Structured outpatient treatment of alcohol vs. drug dependencies.

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Washton, A M

1990-01-01

This chapter describes the rationale, indications, design, and use of a structured outpatient treatment approach as an effective alternative to residential treatment for alcohol and drug dependencies. An increasing demand for outpatient treatment services is being created by a combination of clinical and economic factors, including the influx of employed drug abusers who do not need or desire residential care and mounting financial pressures to contain health care costs. To be effective as a primary treatment modality, outpatient programs must be highly structured and intensive and able to deal with the full spectrum of alcohol and drug addictions. Perpetuating the historical separation between alcoholism and drug abuse treatment programs is unnecessary and counterproductive, although certain modifications in treatment approaches are needed to accommodate the distinctive characteristics of particular classes of drugs and the people who use them. The "outpatient rehab," a treatment model that approximates the intensity of inpatient treatment on an outpatient basis, may help to maximize the clinical efficacy and cost-effectiveness of outpatient treatment as a viable alternative to residential care. Initial treatment results with this model are encouraging.

The relevance of the psychological evaluation in drug dependence

OpenAIRE

Popescu, G; Negrei, C; B?l?l?u, D; Ciobanu, AM; Baconi, D

2014-01-01

Psychological interventions are considered a central part of the individual psychotherapy in the rehabilitation counseling of psychiatrically symptomatic drug-dependent patients during methadone maintenance treatment in community programs. The need for psychological counseling should be evaluated for each individual patient. Medication is an important part of the treatment and individual psychotherapy focuses on the reduction or total cessation of drug use. The Recipient is G.M. 31, sentenced...

A theory of drug tolerance and dependence I: a conceptual analysis.

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Peper, Abraham

2004-08-21

A mathematical model of drug tolerance and its underlying theory is presented. The model extends a first approach, published previously. The model is essentially more complex than the generally used model of homeostasis, which is demonstrated to fail in describing tolerance development to repeated drug administrations. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary only in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behavior to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes. In addition, it establishes a relation between the drug dose at any moment, and the resulting drug effect and relates the magnitude of the reactions following withdrawal to the rate of tolerance and other parameters involved in the tolerance process. The present paper analyses the concept behind the model. The next paper discusses the mathematical model.

Genome-wide discovery of drug-dependent human liver regulatory elements.

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Robin P Smith

2014-10-01

Full Text Available Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR and three active regulatory marks (p300, H3K4me1, H3K27ac on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4% that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements.

THE RESOCIALIZATION OF DRUG-DEPENDENT PEOPLE IN REHABILITATION CENTERS: SOCIAL AND PEDAGOGICAL ASPECTS

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Юлія Чернецька

2015-12-01

Full Text Available The article deals with the resocialization of drug-dependent people in rehabilitation centers.  In the of resocialization the restoration of social relationships (social rehabilitation and social adaptation, and the accumulation of new socially positive experience are ensured. Resocialization is possible through the study and assimilation of cultural values, norms, attitudes, patterns of behavior, and the implementation of social activity of drug-dependent people in various activities. The article explains the meaning of “resocialization” through the categories of “social environment” and “social education”. It is roved that the resocialization of drug-dependent personality is carried out directly under the influence of social conditions (environmental factors. This process is the product of direct relations between the subjects of environment (agents and is determined by the influence material culture (means which depend on the result of resocialization is dependent.

Neural and psychological mechanisms underlying compulsive drug seeking habits and drug memories – indications for novel treatments of addiction*

OpenAIRE

Everitt, Barry J

2014-01-01

This review discusses the evidence for the hypothesis that the development of drug addiction can be understood in terms of interactions between Pavlovian and instrumental learning and memory mechanisms in the brain that underlie the seeking and taking of drugs. It is argued that these behaviours initially are goal-directed, but increasingly become elicited as stimulus–response habits by drug-associated conditioned stimuli that are established by Pavlovian conditioning. It is further argued th...

Age-Dependent Cellular and Behavioral Deficits Induced by Molecularly Targeted Drugs Are Reversible.

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Scafidi, Joseph; Ritter, Jonathan; Talbot, Brooke M; Edwards, Jorge; Chew, Li-Jin; Gallo, Vittorio

2018-04-15

Newly developed targeted anticancer drugs inhibit signaling pathways commonly altered in adult and pediatric cancers. However, as these pathways are also essential for normal brain development, concerns have emerged of neurologic sequelae resulting specifically from their application in pediatric cancers. The neural substrates and age dependency of these drug-induced effects in vivo are unknown, and their long-term behavioral consequences have not been characterized. This study defines the age-dependent cellular and behavioral effects of these drugs on normally developing brains and determines their reversibility with post-drug intervention. Mice at different postnatal ages received short courses of molecularly targeted drugs in regimens analagous to clinical treatment. Analysis of rapidly developing brain structures important for sensorimotor and cognitive function showed that, while adult administration was without effect, earlier neonatal administration of targeted therapies attenuated white matter oligodendroglia and hippocampal neuronal development more profoundly than later administration, leading to long-lasting behavioral deficits. This functional impairment was reversed by rehabilitation with physical and cognitive enrichment. Our findings demonstrate age-dependent, reversible effects of these drugs on brain development, which are important considerations as treatment options expand for pediatric cancers. Significance: Targeted therapeutics elicit age-dependent long-term consequences on the developing brain that can be ameliorated with environmental enrichment. Cancer Res; 78(8); 2081-95. ©2018 AACR . ©2018 American Association for Cancer Research.

Association between Experience of Child Abuse and Severity of Drug Addiction Measured by the Addiction Severity Index among Japanese Drug-Dependent Patients

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Ogai, Yasukazu; Senoo, Eiichi; Gardner, Fumiyuki Chin; Haraguchi, Ayako; Saito, Tamaki; Morita, Nobuaki; Ikeda, Kazutaka

2015-01-01

The aim of the present study was to clarify the association between child abuse experiences and drug addiction severity among Japanese drug-dependent patients using the Addiction Severity Index-Japanese version (ASI-J). One hundred and eleven inpatients and outpatients with drug dependence participated in the study. Some of the questions on the ASI-J asked about lifetime experiences of abuse. A higher percentage of female participants experienced child abuse compared with male participants. Male participants who experienced child abuse (MEA) had a significantly higher severity of drug use than men who did not experience it (MNEA). Female participants who experienced child abuse (FEA) had significantly more serious problems in family/social relationships than female participants who did not experience it (FNEA). Patients in the MEA group were arrested less frequently for drug charges, experienced more serious problems with their fathers, and experienced more severe anxiety in their lifetime compared with the MNEA group. The FEA group experienced more serious troubles with their sexual partners, close friends, and families and experienced more severe psychiatric problems in their lifetime compared with the FNEA group. These results suggest gender differences in the problems experienced by drug-dependent patients with child abuse experiences, and gender-specific interventions may be more effective in treating their drug dependence. PMID:25741639

Association between experience of child abuse and severity of drug addiction measured by the Addiction Severity Index among Japanese drug-dependent patients.

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Ogai, Yasukazu; Senoo, Eiichi; Gardner, Fumiyuki Chin; Haraguchi, Ayako; Saito, Tamaki; Morita, Nobuaki; Ikeda, Kazutaka

2015-03-03

The aim of the present study was to clarify the association between child abuse experiences and drug addiction severity among Japanese drug-dependent patients using the Addiction Severity Index-Japanese version (ASI-J). One hundred and eleven inpatients and outpatients with drug dependence participated in the study. Some of the questions on the ASI-J asked about lifetime experiences of abuse. A higher percentage of female participants experienced child abuse compared with male participants. Male participants who experienced child abuse (MEA) had a significantly higher severity of drug use than men who did not experience it (MNEA). Female participants who experienced child abuse (FEA) had significantly more serious problems in family/social relationships than female participants who did not experience it (FNEA). Patients in the MEA group were arrested less frequently for drug charges, experienced more serious problems with their fathers, and experienced more severe anxiety in their lifetime compared with the MNEA group. The FEA group experienced more serious troubles with their sexual partners, close friends, and families and experienced more severe psychiatric problems in their lifetime compared with the FNEA group. These results suggest gender differences in the problems experienced by drug-dependent patients with child abuse experiences, and gender-specific interventions may be more effective in treating their drug dependence.

Volatile solvents as drugs of abuse: focus on the cortico-mesolimbic circuitry.

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Beckley, Jacob T; Woodward, John J

2013-12-01

Volatile solvents such as those found in fuels, paints, and thinners are found throughout the world and are used in a variety of industrial applications. However, these compounds are also often intentionally inhaled at high concentrations to produce intoxication. While solvent use has been recognized as a potential drug problem for many years, research on the sites and mechanisms of action of these compounds lags behind that of other drugs of abuse. In this review, we first discuss the epidemiology of voluntary solvent use throughout the world and then consider what is known about their basic pharmacology and how this may explain their use as drugs of abuse. We next present data from preclinical and clinical studies indicating that these substances induce common addiction sequelae such as dependence, withdrawal, and cognitive impairments. We describe how toluene, the most commonly studied psychoactive volatile solvent, alters synaptic transmission in key brain circuits such as the mesolimbic dopamine system and medial prefrontal cortex (mPFC) that are thought to underlie addiction pathology. Finally, we make the case that activity in mPFC circuits is a critical regulator of the mesolimbic dopamine system's ability to respond to volatile solvents like toluene. Overall, this review provides evidence that volatile solvents have high abuse liability because of their selective effects on critical nodes of the addiction neurocircuitry, and underscores the need for more research into how these compounds induce adaptations in neural circuits that underlie addiction pathology.

