them (94.9%) had other substance use disorders. Cocaine addicts did not have higher prevalence rates of dual pathology than addicts with no cocaine abuse or dependence. Cocaine addicts were associated to a diagnosis of antisocial personality disorder, agoraphobia, and post-traumatic stress disorder, and they had an early age of onset of alcohol and cannabis use. Dual pathology is no higher in cocaine addicts in treatment than in addicts who do not use cocaine, however cocaine addicts started other drugs earlier, and were associated with specific mental disorders. Copyright © 2012 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

Factors that lead to the use of crack cocaine in combination with marijuana in Brazil: a qualitative study.

Science.gov (United States)

Gonçalves, Janaina R; Nappo, Solange A

2015-07-25

In Brazil, crack cocaine use remains a healthcare challenge due to the rapid onset of its pleasurable effects, its ability to induce craving and addiction, and the fact that it is easily accessible. Delayed action on the part of the Brazilian Government in addressing the drug problem has led users to develop their own strategies for surviving the effects of crack cocaine use, particularly the drug craving and psychosis. In this context, users have sought the benefits of combining crack cocaine with marijuana. Our aim was to identify the reasons why users combine crack cocaine with marijuana and the health implications of doing so. The present study is a qualitative study, using in-depth interviews and criteria-based sampling, following 27 crack cocaine users who combined its use with marijuana. Participants were recruited using the snowball sampling technique, and the point of theoretical saturation was used to define the sample size. Data were analyzed using the content analysis technique. The interviewees reported that the combination of crack cocaine use with marijuana provided "protection" (reduced undesirable effects, improved sleep and appetite, reduced craving for crack cocaine, and allowed the patients to recover some quality of life). Combined use of cannabis as a strategy to reduce the effects of crack exhibited several significant advantages, particularly an improved quality of life, which "protected" users from the violence typical of the crack culture. Crack use is considered a serious public health problem in Brazil, and there are few solution strategies. Within that limited context, the combination of cannabis and crack deserves more thorough clinical investigation to assess its potential use as a strategy to reduce the damage associated with crack use.

New sorbent materials for selective extraction of cocaine and benzoylecgonine from human urine samples.

Science.gov (United States)

Bujak, Renata; Gadzała-Kopciuch, Renata; Nowaczyk, Alicja; Raczak-Gutknecht, Joanna; Kordalewska, Marta; Struck-Lewicka, Wiktoria; Waszczuk-Jankowska, Małgorzata; Tomczak, Ewa; Kaliszan, Michał; Buszewski, Bogusław; Markuszewski, Michał J

2016-02-20

An increase in cocaine consumption has been observed in Europe during the last decade. Benzoylecgonine, as a main urinary metabolite of cocaine in human, is so far the most reliable marker of cocaine consumption. Determination of cocaine and its metabolite in complex biological samples as urine or blood, requires efficient and selective sample pretreatment. In this preliminary study, the newly synthesized sorbent materials were proposed for selective extraction of cocaine and benzoylecgonine from urine samples. Application of these sorbent media allowed to determine cocaine and benzoylecgonine in urine samples at the concentration level of 100ng/ml with good recovery values as 81.7%±6.6 and 73.8%±4.2, respectively. The newly synthesized materials provided efficient, inexpensive and selective extraction of both cocaine and benzoylecgonine from urine samples, which can consequently lead to an increase of the sensitivity of the current available screening diagnostic tests. Copyright © 2015 Elsevier B.V. All rights reserved.

Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.

Science.gov (United States)

Coe, Marion A; Jufer Phipps, Rebecca A; Cone, Edward J; Walsh, Sharon L

2018-06-01

The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions. Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis, and a two-factor model was used to assess for dose and sex differences. The mean ± SEM oral cocaine bioavailability was 0.32 ± 0.04 after 100 and 0.45 ± 0.06 after 200 mg oral cocaine. Volume of distribution (Vd) and clearance (CL) were both greatest after 100 mg oral (Vd = 4.2 L/kg; CL = 116.2 mL/[min kg]) compared to 200 mg oral (Vd = 2.9 L/kg; CL = 87.5 mL/[min kg]) and 40 mg IV (Vd = 1.3 L/kg; CL = 32.7 mL/[min kg]). Oral cocaine area-under-thecurve (AUC) and peak concentration increased in a dose-related manner. AUC metabolite-to-parent ratios of benzoylecgonine and ecgonine methyl ester were significantly higher after oral compared to IV administration and highest after the lower oral dose. In addition, minor metabolites were detected in higher concentrations after oral compared to IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile. Cocaine bioavailability values were similar to previous estimates. Oral cocaine also produced a unique metabolic profile, with greater concentrations of major and minor metabolites.

[11]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy

International Nuclear Information System (INIS)

Fowler, Joanna S.; Volkow, Nora D.; Wang, Gene-Jack; Gatley, S. John; Logan, Jean

2001-01-01

Cocaine was initially labeled with carbon-11 in order to track the distribution and pharmacokinetics of this powerful stimulant and drug of abuse in the human brain and body. It was soon discovered that [ 11 C]cocaine was not only useful for measuring cocaine pharmacokinetics and its relationship to behavior but that it is also a sensitive radiotracer for dopamine transporter (DAT) availability. Measures of DAT availability were facilitated by the development of a graphical analysis method (Logan Plot) for reversible systems which streamlined kinetic analysis. This expanded the applications of [ 11 C]cocaine to studies of DAT availability in the human brain and allowed the first comparative measures of the degree of DAT occupancy by cocaine and another stimulant drug methylphenidate. This article will summarize preclinical and clinical research with [ 11 C]cocaine

Cannabis use and bone mineral density: NHANES 2007-2010.

Science.gov (United States)

Bourne, Donald; Plinke, Wesley; Hooker, Elizabeth R; Nielson, Carrie M

2017-12-01

Cannabis use is rising in the USA. Its relationship to cannabinoid signaling in bone cells implies its use could affect bone mineral density (BMD) in the population. In a national survey of people ages 20-59, we found no association between self-reported cannabis use and BMD of the hip or spine. Cannabis is the most widely used illegal drug in the USA, and its recreational use has recently been approved in several US states. Cannabinoids play a role in bone homeostasis. We aimed to determine the association between cannabis use and BMD in US adults. In the National Health and Nutrition Examination Survey 2007-2010, 4743 participants between 20 and 59 years old, history of cannabis use was categorized into never, former (previous use, but not in last 30 days), light (1-4 days of use in last 30 days), and heavy (≥5 days of use in last 30 days). Multivariable linear regression was used to test the association between cannabis use and DXA BMD of the proximal femur and lumbar spine with adjustment for age, sex, BMI, and race/ethnicity among other BMD determinants. Sixty percent of the population reported ever using cannabis; 47% were former users, 5% were light users, and 7% were heavy users. Heavy cannabis users were more likely to be male, have a lower BMI, increased daily alcohol intake, increased tobacco pack-years, and were more likely to have used other illegal drugs (cocaine, heroin, or methamphetamines). No association between cannabis and BMD was observed for any level of use (p ≥ 0.28). A history of cannabis use, although highly prevalent and related to other risk factors for low BMD, was not independently associated with BMD in this cross-sectional study of American men and women.

[Cognitive abnormalities and cannabis use].

Science.gov (United States)

Solowij, Nadia; Pesa, Nicole

2010-05-01

Evidence that cannabis use impairs cognitive function in humans has been accumulating in recent decades. The purpose of this overview is to update knowledge in this area with new findings from the most recent literature. Literature searches were conducted using the Web of Science database up to February 2010. The terms searched were: "cannabi*" or "marijuana", and "cogniti*" or "memory" or "attention" or "executive function", and human studies were reviewed preferentially over the animal literature. Cannabis use impairs memory, attention, inhibitory control, executive functions and decision making, both during the period of acute intoxication and beyond, persisting for hours, days, weeks or more after the last use of cannabis. Pharmacological challenge studies in humans are elucidating the nature and neural substrates of cognitive changes associated with various cannabinoids. Long-term or heavy cannabis use appears to result in longer-lasting cognitive abnormalities and possibly structural brain alterations. Greater adverse cognitive effects are associated with cannabis use commencing in early adolescence. The endogenous cannabinoid system is involved in regulatory neural mechanisms that modulate processes underlying a range of cognitive functions that are impaired by cannabis. Deficits in human users most likely therefore reflect neuroadaptations and altered functioning of the endogenous cannabinoid system.

The use of tobacco and cannabis at an international music festival.

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Hesse, M; Tutenges, S; Schliewe, S

2010-01-01

Music festivals are known to attract a high proportion of drug users. Using a survey of 1,772 visitors at the Roskilde Festival in Denmark, we assessed substance use at the festival, the incidence of use of substances among never-users and the incidence of use among lifetime users who had not used a substance in the past 12 months. New onset of tobacco use was reported by 9.2% of never-smokers, and new onset of cannabis use was reported by 9.3% of never-smokers of cannabis. Resumption of tobacco use was reported by 24% of past year abstainers, and resumption of cannabis use was reported by 30% of past year abstainers. New onset of other types of substances was reported by less than 0.5% of subjects, but among past year abstainers, 5-10% reported resumption of amphetamine, ketamine, MDMA and cocaine use. New onset smokers of cannabis were significantly younger than never-smokers. Music festivals such as the Roskilde Festival may be important arenas for the prevention of onset of tobacco and cannabis use and for a return to substance use. Copyright © 2010 S. Karger AG, Basel.

Polysomnographic sleep disturbances in nicotine, caffeine, alcohol, cocaine, opioid, and cannabis use: A focused review.

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Garcia, Alexandra N; Salloum, Ihsan M

2015-10-01

In the United States, approximately 60 million Americans suffer from sleep disorders and about 22 million Americans report substance dependence or use disorders annually. Sleep disturbances are common consequences of substance use disorders and are likely found in primary care as well as in specialty practices. The aim of this review was to evaluate the effects of the most frequently used substances-nicotine, alcohol, opioids, cocaine, caffeine, and cannabis-have on sleep parameters measured by polysomnography (PSG) and related clinical manifestations. We used electronic databases such as PubMED and PsycINFO to search for relevant articles. We only included studies that assessed sleep disturbances using polysomnography and reviewed the effects of these substances on six clinically relevant sleep parameters: Total sleep time, sleep onset latency, rapid-eye movement, REM latency, wake after sleep onset, and slow wave sleep. Our review indicates that these substances have significant impact on sleep and that their effects differ during intoxication, withdrawal, and chronic use. Many of the substance-induced sleep disturbances overlap with those encountered in sleep disorders, medical, and psychiatric conditions. Sleep difficulties also increase the likelihood of substance use disorder relapse, further emphasizing the need for optimizing treatment interventions in these patients. Our review highlights the importance of systematically screening for substance use in patients with sleep disturbances and highlights the need for further research to understand mechanisms underlying substances-induced sleep disturbances and on effective interventions addressing these conditions. © American Academy of Addiction Psychiatry.

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males

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Mokrysz, C; Freeman, T P; Korkki, S; Griffiths, K; Curran, H V

2016-01-01

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16–17 years old) and adult (n=20; 24–28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned', ‘want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents. PMID:27898071

Ethical issues in using a cocaine vaccine to treat and prevent cocaine abuse and dependence.

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Hall, W; Carter, L

2004-08-01

A "cocaine vaccine" is a promising immunotherapeutic approach to treating cocaine dependence which induces the immune system to form antibodies that prevent cocaine from crossing the blood brain barrier to act on receptor sites in the brain. Studies in rats show that cocaine antibodies block cocaine from reaching the brain and prevent the reinstatement of cocaine self administration. A successful phase 1 trial of a human cocaine vaccine has been reported. The most promising application of a cocaine vaccine is to prevent relapse to dependence in abstinent users who voluntarily enter treatment. Any use of a vaccine to treat cocaine addicts under legal coercion raises major ethical issues. If this is done at all, it should be carefully trialled first, and only after considerable clinical experience has been obtained in using the vaccine to treat voluntary patients. There will need to be an informed community debate about what role, if any, a cocaine vaccine may have as a way of preventing cocaine addiction in children and adolescents.

Anormalidades cognitivas no uso da cannabis Cognitive abnormalities and cannabis use

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Nadia Solowij

2010-05-01

Full Text Available OBJETIVO: Evidências de que o uso de cannabis prejudica funções cognitivas em humanos têm-se acumulado nas décadas recentes. O propósito desta revisão é o de atualizar o conhecimento nesta área com novos achados a partir da literatura mais recente. MÉTODO: As buscas na literatura foram realizadas utilizando-se o banco de dados Web of Science até fevereiro de 2010. Foram buscados os termos "cannabi*" ou "marijuana" e "cogniti*" ou "memory" ou "attention" ou "executive function", e os estudos em humanos foram revisados preferencialmente em relação aos estudos em animais. DISCUSSÃO: O uso de cannabis prejudica a memória, a atenção, o controle inibitório, as funções executivas e a tomada de decisões, tanto durante como após o período de intoxicação aguda, persistindo por horas, dias, semanas ou mais após o último uso. Os estudos de desafio farmacológico em humanos estão elucidando a natureza e os substratos neurais das alterações cognitivas associadas a vários canabinoides. O uso pesado ou de longo prazo de cannabis parece resultar em anormalidades cognitivas mais duradouras e possivelmente em alterações cerebrais estruturais. Efeitos cognitivos adversos maiores estão associados ao uso de cannabis quando este começa no início da adolescência. CONCLUSÃO: O sistema canabinoide endógeno está envolvido nos mecanismos de regulação neural que modulam os processos subjacentes a uma gama de funções cognitivas que estão prejudicadas pela cannabis. Os déficits em usuários humanos muito provavelmente refletem, portanto, neuroadaptações e o funcionamento alterado do sistema canabinoide endógeno.OBJECTIVE: Evidence that cannabis use impairs cognitive function in humans has been accumulating in recent decades. The purpose of this overview is to update knowledge in this area with new findings from the most recent literature. METHOD: Literature searches were conducted using the Web of Science database up to

Modeling of pharmacokinetics of cocaine in human reveals the feasibility for development of enzyme therapies for drugs of abuse.

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Fang Zheng

Full Text Available A promising strategy for drug abuse treatment is to accelerate the drug metabolism by administration of a drug-metabolizing enzyme. The question is how effectively an enzyme can actually prevent the drug from entering brain and producing physiological effects. In the present study, we have developed a pharmacokinetic model through a combined use of in vitro kinetic parameters and positron emission tomography data in human to examine the effects of a cocaine-metabolizing enzyme in plasma on the time course of cocaine in plasma and brain of human. Without an exogenous enzyme, cocaine half-lives in both brain and plasma are almost linearly dependent on the initial cocaine concentration in plasma. The threshold concentration of cocaine in brain required to produce physiological effects has been estimated to be 0.22±0.07 µM, and the threshold area under the cocaine concentration versus time curve (AUC value in brain (denoted by AUC2(∞ required to produce physiological effects has been estimated to be 7.9±2.7 µM·min. It has been demonstrated that administration of a cocaine hydrolase/esterase (CocH/CocE can considerably decrease the cocaine half-lives in both brain and plasma, the peak cocaine concentration in brain, and the AUC2(∞. The estimated maximum cocaine plasma concentration which a given concentration of drug-metabolizing enzyme can effectively prevent from entering brain and producing physiological effects can be used to guide future preclinical/clinical studies on cocaine-metabolizing enzymes. Understanding of drug-metabolizing enzymes is key to the science of pharmacokinetics. The general insights into the effects of a drug-metabolizing enzyme on drug kinetics in human should be valuable also in future development of enzyme therapies for other drugs of abuse.

Modeling of pharmacokinetics of cocaine in human reveals the feasibility for development of enzyme therapies for drugs of abuse.

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Zheng, Fang; Zhan, Chang-Guo

2012-01-01

A promising strategy for drug abuse treatment is to accelerate the drug metabolism by administration of a drug-metabolizing enzyme. The question is how effectively an enzyme can actually prevent the drug from entering brain and producing physiological effects. In the present study, we have developed a pharmacokinetic model through a combined use of in vitro kinetic parameters and positron emission tomography data in human to examine the effects of a cocaine-metabolizing enzyme in plasma on the time course of cocaine in plasma and brain of human. Without an exogenous enzyme, cocaine half-lives in both brain and plasma are almost linearly dependent on the initial cocaine concentration in plasma. The threshold concentration of cocaine in brain required to produce physiological effects has been estimated to be 0.22±0.07 µM, and the threshold area under the cocaine concentration versus time curve (AUC) value in brain (denoted by AUC2(∞)) required to produce physiological effects has been estimated to be 7.9±2.7 µM·min. It has been demonstrated that administration of a cocaine hydrolase/esterase (CocH/CocE) can considerably decrease the cocaine half-lives in both brain and plasma, the peak cocaine concentration in brain, and the AUC2(∞). The estimated maximum cocaine plasma concentration which a given concentration of drug-metabolizing enzyme can effectively prevent from entering brain and producing physiological effects can be used to guide future preclinical/clinical studies on cocaine-metabolizing enzymes. Understanding of drug-metabolizing enzymes is key to the science of pharmacokinetics. The general insights into the effects of a drug-metabolizing enzyme on drug kinetics in human should be valuable also in future development of enzyme therapies for other drugs of abuse.

Attention deficit hyperactivity disorder in cocaine-dependent adults: a psychiatric comorbidity analysis.

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Daigre, Constanza; Roncero, Carlos; Grau-López, Lara; Martínez-Luna, Nieves; Prat, Gemma; Valero, Sergi; Tejedor, Rosa; Ramos-Quiroga, Josep A; Casas, Miguel

2013-01-01

Attention deficit hyperactivity disorder (ADHD) is highly prevalent among drug abusers. We studied the psychiatric comorbidity and characteristics of cocaine use in relation to the presence of ADHD among patients with cocaine dependence. A total of 200 cocaine-dependent patients attending an Outpatient Drug Clinic participated in the study. A systematic evaluation of ADHD (CAADID-II), the severity of addiction (EuropASI) and other axes I and II psychiatric disorders was made (SCID-I and SCID-II). A descriptive, bivariate, and multivariate analysis of the data was performed. In the multivariate analysis, the identified risk factors for the development of ADHD were a history of behavioral disorder in childhood (OR: 3.04), a lifetime history of cannabis dependence in the course of life (OR: 2.68), and age at the start of treatment (OR: 1.08). The bivariate analysis showed ADHD to be associated with other factors such as male gender, age at start of cocaine use and dependence, the amount of cocaine consumed weekly, increased occupational alteration, alcohol consumption, general psychological discomfort, depressive disorder, and antisocial personality disorder. We conclude that ADHD is associated with increased psychiatric comorbidity and greater severity of addiction. Copyright © American Academy of Addiction Psychiatry.

[Addiction to cocaine and other stimulants].

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Lacoste, Jérôme; Delavenne-Garcia, Héloïse; Charles-Nicolas, Aimé; Duarte Garcia, Frederico; Jehel, Louis

2012-12-01

Due to many available forms (powder, pasta base, freebase and crack…) and because of multiple routes of administration (intranasal, intravenous, or smoked), cocaine has become in 30 years one of the most consumed illegal drugs worldwide, after cannabis. While the frequency of consumption decreases in North America, it continues to rise in Europe, and in some countries in South America, including Brazil, despite a growing knowledge of its specific effects, physical complications and psychiatric consequences. Elsewhere (notably in Asia and Indian Ocean), amphetamine and other stimulants (including methamphetamine), whose properties and patterns of use are very similar to those of cocaine, tend to replace it. Another amphetamine derivative, MDMA or ecstasy, is also consumed by many young people of less than 25 years, in Europe and North America, in a festive setting, with specific consequences and special procedures of care. Although there is currently no consensus for a specific medication, the most appropriate therapeutic approach seems to involve a psychosocial treatment associated with an anticraving medication, which will reduce compulsive desire to consume, in order to facilitate the psychotherapeutic and social care. However, pharmacological research remains very active, and many options are explored (GABAergic or dopaminergic agonists, amphetamine derivatives with long half-life, vaccine…), whether to treat addiction to cocaine or to methamphetamine. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

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Siciliano, Cody A.; Fordahl, Steve C.

2016-01-01

Cocaine addiction is a debilitating neuropsychiatric disorder characterized by uncontrolled cocaine intake, which is thought to be driven, at least in part, by cocaine-induced deficits in dopamine system function. A decreased ability of cocaine to elevate dopamine levels has been repeatedly observed as a consequence of cocaine use in humans, and preclinical work has highlighted tolerance to cocaine's effects as a primary determinant in the development of aberrant cocaine taking behaviors. Here we determined that cocaine self-administration in rats produced tolerance to the dopamine transporter-inhibiting effects of cocaine in the nucleus accumbens core, which was normalized following a 14 or 60 d abstinence period; however, although these rats appeared to be similar to controls, a single self-administered infusion of cocaine at the end of abstinence, even after 60 d, fully reinstated tolerance to cocaine's effects. A single cocaine infusion in a naive rat had no effect on cocaine potency, demonstrating that cocaine self-administration leaves the dopamine transporter in a “primed” state, which allows for cocaine-induced plasticity to be reinstated by a subthreshold cocaine exposure. Further, reinstatement of cocaine tolerance was accompanied by decreased cocaine-induced locomotion and escalated cocaine intake despite extended abstinence from cocaine. These data demonstrate that cocaine leaves a long-lasting imprint on the dopamine system that is activated by re-exposure to cocaine. Further, these results provide a potential mechanism for severe cocaine binge episodes, which occur even after sustained abstinence from cocaine, and suggest that treatments aimed at transporter sites may be efficacious in promoting binge termination following relapse. SIGNIFICANCE STATEMENT Tolerance is a DSM-V criterion for substance abuse disorders. Abusers consistently show reduced subjective effects of cocaine concomitant with reduced effects of cocaine at its main site of action

Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain

International Nuclear Information System (INIS)

Volkow, N.D.

1999-01-01

The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo potency at the DAT between these two drugs could account for the differences in their abuse liability the authors compared the levels of DAT occupancies that they had previously reported separately for intravenous methylphenidate in controls and for intravenous cocaine in cocaine abusers. DAT occupancies were measured with Positron Emission Tomography using [ 11 C]cocaine, as a DAT ligand, in 8 normal controls for the methylphenidate study and in 17 active cocaine abusers for the cocaine study. The ratio of the distribution volume of [ 11 C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd+1, was used as measure of DAT availability. Parallel measures were obtained to assess the cardiovascular effects of these two drugs. Methylphenidate and cocaine produced comparable dose-dependent blockage of DAT with an estimated ED 50 for methylphenidate of 0.07 mg/kg and for cocaine of 0.13 mg/kg. Both drugs induced similar increases in heart rate and blood pressure but the duration of the effects were significantly longer for methylphenidate than for cocaine

Cannabis induced asystole.

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Brancheau, Daniel; Blanco, Jessica; Gholkar, Gunjan; Patel, Brijesh; Machado, Christian

2016-01-01

Cannabis or marijuana is the most used recreational, and until recently illegal, drug in the United States. Although cannabis has medicinal use, its consumption has been linked to motor vehicle accidents in dose dependent fashion. Marijuana and other cannabinoids produce a multitude of effects on the human body that may result in these motor vehicle accidents. Some of the effects that marijuana has been known to cause include altered sensorium, diminished reflexes, and increased vagal tone. We present a case of cannabis induced asystole from hypervagotonia. Copyright © 2016 Elsevier Inc. All rights reserved.

Thinking high : the impact of cannabis on human cognition

NARCIS (Netherlands)

Kowal, M.A.

2016-01-01

The research presented in this thesis focused on the effects of cannabis on mental functions and the brain. Specifically, the investigation aimed at exploring how cannabis affects creative thinking, awareness of errors, and the neurotransmitter dopamine among regular cannabis users. It was

Abuse or dependence on cannabis and other psychiatric disorders. Madrid study on dual pathology prevalence.

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Arias, Francisco; Szerman, Nestor; Vega, Pablo; Mesias, Beatriz; Basurte, Ignacio; Morant, Consuelo; Ochoa, Enriqueta; Poyo, Félix; Babin, Francisco

2013-01-01

Cannabis use has been associated to a wide variety of mental disorders, the possible causal role of this use in the etiology of severe mental disorders as schizophrenia or bipolar disorder standing out. Moreover, the cannabinoid system is involved in emotional regulation, so cannabis use could disturb this process and provoke anxiety and mood disorders. The main objective of this study was to analyze the cannabis addict subgroup from Madrid study of prevalence of dual disorders in community mental health and substance misuse services. The sample consisted of 837 outpatients under treatment in the mental health network or drug network of the Community of Madrid (Spain). Of these, 353 subjects had a lifetime diagnosis of cannabis abuse or dependence and 357 subjects did not have cannabis substance use disorder. We used the Mini International Neuropsychiatric Interview (MINI) to evaluate axis I mental disorders, and Personality Disorder Questionnaire to evaluate personality disorders. It was considered that 76.5% of the cannabis addicts had a current dual disorder. The most prevalent ones were mood and anxiety disorders. Of those addicted to cannabis, 51% had a personality disorder. Most of them had several substance use disorders. Cannabis abuse or dependence subjects had an earlier onset in consumption of other drugs such as alcohol, cocaine, and tobacco than addicts without cannabis abuse or dependence. The cannabis addicts also differed from the other addicts because of an association to antisocial personality disorder, bipolar disorder, psychosis and agoraphobia. The presence of these mental disorders was significantly associated to a lower age at initiation of cannabis use. Dual pathology is very high in cannabis addicts under treatment. Said consumption of cannabis, probably within a polysubstance use pattern, is associated to severe mental disorders as psychosis and bipolar disorder. An earlier age of onset in cannabis use is associated to a greater risk of

Persistency of Cannabis Use Predicts Violence following Acute Psychiatric Discharge

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Jules R. Dugré

2017-09-01

Full Text Available BackgroundViolence is a major concern and is prevalent across several mental disorders. The use of substances has been associated with an exacerbation of psychiatric symptoms as well as with violence. Compared to other substances such as alcohol and cocaine, existing literature on the cannabis–violence relationship has been more limited, with most studies being conducted in the general population, and has shown controversial results. Evidence has suggested a stronger relationship when examining the effects of the persistency of cannabis use on future violent behaviors. Though, while cannabis use is highly prevalent amid psychiatric patients, far less literature on the subject has been conducted in this population. Hence, the present prospective study aims to investigate the persistency of cannabis use in psychiatric patients.MethodThe sample comprised of 1,136 recently discharged psychiatric patients provided by the MacArthur Risk Assessment Study. A multi-wave (five-assessment follow-up design was employed to allow temporal sequencing between substance use and violent behaviors. Generalized estimating equations (GEE were used to examine the effect of persistency of cannabis use on violence, while controlling for potential confounding factors. Potential bidirectional association was also investigated using the same statistical approach.ResultsOur results suggest a unidirectional association between cannabis use and violence. GEE model revealed that the continuity of cannabis use across more than one time wave was associated with increased risks of future violent behavior. Patients who reported having used cannabis at each follow-up periods were 2.44 times more likely to display violent behaviors (OR = 2.44, 95% CI: 1.06–5.63, p < 0.05.ConclusionThese findings are particularly relevant as they suggest that the longer individuals report having used cannabis after a psychiatric discharge, the more likely they are of being violent in the

Cannabis e humor Cannabis and mood

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Rafael Faria Sanches

2010-06-01

Full Text Available OBJETIVO: Avaliar as relações entre o uso agudo e crônico de cannabis e alterações do humor. MÉTODO: Os artigos foram selecionados por meio de busca eletrônica no indexador PubMed. Capítulos de livros e as listas de referências dos artigos selecionados também foram revisados. RESULTADOS: Observam-se elevados índices de comorbidade entre abuso/dependência de cannabis e transtornos afetivos em estudos transversais e em amostras clínicas. Estudos longitudinais indicam que, em longo prazo, o uso mais intenso de cannabis está relacionado com um risco maior de desenvolvimento de doença bipolar e, talvez, depressão maior em indivíduos inicialmente sem quadros afetivos; porém, os mesmos não encontraram maior risco de uso de cannabis entre aqueles com mania ou depressão sem esta comorbidade. Outra importante observação é que o uso de substâncias psicoativas em bipolares pode estar associado a uma série de características negativas, como dificuldade na recuperação dos sintomas afetivos, maior número de internações, piora na adesão ao tratamento, risco aumentado de suicídio, agressividade e a uma pobre resposta ao lítio. Tratamentos psicossociais e farmacológicos são indicados para o manejo da comorbidade entre cannabis e transtornos afetivos. CONCLUSÃO: As relações entre o uso de cannabis e alterações do humor são observadas tanto epidemiologicamente quanto nos contextos clínicos.OBJECTIVE: Evaluate the relationship between acute and chronic use of cannabis and mood changes. METHOD: Articles were selected by electronic search in PubMed. Chapters in books and reference lists of selected articles were also reviewed. As the research did not involve humans, there was no evaluation by a Research Ethics Committee. RESULTS: High rates of comorbidity between use/abuse/dependence of cannabis and affective disorders in longitudinal studies and in clinical samples were observed. Longitudinal studies indicate that, in long

Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys.

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Johnson, Amy R; Banks, Matthew L; Blough, Bruce E; Lile, Joshua A; Nicholson, Katherine L; Negus, S Stevens

2016-08-01

Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper. Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43mg/kg/injection) and food (0, 1, 3, or 10 1g banana-flavored food pellets). During daily 5h sessions, a single cocaine dose and a single food-reinforcer magnitude were available in 10 30-min trials. During the initial "sample" trial, the available cocaine and food reinforcer were delivered non-contingently. During each of the subsequent nine "choice" trials, responding could produce either the cocaine or food reinforcer under an independent concurrent progressive-ratio schedule. Preference was governed by the cocaine dose and food-reinforcer magnitude, and increasing cocaine doses produced dose-dependent increases in cocaine choice at all food-reinforcer magnitudes. Effects of the candidate medication lisdexamfetamine (0.32-3.2mg/kg/day) were then examined on choice between 0.14mg/kg/injection cocaine and 10 pellets. Under baseline conditions, this reinforcer pair maintained an average of approximately 6 cocaine and 3 food choices. Lisdexamfetamine dose-dependently decreased cocaine choice in all monkeys, but food choice was not significantly altered. These results support utility of this procedure in rhesus monkeys as one component of a platform for translational research on medications development to treat cocaine use disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Consequences of tobacco, cocaine and cannabis consumption during pregnancy on the pregnancy itself, on the newborn and on child development: A review].

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Lamy, S; Laqueille, X; Thibaut, F

2015-06-01

Substance use has increased worldwide. Based on these data, we may think that substance use has also increased during pregnancy, but epidemiological data are scarce in this population. The potential consequences of tobacco, cocaine or cannabis use during pregnancy are a major public health concern. The combined use of different substances during pregnancy may have serious consequences on the pregnancy and on child development. In this paper, we will describe the potential consequences for the newborn, child and adolescent after being exposed to tobacco, cannabis and cocaine in utero. For this purpose, we will review all retrospective and prospective studies (in English and French) referenced in PubMed reporting on the somatic or psychiatric consequences of alcohol, tobacco and drug consumption by pregnant women on newborn and children. Consumption during pregnancy was assessed in these studies using simple questionnaires, biomarkers analysis or both. Generally speaking, these pregnancies are at high risk for both the mother and the foetus: for example, an increased risk of miscarriage or of reduced length of gestation, an increased risk of uterine apoplexy and placenta praevia, more premature births and/or hypotrophy were reported. The occurrence of a newborn's withdrawal syndrome may be misdiagnosed. Many consequences on child development may be observed such as growth disorders, learning or motor disorders, language disorders, cognitive disorders (attention, memory, executive functions), attention deficit disorders with impulsivity or with hyperactivity (ADHD), and memory disorders. The prevalence of depressive or anxiety disorders may also be increased in these children. The risk of addictive disorders or schizophrenia in children exposed in utero to illicit drugs or tobacco is still unknown. The combined use of different substances increases, consequently it is difficult to disentangle the consequences on child development of each of the drugs used during

Cannabis as a substitute for alcohol and other drugs

Directory of Open Access Journals (Sweden)

Reiman Amanda

2009-12-01

Full Text Available Abstract Background Substitution can be operationalized as the conscious choice to use one drug (legal or illicit instead of, or in conjunction with, another due to issues such as: perceived safety; level of addiction potential; effectiveness in relieving symptoms; access and level of acceptance. This practice of substitution has been observed among individuals using cannabis for medical purposes. This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients. Methods Anonymous survey data were collected at the Berkeley Patient's Group (BPG, a medical cannabis dispensary in Berkeley, CA. (N = 350 The sample was 68% male, 54% single, 66% White, mean age was 39; 74% have health insurance (including MediCal, 41% work full time, 81% have completed at least some college, 55% make less than $40,000 a year. Seventy one percent report having a chronic medical condition, 52% use cannabis for a pain related condition, 75% use cannabis for a mental health issue. Results Fifty three percent of the sample currently drinks alcohol, 2.6 was the average number of drinking days per week, 2.9 was the average number of drinks on a drinking occasion. One quarter currently uses tobacco, 9.5 is the average number of cigarettes smoked daily. Eleven percent have used a non-prescribed, non OTC drug in the past 30 days with cocaine, MDMA and Vicodin reported most frequently. Twenty five percent reported growing up in an abusive or addictive household. Sixteen percent reported previous alcohol and/or drug treatment, and 2% are currently in a 12-step or other recovery program. Forty percent have used cannabis as a substitute for alcohol, 26% as a substitute for illicit drugs and 66% as a substitute for prescription drugs. The most common reasons given for substituting were: less adverse side effects (65%, better symptom management (57%, and less withdrawal potential (34% with cannabis. Conclusion The substitution of one

LIQUID CHROMATOGRAPHIC / MASS SPECTROMETRIC DETERMINATION OF MORPHINE, CODEINE AND COCAINE IN HUMAN SERA USING A NEW INTERNAL SURFACE REVERSED PHASE COLUMN

OpenAIRE

Hattori, Hideki; Arinobu, Tetsuya; Iwai, Masae; Suzuki, Osamu; Seno, Hiroshi

2003-01-01

A new internal surface reversed phase column (Shim-pack MAYI-ODS) was used for analysis of morphine, codeine and cocaine in human sera by LC/MS/MS. The column enabled direct injection of crude biological samples without pretreatment realizing a rapid analytical procedure. Therecoveries of morphine, codeine and cocaine spiked into human sera were 50-60 %. The regression equations for morphine, codeine and cocaine in sera, using atropine as internal standard, showed good linearity in the ranges...

Cannabis Smoking in 2015

Science.gov (United States)

Biehl, Jason R.

2015-01-01

Recent legislative successes allowing expanded access to recreational and medicinal cannabis have been associated with its increased use by the public, despite continued debates regarding its safety within the medical and scientific communities. Despite legislative changes, cannabis is most commonly used by smoking, although alternatives to inhalation have also emerged. Moreover, the composition of commercially available cannabis has dramatically changed in recent years. Therefore, developing sound scientific information regarding its impact on lung health is imperative, particularly because published data conducted prior to widespread legalization are conflicting and inconclusive. In this commentary, we delineate major observations of epidemiologic investigations examining cannabis use and the potential associated development of airways disease and lung cancer to highlight gaps in pulmonary knowledge. Additionally, we review major histopathologic alterations related to smoked cannabis and define specific areas in animal models and human clinical translational investigations that could benefit from additional development. Given that cannabis has an ongoing classification as a schedule I medication, federal funding to support investigations of modern cannabis use in terms of medicinal efficacy and safety profile on lung health have been elusive. It is clear, however, that the effects of inhaled cannabis on lung health remain uncertain and given increasing use patterns, are worthy of further investigation. PMID:25996274

Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

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Haney, Margaret; Ramesh, Divya; Glass, Andrew; Pavlicova, Martina; Bedi, Gillinder; Cooper, Ziva D

2015-01-01

Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4–6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects (‘good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1–51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of ‘good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder. PMID:25881117

Positive posttraumatic stress disorder screens among first-time medical cannabis patients: prevalence and association with other substance use.

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Bohnert, Kipling M; Perron, Brian E; Ashrafioun, Lisham; Kleinberg, Felicia; Jannausch, Mary; Ilgen, Mark A

2014-10-01

Twenty-one states and the District of Columbia have passed legislation allowing for the use of medical cannabis for those individuals with qualifying medical conditions, which include posttraumatic stress disorder (PTSD) for a growing number of states. Little information is available regarding PTSD among medical cannabis patients. This study seeks to provide initial data on this topic by examining the prevalence and correlates of positive PTSD screens among a sample of patients seeking medical cannabis certification for the first time (n=186). Twenty-three percent (42/186; 95% confidence interval [CI] =17%-29%) of the patients in the study sample screened positive for PTSD. Moreover, the group that screened positive for PTSD had higher percentages of lifetime prescription opioid, cocaine, prescription sedative, and street opioid use, as well as a higher percentage of recent prescription sedative use, than the group that screened negative for PTSD. These findings highlight the relatively common use of other substances among medical cannabis patients with significant PTSD symptoms, even when compared with other patients seeking medical cannabis for the first time. As a growing number of states include PTSD among the list of qualifying medical conditions for medical cannabis, additional research is needed to better characterize the longitudinal relationship between medical cannabis use and PTSD symptoms. Published by Elsevier Ltd.

Prevalence of Cannabis Residues in Psychiatric Patients: A Case Study of Two Mental Health Referral Hospitals in Uganda

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Epaenetus A. Awuzu

2014-01-01

Full Text Available Various studies have reported that abuse of cannabis is a risk factor for psychosis. The aims of this study were to determine the prevalence of delta 9-tetrahydrocanabinol (Δ 9 -THC, a major metabolite of cannabis, in psychiatric patients in Uganda, and to assess the diagnostic capacity of two referral mental health hospitals to screen patients for exposure to cannabis in Uganda. Socio-demographic characteristics of the patients were collected through questionnaires and review of medical records. Urine samples were collected from 100 patients and analyzed using Δ 9 -THC immunochromatographic kit (Standard Diagnostics®, South Korea. Seventeen percent of the patients tested positive for Δ 9 -THC residues in their urine. There was strong association ( p < 0.05 between history of previous abuse of cannabis and presence of Δ 9 -THC residues in the urine. Alcohol, cocaine, heroin, pethidine, tobacco, khat and kuber were the other substances abused in various combinations. Both referral hospitals lacked laboratory diagnostic kits for detection of cannabis in psychiatric patients. In conclusion, previous abuse of cannabis is associated with occurrence of the residues in psychiatric patients, yet referral mental health facilities in Uganda do not have the appropriate diagnostic kits for detection of cannabis residues as a basis for evidence-based psychotherapy.

Postmortem diagnosis and toxicological validation of illicit substance use

OpenAIRE

Lehrmann, E; Afanador, ZR; Deep-Soboslay, A; Gallegos, G; Darwin, WD; Lowe, RH; Barnes, AJ; Huestis, MA; Cadet, JL; Herman, MM; Hyde, TM; Kleinman, JE; Freed, WJ

2008-01-01

The present study examines the diagnostic challenges of identifying ante-mortem illicit substance use in human postmortem cases. Substance use, assessed by clinical case history reviews, structured next-of-kin interviews, by general toxicology of blood, urine, and/or brain, and by scalp hair testing, identified 33 cocaine, 29 cannabis, 10 phencyclidine and 9 opioid cases. Case history identified 42% cocaine, 76% cannabis, 10% phencyclidine, and 33% opioid cases. Next-of-kin interviews identif...

Sex Differences in Cannabis Use and Effects: A Cross-Sectional Survey of Cannabis Users

Science.gov (United States)

Cuttler, Carrie; Mischley, Laurie K.; Sexton, Michelle

2016-01-01

Abstract Introduction: Despite known sex differences in the endocannabinoid system of animals, little attention has been paid to sex differences in human's cannabis use patterns and effects. The purpose of the present study was to examine sex differences in cannabis use patterns and effects in a large sample of recreational and medical cannabis users. Methods: A large sample (n=2374) of cannabis users completed an anonymous, online survey that assessed their cannabis use practices and experiences, including the short-term acute effects of cannabis and withdrawal effects. A subsample of 1418 medical cannabis users further indicated the medical conditions for which they use cannabis and its perceived efficacy. Results: The results indicated that men reported using cannabis more frequently and in higher quantities than did women. Men were more likely to report using joints/blunts, vaporizers, and concentrates, while women were more likely to report using pipes and oral administration. Men were more likely than women to report increased appetite, improved memory, enthusiasm, altered time perception, and increased musicality when high, while women were more likely than men to report loss of appetite and desire to clean when high. Men were more likely than women to report insomnia and vivid dreams during periods of withdrawal, while women were more likely than men to report nausea and anxiety as withdrawal symptoms. Sex differences in the conditions for which medical cannabis is used, and its efficacy, were trivial. Conclusions: These results may be used to focus research on biological and psychosocial mechanisms underlying cannabis-related sex differences, to inform clinicians treating individuals with cannabis use disorders, and to inform cannabis consumers, clinicians, and policymakers about the risks and benefits of cannabis for both sexes. PMID:28861492

Sex Differences in Cannabis Use and Effects: A Cross-Sectional Survey of Cannabis Users.

Science.gov (United States)

Cuttler, Carrie; Mischley, Laurie K; Sexton, Michelle

2016-01-01

Introduction: Despite known sex differences in the endocannabinoid system of animals, little attention has been paid to sex differences in human's cannabis use patterns and effects. The purpose of the present study was to examine sex differences in cannabis use patterns and effects in a large sample of recreational and medical cannabis users. Methods: A large sample ( n =2374) of cannabis users completed an anonymous, online survey that assessed their cannabis use practices and experiences, including the short-term acute effects of cannabis and withdrawal effects. A subsample of 1418 medical cannabis users further indicated the medical conditions for which they use cannabis and its perceived efficacy. Results: The results indicated that men reported using cannabis more frequently and in higher quantities than did women. Men were more likely to report using joints/blunts, vaporizers, and concentrates, while women were more likely to report using pipes and oral administration. Men were more likely than women to report increased appetite, improved memory, enthusiasm, altered time perception, and increased musicality when high, while women were more likely than men to report loss of appetite and desire to clean when high. Men were more likely than women to report insomnia and vivid dreams during periods of withdrawal, while women were more likely than men to report nausea and anxiety as withdrawal symptoms. Sex differences in the conditions for which medical cannabis is used, and its efficacy, were trivial. Conclusions: These results may be used to focus research on biological and psychosocial mechanisms underlying cannabis-related sex differences, to inform clinicians treating individuals with cannabis use disorders, and to inform cannabis consumers, clinicians, and policymakers about the risks and benefits of cannabis for both sexes.

Characterization of a recombinant humanized anti-cocaine monoclonal antibody and its Fab fragment.

Science.gov (United States)

Kirley, Terence L; Norman, Andrew B

2015-01-01

Variations of post-translational modifications are important for stability and in vivo behavior of therapeutic antibodies. A recombinant humanized anti-cocaine monoclonal antibody (h2E2) was characterized for heterogeneity of N-linked glycosylation and disulfide bonds. In addition, charge heterogeneity, which is partially due to the presence or absence of C-terminal lysine on the heavy chains, was examined. For cocaine overdose therapy, Fab fragments may be therapeutic, and thus, a simplified method of generation, purification, and characterization of the Fab fragment generated by Endoproteinase Lys-C digestion was devised. Both the intact h2E2 antibody and purified Fab fragments were analyzed for their affinities for cocaine and 2 of its metabolites, benzoylecgonine and cocaethylene, by fluorescence quenching of intrinsic antibody tyrosine and tryptophan fluorescence resulting from binding of these drugs. Binding constants obtained from fluorescence quenching measurements are in agreement with recently published radioligand and ELISA binding assays. The dissociation constants determined for the h2E2 monoclonal and its Fab fragment are approximately 1, 5, and 20 nM for cocaethylene, cocaine, and benzoylecgonine, respectively. Tryptophan fluorescence quenching (emission at 330 nm) was measured after either excitation of tyrosine and tryptophan (280 nm) or selective excitation of tryptophan alone (295 nm). More accurate binding constants are obtained using tryptophan selective excitation at 295 nm, likely due to interfering absorption of cocaine and metabolites at 280 nm. These quenching results are consistent with multiple tryptophan and tyrosine residues in or near the predicted binding location of cocaine in a previously published 3-D model of this antibody's variable region.

Chemistry, metabolism, and toxicology of cannabis: clinical implications.