Neural and psychological mechanisms underlying compulsive drug seeking habits and drug memories--indications for novel treatments of addiction.

Science.gov (United States)

Everitt, Barry J

2014-07-01

This review discusses the evidence for the hypothesis that the development of drug addiction can be understood in terms of interactions between Pavlovian and instrumental learning and memory mechanisms in the brain that underlie the seeking and taking of drugs. It is argued that these behaviours initially are goal-directed, but increasingly become elicited as stimulus-response habits by drug-associated conditioned stimuli that are established by Pavlovian conditioning. It is further argued that compulsive drug use emerges as the result of a loss of prefrontal cortical inhibitory control over drug seeking habits. Data are reviewed that indicate these transitions from use to abuse to addiction depend upon shifts from ventral to dorsal striatal control over behaviour, mediated in part by serial connectivity between the striatum and midbrain dopamine systems. Only some individuals lose control over their drug use, and the importance of behavioural impulsivity as a vulnerability trait predicting stimulant abuse and addiction in animals and humans, together with consideration of an emerging neuroendophenotype for addiction are discussed. Finally, the potential for developing treatments for addiction is considered in light of the neuropsychological advances that are reviewed, including the possibility of targeting drug memory reconsolidation and extinction to reduce Pavlovian influences on drug seeking as a means of promoting abstinence and preventing relapse. © 2014 The Author. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Brain Phosphorus Magnetic Resonance Spectroscopy Imaging of Sleep Homeostasis and Restoration in Drug Dependence

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George H. Trksak

2007-01-01

Full Text Available Numerous reports have documented a high occurrence of sleep difficulties in drug-dependent populations, prompting researchers to characterize sleep profiles and physiology in drug abusing populations. This mini-review examines studies indicating that drug-dependent populations exhibit alterations in sleep homeostatic and restoration processes in response to sleep deprivation. Sleep deprivation is a principal sleep research tool that results in marked physiological challenge, which provides a means to examine sleep homeostatic processes in response to extended wakefulness. A report from our laboratory demonstrated that following recovery sleep from sleep deprivation, brain high-energy phosphates particularly beta–nucleoside triphosphate (beta-NTP are markedly increased as measured with phosphorus magnetic resonance spectroscopy (MRS. A more recent study examined the effects of sleep deprivation in opiate-dependent methadone-maintained (MM subjects. The study demonstrated increases in brain beta-NTP following recovery sleep. Interestingly, these increases were of a markedly greater magnitude in MM subjects compared to control subjects. A similar study examined sleep deprivation in cocaine-dependent subjects demonstrating that cocaine-dependent subjects exhibit greater increases in brain beta-NTP following recovery sleep when compared to control subjects. The studies suggest that sleep deprivation in both MM subjects and cocaine-dependent subjects is characterized by greater changes in brain ATP levels than control subjects. Greater enhancements in brain ATP following recovery sleep may reflect a greater disruption to or impact of sleep deprivation in drug dependent subjects, whereby sleep restoration processes may be unable to properly regulate brain ATP and maintain brain high-energy equilibrium. These studies support the notion of a greater susceptibility to sleep loss in drug dependent populations. Additional sleep studies in drug abusing

Association between Experience of Child Abuse and Severity of Drug Addiction Measured by the Addiction Severity Index among Japanese Drug-Dependent Patients

Directory of Open Access Journals (Sweden)

Yasukazu Ogai

2015-03-01

Full Text Available The aim of the present study was to clarify the association between child abuse experiences and drug addiction severity among Japanese drug-dependent patients using the Addiction Severity Index-Japanese version (ASI-J. One hundred and eleven inpatients and outpatients with drug dependence participated in the study. Some of the questions on the ASI-J asked about lifetime experiences of abuse. A higher percentage of female participants experienced child abuse compared with male participants. Male participants who experienced child abuse (MEA had a significantly higher severity of drug use than men who did not experience it (MNEA. Female participants who experienced child abuse (FEA had significantly more serious problems in family/social relationships than female participants who did not experience it (FNEA. Patients in the MEA group were arrested less frequently for drug charges, experienced more serious problems with their fathers, and experienced more severe anxiety in their lifetime compared with the MNEA group. The FEA group experienced more serious troubles with their sexual partners, close friends, and families and experienced more severe psychiatric problems in their lifetime compared with the FNEA group. These results suggest gender differences in the problems experienced by drug-dependent patients with child abuse experiences, and gender-specific interventions may be more effective in treating their drug dependence.

Biological basis of sex differences in drug abuse: preclinical and clinical studies.

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Lynch, Wendy J; Roth, Megan E; Carroll, Marilyn E

2002-11-01

The recent focus on drug abuse in women has brought attention to numerous differences between women and men. In this review, we discuss both preclinical and clinical findings of sex differences in drug abuse as well as mechanisms that may underlie these differences. Recent evidence suggests that the progression to dependence and abuse may differ between women and men; thus, different prevention and treatment strategies may be required. Similar sex differences in drug sensitivity and self-administration have been reported in laboratory animal studies. Females appear to be more vulnerable than males to the reinforcing effects of psychostimulants, opiates, and nicotine during many phases of the addiction process (e.g. acquisition, maintenance, dysregulation-escalation, relapse). Male and female animals differ in their behavioral, neurological, and pharmacological responses to drugs. Although the role of sex in the mechanisms of drug action remains unclear, preclinical and clinical studies indicate that ovarian hormones, particularly estrogen, play a role in producing sex differences in drug abuse. Future research is necessary to provide information on how to design more effective drug abuse treatment programs and resources that are sex specific.

38 CFR 17.82 - Contracts for outpatient services for veterans with alcohol or drug dependence or abuse...

Science.gov (United States)

2010-07-01

... services for veterans with alcohol or drug dependence or abuse disabilities. 17.82 Section 17.82 Pensions... Agencies § 17.82 Contracts for outpatient services for veterans with alcohol or drug dependence or abuse... sponsored residents to adjust to and maintain freedom from dependence on or involvement with alcohol or drug...

Substance abuse and pharmacy practice: what the community pharmacist needs to know about drug abuse and dependence

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Tommasello Anthony C

2004-04-01

Full Text Available Abstract Pharmacists, the most accessible of health care professionals, are well positioned to help prevent and treat substance use disorders and should prepare themselves to perform these functions. New research improves our knowledge about the pharmacological and behavioral risks of drug abuse, supports the clinical impression that drug dependence is associated with long-lasting neurochemical changes, and demonstrates effective pharmacological treatments for certain kinds of drug dependencies. The profession is evolving. Pharmacists are engaging in new practice behaviors such as helping patients manage their disease states. Collaborative practice agreements and new federal policies set the stage for pharmacists to assist in the clinical management of opioid and other drug dependencies. Pharmacists need to be well informed about issues related to addiction and prepared not only to screen, assess, and refer individual cases and to collaborate with physicians caring for chemically dependent patients, but also to be agents of change in their communities in the fight against drug abuse. At the end of this article the pharmacist will be better able to: 1. Explain the disease concept of chemical dependence 2. Gather the information necessary to conduct a screen for chemical dependence 3. Inform patients about the treatment options for chemical dependence 4. Locate resources needed to answer questions about the effects of common drugs of abuse (alcohol, marijuana, narcotics, "ecstasy", and cocaine 5. Develop a list of local resources for drug abuse treatment 6. Counsel parents who are concerned about drug use by their children 7. Counsel individuals who are concerned about drug use by a loved one. 8. Counsel individuals who are concerned about their own drug use

Neural correlates of stress-induced and cue-induced drug craving: influences of sex and cocaine dependence.

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Potenza, Marc N; Hong, Kwang-ik Adam; Lacadie, Cheryl M; Fulbright, Robert K; Tuit, Keri L; Sinha, Rajita

2012-04-01

Although stress and drug cue exposure each increase drug craving and contribute to relapse in cocaine dependence, no previous research has directly examined the neural correlates of stress-induced and drug cue-induced craving in cocaine-dependent women and men relative to comparison subjects. Functional MRI was used to assess responses to individualized scripts for stress, drug/alcohol cue and neutral-relaxing-imagery conditions in 30 abstinent cocaine-dependent individuals (16 women, 14 men) and 36 healthy recreational-drinking comparison subjects (18 women, 18 men). Significant three-way interactions between diagnostic group, sex, and script condition were observed in multiple brain regions including the striatum, insula, and anterior and posterior cingulate. Within women, group-by-condition interactions were observed involving these regions and were attributable to relatively increased regional activations in cocaine-dependent women during the stress and, to a lesser extent, neutral-relaxing conditions. Within men, group main effects were observed involving these same regions, with cocaine-dependent men demonstrating relatively increased activation across conditions, with the main contributions from the drug and neutral-relaxing conditions. In men and women, subjective drug-induced craving measures correlated positively with corticostriatal-limbic activations. In cocaine dependence, corticostriatal-limbic hyperactivity appears to be linked to stress cues in women, drug cues in men, and neutral-relaxing conditions in both. These findings suggest that sex should be taken into account in the selection of therapies in the treatment of addiction, particularly those targeting stress reduction.

38 CFR 17.80 - Alcohol and drug dependence or abuse treatment and rehabilitation in residential and...

Science.gov (United States)

2010-07-01

... dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. 17... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or abuse...

Antibody drug conjugates and bystander killing: is antigen-dependent internalisation required?