Science.gov (United States)

Sharma, Priyamvada; Murthy, Pratima; Bharath, M M Srinivas

2012-01-01

Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (▵(9_)THC), produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders.Many studies that endeavor to understand the mechanism of action of cannabis concentrate on pharmacokinetics and pharmacodynamics of cannabinoids in humans. However, there is limited research on the chronic adverse effects and retention of cannabinoids in human subjects.Cannabis can be detected in body fluids following exposure through active/passive inhalation and exposure through breastfeeding. Cannabis detection is directly dependent on accurate analytical procedures for detection of metabolites and verification of recent use.In this review, an attempt has been made to summarize the properties of cannabis and its derivatives, and to discuss the implications of its use with emphasis on bioavailability, limit of detection, carry over period and passive inhalation, important factors for detection and diagnosis.

Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications

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M.M. Srinivas Bharath

2012-12-01

Full Text Available Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (Δ9_THC, produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders.Many studies that endeavor to understand the mechanism of action of cannabis concentrate on pharmacokinetics and pharmacodynamics of cannabinoids in humans. However, there is limited research on the chronic adverse effects and retention of cannabinoids in human subjects.Cannabis can be detected in body fluids following exposure through active/passive inhalation and exposure through breastfeeding. Cannabis detection is directly dependent on accurate analytical procedures for detection of metabolites and verification of recent use.In this review, an attempt has been made to summarize the properties of cannabis and its derivatives, and to discuss the implications of its use with emphasis on bioavailability, limit of detection, carry over period and passive inhalation, important factors for detection and diagnosis.

Cannabis consumption by female psychology students: the influence of perceived stress, coping and consumption of drugs in their social environment [Consumo de cannabis en alumnas de Psicología: influencia del estrés percibido, afrontamiento y consumo de drogas en su entorno

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Cristina Vargas

2012-03-01

Full Text Available The consumption of cannabis has increased in the female population. The risk and protection factors associated with an increase or decrease in its consumption may differ as a function of gender, age and substance consumed. The objectives of the present study were to examine the relevance to cannabis consumption by female students of legal drugs consumed by the university students and family members, the consumption of legal and illicit drugs by friends, sociodemographic factors and, psychological variables (perceived stress and different coping strategies. Three questionnaires were administered to 465 female students studying for Psychology degrees. The prevalence of cannabis consumption was 36.3%. The variables predicting its consumption were: a consumption of illicit drugs and cocaine by friends; b consumption of tobacco by the students; c emotion-oriented coping.

N-Acetylcysteine reduces cocaine-cue attentional bias and differentially alters cocaine self-administration based on dosing order.

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Levi Bolin, B; Alcorn, Joseph L; Lile, Joshua A; Rush, Craig R; Rayapati, Abner O; Hays, Lon R; Stoops, William W

2017-09-01

Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60mg). Fourteen individuals (N=14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. Cocaine-cue attentional bias was greatest following administration of 0mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. These results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage.

Science.gov (United States)

Gao, Yang; Geng, Liyi; Orson, Frank; Kinsey, Berma; Kosten, Thomas R; Shen, Xiaoyun; Brimijoin, Stephen

2013-03-25

In developing an vivo drug-interception therapy to treat cocaine abuse and hinder relapse into drug seeking provoked by re-encounter with cocaine, two promising agents are: (1) a cocaine hydrolase enzyme (CocH) derived from human butyrylcholinesterase and delivered by gene transfer; (2) an anti-cocaine antibody elicited by vaccination. Recent behavioral experiments showed that antibody and enzyme work in a complementary fashion to reduce cocaine-stimulated locomotor activity in rats and mice. Our present goal was to test protection against liver damage and muscle weakness in mice challenged with massive doses of cocaine at or near the LD50 level (100-120 mg/kg, i.p.). We found that, when the interceptor proteins were combined at doses that were only modestly protective in isolation (enzyme, 1mg/kg; antibody, 8 mg/kg), they provided complete protection of liver tissue and motor function. When the enzyme levels were ~400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum

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Rosa M López-Pedrajas

2015-07-01

Full Text Available Different mechanisms have been suggested for cocaine neurotoxicity, including oxidative stress alterations. Nuclear factor kappa B (NF-κB, considered a sensor of oxidative stress and inflammation, is involved in drug toxicity and addiction. NF-κB is a key mediator for immune responses that induces microglial/macrophage activation under inflammatory processes and neuronal injury/degeneration. Although cerebellum is commonly associated to motor control, muscular tone and balance. Its relation with addiction is getting relevance, being associated to compulsive and perseverative behaviors. Some reports indicate that cerebellar microglial activation induced by cannabis or ethanol, promote cerebellar alterations and these alterations could be associated to addictive-related behaviors. After considering the effects of some drugs on cerebellum, the aim of the present work analyzes pro-inflammatory changes after cocaine exposure. Rats received daily 15 mg/kg cocaine i.p. for 18 days. Reduced and oxidized forms of glutathione (GSH and GSSG, glutathione peroxidase (GPx activity and glutamate were determined in cerebellar homogenates. NF-κB activity, CD68 and GFAP expression were determined.Cerebellar GPx activity and GSH/GSSG ratio are significantly decreased after cocaine exposure. A significant increase of glutamate concentration is also observed. Interestingly, increased NF-κB activity is also accompanied by an increased expression of the lysosomal mononuclear phagocytic marker ED1 without GFAP alterations.Current trends in addiction biology are focusing on the role of cerebellum on addictive behaviors. Cocaine-induced cerebellar changes described herein fit with previosus data showing cerebellar alterations on addict subjects and support the proposed role of cerebelum in addiction.

Pain, Cannabis Species, and Cannabis Use Disorders

Science.gov (United States)

Cohen, Nicole L.; Heinz, Adrienne J.; Ilgen, Mark; Bonn-Miller, Marcel O.

2016-01-01

Objective: The purpose of this study was to examine whether individuals who used medical cannabis for chronic pain were at increased risk for cannabis use problems compared with individuals who used medical cannabis for other reasons (e.g., anxiety, insomnia, and muscle spasms). An additional aim was to determine whether individuals who used cannabis for chronic pain, as well as those who reported greater within-group pain levels, demonstrated a species preference (i.e., sativa, indica, hybrids) and the extent to which species preference was associated with cannabis use problems. Method: Participants were 163 medical cannabis users (77% male), recruited from a medical marijuana dispensary in California, who completed assessments of medical cannabis use motives, history, preferences (species type), and problems, as well as current pain level. Results: Individuals who used cannabis to manage chronic pain experienced fewer cannabis use problems than those who did not use it for pain; among those who used it for pain, the average pain level in the past week was not associated with cannabis use problems. Furthermore, individuals who used cannabis for chronic pain were more likely to use indica over sativa. Preference for indica was associated with fewer cannabis use problems than preference for hybrid species. Conclusions: Individuals who use cannabis to manage chronic pain may be at a lower risk for cannabis use problems, relative to individuals who use it for other indications, potentially as a function of their species preference. PMID:27172585

Pain, Cannabis Species, and Cannabis Use Disorders.

Science.gov (United States)

Cohen, Nicole L; Heinz, Adrienne J; Ilgen, Mark; Bonn-Miller, Marcel O

2016-05-01

The purpose of this study was to examine whether individuals who used medical cannabis for chronic pain were at increased risk for cannabis use problems compared with individuals who used medical cannabis for other reasons (e.g., anxiety, insomnia, and muscle spasms). An additional aim was to determine whether individuals who used cannabis for chronic pain, as well as those who reported greater within-group pain levels, demonstrated a species preference (i.e., sativa, indica, hybrids) and the extent to which species preference was associated with cannabis use problems. Participants were 163 medical cannabis users (77% male), recruited from a medical marijuana dispensary in California, who completed assessments of medical cannabis use motives, history, preferences (species type), and problems, as well as current pain level. Individuals who used cannabis to manage chronic pain experienced fewer cannabis use problems than those who did not use it for pain; among those who used it for pain, the average pain level in the past week was not associated with cannabis use problems. Furthermore, individuals who used cannabis for chronic pain were more likely to use indica over sativa. Preference for indica was associated with fewer cannabis use problems than preference for hybrid species. Individuals who use cannabis to manage chronic pain may be at a lower risk for cannabis use problems, relative to individuals who use it for other indications, potentially as a function of their species preference.

Conditioned Contribution of Peripheral Cocaine Actions to Cocaine Reward and Cocaine-Seeking

OpenAIRE

Wang, Bin; You, Zhi-Bing; Oleson, Erik B; Cheer, Joseph F; Myal, Stephanie; Wise, Roy A

2013-01-01

Cocaine has actions in the peripheral nervous system that reliably precede—and thus predict—its soon-to-follow central rewarding effects. In cocaine-experienced animals, the peripheral cocaine signal is relayed to the central nervous system, triggering excitatory input to the ventral tegmental origin of the mesocorticolimbic dopamine system, the system that mediates the rewarding effects of the drug. We used cocaine methiodide, a cocaine analog that does not cross the blood–brain barrier, to ...

Cannabis abuse and addiction: a contemporary literature review.

Science.gov (United States)

Iyalomhe, G B S

2009-01-01

Drug addiction, particularly among teenagers and young adults, has become a serious public health problem globally. Drugs with addictive potential include the non-therapeutic drugs that are licit/legal (caffeine, tobacco or nicotine, alcohol) and those that are illegal/illicit for common use such as benzodiazepines, amphetamines, cocaine and crack, heroin and cannabis. Worldwide, the challenge of cannabis abuse and addiction is particularly devastating, nay in Nigeria. Despite this ugly scenario, the use of cannabis continues unabated and its control remains enigmatic. The aim of the present review is to provide a contemporary comprehensible overview of exciting recent developments in the understanding of brain circuits related to the nature and effects of cannabis abuse and addiction as well as to highlight the current therapeutic approach to effective management. A thorough manual literature and internet (Medline and HINARI databases) search were conducted. It was found that recent advances in the neurobiology of drug abuse and addiction have led to the identification of neuronal substrates (eg dopamine, 5-hydroxyltrypytamine etc) as being responsible for the rewarding effects of cannabis and are also crucial to the addictive process/behaviour. There is increasing evidence that prolonged exposure to drugs of abuse including cannabis, produces long-lasting effects in cognitive and drug-rewarding brain circuits. Hence, addiction is now generally considered a chronic brain disease. Chronic use of cannabis impairs cognitive functions, perception, reaction time, learning, memory, concentration, social skills and control of emotions. There may also be panic reactions, hallucinations, paranoid states with fixed delusions and even acute psychosis. These impairments have obvious negative implications for the operation of a motor vehicle or machinery and performance at school or workplace as well as the development of a healthy family, a strong national economy and a

[Cannabis smoking and lung cancer].

Science.gov (United States)

Underner, M; Urban, T; Perriot, J; de Chazeron, I; Meurice, J-C

2014-06-01

Cannabis is the most commonly smoked illicit substance in the world. It can be smoked alone in plant form (marijuana) but it is mainly smoked mixed with tobacco. The combined smoking of cannabis and tobacco is a common-place phenomenon in our society. However, its use is responsible for severe pulmonary consequences. The specific impact of smoking cannabis is difficult to assess precisely and to distinguish from the effect of tobacco. Marijuana smoke contains polycyclic aromatic hydrocarbons and carcinogens at higher concentration than tobacco smoke. Cellular, tissue, animal and human studies, and also epidemiological studies, show that marijuana smoke is a risk factor for lung cancer. Cannabis exposure doubles the risk of developing lung cancer. This should encourage clinicians to identify cannabis use and to offer patients support in quitting. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Cannabis use and support for cannabis legalization

OpenAIRE

Palali, A. (Ali); Ours, Jan

2016-01-01

textabstractWe investigate the determinants of the support for cannabis legalization finding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this finding to self-interest and inside information about potential dangers of cannabis. While the self-interest effect is not very surprising, the effect of inside information suggests that cannabis use is not as harmful as cannabis users originally thought it was be...

The role of progestins in the behavioral effects of cocaine and other drugs of abuse: human and animal research.

Science.gov (United States)

Anker, Justin J; Carroll, Marilyn E

2010-11-01

This review summarizes findings from human and animal research investigating the influence of progesterone and its metabolites allopreganolone and pregnanolone (progestins) on the effects of cocaine and other drugs of abuse. Since a majority of these studies have used cocaine, this will be the primary focus; however, the influence of progestins on other drugs of abuse will also be discussed. Collectively, findings from these studies support a role for progestins in (1) attenuating the subjective and physiological effects of cocaine in humans, (2) blocking the reinforcing and other behavioral effects of cocaine in animal models of drug abuse, and (3) influencing behavioral responses to other drugs of abuse such as alcohol and nicotine in animals. Administration of several drugs of abuse in both human and nonhuman animals significantly increased progestin levels, and this is explained in terms of progestins acting as homeostatic regulators that decrease and normalize heightened stress and reward responses which lead to increased drug craving and relapse. The findings discussed here highlight the complexity of progestin-drug interactions, and they suggest a possible use for these agents in understanding the etiology of and developing treatments for drug abuse. Copyright © 2010 Elsevier Ltd. All rights reserved.

Brain Imaging Studies on the Cognitive, Pharmacological and Neurobiological Effects of Cannabis in Humans: Evidence from Studies of Adult Users.

Science.gov (United States)

Weinstein, Aviv; Livny, Abigail; Weizman, Abraham

2016-01-01

Cannabis is the most widely used illicit drug worldwide. Regular cannabis use has been associated with a range of acute and chronic mental health problems, such as anxiety, depression, psychotic symptoms and neurocognitive impairments and their neural mechanisms need to be examined. This review summarizes and critically evaluates brain-imaging studies of cannabis in recreational and regular cannabis users between January 2000 and January 2016. The search has yielded eligible 103 structural and functional studies. Regular use of cannabis results in volumetric, gray matter and white matter structural changes in the brain, in particular in the hippocampus and the amygdala. Regular use of cannabis affects cognitive processes such as attention, memory, inhibitory control, decision-making, emotional processing, social cognition and their associated brain areas. There is evidence that regular cannabis use leads to altered neural function during attention and working memory and that recruitment of activity in additional brain regions can compensate for it. Similar to other drugs of abuse, cannabis cues activated areas in the reward pathway. Pharmacological studies showed a modest increase in human striatal dopamine transmission after administration of THC in healthy volunteers. Regular cannabis use resulted in reduced dopamine transporter occupancy and reduced dopamine synthesis but not in reduced striatal D2/D3 receptor occupancy compared with healthy control participants. Studies also showed different effects of Δ-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on emotion, cognition and associated brain regions in healthy volunteers, whereby CBD protects against the psychoactive effects of THC. Brain imaging studies using selective high-affinity radioligands for the imaging of cannabinoid CB1 receptor availability in Positron Emission Tomography (PET) showed downregulation of CB1 in regular users of cannabis. In conclusion, regular use of the cannabinoids exerts

Efficacy of an Adenovirus-based Anti-cocaine Vaccine to Reduce Cocaine Self-administration and Reacqusition using a Choice Procedure in Rhesus Macaques

Science.gov (United States)

Evans, Suzette M.; Foltin, Richard W.; Hicks, Martin J.; Rosenberg, Jonathan B.; De, Bishnu P.; Janda, Kim D.; Kaminsky, Stephen M.; Crystal, Ronald G.

2016-01-01

Immunopharmacotherapy offers an approach for treating cocaine abuse by specifically targeting the cocaine molecule and preventing its access to the CNS. dAd5GNE is a novel cocaine vaccine that attenuates the stimulant and the reinforcing effects of cocaine in rats. The goal of this study was to extend and validate dAd5GNE vaccine efficacy in non-human primates. Six experimentally naïve adult female rhesus monkeys (Macaca mulatta) were trained to self-administer 0.1 mg/kg/injection intravenous (i.v.) cocaine or receive candy; then 4 monkeys were administered the vaccine and 2 monkeys were administered vehicle intramuscularly, with additional vaccine boosts throughout the study. The reinforcing effects of cocaine were measured during self-administration, extinction, and reacquisition (relapse) phases. Serum antibody titers in the vaccinated monkeys remained high throughout the study. There was no change in the preference for cocaine over candy over a 20-week period in 5 of the 6 monkeys; only one of the 4 (25%) vaccinated monkeys showed a decrease in cocaine choice. All 6 monkeys extinguished responding for cocaine during saline extinction testing; vaccinated monkeys tended to take longer to extinguish responding than control monkeys (17.5 vs. 7.0 sessions). Vaccination substantially retarded reacquisition of cocaine self-administration; control monkeys resumed cocaine self-administration within 6–41 sessions and 1 vaccinated monkey resumed cocaine self-administration in 19 sessions. The other 3 vaccinated monkeys required between 57–94 sessions to resume cocaine self-administration even in the context of employing several manipulations to encourage cocaine reacquisition. These data suggest that the dAdGNE vaccine may have therapeutic potential for humans who achieve cocaine abstinence as part of a relapse prevention strategy. PMID:27697554

21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite...

Behavioral Pharmacology of Human Drug Dependence

Science.gov (United States)

1981-07-01

1978. pp. 1-37. Pickens, I., Thompson, T., and Muchow, D.C. Cannabis and phenoy- olidine self-adinistration by animals. In: Goldberg, L., and...phenyl- ethylamines: cocaine, caffeine , and nicotine. Cocaine maintained high levels of self-infusion performance through a broader range of doses than...any of the 16 other drugs tested (0.032-3.2 mg/kg). Figure 2 shows that mean levels of self-infusion of both nicotine and caffeine were within the

Cocaine choice procedures in animals, humans, and treatment-seekers: Can we bridge the divide?

Science.gov (United States)

Moeller, Scott J.; Stoops, William W.

2015-01-01

Individuals with cocaine use disorder chronically self-administer cocaine to the detriment of other rewarding activities, a phenomenon best modeled in laboratory drug-choice procedures. These procedures can evaluate the reinforcing effects of drugs versus comparably valuable alternatives under multiple behavioral arrangements and schedules of reinforcement. However, assessing drug-choice in treatment-seeking or abstaining humans poses unique challenges: for ethical reasons, these populations typically cannot receive active drugs during research studies. Researchers have thus needed to rely on alternative approaches that approximate drug-choice behavior or assess more general forms of decision-making, but whether these alternatives have relevance to real-world drug-taking that can inform clinical trials is not well-understood. In this mini-review, we (A) summarize several important modulatory variables that influence cocaine choice in nonhuman animals and non-treatment seeking humans; (B) discuss some of the ethical considerations that could arise if treatment-seekers are enrolled in drug-choice studies; (C) consider the efficacy of alternative procedures, including non-drug-related decision-making and ‘simulated’ drug-choice (a choice is made, but no drug is administered) to approximate drug choice; and (D) suggest opportunities for new translational work to bridge the current divide between preclinical and clinical research. PMID:26432174

Cannabis Use and Support for Cannabis Legalization

NARCIS (Netherlands)

Palali, A.; van Ours, J.C.

2014-01-01

We investigate the determinants of the support for cannabis legalizationfinding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this to self-interest and inside information about potential dangers of cannabis use.

Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities.

Science.gov (United States)

Staley, J K; Mash, D C

1996-10-01

The mesolimbic dopaminergic system plays a primary role in mediating the euphoric and rewarding effects of most abused drugs. Chronic cocaine use is associated with an increase in dopamine neurotransmission resulting from the blockade of dopamine uptake and is mediated by the activation of dopamine receptors. Recent studies have suggested that the D3 receptor subtype plays a pivotal role in the reinforcing effects of cocaine. The D3 receptor-preferring agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) is a reinforcer in rhesus monkeys trained to self-administer cocaine, but not in cocainenaive monkeys. In vitro autoradiographic localization of [3H]-(+)-7-OH-DPAT binding in the human brain demonstrated that D3 receptors were prevalent and highly localized over the ventromedial sectors of the striatum. Pharmacological characterization of [3H]-(+)-7-OH-DPAT binding to the human nucleus accumbens demonstrated a rank order of potency similar to that observed for binding to the cloned D3 receptor expressed in transfected cell lines. Region-of-interest analysis of [3H]-(+)-7-OH-DPAT binding to the D3 receptor demonstrated a one- to threefold elevation in the number of binding sites over particular sectors of the striatum and substantia nigra in cocaine overdose victims as compared with age-matched and drug-free control subjects. The elevated number of [3H]-(+)-7-OH-DPAT binding sites demonstrates that adaptive changes in the D3 receptor in the reward circuitry of the brain are associated with chronic cocaine abuse. These results suggest that the D3 receptor may be a useful target for drug development of anticocaine medications.

Recreational stimulants, herbal, and spice cannabis: The core psychobiological processes that underlie their damaging effects.

Science.gov (United States)

Parrott, Andrew C; Hayley, Amie C; Downey, Luke A

2017-05-01

Recreational drugs are taken for their positive mood effects, yet their regular usage damages well-being. The psychobiological mechanisms underlying these damaging effects will be debated. The empirical literature on recreational cannabinoids and stimulant drugs is reviewed. A theoretical explanation for how they cause similar types of damage is outlined. All psychoactive drugs cause moods and psychological states to fluctuate. The acute mood gains underlie their recreational usage, while the mood deficits on withdrawal explain their addictiveness. Cyclical mood changes are found with every central nervous system stimulant and also occur with cannabis. These mood state changes provide a surface index for more profound psychobiological fluctuations. Homeostatic balance is altered, with repetitive disturbances of the hypothalamic-pituitary-adrenal axis, and disrupted cortisol-neurohormonal secretions. Hence, these drugs cause increased stress, disturbed sleep, neurocognitive impairments, altered brain activity, and psychiatric vulnerability. Equivalent deficits occur with novel psychoactive stimulants such as mephedrone and artificial "spice" cannabinoids. These psychobiological fluctuations underlie drug dependency and make cessation difficult. Psychobiological stability and homeostatic balance are optimally restored by quitting psychoactive drugs. Recreational stimulants such as cocaine or MDMA (3.4-methylenedioxymethamphetamine) and sedative drugs such as cannabis damage human homeostasis and well-being through similar core psychobiological mechanisms. Copyright © 2017 John Wiley & Sons, Ltd.

Overlapping patterns of brain activation to food and cocaine cues in cocaine abusers: association to striatal D2/D3 receptors

OpenAIRE

Tomasi, Dardo; Wang, Gene-Jack; Wang, Ruiliang; Caparelli, Elisabeth C.; Logan, Jean; Volkow, Nora D.

2014-01-01

Cocaine, through its activation of dopamine (DA) signaling, usurps pathways that process natural rewards. However, the extent to which there is overlap between the networks that process natural and drug rewards and whether DA signaling associated with cocaine abuse influences these networks have not been investigated in humans. We measured brain activation responses to food and cocaine cues with fMRI, and D2/D3 receptors in the striatum with [11C]raclopride and PET in 20 active cocaine abuser...

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

Science.gov (United States)

Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

2016-01-01

ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

Cannabis use during adolescent development: susceptibility to psychiatric illness

Directory of Open Access Journals (Sweden)

Benjamin eChadwick

2013-10-01

Full Text Available Cannabis use is increasingly pervasive among adolescents today, even more common than cigarette smoking. The evolving policy surrounding the legalization of cannabis reaffirms the need to understand the relationship between cannabis exposure early in life and psychiatric illnesses. Cannabis contains psychoactive components, notably Δ9-tetrahydrocannbinol (THC, that interfere with the brain’s endogenous endocannabinoid system, which is critically involved in both pre- and post-natal neurodevelopment. Consequently, THC and related compounds could potentially usurp normal adolescent neurodevelopment, shifting the brain’s developmental trajectory towards a disease-vulnerable state, predisposing early cannabis-users to motivational, affective and psychotic disorders. Numerous human studies, including prospective longitudinal studies, demonstrate that early cannabis use is associated with major depressive disorder and drug addiction. A strong association between schizophrenia and cannabis use is also apparent, especially when considering genetic factors that interact with this environmental exposure. These human studies set a foundation for carefully controlled animal studies which demonstrate similar patterns following early cannabinoid exposure. Given the vulnerable nature of adolescent neurodevelopment and the persistent changes that follow early cannabis exposure, the experimental findings outlined should be carefully considered by policymakers. In order to fully address the growing issues of psychiatric illnesses and to ensure a healthy future, measures should be taken to reduce cannabis use among teens.

Cocaine adulteration.

Science.gov (United States)

Kudlacek, Oliver; Hofmaier, Tina; Luf, Anton; Mayer, Felix P; Stockner, Thomas; Nagy, Constanze; Holy, Marion; Freissmuth, Michael; Schmid, Rainer; Sitte, Harald H

2017-10-01

Cocaine is a naturally occurring and illicitly used psychostimulant drug. Cocaine acts at monoaminergic neurotransmitter transporters to block uptake of the monoamines, dopamine, serotonin and norepinephrine. The resulting increase of monoamines in the extracellular space underlies the positively reinforcing effects that cocaine users seek. In turn, this increase in monoamines underlies the development of addiction, and can also result in a number of severe side effects. Currently, cocaine is one of the most common illicit drugs available on the European market. However, cocaine is increasingly sold in impure forms. This trend is driven by cocaine dealers seeking to increase their profit margin by mixing ("cutting") cocaine with numerous other compounds ("adulterants"). Importantly, these undeclared compounds put cocaine consumers at risk, because consumers are not aware of the additional potential threats to their health. This review describes adulterants that have been identified in cocaine sold on the street market. Their typical pharmacological profile and possible reasons why these compounds can be used as cutting agents will be discussed. Since a subset of these adulterants has been found to exert effects similar to cocaine itself, we will discuss levamisole, the most frequently used cocaine cutting agent today, and its metabolite aminorex. Copyright © 2017. Published by Elsevier B.V.

Impact of Sex and Gonadal Hormones on Cocaine and Food Reinforcement Paradigms

OpenAIRE

Kerstetter, Kerry A.; Kippin, Tod E.

2011-01-01

Men and women express sexually dimorphic patterns of cocaine abuse, such that women progress faster from initially trying cocaine to becoming dependent upon the drug and display a greater incidence of relapse. Sex differences in response to cocaine are also seen in the laboratory in both humans and animal models. In this review, animal models of cocaine abuse that have reported sex differences in appetitive reinforcement are discussed. In both human and animal studies, sex differences in the ...

The neuropsychology of cannabis and other substance use in schizophrenia: review of the literature and critical evaluation of methodological issues.

Science.gov (United States)

Coulston, Carissa M; Perdices, Michael; Tennant, Christopher C

2007-11-01

Research on the neuropsychology of substance use in schizophrenia has been steadily growing over the past decade. However, significant gaps remain in the knowledge of individual substances and their relationship to cognition in the schizophrenia spectrum disorders. Approximately 65 studies to date have directly examined this relationship. Of these, approximately 20 have focused on nicotine, 15 on alcohol, 10 on cocaine, three on stimulants/hallucinogens, one on benzodiazepines, 10 on polydrug abuse, and seven on cannabis. Research on cannabis is especially lacking, given that worldwide it is the most commonly used illicit drug in schizophrenia, is used at higher rates in schizophrenia than in the general population, and makes its own unique contribution to the onset and prognosis of schizophrenia. In the present paper an overview of the neuropsychology literature on substance use in schizophrenia is presented, with special emphasis on cannabis. This incorporates a discussion of the methodological limitations inherent in these studies, and range of potential confounding variables that were not considered or controlled, providing directions for future research into the cognitive correlates of cannabis and other substance use in schizophrenia.

Increased sensorimotor gating in recreational and dependent cocaine users is modulated by craving and attention-deficit/hyperactivity disorder symptoms.

Science.gov (United States)

Preller, Katrin H; Ingold, Nina; Hulka, Lea M; Vonmoos, Matthias; Jenni, Daniela; Baumgartner, Markus R; Vollenweider, Franz X; Quednow, Boris B

2013-02-01

Cocaine dependence has been associated with blunted dopamine and norepinephrine signaling, but it is unknown if recreational cocaine use is also associated with alterations of catecholamine systems. Prepulse inhibition (PPI) of the acoustic startle response-a measure of sensorimotor gating-is highly sensitive for manipulations of the catecholamine system. Therefore, we investigated whether relatively pure recreational users (RCU) and dependent cocaine users (DCU) display alterations of PPI, startle reactivity, and habituation. Moreover, the influences of methylenedioxymethamphetamine and cannabis co-use, craving, and attention-deficit/hyperactivity disorder (ADHD) symptoms on startle measures were examined. In 64 RCU, 29 DCU, and 66 stimulant-naïve control subjects, PPI of acoustic startle response, startle reactivity, habituation, ADHD symptoms, and cocaine craving were assessed. Drug use of all participants was controlled by hair and urine toxicologies. Both RCU and DCU showed increased PPI in comparison with control participants (Cohen's d=.38 and d=.67, respectively), while RCU and DCU did not differ in PPI measures (d=.12). No significant group differences were found in startle reactivity or habituation measures. In cocaine users, PPI was positively correlated with cumulative cocaine dose used, craving for cocaine, and ADHD symptoms. Users with a diagnosis of ADHD and strong craving symptoms displayed the highest PPI levels compared with control subjects (d=.78). The augmented PPI in RCU and DCU suggests that recreational use of cocaine is associated with altered catecholamine signaling, in particular if ADHD or craving symptoms are present. Finally, ADHD might be a critical risk factor for cocaine-induced changes of the catecholamine system. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Demand curves for hypothetical cocaine in cocaine-dependent individuals.

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Bruner, Natalie R; Johnson, Matthew W

2014-03-01

Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

A bacterial cocaine esterase protects against cocaine-induced epileptogenic activity and lethality.

Science.gov (United States)

Jutkiewicz, Emily M; Baladi, Michelle G; Cooper, Ziva D; Narasimhan, Diwahar; Sunahara, Roger K; Woods, James H

2009-09-01

Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (-)-2beta-carbomethoxy-3beta-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted.

Self-reported cannabis products and other illicit drugs consumption in older school-age children in Northern Lithuania: a comparison between 2006 and 2012.

Science.gov (United States)

Miniauskienė, Dalia; Jurgaitienė, Dalia; Strukčinskienė, Birutė

2014-01-01

Cannabis use is widespread among young people in Europe. The aim of this study was to analyze and to compare the associations between the self-reported consumption of cannabis products and other illicit drugs among older schoolchildren in 2006 and in 2012. Two cross-sectional surveys were conducted in 2006 and 2012 in Northern Lithuania. In total 3447 young people aged 17-19 years were investigated (1585 male and 1862 female). For this survey, the ESPAD questionnaire was used. In Northern Lithuania, the schoolchildren aged 17-19 years self-reported that 16.7% in 2006 and 23.9% in 2012 of them tried cannabis products. The consumption of cannabis products in the age group of 17 years increased from 14.9% in 2006 to 21.5% in 2012. The consumption of cannabis together with alcohol increased from 7.6% to 14.3%. Cannabis consumers more often tried amphetamines, heroin, LSD, cocaine, crack, ecstasy, hallucinogenic mushrooms, and injective drugs. In 2012, cannabis consumers girls less than boys used only crack and injective drugs; all other illicit drugs they used the same often as boys. The cannabis products consumption in schoolchildren has increased by 7%. Nearly twofold increase was observed in the consumption of cannabis together with alcohol. Young people who used cannabis products more often tried other illicit drugs. There were no differences by gender in the consumption of illicit drugs among cannabis consumers. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Cocaine

Science.gov (United States)

Cocaine is a white powder. It can be snorted up the nose or mixed with water and injected with a needle. Cocaine can also be made into small white rocks, ... Crack is smoked in a small glass pipe. Cocaine speeds up your whole body. You may feel ...

Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

International Nuclear Information System (INIS)

Moeller, S.J.; Goldstein, R.; Moeller, S.J.; Maloney, T.; Parvaz, M.A.; Dunning, J.P.; Alia-Klein, N.; Woicik, P.A.; Hajcak, G.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

2009-01-01

Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.

Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

Energy Technology Data Exchange (ETDEWEB)

Moeller, S.J.; Goldstein, R.; Moeller, S.J.; Maloney, T. Parvaz, M.A.; Dunning, J.P.; Alia-Klein, N.; Woicik, P.A.; Hajcak, G.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

2009-02-01

Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.

Cannabis arteritis.

Science.gov (United States)

El Omri, Naoual; Eljaoudi, Rachid; Mekouar, Fadwa; Jira, Mohammed; Sekkach, Youssef; Amezyane, Taoufik; Ghafir, Driss

2017-01-01

Cannabis is the most consumed psychoactive substance by young people. Chronic use of cannabis can lead to cannabis arteritis, which is a very rare peripheral vascular disease similar to Buerger's disease. It is affecting young adults, especially men, consuming cannabis. A 27-year old woman, with no particular past medical history except for long-term use of cannabis and tobacco developed a digital necrosis in the left hand. She denied using other illicit drugs. Doppler ultrasound examination of the upper limbs was unremarkable. Toxicological analysis revealed the presence of cannabis in both biological fluid and hair strand. Despite medical treatment, cessation of the cannabis and tobacco consumption and hyperbaric oxygen therapy, an amputation of necrotic parts was then required. This case shows the prolonged use of cannabis could be a risk factor for young adult arteritis. Faced with a rapidly progressive arteritis occurring in young adult, the physician should consider the history of use of cannabis. Hair analysis can be useful for confirmation of the chronic consumption of drugs.

Motivated attention to cocaine and emotional cues in abstinent and current cocaine users--an ERP study.

Science.gov (United States)

Dunning, Jonathan P; Parvaz, Muhammad A; Hajcak, Greg; Maloney, Thomas; Alia-Klein, Nelly; Woicik, Patricia A; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D; Goldstein, Rita Z

2011-05-01

Event-related potentials (ERPs) are a direct measure of neural activity and are ideally suited to study the time-course of attentional engagement with emotional and drug-related stimuli in addiction. In particular, the late positive potential (LPP) appears to be enhanced following cocaine-related compared with neutral stimuli in human participants with cocaine use disorders (CUD). However, previous studies have not directly compared cocaine-related with emotional stimuli while examining potential differences between abstinent and current cocaine users. The present study examined ERPs in 55 CUD (27 abstinent and 28 current users) and 29 matched healthy controls while they passively viewed pleasant, unpleasant, neutral and cocaine-related pictures. To examine the time-course of attention to these stimuli, we analysed both an early and later window in the LPP as well as the early posterior negativity (EPN), established in assessing motivated attention. Cocaine pictures elicited increased electrocortical measures of motivated attention in ways similar to affectively pleasant and unpleasant pictures in all CUD, an effect that was no longer discernible during the late LPP window for the current users. This group also exhibited deficient processing of the other emotional stimuli (early LPP window - pleasant pictures; late LPP window - pleasant and unpleasant pictures). Results were unique to the LPP and not EPN. Taken together, results support a relatively early attention bias to cocaine stimuli in cocaine-addicted individuals, further suggesting that recent cocaine use decreases such attention bias during later stages of processing but at the expense of deficient processing of other emotional stimuli. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

The cannabis withdrawal syndrome: current insights

Science.gov (United States)

Bonnet, Udo; Preuss, Ulrich W

2017-01-01

The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders (CUDs) (Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition) and cannabis dependence (International Classification of Diseases [ICD]-10). Several lines of evidence from animal and human studies indicate that cessation from long-term and regular cannabis use precipitates a specific withdrawal syndrome with mainly mood and behavioral symptoms of light to moderate intensity, which can usually be treated in an outpatient setting. Regular cannabis intake is related to a desensitization and downregulation of human brain cannabinoid 1 (CB1) receptors. This starts to reverse within the first 2 days of abstinence and the receptors return to normal functioning within 4 weeks of abstinence, which could constitute a neurobiological time frame for the duration of CWS, not taking into account cellular and synaptic long-term neuroplasticity elicited by long-term cannabis use before cessation, for example, being possibly responsible for cannabis craving. The CWS severity is dependent on the amount of cannabis used pre-cessation, gender, and heritable and several environmental factors. Therefore, naturalistic severity of CWS highly varies. Women reported a stronger CWS than men including physical symptoms, such as nausea and stomach pain. Comorbidity with mental or somatic disorders, severe CUD, and low social functioning may require an inpatient treatment (preferably qualified detox) and post-acute rehabilitation. There are promising results with gabapentin and delta-9-tetrahydrocannabinol analogs in the treatment of CWS. Mirtazapine can be beneficial to treat CWS insomnia. According to small studies, venlafaxine can worsen the CWS, whereas other antidepressants, atomoxetine, lithium, buspirone, and divalproex had no relevant effect. Certainly, further research is required with respect to the impact of the CWS treatment setting on long-term CUD prognosis and with respect to

Modeling evolution of hydrogen bonding and stabilization of transition states in the process of cocaine hydrolysis catalyzed by human butyrylcholinesterase.

Science.gov (United States)

Gao, Daquan; Zhan, Chang-Guo

2006-01-01

Molecular dynamics (MD) simulations and quantum mechanical/molecular mechanical (QM/MM) calculations were performed on the prereactive enzyme-substrate complex, transition states, intermediates, and product involved in the process of human butyrylcholinesterase (BChE)-catalyzed hydrolysis of (-)-cocaine. The computational results consistently reveal a unique role of the oxyanion hole (consisting of G116, G117, and A199) in BChE-catalyzed hydrolysis of cocaine, compared to acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylcholine. During BChE-catalyzed hydrolysis of cocaine, only G117 has a hydrogen bond with the carbonyl oxygen (O31) of the cocaine benzoyl ester in the prereactive BChE-cocaine complex, and the NH groups of G117 and A199 are hydrogen-bonded with O31 of cocaine in all of the transition states and intermediates. Surprisingly, the NH hydrogen of G116 forms an unexpected hydrogen bond with the carboxyl group of E197 side chain and, therefore, is not available to form a hydrogen bond with O31 of cocaine in the acylation. The NH hydrogen of G116 is only partially available to form a weak hydrogen bond with O31 of cocaine in some structures involved in the deacylation. The change of the estimated hydrogen-bonding energy between the oxyanion hole and O31 of cocaine during the reaction process demonstrates how the protein environment can affect the energy barrier for each step of the BChE-catalyzed hydrolysis of cocaine. These insights concerning the effects of the oxyanion hole on the energy barriers provide valuable clues on how to rationally design BChE mutants with a higher catalytic activity for the hydrolysis of (-)-cocaine. 2005 Wiley-Liss, Inc.

Effects of chronic cocaine abuse on postsynaptic dopamine receptors

International Nuclear Information System (INIS)

Volkow, N.D.; Fowler, J.S.; Wolf, A.P.; Schlyer, D.; Shiue, C.Y.; Alpert, R.; Dewey, S.L.; Logan, J.; Bendriem, B.; Christman, D.

1990-01-01

To assess the effects of chronic cocaine intoxication on dopamine receptors in human subjects, the authors evaluated [ 18 F]N-methylspiroperidol binding using positron emission tomography in 10 cocaine abusers and 10 normal control subjects. Cocaine abusers who had been detoxified for 1 week or less showed significantly lower values for uptake of [ 18 F]N-methylspiroperidol in striatum than the normal subjects, whereas the cocaine abusers who had been detoxified for 1 month showed values comparable to those obtained from normal subjects. The authors conclude that postsynaptic dopamine receptor availability decreases with chronic cocaine abuse but may recover after a drug-free interval

Cannabis use and support for cannabis legalization

NARCIS (Netherlands)

Palali, Ali; van Ours, Jan

2017-01-01

We investigate the determinants of the support for cannabis legalization finding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this finding to self-interest and inside information about potential dangers of

Sex-dependent effects of cannabis-induced analgesia.

Science.gov (United States)

Cooper, Ziva D; Haney, Margaret

2016-10-01

Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to humans. This retrospective analysis compared the analgesic, subjective and physiological effects of active cannabis (3.56-5.60% THC) and inactive cannabis (0.00% THC) in male (N=21) and female (N=21) cannabis smokers under double-blind, placebo-controlled conditions. Pain response was measured using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4°C); times to report pain (pain sensitivity) and withdraw the hand (pain tolerance) were recorded. Subjective drug ratings were also measured. Among men, active cannabis significantly decreased pain sensitivity relative to inactive cannabis (pcannabis failed to decrease pain sensitivity relative to inactive. Active cannabis increased pain tolerance in both men women immediately after smoking (pcannabis also increased subjective ratings of cannabis associated with abuse liability ('Take again,' 'Liking,' 'Good drug effect'), drug strength, and 'High' relative to inactive in both men and women (pcannabis smokers, men exhibit greater cannabis-induced analgesia relative to women. These sex-dependent differences are independent of cannabis-elicited subjective effects associated with abuse-liability, which were consistent between men and women. As such, sex-dependent differences in cannabis's analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Attitudes of cannabis growers to regulation of cannabis cultivation under a non-prohibition cannabis model.

Science.gov (United States)

Lenton, Simon; Frank, Vibeke A; Barratt, Monica J; Dahl, Helle Vibeke; Potter, Gary R

2015-03-01

How cannabis cultivation is dealt with under various examples of cannabis legalization or regulation is an important consideration in design of such schemes. This study aimed to (i) investigate support among current or recent cannabis growers, for various potential policy options for cannabis cultivation if prohibition were repealed, and (ii) explore the support for these options across countries, scale of growing operations, demographics, drug use and cannabis supply involvement variables. This study utilized data from the online web survey of largely 'small-scale' cannabis cultivators, aged 18yrs and over, in eleven countries conducted by the Global Cannabis Cultivation Research Consortium (GCCRC). Data from 1722 current and recent cannabis growers in Australia, Denmark and the UK, who were all asked about policy, were included in the analysis. It investigated support for various frameworks for cultivation: (no regulation (free market); adult only; growing licenses; restrictions on plant numbers; licensed business-only sale; approved commercial growing; etc.). Among current growers, support for these options were compared across countries, across scale of growing operations, and by demographics, drug use and crime variables. Although there were some between country differences in support for the various policy options, what was striking was the similarity of the proportions for each of the eight most popular policy options. Among current growers, many of these positions were predicted by demographic, drug use and cannabis growing variables which were conceptually congruent with these positions. The results have relevance for the provisions regarding cannabis cultivation in the design of new non-prohibitionist models of cannabis which are increasingly under consideration. It should be of interest to policy makers, drug policy researchers, law enforcement and cannabis cultivators. Copyright © 2014 Elsevier B.V. All rights reserved.

Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications

OpenAIRE

Sharma, Priyamvada; Murthy, Pratima; Bharath, M.M. Srinivas

2012-01-01

Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (?9_THC), produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders. Many studies that endeavor to understand the mechanism of action of cannabis concentrate o...

Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

Science.gov (United States)

Fischer, Benedikt; Kuganesan, Sharan; Gallassi, Andrea; Malcher-Lopes, Renato; van den Brink, Wim; Wood, Evan

2015-12-01

Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for

Positron emitting tracers for studies of cocaine

International Nuclear Information System (INIS)

Fowler, J.S.; Gatley, S.J.; MacGregor, R.R.; Wolf, A.P.; Yu, D.W.; Dewey, S.L.; Schlyer, D.J.; Volkow, N.D.; Bendriem, B.; Logan, J.

1990-01-01

The use of PET to study the behavior and mechanism of action of therapeutic drugs and substances of abuse can be approached from a number of perspectives. The most common approach is to measure the effect of a drug on some aspect of metabolism and requires well characterized radiotracers whose behavior in vivo can be related to a discrete biochemical transformation. A second approach is to study the labeled drug itself. This provides information on the drug's regional distribution and kinetics as well as its pharmacological profile and metabolism. Cocaine has been labeled in different positions with carbon-11 and with fluorine-18 and the stereoisomers of cocaine have also been labeled to characterize its binding and metabolism in human and baboon brain. Regional cocaine binding as measured by PET is consistent with reversible binding to striatal dopamine reuptake sites and its time course parallels the behavioral activation of cocaine. The behaviorally inactive enantiomer (+)-cocaine is rapidly metabolized in serum preventing its entry into the brain. These PET tracers are useful in understanding the neurochemical basis of cocaine's action

Cocrystallization studies of full-length recombinant butyrylcholinesterase (BChE) with cocaine

Energy Technology Data Exchange (ETDEWEB)

Asojo, Oluwatoyin Ajibola; Asojo, Oluyomi Adebola; Ngamelue, Michelle N.; Homma, Kohei; Lockridge, Oksana (Nebraska-Med)

2011-09-16

Human butyrylcholinesterase (BChE; EC 3.1.1.8) is a 340 kDa tetrameric glycoprotein that is present in human serum at about 5 mg l{sup -1} and has well documented therapeutic effects on cocaine toxicity. BChE holds promise as a therapeutic that reduces and finally eliminates the rewarding effects of cocaine, thus weaning an addict from the drug. There have been extensive computational studies of cocaine hydrolysis by BChE. Since there are no reported structures of BChE with cocaine or any of the hydrolysis products, full-length monomeric recombinant wild-type BChE was cocrystallized with cocaine. The refined 3 {angstrom} resolution structure appears to retain the hydrolysis product benzoic acid in sufficient proximity to form a hydrogen bond to the active-site Ser198.

Cannabis use in children and adolescents with first episode psychosis: influence on psychopathology and short-term outcome (CAFEPS study).

Science.gov (United States)

Baeza, Immaculada; Graell, Montserrat; Moreno, Dolores; Castro-Fornieles, Josefina; Parellada, Mara; González-Pinto, Ana; Payá, Beatriz; Soutullo, César; de la Serna, Elena; Arango, Celso

2009-09-01

To know the prevalence of substance use and its relationship with psychopathology at onset and after six months in children and adolescents with first episode psychosis (FEP). 110 FEP patients, aged 9-17, were assessed for substance use, and with the Positive and Negative Syndrome Scale (PANSS) and other psychopathological and general functioning scales at baseline and after a six-month follow-up. Patients' substance use at baseline was: tobacco (30.9%), cannabis (29.1%), alcohol (21.8%), cocaine (8.2%), amphetamines (2.7%), LSD (1.8%) and opiates (0.90%). Six months later, there was a decrease in patients' use of cannabis (p=0.004) and other drugs, except tobacco. Patients were divided, according to their baseline cannabis use, into 32 cannabis users (CU) and 78 non-cannabis users (NCU). CU were older (p=0.002) and had higher PANSS positive scores (p=0.002) and lower PANSS negative (p<0.001), PANSS general (p=0.002) and PANSS total (p=0.007) scores than NCU. At six months, CU had significantly lower PANSS positive (p=0.010), negative (p=0.0001), general (p=0.002) and total (p=0.002) scores than NCU. When we divided CU at six months into previous CU (n=16) and current CU (n=15), previous CU had the best outcome, NCU the worst and current CU had an intermediate profile. Cannabis use may be related to higher positive symptom scores for FEP patients, with greater improvement after six months for those who cease using cannabis.

Measuring cannabis consumption: Psychometric properties of the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU).

Science.gov (United States)

Cuttler, Carrie; Spradlin, Alexander

2017-01-01

We created the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU) because the current lack of psychometrically sound inventories for measuring these dimensions of cannabis use has impeded research on the effects of cannabis in humans. A sample of 2,062 cannabis users completed the DFAQ-CU and was used to assess the DFAQ-CU's factor structure and reliability. To assess validity, a subsample of 645 participants completed additional measures of cannabis dependence and problems (Marijuana Smoking History Questionnaire [MSHQ], Timeline Followback [TLFB], Cannabis Abuse Screening Test [CAST], Cannabis Use Disorders Identification Test Revised [CUDIT-R], Cannabis Use Problems Identification Test [CUPIT], and Alcohol Use Disorder Identification Test [AUDIT]). A six-factor structure was revealed, with factors measuring: daily sessions, frequency, age of onset, marijuana quantity, cannabis concentrate quantity, and edibles quantity. The factors were reliable, with Cronbach's alpha coefficients ranging from .69 (daily sessions) to .95 (frequency). Results further provided evidence for the factors' convergent (MSHQ, TLFB), predictive (CAST, CUDIT-R, CUPIT), and discriminant validity (AUDIT). The DFAQ-CU is the first psychometrically sound inventory for measuring frequency, age of onset, and quantity of cannabis use. It contains pictures of marijuana to facilitate the measurement of quantity of marijuana used, as well as questions to assess the use of different forms of cannabis (e.g., concentrates, edibles), methods of administering cannabis (e.g., joints, hand pipes, vaporizers), and typical THC levels. As such, the DFAQ-CU should help facilitate research on frequency, quantity, and age of onset of cannabis use.

Measuring cannabis consumption: Psychometric properties of the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU.

Directory of Open Access Journals (Sweden)

Carrie Cuttler

Full Text Available We created the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU because the current lack of psychometrically sound inventories for measuring these dimensions of cannabis use has impeded research on the effects of cannabis in humans.A sample of 2,062 cannabis users completed the DFAQ-CU and was used to assess the DFAQ-CU's factor structure and reliability. To assess validity, a subsample of 645 participants completed additional measures of cannabis dependence and problems (Marijuana Smoking History Questionnaire [MSHQ], Timeline Followback [TLFB], Cannabis Abuse Screening Test [CAST], Cannabis Use Disorders Identification Test Revised [CUDIT-R], Cannabis Use Problems Identification Test [CUPIT], and Alcohol Use Disorder Identification Test [AUDIT].A six-factor structure was revealed, with factors measuring: daily sessions, frequency, age of onset, marijuana quantity, cannabis concentrate quantity, and edibles quantity. The factors were reliable, with Cronbach's alpha coefficients ranging from .69 (daily sessions to .95 (frequency. Results further provided evidence for the factors' convergent (MSHQ, TLFB, predictive (CAST, CUDIT-R, CUPIT, and discriminant validity (AUDIT.The DFAQ-CU is the first psychometrically sound inventory for measuring frequency, age of onset, and quantity of cannabis use. It contains pictures of marijuana to facilitate the measurement of quantity of marijuana used, as well as questions to assess the use of different forms of cannabis (e.g., concentrates, edibles, methods of administering cannabis (e.g., joints, hand pipes, vaporizers, and typical THC levels. As such, the DFAQ-CU should help facilitate research on frequency, quantity, and age of onset of cannabis use.

Prevalence of DSM-IV and DSM-5 Alcohol, Cocaine, Opioid, and Cannabis Use Disorders in a Largely Substance Dependent Sample

Science.gov (United States)

Peer, Kyle; Rennert, Lior; Lynch, Kevin G.; Farrer, Lindsay; Gelernter, Joel; Kranzler, Henry R.

2012-01-01

BACKGROUND The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) will soon replace the DSM-IV, which has existed for nearly two decades. The changes in diagnostic criteria have important implications for research and for the clinical care of individuals with Substance Use Disorders (SUDs). METHODS We used the Semi-Structured Assessment for Drug Dependence and Alcoholism to evaluate the lifetime presence of DSM-IV abuse and dependence diagnoses and DSM-5 mild, moderate, or severe SUDs for alcohol, cocaine, opioids, and cannabis in a sample of 7,543 individuals recruited to participate in genetic studies of substance dependence. RESULTS Switches between diagnostic systems consistently resulted in a modestly greater prevalence for DSM-5 SUDs, based largely on the assignment of DSM-5 diagnoses to DSM-IV “diagnostic ophans” (i.e., individuals meeting one or two criteria for dependence and none for abuse, and thus not receiving a DSM-IV SUD diagnosis). The vast majority of these diagnostic switches were attributable to the requirement that only two of 11 criteria be met for a DSM-5 SUD diagnosis. We found evidence to support the omission from DSM-5 of the legal criterion due to its limited diagnostic utility. The addition of craving as a criterion in DSM-5 did not substantially affect the likelihood of an SUD diagnosis. CONCLUSION The greatest advantage of DSM-5 appears to be its ability to capture diagnostic orphans. In this sample, changes reflected in DSM-5 had a minimal impact on the prevalence of SUD diagnoses. PMID:22884164

PET imaging predicts future body weight and cocaine preference

International Nuclear Information System (INIS)

Michaelides, M.; Wang, G.; Michaelides, M.; Thanos, P.K.; Kim, R.; Cho, J.; Ananth, M.; Wang, G.-J.; Volkow N.D.

2012-01-01

Deficits in dopamine D2/D3 receptor (D2R/D3R) binding availability using PET imaging have been reported in obese humans and rodents. Similar deficits have been reported in cocaine-addicts and cocaine-exposed primates. We found that D2R/D3R binding availability negatively correlated with measures of body weight at the time of scan (ventral striatum), at 1 (ventral striatum) and 2 months (dorsal and ventral striatum) post scan in rats. Cocaine preference was negatively correlated with D2R/D3R binding availability 2 months (ventral striatum) post scan. Our findings suggest that inherent deficits in striatal D2R/D3R signaling are related to obesity and drug addiction susceptibility and that ventral and dorsal striatum serve dissociable roles in maintaining weight gain and cocaine preference. Measuring D2R/D3R binding availability provides a way for assessing susceptibility to weight gain and cocaine abuse in rodents and given the translational nature of PET imaging, potentially primates and humans.

PET imaging predicts future body weight and cocaine preference

Energy Technology Data Exchange (ETDEWEB)

Michaelides M.; Wang G.; Michaelides M.; Thanos P.K. Kim R.; Cho J.; Ananth M.; Wang G.-J.; Volkow N.D.

2011-08-28

Deficits in dopamine D2/D3 receptor (D2R/D3R) binding availability using PET imaging have been reported in obese humans and rodents. Similar deficits have been reported in cocaine-addicts and cocaine-exposed primates. We found that D2R/D3R binding availability negatively correlated with measures of body weight at the time of scan (ventral striatum), at 1 (ventral striatum) and 2 months (dorsal and ventral striatum) post scan in rats. Cocaine preference was negatively correlated with D2R/D3R binding availability 2 months (ventral striatum) post scan. Our findings suggest that inherent deficits in striatal D2R/D3R signaling are related to obesity and drug addiction susceptibility and that ventral and dorsal striatum serve dissociable roles in maintaining weight gain and cocaine preference. Measuring D2R/D3R binding availability provides a way for assessing susceptibility to weight gain and cocaine abuse in rodents and given the translational nature of PET imaging, potentially primates and humans.

Cocaine Versus Food Choice Procedure in Rats: Environmental Manipulations and Effects of Amphetamine

Science.gov (United States)

Thomsen, Morgane; Barrett, Andrew C.; Negus, S. Stevens; Caine, S. Barak

2014-01-01

We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0–1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. PMID:23319458

The intersection between cannabis and cancer in the United States.

Science.gov (United States)

Bowles, Daniel W; O'Bryant, Cindy L; Camidge, D Ross; Jimeno, Antonio

2012-07-01

In the last 15 years there has been a major shift in the laws governing medical use of cannabis in the United States. Corresponding with this change there has been escalating interest in the role that cannabis, commonly referred to as marijuana, and cannabinoids play in the care of patients with cancer. This review will examine cannabis' and cannabinoids' current and potential roles in cancer care. Specifically, we will examine five areas of cannabis medicine: (1) pharmacologic properties of cannabis; (2) its potential role in the development of human cancers, particularly smoking-related malignancies; (3) cannabinoids' potential as anti-cancer therapies; (4) cannabis and cannabinoids in the palliation of common cancer-associated symptoms; (5) current legal status of cannabis for medical purposes in the United States. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

Science.gov (United States)

Hirvonen, J; Goodwin, R S; Li, C-T; Terry, G E; Zoghbi, S S; Morse, C; Pike, V W; Volkow, N D; Huestis, M A; Innis, R B

2012-06-01

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

Distance to Cannabis-Shops and Age of Onset of Cannabis Use

NARCIS (Netherlands)

Palali, A.; van Ours, J.C.

2013-01-01

Abstract: In the Netherlands cannabis use is quasi-legalized. Small quantities of cannabis can be bought in cannabis-shops. We investigate how the distance to the nearest cannabis- shop affects the age of onset of cannabis use. We use a Mixed Proportional Hazard rate framework to take account of

The toxicology of cannabis and cannabis prohibition.

Science.gov (United States)

Grotenhermen, Franjo

2007-08-01

The acute side effects caused by cannabis use are mainly related to psyche and cognition, and to circulation. Euphoria, anxiety, changes in sensory perception, impairment of memory and psychomotor performance are common effects after a dose is taken that exceeds an individually variable threshold. Cannabis consumption may increase heart rate and change blood pressure, which may have serious consequences in people with heart disease. Effects of chronic use may be induction of psychosis and development of dependency to the drug. Effects on cognitive abilities seem to be reversible after abstinence, except possibly in very heavy users. Cannabis exposure in utero may have negative consequences on brain development with subtle impairment of cognitive abilities in later life. Consequences of cannabis smoking may be similar to those of tobacco smoking and should be avoided. Use by young people has more detrimental effects than use by adults. There appear to be promising therapeutic uses of cannabis for a range of indications. Use of moderate doses in a therapeutic context is usually not associated with severe side effects. Current prohibition on cannabis use may also have harmful side effects for the individual and the society, while having little influence on prevalence of use. Harm is greatest for seriously ill people who may benefit from a treatment with cannabis. This makes it difficult to justify criminal penalties against patients.

Modeling Evolution of Hydrogen Bonding and Stabilization of Transition States in the Process of Cocaine Hydrolysis Catalyzed by Human Butyrylcholinesterase

OpenAIRE

Gao, Daquan; Zhan, Chang-Guo

2006-01-01

Molecular dynamics (MD) simulations and quantum mechanical/molecular mechanical (QM/MM) calculations were performed on the prereactive enzyme-substrate complex, transition states, intermediates, and product involved in the process of human butyrylcholinesterase (BChE)-catalyzed hydrolysis of (−)-cocaine. The computational results consistently reveal a unique role of the oxyanion hole (consisting of G116, G117, and A199) in BChE-catalyzed hydrolysis of cocaine, as compared to acetylcholinester...

Treatment of Crohn's disease with cannabis: an observational study.

Science.gov (United States)

Naftali, Timna; Lev, Lihi Bar; Yablecovitch, Doron; Yablekovitz, Doron; Half, Elisabeth; Konikoff, Fred M

2011-08-01

The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn's disease (CD) was ever published. To describe the effects of cannabis use in patients suffering from CD. In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn's disease. Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 +/- 6.7 to 7 +/- 4.7 (P disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.

The cannabis withdrawal syndrome: current insights

Directory of Open Access Journals (Sweden)

Bonnet U

2017-04-01

Full Text Available Udo Bonnet,1,2 Ulrich W Preuss3,4 1Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg-Essen, Castrop-Rauxel, 2Department of Psychiatry and Psychotherapy, Faculty of Medicine, LVR-Hospital Essen, University of Duisburg-Essen, Essen, 3Vitos-Klinik Psychiatrie und Psychotherapie Herborn, Herborn, 4Martin Luther University Halle-Wittenberg, Halle (Saale, Germany Abstract: The cannabis withdrawal syndrome (CWS is a criterion of cannabis use disorders (CUDs (Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition and cannabis dependence (International Classification of Diseases [ICD]-10. Several lines of evidence from animal and human studies indicate that cessation from long-term and regular cannabis use precipitates a specific withdrawal syndrome with mainly mood and behavioral symptoms of light to moderate intensity, which can usually be treated in an outpatient setting. Regular cannabis intake is related to a desensitization and downregulation of human brain cannabinoid 1 (CB1 receptors. This starts to reverse within the first 2 days of abstinence and the receptors return to normal functioning within 4 weeks of abstinence, which could constitute a neurobiological time frame for the duration of CWS, not taking into account cellular and synaptic long-term neuroplasticity elicited by long-term cannabis use before cessation, for example, being possibly responsible for cannabis craving. The CWS severity is dependent on the amount of cannabis used pre-cessation, gender, and heritable and several environmental factors. Therefore, naturalistic severity of CWS highly varies. Women reported a stronger CWS than men including physical symptoms, such as nausea and stomach pain. Comorbidity with mental or somatic disorders, severe CUD, and low social functioning may require an inpatient treatment (preferably qualified detox and

Features and prevalence of patients with probable adult attention deficit hyperactivity disorder who request treatment for cocaine use disorders.

Science.gov (United States)

Pérez de Los Cobos, José; Siñol, Núria; Puerta, Carmen; Cantillano, Vanessa; López Zurita, Cristina; Trujols, Joan

2011-01-30

To characterize those patients with probable adult attention deficit hyperactivity disorder (ADHD) who ask for treatment of cocaine use disorders; to estimate the prevalence of probable adult ADHD among these patients. This is a cross-sectional and multi-center study performed at outpatient resources of 12 addiction treatment centers in Spain. Participants were treatment-seeking primary cocaine abusers recruited consecutively at one center and through convenience sampling at the other centers. Assessments included semi-structured clinical interview focused on Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) ADHD criteria adapted to adulthood, and the Wender-Utah Rating Scale (WURS) for screening childhood history of ADHD according to patients. Probable adult ADHD was diagnosed when patients met DSM-IV criteria of ADHD in adulthood and scored WURS>32. All participants were diagnosed with current cocaine dependence (n=190) or abuse (n=15). Patients with probable adult ADHD, compared with patients having no lifetime ADHD, were more frequently male, reported higher impulsivity, and began to use nicotine, alcohol, cannabis, or cocaine earlier. Before starting the current treatment, patients with probable adult ADHD also showed higher cocaine craving for the previous day, less frequent cocaine abstinence throughout the previous week, and higher use of cocaine and tobacco during the previous month. Impulsivity and male gender were the only independent risk factors of probable adult ADHD in a logistic regression analysis. The prevalence of probable adult ADHD was 20.5% in the sub-sample of patients consecutively recruited (n=78). A diagnosis of probable adult ADHD strongly distinguishes among treatment-seeking cocaine primary abusers regarding past and current key aspects of their addictive disorder; one-fifth of these patients present with probable adult ADHD. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Assessing Topographical Orientation Skills in Cannabis Users

Directory of Open Access Journals (Sweden)

Liana Palermo

2012-01-01

Full Text Available The long-term effects of cannabis on human cognition are still unclear, but, considering that cannabis is a widely used substance and, overall, its potential use in therapeutic interventions, it is important to evaluate them. We hypothesize that the discrepancies among studies could be attributed to the specific cognitive function investigated and that skills subserved by the hippocampus, such as the spatial orientation abilities and, specifically, the ability to form and use cognitive maps, should be more compromised than others. Indeed it has been showed that cannabis users have a reduced hippocampus and that the hippocampus is the brain region in which cannabis has the greatest effect since it contains the highest concentration of cannabinoid receptors. To test this hypothesis we asked 15 heavy cannabis users and 19 nonusers to perform a virtual navigational test, the CMT, that assesses the ability to form and use cognitive maps. We found that using cannabis has no effect on these hippocampus-dependent orientation skills. We discuss the implications of our findings and how they relate to evidence reported in the literature that the intervention of functional reorganization mechanisms in cannabis user allows them to cope with the cognitive demands of navigational tasks.

Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users.

Science.gov (United States)

Belendiuk, Katherine A; Babson, Kimberly A; Vandrey, Ryan; Bonn-Miller, Marcel O

2015-11-01

Individuals report using cannabis for the promotion of sleep, and the effects of cannabis on sleep may vary by cannabis species. Little research has documented preferences for particular cannabis types or cannabinoid concentrations as a function of use for sleep disturbances. 163 adults purchasing medical cannabis for a physical or mental health condition at a cannabis dispensary were recruited. They provided self-report of (a) whether cannabis use was intended to help with sleep problems (e.g. insomnia, nightmares), (b) sleep quality (PSQI), (c) cannabis use (including preferred type), and (d) symptoms of DSM-5 cannabis dependence. 81 participants reported using cannabis for the management of insomnia and 14 participants reported using cannabis to reduce nightmares. Individuals using cannabis to manage nightmares preferred sativa to indica strains (Fisher's exact test (2) = 6.83, p < 0.05), and sativa users were less likely to endorse DSM-5 cannabis dependence compared with those who preferred indica strains (χ(2)(2) = 4.09, p < 0.05). Individuals with current insomnia (t(9) = 3.30, p < 0.01) and greater sleep latency (F(3,6) = 46.7, p < 0.001) were more likely to report using strains of cannabis with significantly higher concentrations of CBD. Individuals who reported at least weekly use of hypnotic medications used cannabis with lower THC concentrations compared to those who used sleep medications less frequently than weekly (t(17) = 2.40, p < 0.05). Associations between sleep characteristics and the type of cannabis used were observed in this convenience sample of individuals using cannabis for the management of sleep disturbances. Controlled prospective studies are needed to better characterize the impact that specific components of cannabis have on sleep. Copyright © 2015. Published by Elsevier Ltd.

Screening and Evaluation of Medications for Treating Cannabis Use Disorder

Science.gov (United States)

Panlilio, Leigh V.; Justinova, Zuzana; Trigo, Jose M.; Le Foll, Bernard

2016-01-01

Cannabis use has been increasingly accepted legally and in public opinion. However, cannabis has the potential to produce adverse physical and mental health effects and can result in cannabis use disorder (CUD) in a substantial percentage of both occasional and daily cannabis users. Many people have difficulty discontinuing use. Therefore, it would be beneficial to develop safe and effective medications for treating CUD. To achieve this, methods have been developed for screening and evaluating potential medications using animal models and controlled experimental protocols in human volunteers. In this chapter we describe: 1) animal models available for assessing the effect of potential medications on specific aspects of CUD; 2) the main findings obtained so far with these animal models; 3) the approaches used to assess potential medications in humans in laboratory experiments and clinical trials; and 4) the effectiveness of several potential pharmacotherapies on the particular aspects of CUD modeled in these human studies. PMID:27055612

Association between increased EEG signal complexity and cannabis dependence.

Science.gov (United States)

Laprevote, Vincent; Bon, Laura; Krieg, Julien; Schwitzer, Thomas; Bourion-Bedes, Stéphanie; Maillard, Louis; Schwan, Raymund

2017-12-01

Both acute and regular cannabis use affects the functioning of the brain. While several studies have demonstrated that regular cannabis use can impair the capacity to synchronize neural assemblies during specific tasks, less is known about spontaneous brain activity. This can be explored by measuring EEG complexity, which reflects the spontaneous variability of human brain activity. A recent study has shown that acute cannabis use can affect that complexity. Since the characteristics of cannabis use can affect the impact on brain functioning, this study sets out to measure EEG complexity in regular cannabis users with or without dependence, in comparison with healthy controls. We recruited 26 healthy controls, 25 cannabis users without cannabis dependence and 14 cannabis users with cannabis dependence, based on DSM IV TR criteria. The EEG signal was extracted from at least 250 epochs of the 500ms pre-stimulation phase during a visual evoked potential paradigm. Brain complexity was estimated using Lempel-Ziv Complexity (LZC), which was compared across groups by non-parametric Kruskall-Wallis ANOVA. The analysis revealed a significant difference between the groups, with higher LZC in participants with cannabis dependence than in non-dependent cannabis users. There was no specific localization of this effect across electrodes. We showed that cannabis dependence is associated to an increased spontaneous brain complexity in regular users. This result is in line with previous results in acute cannabis users. It may reflect increased randomness of neural activity in cannabis dependence. Future studies should explore whether this effect is permanent or diminishes with cannabis cessation. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Relapse to cocaine seeking in an invertebrate.

Science.gov (United States)

Amaning-Kwarteng, Akua O; Asif-Malik, Aman; Pei, Yue; Canales, Juan J

2017-06-01

Addiction is characterised by cycles of compulsive drug taking, periods of abstinence and episodes of relapse. The extinction/reinstatement paradigm has been extensively used in rodents to model human relapse and explore underlying mechanisms and therapeutics. However, relapse to drug seeking behaviour has not been previously demonstrated in invertebrates. Here, we used a cocaine conditioned place preference (CPP) paradigm in the flatworm, planarian, followed by extinction and reinstatement of drug seeking. Once baseline preference was established for one of two distinctly textured environments (i.e. compartments with a coarse or smooth surface), planarian received pairings of cocaine (5μM) in the non-preferred, and vehicle in the most preferred, environment, and were tested for conditioning thereafter. Cocaine produced robust CPP, measured as a significant increase in the time spent in the cocaine-paired compartment. Subsequently, planarian underwent extinction training, reverting back to their original preference within three sessions. Brief exposure to cocaine (5μM) or methamphetamine (5μM) reinstated cocaine-seeking behaviour. By contrast, the high affinity dopamine transporter inhibitor, (N-(n-butyl)-3α-[bis (4-fluorophenyl) methoxy]-tropane) (JHW007), which in rodents exhibits a neurochemical and behavioural profile distinct from cocaine, was ineffective. The present findings demonstrate for the first time reinstatement of extinguished cocaine seeking in an invertebrate model and suggest that the long-term adaptations underlying drug conditioning and relapse are highly conserved through evolution. Copyright © 2017 Elsevier Inc. All rights reserved.

Exposure to cannabis in popular music and cannabis use among adolescents.

Science.gov (United States)

Primack, Brian A; Douglas, Erika L; Kraemer, Kevin L

2010-03-01

Cannabis use is referenced frequently in American popular music, yet it remains uncertain whether exposure to these references is associated with actual cannabis use. We aimed to determine if exposure to cannabis in popular music is associated independently with current cannabis use in a cohort of urban adolescents. We surveyed all 9th grade students at three large US urban high schools. We estimated participants' exposure to lyrics referent to cannabis with overall music exposure and content analyses of their favorite artists' songs. Outcomes included current (past 30 days) and ever use of cannabis. We used multivariable regression to assess independent associations between exposures and outcomes while controlling for important covariates. Each of the 959 participants was exposed to an estimated 27 cannabis references per day [correction added on 19 January 2010, after first online publication: 40 has been changed to 27] (standard deviation = 73 [correction added on 19 January 2010, after first online publication: 104 has been changed to 73]). Twelve per cent (n = 108) were current cannabis users and 32% (n = 286) had ever used cannabis. Compared with those in the lowest tertile of total cannabis exposure in music, those in the highest tertile of exposure were almost twice as likely to have used cannabis in the past 30 days (odds ratio = 1.83; 95% confidence interval = 1.04, 3.22), even after adjusting for socio-demographic variables, personality characteristics and parenting style. As expected, however, there was no significant relationship between our cannabis exposure variable and a sham outcome variable of alcohol use. This study supports an independent association between exposure to cannabis in popular music and early cannabis use among urban American adolescents.

Cocaine versus food choice procedure in rats: environmental manipulations and effects of amphetamine.

Science.gov (United States)

Thomsen, Morgane; Barrett, Andrew C; Negus, S Stevens; Caine, S Barak

2013-03-01

We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0-1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. © Society for the Experimental Analysis of Behavior.

High affinity binding of [3H]cocaine to rat liver microsomes

International Nuclear Information System (INIS)

El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

1988-01-01

] 3 H]cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in [ 3 H]cocaine binding. On the other hand, chronic administration of cocaine reduced [ 3 H]cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of [ 3 H]cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced [ 3 H]cocaine binding to liver with a different rank order of potency than their displacement of [ 3 H]cocaine binding to striatum. This high affinity [ 3 H]cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

N-Acetylcysteine Reverses Cocaine Induced Metaplasticity

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Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M. Foster; Gass, Justin T.; Lavin, Antonieta; Kalivas, Peter W

2009-01-01

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry critical for regulating motivated behavior. RWe found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentation (LTP) and depression (LTD) in the nucleus accumbens core subregion following stimulation of prefrontal cortex. N-acetylcysteine treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). N-acetylcysteine treatment restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Cocaine self-administration induces metaplasticity that inhibits the further induction of synaptic plasticity, and this impairment can be reversed by N-acetylcysteine, a drug that also prevents relapse. PMID:19136971

N-Acetylcysteine reverses cocaine-induced metaplasticity.

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Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M Foster; Gass, Justin T; Lavin, Antonieta; Kalivas, Peter W

2009-02-01

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry crucial for regulating motivated behavior. We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the nucleus accumbens core subregion after stimulation of the prefrontal cortex. N-acetylcysteine (NAC) treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). NAC treatment of rats restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Our findings show that cocaine self-administration induces metaplasticity that inhibits further induction of synaptic plasticity, and this impairment can be reversed by NAC, a drug that also prevents relapse.

Cigarette Cue Attentional Bias in Cocaine-Smoking and Non-Cocaine-Using Cigarette Smokers.

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Marks, Katherine R; Alcorn, Joseph L; Stoops, William W; Rush, Craig R

2016-09-01

Cigarette smoking in cocaine users is nearly four times higher than the national prevalence and cocaine use increases cigarette smoking. The mechanisms underlying cigarette smoking in cocaine-using individuals need to be identified to promote cigarette and cocaine abstinence. Previous studies have examined the salience of cigarette and cocaine cues separately. The present aim was to determine whether cigarette attentional bias (AB) is higher in cigarettes smokers who smoke cocaine relative to individuals who only smoke cigarettes. Twenty cigarette smokers who smoke cocaine and 20 non-cocaine-using cigarette smokers completed a visual probe task with eye-tracking technology. During this task, the magnitude of cigarette and cocaine AB was assessed through orienting bias, fixation time, and response time. Cocaine users displayed an orienting bias towards cigarette cues. Cocaine users also endorsed a more urgent desire to smoke to relieve negative affect associated with cigarette craving than non-cocaine users (g = 0.6). Neither group displayed a cigarette AB, as measured by fixation time. Cocaine users, but not non-cocaine users, displayed a cocaine AB as measured by orienting bias (g = 2.0) and fixation time (g = 1.2). There were no significant effects for response time data. Cocaine-smoking cigarettes smokers display an initial orienting bias toward cigarette cues, but not sustained cigarette AB. The incentive motivation underlying cigarette smoking also differs. Cocaine smokers report more urgent desire to smoke to relieve negative affect. Identifying differences in motivation to smoke cigarettes may provide new treatment targets for cigarette and cocaine use disorders. These results suggest that cocaine-smoking cigarette smokers display an initial orienting bias towards cigarette cues, but not sustained attention towards cigarette cues, relative to non-cocaine-using smokers. Smoked cocaine users also report a more urgent desire to smoke to relieve negative affect

Implicit associations and explicit expectancies towards cannabis in heavy cannabis users and controls

Directory of Open Access Journals (Sweden)

Esther eBeraha

2013-06-01

Full Text Available Cognitive biases, including implicit memory associations are thought to play an important role in the development of addictive behaviors. The aim of the present study was to investigate implicit affective memory associations in heavy cannabis users. Implicit positive-arousal, sedation, and negative associations towards cannabis were measured with three Single Category Implicit Association Tests (SC-IAT’s and compared between 59 heavy cannabis users and 89 controls. Moreover, we investigated the relationship between these implicit affective associations and explicit expectancies, subjective craving, cannabis use, and cannabis related problems. Results show that heavy cannabis users had stronger implicit positive-arousal associations but weaker implicit negative associations towards cannabis compared to controls. Moreover, heavy cannabis users had stronger sedation but weaker negative explicit expectancies towards cannabis compared to controls. Within heavy cannabis users, more cannabis use was associated with stronger implicit negative associations whereas more cannabis use related problems was associated with stronger explicit negative expectancies, decreasing the overall difference on negative associations between cannabis users and controls. No other associations were observed between implicit associations, explicit expectancies, measures of cannabis use, cannabis use related problems, or subjective craving. These findings indicate that, in contrast to other substances of abuse like alcohol and tobacco, the relationship between implicit associations and cannabis use appears to be weak in heavy cannabis users.

Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats.

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Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

2016-02-01

Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin's impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin's attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin's effect on cocaine seeking may be mediated by different mechanisms in male and females. PsycINFO Database Record (c) 2016 APA, all rights reserved.

Solitary cannabis use in adolescence as a correlate and predictor of cannabis problems.

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Creswell, Kasey G; Chung, Tammy; Clark, Duncan B; Martin, Christopher S

2015-11-01

Most adolescent cannabis use occurs in social settings among peers. Solitary cannabis use during adolescence may represent an informative divergence from normative behavior with important implications for understanding risk for cannabis problems. This longitudinal study examined associations of adolescent solitary cannabis use with levels of cannabis use and problems in adolescence and in young adulthood. Cannabis using-adolescents aged 12-18 were recruited from clinical programs (n=354; 43.8% female; 83.3% Caucasian) and community sources (n=93; 52.7% female; 80.6% Caucasian). Participants reported on cannabis use patterns and diagnostic symptoms at baseline and multiple follow-ups into young adulthood. Compared to social-only users, adolescent solitary cannabis users were more likely to be male and reported more frequent cannabis use and more DSM-IV cannabis use disorder (CUD) symptoms. Regression analyses showed that solitary cannabis use in adolescence predicted CUD symptom counts in young adulthood (age 25) after controlling for demographic variables and the frequency of adolescent cannabis use. However, solitary adolescent cannabis use was no longer predictive of age 25 CUD symptoms after additionally controlling for adolescent CUD symptoms. Solitary cannabis use is associated with greater cannabis use and problems during adolescence, but evidence is mixed that it predicts young adult cannabis problems. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cocaine

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... Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal with Naloxone (Narcan, Evzio) Pain Prevention Recovery Substance ... cocaine impairs judgment, which can lead to risky sexual behavior with infected partners (see " Cocaine, HIV, and ...

[Alternative biological materials to detect prenatal exposure to drugs of abuse in the third trimester of pregnancy].

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García-Serra, J; Ramis, J; Simó, S; Joya, X; Pichini, S; Vall, O; García-Algar, O

2012-11-01

Detection of prenatal drug abuse exposure is essential to ensure an appropriate monitoring of affected children. A maternal questionnaire is not an efficient screening tool. The usefulness of maternal hair and meconium as biological materials to assess this exposure has been described in last few years. The aim of this study was to compare both these alternative biological materials for prenatal drug exposure detection in the third trimester of pregnancy, in order to assess its use as a screening tool. Between January and March 2010, samples of maternal hair and meconium from 107 mother-infant dyads were collected in Can Misses Hospital, Ibiza. The presence of opiates, cocaine, cannabis, and amphetamines, was determined in both materials, using standard chromatographic techniques. Maternal hair analysis showed a 15.9% positivity for drugs of abuse (17 cases): 11 cannabis, 7 cocaine, 1 cannabis and ecstasy, and 1 cannabis and cocaine. Only one mother reported cannabis consumption and another one, cocaine. Of the 7 cocaine positive cases in hair, 6 were confirmed in meconium analysis, while of 11 cannabis positive cases, only 3 were confirmed in meconium. Two different consumer profiles were defined: cocaine consumers and cannabis consumers (with only 2 cases of multiple drug use). The highest level of cocaine ever published was detected (1.582ng/g) in one case. This study reveals a high prevalence of drug abuse in this cohort during pregnancy. Improved screening methods may optimize prevention and monitoring of exposed infants. Maternal hair seems to be more sensitive than meconium to detect prenatal exposure to cannabis during the third trimester, so it might become a good screening tool. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

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Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-09-01

Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Substance use - cocaine

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Substance abuse - cocaine; Drug abuse - cocaine; Drug use - cocaine ... thinking clearly Mood and emotional problems, such as aggressive or violent behavior Restlessness and tremors Sleep problems ...

Cocaine and other illicit drugs in airborne particulates in urban environments: A reflection of social conduct and population size

International Nuclear Information System (INIS)

Viana, M.; Postigo, C.; Querol, X.; Alastuey, A.; Lopez de Alda, M.J.; Barcelo, D.; Artinano, B.; Lopez-Mahia, P.; Garcia Gacio, D.; Cots, N.

2011-01-01

Levels of cocaine and other psychoactive substances in atmospheric particulate matter (PM) were determined in urban environments representing distinct social behaviours with regard to drug abuse: night-life, university and residential areas. Three cities (with population >1 million and 3 for cocaine, 23-34 pg/m 3 for cannabinoids, and 5-90 pg/m 3 for heroin. The highest levels were recorded on weekends, with factors with respect to weekdays of 1-3 for cocaine, 1-2 for cannabinoids and 1.1-1.7 for heroin. Higher levels were detected in the night-life areas, pointing towards consumption and trafficking as major emission sources, and possibly ruling out drug manufacture. The similarities in temporal trends at all sites suggested a city-scale transport of psychoactive substances. Correlations were detected between cocaine and amphetamine consumption (r 2 = 0.98), and between heroin and cannabinoids (r 2 >0.82). - Highlights: → Cocaine, heroin, cannabis and related illicit drugs are found in detectable amounts in urban air. → Illicit drug consumption and small-scale trafficking are the major emission sources. → Illicit drugs remain in atmospheric particles and are transported across cities during at least 5 days. → Levels of illicit drugs increase from residential to night-life areas, and maximise on weekends. → Correlations between illicit drugs were detected, suggesting differences in consumer groups. - The presence of illicit drugs in atmospheric particles can be used to track illicit drug abuse.

Integrating cannabis into clinical cancer care.

Science.gov (United States)

Abrams, D I

2016-03-01

Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use. For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia. Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects.

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

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

2018-04-15

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.

Statistics on cannabis users skew perceptions of cannabis use

Directory of Open Access Journals (Sweden)

Rachel Melissa Burns

2013-11-01

Full Text Available Collecting information about the prevalence of cannabis use is necessary but not sufficient for understanding the size, dynamics, and outcomes associated with cannabis markets. This paper uses two data sets describing cannabis consumption in the United States and Europe to highlight 1 differences in inferences about sub-populations based on the measure used to quantify cannabis-related activity; 2 how different measures of cannabis-related activity can be used to more accurately describe trends in cannabis usage over time; and 3 the correlation between frequency of use in the past month and average grams consumed per day. Key findings: Focusing on days of use instead of prevalence shows substantially greater increases in U.S. cannabis use in recent years; however, the recent increase is mostly among adults, not youth. Relatively more rapid growth in use days also occurred among the college-educated and Hispanic. Further, data from a survey conducted in several European countries show a strong positive correlation between frequency of use and quantity consumed per day of use, suggesting consumption is even more skewed toward the minority of heavy users than is suggested by days-of-use calculations.

[Medical cannabis: the opportunity versus the temptation].

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Naftali, Timna

2011-12-01

The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea, and inflammation. Current research has shown cannabis to be a useful remedy for many diseases, including multiple sclerosis, dystonia, and chronic pain. Cannabinoids are used to improve food intake in anorexia of AIDS patients and to prevent vomiting due to cancer chemotherapy. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and pain and diarrhea in Crohn's disease. Cannabinoids reduce the size of brain infarct and cardiac reperfusion injury. However, cannabinoid treatment is not free of side effects including euphoria, psychosis, anxiety, paranoia, dependence and abuse. Since the cannabinoid system is involved in many physiological and pathological processes, the therapeutic potential is great. We must not be blind to the opportunity offered to us by medical cannabis just because it is an illicit drug, nor should we be temped by the quick response of patients to the central effect of cannabis. More research is warranted to explore the full potential of cannabis as medicine.

Cannabis, alcohol and fatal road accidents.

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Martin, Jean-Louis; Gadegbeku, Blandine; Wu, Dan; Viallon, Vivian; Laumon, Bernard

2017-01-01

This research aims to estimate the relative risks of responsibility for a fatal accident linked to driving under the influence of cannabis or alcohol, the prevalence of these influences among drivers and the corresponding attributable risk ratios. A secondary goal is to estimate the same items for three other groups of illicit drugs (amphetamines, cocaine and opiates), and to compare the results to a similar study carried out in France between 2001 and 2003. Police procedures for fatal accidents in Metropolitan France during 2011 were analyzed and 300 characteristics encoded to provide a database of 4,059 drivers. Information on alcohol and four groups of illicit drugs derived from tests for positivity and potential confirmation through blood analysis. The study compares drivers responsible for causing the accident, that is to say having directly contributed to its occurrence, to drivers involved in an accident for which they were not responsible, and who can be assimilated to drivers in general. The proportion of persons driving under the influence of alcohol is estimated at 2.1% (95% CI: 1.4-2.8) and under the influence of cannabis at 3.4% (2.9%-3.9%). Drivers under the influence of alcohol are 17.8 times (12.1-26.1) more likely to be responsible for a fatal accident, and the proportion of fatal accidents which would be prevented if no drivers ever exceeded the legal limit for alcohol is estimated at 27.7% (26.0%-29.4%). Drivers under the influence of cannabis multiply their risk of being responsible for causing a fatal accident by 1.65 (1.16-2.34), and the proportion of fatal accidents which would be prevented if no drivers ever drove under the influence of cannabis is estimated at 4.2% (3.7%-4.8%). An increased risk linked to opiate use has also been found to be significant, but with low prevalence, requiring caution in interpreting this finding. Other groups of narcotics have even lower prevalence, and the associated extra risks cannot be assessed. Almost a

Cannabis, alcohol and fatal road accidents.

Directory of Open Access Journals (Sweden)

Jean-Louis Martin

Full Text Available This research aims to estimate the relative risks of responsibility for a fatal accident linked to driving under the influence of cannabis or alcohol, the prevalence of these influences among drivers and the corresponding attributable risk ratios. A secondary goal is to estimate the same items for three other groups of illicit drugs (amphetamines, cocaine and opiates, and to compare the results to a similar study carried out in France between 2001 and 2003.Police procedures for fatal accidents in Metropolitan France during 2011 were analyzed and 300 characteristics encoded to provide a database of 4,059 drivers. Information on alcohol and four groups of illicit drugs derived from tests for positivity and potential confirmation through blood analysis. The study compares drivers responsible for causing the accident, that is to say having directly contributed to its occurrence, to drivers involved in an accident for which they were not responsible, and who can be assimilated to drivers in general.The proportion of persons driving under the influence of alcohol is estimated at 2.1% (95% CI: 1.4-2.8 and under the influence of cannabis at 3.4% (2.9%-3.9%. Drivers under the influence of alcohol are 17.8 times (12.1-26.1 more likely to be responsible for a fatal accident, and the proportion of fatal accidents which would be prevented if no drivers ever exceeded the legal limit for alcohol is estimated at 27.7% (26.0%-29.4%. Drivers under the influence of cannabis multiply their risk of being responsible for causing a fatal accident by 1.65 (1.16-2.34, and the proportion of fatal accidents which would be prevented if no drivers ever drove under the influence of cannabis is estimated at 4.2% (3.7%-4.8%. An increased risk linked to opiate use has also been found to be significant, but with low prevalence, requiring caution in interpreting this finding. Other groups of narcotics have even lower prevalence, and the associated extra risks cannot be assessed

Effects of frequent cannabis use on hippocampal activity during an associative memory task

NARCIS (Netherlands)

Jager, Gerry; van Hell, Hendrika H.; de Win, Maartje M. L.; Kahn, Rene S.; van den Brink, Wim; van Ree, Jan M.; Ramsey, Nick F.

2007-01-01

Interest is growing in the neurotoxic potential of cannabis on human brain function. We studied non-acute effects of frequent cannabis use on hippocampus-dependent associative memory, investigated with functional Magnetic Resonance Imaging (fMRI) in 20 frequent cannabis users and 20 non-users

Occurrence of pharmaceuticals and cocaine in a Brazilian coastal zone.

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Pereira, Camilo D Seabra; Maranho, Luciane A; Cortez, Fernando S; Pusceddu, Fabio H; Santos, Aldo R; Ribeiro, Daniel A; Cesar, Augusto; Guimarães, Luciana L

2016-04-01

The present study determined environmental concentrations of pharmaceuticals, cocaine, and the main human metabolite of cocaine in seawater sampled from a subtropical coastal zone (Santos, Brazil). The Santos Bay is located in a metropolitan region and receives over 7367m(3) of wastewater per day. Five sample points under strong influence of the submarine sewage outfall were chosen. Through quantitative analysis by LC-MS/MS, 33 compounds were investigated. Seven pharmaceuticals (atenolol, acetaminophen, caffeine, losartan, valsartan, diclofenac, and ibuprofen), an illicit drug (cocaine), and its main human metabolite (benzoylecgonine) were detected at least once in seawater sampled from Santos Bay at concentrations that ranged from ng·L(-1) to μg·L(-1). In light of the possibility of bioaccumulation and harmful effects, the high concentrations of pharmaceuticals and cocaine found in this marine subtropical ecosystem are of environmental concern. Copyright © 2016 Elsevier B.V. All rights reserved.

[Medicinal cannabis].

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Van der Meersch, H; Verschuere, A P; Bottriaux, F

2006-01-01

Pharmaceutical grade cannabis is available to Dutch patients from public pharmacies in the Netherlands. The first part of this paper reviews the pharmaceutical and pharmacological properties of medicinal cannabis. Detailed information about its composition and quality, potential applications, methods of administration, adverse reactions, drug interactions and safety during pregnancy or breastfeeding are given. The second part deals with the legal aspects of dispensing medicinal cannabis through pharmacies in view of the Belgian and Dutch legislation. The last part discusses the present Belgian regulation about the possession of cannabis.

Monitoring cocaine use and abstinence among cocaine users for contingency management interventions.