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Staudacher, Alexander H; Brown, Michael P

2017-12-05

Antibody drug conjugates (ADCs) employ the exquisite specificity of tumour-specific monoclonal antibodies (mAb) for the targeted delivery of highly potent cytotoxic drugs to the tumour site. The chemistry of the linker, which connects the drug to the mAb, determines how and when the drug is released from the mAb. This, as well as the chemistry of the drug, can dictate whether the drug can diffuse into surrounding cells, resulting in 'bystander killing'. Initially, any bystander killing mechanism of action of an ADC was understood to involve an essential sequence of steps beginning with surface antigen targeting, internalisation, intracellular linker cleavage, drug release, and diffusion of drug away from the targeted cell. However, recent studies indicate that, depending on the linker and drug combination, this mechanism may not be essential and ADCs can be cleaved extracellularly or via other mechanisms. In this minireview, we will examine the role of bystander killing by ADCs and explore the emerging evidence of how this can occur independently of internalisation.

Taste perception: Risk factor or protection for dependents during drug use cessation

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Carla Rosane Paz Arruda Teo

2014-08-01

Full Text Available The increase in appetite and, consequently, in body weight, evidenced in the majority of addicts under treatment, may be related to taste, since heavy drug use can lead to changes in taste buds. This study aimed to investigate the association between taste perception and nutritional status of drug addicts under treatment. The study was conducted in two therapeutic communities in the municipality of Chapecó, Santa Catarina state, with 39 male addicts over 18 years old. Primary data on weight and height were collected for assessment of nutritional status, and a taste acuity test was applied; also, secondary data were collected on age, length of stay, types of drugs used, and age of drug use onset, from the addicts’ records. It was possible to observe that 56.5% of dependents were at nutritional risk for being overweight. Taste acuity significantly differed for the basic tastes evaluated (p= 0.014, being higher for salty (94.9%, followed by sweet (89.7%, acid (79.5%, and bitter (38, 5% tastes, but it was not associated with the study variables. We conclude that the drug use cessation can have a similar effect to that of caloric deprivation on the taste acuity of dependents, interfering on excessive weight gain. However, it is suggested that the improvement of taste perception be oriented in the therapeutic setting, so that it becomes, in these conditions, a protection factor for dependents, strengthening them to overcome their condition of vulnerability.

Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

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Ahn, Woo-Young; Vassileva, Jasmin

2016-04-01

Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The impact of race, income, drug abuse and dependence on health insurance coverage among US adults.

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Wang, Nianyang; Xie, Xin

2017-06-01

Little is known about the impact of drug abuse/dependence on health insurance coverage, especially by race groups and income levels. In this study, we examine the disparities in health insurance predictors and investigate the impact of drug use (alcohol abuse/dependence, nicotine dependence, and illicit drug abuse/dependence) on lack of insurance across different race and income groups. To perform the analysis, we used insurance data (8057 uninsured and 28,590 insured individual adults) from the National Surveys on Drug Use and Health (NSDUH 2011). To analyze the likelihood of being uninsured we performed weighted binomial logistic regression analyses. The results show that the overall prevalence of lacking insurance was 19.6 %. However, race differences in lack of insurance exist, especially for Hispanics who observe the highest probability of being uninsured (38.5 %). Furthermore, we observe that the lowest income level bracket (annual income <$20,000) is associated with the highest likelihood of being uninsured (37.3 %). As the result of this investigation, we observed the following relationship between drug use and lack of insurance: alcohol abuse/dependence and nicotine dependence tend to increase the risk of lack of insurance for African Americans and whites, respectively; illicit drug use increases such risk for whites; alcohol abuse/dependence increases the likelihood of lack of insurance for the group with incomes $20,000-$49,999, whereas nicotine dependence is associated with higher probability of lack of insurance for most income groups. These findings provide some useful insights for policy makers in making decisions regarding unmet health insurance coverage.

The clinical implication of drug dependency in children and adults with inflammatory bowel disease: a review

DEFF Research Database (Denmark)

Duricova, Dana; Pedersen, Natalia; Lenicek, Martin

2011-01-01

Drug dependency in adult and paediatric patients with inflammatory bowel disease (IBD) is described and the significance of this response pattern in clinical practice discussed in this review. Dependent patients maintain remission while on the treatment, but they relapse shortly after drug...... corticosteroid dependency. Infliximab dependency was described in 42-66% of children and 29% of adults with Crohn's disease. The risk of surgery 50 and 40 months after treatment start was 10% and 23% in infliximab dependent children and adults, respectively. Maintenance of infliximab in dependent patients...... was suggested to postpone if not avoid the need of surgery. Lastly, mesalazine dependency was identified in 23% of adults with Crohn's disease. These patients were characterized by mild disease course and lower surgical risk compared to non-responders to mesalazine (32 vs. 61%). Identification of drug...

Role of the limbic system in dependence on drugs.

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Rodríguez de Fonseca, F; Navarro, M

1998-08-01

The limbic system is a group of structurally and functionally related areas of the brain that provides the anatomical substrate for emotions and motivated behaviour, including the circuitry for the stress response and reward-related events. This system is strongly implicated in drug abuse from the pleasure and/or positive side associated with acute exposure to the dysphoria and craving associated with withdrawal. The contribution of the main cortical and subcortical elements of the limbic system to drug dependence is briefly reviewed in the present work with a focus on the role of the extended amygdala and its connections as well as on the peripheral feedback signals mediated by adrenal glucocorticoids. The elucidation of the neuroadaptive responses of the limbic system to chronic drug exposure will undoubtedly help to design rational strategies for the treatment of addiction.

Use-Dependent Inhibition of Synaptic Transmission by the Secretion of Intravesicularly Accumulated Antipsychotic Drugs

DEFF Research Database (Denmark)

Tischbirek, Carsten H.; Wenzel, Eva M.; Zheng, Fang

2012-01-01

Tischbirek et al. find that weak-base antipsychotic drugs are accumulated in synaptic vesicles and are secreted upon exocytosis, leading to increased extracellular drug concentrations following neuronal activity. The secretion of the drugs in turn inhibits synaptic transmission in a use-dependent...

Drug ratio-dependent antagonism: a new category of multidrug resistance and strategies for its circumvention.

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Harasym, Troy O; Liboiron, Barry D; Mayer, Lawrence D

2010-01-01

A newly identified form of multidrug resistance (MDR) in tumor cells is presented, pertaining to the commonly encountered resistance of cancer cells to anticancer drug combinations at discrete drug:drug ratios. In vitro studies have revealed that whether anticancer drug combinations interact synergistically or antagonistically can depend on the ratio of the combined agents. Failure to control drug ratios in vivo due to uncoordinated pharmacokinetics could therefore lead to drug resistance if tumor cells are exposed to antagonistic drug ratios. Consequently, the most efficacious drug combination may not occur at the typically employed maximum tolerated doses of the combined drugs if this leads to antagonistic ratios in vivo after administration and resistance to therapeutic effects of the drug combination. Our approach to systematically screen a wide range of drug ratios and concentrations and encapsulate the drug combination in a liposomal delivery vehicle at identified synergistic ratios represents a means to mitigate this drug ratio-dependent MDR mechanism. The in vivo efficacy of the improved agents (CombiPlex formulations) is demonstrated and contrasted with the decreased efficacy when drug combinations are exposed to tumor cells in vivo at antagonistic ratios.

a Comparison Between Chemically Dependent Mothers and Drug-Free Mothers: Lifestyle during the Perinatal Period

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Uskokovic, Lila Milica

This study compared maternal lifestyle variables pertinent to the perinatal period in groups of chemically dependent mothers and drug-free mothers. Twenty-nine cocaine -abusing mothers were compared to 29 drug-free mothers carefully matched on age, race, education, and primipara versus multipara status. The drug history of each chemically dependent woman was explicitly documented. The chemically dependent group was subdivided into two groups, mothers who abused cocaine and those who abused cocaine with concomitant opiate use. Each of these two subgroups was compared to its respective matched drug-free control group. Finally, a comparison was made between the two drug subgroups. All subjects were interviewed within 48 hours after delivery using the following measures: State-Trait Anxiety Inventory (A-State), Center for Epidemiologic Studies - Depression Scale, The Self-Esteem Scale, Maternal Adjustment and Maternal Attitude Questionnaire, The Neonatal Perception Inventory, The Psychiatric Epidemiology Research Interview Life Events Scale, Maternal Social Support Index, and Short Marital Adjustment Test. A t-test analysis revealed significant differences (p abused opiates with cocaine did not differ from their controls on depression and maternal adjustment and attitudes. No significant differences were obtained in the drug subgroup comparisons. These results identify increased life events and specific negative affect states that clinical intervention programs should address to assure the best possible outcome for chemically dependent mothers and their infants.

Benefits of Exercise for the Quality of Life of Drug-Dependent Patients.

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Giménez-Meseguer, Jorge; Tortosa-Martínez, Juan; de los Remedios Fernández-Valenciano, María

2015-01-01

This study combined quantitative and qualitative research methods to evaluate quality-of-life changes in drug-dependent patients after participation in a group-based exercise program. Quality of life (SF-36) and physical fitness (six-minute Walk Test, Timed Get Up and Go Test, and Chair Stand Test) were quantitatively determined in a group (n=37) of drug-dependent patients before and after a 12-week group exercise program (n=18) or routine care (n=19). Additionally, in-depth interviews were conducted at the end of the program with a subsample of 11 participants from the exercise group. Quantitative results showed improvements in fitness and different aspects of quality of life, such as physical function, mental health, vitality, social function, and general health perception. Qualitative results showed specific physical benefits (decreased injuries and muscle pain, decreased weight, and increased vitality with improvement in activities of daily living), psychological benefits (forgetting about everyday problems, improved mood, decreased stress and anxiety), social benefits, and a reduction in craving. The results of this study provide insight into the importance of exercise for the quality of life and recovery process of drug-dependent patients.