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Holtyn, August F; Knealing, Todd W; Jarvis, Brantley P; Subramaniam, Shrinidhi; Silverman, Kenneth

2017-06-01

During contingency management interventions, reinforcement of cocaine abstinence is arranged by delivering an incentive when a urine sample tests cocaine-negative. The use of qualitative versus quantitative urinalysis testing may have important implications for effects on cocaine abstinence. Qualitative testing (i.e., testing that solely identifies whether a particular substance is present or absent) may not detect short-term cocaine abstinence because a single instance of cocaine use can result in cocaine-positive urine over many days. Quantitative testing (i.e., testing that identifies how much of a substance is present) may be more sensitive to short-term cocaine abstinence; however, the selection of a criterion for distinguishing new use versus carryover from previous use is an important consideration. The present study examined benzoylecgonine concentrations, the primary metabolite of cocaine, in urine samples collected three times per week for 30 weeks from 28 cocaine users who were exposed to a cocaine abstinence contingency. Of the positive urine samples (benzoylecgonine concentration >300 ng/ml), 29%, 21%, 14%, and 5% of the samples decreased in benzoylecgonine concentration by more than 20%, 40%, 60%, and 80% per day, respectively. As the size of the decrease increased, the likelihood of that sample occurring during a period leading to a cocaine-negative urine sample (benzoylecgonine concentration ≤300 ng/ml) also increased. The number of days required to produce a cocaine-negative sample following a positive sample ranged from 1 to 10 days and was significantly correlated with the starting benzoylecgonine level ( r = 0.43, p contingency management interventions.

Acute and Non-acute Effects of Cannabis on Human Memory Function: A Critical Review of Neuroimaging Studies

NARCIS (Netherlands)

Bossong, M.G.; Jager, G.; Bhattacharyya, S.; Allen, P.

2014-01-01

Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and

Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo.

Science.gov (United States)

Tallarida, Christopher S; Egan, Erin; Alejo, Gissel D; Raffa, Robert; Tallarida, Ronald J; Rawls, Scott M

2014-04-01

Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

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Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

2005-09-01

We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

Cannabis Smoking in 2015: A Concern for Lung Health?

Science.gov (United States)

Biehl, Jason R; Burnham, Ellen L

2015-09-01

Recent legislative successes allowing expanded access to recreational and medicinal cannabis have been associated with its increased use by the public, despite continued debates regarding its safety within the medical and scientific communities. Despite legislative changes, cannabis is most commonly used by smoking, although alternatives to inhalation have also emerged. Moreover, the composition of commercially available cannabis has dramatically changed in recent years. Therefore, developing sound scientific information regarding its impact on lung health is imperative, particularly because published data conducted prior to widespread legalization are conflicting and inconclusive. In this commentary, we delineate major observations of epidemiologic investigations examining cannabis use and the potential associated development of airways disease and lung cancer to highlight gaps in pulmonary knowledge. Additionally, we review major histopathologic alterations related to smoked cannabis and define specific areas in animal models and human clinical translational investigations that could benefit from additional development. Given that cannabis has an ongoing classification as a schedule I medication, federal funding to support investigations of modern cannabis use in terms of medicinal efficacy and safety profile on lung health have been elusive. It is clear, however, that the effects of inhaled cannabis on lung health remain uncertain and given increasing use patterns, are worthy of further investigation.

Cocaine (Coke, Crack) Facts

Science.gov (United States)

... That People Abuse » Cocaine (Coke, Crack) Facts Cocaine (Coke, Crack) Facts Listen Cocaine is a white ... 69 KB) "My life was built around getting cocaine and getting high." ©istock.com/ Marjot Stacey is ...

Cannabis for inflammatory bowel disease.

Science.gov (United States)

Naftali, Timna; Mechulam, Raphael; Lev, Lihi Bar; Konikoff, Fred M

2014-01-01

The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds. Studies have revealed that the endocannabinoid system is involved in almost all major immune events. Cannabinoids may, therefore, be beneficial in inflammatory disorders. In murine colitis, cannabinoids decrease histologic and microscopic inflammation. In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis. Despite anecdotal reports on medical cannabis in inflammatory bowel disease (IBD), there are few controlled studies. In an observational study in 30 patients with Crohn's disease (CD), we found that medical cannabis was associated with improvement in disease activity and reduction in the use of other medications. In a more recent placebo-controlled study in 21 chronic CD patients, we showed a decrease in the CD activity index >100 in 10 of 11 subjects on cannabis compared to 4 of 10 on placebo. Complete remission was achieved in 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity. In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use. © 2014 S. Karger AG, Basel.

Cocaine Conditioned Behavior: A Cocaine Memory Trace or an Anti-Habituation Effect

OpenAIRE

Carey, Robert J.; Damianopoulos, Ernest N.; Shanahan, Arielle B.

2008-01-01

Whether cocaine locomotor conditioning represents a cocaine positive effect; i.e., a Pavlovian cocaine conditioned response; or, a cocaine negative effect; i.e., interference with habituation to the test environment, is a subject of some controversy. Three separate experiments were conducted to compare the behavior (locomotion and grooming) of separate groups of rats given 1, 9 or 14 cocaine (10 mg/kg) treatments paired/unpaired with placement into an open-field arena. The behavior of the coc...

Psychosis and cannabis

Directory of Open Access Journals (Sweden)

Heinz Häfner

2005-01-01

Full Text Available Alcohol and cannabis misuse is currently the most frequent co-morbidity disorder of schizophrenia. The following four issues will be dealt with: 1 the neurobiological basis of the psychosis-inducing, pathogenic effects of THC, the agent contained in cannabis products. 2 Can cannabis use - and for comparison alcohol abuse - prematurely trigger or even cause schizophrenia? 3 Are persons genetically liable to schizophrenia, psychosis-prone individuals or young persons before completion of brain development at an increased risk? 4 What consequences does cannabis use have on the symptomatology and further course of schizophrenia? Results from recent literature and the ABC Schizophrenia Study show that the risk for cannabis use in schizophrenia is about twice the size in healthy controls. In most cases cannabis use starts before first admission, in a third of cases before schizophrenia onset. There is an increased affinity to misuse already at the prodromal stage. Cannabis can prematurely trigger schizophrenia onset - on average eight years earlier than in non-use - and cause the illness partly in interaction with predisposing factors. Cannabis use in the course of schizophrenia increases positive symptoms and reduces affective flattening, thus leading to dysfunctional coping in some cases.

Characterization of a recombinant humanized anti-cocaine monoclonal antibody produced from multiple clones for the selection of a master cell bank candidate.

Science.gov (United States)

Wetzel, Hanna N; Webster, Rose P; Saeed, Fatima O; Kirley, Terence L; Ball, William J; Norman, Andrew B

2017-06-03

We have generated a humanized anti-cocaine monoclonal antibody (mAb), which is at an advanced stage of pre-clinical development. We report here in vitro binding affinity studies, and in vivo pharmacokinetic and efficacy studies of the recombinant mAb. The overall aim was to characterize the recombinant antibody from each of the three highest producing transfected clones and to select one to establish a master cell bank. In mAb pharmacokinetic studies, after injection with h2E2 (120 mg/kg iv) blood was collected from the tail tip of mice over 28 days. Antibody concentrations were quantified using ELISA. The h2E2 concentration as a function of time was fit using a two-compartment pharmacokinetic model. To test in vivo efficacy, mice were injected with h2E2 (120 mg/kg iv), then one hour later injected with an equimolar dose of cocaine. Blood and brain were collected 5 min after cocaine administration. Cocaine concentrations were quantified using LC/MS. The affinity of the antibody for cocaine was determined using a [ 3 H] cocaine binding assay. All three antibodies had long elimination half-lives, 2-5 nM Kd for cocaine, and prevented cocaine's entry into the brain by sequestering it in the plasma. Pharmacokinetic and radioligand binding assays supported designation of the highest producing clone 85 as the master cell bank candidate. Overall, the recombinant h2E2 showed favorable binding properties, pharmacokinetics, and in vivo efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

Medical Cannabis in Arizona: Patient Characteristics, Perceptions, and Impressions of Medical Cannabis Legalization.

Science.gov (United States)

Troutt, William D; DiDonato, Matthew D

2015-01-01

Many advances have been made toward understanding the benefits of medical cannabis. However, less is known about medical cannabis patients themselves. Prior research has uncovered many important patient characteristics, but most of that work has been conducted with participants in California, who may not represent medical cannabis patients throughout the United States. Furthermore, it is unknown if medical cannabis legalization, which typically imposes strict regulations on cannabis cultivation and sale, impacts patients' experiences acquiring and using cannabis. The goal of this study was to address these limitations by (1) examining the characteristics, perceptions, and behaviors of medical cannabis patients in Arizona; and (2) questioning participants with a history of cannabis use regarding their experiences with cannabis before and after legalization. Patients in Arizona share many characteristics with those in California, but also key differences, such as average age and degree of cannabis consumption. Participants also had positive perceptions of the effect of medical cannabis legalization, reporting that feelings of safety and awareness were higher after legalization compared to before. The results are discussed in relation to evidence from patients in other states and in terms of their potential policy implications.

Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

Energy Technology Data Exchange (ETDEWEB)

Moeller, S.J.; Moeller, S.J.; Maloney, T.; Parvaz, M.A.; Alia-Klein, N.; Woicik, P.A.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

2010-04-15

Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.

Alcohol consumption moderates the link between cannabis use and cannabis dependence in an internet survey.

Science.gov (United States)

Smucker Barnwell, Sara; Earleywine, Mitch; Gordis, Elana B

2005-06-01

The link between cannabis use and cannabis dependence remains poorly understood. Some people use cannabis regularly without signs of dependence; others show dependence despite using less. This study examined alcohol consumption as a moderator of this association. A sample of 476 people (primarily Caucasian men) who used cannabis at least once per week reported their alcohol consumption, cannabis use, and cannabis dependence symptoms in an Internet survey. Regressions revealed significant interactions between measures of cannabis use and alcohol consumption when predicting cannabis dependence. Cannabis use covaried with cannabis dependence, particularly in people who consumed alcohol frequently or in large amounts per week. Despite limitations, these data suggest that alcohol may decrease the safety of cannabis consumption. Copyright 2005 APA, all rights reserved.

Cannabis Decriminalization and the Age of Onset of Cannabis Use

OpenAIRE

Cervený, J.; van Ours, J.C.; Chomynova, Pavla; Mravcik, Viktor

2015-01-01

This paper examines the effect of a change in drugs policy on the age of onset of cannabis use. We use 2012 survey data from the Czech Republic where in 2010 a law was introduced decriminalizing personal possession of small quantities of several illicit drugs, including cannabis. We estimate the effect of the policy change using a mixed proportional hazards framework that models the starting rate of cannabis use, i.e. the transition to first cannabis use. We find that the decriminalization of...

Seeing through the smoke: human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks

Science.gov (United States)

Silveira, Mason M.; Arnold, Jonathon C.; Laviolette, Steven R.; Hillard, Cecilia J.; Celorrio, Marta; Aymerich, María S.; Adams, Wendy K.

2016-01-01

Public opinion surrounding the recreational use and therapeutic potential of cannabis is shifting. This review describes new work examining the behavioural and neural effects of cannabis and the endocannabinoid system, highlighting key regions within corticolimbic brain circuits. First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating that THC-induced impairments in decision-making processes are mediated by actions at prefrontal CB1 receptors. We further describe evidence that signalling through prefrontal or ventral hippocampal CB1 receptors modulates mesolimbic dopamine activity, aberrations of which may contribute to emotional processing deficits in schizophrenia. Lastly, we review studies suggesting that endocannabinoid tone in the amygdala is a critical regulator of anxiety, and report new data showing that FAAH activity is integral to this response. Together, these findings underscore the importance of cannabinoid signalling in the regulation of cognitive and affective behaviours, and encourage further research given their social, political, and therapeutic implications. PMID:27639448

Self-reported cannabis use characteristics, patterns and helpfulness among medical cannabis users.

Science.gov (United States)

Bonn-Miller, Marcel O; Boden, Matthew Tyler; Bucossi, Meggan M; Babson, Kimberly A

2014-01-01

Little research has investigated the demographic and symptom profile of medical cannabis users in states in the USA that have legalized cannabis use. In the present cross-sectional study, we investigated the demographic profile of 217 adults currently receiving medical cannabis, as well as differences in problematic use and perceived helpfulness in terms of (i) symptoms of psychological disorders and pain, and (ii) motives for use. Findings indicated that medical cannabis users (i) use and perceive cannabis to be beneficial for multiple conditions, some for which cannabis is not specifically prescribed or allowed at the state level; and (ii) report similar rates of disordered use as compared with population estimates among regular users. Furthermore, problematic cannabis use was predicted by several symptoms of psychological disorders (e.g. depression) and a variety of use motives (e.g. coping), while cannabis was reported as particularly helpful among those with several psychological symptoms (e.g. traumatic intrusions), as well as those reporting use for social anxiety reasons. Results are discussed in terms of future directions for research given the current debates regarding legalization of cannabis for medical purposes and, more generally, the lack of empirical data to inform such debates.

Cannabis-associated arterial disease.

Science.gov (United States)

Desbois, Anne Claire; Cacoub, Patrice

2013-10-01

The aim of this study was to describe the different arterial complications reported in cannabis smokers. This study was a literature review. Cannabis use was found to be associated with stroke, myocardial infarction, and lower limb arteritis. Arterial disease involved especially young men. There was a very strong temporal link between arterial complications and cannabis use for stroke and myocardial infarction episodes. Patient outcome was closely correlated with cannabis withdrawal and relapses associated with cannabis rechallenge. Cannabis use was associated with particular characteristics of arterial disease. The increased risk of myocardial infarction onset occurred within 1 hour of smoking marijuana compared with periods of non-use. Strokes occurred mainly in the posterior cerebral circulation. Compared with cohorts of thromboangiitis obliterans patients, those with cannabis-associated limb arteritis were younger, more often male, and had more frequent unilateral involvement of the lower limbs at clinical presentation. Cannabis use is associated with arterial disease such as stroke, myocardial infarction, and limbs arteritis. It appears essential to investigate cannabis use in young patients presenting with such arterial manifestations, as outcome is closely correlated with cannabis withdrawal. Copyright © 2013 Elsevier Inc. All rights reserved.

New insights into cannabis consumption; abuses and possible therapeutic effects

Directory of Open Access Journals (Sweden)

Daniela Luiza Baconi

2014-10-01

Full Text Available Cannabis is one of the oldest psychotropic drugs known to humanity. The paper assesses the current knowledge on the cannabis, including the mechanisms of action and the therapeutic potential of cannabinoids. Three varieties of Cannabis plant are recognised: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. The variety indica is used predominantly to obtain the drugs. Cannabis herb is usually named marijuana, while the cannabis oleoresin secreted by the glandular hairs found mainly on the flowering or fruiting tops of the plant is known as hashish. More than 400 known chemicals are present in cannabis, at least 70 of which are called cannabinoids. The major psychoactive constituent in cannabis is delta-9-tetrahydrocannabinol (Δ9-THC. It is now recognized that there are three types of cannabinoids: natural (phytocannabinoids, endogenous cannabinoids, and synthetic cannabioids. Cannabinoids exert their actions by binding to specific membrane protein, the cannabinoid receptor. To date, two subtypes of cannabinoid receptors, named cannabinoid-1 (CB1, most abundantly expressed in the central nervous system and cannabinoid-2 (CB2 receptors, found predominantly in peripheral tissues with immune functions have been cloned. Therefore, the concept of endogenous cannabinoid system (endocannabinoid system, SEC has been developed. Based on the current scientific evidence, there are several effects of cannabinoids with potential therapeutic use: antiemetic, analgesic in cancerous pains, and chronic neuropathic pain, in multiple sclerosis or spinal cord injuries. Cannabis consume can result in a state of drug dependency and cannabis withdrawal has been included in DSM-V. Cannabis plant remains controversial in the twenty-first century and the potential therapeutic of specific cannabinoid compounds and medical marijuana remains under active medical research.

The Cannabis Information Helpline: Assessing Interest in the Medicinal Use of Cannabis in Australia.

Science.gov (United States)

Gates, Peter J; Albertella, Lucy

2017-10-15

The majority of Australians support a change in legislation to allow the use of cannabis for medical purposes. Despite strong public support, very little is known about the patterns of medicinal cannabis use among Australians. This study aims to gain a better understanding of Australian medicinal cannabis users and their patterns of use. The nature of calls to the Cannabis Information and Helpline (N = 15701), a free national service for Australians with concerns regarding cannabis use, were investigated to determine the number of calls made by those who inquired about the medicinal use of cannabis (N = 275) and the implied reasons for use among those who identify using cannabis in this way. The majority of medicinal cannabis inquirers mentioned cannabis to alleviate pain. Further, compared to other callers, medicinal cannabis inquirers were more likely to be male, unemployed, older, and have recently started using cannabis. These findings highlight the need for future research to better understand the issues faced by Australians regarding the use of cannabis for medicinal purposes and how they may be meaningfully addressed. Particular focus should be placed toward older, unemployed males.

Cannabis and psychosis

DEFF Research Database (Denmark)

Shevlin, Mark; McElroy, Eoin; Murphy, Jamie

2017-01-01

Purpose: While research has consistently identified an association between cannabis use and psychosis, few studies have examined this relationship in a polydrug context (i.e. combining cannabis with other illicit substances). The paper aims to discuss this issue. Design/methodology/approach: The ......Purpose: While research has consistently identified an association between cannabis use and psychosis, few studies have examined this relationship in a polydrug context (i.e. combining cannabis with other illicit substances). The paper aims to discuss this issue. Design....../methodology/approach: The present study sought to examine the association between recreational drug use (cannabis only vs polydrug) and psychotic disorders. Analysis was conducted on a large, representative survey of young Danish people aged 24 (n=4,718). Participants completed self-report measures of lifetime drug use...... and this information was linked to the Danish psychiatric registry system. Findings: Multivariate binary logistic regression analysis was used to examine the association between drug use (no drug use, cannabis only, cannabis and other drug) and ICD-10 psychotic disorders, while controlling for gender and parental...

Cocaine and other illicit drugs in airborne particulates in urban environments: A reflection of social conduct and population size

Energy Technology Data Exchange (ETDEWEB)

Viana, M [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Postigo, C [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Querol, X [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Alastuey, A [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Lopez de Alda, M.J., E-mail: mlaqam@cid.csic.es [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Barcelo, D [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); King Saud University, Box 2454, Riyadh 11451 (Saudi Arabia); Artinano, B [Centre for Energy, Environment and Technology Research (CIEMAT), Av. Complutense 22, 28040 Madrid (Spain); Lopez-Mahia, P [Department of Analytical Chemistry, University of A Coruna, Campus A Zapateira, 15071 A Coruna (Spain); Garcia Gacio, D., E-mail: dgarcia@udc.es [Department of Analytical Chemistry, University of A Coruna, Campus A Zapateira, 15071 A Coruna (Spain); Cots, N [Department of the Environment, Catalonia Regional Government, Av. Diagonal 525, 08193 Barcelona (Spain)

2011-05-15

Levels of cocaine and other psychoactive substances in atmospheric particulate matter (PM) were determined in urban environments representing distinct social behaviours with regard to drug abuse: night-life, university and residential areas. Three cities (with population >1 million and <0.3 million inhabitants) were selected. Mean daily levels of drugs in PM were 11-336 pg/m{sup 3} for cocaine, 23-34 pg/m{sup 3} for cannabinoids, and 5-90 pg/m{sup 3} for heroin. The highest levels were recorded on weekends, with factors with respect to weekdays of 1-3 for cocaine, 1-2 for cannabinoids and 1.1-1.7 for heroin. Higher levels were detected in the night-life areas, pointing towards consumption and trafficking as major emission sources, and possibly ruling out drug manufacture. The similarities in temporal trends at all sites suggested a city-scale transport of psychoactive substances. Correlations were detected between cocaine and amphetamine consumption (r{sup 2} = 0.98), and between heroin and cannabinoids (r{sup 2}>0.82). - Highlights: > Cocaine, heroin, cannabis and related illicit drugs are found in detectable amounts in urban air. > Illicit drug consumption and small-scale trafficking are the major emission sources. > Illicit drugs remain in atmospheric particles and are transported across cities during at least 5 days. > Levels of illicit drugs increase from residential to night-life areas, and maximise on weekends. > Correlations between illicit drugs were detected, suggesting differences in consumer groups. - The presence of illicit drugs in atmospheric particles can be used to track illicit drug abuse.

[Cannabis: A Cognitive Illusion].

Science.gov (United States)

Galván, Gonzalo; Guerrero-Martelo, Manuel; Vásquez De la Hoz, Francisco

The vision of cannabis as a soft drug is due to the low risk perception that young and old people have of the drug. This perception is based on erroneous beliefs that people have about the drug. To compare the beliefs of cannabis use and consequences among adolescents with a lifetime prevalence of cannabis use and those without a lifetime prevalence of cannabis use. Quantitative, descriptive and cross-sectional study with a probability sample of 156 high school students who completed an ad-hoc questionnaire that included sociodemographic data and 22 questions about the beliefs that young people had about cannabis use and its consequences. The lifetime prevalence of cannabis use was 13.5%. The prevalence group consisted mostly of males. Statistically significant differences between different groups and different beliefs were found. The group with no lifetime prevalence of cannabis use perceived higher risk as regards the damage that cannabis can cause to memory, other cognitive functions, neurons, mental health, and general health. The group with a lifetime prevalence of cannabis use perceived a lower risk as regards the use of cannabis, and think that intelligent people smoke cannabis, and that cannabis has positive effects on the brain, increasing creativity. and is used to cure mental diseases. Those who used cannabis once in their life perceive the use of the substance as less harmful or less potential danger to health compared to those who never consumed. In fact those who consumed at some time even have beliefs that suggest positive effects in those people that consume it. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

Science.gov (United States)

Maloney, Thomas; Parvaz, Muhammad A.; Alia-Klein, Nelly; Woicik, Patricia A.; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D.; Goldstein, Rita Z.

2010-01-01

Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects’ self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes. PMID:20395264

Cannabis Use in Psychiatrie Patients.

Science.gov (United States)

Chaudhury, S; Sudarsanan, S; Salujha, S K; Srivastava, K

2005-02-01

Cannabis abuse has been associated with psychiatric disorders. The pattern of cannabis use and incidence of cannabis dependence and cannabis psychosis among 471 consecutive patients admitted to a tertiary care psychiatric center was investigated. Cannabis use was reported by 67 (14.23%) patients of whom 42 (8.92%) were occasional users, 18 (3.82%) were classified as frequent users while 7 (1.49%) fulfilled criteria for cannabis dependence. 3 (0.64%) patients showed symptoms which were characteristic of cannabis psychosis. Among the 67 cannabis users, 56 (83.58%) had their first exposure to cannabis before entering service at 13-19 years of age. The remaining 14 (16.09%) began consuming cannabis 1-5 years after joining service. The reasons given for using cannabis were curiosity about its effects 32 (47.76%), peer pressure 17 (25.37%) or traditional use during festivals 18 (26.87%).

Acute heroin intoxication in a baby chronically exposed to cocaine and heroin: a case report

Directory of Open Access Journals (Sweden)

Pichini Simona

2011-07-01

Full Text Available Abstract Introduction Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure. Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs. Case presentation We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and neurological abnormalities. A routine urine test was positive for opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as cocaine, cannabis, amphetamines or derivatives, were detected in the baby's urine. Subsequently, hair samples from the baby and the parents were collected to evaluate the possibility of chronic exposure to drug misuse by segmental analysis. Opiates and cocaine metabolites were detected in hair samples from the baby boy and his parents. Conclusions In light of these and previous results, we recommend hair analysis in babies and children from risky environments to detect exposure to heroin and other drug misuse, which could provide the basis for specific social and health interventions.

Cannabis and Breastfeeding

OpenAIRE

Garry, Aurélia; Rigourd, Virginie; Amirouche, Ammar; Fauroux, Valérie; Aubry, Sylvie; Serreau, Raphaël

2009-01-01

Cannabis is a drug derived from hemp plant, Cannabis sativa, used both as a recreational drug or as medicine. It is a widespread illegal substance, generally smoked for its hallucinogenic properties. Little is known about the adverse effects of postnatal cannabis exposure throw breastfeeding because of a lack of studies in lactating women. The active substance of cannabis is the delta 9 TetraHydroCannabinol (THC). Some studies conclude that it could decrease motor development of the child at ...

Quantitative EEG findings associated with chronic stimulant and cannabis abuse and ADHD in an adult male substance use disorder population.

Science.gov (United States)

Trudeau, D L; Thuras, P; Stockley, H

1999-10-01

QEEG was studied in a population of chronic male PSUD/ADHD (psychoactive substance use disorder/attention deficit hyperactivity disorder) subjects vs. a matched sample of non-ADHD subjects with PSUD. Our first interest in conducting this study was to determine if the Thatcher University of Maryland database and complex demodulation method could replicate the specific QEEG findings reported for cocaine and cannabis using the John-NYU database and Fourier Transform method. The effects of cannabis and stimulants were also studied both separately and together to see if there were interactions and to see if the QEEG changes associated with chronic stimulant dependence were predicted by childhood ADHD status. Eyes-closed QEEGs were obtained and two independent artifacted 60 second samples were compared for reliability. The Thatcher database was used to analyze QEEG data from 56 subjects with mixed substance use disorder. Results showed that the Thatcher database replicates the John database for chronic stimulant dependence findings. Because of confounding variables of alcohol and polysubstance abuse, the findings related to cannabis and stimulant interaction were difficult to assess. Cannabis and stimulant dependence together produced more QEEG changes than either alone. More right temporal abnormalities were observed with stimulant dependence. In the absence of stimulant use, the QEEG effects of cannabis were relatively small; however, sample selection and methods used precluded comparison to previous studies. The persistent QEEG abnormalities associated with chronic stimulant dependence were independent of ADHD status in this sample using the methods of this study. Further research is needed to clarify the relationship of stimulant dependence with QEEG changes and ADHD status, and to clarify the interactions of chronic stimulant and cannabis abuse on QEEG.

The International Cannabis Consortium: What did we learn about the genetics of cannabis

NARCIS (Netherlands)

Verweij, K.J.H.; Minica, C.C.; Stringer, S.; Most, P.J. van der; Mbarek, H.; Nivard, M.G.; Abdellaoui, A.; Hottenga, J.J.; Martin, N.G.; Boomsma, D.I.; Gillespie, N.A.; Derks, E.M.; Vink, J.M.

2017-01-01

Background: Cannabis is the most frequently used and abused illicit drug worldwide and cannabis (ab)use is associated with social, physical, and psychological problems. Twin and family studies have shown that cannabis use and abuse are heritable traits. The International Cannabis Consortium was

Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

Directory of Open Access Journals (Sweden)

Nora D Volkow

2010-07-01

Full Text Available Dopamine (phasic release is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function was measured with PET and (18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg. The Cocaine-cues video increased craving to the same extent with placebo (68% and with methylphenidate (64%. In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005 in left limbic regions (insula, orbitofrontal, accumbens and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005, amygdala, striatum and middle insula (p<0.05. This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes, which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers

International Nuclear Information System (INIS)

Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Telang, F.; Fowler, J.S.; Pradhan, K.; Jayne, M.; Logan, J.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

2010-01-01

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18 FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

N-acetylcysteine amide (AD4) reduces cocaine-induced reinstatement.

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Jastrzębska, Joanna; Frankowska, Malgorzata; Filip, Malgorzata; Atlas, Daphne

2016-09-01

Chronic exposure to drugs of abuse changes glutamatergic transmission in human addicts and animal models. N-acetylcysteine (NAC) is a cysteine prodrug that indirectly activates cysteine-glutamate antiporters. In the extrasynaptic space, NAC restores basal glutamate levels during drug abstinence and normalizes increased glutamatergic tone in rats during reinstatement to drugs of abuse. In initial clinical trials, repeated NAC administration seems to be promising for reduced craving in cocaine addicts. In this study, NAC-amide, called AD4 or NACA, was examined in intravenous cocaine self-administration and extinction/reinstatement procedures in rats. We investigated the behavioral effects of AD4 in the olfactory bulbectomized (OBX) rats, considered an animal model of depression. Finally, we tested rats injected with AD4 or NAC during 10-daily extinction training sessions to examine subsequent cocaine seeking. AD4 (25-75 mg kg(-1)) given acutely did not alter the rewarding effects of cocaine in OBX rats and sham-operated controls. However, at 6.25-50 mg kg(-1), AD4 decreased dose-dependently cocaine seeking and relapse triggered by cocaine priming or drug-associated conditioned cues in both phenotypes. Furthermore, repeated treatment with AD4 (25 mg kg(-1)) or NAC (100 mg kg(-1)) during daily extinction trials reduced reinstatement of drug-seeking behavior in sham-operated controls. In the OBX rats only, AD4 effectively blocked cocaine-seeking behavior. Our results demonstrate that AD4 is effective at blocking cocaine-seeking behavior, highlighting its potential clinical use toward cocaine use disorder.

Structural analysis of thermostabilizing mutations of cocaine esterase

Energy Technology Data Exchange (ETDEWEB)

Narasimhan, Diwahar; Nance, Mark R.; Gao, Daquan; Ko, Mei-Chuan; Macdonald, Joanne; Tamburi, Patricia; Yoon, Dan; Landry, Donald M.; Woods, James H.; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K. (Michigan); (Columbia); (Kentucky)

2010-09-03

Cocaine is considered to be the most addictive of all substances of abuse and mediates its effects by inhibiting monoamine transporters, primarily the dopamine transporters. There are currently no small molecules that can be used to combat its toxic and addictive properties, in part because of the difficulty of developing compounds that inhibit cocaine binding without having intrinsic effects on dopamine transport. Most of the effective cocaine inhibitors also display addictive properties. We have recently reported the use of cocaine esterase (CocE) to accelerate the removal of systemic cocaine and to prevent cocaine-induced lethality. However, wild-type CocE is relatively unstable at physiological temperatures ({tau}{sub 1/2} {approx} 13 min at 37 C), presenting challenges for its development as a viable therapeutic agent. We applied computational approaches to predict mutations to stabilize CocE and showed that several of these have increased stability both in vitro and in vivo, with the most efficacious mutant (T172R/G173Q) extending half-life up to 370 min. Here we present novel X-ray crystallographic data on these mutants that provide a plausible model for the observed enhanced stability. We also more extensively characterize the previously reported variants and report on a new stabilizing mutant, L169K. The improved stability of these engineered CocE enzymes will have a profound influence on the use of this protein to combat cocaine-induced toxicity and addiction in humans.

The effect of cannabis use on memory function: an update

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Schoeler T

2013-01-01

Full Text Available Tabea Schoeler, Sagnik BhattacharyyaDepartment of Psychosis Studies, King's College London, Institute of Psychiatry, London, UKAbstract: Investigating the effects of cannabis use on memory function appears challenging. While early observational investigations aimed to elucidate the longer-term effects of cannabis use on memory function in humans, findings remained equivocal and pointed to a pattern of interacting factors impacting on the relationship between cannabis use and memory function, rather than a simple direct effect of cannabis. Only recently, a clearer picture of the chronic and acute effects of cannabis use on memory function has emerged once studies have controlled for potential confounding factors and started to investigate the acute effects of delta-9-tetrahydrocannabinol (Δ9-THC and cannabidiol (CBD, the main ingredients in the extract of the cannabis plant in pharmacological challenge experiments. Relatively consistent findings have been reported regarding the acute impairments induced by a single dose of Δ9-THC on verbal and working memory. It is unclear whether they may persist beyond the intoxication state. In the long-term, these impairments seem particularly likely to manifest and may also persist following abstinence if regular and heavy use of cannabis strains high in Δ9-THC is started at an early age. Although still at an early stage, studies that employed advanced neuroimaging techniques have started to model the neural underpinnings of the effects of cannabis use and implicate a network of functional and morphological alterations that may moderate the effects of cannabis on memory function. Future experimental and epidemiological studies that take into consideration individual differences, particularly previous cannabis history and demographic characteristics, but also the precise mixture of the ingredients of the consumed cannabis are necessary to clarify the magnitude and the mechanisms by which cannabis

Prevalence and correlates of "Vaping" as a route of cannabis administration in medical cannabis patients.

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Cranford, James A; Bohnert, Kipling M; Perron, Brian E; Bourque, Carrie; Ilgen, Mark

2016-12-01

To examine the prevalence and correlates of vaporization (i.e., "vaping") as a route of cannabis administration in a sample of medical cannabis patients. Adults ages 21 and older (N=1485M age=45.1) who were seeking medical cannabis certification (either for the first time or as a renewal) at medical cannabis clinics in southern Michigan completed a screening assessment. Participants completed measures of route of cannabis administration, cannabis use, alcohol and other substance use. An estimated 39% (n=511) of the sample reported past-month cannabis vaping, but vaping as the sole route of cannabis administration was rare. Specifically, only 30 participants (2.3% of the full sample and 5.9% of those who reported any vaping) indicated vaping as the sole route of cannabis administration. The majority (87.3%) of those who reported vaping also reported smoking (combustion) as a route of cannabis administration. Being younger than age 44, having more than a high school education, engaging in nonmedical stimulant use, being a returning medical cannabis patient, and greater frequency of cannabis use were associated with higher odds of vaping at the bivariate level and with all variables considered simultaneously. Vaping appears to be relatively common among medical cannabis patients, but is seldom used as the sole route of cannabis administration. highlight the importance of monitoring trends in vaping and other substance use behaviors in this population and underscore the need for longitudinal research into the motives, correlates, and consequences of cannabis vaping in medical cannabis patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cannabis Use Disorders and Altered Brain Morphology : Where is the evidence?

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Lorenzetti, V; Batalla, A.; Cousijn, J.

2016-01-01

Cannabis use disorders (CUDs) affect 13.1 million individuals worldwide. Brain morphology specific to CUDs may mediate the adverse behavioral outcomes of CUDs. We reviewed findings from 20 human neuroimaging studies on grey and white matter morphology in cannabis users that specifically included CUD

Dopamine D3 receptors regulate reconsolidation of cocaine memory.

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Yan, Y; Kong, H; Wu, E J; Newman, A H; Xu, M

2013-06-25

Memories of learned associations between the rewarding properties of drugs of abuse and environmental cues contribute to craving and relapse in humans. Disruption of reconsolidation dampens or even erases previous memories. Dopamine (DA) mediates the acquisition of reward memory and drugs of abuse can pathologically change related neuronal circuits in the mesolimbic DA system. Previous studies showed that DA D3 receptors are involved in cocaine-conditioned place preference (CPP) and reinstatement of cocaine-seeking behavior. However, the role of D3 receptors in reconsolidation of cocaine-induced reward memory remains unclear. In the present study, we combined genetic and pharmacological approaches to investigate the role of D3 receptors in reconsolidation of cocaine-induced CPP. We found that the mutation of the D3 receptor gene weakened reconsolidation of cocaine-induced CPP in mice triggered by a 3-min (min) retrieval. Furthermore, treatment of a selective D3 receptor antagonist PG01037 immediately following the 3-min retrieval disrupted reconsolidation of cocaine-induced CPP in wild-type mice and such disruption remained at least 1 week after the 3-min retrieval. These results suggest that D3 receptors play a key role in reconsolidation of cocaine-induced CPP in mice, and that pharmacological blockade of these receptors may be therapeutic for the treatment of cocaine craving and relapse in clinical settings. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

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Hirvonen, J; Goodwin, RS; Li, C-T; Terry, GE; Zoghbi, SS; Morse, C; Pike, VW; Volkow, ND; Huestis, MA; Innis, RB

2011-01-01

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke ca...

Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

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Meriem Gaval-Cruz

Full Text Available The anti-alcoholism medication, disulfiram (Antabuse, decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH, the enzyme that converts dopamine (DA to norepinephrine (NE in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/- mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/- and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor enhance qualitatively different cocaine-induced behaviors.

Chronic Inhibition of Dopamine β-Hydroxylase Facilitates Behavioral Responses to Cocaine in Mice

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Gaval-Cruz, Meriem; Liles, Larry Cameron; Iuvone, Paul Michael; Weinshenker, David

2012-01-01

The anti-alcoholism medication, disulfiram (Antabuse), decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh −/−) mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/−) and Dbh −/− mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh −/− mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/− mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/− mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh −/− mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor) enhance qualitatively different cocaine-induced behaviors. PMID:23209785

Monitoring drug use among HIV/AIDS patients in Brazil: should we combine self-report and urinalysis?

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Malbergier, Andre; do Amaral, Ricardo A; Cardoso, Luciana R D; Castel, Saulo

2012-12-01

Illicit drug use in HIV-infected patients can be linked to impairment of physical and mental health, low health related quality of life, and suboptimal adherence to HIV treatment. This study aimed to evaluate the correlation of self report illicit drug use, urinalysis for cocaine and cannabis metabolites, and severity of dependence among HIV-infected patients on antiretroviral therapy (ART) in a treatment center in Brazil. Four hundred and thirty-eight outpatients of an HIV referral center were interviewed and assessed for drug use (lifetime, last year and last month). Urinalysis was performed to detect the presence of cocaine and cannabis metabolites in urine samples. Overall agreement between self report and urinalysis was almost 68% for cannabis and higher than 85% for cocaine. Positive urinalysis was significantly associated with more than once a week cannabis (pdrugs were correlated. Our findings suggest that positive self-report is a reliable predictor of positive urine sample both for cannabis and cocaine, but since the agreement was not perfect, there is a role for urine drug screening in the care of patients with HIV-related conditions.

First positive reactions to cannabis constitute a priority risk factor for cannabis dependence.

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Le Strat, Yann; Ramoz, Nicolas; Horwood, John; Falissard, Bruno; Hassler, Christine; Romo, Lucia; Choquet, Marie; Fergusson, David; Gorwood, Philip

2009-10-01

To assess the association between first reactions to cannabis and the risk of cannabis dependence. A cross-sectional population-based assessment in 2007. A campus in a French region (Champagne-Ardennes). A total of 1472 participants aged 18-21 years who reported at least one life-time cannabis consumption, of 3056 students who were screened initially [the Susceptibility Addiction Gene Environment (SAGE) study]. Positive and negative effects of first cannabis consumptions, present cannabis dependence and related risk factors were assessed through questionnaires.   The effects of first cannabis consumptions were associated dose-dependently with cannabis dependence at age 18-21 years, both according to the transversal approach of the SAGE study and to the prospective cohort of the Christchurch Health and Development Study (CHDS) assessed at the age of 25 years. Participants of the SAGE study who reported five positive effects of their first cannabis consumption had odds of life-time cannabis dependence that were 28.7 (95% confidence interval: 14.6-56.5) higher than those who reported no positive effects. This association remains significant after controlling for potentially confounding factors, including individual and familial variables. This study suggests an association between positive reactions to first cannabis uses and risk of life-time cannabis dependence, this variable having a central role among, and through, other risk factors. © 2009 The Authors. Journal compilation © 2009 Society for the Study of Addiction.

Cocaine withdrawal

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... RE, Rakel DP, eds. Textbook of Family Medicine . 9th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 50. National Institute on Drug Abuse. What is cocaine? Updated May 2016. www.drugabuse.gov/publications/research-reports/cocaine/ ...

Cannabis careers revisited

DEFF Research Database (Denmark)

Järvinen, Margaretha; Ravn, Signe

2014-01-01

A considerable part of today's sociological research on recreational drug use is (explicitly or implicitly) inspired by Howard Becker's classical model of deviant careers. The aim of the present paper is to directly apply Becker's theory to empirical data on present-day cannabis use and to suggest...... in treatment for cannabis problems in Copenhagen, Denmark. We suggest a revision of Becker's career model in relation to four aspects: initiation of cannabis use, differentiation between socially integrated and individualised, disintegrated use, social control from non-users, and the users' moral stance...... on cannabis. A central point of the paper is that social interaction may both motivate cannabis use, as Becker proposed, and serve as a protective factor against extensive, problematic use....

Illicit drug consumption in school populations measured by wastewater analysis.

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Zuccato, Ettore; Gracia-Lor, Emma; Rousis, Nikolaos I; Parabiaghi, Alberto; Senta, Ivan; Riva, Francesco; Castiglioni, Sara

2017-09-01

Analysis of student consumption of illicit drugs (ID) by school population surveys (SPS) provides information useful for prevention, but the results may be influenced by subjective factors. We explored wastewater (WW) analysis to improve the information. We used WW analysis to measure ID consumption in eight secondary schools in Italy in 2010-13 (students aged 15-19). Samples were collected from the sewage pipes of the schools during lessons for one week each year. Samples were analysed by mass spectrometry to measure ID and consumption by students was compared to that of the general population. We found THCCOOH (human metabolite of THC) concentrations in 2010 indicating significant consumption of cannabis in all the schools and benzoylecgonine (human metabolite of cocaine) suggesting a limited consumption of cocaine in all but one school. Morphine was only found in traces, and amphetamine, methamphetamine, ecstasy, ketamine and mephedrone were not detectable. Repeated analysis showed cannabis stable until 2012 with increases in 2013, low cocaine and morphine levels, and none of the other ID. WW analysis suggested that students used amounts of cannabis comparable to the general population, with low, sporadic use of cocaine and opioids, but excluded the use of significant amounts of amphetamine, methamphetamine, ecstasy, ketamine and mephedrone. WW analysis was useful to confirm SPS figures and provides complementary findings for effective prevention strategies. This is the first time WW analysis has been used to investigate consumption of a large number of ID and new psychoactive substances (NPS) in schools. Copyright © 2017 Elsevier B.V. All rights reserved.

When cannabis is available and visible at school - A multilevel analysis of students' cannabis use

NARCIS (Netherlands)

Kuntsche, E.N.

2010-01-01

Aims - To investigate the links between the visibility of cannabis use in school (measured by teachers’ reports of students being under the influence of cannabis on school premises), the proportion of cannabis users in the class, perceived availability of cannabis, as well as adolescent cannabis

Cannabis, cannabinoids, and health.

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Lafaye, Genevieve; Karila, Laurent; Blecha, Lisa; Benyamina, Amine

2017-09-01

Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a "soft" drug, studies have proven the harmful psychiatric and addictive effects associated with its use. A number of elements are responsible for the increased complications of cannabis use, including the increase in the potency of cannabis and an evolution in the ratio between the two primary components, Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (toward a higher proportion of Δ 9 -THC), Synthetic cannabinoid (SC) use has rapidly progressed over the last few years, primarily among frequent cannabis users, because SCs provide similar psychoactive effects to cannabis. However, their composition and pharmacological properties make them dangerous substances. Cannabis does have therapeutic properties for certain indications. These therapeutic applications pertain only to certain cannabinoids and their synthetic derivatives. The objective of this article is to summarize current developments concerning cannabis and the spread of SCs. Future studies must further explore the benefit-risk profile of medical cannabis use.

Cocaine treatment admissions at three sentinel sites in South Africa (1997–2006: findings and implications for policy, practice and research

Directory of Open Access Journals (Sweden)

Plüddemann Andreas

2007-12-01

Full Text Available Abstract Background Accurate prevalence data on cocaine use, that points to where problems exist and the extent of these problems, is necessary to guide the formulation of effective substance abuse policy and practice. The purpose of this study was to provide surveillance information about the nature and extent of problematic cocaine use in South Africa. Methods Data were collected between January 1997 and December 2006 on admissions for drug abuse treatment through a regular monitoring system involving 56 drug treatment centres and programmes in Cape Town, Gauteng Province (Johannesburg and Pretoria and the Eastern Cape every six months as part of the South African Community Epidemiology Network on Drug Use (SACENDU. A one-page form was completed by treatment centre personnel to obtain demographic data, the patients' primary and secondary substances of abuse, the mode, frequency and age of first use of substance, and information on prior treatment. Results Treatment indicators point to a significant increase in cocaine related admissions over time in all sites, but with substantial inter-site variation, particularly in recent years. The data indicate high levels of crack cocaine use and high levels of daily usage among patients, most of whom were first time admissions. Patients with cocaine related problems continue to be predominantly male, with a mean age of around 30 years. Substantial changes in the racial profile of patients have occurred over time. Poly drug use is high with cocaine often used with alcohol, cannabis and other drugs. Conclusion These trends point to the possibility of cocaine use becoming a serious health and social issue in South Africa and demonstrate the utility of continued monitoring of cocaine treatment admissions in the future. They also highlight the need to address cocaine use in national and provincial policy planning and intervention efforts. In terms of treatment, the findings highlight the need to ensure that

Chronic toxicology of cannabis.