Mobile phone messaging for illicit drug and alcohol dependence: A systematic review of the literature.

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Tofighi, Babak; Nicholson, Joseph M; McNeely, Jennifer; Muench, Frederick; Lee, Joshua D

2017-07-01

Mobile phone use has increased dramatically and concurrent with rapid developments in mobile phone-based health interventions. The integration of text messaging interventions promises to optimise the delivery of care for persons with substance dependence with minimal disruption to clinical workflows. We conducted a systematic review to assess the acceptability, feasibility and clinical impact of text messaging interventions for persons with illicit drug and alcohol dependence. Studies were required to evaluate the use of text messaging as an intervention for persons who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition criterion for a diagnosis of illicit drug and/or alcohol dependence. Authors searched for articles published to date in MEDLINE (pubmed.gov), the Cochrane Library, EMBASE, CINAHL, Google Scholar and PsychINFO. Eleven articles met the search criteria for this review and support the acceptability and feasibility of text messaging interventions for addressing illicit drug and alcohol dependence. Most studies demonstrated improved clinical outcomes, medication adherence and engagement with peer support groups. Text messaging interventions also intervened on multiple therapeutic targets such as appointment attendance, motivation, self-efficacy, relapse prevention and social support. Suggestions for future research are described, including intervention design features, clinician contact, privacy measures and integration of behaviour change theories. Text messaging interventions offer a feasible platform to address a range of substances (i.e. alcohol, methamphetamine, heroin and alcohol), and there is increasing evidence supporting further larger-scale studies. [Tofighi B, Nicholson JM, McNeely J, Muench F, Lee JD. Mobile phone messaging for illicit drug and alcohol dependence: A systematic review of the literature. Drug Alcohol Rev 2017;36:477-491]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Neuronal extracellular signal-regulated kinase (ERK activity as marker and mediator of alcohol and opioid dependence

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Eva R. Zamora-Martinez

2014-03-01

Full Text Available Early pioneering work in the field of biochemistry identified phosphorylation as a crucial post-translational modification of proteins with the ability to both indicate and arbitrate complex physiological processes. More recent investigations have functionally linked phosphorylation of extracellular signal-regulated kinase (ERK to a variety of neurophysiological mechanisms ranging from acute neurotransmitter action to long-term gene expression. ERK phosphorylation serves as an intracellular bridging mechanism that facilitates neuronal communication and plasticity. Drugs of abuse, including alcohol and opioids, act as artificial yet powerful rewards that impinge upon natural reinforcement processes critical for survival. The graded progression from initial exposure to addiction (or substance dependence is believed to result from drug- and drug context-induced adaptations in neuronal signaling processes across brain reward and stress circuits following excessive drug use. In this regard, commonly abused drugs as well as drug-associated experiences are capable of modifying the phosphorylation of ERK within central reinforcement systems. In addition, chronic drug and alcohol exposure may drive ERK-regulated epigenetic and structural alterations that underlie a long-term propensity for escalating drug use. Under the influence of such a neurobiological vulnerability, encountering drug-associated cues and contexts can produce subsequent alterations in ERK signaling that drive relapse to drug and alcohol seeking. Current studies are determining precisely which molecular and regional ERK phosphorylation-associated events contribute to the addiction process, as well as which neuroadaptations need to be targeted in order to return dependent individuals to a healthy state.

Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization.

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Cullen, Patrick K; Gilman, T Lee; Winiecki, Patrick; Riccio, David C; Jasnow, Aaron M

2015-10-01

Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization. Copyright © 2015 Elsevier Inc. All rights reserved.

Cancer drug addiction is relayed by an ERK2-dependent phenotype switch.

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Kong, Xiangjun; Kuilman, Thomas; Shahrabi, Aida; Boshuizen, Julia; Kemper, Kristel; Song, Ji-Ying; Niessen, Hans W M; Rozeman, Elisa A; Geukes Foppen, Marnix H; Blank, Christian U; Peeper, Daniel S

2017-10-12

Observations from cultured cells, animal models and patients raise the possibility that the dependency of tumours on the therapeutic drugs to which they have acquired resistance represents a vulnerability with potential applications in cancer treatment. However, for this drug addiction trait to become of clinical interest, we must first define the mechanism that underlies it. We performed an unbiased CRISPR-Cas9 knockout screen on melanoma cells that were both resistant and addicted to inhibition of the serine/threonine-protein kinase BRAF, in order to functionally mine their genome for 'addiction genes'. Here we describe a signalling pathway comprising ERK2 kinase and JUNB and FRA1 transcription factors, disruption of which allowed addicted tumour cells to survive on treatment discontinuation. This occurred in both cultured cells and mice and was irrespective of the acquired drug resistance mechanism. In melanoma and lung cancer cells, death induced by drug withdrawal was preceded by a specific ERK2-dependent phenotype switch, alongside transcriptional reprogramming reminiscent of the epithelial-mesenchymal transition. In melanoma cells, this reprogramming caused the shutdown of microphthalmia-associated transcription factor (MITF), a lineage survival oncoprotein; restoring this protein reversed phenotype switching and prevented the lethality associated with drug addiction. In patients with melanoma that had progressed during treatment with a BRAF inhibitor, treatment cessation was followed by increased expression of the receptor tyrosine kinase AXL, which is associated with the phenotype switch. Drug discontinuation synergized with the melanoma chemotherapeutic agent dacarbazine by further suppressing MITF and its prosurvival target, B-cell lymphoma 2 (BCL-2), and by inducing DNA damage in cancer cells. Our results uncover a pathway that underpins drug addiction in cancer cells, which may help to guide the use of alternating therapeutic strategies for enhanced

Drug Use, Dependence, and Addiction at a British Columbia University: Good News and Bad News.

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Alexander, Bruce K.

1985-01-01

Two studies of perceived and actual drug use at Simon Fraser University found students estimating greater drug use among friends than for themselves, but 31 percent reported dependence and 5 percent reported current addiction, especially to caffeine and nicotine. An approach to drug abuse focusing on familiar substances is recommended. (MSE)

Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.

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Ersche, Karen D; Bullmore, Edward T; Craig, Kevin J; Shabbir, Shaila S; Abbott, Sanja; Müller, Ulrich; Ooi, Cinly; Suckling, John; Barnes, Anna; Sahakian, Barbara J; Merlo-Pich, Emilio V; Robbins, Trevor W

2010-06-01

There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges. To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D(2)/D(3) receptor antagonist and agonist challenges. Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging. Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England. Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18). Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions. Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire. Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups. Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation

Definition of drug resistance of Mycobacterium tuberculosis to antituberculosis drugs in patients with multidrugresistant tuberculosis and TB with extremely drug resistant depending on the case of the disease

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Kryzhanovsky D.G.

2014-11-01

Full Text Available There was studied the profile of drug resistance to the main (I line and reserve (II line antituberculosis drugs in patients with MDR and XDR tuberculosis, depending of the case of the disease. According to the randomized retrospective research 200 patients with MDR and XDR tuberculosis, who received treatment in the clinic of hospital Municipal institution «Dnipropetrovsk rigional clinical association «Phthisiology» Dnipropetrovsk regional Council» during the period 2010 – 2012 were involved. Data about patients contained the data on a case of the disease and the results of the test of drug sensitivity to MBT. XDR – TB was revealed in 7.5% of patients with MDR tuberculosis. In patients with MDR tuberculosis as compared with patients with XDR tuberculosis «new cases» were diagnosed in 19.5% against 18.5% (p <0.05. In patients with MDR tuberculosis and with XDR tuberculosis resistance to the antituberculosis drug more commonly developed to S - 88.5%, E - 55% and Z - 24%. The presence of MDR-TB and XDR-TB prevails in patients, who underwent previous courses of treatment with anti-TB drugs in case history as compared with patients with «new cases» of treatment. The development of resistance to anti-TB drugs depends on the availability of these drugs in the previous treatment regimens.

38 CFR 17.83 - Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment and...

Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition.

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Falgreen, Steffen; Laursen, Maria Bach; Bødker, Julie Støve; Kjeldsen, Malene Krag; Schmitz, Alexander; Nyegaard, Mette; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

2014-06-05

In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves' dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological

Dependent Prior: An Application in Spinal Anaesthesia Drug Therapy on SBP in Cesarean patients.

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Atanu Bhattacharjee

2013-12-01

Full Text Available Cesarean section is widely used operation procedure in the world. The regional anesthesia is preferred than general anesthesia. The risk of fetus is higher in general than in regional anesthesia. The drug treatment effect on regional anesthesia plays an important role to control the systolic blood pressure (SBP during the surgery. The goal of this work is to know the effective drug to control the SBP among cesarean anesthetic patients. The dependent prior with Bayesian approach is applied in the binary response data set. The secondary data in anesthesia has been applied to compare the two drug treatments, viz. (1 Phenylephrine and (2 Ephedrine, in cesarean patients with spinal anesthesia. In both drug groups the mean of SBP has been found controlled over the duration of the surgery. No rapid changes of SBP level among the patients are observed. At the end of study it is found that the means of SBP cesarean anesthetic patients are found higher in Phenylephrine group. The Bayesian dependent prior is found to offer effective tool for drug treatment effect comparison. The drug treatment effect Ephedrine is found to be more effective to control the SBP over the duration of surgery than Phenylephrine.