Science.gov (United States)

Reece, Albert Stuart

2009-07-01

Cannabis is the most widely used illicit drug worldwide. As societies reconsider the legal status of cannabis, policy makers and clinicians require sound knowledge of the acute and chronic effects of cannabis. This review focuses on the latter. A systematic review of Medline, PubMed, PsychInfo, and Google Scholar using the search terms "cannabis," "marijuana," "marihuana," "toxicity," "complications," and "mechanisms" identified 5,198 papers. This list was screened by hand, and papers describing mechanisms and those published in more recent years were chosen preferentially for inclusion in this review. There is evidence of psychiatric, respiratory, cardiovascular, and bone toxicity associated with chronic cannabis use. Cannabis has now been implicated in the etiology of many major long-term psychiatric conditions including depression, anxiety, psychosis, bipolar disorder, and an amotivational state. Respiratory conditions linked with cannabis include reduced lung density, lung cysts, and chronic bronchitis. Cannabis has been linked in a dose-dependent manner with elevated rates of myocardial infarction and cardiac arrythmias. It is known to affect bone metabolism and also has teratogenic effects on the developing brain following perinatal exposure. Cannabis has been linked to cancers at eight sites, including children after in utero maternal exposure, and multiple molecular pathways to oncogenesis exist. Chronic cannabis use is associated with psychiatric, respiratory, cardiovascular, and bone effects. It also has oncogenic, teratogenic, and mutagenic effects all of which depend upon dose and duration of use.

Cannabis Liberalization and Adolescent Cannabis Use: A Cross-National Study in 38 Countries

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Shi, Yuyan; Lenzi, Michela; An, Ruopeng

2015-01-01

Aims To assess the associations between types of cannabis control policies at country level and prevalence of adolescent cannabis use. Setting, Participants and Design Multilevel logistic regressions were performed on 172,894 adolescents 15 year of age who participated in the 2001/2002, 2005/2006, or 2009/2010 cross-sectional Health Behaviour in School-Aged Children (HBSC) survey in 38 European and North American countries. Measures Self-reported cannabis use status was classified into ever use in life time, use in past year, and regular use. Country-level cannabis control policies were categorized into a dichotomous measure (whether or not liberalized) as well as 4 detailed types (full prohibition, depenalization, decriminalization, and partial prohibition). Control variables included individual-level sociodemographic characteristics and country-level economic characteristics. Findings Considerable intra-class correlations (.15-.19) were found at country level. With respect to the dichotomized cannabis control policy, adolescents were more likely to ever use cannabis (odds ratio (OR) = 1.10, p = .001), use in past year (OR = 1.09, p = .007), and use regularly (OR = 1.26, p = .004). Although boys were substantially more likely to use cannabis, the correlation between cannabis liberalization and cannabis use was smaller in boys than in girls. With respect to detailed types of policies, depenalization was associated with higher odds of past-year use (OR = 1.14, p = .013) and regular use (OR = 1.23, p = .038), and partial prohibition was associated with higher odds of regular use (OR = 2.39, p = .016). The correlation between cannabis liberalization and regular use was only significant after the policy had been introduced for more than 5 years. Conclusions Cannabis liberalization with depenalization and partial prohibition policies was associated with higher levels of regular cannabis use among adolescents. The correlations were heterogeneous between genders and

Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms.

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Bloomfield, Michael A P; Morgan, Celia J A; Egerton, Alice; Kapur, Shitij; Curran, H Valerie; Howes, Oliver D

2014-03-15

Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function. We compared dopamine synthesis capacity in 19 regular cannabis users who experienced psychotic-like symptoms when they consumed cannabis with 19 nonuser sex- and age-matched control subjects. Dopamine synthesis capacity (indexed as the influx rate constant [Formula: see text] ) was measured with positron emission tomography and 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine ([(18)F]-DOPA). Cannabis users had reduced dopamine synthesis capacity in the striatum (effect size: .85; t36 = 2.54, p = .016) and its associative (effect size: .85; t36 = 2.54, p = .015) and limbic subdivisions (effect size: .74; t36 = 2.23, p = .032) compared with control subjects. The group difference in dopamine synthesis capacity in cannabis users compared with control subjects was driven by those users meeting cannabis abuse or dependence criteria. Dopamine synthesis capacity was negatively associated with higher levels of cannabis use (r = -.77, p < .001) and positively associated with age of onset of cannabis use (r = .51, p = .027) but was not associated with cannabis-induced psychotic-like symptoms (r = .32, p = .19). These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The effect of crack cocaine addiction on the microstructure and morphology of the human striatum and thalamus using novel shape analysis and fast diffusion kurtosis imaging

DEFF Research Database (Denmark)

Garza-Villarreal, Eduardo A.; Mallar, Chakravarty; Hansen, Brian

2016-01-01

The striatum and thalamus are subcortical structures intimately involved in addiction, and the morphology and microstructure of these has been studied in murine models of cocaine addiction. However, human studies using non-invasive MRI has shown inconsistencies in morphology using volumetric...... analysis. In our study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack cocaine addiction (CA) compared to matched healthy controls (HC). We did not find....... Our findings suggest that the use of finer methods and sequences is needed to characterize morphological and microstructural changes in cocaine addiction, and that brain changes in cocaine addiction are related to age....

Medical uses of marijuana (Cannabis sativa): fact or fallacy?

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Maule, W J

2015-01-01

Marijuana (Cannabis sativa) has been used throughout the world medically, recreationally and spiritually for thousands of years. In South Africa, from the mid-19th century to the 1920s, practitioners prescribed it for a multitude of conditions. In 1928 it was classified as a Schedule I substance, illegal, and without medical value. Ironically, with this prohibition, cannabis became the most widely used illicit recreational drug, not only in South Africa, but worldwide. Cannabis is generally regarded as enjoyable and relaxing without the addictive risks of opioids or stimulants. In alternative medicine circles it has never lost its appeal. To date 23 States in the USA have legalised its medical use despite the federal ban. Unfortunately, little about cannabis is not without controversy. Its main active ingredient, δ-9-tetrahydrocannabinol (THC), was not isolated until 1964, and it was not until the 1990s that the far-reaching modulatory activities of the endocannabinoid system in the human body was studied. This system's elucidation raises the possibility of many promising pharmaceutical applications, even as restrictions show no sign of abating. Recreational use of cannabis continues to increase, despite growing evidence of its addictive potential, particularly in the young. Public approval drives medical cannabis legalisation efforts without the scientific data normally required to justify a new medication's introduction. This review explores these controversies and whether cannabis is a panacea, a scourge, or both.

Associations between behavioral disinhibition and cocaine use history in individuals with cocaine dependence.

Science.gov (United States)

Prisciandaro, James J; Korte, Jeffrey E; McRae-Clark, Aimee L; Brady, Kathleen T

2012-10-01

Behavioral disinhibition has been suggested as both a cause and consequence of substance use disorders. Many studies examining associations between behavioral disinhibition and substance use history have focused on individuals with alcohol dependence or non-dependent college students. In the present study, the relationship between behavioral disinhibition and cocaine use history in individuals with cocaine dependence is examined. Forty-six non-treatment-seeking cocaine-dependent men and women completed impulsivity (Barratt impulsiveness scale; BIS) and novelty seeking (temperament and character inventory; TCI) questionnaires at the baseline visit of an ongoing study. Unadjusted, and adjusted for gender and age, Pearson correlations were calculated between BIS, TCI, and cocaine use variables from the structured clinical interview for DSM-IV and timeline follow-back (age of onset, quantity/frequency of past 30 day cocaine use). As expected, elevated motor impulsivity and novelty seeking were each associated with younger age of dependence onset. Also, individuals with lower levels of persistence on the TCI reported more days of cocaine use over the previous month. Unexpectedly, increased novelty seeking and attentional impulsivity were associated with fewer days of cocaine use and less money spent on cocaine, respectively. Controlling for age and gender did not substantially change the pattern of observed associations. The present study provides preliminary evidence for associations between behavioral disinhibition and cocaine use history in cocaine-dependent individuals. Given our relatively small sample size and the correlational nature of our findings, further research is needed to replicate and extend our results. Copyright © 2012 Elsevier Ltd. All rights reserved.

When Cannabis Is Available and Visible at School--A Multilevel Analysis of Students' Cannabis Use

Science.gov (United States)

Kuntsche, Emmanuel

2010-01-01

Aims: To investigate the links between the visibility of cannabis use in school (measured by teachers' reports of students being under the influence of cannabis on school premises), the proportion of cannabis users in the class, perceived availability of cannabis, as well as adolescent cannabis use. Methods: A multilevel regression model was…

Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

OpenAIRE

Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

2016-01-01

Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxyt...

Prevalence and Correlates of “Vaping” as a Route of Cannabis Administration in Medical Cannabis Patients

Science.gov (United States)

Cranford, James A.; Bohnert, Kipling M.; Perron, Brian E.; Bourque, Carrie; Ilgen, Mark

2016-01-01

Purpose To examine the prevalence and correlates of vaporization (i.e., “vaping”) as a route of cannabis administration in a sample of medical cannabis patients. Procedures Adults ages 21 and older (N = 1,485 M age = 45.1) who were seeking medical cannabis certification (either for the first time or as a renewal) at medical cannabis clinics in southern Michigan completed a screening assessment. Participants completed measures of route of cannabis administration, cannabis use, alcohol and other substance use. Findings An estimated 39% (n=511) of the sample reported past-month cannabis vaping, but vaping as the sole route of cannabis administration was rare. Specifically, only 30 participants (2.3% of the full sample and 5.9% of those who reported any vaping) indicated vaping as the sole route of cannabis administration. The majority (87.3%) of those who reported vaping also reported smoking (combustion) as a route of cannabis administration. Being younger than age 44, having more than a high school education, engaging in nonmedical stimulant use, being a returning medical cannabis patient, and greater frequency of cannabis use were associated with higher odds of vaping at the bivariate level and with all variables considered simultaneously. Conclusions Vaping appears to be relatively common among medical cannabis patients, but is seldom used as the sole route of cannabis administration. Results highlight the importance of monitoring trends in vaping and other substance use behaviors in this population and underscore the need for longitudinal research into the motives, correlates, and consequences of cannabis vaping in medical cannabis patients. PMID:27770657

Examining the profile of high-potency cannabis and its association with severity of cannabis dependence.

Science.gov (United States)

Freeman, T P; Winstock, A R

2015-11-01

Cannabis use is decreasing in England and Wales, while demand for cannabis treatment in addiction services continues to rise. This could be partly due to an increased availability of high-potency cannabis. Adults residing in the UK were questioned about their drug use, including three types of cannabis (high potency: skunk; low potency: other grass, resin). Cannabis types were profiled and examined for possible associations between frequency of use and (i) cannabis dependence, (ii) cannabis-related concerns. Frequent use of high-potency cannabis predicted a greater severity of dependence [days of skunk use per month: b = 0.254, 95% confidence interval (CI) 0.161-0.357, p effect became stronger as age decreased (b = -0.006, 95% CI -0.010 to -0.002, p = 0.004). By contrast, use of low-potency cannabis was not associated with dependence (days of other grass use per month: b = 0.020, 95% CI -0.029 to 0.070, p = 0.436; days of resin use per month: b = 0.025, 95% CI -0.019 to 0.067, p = 0.245). Frequency of cannabis use (all types) did not predict severity of cannabis-related concerns. High-potency cannabis was clearly distinct from low-potency varieties by its marked effects on memory and paranoia. It also produced the best high, was preferred, and most available. High-potency cannabis use is associated with an increased severity of dependence, especially in young people. Its profile is strongly defined by negative effects (memory, paranoia), but also positive characteristics (best high, preferred type), which may be important when considering clinical or public health interventions focusing on cannabis potency.

A population-based Swedish Twin and Sibling Study of cannabis, stimulant and sedative abuse in men.

Science.gov (United States)

Kendler, Kenneth S; Ohlsson, Henrik; Maes, Hermine H; Sundquist, Kristina; Lichtenstein, Paul; Sundquist, Jan

2015-04-01

Prior studies, utilizing interview-based assessments, suggest that most of the genetic risk factors for drug abuse (DA) are non-specific with a minority acting specifically on risk for abuse of particular psychoactive substance classes. We seek to replicate these findings using objective national registry data. We examined abuse of cannabis, stimulants (including cocaine) and sedatives ascertained from national Swedish registers in male-male monozygotic (1720 pairs) and dizygotic twins (1219 pairs) combined with near-age full siblings (76,457 pairs) to provide sufficient power. Modeling was performed using Mx. A common pathway model fitted better than an independent pathway model. The latent liability to DA was highly heritable but also influenced by shared environment. Cannabis, stimulant and sedative abuse all loaded strongly on the common factor. Estimates for the total heritability for the three forms of substance abuse ranged from 64 to 70%. Between 75 and 90% of that genetic risk was non-specific, coming from the common factor with the remainder deriving from substance specific genetic risk factors. By contrast, all of the shared environmental effects, which accounted for 18-20% of the variance in liability, were non-specific. In accord with prior studies based on personal interviews, the large preponderance of genetic risk factors for abuse of specific classes of psychoactive substance are non-specific. These results suggest that genetic variation in the primary sites of action of the psychoactive drugs, which differ widely across most drug classes, play a minor role in human individual differences in risk for DA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Medicinsk cannabis

OpenAIRE

Salehi, Nazu; Lambert-Jensen, Mikkel Mørch; Hansen, Sebastian Lorentz; Hansen, Caroline Pulz; Nadir, Atifa Mohammad; Ernst, Line; Showiki, Omar Isac

2016-01-01

AbstractCannabis har, blandt nogle kulturer, været værdsat for sine medicinske egenskaber i årtusinder. Formålet med denne rapport er, at undersøge de helende effekter cannabis har på cancer og multipel sclerose. Dette gør vi, ved at se på moderne forskning indenfor emnet. Endvidere vil vi prøve at forudsige, hvilke fremtidige studier der skal foretages for at opnå implementering af medicinsk cannabis, ved at bruge Rogers’ Diffusion of Innovations. VI har valgt at interviewe 3 forskellige per...

Psychosocial functioning among regular cannabis users with and without cannabis use disorder.

Science.gov (United States)

Foster, Katherine T; Arterberry, Brooke J; Iacono, William G; McGue, Matt; Hicks, Brian M

2017-11-27

In the United States, cannabis accessibility has continued to rise as the perception of its harmfulness has decreased. Only about 30% of regular cannabis users develop cannabis use disorder (CUD), but it is unclear if individuals who use cannabis regularly without ever developing CUD experience notable psychosocial impairment across the lifespan. Therefore, psychosocial functioning was compared across regular cannabis users with or without CUD and a non-user control group during adolescence (age 17; early risk) and young adulthood (ages 18-25; peak CUD prevalence). Weekly cannabis users with CUD (n = 311), weekly users without CUD (n = 111), and non-users (n = 996) were identified in the Minnesota Twin Family Study. Groups were compared on alcohol and illicit drug use, psychiatric problems, personality, and social functioning at age 17 and from ages 18 to 25. Self-reported cannabis use and problem use were independently verified using co-twin informant report. In both adolescence and young adulthood, non-CUD users reported significantly higher levels of substance use problems and externalizing behaviors than non-users, but lower levels than CUD users. High agreement between self- and co-twin informant reports confirmed the validity of self-reported cannabis use problems. Even in the absence of CUD, regular cannabis use was associated with psychosocial impairment in adolescence and young adulthood. However, regular users with CUD endorsed especially high psychiatric comorbidity and psychosocial impairment. The need for early prevention and intervention - regardless of CUD status - was highlighted by the presence of these patterns in adolescence.

The effects of the novel DA D3 receptor antagonist SR 21502 on cocaine reward, cocaine seeking and cocaine-induced locomotor activity in rats.

Science.gov (United States)

Galaj, E; Ananthan, S; Saliba, M; Ranaldi, Robert

2014-02-01

There is a focus on developing D3 receptor antagonists as cocaine addiction treatments. We investigated the effects of a novel selective D3 receptor antagonist, SR 21502, on cocaine reward, cocaine-seeking, food reward, spontaneous locomotor activity and cocaine-induced locomotor activity in rats. In Experiment 1, rats were trained to self-administer cocaine under a progressive ratio (PR) schedule of reinforcement and tested with vehicle or one of three doses of SR 21502. In Experiment 2, animals were trained to self-administer cocaine under a fixed ratio schedule of reinforcement followed by extinction of the response. Then, animals were tested with vehicle or one of the SR 21502 doses on cue-induced reinstatement of responding. In Experiment 3, animals were trained to lever press for food under a PR schedule and tested with vehicle or one dose of the compound. In Experiments 4 and 5, in separate groups of animals, the vehicle and three doses of SR 21502 were tested on spontaneous or cocaine (10 mg/kg, IP)-induced locomotor activity, respectively. SR 21502 produced significant, dose-related (3.75, 7.5 and 15 mg/kg) reductions in breakpoint for cocaine self-administration, cue-induced reinstatement (3.75, 7.5 and 15 mg/kg) and cocaine-induced locomotor activity (3.75, 7.5 and 15 mg/kg) but failed to reduce food self-administration and spontaneous locomotor activity. SR 21502 decreases cocaine reward, cocaine-seeking and locomotor activity at doses that have no effect on food reward or spontaneous locomotor activity. These data suggest SR 21502 may selectively inhibit cocaine's rewarding, incentive motivational and stimulant effects.

Public opinion and medical cannabis policies: examining the role of underlying beliefs and national medical cannabis policies

OpenAIRE

Sznitman, Sharon R.; Bretteville-Jensen, Anne Line

2015-01-01

Background Debate about medical cannabis legalization are typically informed by three beliefs: (1) cannabis has medical effects, (2) medical cannabis is addictive and (3) medical cannabis legalization leads to increased used of cannabis for recreational purposes (spillover effects). We examined how strongly these beliefs are associated with public support for medical cannabis legalization and whether this association differs across divergent medical cannabis policy regimes. Methods Robust reg...

The Neuropsychology of Cocaine Addiction: Recent Cocaine Use Masks Impairment

Science.gov (United States)

Woicik, Patricia A; Moeller, Scott J; Alia-Klein, Nelly; Maloney, Thomas; Lukasik, Tanya M; Yeliosof, Olga; Wang, Gene-Jack; Volkow, Nora D; Goldstein, Rita Z

2009-01-01

Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy comparison subjects on gender and race; the groups also did not differ in measures of general intellectual functioning. All subjects were administered an extensive NP battery measuring attention, executive function, memory, facial and emotion recognition, and motor function. Compared with healthy control subjects, CUD exhibited performance deficits on tasks of attention, executive function, and verbal memory (within one standard deviation of controls). Although CUD with positive urine status, who had higher frequency and more recent cocaine use, reported greater symptoms of dysphoria, these cognitive deficits were most pronounced in the CUD with negative urine status. Cigarette smoking, frequency of alcohol consumption, and dysphoria did not alter these results. The current findings replicate a previously reported statistically significant, but relatively mild NP impairment in CUD as compared with matched healthy control individuals and further suggest that frequent/recent cocaine may mask underlying cognitive (but not mood) disturbances. These results call for development of pharmacological agents targeted to enhance cognition, without negatively impacting mood in individuals addicted to cocaine. PMID:18496524

Cannabis effects on driving skills.

Science.gov (United States)

Hartman, Rebecca L; Huestis, Marilyn A

2013-03-01

Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ(9)-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. We review and evaluate the current literature on cannabis' effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention, and include occasional and

Is cannabis an effective treatment for joint pain?

Science.gov (United States)

Miller, Richard J; Miller, Rachel E

2017-01-01

Cannabis has been used to treat pain for thousands of years. However, since the early part of the 20th century, laws restricting cannabis use have limited its evaluation using modern scientific criteria. Over the last decade, the situation has started to change because of the increased availability of cannabis in the United States for either medical or recreational purposes, making it important to provide the public with accurate information as to the effectiveness of the drug for joint pain among other indications. The major psychotropic component of cannabis is Δ9-tetrahydrocannabinol (THC), one of some 120 naturally occurring phytocannabinoids. Cannabidiol (CBD) is another molecule found in herbal cannabis in large amounts. Although CBD does not produce psychotropic effects, it has been shown to produce a variety of pharmacological effects. Hence, the overall effects of herbal cannabis represent the collective activity of THC, CBD and a number of minor components. The action of THC is mediated by two major G-protein coupled receptors, cannabinoid receptor type 1 (CB1) and CB2, and recent work has suggested that other targets may also exist. Arachidonic acid derived endocannabinoids are the normal physiological activators of the two cannabinoid receptors. Natural phytocannabinoids and synthetic derivatives have produced clear activity in a variety of models of joint pain in animals. These effects are the result of both inhibition of pain pathway signalling (mostly CB1) and anti-inflammatory effects (mostly CB2). There are also numerous anecdotal reports of the effectiveness of smoking cannabis for joint pain. Indeed, it is the largest medical request for the use of the drug. However, these reports generally do not extend to regulated clinical trials for rheumatic diseases. Nevertheless, the preclinical and human data that do exist indicate that the use of cannabis should be taken seriously as a potential treatment of joint pain.

A critique of cannabis legalization proposals in Canada.

Science.gov (United States)

Kalant, Harold

2016-08-01

An editorial in this issue describes a cannabis policy framework document issued by a major Canadian research centre, calling for legalization of non-medical use under strict controls to prevent increase in use, especially by adolescents and young adults who are most vulnerable to adverse effects of cannabis. It claims that such a system would eliminate the severe personal, social and monetary costs of prohibition, diminish the illicit market, and provide more humane management of cannabis use disorders. It claims that experience with regulation of alcohol and tobacco will enable a system based on public health principles to control access of youth to cannabis without the harm caused by prohibition. The present critique argues that the claims made against decriminalization and for legalization are unsupported, or even contradicted, by solid evidence. Early experience in other jurisdictions suggests that legalization increases use by adolescents and its attendant harms. Regulation of alcohol use does not provide a good model for cannabis controls because there is widespread alcohol use and harm among adolescents and young adults. Government monopolies of alcohol sale have been used primarily as sources of revenue rather than for guarding public health, and no reason has been offered to believe they would act differently with respect to cannabis. Good policy decisions require extensive unbiased information about the individual and social benefits and costs of both drug use and proposed control measures, and value judgments about the benefit/harm balance of each option. Important parts of the necessary knowledge about cannabis are not yet available, so that the value judgments are not yet possible. Therefore, a better case can be made for eliminating some of the harms of prohibition by decriminalization of cannabis possession and deferring decision about legalization until the necessary knowledge has been acquired. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of general parenting and cannabis-specific parenting practices in adolescent cannabis and other illicit drug use.

Science.gov (United States)

Vermeulen-Smit, E; Verdurmen, J E E; Engels, R C M E; Vollebergh, W A M

2015-02-01

To investigate general and cannabis-specific parenting practices in relation to adolescent cannabis and other illicit drug use. Data were derived from the Dutch National School Survey on Substance Use among students (N=3209; aged 12-16 years) and one of their parents in 2011. Logistic regression analyses revealed that 1) parental cannabis use was significantly related to more adolescent lifetime and recent cannabis use, and 2) restrictive cannabis-specific parental rules were associated with less adolescent recent cannabis and lifetime use of other illicit drugs, even when controlled for sociodemographic factors, general parenting, adolescent tobacco use, and tobacco-specific parenting. In addition, no significant interaction was observed between parental cannabis use and cannabis-specific rules in their relation to adolescent cannabis and other illicit drug use, indicating that cannabis rules are evenly associated with adolescent drug use for families with and without parental cannabis experience. In addition to general parenting practices, restrictive cannabis-specific rules are related to lower adolescent cannabis and other illicit drug rates. Parents who ever used cannabis have children with a higher prevalence of cannabis use. However, their restrictive cannabis-specific rules are equally related to a lower chance of adolescent cannabis use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Vascular disease in cocaine addiction.

Science.gov (United States)

Bachi, Keren; Mani, Venkatesh; Jeyachandran, Devi; Fayad, Zahi A; Goldstein, Rita Z; Alia-Klein, Nelly

2017-07-01

Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression. Copyright © 2017 Elsevier B.V. All rights reserved.

[Cocaine - Characteristics and addiction].

Science.gov (United States)

Girczys-Połedniok, Katarzyna; Pudlo, Robert; Jarząb, Magdalena; Szymlak, Agnieszka

Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4):537-544. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Substitution and Complementarity of Alcohol and Cannabis: A Review of the Literature.

Science.gov (United States)

Subbaraman, Meenakshi Sabina

2016-09-18

Whether alcohol and cannabis are used as substitutes or complements remains debated, and findings across various disciplines have not been synthesized to date. This article is a first step towards organizing the interdisciplinary literature on alcohol and cannabis substitution and complementarity. Electronic searches were performed using PubMed and ISI Web of Knowledge. Behavioral studies of humans with "alcohol" (or "ethanol") and "cannabis" (or "marijuana") and "complement(*)" (or "substitut(*)") in the title or as a keyword were considered. Studies were organized according to sample characteristics (youth, general population, clinical and community-based). These groups were not set a priori, but were informed by the literature review process. Of the 39 studies reviewed, 16 support substitution, ten support complementarity, 12 support neither and one supports both. Results from studies of youth suggest that youth may reduce alcohol in more liberal cannabis environments (substitute), but reduce cannabis in more stringent alcohol environments (complement). Results from the general population suggest that substitution of cannabis for alcohol may occur under more lenient cannabis policies, though cannabis-related laws may affect alcohol use differently across genders and racial groups. Alcohol and cannabis act as both substitutes and complements. Policies aimed at one substance may inadvertently affect consumption of other substances. Future studies should collect fine-grained longitudinal, prospective data from the general population and subgroups of interest, especially in locations likely to legalize cannabis.

Long term stability of cannabis resin and cannabis extracts

DEFF Research Database (Denmark)

Lindholst, Christian

2010-01-01

  The aim of the present study was to investigate the stability of cannabinoids in cannabis resin slabs and cannabis extracts upon long-term storage. The levels of tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD) and cannabigerol (CBG) on both neutral and acidic form were measured...... stored in extracted form at room temperature the degradation rate of acidic THC increased significantly relative to resin material with concentration halve-lives of 35 and 91 days in daylight and darkness, respectively. Once cannabis material is extracted into organic solvents, care should be taken...

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

Science.gov (United States)

Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

2015-05-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

Selective dopamine D3 receptor antagonism by SB-277011A attenuates cocaine reinforcement as assessed by progressive-ratio and variable-cost–variable-payoff fixed-ratio cocaine self-administration in rats

Science.gov (United States)

Xi, Zheng-Xiong; Gilbert, Jeremy G.; Pak, Arlene C.; Ashby, Charles R.; Heidbreder, Christian A.; Gardner, Eliot L.

2013-01-01

In rats, acute administration of SB-277011A, a highly selective dopamine (DA) D3 receptor antagonist, blocks cocaine-enhanced brain stimulation reward, cocaine-seeking behaviour and reinstatement of cocaine-seeking behaviour. Here, we investigated whether SB-277011A attenuates cocaine reinforcement as assessed by cocaine self-administration under variable-cost–variable-payoff fixed-ratio (FR) and progressive-ratio (PR) reinforcement schedules. Acute i.p. administration of SB-277011A (3–24 mg/kg) did not significantly alter cocaine (0.75 mg/kg/infusion) self-administration reinforced under FR1 (one lever press for one cocaine infusion) conditions. However, acute administration of SB-277011A (24 mg/kg, i.p.) progressively attenuated cocaine self-administration when: (a) the unit dose of self-administered cocaine was lowered from 0.75 to 0.125–0.5 mg/kg, and (b) the work demand for cocaine reinforcement was increased from FR1 to FR10. Under PR (increasing number of lever presses for each successive cocaine infusion) cocaine reinforcement, acute administration of SB-277011A (6–24 mg/kg i.p.) lowered the PR break point for cocaine self-administration in a dose-dependent manner. The reduction in the cocaine (0.25–1.0 mg/kg) dose–response break-point curve produced by 24 mg/kg SB-277011A is consistent with a reduction in cocaine’s reinforcing efficacy. When substituted for cocaine, SB-277011A alone did not sustain self-administration behaviour. In contrast with the mixed DA D2/D3 receptor antagonist haloperidol (1 mg/kg), SB-277011A (3, 12 or 24 mg/kg) failed to impede locomotor activity, failed to impair rearing behaviour, failed to produce catalepsy and failed to impair rotarod performance. These results show that SB-277011A significantly inhibits acute cocaine-induced reinforcement except at high cocaine doses and low work requirement for cocaine. If these results extrapolate to humans, SB-277011A or similar selective DA D3 receptor antagonists may be

Reaching out towards cannabis: approach-bias in heavy cannabis users predicts changes in cannabis use

NARCIS (Netherlands)

Cousijn, Janna; Goudriaan, Anna E.; Wiers, Reinout W.

2011-01-01

Aims Repeated drug exposure can lead to an approach-bias, i.e. the relatively automatically triggered tendencies to approach rather that avoid drug-related stimuli. Our main aim was to study this approach-bias in heavy cannabis users with the newly developed cannabis Approach Avoidance Task

Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile

Science.gov (United States)

Li, Kong M.; Arnold, Jonathon C.; McGregor, Iain S.

2013-01-01

Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ9-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales “Cannabis Cautioning” scheme. A further 26 “Known Provenance” samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The “Cannabis Cautioning” samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed. PMID:23894589

Cannabis use patterns and motives: A comparison of younger, middle-aged, and older medical cannabis dispensary patients.

Science.gov (United States)

Haug, Nancy A; Padula, Claudia B; Sottile, James E; Vandrey, Ryan; Heinz, Adrienne J; Bonn-Miller, Marcel O

2017-09-01

Medical cannabis is increasingly being used for a variety of health conditions as more states implement legislation permitting medical use of cannabis. Little is known about medical cannabis use patterns and motives among adults across the lifespan. The present study examined data collected at a medical cannabis dispensary in San Francisco, California. Participants included 217 medical cannabis patients who were grouped into age-defined cohorts (younger: 18-30, middle-aged: 31-50, and older: 51-72). The age groups were compared on several measures of cannabis use, motives and medical conditions using one-way ANOVAs, chi-square tests and linear regression analyses. All three age groups had similar frequency of cannabis use over the past month; however, the quantity of cannabis used and rates of problematic cannabis use were higher among younger users relative to middle-aged and older adults. The association between age and problematic cannabis use was moderated by age of regular use initiation such that earlier age of regular cannabis use onset was associated with more problematic use in the younger users, but not among older users. Middle-aged adults were more likely to report using medical cannabis for insomnia, while older adults were more likely to use medical cannabis for chronic medical problems such as cancer, glaucoma and HIV/AIDS. Younger participants reported cannabis use when bored at a greater rate than middle-aged and older adults. Findings suggest that there is an age-related risk for problematic cannabis use among medical cannabis users, such that younger users should be monitored for cannabis use patterns that may lead to deleterious consequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cannabis Use Patterns and Motives: A Comparison of Younger, Middle-Aged, and Older Medical Cannabis Dispensary Patients

Science.gov (United States)

Haug, Nancy A.; Padula, Claudia B.; Sottile, James E.; Vandrey, Ryan; Heinz, Adrienne J.; Bonn-Miller, Marcel O.

2017-01-01

Introduction Medical cannabis is increasingly being used for a variety of health conditions as more states implement legislation permitting medical use of cannabis. Little is known about medical cannabis use patterns and motives among adults across the lifespan. Methods The present study examined data collected at a medical cannabis dispensary in San Francisco, California. Participants included 217 medical cannabis patients who were grouped into age-defined cohorts (younger: 18–30, middle-aged: 31–50, and older: 51–72). The age groups were compared on several measures of cannabis use, motives and medical conditions using one-way ANOVAs, chi-square tests and linear regression analyses. Results All three age groups had similar frequency of cannabis use over the past month; however, the quantity of cannabis used and rates of problematic cannabis use were higher among younger users relative to middle-aged and older adults. The association between age and problematic cannabis use was moderated by age of regular use initiation such that earlier age of regular cannabis use onset was associated with more problematic use in the younger users, but not among older users. Middle-aged adults were more likely to report using medical cannabis for insomnia, while older adults were more likely to use medical cannabis for chronic medical problems such as cancer, glaucoma and HIV/AIDS. Younger participants reported cannabis use when bored at a greater rate than middle-aged and older adults. Conclusions Findings suggest that there is an age-related risk for problematic cannabis use among medical cannabis users, such that younger users should be monitored for cannabis use patterns that may lead to deleterious consequences. PMID:28340421

fMRI study of neural sensitization to hedonic stimuli in long-term, daily cannabis users.

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Filbey, Francesca M; Dunlop, Joseph; Ketcherside, Ariel; Baine, Jessica; Rhinehardt, Tyler; Kuhn, Brittany; DeWitt, Sam; Alvi, Talha

2016-10-01

Although there is emergent evidence illustrating neural sensitivity to cannabis cues in cannabis users, the specificity of this effect to cannabis cues as opposed to a generalized hyper-sensitivity to hedonic stimuli has not yet been directly tested. Using fMRI, we presented 53 daily, long-term cannabis users and 68 non-using controls visual and tactile cues for cannabis, a natural reward, and, a sensory-perceptual control object to evaluate brain response to hedonic stimuli in cannabis users. The results showed an interaction between group and reward type such that the users had greater response during cannabis cues relative to natural reward cues (i.e., fruit) in the orbitofrontal cortex, striatum, anterior cingulate gyrus, and ventral tegmental area compared to non-users (cluster-threshold z = 2.3, P brain-behavior correlations between neural response to cannabis cues in fronto-striatal-temporal regions and subjective craving, marijuana-related problems, withdrawal symptoms, and levels of THC metabolites (cluster-threshold z = 2.3, P brain response to cannabis cues in long-term cannabis users that are above that of response to natural reward cues. These observations are concordant with incentive sensitization models suggesting sensitization of mesocorticolimbic regions and disruption of natural reward processes following drug use. Although the cross-sectional nature of this study does not provide information on causality, the positive correlations between neural response and indicators of cannabis use (i.e., THC levels) suggest that alterations in the reward system are, in part, related to cannabis use. Hum Brain Mapp 37:3431-3443, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Antecedents and consequences of cannabis use among racially diverse cannabis users: an analysis from Ecological Momentary Assessment.

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Buckner, Julia D; Zvolensky, Michael J; Crosby, Ross D; Wonderlich, Stephen A; Ecker, Anthony H; Richter, Ashley

2015-02-01

Cannabis remains the most commonly used illicit substance and use rates are rising. Notably, the prevalence of cannabis use disorders (CUD) nearly equals that of other illicit substance use disorders combined. Thus, the present study aimed to identify cognitive, affective, and situational predictors and consequences of ad-lib cannabis use in a racially diverse sample. The sample consisted of 93 current cannabis users (34.4% female; 57.1% non-Hispanic Caucasian), 87.1% of whom evinced a current CUD. Ecological Momentary Assessment was used to collect frequent ratings of cannabis withdrawal, craving, affect, cannabis use motives, and peer cannabis use over two weeks. Mixed effects linear models examined within- and between-day correlates and consequences of cannabis use. Withdrawal and craving were higher on cannabis use days than non-use days. Withdrawal, craving, and positive and negative affect were higher immediately prior to cannabis use compared to non-use episodes. Withdrawal and craving were higher among those who subsequently used cannabis than those who did not. Cannabis use resulted in less subsequent withdrawal, craving, and negative affect. Enhancement and coping motives were the most common reasons cited for use. Withdrawal and negative affect were related to using cannabis for coping motives and social motives. Participants were most likely to use cannabis if others were using, and withdrawal and craving were greater in social situations when others were using. Data support the contention that cannabis withdrawal and craving and affect and peer use play important roles in the maintenance of cannabis use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The potential impact of cannabis legalization on the development of cannabis use disorders.

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Budney, Alan J; Borodovsky, Jacob T

2017-11-01

Specific provisions of legal cannabis legislation and regulation could influence cannabis initiation, frequency and quantity of use, and progression to cannabis use disorder. This brief essay highlights scientifically based principles and risk factors that underlie substance use and addiction that can be leveraged to inform policies that might mitigate the development and consequences of cannabis use disorder. Specifically, pharmacologic, access/availability, and environmental factors are discussed in relation to their influence on substance use disorders to illustrate how regulatory provisions can differentially affect these factors and risk for addiction. Relevant knowledge from research and experience with alcohol and tobacco regulation are also considered. Research designed to inform regulatory policy and to evaluate the impact of cannabis legislation on cannabis use and problems is progressing. However, definitive findings will come slowly, and more concerted efforts and resources are needed to expedite this process. In the meantime, policymakers should take advantage of the large body of scientific literature on substance use to foster empirically-guided, common sense approaches to cannabis policy that focus on prevention of addiction. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety of atomoxetine in combination with intravenous cocaine in cocaine-experienced participants.

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Cantilena, Louis; Kahn, Roberta; Duncan, Connie C; Li, Shou-Hua; Anderson, Ann; Elkashef, Ahmed

2012-12-01

Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine and also whether cognitive function was affected by atomoxetine during short-term administration. In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 and 40 mg) was infused intravenously in sequential daily sessions. Preinfusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Preinfusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80- and 100-mg atomoxetine doses. All electrocardiogram parameters were unchanged. Visual Analog Scale (VAS) scores for "bad effect" in the atomoxetine group were significantly higher at baseline, then declined, and for "likely to use" declined with atomoxetine treatment. On the Addiction Research Center Inventory, the atomoxetine group scored significantly lower on amphetamine, euphoria, and energy subscales (P affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine. Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine.

Psychiatric effects of cannabis use.

Science.gov (United States)

Tunving, K

1985-09-01

That cannabis use may provoke mental disturbances is well known to Scandinavian psychiatrists today. A review of the psychiatric aspects of cannabis use is given, and the clinical signs of 70 cases of cannabis psychoses collected in Sweden are described. The bluntness and "amotivation" following chronic cannabis use are discussed. Anxiety reactions, flashbacks, dysphoric reactions and an abstinence syndrome are all sequels of cannabis use. Three risk groups begin to emerge: a) Young teenage cannabis users who lose some of their capacity to learn complex functions and who flee from reality to a world of dreams. With its sedative effect, cannabis could modify such emotions as anger and anxiety and slow down the liberation process of adolescence. b) Heavy daily users, often persons who cannot cope with depression or their life circumstances. c) Psychiatric patients whose resistance to relapses into psychotic reactions might be diminished according to the psychotropic effects of cannabis.

Harm reduction-the cannabis paradox

Directory of Open Access Journals (Sweden)

Melamede Robert

2005-09-01

Full Text Available Abstract This article examines harm reduction from a novel perspective. Its central thesis is that harm reduction is not only a social concept, but also a biological one. More specifically, evolution does not make moral distinctions in the selection process, but utilizes a cannabis-based approach to harm reduction in order to promote survival of the fittest. Evidence will be provided from peer-reviewed scientific literature that supports the hypothesis that humans, and all animals, make and use internally produced cannabis-like products (endocannabinoids as part of the evolutionary harm reduction program. More specifically, endocannabinoids homeostatically regulate all body systems (cardiovascular, digestive, endocrine, excretory, immune, nervous, musculo-skeletal, reproductive. Therefore, the health of each individual is dependant on this system working appropriately.

Stress responding in cannabis smokers as a function of trauma exposure, sex, and relapse in the human laboratory.

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Chao, Thomas; Radoncic, Vanya; Hien, Denise; Bedi, Gillinder; Haney, Margaret

2018-04-01

Stress responding is linked to drug use, but little is known about stress responses in cannabis smokers. We investigated acute stress responding in cannabis smokers as a function of trauma exposure and sex, and relationships between stress responses and cannabis relapse. 125 healthy, non-treatment-seeking daily cannabis smokers (23F, 102 M) completed the Trier Social Stress Task (TSST), a standardized laboratory stressor; subsets also completed a trauma questionnaire (n = 106) and a laboratory cannabis relapse measure (n = 54). Stress responding was assessed with heart rate (HR), salivary cortisol (CORT), and self-rated mood. Cannabis smokers reporting at least one trauma exposure had higher CORT and anxiety overall compared to those reporting no trauma. Stress responding did not differ as a function of binary trauma exposure, although total number of exposures correlated positively with CORT and anxiety during stress. Females reported increased nervousness after stress relative to males matched to the females for cannabis and cigarette use. An interactive effect of sex and trauma on HR suggested that females with trauma exposure have increased cardiovascular stress responding relative to those without such exposure, with no differential effect in males. Stress responding did not predict laboratory cannabis relapse. We report differences in acute stress responding as a function of trauma, sex, and their interaction in a large sample of relatively homogenous cannabis smokers. Further investigation of how trauma impacts stress responding in male and female cannabis smokers, and how this relates to different aspects of cannabis use, is warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

Use of micronutrients attenuates cannabis and nicotine abuse as evidenced from a reversal design: a case study.

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Harrison, Rachel; Rucklidge, Julia J; Blampied, Neville

2013-01-01

Prior research shows that micronutrients, particularly amino acids, can assist individuals with substance dependence to quit various drugs of abuse, including cannabis, alcohol, and cocaine. As part of a wider investigation of the impact of micronutrients (mostly vitamins and minerals) on psychiatric symptoms, such as Attention-Deficit/Hyperactivity Disorder (ADHD), depression, and anxiety, we observed that many participants reduced or eliminated use of alcohol, cigarettes, and cannabis. One case using a single-case reversal (off-on-off-on-off) design is presented and shows not only on-off control of psychiatric symptoms as micronutrients are consumed or withdrawn, but also simultaneous on-off use of cannabis and cigarettes, despite not directly targeting this substance use as part of the treatment protocol. This case adds to a growing body of research supporting the use of micronutrients in the treatment of psychiatric symptoms and suggests it may extend to substance dependence. Micronutrients, by assisting with mood regulation and reductions in anxiety, may assist with successful cessation of drug use. Alternatively, they may directly impact on the brain reward circuitry believed to be involved in the expression of addictions, thereby providing the appropriate precursors and cofactors necessary for adequate neurotransmitter synthesis. This case should continue to stimulate researchers to consider the role of nutrients, in particular vitamins and minerals, in drug treatment programs and encourage more rigorous trials.

Cannabis Effects on Driving Skills

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Hartman, Rebecca L.; Huestis, Marilyn A.

2013-01-01

BACKGROUND Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ9-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. CONTENT We review and evaluate the current literature on cannabis’ effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. SUMMARY Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2–5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention

Cannabis and related impairment: the unique roles of cannabis use to cope with social anxiety and social avoidance.

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Buckner, Julia D; Zvolensky, Michael J

2014-01-01

Social anxiety appears to be a risk factor for cannabis-related problems. Socially anxious individuals are vulnerable to using cannabis to cope in social situations and to avoiding social situations if marijuana is unavailable. Yet, the relative impact of cannabis use to cope with social anxiety relative to use to cope with negative affect more broadly has yet to be examined. The present study used the Marijuana to Cope with Social Anxiety Scale (MCSAS) to examine the incremental validity of using cannabis use to cope in social situations (MCSAS-Cope) and avoidance of social situations if cannabis is unavailable (MCSAS-Avoid) in a community-recruited sample of 123 (34.1% female) current cannabis users. After controlling for age of first cannabis use, gender, alcohol and tobacco use, other cannabis use motives, and cannabis expectancies, MCSAS-Cope remained significantly positively related to cannabis use frequency and cannabis-related problems. After controlling for age of first cannabis use, gender, alcohol and tobacco use, and experiential avoidance, MCSAS-Avoid remained significantly related to cannabis problems but not frequency. The present findings suggest that cannabis use to manage social forms of anxiety may be important to understanding cannabis use behaviors. The current findings identify cognitive/motivational factors implicated in more frequent cannabis use and in cannabis-related impairment, which may be essential to inform efforts to further refine prevention and treatment efforts. © American Academy of Addiction Psychiatry.

Cannabis Use Disorder in Adolescence.

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Simpson, Annabelle K; Magid, Viktoriya

2016-07-01

Cannabis use in the adolescent population poses a significant threat of addiction potential resulting in altered neurodevelopment. There are multiple mechanisms of treatment of cannabis use disorder including behavioral therapy management and emerging data on treatment via pharmacotherapy. Recognizing the diagnostic criteria for cannabis use disorder, cannabis withdrawal syndrome, and mitigating factors that influence adolescent engagement in cannabis use allows for comprehensive assessment and management in the adolescent population. Copyright © 2016 Elsevier Inc. All rights reserved.

Noradrenergic α1 Receptor Antagonist Treatment Attenuates Positive Subjective Effects of Cocaine in Humans: A Randomized Trial

Science.gov (United States)

Newton, Thomas F.; De La Garza, Richard; Brown, Gregory; Kosten, Thomas R.; Mahoney, James J.; Haile, Colin N.

2012-01-01

Background Preclinical research implicates dopaminergic and noradrenergic mechanisms in mediating the reinforcing effects of drugs of abuse, including cocaine. The objective of this study was to evaluate the impact of treatment with the noradrenergic α1 receptor antagonist doxazosin on the positive subjective effects of cocaine. Methods Thirteen non-treatment seeking, cocaine-dependent volunteers completed this single-site, randomized, placebo-controlled, within-subjects study. In one study phase volunteers received placebo and in the other they received doxazosin, with the order counterbalanced across participants. Study medication was masked by over-encapsulating doxazosin tablets and matched placebo lactose served as the control. Study medication treatment was initiated at 1 mg doxazosin or equivalent number of placebo capsules PO/day and increased every three days by 1 mg. After receiving 4 mg doxazosin or equivalent number of placebo capsules participants received masked doses of 20 and 40 mg cocaine IV in that order with placebo saline randomly interspersed to maintain the blind. Results Doxazosin treatment was well tolerated and doxazosin alone produced minimal changes in heart rate and blood pressure. During treatment with placebo, cocaine produced dose-dependent increases in subjective effect ratings of “high”, “stimulated”, “like cocaine”, “desire cocaine”, “any drug effect”, and “likely to use cocaine if had access” (p<.001). Doxazosin treatment significantly attenuated the effects of 20 mg cocaine on ratings of “stimulated”, “like cocaine”, and “likely to use cocaine if had access” (p<.05). There were trends for doxazosin to reduce ratings of “stimulated”, “desire cocaine”, and “likely to use cocaine if had access” (p<.10). Conclusions Medications that block noradrenergic α1 receptors, such as doxazosin, may be useful as treatments for cocaine dependence, and should be evaluated further. Trial

Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile.

Directory of Open Access Journals (Sweden)

Wendy Swift

Full Text Available Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ(9-tetrahydrocannabinol (THC and low levels of other phytocannabinoids, particularly cannabidiol (CBD. Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales "Cannabis Cautioning" scheme. A further 26 "Known Provenance" samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG, and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC, cannabinol (CBN and tetrahydrocannabivarin (THC-V. The "Cannabis Cautioning" samples showed high mean THC content (THC+THC-A = 14.88% and low mean CBD content (CBD+CBD-A = 0.14%. A modest level of CBG was detected (CBG+CBG-A = 1.18% and very low levels of CBC, CBN and THC-V (<0.1%. "Known Provenance" samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed.

Cannabis and sport.

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Saugy, M; Avois, L; Saudan, C; Robinson, N; Giroud, C; Mangin, P; Dvorak, J

2006-07-01

Cannabis is on the list of prohibited substances in the practice of sport, although its performance enhancing effect has not yet been proved. Its popularity among the younger generations as a social drug puts cannabis at the top of the list of compounds detected by the anti-doping laboratories accredited by the World Anti-Doping Agency worldwide. The management of the results of urine analysis is quite difficult for the medical and disciplinary committees not only because of the social use of the substance, but also because of the interpretation of the analytical data from urine samples. This paper gives an overview of what is presently known about cannabis in relation with the practice of sport. Review of literature on the cannabis and exercise, its effect in the body, and the problems with interpretation of results when it is detected in urine. The paper outlines the major effects of cannabis in the context of its social use and its use for sport activities. The difficulties in the interpretation of urine sample analysis results because of the protracted excretion time of the main metabolite, long after the intake, are described. There is an urgent need for sport authorities to take measures necessary to avoid players misusing cannabis.

Toxic Effects of Cannabis and Cannabinoids: Animal Data

Directory of Open Access Journals (Sweden)

Pierre Beaulieu

2005-01-01

Full Text Available The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.

Cannabis Users' Recommended Warnings for Packages of Legally Sold Cannabis: An Australia-Centered Study.

Science.gov (United States)

Malouff, John M; Johnson, Caitlin E; Rooke, Sally E

2016-01-01

Introduction: Although cannabis use creates health risks, governments have recently been legalizing either medical use or leisure use. These governments can mandate health warnings on cannabis packages. Prior research examined recommended warnings of cannabis experts. The aim of this study was to obtain suggested cannabis health and safety warnings from cannabis users. Methods: We used a media release, Facebook postings, and announcements in university classes to seek individuals who had used cannabis at least once according to their own report. Using online data collection software that keeps participants anonymous, we asked the individuals to suggest a warning that governments could mandate on cannabis packages. Results: In total, 288 users suggested warnings. Categorizing the warnings into content categories led to six warning topics: (1) risk of harm to mental health and psychological functioning; (2) risk of operating machinery while under the influence; (3) short-term physical side effects; (4) responsible use; (5) long-term negative physical effects; and (6) dependence, addiction, or abuse. The user-suggested warnings overlapped with six expert-recommended warnings identified in prior survey research and included two content areas that did not feature in expert-recommended warnings: short-term physical side effects and the importance of responsible use. Conclusions: The results are consistent with prior findings that some youths perceive cannabis use as potentially harmful. The current findings provide possible new content for warnings on cannabis packages.

Safety of Atomoxetine in Combination with Intravenous Cocaine in Cocaine- Experienced Participants

Science.gov (United States)

Cantilena, Louis; Kahn, Roberta; Duncan, Connie C.; Li, Shou-Hua; Anderson, Ann; Elkashef, Ahmed

2012-01-01

Objectives Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine, and also whether cognitive function was affected by atomoxetine during short-term administration. Methods In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 mg and 40 mg) was infused intravenously in sequential daily sessions. Results Pre-infusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Pre-infusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80 mg and 100 mg atomoxetine doses. All ECG parameters were unchanged. VAS scores for “bad effect” in the atomoxetine group were significantly higher at baseline, then declined, and for “likely to use” declined with atomoxetine treatment. On the ARCI the atomoxetine group scored significantly lower on amphetamine, euphoria and energy subscales (pAtomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine. Conclusions Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine. PMID:22987022

Cannabis and Pain: A Clinical Review

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Hill, Kevin P.; Palastro, Matthew D.; Johnson, Brian; Ditre, Joseph W.

2017-01-01

Abstract Introduction: Cannabis has been used for medical purposes across the world for centuries. As states and countries implement medical and recreational cannabis policies, increasing numbers of people are using cannabis pharmacotherapy for pain. There is a theoretical rationale for cannabis' efficacy for pain management, although the subjective pain relief from cannabis may not match objective measurements of analgesia. As more patients turn to cannabis for pain relief, there is a need f...

Functional MRI studies in human Ecstasy and cannabis users

NARCIS (Netherlands)

Jager, G.

2006-01-01

Cannabis and ecstasy are among the most widely used illicit drugs in the world. However, there are substantial concerns about their neurotoxic potential for brain and brain function. Despite previous research, some crucial questions regarding the causality, course and clinical relevance have

Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

Science.gov (United States)

Wee, Sunmee; Hicks, Martin J; De, Bishnu P; Rosenberg, Jonathan B; Moreno, Amira Y; Kaminsky, Stephen M; Janda, Kim D; Crystal, Ronald G; Koob, George F

2012-01-01

Immunotherapy is a promising treatment for drug addiction. However, insufficient immune responses to vaccines in most subjects pose a challenge. In this study, we tested the efficacy of a new cocaine vaccine (dAd5GNE) in antagonizing cocaine addiction-related behaviors in rats. This vaccine used a disrupted serotype 5 adenovirus (Ad) gene transfer vector coupled to a third-generation cocaine hapten, termed GNE (6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido-hexanoic acid). Three groups of rats were immunized with dAd5GNE. One group was injected with 3H-cocaine, and radioactivity in the blood and brain was determined. A second group was tested for cocaine-induced locomotor sensitization. A third group was examined for cocaine self-administration, extinction, and reinstatement of responding for cocaine. Antibody titers were determined at various time-points. In each experiment, we added a control group that was immunized with dAd5 without a hapten. The vaccination with dAd5GNE produced long-lasting high titers (>105) of anti-cocaine antibodies in all of the rats. The vaccination inhibited cocaine-induced hyperlocomotor activity and sensitization. Vaccinated rats acquired cocaine self-administration, but they showed less motivation to self-administer cocaine under a progressive-ratio schedule than control rats. When cocaine was not available in a session, control rats exhibited ‘extinction burst' responding, whereas vaccinated rats did not. Moreover, when primed with cocaine, vaccinated rats did not reinstate responding, suggesting a blockade of cocaine-seeking behavior. These data strongly suggest that our dAd5GNE vector-based vaccine may be effective in treating cocaine abuse and addiction. PMID:21918504

Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Som, P.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States); Oster, Z.H. [State Univ. of New York, Stony Brook, NY (United States); Knapp, F.F. Jr. [Oak Ridge National Lab., TN (United States); Yonekura, Y. [Kyoto Univ. (Japan). Faculty of Medicine; Fujibayashi, Y. [Kyoto Univ. (Japan). Hospital; Yamamoto, K. [Fukui Univ. (Japan). Medical School; Kubota, K. [Tohoku Univ., Sendai (Japan)

1992-12-31

Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Som, P.; Wang, G.J. (Brookhaven National Lab., Upton, NY (United States)); Oster, Z.H. (State Univ. of New York, Stony Brook, NY (United States)); Knapp, F.F. Jr. (Oak Ridge National Lab., TN (United States)); Yonekura, Y. (Kyoto Univ. (Japan). Faculty of Medicine); Fujibayashi, Y. (Kyoto Univ. (Japan). Hospital); Yamamoto, K. (Fukui Univ. (Japan). Medical School); Kubota, K. (Tohoku Univ., Sendai

1992-01-01

Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

Cannabis Mobile Apps: A Content Analysis.

Science.gov (United States)

Ramo, Danielle E; Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

2015-08-12

Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. The Apple and Google Play app stores were searched using the terms "cannabis" and "marijuana." Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated "17+" years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated "high maturity" (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Cannabis apps are generally free and highly rated. Apps were most often informational (facts, strain classification), or recreational (games), likely

[Cannabis-induced disorders].

Science.gov (United States)

Soyka, M; Preuss, U; Hoch, E

2017-03-01

Use and misuse of cannabis and marihuana are frequent. About 5% of the adult population are current users but only 1.2% are dependent. The medical use of cannabis is controversial but there is some evidence for improvement of chronic pain and spasticity. The somatic toxicity of cannabis is well proven but limited and psychiatric disorders induced by cannabis are of more relevance, e.g. cognitive disorders, amotivational syndrome, psychoses and delusional disorders as well as physical and psychological dependence. The withdrawal symptoms are usually mild and do not require pharmacological interventions. To date there is no established pharmacotherapy for relapse prevention. Psychosocial interventions include psychoeducation, behavioral therapy and motivational enhancement. The CANDIS protocol is the best established German intervention among abstinence-oriented therapies.

Individual and combined effects of cannabis and tobacco on drug reward processing in non-dependent users.

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Hindocha, Chandni; Lawn, Will; Freeman, Tom P; Curran, H Valerie

2017-11-01

Cannabis and tobacco are often smoked simultaneously in joints, and this practice may increase the risks of developing tobacco and/or cannabis use disorders. Currently, there is no human experimental research on how these drugs interact on addiction-related measures. This study aimed to investigate how cannabis and tobacco, each alone and combined together in joints, affected individuals' demand for cannabis puffs and cigarettes, explicit liking of drug and non-drug-related stimuli and craving. A double-blind, 2 (active cannabis, placebo cannabis) × 2 (active tobacco, placebo tobacco) crossover design was used with 24 non-dependent cannabis and tobacco smokers. They completed a pleasantness rating task (PRT), a marijuana purchase task (MPT) and a cigarette purchase task (CPT) alongside measures of craving pre- and post-drug administration. Relative to placebo cannabis, active cannabis reduced liking of cannabis-associated stimuli and increased response time to all stimuli except cigarette-related stimuli. Relative to placebo cannabis, active cannabis decreased demand for cannabis puffs (trends for breakpoint and elasticity) and cigarettes (breakpoint, P max , O max ) on several characteristics of the purchase tasks. We found no evidence that active tobacco, both alone or combined with cannabis, had an effect on liking, demand or craving. Acutely, cannabis reduced liking of cannabis-related stimuli and demand for cannabis itself. Acute cannabis also reduced demand for cigarettes on the CPT. Acute tobacco administration did not affect demand or pleasantness ratings for cigarettes themselves or cannabis. In non-dependent cannabis and tobacco co-users, tobacco did not influence the rewarding effects of cannabis.

Prenatal IV Cocaine: Alterations in Auditory Information Processing

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Charles F. Mactutus

2011-06-01

Full Text Available One clue regarding the basis of cocaine-induced deficits in attentional processing is provided by the clinical findings of changes in the infants’ startle response; observations buttressed by neurophysiological evidence of alterations in brainstem transmission time. Using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, the present study examined the effects of prenatal cocaine on auditory information processing via tests of the acoustic startle response (ASR, habituation, and prepulse inhibition (PPI in the offspring. Nulliparous Long-Evans female rats, implanted with an IV access port prior to breeding, were administered saline, 0.5, 1.0, or 3.0 mg/kg/injection of cocaine HCL (COC from gestation day (GD8-20 (1x/day-GD8-14, 2x/day-GD15-20. COC had no significant effects on maternal/litter parameters or growth of the offspring. At 18-20 days of age, one male and one female, randomly selected from each litter displayed an increased ASR (>30% for males at 1.0 mg/kg and >30% for females at 3.0 mg/kg. When reassessed in adulthood (D90-100, a linear dose-response increase was noted on response amplitude. At both test ages, within-session habituation was retarded by prenatal cocaine treatment. Testing the females in diestrus vs. estrus did not alter the results. Prenatal cocaine altered the PPI response function across interstimulus interval (ISI and induced significant sex-dependent changes in response latency. Idazoxan, an alpha2-adrenergic receptor antagonist, significantly enhanced the ASR, but less enhancement was noted with increasing doses of prenatal cocaine. Thus, in utero exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, causes persistent, if not permanent, alterations in auditory information processing, and suggests dysfunction of the central noradrenergic circuitry modulating, if not mediating, these responses.

Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

OpenAIRE

Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Telang, Frank; Fowler, Joanna S.; Pradhan, Kith; Jayne, Millard; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher

2010-01-01

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and...

[Therapeutic use of cannabis derivatives].

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Benyamina, Amine; Reynaud, Michel

2014-02-01

The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

Cannabis Use is Associated with Lower Odds of Prescription Opioid Analgesic Use Among HIV-Infected Individuals with Chronic Pain.

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Sohler, Nancy L; Starrels, Joanna L; Khalid, Laila; Bachhuber, Marcus A; Arnsten, Julia H; Nahvi, Shadi; Jost, John; Cunningham, Chinazo O

2018-01-17

Chronic pain is common in the United States and prescribed opioid analgesics use for noncancer pain has increased dramatically in the past two decades, possibly accounting for the current opioid addiction epidemic. Co-morbid drug use in those prescribed opioid analgesics is common, but there are few data on polysubstance use patterns. We explored patterns of use of cigarette, alcohol, and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics. We conducted a secondary data analysis of screening interviews conducted as part of a parent randomized trial of financial incentives to improve HIV outcomes among drug users. In a convenience sample of people with HIV and chronic pain, we collected self-report data on demographic characteristics; pain; patterns of opioid analgesic use (both prescribed and illicit); cigarette, alcohol, and illicit drug use (including cannabis, heroin, and cocaine) within the past 30 days; and current treatment for drug use and HIV. Almost half of the sample of people with HIV and chronic pain reported current prescribed opioid analgesic use (N = 372, 47.1%). Illicit drug use was common (N = 505, 63.9%), and cannabis was the most commonly used illicit substance (N = 311, 39.4%). In multivariate analyses, only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use (adjusted odds ratio = 0.57; 95% confidence interval: 0.38-0.87). Conclusions/Importance: Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management, which could help to address adverse events associated with opioid analgesic use.

Sex differences in selecting between food and cocaine reinforcement are mediated by estrogen.

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Kerstetter, Kerry A; Ballis, Maya A; Duffin-Lutgen, Stevie; Carr, Amanda E; Behrens, Alexandra M; Kippin, Tod E

2012-11-01

Cocaine-dependent women, relative to their male counterparts, report shorter cocaine-free periods and report transiting faster from first use to entering treatment for addiction. Similarly, preclinical studies indicate that female rats, particularly those in the estrus phase of their reproductive cycle, show increased operant responding for cocaine under a wide variety of schedules. Making maladaptive choices is a component of drug dependence, and concurrent reinforcement schedules that examine cocaine choice offers an animal model of the conditions of human drug use; therefore, the examination of sex differences in decision-making may be critical to understanding why women display a more severe profile of cocaine addiction than men. Accordingly, we assessed sex and estrous cycle differences in choice between food (45 mg grain pellets) and intravenous cocaine (0.4 or 1.0 mg/kg per infusion) reinforcement in male, female (freely cycling), and ovariectomized (OVX) females treated with either estrogen benzoate (EB; 5 μg per day) or vehicle. At both cocaine doses, intact female rats choose cocaine over food significantly more than male rats. However, the estrous cycle did not impact the level of cocaine choice in intact females. Nevertheless, OVX females treated with vehicle exhibited a substantially lower cocaine choice compared with those receiving daily EB or to intact females. These results demonstrate that intact females have a greater preference for cocaine over food compared with males. Furthermore, this higher preference is estrogen-dependent, but does not vary across the female reproductive cycle, suggesting that ovarian hormones regulate cocaine choice. The present findings indicate that there is a biological predisposition for females to forgo food reinforcement to obtain cocaine reinforcement, which may substantially contribute to women experiencing a more severe profile of cocaine addiction than men.

History of cannabis use is associated with altered gait.

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Pearson-Dennett, Verity; Todd, Gabrielle; Wilcox, Robert A; Vogel, Adam P; White, Jason M; Thewlis, Dominic

2017-09-01

Despite evidence that cannabinoid receptors are located in movement-related brain regions (e.g., basal ganglia, cerebral cortex, and cerebellum), and that chronic cannabis use is associated with structural and functional brain changes, little is known about the long-term effect of cannabis use on human movement. The aim of the current study was to investigate balance and walking gait in adults with a history of cannabis use. We hypothesised that cannabis use is associated with subtle changes in gait and balance that are insufficient in magnitude for detection in a clinical setting. Cannabis users (n=22, 24±6years) and non-drug using controls (n=22, 25±8years) completed screening tests, a gait and balance test (with a motion capture system and in-built force platforms), and a clinical neurological examination of movement. Compared to controls, cannabis users exhibited significantly greater peak angular velocity of the knee (396±30 versus 426±50°/second, P=0.039), greater peak elbow flexion (53±12 versus 57±7°, P=0.038) and elbow range of motion (33±13 versus 36±10°, P=0.044), and reduced shoulder flexion (41±19 versus 26±16°, P=0.007) during walking gait. However, balance and neurological parameters did not significantly differ between the groups. The results suggest that history of cannabis use is associated with long-lasting changes in open-chain elements of walking gait, but the magnitude of change is not clinically detectable. Further research is required to investigate if the subtle gait changes observed in this population become more apparent with aging and increased cannabis use. Copyright © 2017 Elsevier B.V. All rights reserved.

Terpene synthases from Cannabis sativa.

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Booth, Judith K; Page, Jonathan E; Bohlmann, Jörg

2017-01-01

Cannabis (Cannabis sativa) plants produce and accumulate a terpene-rich resin in glandular trichomes, which are abundant on the surface of the female inflorescence. Bouquets of different monoterpenes and sesquiterpenes are important components of cannabis resin as they define some of the unique organoleptic properties and may also influence medicinal qualities of different cannabis strains and varieties. Transcriptome analysis of trichomes of the cannabis hemp variety 'Finola' revealed sequences of all stages of terpene biosynthesis. Nine cannabis terpene synthases (CsTPS) were identified in subfamilies TPS-a and TPS-b. Functional characterization identified mono- and sesqui-TPS, whose products collectively comprise most of the terpenes of 'Finola' resin, including major compounds such as β-myrcene, (E)-β-ocimene, (-)-limonene, (+)-α-pinene, β-caryophyllene, and α-humulene. Transcripts associated with terpene biosynthesis are highly expressed in trichomes compared to non-resin producing tissues. Knowledge of the CsTPS gene family may offer opportunities for selection and improvement of terpene profiles of interest in different cannabis strains and varieties.

Estimating the harms and costs of cannabis-attributable collisions in the Canadian provinces.

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Wettlaufer, Ashley; Florica, Roxana O; Asbridge, Mark; Beirness, Douglas; Brubacher, Jeffrey; Callaghan, Russell; Fischer, Benedikt; Gmel, Gerrit; Imtiaz, Sameer; Mann, Robert E; McKiernan, Anna; Rehm, Jürgen

2017-04-01

In 2012, 10% of Canadians used cannabis and just under half of those who use cannabis were estimated to have driven under the influence of cannabis. Substantial evidence has accumulated to indicate that driving after cannabis use increases collision risk significantly; however, little is known about the extent and costs associated with cannabis-related traffic collisions. This study quantifies the costs of cannabis-related traffic collisions in the Canadian provinces. Province and age specific cannabis-attributable fractions (CAFs) were calculated for traffic collisions of varying severity. The CAFs were applied to traffic collision data in order to estimate the total number of persons involved in cannabis-attributable fatal, injury and property damage only collisions. Social cost values, based on willingness-to-pay and direct costs, were applied to estimate the costs associated with cannabis-related traffic collisions. The 95% confidence intervals were calculated using Monte Carlo methodology. Cannabis-attributable traffic collisions were estimated to have caused 75 deaths (95% CI: 0-213), 4407 injuries (95% CI: 20-11,549) and 7794 people (95% CI: 3107-13,086) were involved in property damage only collisions in Canada in 2012, totalling $1,094,972,062 (95% CI: 37,069,392-2,934,108,175) with costs being highest among younger people. The cannabis-attributable driving harms and costs are substantial. The harm and cost of cannabis-related collisions is an important factor to consider as Canada looks to legalize and regulate the sale of cannabis. This analysis provides evidence to help inform Canadian policy to reduce the human and economic costs of drug-impaired driving. Copyright © 2017 Canadian Centre on Substance Abuse. Published by Elsevier B.V. All rights reserved.

Cocaine dependent individuals discount future rewards more than future losses for both cocaine and monetary outcomes.

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Johnson, Matthew W; Bruner, Natalie R; Johnson, Patrick S

2015-01-01

Cocaine dependence and other forms of drug dependence are associated with steeper devaluation of future outcomes (delay discounting). Although studies in this domain have typically assessed choices between monetary gains (e.g., receive less money now versus receive more money after a delay), delay discounting is also applicable to decisions involving losses (e.g., small loss now versus larger delayed loss), with gains typically discounted more than losses (the "sign effect"). It is also known that drugs are discounted more than equivalently valued money. In the context of drug dependence, however, relatively little is known about the discounting of delayed monetary and drug losses and the presence of the sign effect. In this within-subject, laboratory study, delay discounting for gains and losses was assessed for cocaine and money outcomes in cocaine-dependent individuals (n=89). Both cocaine and monetary gains were discounted at significantly greater rates than cocaine and monetary losses, respectively (i.e., the sign effect). Cocaine gains were discounted significantly more than monetary gains, but cocaine and monetary losses were discounted similarly. Results suggest that cocaine is discounted by cocaine-dependent individuals in a systematic manner similar to other rewards. Because the sign effect was shown for both cocaine and money, delayed aversive outcomes may generally have greater impact than delayed rewards in shaping present behavior in this population. Copyright © 2014. Published by Elsevier Ltd.

Medicinsk cannabis : En litteraturstudie om användningen av medicinsk cannabis inom cancervården

OpenAIRE

Nygård, Sofia

2017-01-01

Detta examensarbete handlar om användningen av medicinsk cannabis inom cancervården. Syftet med examensarbetet var att undersöka vilken roll cannabis kan ha i cancervården. Frågeställningarna var: Hur upplever patienten användning av medicinsk cannabis? Vilken hjälp kan patienten väntas få av medicinsk cannabis? vilka attityder har vårdpersonal mot medicinsk cannabis? Som utgångsteorier i denna studie användes Ruland och Moors teori om ett fridfullt slut på livet samt Erikssons teori om ...

Approach-bias predicts development of cannabis problem severity in heavy cannabis users: results from a prospective FMRI study.

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Janna Cousijn

Full Text Available A potentially powerful predictor for the course of drug (abuse is the approach-bias, that is, the pre-reflective tendency to approach rather than avoid drug-related stimuli. Here we investigated the neural underpinnings of cannabis approach and avoidance tendencies. By elucidating the predictive power of neural approach-bias activations for future cannabis use and problem severity, we aimed at identifying new intervention targets. Using functional Magnetic Resonance Imaging (fMRI, neural approach-bias activations were measured with a Stimulus Response Compatibility task (SRC and compared between 33 heavy cannabis users and 36 matched controls. In addition, associations were examined between approach-bias activations and cannabis use and problem severity at baseline and at six-month follow-up. Approach-bias activations did not differ between heavy cannabis users and controls. However, within the group of heavy cannabis users, a positive relation was observed between total lifetime cannabis use and approach-bias activations in various fronto-limbic areas. Moreover, approach-bias activations in the dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC independently predicted cannabis problem severity after six months over and beyond session-induced subjective measures of craving. Higher DLPFC/ACC activity during cannabis approach trials, but lower activity during cannabis avoidance trials were associated with decreases in cannabis problem severity. These findings suggest that cannabis users with deficient control over cannabis action tendencies are more likely to develop cannabis related problems. Moreover, the balance between cannabis approach and avoidance responses in the DLPFC and ACC may help identify individuals at-risk for cannabis use disorders and may be new targets for prevention and treatment.

Approach-bias predicts development of cannabis problem severity in heavy cannabis users: results from a prospective FMRI study.

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Cousijn, Janna; Goudriaan, Anna E; Ridderinkhof, K Richard; van den Brink, Wim; Veltman, Dick J; Wiers, Reinout W

2012-01-01

A potentially powerful predictor for the course of drug (ab)use is the approach-bias, that is, the pre-reflective tendency to approach rather than avoid drug-related stimuli. Here we investigated the neural underpinnings of cannabis approach and avoidance tendencies. By elucidating the predictive power of neural approach-bias activations for future cannabis use and problem severity, we aimed at identifying new intervention targets. Using functional Magnetic Resonance Imaging (fMRI), neural approach-bias activations were measured with a Stimulus Response Compatibility task (SRC) and compared between 33 heavy cannabis users and 36 matched controls. In addition, associations were examined between approach-bias activations and cannabis use and problem severity at baseline and at six-month follow-up. Approach-bias activations did not differ between heavy cannabis users and controls. However, within the group of heavy cannabis users, a positive relation was observed between total lifetime cannabis use and approach-bias activations in various fronto-limbic areas. Moreover, approach-bias activations in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) independently predicted cannabis problem severity after six months over and beyond session-induced subjective measures of craving. Higher DLPFC/ACC activity during cannabis approach trials, but lower activity during cannabis avoidance trials were associated with decreases in cannabis problem severity. These findings suggest that cannabis users with deficient control over cannabis action tendencies are more likely to develop cannabis related problems. Moreover, the balance between cannabis approach and avoidance responses in the DLPFC and ACC may help identify individuals at-risk for cannabis use disorders and may be new targets for prevention and treatment.

Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa.

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Pomahacova, B; Van der Kooy, F; Verpoorte, R

2009-11-01

Cannabis sativa is a well-known recreational drug and, as such, a controlled substance of which possession and use are illegal in most countries of the world. Due to the legal constraints on the possession and use of C. sativa, relatively little research on the medicinal qualities of this plant has been conducted. Interest in the medicinal uses of this plant has, however, increased in the last decades. The methods of administration for medicinal purposes are mainly through oral ingestion, smoking, and nowadays also inhalation through vaporization. During this study the commercially available Volcano vaporizing device was compared with cannabis cigarette smoke. The cannabis smoke and vapor (obtained at different temperatures) were quantitatively analyzed by high-performance liquid chromatography (HPLC). In addition, different quantities of cannabis material were also tested with the vaporizer. The cannabinoids:by-products ratio in the vapor obtained at 200 degrees C and 230 degrees C was significantly higher than in the cigarette smoke. The worst ratio of cannabinoids:by-products was obtained from the vaporized cannabis sample at 170 degrees C.

Cannabis and Neuropsychiatry, 2: The Longitudinal Risk of Psychosis as an Adverse Outcome.

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Andrade, Chittaranjan

2016-06-01

Psychosis is one of the most serious among the adverse effects associated with cannabis use. The association between cannabis use and psychosis has been variously explored in a series of recent meta-analyses. The results of these meta-analyses show that persons who develop psychosis experience onset of psychosis about 2-3 years earlier if they are cannabis users; this effect is not observed with alcohol or other substance use. Higher levels of cannabis use are associated with greater risk of psychosis. Current cannabis abuse or dependence (but not past use or lower levels of current use) increases the risk of transition into psychosis in persons at ultrahigh risk of psychosis. About a third of patients with first-episode psychosis are cannabis users, and, at follow-up, about half of these users are found to continue their cannabis use. Continued cannabis use (in those who are treated after developing psychosis) is associated with higher risk of relapse into psychosis, and discontinuation of cannabis use reduces the risk of relapse to that in cannabis nonusers. Finally, persons with psychosis who continue to use cannabis have more severe positive symptoms and poorer levels of functioning. Because experimental studies in humans show that cannabinoids and cannabis can induce psychotic symptoms, it is reasonable to assume that the epidemiologic data indicate a causal effect of cannabis in anticipating, triggering, or exacerbating psychosis in vulnerable individuals and in worsening the course and outcome of the illness in those who continue to use the substance. Given the public health implications of these findings, the trend to legalize medical marijuana must be viewed with concern, and efforts are necessary to educate patients and the public about the serious mental and physical health risks associated with cannabis use and abuse. © Copyright 2016 Physicians Postgraduate Press, Inc.

Cue-induced craving in patients with cocaine use disorder predicts cognitive control deficits toward cocaine cues.

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DiGirolamo, Gregory J; Smelson, David; Guevremont, Nathan

2015-08-01

Cue-induced craving is a clinically important aspect of cocaine addiction influencing ongoing use and sobriety. However, little is known about the relationship between cue-induced craving and cognitive control toward cocaine cues. While studies suggest that cocaine users have an attentional bias toward cocaine cues, the present study extends this research by testing if cocaine use disorder patients (CDPs) can control their eye movements toward cocaine cues and whether their response varied by cue-induced craving intensity. Thirty CDPs underwent a cue exposure procedure to dichotomize them into high and low craving groups followed by a modified antisaccade task in which subjects were asked to control their eye movements toward either a cocaine or neutral drug cue by looking away from the suddenly presented cue. The relationship between breakdowns in cognitive control (as measured by eye errors) and cue-induced craving (changes in self-reported craving following cocaine cue exposure) was investigated. CDPs overall made significantly more errors toward cocaine cues compared to neutral cues, with higher cravers making significantly more errors than lower cravers even though they did not differ significantly in addiction severity, impulsivity, anxiety, or depression levels. Cue-induced craving was the only specific and significant predictor of subsequent errors toward cocaine cues. Cue-induced craving directly and specifically relates to breakdowns of cognitive control toward cocaine cues in CDPs, with higher cravers being more susceptible. Hence, it may be useful identifying high cravers and target treatment toward curbing craving to decrease the likelihood of a subsequent breakdown in control. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cocaine – Characteristics and addiction

Directory of Open Access Journals (Sweden)

Katarzyna Girczys-Połedniok

2016-08-01

Full Text Available Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4:537–544

Cocaine use and the breastfeeding mother.

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Jones, Wendy

2015-01-01

Cocaine is the second most commonly used illicit drug. Use in pregnancy and breastfeeding may have severe consequences for the baby due to its pharmacokinetic properties. Midwives need to be aware of the prolonged action of cocaine and be alert to the possibility of cocaine toxicity if a baby is excessively irritable and tachycardic. Euphoric highs are brief but breast milk and urine remain positive for long periods. Infant urine following exposure to cocaine via breast milk may remain positive for up to 60 hours. Mothers who snort cocaine should pump and dump breast milk for 24-48 hours. Passive inhalation of crack cocaine smoke may also result in infants with positive toxicology screens. Cocaine powder should never be applied to the nipples of breastfeeding mothers.

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.

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Adriaan W Bruijnzeel

Full Text Available Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1 receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has

Substitution and complementarity of alcohol and cannabis: A review of the literature

Science.gov (United States)

2016-01-01

Background Whether alcohol and cannabis are used as substitutes or complements remains debated, and findings across various disciplines have not been synthesized to date. Objective This paper is a first step towards organizing the interdisciplinary literature on alcohol and cannabis substitution and complementarity. Method Electronic searches were performed using PubMed and ISI Web of Knowledge. Behavioral studies of humans with ‘alcohol’ (or ‘ethanol’) and ‘cannabis’ (or ‘marijuana”) and ‘complement*’ (or ‘substitut*’) in the title or as a keyword were considered. Studies were organized according to sample characteristics (youth, general population, clinical and community-based). These groups were not set a priori, but were informed by the literature review process. Results Of the 39 studies reviewed, 16 support substitution, ten support complementarity, 12 support neither and one supports both. Results from studies of youth suggest that youth may reduce alcohol in more liberal cannabis environments (substitute), but reduce cannabis in more stringent alcohol environments (complement). Results from the general population suggest that substitution of cannabis for alcohol may occur under more lenient cannabis policies, though cannabis-related laws may affect alcohol use differently across genders and racial groups. Conclusions Alcohol and cannabis act as both substitutes and complements. Policies aimed at one substance may inadvertently affect consumption of other substances. Future studies should collect fine-grained longitudinal, prospective data from the general population and subgroups of interest, especially in locations likely to legalize cannabis. PMID:27249324

Levamisole-Contaminated Cocaine: An Emergent Cause of Vasculitis and Skin Necrosis

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Osama Souied

2014-01-01

Full Text Available The prevalence of cocaine adulterated with levamisole-induced vasculitis is increasing and physicians should be aware of this unique entity. There have been many reports of cutaneous vasculitis syndrome caused by cocaine which is contaminated with levamisole. Levamisole was used as an antihelminth drug and later was rescinded from use in humans due to adverse effects. Through this paper, we will report a 39-year-old crack cocaine user who presented with purpuric rash and skin necrosis of his ear lobes. Levamisole-induced vasculitis syndrome was suspected. A urine toxicology screen was positive for cocaine, opiates, and marijuana. Blood work revealed positive titres of ANA and p-ANCA, as well as anti-cardiolipin antibody. Biopsy taken from the left ear showed focal acute inflammation, chronic inflammation with thrombus formation, and extravasated blood cells. Treatment was primarily supportive with wound care.

Cannabis og psykose

DEFF Research Database (Denmark)

Nordentoft, Merete

2006-01-01

Longitudinal studies of the association between use of cannabis and later psychosis or schizophrenia were reviewed. Studies included were studies in the general population and in conscripts, using information from interviews about use of cannabis and register-based follow-up in psychiatric case......-registers or in personal interviews. There was a consistent finding that use of cannabis was associated with an increased risk of later psychosis with an odds ratio of approximately 2, when adjusted for predisposition to mental illness and socio-demographic risk factors....

Substituting cannabis for prescription drugs, alcohol and other substances among medical cannabis patients: The impact of contextual factors.

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Lucas, Philippe; Walsh, Zach; Crosby, Kim; Callaway, Robert; Belle-Isle, Lynne; Kay, Robert; Capler, Rielle; Holtzman, Susan

2016-05-01

Recent years have witnessed increased attention to how cannabis use impacts the use of other psychoactive substances. The present study examines the use of cannabis as a substitute for alcohol, illicit substances and prescription drugs among 473 adults who use cannabis for therapeutic purposes. The Cannabis Access for Medical Purposes Survey is a 414-question cross-sectional survey that was available to Canadian medical cannabis patients online and by hard copy in 2011 and 2012 to gather information on patient demographics, medical conditions and symptoms, patterns of medical cannabis use, cannabis substitution and barriers to access to medical cannabis. Substituting cannabis for one or more of alcohol, illicit drugs or prescription drugs was reported by 87% (n = 410) of respondents, with 80.3% reporting substitution for prescription drugs, 51.7% for alcohol, and 32.6% for illicit substances. Respondents who reported substituting cannabis for prescription drugs were more likely to report difficulty affording sufficient quantities of cannabis, and patients under 40 years of age were more likely to substitute cannabis for all three classes of substance than older patients. The finding that cannabis was substituted for all three classes of substances suggests that the medical use of cannabis may play a harm reduction role in the context of use of these substances, and may have implications for abstinence-based substance use treatment approaches. Further research should seek to differentiate between biomedical substitution for prescription pharmaceuticals and psychoactive drug substitution, and to elucidate the mechanisms behind both. [Lucas P, Walsh Z, Crosby K, Callaway R, Belle-Isle L, Kay B, Capler R, Holtzman S. Substituting cannabis for prescription drugs, alcohol, and other substances among medical cannabis patients: The impact of contextual factors. Drug Alcohol Rev 2016;35:326-333]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Reduced Metabolism in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

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Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

2011-01-01

Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and 18 FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% ± 10) whereas males tended to increase it (+5.5% ± 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

Cocaine affects foraging behaviour and biogenic amine modulated behavioural reflexes in honey bees

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Eirik Søvik

2014-11-01

Full Text Available In humans and other mammals, drugs of abuse alter the function of biogenic amine pathways in the brain leading to the subjective experience of reward and euphoria. Biogenic amine pathways are involved in reward processing across diverse animal phyla, however whether cocaine acts on these neurochemical pathways to cause similar rewarding behavioural effects in animal phyla other than mammals is unclear. Previously, it has been shown that bees are more likely to dance (a signal of perceived reward when returning from a sucrose feeder after cocaine treatment. Here we examined more broadly whether cocaine altered reward-related behaviour, and biogenic amine modulated behavioural responses in bees. Bees developed a preference for locations at which they received cocaine, and when foraging at low quality sucrose feeders increase their foraging rate in response to cocaine treatment. Cocaine also increased reflexive proboscis extension to sucrose, and sting extension to electric shock. Both of these simple reflexes are modulated by biogenic amines. This shows that systemic cocaine treatment alters behavioural responses that are modulated by biogenic amines in insects. Since insect reward responses involve both octopamine and dopamine signalling, we conclude that cocaine treatment altered diverse reward-related aspects of behaviour in bees. We discuss the implications of these results for understanding the ecology of cocaine as a plant defence compound. Our findings further validate the honey bee as a model system for understanding the behavioural impacts of cocaine, and potentially other drugs of abuse.

Effect of reclassification of cannabis on hospital admissions for cannabis psychosis: a time series analysis.

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Hamilton, Ian; Lloyd, Charlie; Hewitt, Catherine; Godfrey, Christine

2014-01-01

The UK Misuse of Drugs Act (1971) divided controlled drugs into three groups A, B and C, with descending criminal sanctions attached to each class. Cannabis was originally assigned by the Act to Group B but in 2004, it was transferred to the lowest risk group, Group C. Then in 2009, on the basis of increasing concerns about a link between high strength cannabis and schizophrenia, it was moved back to Group B. The aim of this study is to test the assumption that changes in classification lead to changes in levels of psychosis. In particular, it explores whether the two changes in 2004 and 2009 were associated with changes in the numbers of people admitted for cannabis psychosis. An interrupted time series was used to investigate the relationship between the two changes in cannabis classification and their impact on hospital admissions for cannabis psychosis. Reflecting the two policy changes, two interruptions to the time series were made. Hospital Episode Statistics admissions data was analysed covering the period 1999 through to 2010. There was a significantly increasing trend in cannabis psychosis admissions from 1999 to 2004. However, following the reclassification of cannabis from B to C in 2004, there was a significant change in the trend such that cannabis psychosis admissions declined to 2009. Following the second reclassification of cannabis back to class B in 2009, there was a significant change to increasing admissions. This study shows a statistical association between the reclassification of cannabis and hospital admissions for cannabis psychosis in the opposite direction to that predicted by the presumed relationship between the two. However, the reasons for this statistical association are unclear. It is unlikely to be due to changes in cannabis use over this period. Other possible explanations include changes in policing and systemic changes in mental health services unrelated to classification decisions. Copyright © 2013 Elsevier B.V. All rights

Aerobic exercise training reduces cannabis craving and use in non-treatment seeking cannabis-dependent adults.

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Maciej S Buchowski

2011-03-01

Full Text Available Cannabis dependence is a significant public health problem. Because there are no approved medications for this condition, treatment must rely on behavioral approaches empirically complemented by such lifestyle change as exercise.To examine the effects of moderate aerobic exercise on cannabis craving and use in cannabis dependent adults under normal living conditions.Participants attended 10 supervised 30-min treadmill exercise sessions standardized using heart rate (HR monitoring (60-70% HR reserve over 2 weeks. Exercise sessions were conducted by exercise physiologists under medical oversight.Sedentary or minimally active non-treatment seeking cannabis-dependent adults (n = 12, age 25±3 years, 8 females met criteria for primary cannabis dependence using the Substance Abuse module of the Structured Clinical Interview for DSM-IV (SCID.Self-reported drug use was assessed for 1-week before, during, and 2-weeks after the study. Participants viewed visual cannabis cues before and after exercise in conjunction with assessment of subjective cannabis craving using the Marijuana Craving Questionnaire (MCQ-SF.Daily cannabis use within the run-in period was 5.9 joints per day (SD = 3.1, range 1.8-10.9. Average cannabis use levels within the exercise (2.8 joints, SD = 1.6, range 0.9-5.4 and follow-up (4.1 joints, SD = 2.5, range 1.1-9.5 periods were lower than during the run-in period (both P<.005. Average MCQ factor scores for the pre- and post-exercise craving assessments were reduced for compulsivity (P  = .006, emotionality (P  = .002, expectancy (P  = .002, and purposefulness (P  = .002.The findings of this pilot study warrant larger, adequately powered controlled trials to test the efficacy of prescribed moderate aerobic exercise as a component of cannabis dependence treatment. The neurobiological mechanisms that account for these beneficial effects on cannabis use may lead to understanding of the physical and

Cardiovascular manifestations of substance abuse: part 2: alcohol, amphetamines, heroin, cannabis, and caffeine.

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Frishman, William H; Del Vecchio, Alexander; Sanal, Shirin; Ismail, Anjum

2003-01-01

The abuse of alcohol is associated with chronic cardiomyopathy, hypertension, and arrhythmia. Abstinence or using alcohol in moderation can reverse these cardiovascular problems. Alcohol is also distinguished among the substances of abuse by having possible protective effects against coronary artery disease and stroke when used in moderate amounts. Amphetamines (eg, speed, ice, ecstasy) have many of the cardiovascular toxicities seen with cocaine, including acute and chronic cardiovascular diseases. Heroin and other opiates can cause arrhythmias and noncardiac pulmonary edema, and may reduce cardiac output. Cardiovascular problems are less common with cannabis (marijuana) than with opiates, but major cognitive disorders may be seen with its chronic use. It is still controversial whether caffeine can cause hypertension and coronary artery disease, and questions have been raised about its safety in patients with heart failure and arrhythmia.

Cannabis use and first manic episode.

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Bally, Nathalie; Zullino, Daniele; Aubry, Jean-Michel

2014-08-01

Cannabis is the most commonly abused drug among patients with bipolar disorder. Available data has shown that the risk of psychotic disorders increases with the frequency and intensity of cannabis abuse. The present purpose was to review relevant studies to investigate whether cannabis use can be linked to the onset of mania in bipolar disorder. Articles published between 1972 and December 2013 were searched on Medline and PsychInfo using the following keywords: first manic episode, or onset mania, or bipolar disorder and cannabis. Relevant papers cited in the references of selected articles were further considered for inclusion into the review. Lifetime use of cannabis among bipolar patients appears to be around 70% and approximately 30% of patients with a bipolar disorder present a comorbidity of cannabis abuse or dependence. Cannabis use is associated with younger age at onset of first mania and with more frequent depressive or manic episodes, although the evidence is somewhat inconsistent. Likewise cannabis consumption is related to poorer outcome and an increased risk of rapid cycling or mixed episodes. In contrast, neuro-cognitive functioning seems to be positively affected in patients with psychiatric comorbidity. While cannabis use often precedes first manic episodes, the causal direction remains to be determined. Variations in definition of cannabis use/dependence. Lack of controlled studies limiting definite conclusions about a putative causal relationship between cannabis and onset of mania. Further investigations are needed to clarify the relationships between cannabis use and first manic episode. Copyright © 2014 Elsevier B.V. All rights reserved.