Sodium dependent multivitamin transporter (SMVT): a potential target for drug delivery.

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Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Mitra, Ashim K

2012-06-01

Sodium dependent multivitamin transporter (SMVT; product of the SLC5A6 gene) is an important transmembrane protein responsible for translocation of vitamins and other essential cofactors such as biotin, pantothenic acid and lipoic acid. Hydropathy plot (Kyte-Dolittle algorithm) revealed that human SMVT protein consists of 635 amino acids and 12 transmembrane domains with both amino and carboxyl termini oriented towards the cytoplasm. SMVT is expressed in various tissues such as placenta, intestine, brain, liver, lung, kidney, cornea, retina and heart. This transporter displays broad substrate specificity and excellent capacity for utilization in drug delivery. Drug absorption is often limited by the presence of physiological (epithelial tight junctions), biochemical (efflux transporters and enzymatic degradation) and chemical (size, lipophilicity, molecular weight, charge etc.) barriers. These barriers may cause many potential therapeutics to be dropped from the preliminary screening portfolio and subsequent entry into the market. Transporter targeted delivery has become a powerful approach to deliver drugs to target tissues because of the ability of the transporter to translocate the drug to intracellular organelles at a higher rate. This review highlights studies employing SMVT transporter as a target for drug delivery to improve bioavailability and investigate the feasibility of developing SMVT targeted drug delivery systems.

Relationship between drug dreams, affect, and craving during treatment for substance dependence.

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Tanguay, Hélène; Zadra, Antonio; Good, Daniel; Leri, Francesco

2015-01-01

To explore the relationship between occurrence of drug dreams (DDs) and daytime negative affect and drug craving during the course of a 5-week treatment program for substance dependence. Using the dream journal methodology, 86 participants reported occurrence of dreams, dream content, and ratings of affect and drug craving. The relationships between the experience of DD, dream content ("active" vs "passive"), and affect and craving were analyzed using mixed model methods. The experience of DD was associated with higher levels of negative affect (P < 0.001) and craving (P < 0.001). The occurrence of DD did not decrease significantly over the 5 weeks of the study. Cocaine/crack users reported a higher occurrence of DD (P < 0.05) than the other drug groups (opiates and alcohol), and DD involving "active" drug use was associated with larger (P < 0.05) changes in negative affect. These results are consistent with the hypothesis that DD can act as drug-conditioned stimuli to elevate negative affect and craving in abstaining individuals. Although correlational, such findings support the implementation of psychological and pharmacological interventions aimed at minimizing the impact of DD on individuals in recovery from drug addiction.

Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence.

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Becker, Alena; Kirsch, Martina; Gerchen, Martin Fungisai; Kiefer, Falk; Kirsch, Peter

2017-05-01

According to prevailing neurobiological theories of addiction, altered function in neural reward circuitry is a central mechanism of alcohol dependence. Growing evidence postulates that the ventral striatum (VS), as well as areas of the prefrontal cortex, contribute to the increased incentive salience of alcohol-associated cues, diminished motivation to pursue non-drug rewards and weakened strength of inhibitory cognitive control, which are central to addiction. The present study aims to investigate the neural response and functional connectivity underlying monetary, non-drug reward processing in alcohol dependence. We utilized a reward paradigm to investigate the anticipation of monetary reward in 32 alcohol-dependent inpatients and 35 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation and connectivity. Alcohol-dependent patients showed increased activation of the VS during anticipation of monetary gain compared with healthy controls. Generalized psychophysiological interaction analyses revealed decreased functional connectivity between the VS and the dorsolateral prefrontal cortex in alcohol dependent patients relative to controls. Increased activation of the VS and reduced frontostriatal connectivity were associated with increased craving. These findings provide evidence that alcohol dependence is rather associated with disrupted integration of striatal and prefrontal processes than with a global reward anticipation deficit. © 2016 Society for the Study of Addiction.

Adolescent neurocognitive development, self-regulation, and school-based drug use prevention.

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Pokhrel, Pallav; Herzog, Thaddeus A; Black, David S; Zaman, Adnin; Riggs, Nathaniel R; Sussman, Steve

2013-06-01

Adolescence is marked by several key development-related changes, including neurocognitive changes. Cognitive abilities associated with self-regulation are not fully developed until late adolescence or early adulthood whereas tendencies to take risks and seek thrilling and novel experience seem to increase significantly throughout this phase, resulting in a discrepancy between increased susceptibility to poor regulation and lower ability to exercise self-control. Increased vulnerability to drug use initiation, maintenance, and dependence during adolescence may be explained based on this imbalance in the self-regulation system. In this paper, we highlight the relevance of schools as a setting for delivering adolescent drug use prevention programs that are based on recent findings from neuroscience concerning adolescent brain development. We discuss evidence from school-based as well as laboratory research that suggests that suitable training may improve adolescents' executive brain functions that underlie self-regulation abilities and, as a result, help prevent drug use and abuse. We note that considerable further research is needed in order (1) to determine that self-regulation training has effects at the neurocognitive level and (2) to effectively incorporate self-regulation training based on neuropsychological models into school-based programming.

Identifying kinase dependency in cancer cells by integrating high-throughput drug screening and kinase inhibition data.

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Ryall, Karen A; Shin, Jimin; Yoo, Minjae; Hinz, Trista K; Kim, Jihye; Kang, Jaewoo; Heasley, Lynn E; Tan, Aik Choon

2015-12-01

Targeted kinase inhibitors have dramatically improved cancer treatment, but kinase dependency for an individual patient or cancer cell can be challenging to predict. Kinase dependency does not always correspond with gene expression and mutation status. High-throughput drug screens are powerful tools for determining kinase dependency, but drug polypharmacology can make results difficult to interpret. We developed Kinase Addiction Ranker (KAR), an algorithm that integrates high-throughput drug screening data, comprehensive kinase inhibition data and gene expression profiles to identify kinase dependency in cancer cells. We applied KAR to predict kinase dependency of 21 lung cancer cell lines and 151 leukemia patient samples using published datasets. We experimentally validated KAR predictions of FGFR and MTOR dependence in lung cancer cell line H1581, showing synergistic reduction in proliferation after combining ponatinib and AZD8055. KAR can be downloaded as a Python function or a MATLAB script along with example inputs and outputs at: http://tanlab.ucdenver.edu/KAR/. aikchoon.tan@ucdenver.edu. Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Medication development of ibogaine as a pharmacotherapy for drug dependence.

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Mash, D C; Kovera, C A; Buck, B E; Norenberg, M D; Shapshak, P; Hearn, W L; Sanchez-Ramos, J

1998-05-30

The potential for deriving new psychotherapeutic medications from natural sources has led to renewal interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and cocaine. Anecdotal reports attest that a single dose of ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of ibogaine for treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of ibogaine in humans are assessed by analyzing the concentration-time data of ibogaine and its desmethyl metabolite (noribogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.

Hypocretin/Orexin and Plastic Adaptations Associated with Drug Abuse.

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Baimel, Corey; Borgland, Stephanie L

Dopamine neurons in the ventral tegmental area (VTA) are a critical part of the neural circuits that underlie reward learning and motivation. Dopamine neurons send dense projections throughout the brain and recent observations suggest that both the intrinsic properties and the functional output of dopamine neurons are dependent on projection target and are subject to neuromodulatory influences. Lateral hypothalamic hypocretin (also termed orexin) neurons project to the VTA and contain both hypocretin and dynorphin peptides in the same dense core vesicles suggesting they may be co-released. Hypocretin peptides act at excitatory G αq protein-coupled receptors and dynorphin acts at inhibitory G αi/o protein-coupled receptors, which are both expressed on subpopulations of dopamine neurons. This review describes a role for neuromodulation of dopamine neurons and the influence on motivated behaviour in response to natural and drug rewards.

Overlooked and underestimated? Problematic alcohol use in clients recovering from drug dependence.

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Staiger, Petra K; Richardson, Ben; Long, Caroline M; Carr, Victoria; Marlatt, G Alan

2013-07-01

Despite recognition of the harms related to alcohol misuse and its potential to interfere substantially with sustained recovery from drug dependency, research evaluating drug treatment outcomes has not addressed the issue comprehensively. It has been overlooked possibly because treatment research has been framed according to the primary drug of choice, rather than investigating the interactions between different combinations of drugs and/or alcohol use. This paper reports on a systematic review investigating whether concurrent alcohol use could impede recovery from illicit drug use in two potential ways: first, alcohol could become a substitute addiction and/or secondly, alcohol misuse post-treatment may place an individual at risk for relapse to their primary drug problem. A systematic search of four relevant databases was undertaken to identify peer-reviewed, quantitative drug treatment outcome studies that reported alcohol use pre-, post-treatment and follow-up. The search revealed 567 papers, of which 13 were assessed as fulfilling the key inclusion criteria.The review indicated inconsistent and therefore inconclusive support for the substitution hypothesis. However, the data revealed consistent support for the hypothesis that alcohol use increases relapse to drug use. (i) The potential negative impact of alcohol misuse on drug treatment outcomes remains under-researched and overlooked; (ii) alcohol consumption post-drug treatment may increase the likelihood that an individual will relapse to their primary drug; (ii) existing evidence regarding the substitution hypothesis is inconclusive, although there was an indication that a subgroup of participants will be vulnerable to alcohol becoming the primary addiction instead of drugs. We argue that future drug treatment outcome studies need to include detailed analysis of the influence of alcohol use pre- and post-drug treatment. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Willingness to treat drug dependence and depression: comparisons of future health professionals