Cannabis Mobile Apps: A Content Analysis

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Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

2015-01-01

Background Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. Objective We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. Methods The Apple and Google Play app stores were searched using the terms “cannabis” and “marijuana.” Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Results Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated “17+” years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated “high maturity” (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Conclusions Cannabis apps are generally free and highly rated. Apps were most often informational

White Matter Changes in HIV+ Women with a History of Cocaine Dependence

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Kathryn-Mary Wakim

2017-10-01

Full Text Available Cocaine use is associated with the transmission of human immunodeficiency (HIV virus through risky sexual behavior. In HIV+ individuals, cocaine use is linked with poor health outcomes, including HIV-medication non-adherence and faster disease progression. Both HIV and cocaine dependence are associated with reduced integrity of cerebral white matter (WM, but the effects of HIV during cocaine abstinence have not yet been explored. We used diffusion tensor imaging (DTI to understand the effect of combined HIV+ serostatus and former cocaine dependence on cerebral WM integrity. DTI data obtained from 15 HIV+ women with a history of cocaine dependence (COC+/HIV+ and 21 healthy females were included in the analysis. Diffusion-based measures [fractional anisotropy (FA, radial diffusivity (RD, mean diffusivity, and axial diffusivity] were examined using tract-based spatial statistics and region-of-interest analyses. In a whole-brain analysis, COC+/HIV+ women showed significantly reduced FA and increased RD in all major WM tracts, except the left corticospinal tract for RD. The tract with greatest percentage of voxels showing significant between-group differences was the forceps minor (FA: 75.6%, RD: 59.7%. These widespread changes in diffusion measures indicate an extensive neuropathological effect of HIV and former cocaine dependence on WM.

[Motivations for cannabis cessation, coping and adaptation strategies, and perceived benefits: impact on cannabis use relapse and abstinence].

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Chauchard, E; Septfons, A; Chabrol, H

2013-12-01

While cannabis has been recognized as the most illicit drug use in the world, few studies focusing on cannabis self-change and cannabis relapse or abstinence in adult non-treatment samples have been conducted. The first aim of this study was to understand cannabis self-change motives, coping and adaptation strategies and evaluating perceived benefits from cannabis cessation. The second aim was to compare, in a convenience sample of non-treatment-seeking adult cannabis smokers, motivations to quit smoking cannabis, coping and adaptive strategies, as well as perceived benefit from cessation between cannabis abstinent and participants who relapse. Sixty-three participants (31 men and 32 women) who attempted to quit cannabis in a non-controlled environment without medical help and were enrolled. They completed the Marijuana Quit Questionnaire (MJQQ), a self-report questionnaire collecting information in three areas: sociodemographic characteristics, cannabis use history (including any associated problems), and participants' characteristics regarding their "most difficult" (self-defined) attempt to quit in a non-controlled environment. For this study the index quit attempt was characterized in two areas: reasons for quitting marijuana, coping strategies used while quitting. Two additional questionnaires were added to the MJQQ; the Brief Cope, and a questionnaire assessing perceived benefit of the cannabis quit attempt. The participants were on average 28.5 years old (±5.1), and started using cannabis on average at 15.8 years (±2.8). Seventy-four percent (n=45) of the participants met the DSM-IV criteria for cannabis dependence before cannabis cessation. T-tests were used to compare abstainers and participants who relapsed after the quit attempt. Realizing that cannabis induces disabling cognitive disorders such as affection of memory, concentration and attention were reported by 71% of the participant as a motivation for quitting cannabis use. Then, being more

[Consumption of cannabis in adolescents].

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Phan, O; Obradovic, I; Har, A

2017-01-01

Over the past 10 years, the consumption of cannabis among adolescents has dramatically increased. Today, adolescent cannabis use is a major public health problem. Two forms of cannabis are commonly smoked: herb (marijuana) and resin. These forms have a high concentration of tetrahydrocannabinol, the active molecule of cannabis. Recent research has helped understand how the cannabinoid system works. This system combines specific receptors and specific molecules: the endocannabinoids. The effects of cannabis use are now well documented. Some adolescents report subjective positive effects. They use it not only on a recreational basis, but also to deal with their emotions. Over the long term, cannabis increases the risk of depression and schizophrenia for those adolescents who are at risk. Use, misuse, and dependence are frequently associated with heavy psychopathologic problems such as vulnerability and depression. Many cannabis dependence psychotherapies have shown their efficacy and efficiency. Motivational interviews, cognitive behavioral therapy, multidimensional family therapy (MDFT), and residential treatment have proved highly effective. MDFT seems very effective, especially in cases of heavy use. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Terpene synthases from Cannabis sativa.

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Judith K Booth

Full Text Available Cannabis (Cannabis sativa plants produce and accumulate a terpene-rich resin in glandular trichomes, which are abundant on the surface of the female inflorescence. Bouquets of different monoterpenes and sesquiterpenes are important components of cannabis resin as they define some of the unique organoleptic properties and may also influence medicinal qualities of different cannabis strains and varieties. Transcriptome analysis of trichomes of the cannabis hemp variety 'Finola' revealed sequences of all stages of terpene biosynthesis. Nine cannabis terpene synthases (CsTPS were identified in subfamilies TPS-a and TPS-b. Functional characterization identified mono- and sesqui-TPS, whose products collectively comprise most of the terpenes of 'Finola' resin, including major compounds such as β-myrcene, (E-β-ocimene, (--limonene, (+-α-pinene, β-caryophyllene, and α-humulene. Transcripts associated with terpene biosynthesis are highly expressed in trichomes compared to non-resin producing tissues. Knowledge of the CsTPS gene family may offer opportunities for selection and improvement of terpene profiles of interest in different cannabis strains and varieties.

Effects of inhibitory GABA-active neurosteroids on cocaine seeking and cocaine taking in rats.

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Schmoutz, Christopher D; Runyon, Scott P; Goeders, Nicholas E

2014-09-01

Several compounds that potentiate GABA-induced inhibitory currents also decrease stress, anxiety and addiction-related behaviors. Because of the well-established connection between stress and addiction, compounds that reduce stress-induced responses might be efficacious in treating addiction. Since endogenous neurosteroids such as allopregnanolone may function in a manner similar to benzodiazepines to reduce HPA axis activation and anxiety following stressful stimuli, we hypothesized that exogenously applied neurosteroids would reduce cocaine reinforcement in two animal models. Male Wistar rats were trained to self-administer cocaine and food under a concurrent alternating operant schedule of reinforcement. Two separate groups of rats were trained to self-administer cocaine or food pellets and were then exposed to similar cue-induced reinstatement paradigms. Both groups of rats were pretreated with various doses of neurosteroids. Allopregnanolone and 3α-hydroxy-3β-methyl-17β-nitro-5α-androstane (R6305-7, a synthetic neurosteroid) were ineffective in selectively decreasing cocaine relative to food self-administration. On the other hand, both allopregnanolone and R6305-7 significantly decreased the cue-induced reinstatement of extinguished cocaine seeking, confirmed by one-way ANOVA. These results suggest that neurosteroids may be effective in reducing the relapse to cocaine use without affecting ongoing cocaine self-administration.

Marijuana (Cannabis) and Multiple Sclerosis

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... progression of MS: Effect of oral dronabinol (a synthetic Cannabis/marijuana derivative) on progression in progressive MS: Previous ... the evidence regarding marijuana and its derivatives: Oral cannabis extract and synthetic THC (tetrahydrocannabinol — a major active component of cannabis) ...

Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations.

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Zhang, Yuxin; Huang, Xiaoqin; Han, Keli; Zheng, Fang; Zhan, Chang-Guo

2016-11-25

The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profile of the CocE)-(+)-cocaine binding process in comparison with that of the corresponding CocE-(-)-cocaine binding process. According to the MD simulations, the equilibrium CocE-(+)-cocaine binding mode is similar to the CocE-(-)-cocaine binding mode. However, based on the simulated free energy profiles, a significant free energy barrier (∼5 kcal/mol) exists in the CocE-(+)-cocaine binding process whereas no obvious free energy barrier exists in the CocE-(-)-cocaine binding process, although the free energy barrier of ∼5 kcal/mol is not high enough to really slow down the CocE-(+)-cocaine binding process. In addition, the obtained free energy profiles also demonstrate that (+)-cocaine and (-)-cocaine have very close binding free energies with CocE, with a negligible difference (∼0.2 kcal/mol), which is qualitatively consistent with the nearly same experimental K M values of the CocE enzyme for (+)-cocaine and (-)-cocaine. The consistency between the computational results and available experimental data suggests that the mechanistic insights obtained from this study are reasonable. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cannabis Use and Mental Health Problems

NARCIS (Netherlands)

van Ours, J.C.; Williams, J.

2009-01-01

This paper investigates whether cannabis use leads to worse mental health. To do so, we account for common unobserved factors affecting mental health and cannabis consumption by modeling mental health jointly with the dynamics of cannabis use. Our main finding is that using cannabis increases the

The draft genome and transcriptome of Cannabis sativa.

Science.gov (United States)

van Bakel, Harm; Stout, Jake M; Cote, Atina G; Tallon, Carling M; Sharpe, Andrew G; Hughes, Timothy R; Page, Jonathan E

2011-10-20

Cannabis sativa has been cultivated throughout human history as a source of fiber, oil and food, and for its medicinal and intoxicating properties. Selective breeding has produced cannabis plants for specific uses, including high-potency marijuana strains and hemp cultivars for fiber and seed production. The molecular biology underlying cannabinoid biosynthesis and other traits of interest is largely unexplored. We sequenced genomic DNA and RNA from the marijuana strain Purple Kush using shortread approaches. We report a draft haploid genome sequence of 534 Mb and a transcriptome of 30,000 genes. Comparison of the transcriptome of Purple Kush with that of the hemp cultivar 'Finola' revealed that many genes encoding proteins involved in cannabinoid and precursor pathways are more highly expressed in Purple Kush than in 'Finola'. The exclusive occurrence of Δ9-tetrahydrocannabinolic acid synthase in the Purple Kush transcriptome, and its replacement by cannabidiolic acid synthase in 'Finola', may explain why the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) is produced in marijuana but not in hemp. Resequencing the hemp cultivars 'Finola' and 'USO-31' showed little difference in gene copy numbers of cannabinoid pathway enzymes. However, single nucleotide variant analysis uncovered a relatively high level of variation among four cannabis types, and supported a separation of marijuana and hemp. The availability of the Cannabis sativa genome enables the study of a multifunctional plant that occupies a unique role in human culture. Its availability will aid the development of therapeutic marijuana strains with tailored cannabinoid profiles and provide a basis for the breeding of hemp with improved agronomic characteristics.

Neurobiologia da Cannabis: do sistema endocanabinoide aos transtornos por uso de Cannabis

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José Luis G. Pinho Costa

2011-01-01

Full Text Available OBJETIVOS: Diante das lacunas na efetividade das terapêuticas para transtornos por uso de Cannabis, a droga ilícita mais consumida no mundo, este trabalho propõe-se a rever os conhecimentos sobre o substrato neuroanatômico, biomolecular e celular do sistema endocanabinoide, descrever os mecanismos de neuroplasticidade dependente dos canabinoides e relacioná-los com a neurobiologia dos transtornos por uso de Cannabis (abuso e dependência. MÉTODOS: Recorreu-se às bases de dados Medline, Scopus e ISI Web of Knowledge; as palavras-chave pesquisadas foram "Cannabis", "neurobiology", "endocannabinoid system", "endocannabinoids", "receptors, cannabinoid", "neuronal plasticity", "long-term synaptic depression", "long-term potentiation", "marijuana abuse" e "tetrahydrocannabinol". Foram incluídos 80 trabalhos nesta revisão. DISCUSSÃO: A distribuição neuroanatômica, celular e biomolecular do sistema endocanabinoide adequa-se perfeitamente às suas funções de neuromodulação (via neuroplasticidade e metaplasticidade, nomeadamente em vias relacionadas aos transtornos por uso de substâncias. Os canabinoides exógenos perturbam essas funções. CONCLUSÃO: O sistema endocanabinoide contribui para a definição de setpoints em diversas vias neuronais, incluindo vias cruciais na instalação de transtornos por uso de substâncias; com o uso de Cannabis, esses setpoints tornar-se-ão mais permissivos, facilitando os transtornos por uso de Cannabis. Os avanços no entendimento da neurobiologia da Cannabis abrem uma janela de oportunidades para novas estratégias terapêuticas nos transtornos por uso de Cannabis.

Effects of phendimetrazine treatment on cocaine vs food choice and extended-access cocaine consumption in rhesus monkeys.

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Banks, Matthew L; Blough, Bruce E; Fennell, Timothy R; Snyder, Rodney W; Negus, S Stevens

2013-12-01

There is currently no Food and Drug Administration-approved pharmacotherapy for cocaine addiction. Monoamine releasers such as d-amphetamine constitute one class of candidate medications, but clinical use and acceptance are hindered by their own high-abuse liability. Phendimetrazine (PDM) is a schedule III anorectic agent that functions as both a low-potency monoamine-uptake inhibitor and as a prodrug for the monoamine-releaser phenmetrazine (PM), and it may serve as a clinically available, effective, and safer alternative to d-amphetamine. This study determined efficacy of chronic PDM to reduce cocaine self-administration by rhesus monkeys (N=4) using a novel procedure that featured both daily assessments of cocaine vs food choice (to assess medication efficacy to reallocate behavior away from cocaine choice and toward choice of an alternative reinforcer) and 20 h/day cocaine access (to allow high-cocaine intake). Continuous 21-day treatment with ramping PDM doses (days 1-7: 0.32 mg/kg/h; days 8-21: 1.0 mg/kg/h) reduced cocaine choices, increased food choices, and nearly eliminated extended-access cocaine self-administration without affecting body weight. There was a trend for plasma PDM and PM levels to correlate with efficacy to decrease cocaine choice such that the monkey with the highest plasma PDM and PM levels also demonstrated the greatest reductions in cocaine choice. These results support further consideration of PDM as a candidate anti-cocaine addiction pharmacotherapy. Moreover, PDM may represent a novel pharmacotherapeutic approach for cocaine addiction because it may simultaneously function as both a monoamine-uptake inhibitor (via the parent drug PDM) and as a monoamine releaser (via the active metabolite PM).

Evaluation of cocaine-induced hepatotoxicity

International Nuclear Information System (INIS)

Wang, G.J.; Som, P.; Volkow, N.D.; Oster, Z.H.

1991-01-01

The effect of repeated administrations (1,5 weeks) of cocaine on the liver was studied using two radiopharmaceuticals, 99m Tc sulfur colloid (SC) and 99m Tc DISIDA. Uptake and clearance kinetics as well as liver enzyme determinations and histopathology were compared. In cocaine-treated animals hepatomegaly was noted (36% increase in liver weight over non-treated animals), and SGPT levels were 5 times higher than in non-treated animals. Periportal necrosis, fatty infiltration, and inflammation were noted on histological sections. The total uptake of 99m Tc SC in cocaine-treated mice was 8% higher, but the concentration (% ID/gm) was 18% lower, than in non-treated animals. Decreased uptake and concentration of 99m Tc SC was seen in the spleen. In contrast, the uptake and clearance of 99m Tc DISIDA were not affected by cocaine treatment. It is concluded that in this model 99m Tc DISIDA was not a sensitive agent for evaluation of cocaine-induced hepatoxicity, and that 99m Tc SC was a more sensitive agent for the determination of hepatic and splenic toxicity due to cocaine. Cocaine-mediated hepato-splenic toxicity warrants further clinical investigations. (orig.) [de

2011 Health Related Behaviors Survey of Active Duty Military Personnel

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2013-02-01

drug use began by asking about the use of a variety of illicit drugs such as marijuana , cocaine, and heroin. Two substances, synthetic cannabis and...a. Marijuana or hashish (such as “pot,” THC, “weed”) b. Synthetic cannabis ("spice", K2, herbal smoking blend) c. Cocaine (including crack) d...10 days 3. Used 1 to 3 days 4. 0 days a. Marijuana or hashish (such as “pot,” THC, “weed”) b. Synthetic cannabis ("spice", K2, herbal smoking

Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers.

Directory of Open Access Journals (Sweden)

Nora D Volkow

2011-02-01

Full Text Available Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved.To test this we compared brain metabolism (using PET and ¹⁸FDG between female (n = 10 and male (n = 16 active cocaine abusers when they watched a neutral video (nature scenes versus a cocaine-cues video.Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05; females significantly decreased metabolism (-8.6%±10 whereas males tended to increase it (+5.5%±18. SPM analysis (Cocaine-cues vs Neutral in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001 whereas males showed increases in right inferior frontal gyrus (BA 44/45 (only at p<0.005. The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001 in frontal (BA 8, 9, 10, anterior cingulate (BA 24, 32, posterior cingulate (BA 23, 31, inferior parietal (BA 40 and thalamus (dorsomedial nucleus.Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from "control networks" (prefrontal, cingulate, inferior parietal, thalamus in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition. This highlights the importance of gender tailored interventions for cocaine addiction.

Daily Use, Especially of High-Potency Cannabis, Drives the Earlier Onset of Psychosis in Cannabis Users

Science.gov (United States)

Di Forti, Marta; Sallis, Hannah; Allegri, Fabio; Trotta, Antonella; Ferraro, Laura; Stilo, Simona A.; Marconi, Arianna; La Cascia, Caterina; Reis Marques, Tiago; Pariante, Carmine; Dazzan, Paola; Mondelli, Valeria; Paparelli, Alessandra; Kolliakou, Anna; Prata, Diana; Gaughran, Fiona; David, Anthony S.; Morgan, Craig; Stahl, Daniel; Khondoker, Mizanur; MacCabe, James H.; Murray, Robin M.

2014-01-01

Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16–1.74; P cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06–1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. PMID:24345517

The importance of family relations for cannabis users: the case of serbian adolescents.

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Terzic Supic, Zorica; Santric Milicevic, Milena; Sbutega, Isidora; Vasic, Vladimir

2013-01-01

Adolescence is transitional stage of physical and mental human development occuring between childhood and adult life. Social interactions and environmental factors together are important predictors of adolescent cannabis use. This study aimed to examine the relationship between the social determinants and adolescents behavior with cannabis consumption. A cross sectional study as part of the European School Survey Project on Alcohol and other Drugs was conducted among 6.150 adolescents aged 16 years in three regions of Serbia, and three types of schools (gymnasium, vocational - professional, and vocational - handicraft) during May - June 2008. A multivariate logistic regression analysis was carried out to obtain adjusted odds ratios with 95% confidence intervals in which the dependent variable was cannabis consumption non-user and user. Among 6.7% of adolescents who had tried cannabis at least one in their lives, boys were more involved in cannabis use than girls, especially boys from gymnasium school. Well off family, lower education of mother, worse relations with parents were significantly associated with cannabis use (P related to cannabis use (P study confirmed the importance of family relationship development. Drug use preventive programmes should include building interpersonal trust in a family lifecycle and school culture.

Kappa-opioid receptor signaling in the striatum as a potential modulator of dopamine transmission in cocaine dependence

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Pierre eTrifilieff

2013-06-01

Full Text Available Cocaine addiction is accompanied by a decrease in striatal dopamine signaling, measured as a decrease in dopamine D2 receptor binding as well as blunted dopamine release in the striatum. These alterations in dopamine transmission have clinical relevance, and have been shown to correlate with cocaine-seeking behavior and response to treatment for cocaine dependence. However, the mechanisms contributing to the hypodopaminergic state in cocaine addiction remain unknown. Here we review the Positron Emission Tomography (PET imaging studies showing alterations in D2 receptor binding potential and dopamine transmission in cocaine abusers and their significance in cocaine-seeking behavior. Based on animal and human studies, we propose that the kappa receptor/dynorphin system, because of its impact on dopamine transmission and upregulation following cocaine exposure, could contribute to the hypodopaminergic state reported in cocaine addiction, and could thus be a relevant target for treatment development.

Unique prediction of cannabis use severity and behaviors by delay discounting and behavioral economic demand.

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Strickland, Justin C; Lile, Joshua A; Stoops, William W

2017-07-01

Few studies have simultaneously evaluated delay discounting and behavioral economic demand to determine their unique contribution to drug use. A recent study in cannabis users found that monetary delay discounting uniquely predicted cannabis dependence symptoms, whereas cannabis demand uniquely predicted use frequency. This study sought to replicate and extend this research by evaluating delay discounting and behavioral economic demand measures for multiple commodities and including a use quantity measure. Amazon.com's Mechanical Turk was used to sample individuals reporting recent cannabis use (n=64) and controls (n=72). Participants completed measures of monetary delay discounting as well as alcohol and cannabis delay discounting and demand. Cannabis users and controls did not differ on monetary delay discounting or alcohol delay discounting and demand. Among cannabis users, regression analyses indicated that cannabis delay discounting uniquely predicted use severity, whereas cannabis demand uniquely predicted use frequency and quantity. These effects remained significant after controlling for other delay discounting and demand measures. This research replicates previous outcomes relating delay discounting and demand with cannabis use and extends them by accounting for the contribution of multiple commodities. This research also demonstrates the ability of online crowdsourcing methods to complement traditional human laboratory techniques. Copyright © 2017 Elsevier B.V. All rights reserved.

Dutch coffee shops and trends in cannabis use.

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Korf, Dirk J

2002-01-01

Conflicting predictions have been made to the influence of decriminalization on cannabis use. Prohibitionists forecast that decriminalization will lead to an increase in consumption of cannabis, while their opponents hypothesise that cannabis use will decline after decriminalization. Most probably cannabis use in the Netherlands so far evolved in two waves, with a first peak around 1970, a low during the late 1970s and early 1980s, and a second peak in the mid-1990s. It is striking that this trend in cannabis use among youth in the Netherlands rather parallels four identified stages in the availability of cannabis. The number of cannabis users peaked when the cannabis was distributed through an underground market (late 1960s and early 1970s). Then the number decreased as house dealers were superseeding the underground market (1970s), and went up again after coffee shops took over the sale of cannabis (1980s), and stabilised or slightly decreased by the end of the 1990s when the number of coffee shops was reduced. Although changes in cannabis policy went along with changes in availability of cannabis and prevalence of cannabis use, it is questionable whether changes in cannabis policy were causally related to trends in cannabis use. Cannabis use also developed in waves in other European countries that did not decriminalize cannabis, as well as in the US. Consequently, trends in cannabis use seem to develop rather independently of cannabis policy.

Cannabis - from cultivar to chemovar.

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Hazekamp, A; Fischedick, J T

2012-01-01

The medicinal use of Cannabis is increasing as countries worldwide are setting up official programs to provide patients with access to safe sources of medicinal-grade Cannabis. An important question that remains to be answered is which of the many varieties of Cannabis should be made available for medicinal use. Drug varieties of Cannabis are commonly distinguished through the use of popular names, with a major distinction being made between Indica and Sativa types. Although more than 700 different cultivars have already been described, it is unclear whether such classification reflects any relevant differences in chemical composition. Some attempts have been made to classify Cannabis varieties based on chemical composition, but they have mainly been useful for forensic applications, distinguishing drug varieties, with high THC content, from the non-drug hemp varieties. The biologically active terpenoids have not been included in these approaches. For a clearer understanding of the medicinal properties of the Cannabis plant, a better classification system, based on a range of potentially active constituents, is needed. The cannabinoids and terpenoids, present in high concentrations in Cannabis flowers, are the main candidates. In this study, we compared cultivars obtained from multiple sources. Based on the analysis of 28 major compounds present in these samples, followed by principal component analysis (PCA) of the quantitative data, we were able to identify the Cannabis constituents that defined the samples into distinct chemovar groups. The study indicates the usefulness of a PCA approach for chemotaxonomic classification of Cannabis varieties. Copyright © 2012 John Wiley & Sons, Ltd.

Cannabis Decriminalization and the Age of Onset of Cannabis Use

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Cervený, J.; van Ours, J.C.; Chomynova, Pavla; Mravcik, Viktor

2015-01-01

This paper examines the effect of a change in drugs policy on the age of onset of cannabis use. We use 2012 survey data from the Czech Republic where in 2010 a law was introduced decriminalizing personal possession of small quantities of several illicit drugs, including cannabis. We estimate the

Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques.

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Cooper, Ziva D; Foltin, Richard W; Evans, Suzette M

2013-01-01

Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. Copyright © 2012 Elsevier Inc. All rights reserved.

[CANNABIS: ALTERNATIVE REALITIES (CRA)].

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Galván, Gonzalo Daniel; Guerrero, Manuel; Pinedo López, Jhon; García, Ricardo

2015-01-01

In this cross sectional and descriptive study, secondary school students trom the city of Santa Rosa were questioned about their beliefs about cannabis and their risk perception derived from it. The sample consisted in 83 male and 71 female 17 year-old teenagers. On the one hand, it was found that the highest risk perceptions were related to the legal issues that might arise due to cannabis consumption, and to its effects on neurons. On the other hand, the lowest risk perceptions were associated with the belief/ idea that smoking tobacco affects the lungs more than smoking cannabis, which might create dependence, and its use can cause mental disorders. Several significant differences were found as regards gender, since the female students noticed more risk than male students in that the consumption of cannabis can develop mental disorders, amotivational syndrome, lack of enthusiasm and less satisfaction with life. The teenager's risk perception about cannabis is variable.

Atomoxetine Does Not Alter Cocaine Use in Cocaine Dependent Individuals: A Double Blind Randomized Trial

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Middleton, Lisa S.; Wong, Conrad J.; Nuzzo, Paul A.; Campbell, Charles L.; Rush, Craig R.; Lofwall, Michelle R.

2016-01-01

Background Cocaine abuse continues to be a significant public health problem associated with morbidity and mortality. To date, no pharmacotherapeutic approach has proven effective for treating cocaine use disorders. Preclinical and clinical evidence suggests that noradrenergic activity may play a role in mediating some effects of cocaine and may be a rational target for treatment. Methods This double blind, placebo-controlled randomized, parallel group, 12-week outpatient clinical trial enrolled cocaine dependent individuals seeking treatment to examine the potential efficacy of the selective norepinephrine reuptake inhibitor, atomoxetine (80 mg/day; p.o.; n=25), compared to placebo (n=25). Subjects were initially stratified on cocaine use (atomoxetine and placebo groups (X2=0.2, p=.66; OR=0.89 [95% CI 0.41 – 1.74). Atomoxetine was generally well tolerated in this population. Conclusions These data provide no support for the utility of atomoxetine in the treatment of cocaine dependence. PMID:23200303

Manipulating a "cocaine engram" in mice.

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Hsiang, Hwa-Lin Liz; Epp, Jonathan R; van den Oever, Michel C; Yan, Chen; Rashid, Asim J; Insel, Nathan; Ye, Li; Niibori, Yosuke; Deisseroth, Karl; Frankland, Paul W; Josselyn, Sheena A

2014-10-15

Experience with drugs of abuse (such as cocaine) produces powerful, long-lasting memories that may be important in the development and persistence of drug addiction. The neural mechanisms that mediate how and where these cocaine memories are encoded, consolidated and stored are unknown. Here we used conditioned place preference in mice to examine the precise neural circuits that support the memory of a cocaine-cue association (the "cocaine memory trace" or "cocaine engram"). We found that a small population of neurons (∼10%) in the lateral nucleus of amygdala (LA) were recruited at the time of cocaine-conditioning to become part of this cocaine engram. Neurons with increased levels of the transcription factor CREB were preferentially recruited or allocated to the cocaine engram. Ablating or silencing neurons overexpressing CREB (but not a similar number of random LA neurons) before testing disrupted the expression of a previously acquired cocaine memory, suggesting that neurons overexpressing CREB become a critical hub in what is likely a larger cocaine memory engram. Consistent with theories that coordinated postencoding reactivation of neurons within an engram or cell assembly is crucial for memory consolidation (Marr, 1971; Buzsáki, 1989; Wilson and McNaughton, 1994; McClelland et al., 1995; Girardeau et al., 2009; Dupret et al., 2010; Carr et al., 2011), we also found that post-training suppression, or nondiscriminate activation, of CREB overexpressing neurons impaired consolidation of the cocaine memory. These findings reveal mechanisms underlying how and where drug memories are encoded and stored in the brain and may also inform the development of treatments for drug addiction. Copyright © 2014 the authors 0270-6474/14/3414115-13$15.00/0.

Kwaliteitsnormen Medicinale Cannabis

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Slijkhuis C; Hoving R; Blok-Tip L; Kaste D de; KCF

2004-01-01

Medicinal Cannabis can be legally supplied by pharmacists to patients from the first of September 2003, although still only on prescription. The quality of this product is tested conform the monograph Cannabis flos. In this monograph tests and quality standards, such as characteristics, loss on

Cannabis use and mental health

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van Gastel, W.A.

2013-01-01

Cannabis use has been implicated as a risk factor for mental health problems, (subclinical) psychotic symptoms in particular. If cannabis use was a cause of these problems, cessation would lead to improved public mental health. If cannabis use was a mere consequence of a predisposition for mental

Therapeutic Use of Cannabis in Inflammatory Bowel Disease

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Katz, Seymour

2016-01-01

The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, double-blind, randomized, placebo-controlled trials using serial inflammatory markers, biopsy findings, and endoscopic disease severity to demonstrate objective improvement in IBD are necessary before cannabis can be empirically accepted and recommended as an IBD treatment option. Questions concerning its safety profile and adverse effects prompt the need for further research, particularly in regard to dosing and route of administration to maximize benefits and limit potential harms. Cannabis use should be reserved for symptomatic control in patients with severe IBD refractory to the currently available standard-of-care and complementary and alternative medicines. PMID:28035196

Bioanalytical methods for the determination of cocaine and metabolites in human biological samples.

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Barroso, M; Gallardo, E; Queiroz, J A

2009-08-01

Determination of cocaine and its metabolites in biological specimens is of great importance, not only in clinical and forensic toxicology, but also in workplace drug testing. These compounds are normally screened for using sensitive immunological methods. However, screening methods are unspecific and, therefore, the posterior confirmation of presumably positive samples by a specific technique is mandatory. Although GC-MS-based techniques are still the most commonly used for confirmation purposes of cocaine and its metabolites in biological specimens, the advent of LC-MS and LC-MS/MS has enabled the detection of even lower amounts of these drugs, which assumes particular importance when sample volume available is small, as frequently occurs with oral fluid. This paper will review recently-published papers that describe procedures for detection of cocaine and metabolites, not only in the most commonly used specimens, such as blood and urine, but also in other 'alternative' matrices (e.g., oral fluid and hair) with a special focus on sample preparation and chromatographic analysis.

Quantification of Cannabinoid Content in Cannabis

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Tian, Y.; Zhang, F.; Jia, K.; Wen, M.; Yuan, Ch.

2015-09-01

Cannabis is an economically important plant that is used in many fields, in addition to being the most commonly consumed illicit drug worldwide. Monitoring the spatial distribution of cannabis cultivation and judging whether it is drug- or fiber-type cannabis is critical for governments and international communities to understand the scale of the illegal drug trade. The aim of this study was to investigate whether the cannabinoids content in cannabis could be spectrally quantified using a spectrometer and to identify the optimal wavebands for quantifying the cannabinoid content. Spectral reflectance data of dried cannabis leaf samples and the cannabis canopy were measured in the laboratory and in the field, respectively. Correlation analysis and the stepwise multivariate regression method were used to select the optimal wavebands for cannabinoid content quantification based on the laboratory-measured spectral data. The results indicated that the delta-9-tetrahydrocannabinol (THC) content in cannabis leaves could be quantified using laboratory-measured spectral reflectance data and that the 695 nm band is the optimal band for THC content quantification. This study provides prerequisite information for designing spectral equipment to enable immediate quantification of THC content in cannabis and to discriminate drug- from fiber-type cannabis based on THC content quantification in the field.

Cannabis use and cognition in schizophrenia

Directory of Open Access Journals (Sweden)

Else-Marie Løberg

2009-11-01

Full Text Available People with schizophrenia frequently report cannabis use, and cannabis may be a risk factor for schizophrenia, mediated through effects on brain function and biochemistry. Thus, it is conceivable that cannabis may also influence cognitive functioning in this patients group. We report data from our own laboratory on the use of cannabis by schizophrenia patients, and review the existing literature on the effects of cannabis on cognition in schizophrenia and related psychosis. Of the 23 studies that were found, 14 reported that the cannabis users had better cognitive performance than the schizophrenia non-users. Eight studies reported no or minimal differences in cognitive performance in the two groups, but only one study reported better cognitive performance in the schizophrenia non-user group. Our own results confirm the overall impression from the literature review of better cognitive performance in the cannabis user group. These paradoxical findings may have several explanations, which are discussed. We suggest that cannabis causes a transient cognitive breakdown enabling the development of psychosis, imitating the typical cognitive vulnerability seen in schizophrenia. This is further supported by an earlier age of onset and fewer neurological soft signs in the cannabis-related schizophrenia group, suggesting an alternative pathway to psychosis.

Past year cannabis use and problematic cannabis use among adults by ethnicity in Ontario.

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Tuck, Andrew; Hamilton, Hayley A; Agic, Branka; Ialomiteanu, Anca R; Mann, Robert E

2017-10-01

Rates of cannabis use differ around the world; in Ontario, the rate of use has been stable since about 2005. Understanding which population groups are at greater risk for problematic cannabis use can help reduce long-term health effects and service expenses. The aim of this study was to explore differences in cannabis use among Canadian adults of different ethnic origins living in Ontario. Data are based on telephone interviews with 11,560 respondents and are derived from multiple cycles (2005-2011) of the Centre for Addiction and Mental Health's (CAMH) Monitor survey, an ongoing cross-sectional survey of adults in Ontario, Canada, aged 18 years and older. Data were analyzed using bivariate cross-tabulations and logistic regression. Problematic cannabis use was determined with a score of 8+ on the ASSIST-CIS to identify moderate/high problematic users. Lifetime, past year and problematic cannabis use (in the past 3 months) occurs among all ethnic groups: Canadian, East Asian, South East Asian, South Asian, Caribbean, African, East European, South European, North European, and Central West European. When compared to the Canadian group the odds of past year cannabis use was significantly lower for East Asians and South Asians, but higher for the Caribbean group. Significantly higher odds of problematic cannabis use were found for Caribbeans and Northern Europeans compared to Canadians. These results of this study provide an important basis for considering the possible impact of the impending legalization of cannabis in Canada among different ethnic groups. Copyright © 2017 Elsevier B.V. All rights reserved.

The selective dopamine uptake inhibitor, D-84, suppresses cocaine self-administration, but does not occasion cocaine-like levels of generalization.

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Batman, Angela M; Dutta, Aloke K; Reith, Maarten E A; Beardsley, Patrick M

2010-12-01

A successful replacement pharmacotherapy for treating cocaine dependency would likely reduce cocaine's abuse, support a low abuse liability, overlap cocaine's subjective effects, and have a long duration of action. Inhibitors with varying selectivity at the dopamine transporter (DAT) have approximated these properties. The objective of the present study was to characterize the behavioural effects of an extremely selective DAT inhibitor, (+) trans-4-(2-Benzhydryloxyethyl)-1-(4-fluorobenzyl) piperadin-3-ol (D-84), a 3-hydroxy substituted piperidine derivative of GBR-12935, for its cocaine-like discriminative stimulus effects, its effects on cocaine self-administration, and for its own self-administration. During cocaine discrimination tests, cocaine occasioned the 10 mg/kg cocaine training stimulus with an ED(50) value of 3.13 (1.54-6.34) mg/kg, and reduced response rates with an ED(50) value of 20.39 (7.24-57.44) mg/kg. D-84 incompletely generalized to the cocaine stimulus occasioning a maximal 76% cocaine-lever responding, while reducing response rates with lower potency than cocaine (ED(50)=30.94 (12.34-77.60) mg/kg). Pretreatment with D-84 (9.6-30.4 mg/kg) significantly (P<0.05) reduced cocaine intake at 17.1 mg/kg D-84 when cocaine was self-administered at 0.5 mg/kg/infusion, and at 30.4 mg/kg D-84 when cocaine was self-administered at 0.1, 0.5 .and 1.0 mg/kg/infusion. During self-administration tests with D-84 (0.1-1 mg/kg/infusion), numbers of infusions significantly exceeded vehicle levels at 0.3 mg/kg/infusion. These results show that D-84 pretreatment can decrease cocaine intake especially when high doses of cocaine are being self-administered. This observation, combined with its incomplete generalization to the cocaine discriminative stimulus and its reported long duration of action, provides a profile consistent with a potential replacement therapy for treating cocaine-abusing patients. Copyright © 2010 Elsevier B.V. All rights reserved.

Development and validation of a gas chromatography-mass spectrometry assay for opiates and cocaine in human teeth.

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Pellegrini, Manuela; Casá, Adriana; Marchei, Emilia; Pacifici, Roberta; Mayné, Ruth; Barbero, Vanessa; Garcia-Algar, Oscar; Pichini, Simona

2006-02-24

A procedure based on gas chromatography-mass spectrometry (GC-MS) is described for determination of opiates (6-monoacetylmorphine, morphine and codeine) and cocaine and metabolites (cocaine, benzoylecgonine and cocaethylene) in human teeth. After addition of nalorphine as internal standard, pulverized samples were incubated in HCl at 37 degrees C for 18 h. Then, after pH adjustment to 6, and the analytes were extracted with two volumes of 3 ml of chloroform/isopropanol (9:1). Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 7.5 (6.0 in case of codeine) to 500 ng/g with mean absolute recoveries ranged between 74.1 and 92.1% for the different analytes and precision and accuracy always better than 15%. The method was applied to the analysis of teeth from drug-addicts to assess past chronic consumption and verify self-reported declarations. In case of opiates, concentration range was 36.5-570.0 ng/g for 6-monoacetylmorphine, 8.7-154.8 ng/g for morphine and 7.9-127.9 ng/g for codeine. Cocaine concentration ranged between 5.6 and 57.2 ng/g with its principal metabolite benzoylecgonine varying from 12.6 to 81.7 ng/g and cocaethylene present in only one sample at 10 ng/g value. Teeth can be a promising non-invasive biological matrix in biomedical analysis for both clinical and forensic purposes.

Mirtazapine attenuates cocaine seeking in rats.

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Barbosa-Méndez, Susana; Leff, Phillipe; Arías-Caballero, Adriana; Hernández-Miramontes, Ricardo; Heinze, Gerardo; Salazar-Juárez, Alberto

2017-09-01

Relapse to cocaine use is a major problem in the clinical treatment of cocaine addiction. Antidepressants have been studied for their therapeutic potential to treat cocaine use disorder. Research has suggested that antidepressants attenuate both drug craving and the re-acquisition of drug-seeking and drug-taking behaviors. This study examined the efficacy of mirtazapine, an antidepressant/anxiolytic, in decreasing cocaine seeking in rats. We used the cocaine self-administration paradigm to assess the effects of mirtazapine on rats trained to self-administer cocaine or food under a fixed-ratio schedule. Mirtazapine (30 mg/kg, i.p.) was administered during extinction. Mirtazapine significantly attenuated non-reinforced lever-press responses during extinction. Moreover, the mirtazapine dosed for 30 days during extinction produced sustained attenuation of lever-press responses during re-acquisition of cocaine self-administration, without changing food-seeking behavior. Our results showed that mirtazapine attenuated the re-acquisition of cocaine-seeking responses. Our study pointed to the efficacy of mirtazapine in reducing the risk of drug relapse during abstinence, suggesting for its potential use as a novel pharmacological agent to treat drug abuse. Copyright © 2017 Elsevier Ltd. All rights reserved.

Attention problems in childhood and adult substance use.

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Galéra, Cédric; Pingault, Jean-Baptiste; Fombonne, Eric; Michel, Grégory; Lagarde, Emmanuel; Bouvard, Manuel-Pierre; Melchior, Maria

2013-12-01

To assess the link between childhood attention problems (AP) and substance use 18 years later. This cohort study was conducted in a community sample of 1103 French youths followed from 1991 to 2009. Exposures and covariates were childhood behavioral problems (based on parental report at baseline), early substance use, school difficulties, and family adversity. Outcome measures were regular tobacco smoking, alcohol problems, problematic cannabis use, and lifetime cocaine use (based on youth reports at follow-up). Individuals with high levels of childhood AP had higher rates of substance use (regular tobacco smoking, alcohol problems, problematic cannabis use, and lifetime cocaine use). However, when taking into account other childhood behavioral problems, early substance use, school difficulties, and family adversity, childhood AP were related only to regular tobacco smoking and lifetime cocaine use. Early cannabis exposure was the strongest risk factor for all substance use problems. This longitudinal community-based study shows that, except for tobacco and cocaine, the association between childhood AP and substance use is confounded by a range of early risk factors. Early cannabis exposure plays a central role in later substance use. Copyright © 2013 Mosby, Inc. All rights reserved.

Sintomas depressivos e uso de Cannabis em adolescentes Síntomas depresivos en adolescentes usuarios de Cannabis Depressive symptoms in young Cannabis users

Directory of Open Access Journals (Sweden)

Tânia Moraes Ramos Andrade

2008-09-01

Full Text Available A depressão é um dos transtornos psiquiátricos mais comuns na adolescência. Os quadros depressivos costumam apresentar elevadas taxas de comorbidades psiquiátricas, sendo freqüente o abuso de substâncias psicoativas. O artigo investiga a associação dos sintomas depressivos e o uso da cannabis. MÉTODO: Revisão sistemática, análise dos artigos indexados no Medline, PsycInfo, ProQuest, Web of Science e Lilacs, entre 2000 e 2005, descritores: depressive symptoms, depressive, adolescence, teenager e cannabis. RESULTADOS: Revisados 36 artigos completos, resultando no estudo de 9 artigos, que tratam de sintomas depressivos ou depressão e o uso ou dependência de cannabis em adolescentes. Os estudos confirmam a associação entre sintomas depressivos e o uso de cannabis na adolescência, sendo esta associação mais freqüente no uso precoce e regular de cannabis. CONCLUSÃO: Os sintomas depressivos/depressão estão relacionados ao uso/abuso e dependência de cannabis na adolescência. A investigação clínica e os programas de prevenção devem abordar estes transtornos na adolescência.Este artículo busca investigar la asociación de los síntomas depresivos y el uso de cannabis en la adolescencia. MÉTODO: Ha sido realizado, a través de revisión sistemática, el análisis de los artículos indexados localizados en los sistemas Medline, PsycInfo, ProQuest, Web of Science y Lilacs, entre 2000 y 2005, utilizando los descriptores: depressive symptoms, depressive, adolescence, teenager y cannabis. RESULTADOS: La mayoría de los estudios confirma existir una asociación entre síntomas depresivos y el uso de cannabis en la adolescencia, cabe destacar que esta asociación es más frecuente en el uso precoz y regular de cañabais. CONCLUSIÓN: Los síntomas depresivos/Depresión están relacionados al uso/abuso y dependencia de cañabais en la adolescencia, siendo entonces importante que estas variables puedan ser investigadas en la pr

Effects of quitting cannabis on respiratory symptoms

Science.gov (United States)

Hancox, Robert J.; Shin, Hayden H.; Gray, Andrew R.; Poulton, Richie; Sears, Malcolm R.

2016-01-01

Smoking cannabis is associated with symptoms of bronchitis. Little is known about the persistence of symptoms after stopping cannabis use. We assessed associations between changes in cannabis use and respiratory symptoms in a population-based cohort of 1037 young adults. Participants were asked about cannabis and tobacco use at ages 18, 21, 26, 32 and 38 years. Symptoms of morning cough, sputum production, wheeze, dyspnoea on exertion and asthma diagnoses were ascertained at the same ages. Frequent cannabis use was defined as ≥52 occasions over the previous year. Associations between frequent cannabis use and respiratory symptoms were analysed using generalised estimating equations with adjustments for tobacco smoking, asthma, sex and age. Frequent cannabis use was associated with morning cough (OR 1.97, pcannabis use was associated with reductions in the prevalence of cough, sputum and wheeze to levels similar to nonusers. Frequent cannabis use is associated with symptoms of bronchitis in young adults. Reducing cannabis use often leads to a resolution of these symptoms. PMID:25837035

Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine.