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Ríos-Bedoya CF

2011-03-01

Full Text Available Brian K Ahmedani1,2, Sheryl Pimlott Kubiak2, Carlos F Rios-Bedoya3, Maureen Mickus4, James C Anthony51Center for Health Services Research, Henry Ford Health System, Detroit, MI, USA; 2School of Social Work, Michigan State University, East Lansing, MI, USA; 3Department of Family Medicine, Michigan State University, East Lansing, MI, USA; 4Occupational Therapy, Western Michigan University, Kalamazoo, MI, USA; 5Department of Epidemiology, Michigan State University, East Lansing, MI, USAPurpose: Stigma-related feelings, including degree of enthusiasm and willingness to work with alcohol, drug, and mental disorder (ADM patients, as well as anticipated success in such work, will be required for the United States to be successful in its new initiatives for ADM screening, brief intervention, and effective referral to treatment and rehabilitation services (SBIRT. This study investigates students of medicine and social work with respect to their stigma-related feelings and degree of enthusiasm or willingness to treat patients affected by alcohol dependence, nicotine dependence, or major depression. Inference is strengthened by an anonymous online survey approach, with use of randomized reinforcers to gain at least partial experimental control of nonparticipation biases that otherwise are present in student survey data.Material and methods: All students on required course rosters were asked to participate in a two-part in-class and online assessment; 222 participated, with a gradient of participation induced via randomly drawn reinforcers for online survey participation. Between-group comparisons were made with a multivariate generalized linear model and generalized estimating equations approach that adjusts for covariates.Results: Medical and social work students did not differ from each other with respect to their willingness to treat patients affected by major depression, alcohol dependence, or nicotine dependence, but together were less willing to

High Prognostic Specificity of Antisocial Personality Disorder in Patients with Drug Dependence

DEFF Research Database (Denmark)

Fridell, Mats; Hesse, Morten; Johnson, Eva

2006-01-01

personality disorder (ASPD) at intake was associated with incarceration, continuous drug use, dependence on welfare support, and fulfilling criteria of adult ASPD at follow-up. Regardless of ASPD status, a decline was seen in drug-related convictions, but subjects with ASPD were found to continue to commit......A sample of 125 consecutive patients from a Swedish detoxification unit were followed up at five years. Register data on criminal behavior were retrieved for 99% of all subjects, including those who were deceased at follow-up, and 76%of living subjects were interviewed. A diagnosis of antisocial...

Drug Addiction and DNA Modifications.

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Brown, Amber N; Feng, Jian

2017-01-01

Drug addiction is a complex disorder which can be influenced by both genetic and environmental factors. Research has shown that epigenetic modifications can translate environmental signals into changes in gene expression, suggesting that epigenetic changes may underlie the causes and possibly treatment of substance use disorders. This chapter will focus on epigenetic modifications to DNA, which include DNA methylation and several recently defined additional DNA epigenetic changes. We will discuss the functions of DNA modifications and methods for detecting them, followed by a description of the research investigating the function and consequences of drug-induced changes in DNA methylation patterns. Understanding these epigenetic changes may provide us translational tools for the diagnosis and treatment of addiction in the future.

Neural Correlates of Drug-Related Attentional Bias in Heroin Dependence

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Qinglin Zhao

2018-01-01

Full Text Available The attention of drug-dependent persons tends to be captured by stimuli associated with drug consumption. This involuntary cognitive process is considered as attentional bias (AB. AB has been hypothesized to have causal effects on drug abuse and drug relapse, but its underlying neural mechanisms are still unclear. This study investigated the neural basis of AB in abstinent heroin addicts (AHAs, combining event-related potential (ERP analysis and source localization techniques. Electroencephalography data were collected in 21 abstinent heroin addicts and 24 age- and gender-matched healthy controls (HCs during a dot-probe task. In the task, a pair of drug-related image and neutral image was presented randomly in left and right side of the cross fixation, followed by a dot probe replacing one of the images. Behaviorally, AHAs had shorter reaction times (RTs for the congruent condition compared to the incongruent condition, whereas this was not the case in the HCs. This finding demonstrated the presence of AB towards drug cues in AHAs. Furthermore, the image-evoked ERPs in AHAs had significant shorter P1 latency compared to HCs, as well as larger N1, N2, and P2 amplitude, suggesting that drug-related stimuli might capture attention early and overall require more attentional resources in AHAs. The target-related P3 had significantly shorter latency and lower amplitude in the congruent than incongruent condition in AHAs compared to HCs. Moreover, source localization of ERP components revealed increased activity for AHAs as compared to HCs in the dorsal posterior cingulate cortex (dPCC, superior parietal lobule and inferior frontal gyrus (IFG for image-elicited responses, and decreased activity in the occipital and the medial parietal lobes for target-elicited responses. Overall, the results of our study confirmed that AHAs may exhibit AB in drug-related contexts, and suggested that the bias might be related to an abnormal neural activity, both in

Current Trends of Drug Resistance Patterns of Acinetobacter baumannii Infection in Blood Transfusion-dependent Thalassemia Patients.

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Almani, Suhail Ahmed; Naseer, Ali; Maheshwari, Sanjay Kumar; Maroof, Pir; Naseer, Raza; Khoharo, Haji Khan

2017-01-01

The present study aimed to evaluate the current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients. This study was a cross sectional study, conducted at the Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad, Sindh, Pakistan from October 2014 to January 2016. Of 921 blood samples, A. baumannii strains were isolated from 100 blood samples. Blood samples were processed for the isolation, identification, and drugs sensitivity as per the Clinical and Laboratory Standards Institute. A. baumannii strains were identified by microbiological methods and Gram's staining. API 20 E kit (Biomeriuex, USA) was also used for identification. Data were analyzed on Statisti × 8.1 (USA). Mean ± standard deviation age was 11.5 ± 2.8 years. Nearly 70% were male and 30% were female ( P = 0.0001). Of 921 blood transfusion-dependent thalassemia patients, 100 (10.8%) patients showed growth of A. baumannii . Drug resistance was observed against the ceftazidime, cefixime, cefepime, imipenem, meropenem, amikacin, minocycline, tigecycline, and tazocin except for the colistin. The present study reports drug-resistant A. baumannii in blood transfusion-dependent thalassemia patients. National multicenter studies are recommended to estimate the size of the problem.

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

Directory of Open Access Journals (Sweden)

Liliana Basso Musso

2011-06-01

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

The Effect of Group Therapy With Transactional Analysis Approach on Emotional Intelligence, Executive Functions and Drug Dependency.

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Forghani, Masoomeh; Ghanbari Hashem Abadi, Bahram Ali

2016-06-01

The aim of the present study was to evaluate the effect of group psychotherapy with transactional analysis (TA) approach on emotional intelligence (EI), executive functions and substance dependency among drug-addicts at rehabilitation centers in Mashhad city, Iran, in 2013. In this quasi-experimental study with pretest, posttest, case- control stages, 30 patients were selected from a rehabilitation center and randomly divided into two groups. The case group received 12 sessions of group psychotherapy with transactional analysis approach. Then the effects of independent variable (group psychotherapy with TA approach) on EI, executive function and drug dependency were assessed. The Bar-on test was used for EI, Stroop test for measuring executive function and morphine test, meth-amphetamines and B2 test for evaluating drug dependency. Data were analyzed using multifactorial covariance analysis, Levenes' analysis, MANCOVA, t-student and Pearson correlation coefficient tests t with SPSS software. Our results showed that group psychotherapy with the TA approach was effective in improving EI, executive functions and decreasing drug dependency (P addicts and prevents addiction recurrence by improving the coping capabilities and some mental functions of the subjects. However, there are some limitations regarding this study including follow-up duration and sample size.

Persistence of drug use during imprisonment: relationship of drug type, recency of use and severity of dependence to use of heroin, cocaine and amphetamine in prison.

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Strang, John; Gossop, Michael; Heuston, Joan; Green, John; Whiteley, Christopher; Maden, Anthony

2006-08-01

To investigate the persistence of use of heroin, cocaine and amphetamine drugs during imprisonment, and to identify factors associated with increased levels of persistence. The use of heroin, cocaine and amphetamine by current prison inmates has been examined and, in particular, the relationship between drug use within prison and the type of drug used prior to imprisonment, recency of use and severity of dependence. A randomly selected sample of 1009 adult male prisoners in 13 prisons in England and Wales during 1994/95; structured confidential interviews conducted by independent research staff. Enquiry about prior use of heroin, cocaine or amphetamine focused on three time-periods (ever, last year and last month pre-prison) and the use of these drugs during the first month of imprisonment. A total of 557 (55%) of the 1009 prisoners had used previously one of the three drugs selected for study: 58% had used heroin, 69% cocaine and 75% amphetamine. More than half (59%; 327/557) had used these drugs in the month before the current imprisonment. Drug use in prisons was most likely to occur among those who had used in the month prior to imprisonment. The persistence of heroin use in prison occurred more frequently (70%) than use of cocaine (20%) or amphetamine (15%). Of those using heroin pre-imprisonment, 67% considered they were dependent, compared to 15% and 22%, respectively, for cocaine and amphetamine users. Changes in the drug-taking behaviour of drug users after imprisonment vary according to the type of drug being taken. Prisoners were much more likely to continue to use heroin than either cocaine or amphetamines while in prison. Heroin was most likely to be used by those who had been using heroin during the immediate pre-imprisonment period, and particularly by the two-thirds of heroin users who considered themselves dependent. In view of the high prevalence of prior use of these drugs by individuals currently imprisoned, continuing attention is required to

Idiosyncratic Drug-Induced Liver Injury: Is Drug-Cytokine Interaction the Linchpin?