Science.gov (United States)

Sun, HaoSheng; Damez-Werno, Diane M; Scobie, Kimberly N; Shao, Ning-Yi; Dias, Caroline; Rabkin, Jacqui; Wright, Katherine N; Mouzon, Ezekiell; Kabbaj, Mohamed; Neve, Rachael; Turecki, Gustavo; Shen, Li; Nestler, Eric J

2017-06-14

Chromatin regulation, in particular ATP-dependent chromatin remodelers, have previously been shown to be important in the regulation of reward-related behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A, an accessory subunit of the ISWI family of chromatin remodeling complexes, is downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in mouse NAc reduces cocaine reward as assessed by conditioned place preference (CPP), but increases cocaine-induced locomotor activation. Furthermore, we investigate nucleosome repositioning genome-wide by conducting chromatin immunoprecipitation (ChIP)-sequencing for total H3 in NAc of control mice and after repeated cocaine administration, and find extensive nucleosome occupancy and shift changes across the genome in response to cocaine exposure. These findings implicate BAZ1A in molecular and behavioral plasticity to cocaine and offer new insight into the pathophysiology of cocaine addiction. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Cannabis Use When it's Legal

NARCIS (Netherlands)

van Ours, J.C.

2005-01-01

This paper uses information about prime age individuals living in Amsterdam, to study whether the use of alcohol, or tobacco stimulates the use cannabis, i.e. whether alcohol or cannabis are stepping stones for cannabis.The special element of the study is that it concerns the use in an environment

Cannabis-Induced Acute Pancreatitis: A Systematic Review.

Science.gov (United States)

Barkin, Jodie A; Nemeth, Zsuzsanna; Saluja, Ashok K; Barkin, Jamie S

2017-09-01

Cannabis is the most frequently consumed illicit drug in the world, with higher prevalence under the age of 35 years. Cannabis was first reported as a possible cause of acute pancreatitis (AP) in 2004. The aim of this systematic review is to examine cannabis use as an etiology of AP. A search using PubMed/Medline, Embase, Scopus, and Cochrane was performed without language or year limitations to May 1, 2016. Search terms were "Cannabis" and "Acute Pancreatitis" with all permutations. The search yielded 239 results. Acute pancreatitis was defined by meeting 2 of 3 Revised Atlanta Classification criteria. Cannabis-induced AP was defined by preceding use of cannabis and exclusion of common causes of AP when reported. Sixteen papers met inclusion criteria dating from 2004 to 2016. There were 26 cases of cannabis-induced AP (23/26 men; 24/26 under the age of 35 y). Acute pancreatitis correlated with increased cannabis use in 18 patients. Recurrent AP related temporally to cannabis use was reported in 15 of 26. There are 13 reports of no further AP episodes after cannabis cessation. Cannabis is a possible risk factor for AP and recurrent AP, occurring primarily in young patients under the age of 35 years. Toxicology screens should be considered in all patients with idiopathic AP.

Predicting the transition from frequent cannabis use to cannabis dependence: a three-year prospective study

NARCIS (Netherlands)

van der Pol, Peggy; Liebregts, Nienke; de Graaf, Ron; Korf, Dirk J.; van den Brink, Wim; van Laar, Margriet

2013-01-01

Frequent cannabis users are at high risk of dependence, still most (near) daily users are not dependent. It is unknown why some frequent users develop dependence, whereas others do not. This study aims to identify predictors of first-incidence DSM-IV cannabis dependence in frequent cannabis users. A

Attention deficit hyperactivity disorder and drug addiction rehabilitation patients.

Science.gov (United States)

Camargo, Carlos Henrique Ferreira; Dornelles, Tarcísio Fanha; Barszcz, Karin; Martins, Eduardo Antunes

2016-12-01

Attention deficit hyperactivity disorder (ADHD) is characterized by a persistent pattern of inattention or hyperactivity. This study aimed to investigate the relationship between ADHD and drug dependence. The presence and severity of ADHD and substance use were evaluated through questionnaires in 80 adult patients in therapeutic communities. No difference in drug use or dependence prevalence between ADHD and non-ADHD patients was found. However, ADHD patients had lower ages on admission (p = 0.004) and at first contact with cocaine (p = 0.033). In ADHD patients, there was a negative correlation between the age at first use of cannabis and the subsequent severity of cannabis use (p = 0.017) and cocaine use (p = 0.033). Though there was no difference in prevalence of drug use among groups, results show that ADHD in patients in therapeutic communities may cause different addiction patterns, such as earlier use of cocaine and admission, and a more severe use of cocaine correlated to earlier contact with cannabis.

Location-specific immunodetection of cocaine on banknotes.

Science.gov (United States)

van der Heide, Susan; Cunningham, Andrew; Hardwick, Sheila; Russell, David A

2016-10-17

A novel in-gel bioanalytical immunodetection method has been developed to determine both the presence and the location of cocaine on the surface of banknotes. The cocaine was 'fixed' to the surface of the banknote via a coating of a polyacrylamide gel matrix. Immunostaining of the immobilised cocaine on the banknote surface was performed using an anti-cocaine primary antibody, either pre-labelled with horse radish peroxidase (HRP) or in conjunction with a HRP-labelled secondary antibody. Visualisation of the location of the cocaine was achieved through chemiluminescence imaging of the banknote following application of a chemiluminescent substrate. The novel method was applied to the detection of cocaine on partial and whole banknote samples obtained from general circulation. Newly minted banknotes, with or without spiked cocaine, were used as positive and negative controls, respectively. The results obtained, for the first time, demonstrate the successful location-specific immunostaining of cocaine on banknotes. A preliminary analysis of six UK banknotes, obtained from general circulation, suggests that cocaine can be present at variable locations across the whole of the banknote.

Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats.

Science.gov (United States)

Gregg, Ryan A; Tallarida, Christopher S; Reitz, Allen B; Rawls, Scott M

2013-12-01

Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants.

Cannabis and Cannabinoids for Chronic Pain.

Science.gov (United States)

Romero-Sandoval, E Alfonso; Kolano, Ashley L; Alvarado-Vázquez, P Abigail

2017-10-05

The purpose of this study was to provide the most up-to-date scientific evidence of the potential analgesic effects, or lack thereof, of the marijuana plant (cannabis) or cannabinoids, and of safety or tolerability of their long-term use. We found that inhaled (smoked or vaporized) cannabis is consistently effective in reducing chronic non-cancer pain. Oral cannabinoids seem to improve some aspects of chronic pain (sleep and general quality of life), or cancer chronic pain, but they do not seem effective in acute postoperative pain, abdominal chronic pain, or rheumatoid pain. The available literature shows that inhaled cannabis seems to be more tolerable and predictable than oral cannabinoids. Cannabis or cannabinoids are not universally effective for pain. Continued research on cannabis constituents and improving bioavailability for oral cannabinoids is needed. Other aspects of pain management in patients using cannabis require further open discussion: concomitant opioid use, medical vs. recreational cannabis, abuse potential, etc.

Cannabis; extracting the medicine

OpenAIRE

Hazekamp, Arno

2007-01-01

The cannabis plant (Cannabis sativa L.) has a long history as a recreational drug, but also as part of traditional medicine in many cultures. Nowadays, it is used by a large number of patients worldwide, to ameliorate the symptoms of diseases varying from cancer and AIDS to multiple sclerosis and migraine. The discovery of cannabinoid-receptors and the endocannabinoid system have opened up a new and exciting field of research. But despite the pharmaceutical potential of cannabis, its classifi...

Cannabis 'tinny' houses in New Zealand: implications for the use and sale of cannabis and other illicit drugs in New Zealand.

Science.gov (United States)

Wilkins, Chris; Reilly, James L; Casswell, Sally

2005-07-01

To examine the impact of the emergence of cannabis 'tinny' houses on the use and sale of cannabis and other illicit drugs in New Zealand. A national sample of 5800 people aged 13-45 years were interviewed about their drug use using a computer-assisted telephone interview (CATI) system as part of the 2001 National Drug Survey. A question on cannabis procurement was used to create two subgroups of cannabis buyers for further analysis: (i) 'tinny' house buyers--those who had purchased 'some', 'most' or 'all' of their cannabis from a 'tinny' house (n = 145) and (ii) personal market buyers--those who had purchased 'none' or 'hardly any' of their cannabis from a 'tinny' house (n = 342). The two groups of cannabis buyers were compared for a range of variables. ['Tinny' houses are residential properties converted for the 'supermarket' sale of cannabis and other illicit drugs to anyone who attends the premises with cash.] Those purchasing cannabis from 'tinny' houses were significantly more likely than those purchasing cannabis from the personal market to smoke one joint or more on a typical occasion, to purchase cannabis weekly or more often, to purchase small weights of cannabis, to be sold lower quality cannabis than they paid for, to know their cannabis dealer sells other illicit drug types and to use high potency strains of cannabis. There was no significant difference between the 'tinny' house and personal market cannabis buyers with respect to the frequency of cannabis use, prices paid for the same weights of cannabis, levels of other victimization, levels of other drug use or levels of encouragement by cannabis sellers to purchase other drug types. Those purchasing cannabis from 'tinny' houses were more likely to be aged 15-17 years old and to be of Maori ethnicity than those purchasing cannabis from the personal market. Cannabis 'tinny' houses attracted more adolescent and more Maori clientele. However, 'tinny' houses did not appear to be contributing to the spread

Medicinal cannabis (Bedrolite) substitution therapy in inpatients with a psychotic disorder and a comorbid cannabis use disorder: A case series.

Science.gov (United States)

Schipper, Regi; Dekker, Mathilde; de Haan, Lieuwe; van den Brink, Wim

2018-03-01

Cannabis use disorders are frequently comorbid in patients with a psychotic disorder and are associated with worse outcomes. To date there are no proven effective strategies to achieve cannabis abstinence in this population. An alternative for abstinence might be harm reduction, i.e. replacing the use of street cannabis with high tetrahydrocannabinol and low cannabidiol levels by medicinal cannabis variants with relatively low tetrahydrocannabinol and relatively high cannabidiol levels, thereby reducing the psychosis inducing effects of cannabis and enhancing the antipsychotic effects of cannabis. Here we present the data of a case series with seven inpatients diagnosed with a psychotic disorder and a treatment-resistant cannabis use disorder who received substitution therapy with a low tetrahydrocannabinol medicinal cannabis variant (Bedrolite). The results suggest that the low tetrahydrocannabinol medicinal cannabis variant Bedrolite is not effective in the treatment of inpatients with a psychotic disorder and comorbid cannabis use disorder. Bedrolite is thus not very likely to become an effective harm reduction strategy in these patients.

Cannabis use, cognitive functioning and behaviour problems

OpenAIRE

Griffith-Lendering, Merel Frederique Heleen

2013-01-01

During early adolescence, there is no association between internalizing behaviour and cannabis use. There is an association between externalizing behaviour and cannabis use, where externalizing behaviour precedes cannabis use rather than the other way around. Secondly, during adolescence, there is an association between psychosis vulnerability and cannabis use, where cannabis use predicts psychosis vulnerability and vice versa, suggesting a bi-directional cascading association. Thirdly, durin...

Cannabis Epidemiology: A Selective Review.

Science.gov (United States)

Anthony, James C; Lopez-Quintero, Catalina; Alshaarawy, Omayma

2017-01-04

Globally, the most widely used set of compounds among the internationally regulated drugs is cannabis. To review evidence from epidemiological research on cannabis, organized in relation to this field's five main rubrics: quantity, location, causes, mechanisms, and prevention/ control. The review covers a selection of evidence from standardized population surveys, official statistics, and governmental reports, as well as published articles and books identified via MEDLINE, Web of Science, and Google Scholar as of July 2016. In relation to quantity, an estimated 3% to 5% of the world population is thought to have tried a cannabis product, with at least one fairly recent use, mainly extra-medical and outside boundaries of prescribed use. Among cannabis users in the United States, roughly one in 7-8 has engaged in medical marijuana use. In relation to location, prevalence proportions reveal important variations across countries and between subgroups within countries. Regarding causes and mechanisms of starting to use cannabis, there is no compelling integrative and replicable conceptual model or theoretical formulation. Most studies of mechanisms have focused upon a 'gateway sequence' and person-to-person diffusion, with some recent work on disability-adjusted life years. A brief review of cannabis use consequences, as well as prevention and control strategies is also provided. At present, we know much about the frequency and occurrence of cannabis use, with too little replicable definitive evidence with respect to the other main rubrics. Given a changing regulatory environment for cannabis products, new institutions such as an independent International Cannabis Products Safety Commission may be required to produce evidence required to weigh benefits versus costs. It is not clear that governmentsponsored research will be sufficient to meet consumer demand for balanced points of view and truly definitive evidence. Copyright© Bentham Science Publishers; For any queries

Cannabis Epidemiology: A Selective Review

Science.gov (United States)

Anthony, James C.; Lopez-Quintero, Catalina; Alshaarawy, Omayma

2017-01-01

Background Globally, the most widely used set of compounds among the internationally regulated drugs is cannabis. Objective To review evidence from epidemiological research on cannabis, organized in relation to this field’s five main rubrics: quantity, location, causes, mechanisms, and prevention/control. Method The review covers a selection of evidence from standardized population surveys, official statistics, and governmental reports, as well as published articles and books identified via MEDLINE, Web of Science, and Google Scholar as of July 2016. Results In relation to quantity, an estimated 3% to 5% of the world population is thought to have tried a cannabis product, with at least one fairly recent use, mainly extra-medical and outside boundaries of prescribed use. Among cannabis users in the United States, roughly one in 7–8 has engaged in medical marijuana use. In relation to location, prevalence proportions reveal important variations across countries and between subgroups within countries. Regarding causes and mechanisms of starting to use cannabis, there is no compelling integrative and replicable conceptual model or theoretical formulation. Most studies of mechanisms have focused upon a ‘gateway sequence’ and person-to-person diffusion, with some recent work on disability-adjusted life years. A brief review of cannabis use consequences, as well as prevention and control strategies is also provided. Conclusion At present, we know much about the frequency and occurrence of cannabis use, with too little replicable definitive evidence with respect to the other main rubrics. Given a changing regulatory environment for cannabis products, new institutions such as an independent International Cannabis Products Safety Commission may be required to produce evidence required to weigh benefits versus costs. It is not clear that government sponsored research will be sufficient to meet consumer demand for balanced points of view and truly definitive evidence

fMRI study of neural sensitization to hedonic stimuli in long‐term, daily cannabis users

Science.gov (United States)

Dunlop, Joseph; Ketcherside, Ariel; Baine, Jessica; Rhinehardt, Tyler; Kuhn, Brittany; DeWitt, Sam; Alvi, Talha

2016-01-01

Abstract Although there is emergent evidence illustrating neural sensitivity to cannabis cues in cannabis users, the specificity of this effect to cannabis cues as opposed to a generalized hyper‐sensitivity to hedonic stimuli has not yet been directly tested. Using fMRI, we presented 53 daily, long‐term cannabis users and 68 non‐using controls visual and tactile cues for cannabis, a natural reward, and, a sensory‐perceptual control object to evaluate brain response to hedonic stimuli in cannabis users. The results showed an interaction between group and reward type such that the users had greater response during cannabis cues relative to natural reward cues (i.e., fruit) in the orbitofrontal cortex, striatum, anterior cingulate gyrus, and ventral tegmental area compared to non‐users (cluster‐threshold z = 2.3, P cannabis cues in fronto‐striatal‐temporal regions and subjective craving, marijuana‐related problems, withdrawal symptoms, and levels of THC metabolites (cluster‐threshold z = 2.3, P cannabis cues in long‐term cannabis users that are above that of response to natural reward cues. These observations are concordant with incentive sensitization models suggesting sensitization of mesocorticolimbic regions and disruption of natural reward processes following drug use. Although the cross‐sectional nature of this study does not provide information on causality, the positive correlations between neural response and indicators of cannabis use (i.e., THC levels) suggest that alterations in the reward system are, in part, related to cannabis use. Hum Brain Mapp 37:3431–3443, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27168331

Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation

NARCIS (Netherlands)

Spronk, D.B.; De Bruijn, E.R.; van Wel, J.H.; Ramaekers, J.G.; Verkes, R.J.

2016-01-01

Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of

Quantifying the Clinical Significance of Cannabis Withdrawal

Science.gov (United States)

Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

2012-01-01

Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

Quantifying the clinical significance of cannabis withdrawal.

Directory of Open Access Journals (Sweden)

David J Allsop

Full Text Available Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV. This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt.A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p=0.0001. Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p=0.03. Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p=0.001.Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.

Medicinal cannabis: moving the debate forward.

Science.gov (United States)

Newton-Howes, Giles; McBride, Sam

2016-11-18

There has been increased interest in cannabis as a medicine both nationally and internationally. Internationally, cannabis is accepted as a medication for a variety of purposes in a variety of legal guises and this, associated with anecdotes of the utility of cannabis as medication has led for calls for it to be 'medicalised' in New Zealand. This viewpoint discusses the issues associated with this approach to accessing cannabis and some of the difficulties that may be associated with it. It is important doctors are at the forefront of the debate surrounding medicalised cannabis. Recommendations as to the ongoing debate are offered.

Choice between variable and fixed cocaine injections in male rhesus monkeys.

Science.gov (United States)

Huskinson, S L; Freeman, K B; Petry, N M; Rowlett, J K

2017-08-01

The schedule of drug availability may enhance choice of a drug. In non-human subjects, reinforcers are chosen more often when available under variable schedules of reinforcement relative to fixed schedules. To determine whether variable-drug access is an important determinant of cocaine choice by manipulating the schedule, drug dose, and combination of schedule + dose. Four male rhesus monkeys chose between cocaine doses (0.025-0.4 mg/kg/injection). In control conditions, the schedule and dose of each drug delivery were fixed. In other conditions, the reinforcement schedule (i.e., variable-ratio schedule), dose of each cocaine delivery, or both were variable on one lever while all aspects on the other lever remained fixed. When cocaine dose was equal on average (0.1 mg/kg/injection), 2 of 4 subjects chose cocaine associated with the variable schedule more than the fixed schedule. All subjects chose the variable dose that was equal on average to the fixed dose, and this difference was statistically significant. Three of 4 subjects chose cocaine associated with the variable combination over the fixed option (when the dose was equal on average). During dose-response determinations (when dose on the variable and fixed options were not equal), making the schedule, dose, or both variable generally did not alter cocaine's potency as a reinforcer. While many factors contribute to drug choice, unpredictable drug access is a feature that may be common in the natural environment and could play a key role in the allocation of behavior to drug alternatives by patients with substance-use disorders.

Limitations to the Dutch cannabis toleration policy: Assumptions underlying the reclassification of cannabis above 15% THC.

Science.gov (United States)

Van Laar, Margriet; Van Der Pol, Peggy; Niesink, Raymond

2016-08-01

The Netherlands has seen an increase in Δ9-tetrahydrocannabinol (THC) concentrations from approximately 8% in the 1990s up to 20% in 2004. Increased cannabis potency may lead to higher THC-exposure and cannabis related harm. The Dutch government officially condones the sale of cannabis from so called 'coffee shops', and the Opium Act distinguishes cannabis as a Schedule II drug with 'acceptable risk' from other drugs with 'unacceptable risk' (Schedule I). Even in 1976, however, cannabis potency was taken into account by distinguishing hemp oil as a Schedule I drug. In 2011, an advisory committee recommended tightening up legislation, leading to a 2013 bill proposing the reclassification of high potency cannabis products with a THC content of 15% or more as a Schedule I drug. The purpose of this measure was twofold: to reduce public health risks and to reduce illegal cultivation and export of cannabis by increasing punishment. This paper focuses on the public health aspects and describes the (explicit and implicit) assumptions underlying this '15% THC measure', as well as to what extent these are supported by scientific research. Based on scientific literature and other sources of information, we conclude that the 15% measure can provide in theory a slight health benefit for specific groups of cannabis users (i.e., frequent users preferring strong cannabis, purchasing from coffee shops, using 'steady quantities' and not changing their smoking behaviour), but certainly not for all cannabis users. These gains should be weighed against the investment in enforcement and the risk of unintended (adverse) effects. Given the many assumptions and uncertainty about the nature and extent of the expected buying and smoking behaviour changes, the measure is a political choice and based on thin evidence. Copyright © 2016 Springer. Published by Elsevier B.V. All rights reserved.

Evidence on unusual way of cocaine smuggling: cocaine-polymethyl methacrylate (PMMA) solid solution--study of clandestine laboratory samples.

Science.gov (United States)

Gostic, T; Klemenc, S

2007-07-04

An abandoned clandestine laboratory was seized in Slovenia. All confiscated exhibits were analysed in a forensic laboratory, where the following analytical methods were applied: capillary gas chromatography coupled with mass spectrometry (GC-MS) combined also by solid-phase micro extraction (SPME) and pyrolysis (Py) technique, Fourier transform infrared spectrometry (FTIR) and scanning electron microscopy with energy dispersive X-ray detector (SEM-EDX). The most interesting analytical findings can be summarised as follows: at the crime scene some plastic pieces, which contained cocaine dissolved (as solid solution) in polymethyl methacrylate-plexiglass (PMMA), were found. The highest cocaine concentration measured in the plastic sample was about 15% by weight. Two larger lumps of material (12 and 3 kg) were composed mainly of PMMA and CaCO3 and contained only 0.4 and 0.5% of cocaine, respectively. As for the low cocaine concentration, we assume that those two lumps of material represent discarded waste product--residue after the isolation of cocaine from plastic. Higher quantities of pure solvents (41 l) and solvent mixtures (87 l) were seized. We identified three types of pure solvents (acetone, gasoline and benzine) and two different types of solvent mixtures (benzine/acetone and gasoline/acetone). The total seized volume (87 l) of solvent mixtures holds approximately 395 g of solid residue formed mainly of PMMA and cocaine. Obviously solvent mixtures were used for isolation of cocaine from the plastic. Small quantities of relatively pure cocaine base were identified on different objects. There were two cotton sheets, most probably used for filtration. One sheet had traces of cocaine base (76% purity) on the surface, while cocaine in hydrochloride form (96%) was identified on the other sheet. GC-MS analyses of micro traces isolated from analytical balances showed the presence of cocaine and some common adulterants: phenacetine, lidocaine and procaine. A cocaine

Correlates of Intentions to Use Cannabis among US High School Seniors in the Case of Cannabis Legalization

Science.gov (United States)

Palamar, Joseph J.; Ompad, Danielle C.; Petkova, Eva

2014-01-01

Background Support for cannabis (“marijuana”) legalization is increasing in the United States (US). Use was recently legalized in two states and in Uruguay, and other states and countries are expected to follow suit. This study examined intentions to use among US high school seniors if cannabis were to become legally available. Methods Data from the last five cohorts (2007–2011) of high school seniors in Monitoring the Future, an annual nationally representative survey of students in the US were utilized. Data were analyzed separately for the 6,116 seniors who reported no lifetime use of cannabis and the 3,828 seniors who reported lifetime use (weighted Ns). We examined whether demographic characteristics, substance use and perceived friend disapproval towards cannabis use were associated with 1) intention to try cannabis among non-lifetime users, and 2) intention to use cannabis as often or more often among lifetime users, if cannabis was legal to use. Results Ten percent of non-cannabis-using students reported intent to initiate use if legal and this would constitute a 5.6% absolute increase in lifetime prevalence of cannabis use in this age group from 45.6% (95% CI=46.6, 44.6) to 51.2% (95% CI=50.2, 52.2). Eighteen percent of lifetime users reported intent to use cannabis more often if it was legal. Odds for intention to use outcomes increased among groups already at high risk for use (e.g., males, whites, cigarette smokers) and odds were reduced when friends disapproved of use. However, large proportions of subgroups of students normally at low risk for use (e.g., non-cigarette-smokers, religious students, those with friends who disapprove of use) reported intention to use if legal. Recent use was also a risk factor for reporting intention to use as often or more often. Conclusion Prevalence of cannabis use is expected to increase if cannabis is legal to use and legally available. PMID:24589410

Correlates of intentions to use cannabis among US high school seniors in the case of cannabis legalization.

Science.gov (United States)

Palamar, Joseph J; Ompad, Danielle C; Petkova, Eva

2014-05-01

Support for cannabis ("marijuana") legalization is increasing in the United States (US). Use was recently legalized in two states and in Uruguay, and other states and countries are expected to follow suit. This study examined intentions to use among US high school seniors if cannabis were to become legally available. Data from the last five cohorts (2007-2011) of high school seniors in Monitoring the Future, an annual nationally representative survey of students in the US were utilized. Data were analyzed separately for the 6116 seniors who reported no lifetime use of cannabis and the 3829 seniors who reported lifetime use (weighted Ns). We examined whether demographic characteristics, substance use and perceived friend disapproval towards cannabis use were associated with (1) intention to try cannabis among non-lifetime users, and (2) intention to use cannabis as often or more often among lifetime users, if cannabis was legal to use. Ten percent of non-cannabis-using students reported intent to initiate use if legal and this would be consistent with a 5.6% absolute increase in lifetime prevalence of cannabis use in this age group from 45.6% (95% CI=44.6, 46.6) to 51.2% (95% CI=50.2, 52.2). Eighteen percent of lifetime users reported intent to use cannabis more often if it was legal. Odds for intention to use outcomes increased among groups already at high risk for use (e.g., males, whites, cigarette smokers) and odds were reduced when friends disapproved of use. However, large proportions of subgroups of students normally at low risk for use (e.g., non-cigarette-smokers, religious students, those with friends who disapprove of use) reported intention to use if legal. Recent use was also a risk factor for reporting intention to use as often or more often. Prevalence of cannabis use is expected to increase if cannabis is legal to use and legally available. Copyright © 2014 Elsevier B.V. All rights reserved.

Cocaine in the UK--1991.

Science.gov (United States)

Strang, J; Johns, A; Caan, W

1993-01-01

More than 100 years after Freud's original endorsement of the drug, the use of cocaine is a problem for both users and for society, which struggles to organise effective responses to the epidemic of the last decade. During the 1980s the rapid spread of smokeable cocaine (including 'crack') was seen in the Americas (particularly the US). The initial simple predictions of an identical European epidemic were mistaken. The available data on the extent of cocaine use and of cocaine problems in the UK are examined. New forms of cocaine have been developed by black-market entrepreneurs ('freebase' and 'crack'), and new technologies have emerged for their use; with these new technologies have come new effects and new problems. The general psychiatrist now needs a knowledge of directly and indirectly related psychopathology which has an increasing relevance to the diagnosis and management of the younger patient.

Cue-induced striatal activity in frequent cannabis users independently predicts cannabis problem severity three years later

NARCIS (Netherlands)

Vingerhoets, W.A.M.; Koenders, L.; van den Brink, W.P.; Wiers, R.W.; Goudriaan, A.E.; van Amelsvoort, T.; de Haan, L.; Cousijn, J.

2016-01-01

Cannabis is the most frequently used illicit drug worldwide, but little is known about the mechanisms underlying continued cannabis use. Cue-reactivity (the physical, psychological, behavioural and neural reaction to substance-related cues) might be related to continued cannabis use. In this 3-year

Baclofen in the management of cannabis dependence syndrome.

Science.gov (United States)

Imbert, Bruce; Labrune, Nathalie; Lancon, Christophe; Simon, Nicolas

2014-02-01

Cannabis is the most commonly used illicit drug in the world. However, only few studies have shown the efficacy of pharmacologic agents in targeting cannabis withdrawal symptoms or reducing the reinforcing effects of cannabis. Baclofen has been shown to reduce cannabis withdrawal symptoms and the subjective effects of cannabis. We think that the clinical utility of baclofen for cannabis dependence is a reasonable approach. A case report using baclofen is presented and provides preliminary support for the use of baclofen in the management of cannabis dependence.

Assessing the effect of patterns of cocaine and alcohol use on the risk of adverse acute cocaine intoxication.

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Santos, Sara; Brugal, M Teresa; Barrio, Gregorio; Castellano, Yolanda; Domingo-Salvany, Antonia; Espelt, Albert; Bravo, M Jose; de la Fuente, Luis

2012-06-01

Although, in the laboratory, most acute adverse effects of cocaine are dose-dependent and alcohol potentiates some of these effects, there are few observational studies, and scarce awareness that the risk of acute cocaine intoxication (ACI) can increase as the amounts of cocaine and alcohol consumed increase. Our objectives were to assess if the risk of ACI increases with the level cocaine use, both in chronic and binge use; and also to determine whether it increases when a cocaine binge is combined with binge drinking or with regular excessive drinking. Hypotheses were evaluated using logistic regression and case-crossover analyses in a sample of 720 young regular cocaine users who did not regularly use heroin, recruited at drug scenes in 2004-2006. All data on ACI, predictor and confounding variables were obtained through a computer-assisted personal interview. The annual prevalence of ACI was 21%. In the last year 10.3% of the participants reported cocaine binges (≥ 0.5 g in 4 h). ACI risk increased considerably in the 4 h following a cocaine binge (odds ratio = 34.6; 95% confidence interval 11.5-170.8). Also, it increased with increases in the average level of cocaine used over a long period and when users regularly drank excessively. Finally, the results suggest that the high risk of ACI associated with cocaine binge may increase even more when combined with binge drinking. Awareness of the dose-dependent effect of cocaine on ACI risk, as well as the possible synergistic effect of alcohol, ought to be incorporated into preventive and care strategies. © 2012 Australasian Professional Society on Alcohol and other Drugs.

Functions of microRNA in response to cocaine stimulation.

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Xu, L-F; Wang, J; Lv, F B; Song, Q

2013-12-04

MicroRNAs (miRNAs) are a type of non-protein-coding single-stranded RNA, which are typically 20-25 nt in length. miRNAs play important roles in various biological processes, including development, cell proliferation, differentiation, and apoptosis. We aimed to detect the miRNA response to cocaine stimulations and their target genes. Using the miRNA expression data GSE21901 downloaded from the Gene Expression Omnibus database, we screened out the differentially expressed miRNA after short-term (1 h) and longer-term (6 h) cocaine stimulations based on the fold change >1.2. Target genes of differentially expressed miRNAs were retrieved from TargetScan database with the context score -0.3. Functional annotation enrichment analysis was performed for all the target genes with DAVID. A total of 121 differentially expressed miRNAs between the 1-h treatment and the control samples, 58 between the 6-h treatment and the control samples, and 69 between the 1-h and the 6-h treatment samples. Among them, miR-212 results of particular interest, since its expression level was constantly elevated responding to cocaine treatment. After functional and pathway annotations of target genes, we proved that miR-212 was a critical element in cocaine-addiction, because of its involvement in regulating several important cell cycle events. The results may pave the way for further understanding the regulatory mechanisms of cocaine-response in human bodies.

Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability.

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Cooper, Ziva D; Bedi, Gillinder; Ramesh, Divya; Balter, Rebecca; Comer, Sandra D; Haney, Margaret

2018-02-05

Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals. Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability. This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability. Healthy cannabis smokers (N = 18) were administered oxycodone (0, 2.5, and 5.0 mg, PO) with smoked cannabis (0.0, 5.6% Δ 9 tetrahydrocannabinol [THC]) and analgesia was assessed using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4 °C); times to report pain (pain threshold) and withdraw the hand from the water (pain tolerance) were recorded. Abuse-related effects were measured and effects of oxycodone on cannabis self-administration were determined. Alone, 5.0 mg oxycodone increased pain threshold and tolerance (p ≤ 0.05). Although active cannabis and 2.5 mg oxycodone alone failed to elicit analgesia, combined they increased pain threshold and tolerance (p ≤ 0.05). Oxycodone did not increase subjective ratings associated with cannabis abuse, nor did it increase cannabis self-administration. However, the combination of 2.5 mg oxycodone and active cannabis produced small, yet significant, increases in oxycodone abuse liability (p ≤ 0.05). Cannabis enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy, without increases in cannabis's abuse liability. These findings support future research into the therapeutic use of opioid-cannabinoid combinations for pain.

Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment.

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Lee, Dayong; Schroeder, Jennifer R; Karschner, Erin L; Goodwin, Robert S; Hirvonen, Jussi; Gorelick, David A; Huestis, Marilyn A

2014-01-01

Chronic, frequent cannabis smokers may experience residual and offset effects, withdrawal, and craving when abstaining from the drug. We characterized the prevalence, duration, and intensity of these effects in chronic frequent cannabis smokers during abstinence on a closed research unit. Non-treatment-seeking participants (N = 29 on admission, 66% and 34% remaining after 2 and 4 weeks) provided subjective effects data. A battery of five instruments was computer-administered daily to measure psychological, sensory, and physical symptoms associated with cannabinoid intoxication and withdrawal. Plasma and oral fluid specimens were concurrently collected and analyzed for cannabinoids. Outcome variables were evaluated as change from admission (Day 0) with regression models. Most abstinence effects, including irritability and anxiety were greatest on Days 0-3 and decreased thereafter. Cannabis craving significantly decreased over time, whereas decreased appetite began to normalize on Day 4. Strange dreams and difficulty getting to sleep increased over time, suggesting intrinsic sleep problems in chronic cannabis smokers. Symptoms likely induced by residual drug effects were at maximum intensity on admission and positively correlated with plasma and oral fluid cannabinoid concentrations on admission but not afterward; these symptoms showed overall prevalence higher than cannabis withdrawal symptoms. The combined influence of residual/offset drug effects, withdrawal, and craving was observed in chronic cannabis smokers during monitored abstinence. Abstinence symptoms were generally more intense in the initial phase, implying importance of early intervention in cannabis quit attempts. Sleep disturbance persisting for an extended period suggests that hypnotic medications could be beneficial in treating cannabis dependence. © American Academy of Addiction Psychiatry.

Hormones, Nicotine and Cocaine: Clinical Studies

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Mello, Nancy K.

2009-01-01

Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

Beyond Cannabis: Plants and the Endocannabinoid System.

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Russo, Ethan B

2016-07-01

Plants have been the predominant source of medicines throughout the vast majority of human history, and remain so today outside of industrialized societies. One of the most versatile in terms of its phytochemistry is cannabis, whose investigation has led directly to the discovery of a unique and widespread homeostatic physiological regulator, the endocannabinoid system. While it had been the conventional wisdom until recently that only cannabis harbored active agents affecting the endocannabinoid system, in recent decades the search has widened and identified numerous additional plants whose components stimulate, antagonize, or modulate different aspects of this system. These include common foodstuffs, herbs, spices, and more exotic ingredients: kava, chocolate, black pepper, and many others that are examined in this review. Copyright © 2016 Elsevier Ltd. All rights reserved.

Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects

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Russo, Ethan B

2011-01-01

Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL−1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant. LINKED ARTICLES

Decreased respiratory symptoms in cannabis users who vaporize

Directory of Open Access Journals (Sweden)

Barnwell Sara

2007-04-01

Full Text Available Abstract Cannabis smoking can create respiratory problems. Vaporizers heat cannabis to release active cannabinoids, but remain cool enough to avoid the smoke and toxins associated with combustion. Vaporized cannabis should create fewer respiratory symptoms than smoked cannabis. We examined self-reported respiratory symptoms in participants who ranged in cigarette and cannabis use. Data from a large Internet sample revealed that the use of a vaporizer predicted fewer respiratory symptoms even when age, sex, cigarette smoking, and amount of cannabis used were taken into account. Age, sex, cigarettes, and amount of cannabis also had significant effects. The number of cigarettes smoked and amount of cannabis used interacted to create worse respiratory problems. A significant interaction revealed that the impact of a vaporizer was larger as the amount of cannabis used increased. These data suggest that the safety of cannabis can increase with the use of a vaporizer. Regular users of joints, blunts, pipes, and water pipes might decrease respiratory symptoms by switching to a vaporizer

US Epidemiology of Cannabis Use and Associated Problems

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Hasin, Deborah S

2018-01-01

This review provides an overview of the changing US epidemiology of cannabis use and associated problems. Adults and adolescents increasingly view cannabis as harmless, and some can use cannabis without harm. However, potential problems include harms from prenatal exposure and unintentional childhood exposure; decline in educational or occupational functioning after early adolescent use, and in adulthood, impaired driving and vehicle crashes; cannabis use disorders (CUD), cannabis withdrawal, and psychiatric comorbidity. Evidence suggests national increases in cannabis potency, prenatal and unintentional childhood exposure; and in adults, increased use, CUD, cannabis-related emergency room visits, and fatal vehicle crashes. Twenty-nine states have medical marijuana laws (MMLs) and of these, 8 have recreational marijuana laws (RMLs). Many studies indicate that MMLs or their specific provisions did not increase adolescent cannabis use. However, the more limited literature suggests that MMLs have led to increased cannabis potency, unintentional childhood exposures, adult cannabis use, and adult CUD. Ecological-level studies suggest that MMLs have led to substitution of cannabis for opioids, and also possibly for psychiatric medications. Much remains to be determined about cannabis trends and the role of MMLs and RMLs in these trends. The public, health professionals, and policy makers would benefit from education about the risks of cannabis use, the increases in such risks, and the role of marijuana laws in these increases. PMID:28853439

Cannabis its clinical effects

African Journals Online (AJOL)

Cannabis saliva ('dagga') affects the central nervous system. (CNS) in a variety of ... to cannabis use. These include delusional thinking, paranoid ideas ... It is thought to consist of diminished drive, volition and ambition, a loss of motivation,.

Signs of Cocaine Abuse and Addiction

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... Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share You are here Home » Drugs That People Abuse » Cocaine (Coke, Crack) Facts » Signs of Cocaine Use and Addiction Signs of Cocaine Use and Addiction Listen ©istock. ...

Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study.

Science.gov (United States)

Terraneo, Alberto; Leggio, Lorenzo; Saladini, Marina; Ermani, Mario; Bonci, Antonello; Gallimberti, Luigi

2016-01-01

Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity, while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking, providing a strong rationale for applying brain stimulation to reduce cocaine consumption. Thus, we employed repetitive transcranial magnetic stimulation (rTMS), to test if dorsolateral prefrontal cortex (DLPFC) stimulation might prevent cocaine use in humans. Thirty-two cocaine-addicted patients were randomly assigned to either the experimental group (rTMS) on the left DLPFC, or to a control group (pharmacological agents) during a 29-day study (Stage 1). This was followed by a 63-day follow-up (Stage 2), during which all participants were offered rTMS treatment. Amongst the patients who completed Stage 1, 16 were in the rTMS group (100%) and 13 in the control group (81%). No significant adverse events were noted. During Stage 1, there were a significantly higher number of cocaine-free urine drug tests in the rTMS group compared to control (p=0.004). Craving for cocaine was also significantly lower in the rTMS group compared to the controls (p=0.038). Out of 13 patients who completed Stage 1 in the control group, 10 patients received rTMS treatment during Stage 2 and showed significant improvement with favorable outcomes becoming comparable to those of the rTMS group. The present preliminary findings support the safety of rTMS in cocaine-addicted patients, and suggest its potential therapeutic role for rTMS-driven PFC stimulation in reducing cocaine use, providing a strong rationale for developing larger placebo-controlled studies. Trial name: Repetitive transcranial magnetic stimulation (rTMS) in cocaine abusers, URL:〈http://www.isrctn.com/ISRCTN15823943?q=&filters=&sort=&offset=8&totalResults=13530&page=1&pageSize=10&searchType=basic-search〉, ISRCTN15823943. Published by Elsevier B.V.

The Cannabis sativa Versus Cannabis indica Debate: An Interview with Ethan Russo, MD.

Science.gov (United States)

Piomelli, Daniele; Russo, Ethan B

2016-01-01

Dr. Ethan Russo, MD, is a board-certified neurologist, psychopharmacology researcher, and Medical Director of PHYTECS, a biotechnology company researching and developing innovative approaches targeting the human endocannabinoid system. Previously, from 2003 to 2014, he served as Senior Medical Advisor and study physician to GW Pharmaceuticals for three Phase III clinical trials of Sativex ® for alleviation of cancer pain unresponsive to optimized opioid treatment and studies of Epidiolex ® for intractable epilepsy. He has held faculty appointments in Pharmaceutical Sciences at the University of Montana, in Medicine at the University of Washington, and as visiting Professor, Chinese Academy of Sciences. He is a past President of the International Cannabinoid Research Society and former Chairman of the International Association for Cannabinoid Medicines. He serves on the Scientific Advisory Board for the American Botanical Council. He is the author of numerous books, book chapters, and articles on Cannabis, ethnobotany, and herbal medicine. His research interests have included correlations of historical uses of Cannabis with modern pharmacological mechanisms, phytopharmaceutical treatment of migraine and chronic pain, and phytocannabinoid/terpenoid/serotonergic/vanilloid interactions.

Proteasome phosphorylation regulates cocaine-induced sensitization.

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Gonzales, Frankie R; Howell, Kristin K; Dozier, Lara E; Anagnostaras, Stephan G; Patrick, Gentry N

2018-04-01

Repeated exposure to cocaine produces structural and functional modifications at synapses from neurons in several brain regions including the nucleus accumbens. These changes are thought to underlie cocaine-induced sensitization. The ubiquitin proteasome system plays a crucial role in the remodeling of synapses and has recently been implicated in addiction-related behavior. The ATPase Rpt6 subunit of the 26S proteasome is phosphorylated by Ca 2+ /calmodulin-dependent protein kinases II alpha at ser120 which is thought to regulate proteasome activity and distribution in neurons. Here, we demonstrate that Rpt6 phosphorylation is involved in cocaine-induced locomotor sensitization. Cocaine concomitantly increases proteasome activity and Rpt6 S120 phosphorylation in cultured neurons and in various brain regions of wild type mice including the nucleus accumbens and prefrontal cortex. In contrast, cocaine does not increase proteasome activity in Rpt6 phospho-mimetic (ser120Asp) mice. Strikingly, we found a complete absence of cocaine-induced locomotor sensitization in the Rpt6 ser120Asp mice. Together, these findings suggest a critical role for Rpt6 phosphorylation and proteasome function in the regulation cocaine-induced behavioral plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.

Epigenetic Effects of Cannabis Exposure

Science.gov (United States)

Szutorisz, Henrietta; Hurd, Yasmin L.

2015-01-01

The past decade has witnessed a number of societal and political changes that have raised critical questions about the long-term impact of marijuana (Cannabis sativa) that are especially important given the prevalence of its abuse and that potential long-term effects still largely lack scientific data. Disturbances of the epigenome have generally been hypothesized as the molecular machinery underlying the persistent, often tissue-specific transcriptional and behavioral effects of cannabinoids that have been observed within one’s lifetime and even into the subsequent generation. Here, we provide an overview of the current published scientific literature that examined epigenetic effects of cannabinoids. Though mechanistic insights about the epigenome remain sparse, accumulating data in humans and animal models have begun to reveal aberrant epigenetic modifications in brain and the periphery linked to cannabis exposure. Expansion of such knowledge and causal molecular relationships could help provide novel targets for future therapeutic interventions. PMID:26546076

A Thermally Stable Form of Bacterial Cocaine Esterase: A Potential Therapeutic Agent for Treatment of Cocaine Abuse

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Brim, Remy L.; Nance, Mark R.; Youngstrom, Daniel W.; Narasimhan, Diwahar; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K.; Woods, James H. (Michigan); (Michigan-Med); (Kentucky)

2010-09-03

Rhodococcal cocaine esterase (CocE) is an attractive potential treatment for both cocaine overdose and cocaine addiction. CocE directly degrades cocaine into inactive products, whereas traditional small-molecule approaches require blockade of the inhibitory action of cocaine on a diverse array of monoamine transporters and ion channels. The usefulness of wild-type (wt) cocaine esterase is hampered by its inactivation at 37 C. Herein, we characterize the most thermostable form of this enzyme to date, CocE-L169K/G173Q. In vitro kinetic analyses reveal that CocE-L169K/G173Q displays a half-life of 2.9 days at 37 C, which represents a 340-fold improvement over wt and is 15-fold greater than previously reported mutants. Crystallographic analyses of CocE-L169K/G173Q, determined at 1.6-{angstrom} resolution, suggest that stabilization involves enhanced domain-domain interactions involving van der Waals interactions and hydrogen bonding. In vivo rodent studies reveal that intravenous pretreatment with CocE-L169K/G173Q in mice provides protection from cocaine-induced lethality for longer time periods before cocaine administration than wt CocE. Furthermore, intravenous administration (pretreatment) of CocE-L169K/G173Q prevents self-administration of cocaine in a time-dependent manner. Termination of the in vivo effects of CoCE seems to be dependent on, but not proportional to, its clearance from plasma as its half-life is approximately 2.3 h and similar to that of wt CocE (2.2 h). Taken together these data suggest that CocE-L169K/G173Q possesses many of the properties of a biological therapeutic for treating cocaine abuse but requires additional development to improve its serum half-life.

Medical Cannabis: The Oncology Nurse's Role in Patient Education About the Effects of Marijuana on Cancer Palliation
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