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Roth, Robert A; Maiuri, Ashley R; Ganey, Patricia E

2017-02-01

Idiosyncratic drug-induced liver injury continues to be a human health problem in part because drugs that cause these reactions are not identified in current preclinical testing and because progress in prevention is hampered by incomplete knowledge of mechanisms that underlie these adverse responses. Several hypotheses involving adaptive immune responses, inflammatory stress, inability to adapt to stress, and multiple, concurrent factors have been proposed. Yet much remains unknown about how drugs interact with the liver to effect death of hepatocytes. Evidence supporting hypotheses implicating adaptive or innate immune responses in afflicted patients has begun to emerge and is bolstered by results obtained in experimental animal models and in vitro systems. A commonality in adaptive and innate immunity is the production of cytokines, including interferon-γ (IFNγ). IFNγ initiates cell signaling pathways that culminate in cell death or inhibition of proliferative repair. Tumor necrosis factor-α, another cytokine prominent in immune responses, can also promote cell death. Furthermore, tumor necrosis factor-α interacts with IFNγ, leading to enhanced cellular responses to each cytokine. In this short review, we propose that the interaction of drugs with these cytokines contributes to idiosyncratic drug-induced liver injury, and mechanisms by which this could occur are discussed. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Brain functional connectivity in stimulant drug dependence and obsessive-compulsive disorder.

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Meunier, David; Ersche, Karen D; Craig, Kevin J; Fornito, Alex; Merlo-Pich, Emilio; Fineberg, Naomi A; Shabbir, Shaila S; Robbins, Trevor W; Bullmore, Edward T

2012-01-16

There are reasons for thinking that obsessive-compulsive disorder (OCD) and drug dependence, although conventionally distinct diagnostic categories, might share important cognitive and neurobiological substrates. We tested this hypothesis directly by comparing brain functional connectivity measures between patients with OCD, stimulant dependent individuals (SDIs; many of whom were non-dependent users of other recreational drugs) and healthy volunteers. We measured functional connectivity between each possible pair of 506 brain regional functional MRI time series representing low frequency (0.03-0.06 Hz) spontaneous brain hemodynamics in healthy volunteers (N=18), patients with OCD (N=18) and SDIs (N=18). We used permutation tests to identify i) brain regions where strength of connectivity was significantly different in both patient groups compared to healthy volunteers; and ii) brain regions and connections which had significantly different functional connectivity between patient groups. We found that functional connectivity of right inferior and superior orbitofrontal cortex (OFC) was abnormally reduced in both disorders. Whether diagnosed as OCD or SDI, patients with higher scores on measures of compulsive symptom severity showed greater reductions of right orbitofrontal connectivity. Functional connections specifically between OFC and dorsal medial pre-motor and cingulate cortex were attenuated in both patient groups. However, patients with OCD demonstrated more severe and extensive reductions of functional connectivity compared to SDIs. OCD and stimulant dependence are not identical at the level of brain functional systems but they have some important abnormalities in common compared with healthy volunteers. Orbitofrontal connectivity may serve as a human brain systems biomarker for compulsivity across diagnostic categories. Copyright © 2011 Elsevier Inc. All rights reserved.

"Too Far Gone": Dyslexia, Homelessness, and Pathways to Drug Use and Dependency

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Macdonald, Stephen J.; Deacon, Lesley; Merchant, Jacqueline

2016-01-01

This study investigated the relationship between dyslexia, homelessness, and drug use and dependency based on data from the Multiple Exclusion Homelessness Across the United Kingdom Survey, a national survey of 443 respondents who had experienced some form of homelessness in the U.K. Of particular interest was a comparison of the various…

The effects of age and drug dependency on the emotional exhaustion and job satisfaction of adult streetworkers in australia.

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Cregan, Christina; Kulik, Carol T; Salinger, Dani

2013-07-01

This multi-method study investigated a sample of adult streetworkers (n = 107) in Melbourne, Australia in 2008. We contacted outdoor prostitutes through four "drop-in" centers run by not-for-profit organizations. Drug use was the over-riding common characteristic of most of these streetworkers. Using emotional labor theory as a theoretical framework, we hypothesized that individuals who worked on the streets solely to earn money to buy drugs would experience the highest levels of emotional exhaustion and the lowest levels of job satisfaction. We predicted these effects would be most evident for older drug dependent streetworkers. Content analysis of open-ended interview responses identified acting, age, and drug dependency as key themes. Moderator hierarchical regression analysis of responses to closed-ended questions with tests for mediation supported the hypotheses. It also demonstrated that older drug dependent streetworkers felt most trapped in their occupation and this sense of being locked-in was associated with emotional exhaustion but not with job satisfaction. The evidence that age and drug dependency affects the psychological outcomes associated with streetwork suggests that the efforts of police and the courts will be ineffective in dealing with people whose addiction traps them in an occupation that offers few intrinsic rewards. Decriminalization would encourage police to protect streetworkers from violence. Agencies could seek financial support to provide welfare and exit strategies.

Factors Affecting Drug Use During Incarceration: A Cross-Sectional Study of Opioid-Dependent Persons from India.

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Rao, Ravindra; Mandal, Piyali; Gupta, Rishab; Ramshankar, Prashanth; Mishra, Ashwani; Ambekar, Atul; Jhanjee, Sonali; Dhawan, Anju

2016-02-01

Substance abuse and criminality share a complex relationship. The rates of substance use among the prisoners, and that of criminal acts among substance users in community setting are high. Data from South Asian countries, including from India are inadequate. This study aimed to assess the pattern of criminal acts among opioid-dependent subjects and their substance use pattern in the month before, during and after imprisonment. Using a cross-sectional study design and purposive sampling, opioid-dependent subjects (n=101) attending two community drug treatment clinics who have had any contact with the law were assessed using a specifically-designed tool to record criminal acts and substance use before, during and after last imprisonment. Most subjects (93%) had committed illegal acts in their lifetime. Physical assault was the most common illegal act, while 23% reported selling drugs and 9% reported committing serious crimes. About 95% were arrested and 92% had spent time in police lockups. About 29% were arrested for drugs possession or drug use, and 3% of injecting drug users arrested for carrying injection equipment. About 85% had been imprisoned at least once, of whom 88% used psychoactive substances in the 1-month period before their last imprisonment. Opioids were the most common substances used daily (68%), followed by cannabis (34%) and alcohol (22%). Ninety-seven percent reported the availability of substances in prisons, and 65% also used substances during their last imprisonment. Cannabis (35%) was the most common substances used in prison followed by opioids (19%). Seventy-six percent used substances soon after prison release, and 13% of opioid users experienced opioid overdose soon after prison release. Use of cannabis, injecting drugs, and opioid use before imprisonment were predictors of substance use in prison. Opioid-dependent people have various contacts with the law, including imprisonment. Many users are dependent on substances during prison

Women, drug dependency and consequences: a study from a developing country.

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Khajedaluee, Mohammad; Dadgarmoghaddam, Maliheh; Erfanian, Majidreza; Alipourtabrizi, Arash; Khadem-Rezaiyan, Majid

2015-01-01

Introduction. Addiction in women can expose them to malnutrition, high blood pressure, cancer, and some other dangerous diseases like hepatitis, AIDS, or other sexual transmitted diseases. The aim of this study was to assess illegal sexual relations in three groups of women. Methods. This is a cross-sectional study that was done on 236 girls and young women aged 16-25 years in 2012 in three groups: vulnerable women who have substance dependency (crimes that had made women incarcerated were considered as vulnerability in this study), invulnerable women who have substance dependency (substance dependent women without a history of incarceration), and a control group (women with no history of substance dependency or being in prison). Results. 43.8% of vulnerable women who have substance dependency had extramarital sexual relations; this percentage was 55.8% in invulnerable women who have substance dependency and 1.4% in the control group. Crystal and methamphetamine abuse was higher in addicts who had extramarital sexual relations and alcohol abuse was correlated with unsafe sexual intercourse (r = 0.36, P = 0.001). There was a statistically significant difference in extramarital sexual relation based on marital status (P Poverty, drug dependency, divorce, and alcohol consumption make women prone to other high risk behaviors that need more attention.

Chemical dependence - resources

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Substance use - resources, Drug abuse - resources; Resources - chemical dependence ... are a good resource for information on drug dependence: National Council on Alcoholism and Drug Dependence -- ncadd. ...

Reward salience and risk aversion underlie differential ACC activity in substance dependence.

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Alexander, William H; Fukunaga, Rena; Finn, Peter; Brown, Joshua W

2015-01-01

The medial prefrontal cortex, especially the dorsal anterior cingulate cortex (ACC), has long been implicated in cognitive control and error processing. Although the association between ACC and behavior has been established, it is less clear how ACC contributes to dysfunctional behavior such as substance dependence. Evidence from neuroimaging studies investigating ACC function in substance users is mixed, with some studies showing disengagement of ACC in substance dependent individuals (SDs), while others show increased ACC activity related to substance use. In this study, we investigate ACC function in SDs and healthy individuals performing a change signal task for monetary rewards. Using a priori predictions derived from a recent computational model of ACC, we find that ACC activity differs between SDs and controls in factors related to reward salience and risk aversion between SDs and healthy individuals. Quantitative fits of a computational model to fMRI data reveal significant differences in best fit parameters for reward salience and risk preferences. Specifically, the ACC in SDs shows greater risk aversion, defined as concavity in the utility function, and greater attention to rewards relative to reward omission. Furthermore, across participants risk aversion and reward salience are positively correlated. The results clarify the role that ACC plays in both the reduced sensitivity to omitted rewards and greater reward valuation in SDs. Clinical implications of applying computational modeling in psychiatry are also discussed.

38 CFR 17.81 - Contracts for residential treatment services for veterans with alcohol or drug dependence or...

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2010-07-01

... treatment services for veterans with alcohol or drug dependence or abuse disabilities. 17.81 Section 17.81... dependence or abuse disabilities. (a) Contracts for treatment services authorized under § 17.80(a) may be... Department of Veterans Affairs sponsored residents to adjust to and maintain freedom from dependence on or...

Women, Drug Dependency and Consequences: A Study from a Developing Country

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Mohammad Khajedaluee

2015-01-01

Full Text Available Introduction. Addiction in women can expose them to malnutrition, high blood pressure, cancer, and some other dangerous diseases like hepatitis, AIDS, or other sexual transmitted diseases. The aim of this study was to assess illegal sexual relations in three groups of women. Methods. This is a cross-sectional study that was done on 236 girls and young women aged 16–25 years in 2012 in three groups: vulnerable women who have substance dependency (crimes that had made women incarcerated were considered as vulnerability in this study, invulnerable women who have substance dependency (substance dependent women without a history of incarceration, and a control group (women with no history of substance dependency or being in prison. Results. 43.8% of vulnerable women who have substance dependency had extramarital sexual relations; this percentage was 55.8% in invulnerable women who have substance dependency and 1.4% in the control group. Crystal and methamphetamine abuse was higher in addicts who had extramarital sexual relations and alcohol abuse was correlated with unsafe sexual intercourse (r=;0.36, P=0.001. There was a statistically significant difference in extramarital sexual relation based on marital status (P<0.001. Conclusions. Poverty, drug dependency, divorce, and alcohol consumption make women prone to other high risk behaviors that need more attention.

Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.

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Sun, Wei-Lun; Quizon, Pamela M; Zhu, Jun

2016-01-01

Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. Copyright © 2016. Published by Elsevier Inc.

Hospitalizations for Endocarditis and Associated Health Care Costs Among Persons with Diagnosed Drug Dependence - North Carolina, 2010-2015.

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Fleischauer, Aaron T; Ruhl, Laura; Rhea, Sarah; Barnes, Erin

2017-06-09

Opioid dependence and overdose have increased to epidemic levels in the United States. The 2014 National Survey on Drug Use and Health estimated that 4.3 million persons were nonmedical users of prescription pain relievers (1). These users are 40 times more likely than the general population to use heroin or other injection drugs (2). Furthermore, CDC estimated a near quadrupling of heroin-related overdose deaths during 2002-2014 (3). Although overdose contributes most to drug-associated mortality, infectious complications of intravenous drug use constitute a major cause of morbidity leading to hospitalization (4). In addition to infections from hepatitis C virus (HCV) and human immunodeficiency virus (HIV), injecting drug users are at increased risk for acquiring invasive bacterial infections, including endocarditis (5,6). Evidence that hospitalizations for endocarditis are increasing in association with the current opioid epidemic exists (7-9). To examine trends in hospitalizations for endocarditis among persons in North Carolina with drug dependence during 2010-2015, data from the North Carolina Hospital Discharge database were analyzed. The incidence of hospital discharge diagnoses for drug dependence combined with endocarditis increased more than twelvefold from 0.2 to 2.7 per 100,000 persons per year over this 6-year period. Correspondingly, hospital costs for these patients increased eighteenfold, from $1.1 million in 2010 to $22.2 million in 2015. To reduce the risk for morbidity and mortality related to opioid-associated endocarditis, public health programs and health care systems should consider collaborating to implement syringe service programs, harm reduction strategies, and opioid treatment programs.

Alcohol and drug misuse, abuse, and dependence in women veterans.

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Hoggatt, Katherine J; Jamison, Andrea L; Lehavot, Keren; Cucciare, Michael A; Timko, Christine; Simpson, Tracy L

2015-01-01

We conducted a systematic literature review on substance misuse, abuse, and dependence in women veterans, including National Guard/reserve members. We identified 837 articles published between 1980 and 2013. Of 56 included studies, 32 reported rates of alcohol misuse, binge drinking, or other unhealthy alcohol use not meeting diagnostic criteria for abuse or dependence, and 33 reported rates of drug misuse or diagnosed alcohol or drug use disorders. Rates ranged from 4% to 37% for alcohol misuse and from 7% to 25% for binge drinking; among Veterans Health Administration (VA) health-care system outpatients, rates ranged from 3% to 16% for substance use disorder. Studies comparing women veterans and civilians reported no clear differences in binge or heavy drinking. Substance misuse rates were generally lower among women veterans than men veterans. Substance misuse was associated with higher rates of trauma, psychiatric and medical conditions, and increased mortality and suicide rates. Most studies included only VA patients, and many used only VA medical record data; therefore, the reported substance misuse rates likely do not reflect true prevalence. Rates also varied by assessment method, source of data, and the subgroups studied. Further efforts to develop epidemiologically valid prevalence estimates are needed to capture the true health burden of substance misuse in women veterans, particularly those not using VA care. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Effect of quality chronic disease management for alcohol and drug dependence on addiction outcomes.

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Kim, Theresa W; Saitz, Richard; Cheng, Debbie M; Winter, Michael R; Witas, Julie; Samet, Jeffrey H

2012-12-01

We examined the effect of the quality of primary care-based chronic disease management (CDM) for alcohol and/or other drug (AOD) dependence on addiction outcomes. We assessed quality using (1) a visit frequency based measure and (2) a self-reported assessment measuring alignment with the chronic care model. The visit frequency based measure had no significant association with addiction outcomes. The self-reported measure of care-when care was at a CDM clinic-was associated with lower drug addiction severity. The self-reported assessment of care from any healthcare source (CDM clinic or elsewhere) was associated with lower alcohol addiction severity and abstinence. These findings suggest that high quality CDM for AOD dependence may improve addiction outcomes. Quality measures based upon alignment with the chronic care model may better capture features of effective CDM care than a visit frequency measure. Copyright © 2012 Elsevier Inc. All rights reserved.

Toward the virtual screening of potential drugs in the homology modeled NAD+ dependent DNA ligase from Mycobacterium tuberculosis.

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Singh, Vijai; Somvanshi, Pallavi

2010-02-01

DNA ligase is an important enzyme and it plays vital role in the replication and repair; also catalyzes nick joining between adjacent bases of DNA. The NAD(+) dependent DNA ligase is selectively present in eubacteria and few viruses; but missing in humans. Homology modeling was used to generate 3-D structure of NAD(+) dependent DNA ligase (LigA) of Mycobacterium tuberculosis using the known template (PDB: 2OWO). Furthermore, the stereochemical quality and torsion angle of 3-D structure was validated. Numerous effective drugs were selected and the active amino acid residue in LigA was targeted and virtual screening through molecular docking was done. In this analysis, four drugs Chloroquine, Hydroxychloroquine, Putrienscine and Adriamycin were found more potent in inhibition of M. tuberculosis through the robust binding affinity between protein-drug interactions in comparison with the other studied drugs. A phylogenetic tree was constructed and it was observed that homology of LigA in M. tuberculosis resembled with other Mycobacterium species. The conserved active amino acids of LigA may be useful to target these drugs. These findings could be used as the starting point of a rational design of novel antibacterial drugs and its analogs.

Conditioned Place Preference Induced by Licit Drugs: Establishment, Extinction, and Reinstatement

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Yu Liu

2008-01-01

Full Text Available The conditioned place preference (CPP model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine.

Childhood emotional abuse, dissociation, and suicidality among patients with drug dependency in Turkey.

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Tamar-Gurol, Defne; Sar, Vedat; Karadag, Figen; Evren, Cuneyt; Karagoz, Mustafa

2008-10-01

The aim of the present study was to determine the prevalence and correlates of dissociative disorders among patients with drug dependency. The Dissociative Experiences Scale (DES) was used to screen 104 consecutive patients at an addiction treatment center. Thirty-seven patients who had scores >or=30 were compared with 21 patients who scored suicide attempt and/or childhood emotional abuse was significant predictors of a dissociative disorder. The majority (59.3%) of dissociative drug users reported that dissociative experiences had existed prior to substance use. More patients in the dissociative disorder than in the non-dissociative group stopped their treatment prematurely. A considerable proportion of drug users have a dissociative disorder, which may also interfere with treatment process. The relatively young age of this subgroup of patients and frequent reports of childhood emotional abuse underline potential preventive benefits of early intervention among adolescents with developmental trauma history and dissociative psychopathology.

Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate).

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Bohr, Adam; Wang, Yingya; Harmankaya, Necati; Water, Jorrit J; Baldursdottír, Stefania; Almdal, Kristoffer; Beck-Broichsitter, Moritz

2017-06-01

Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half-lives correlated well with the observed in vitro half-times of drug delivery (R 2 =0.96). Here, the PEC of the highest molecular weight resulted in the fastest degradation/drug release. When incubated with macrophages or implanted in animals, the degradation rate of PEC films superimposed the results of in vitro incubations with cholesterol esterase. Interestingly, SEM analysis indicated a distinct surface erosion process for enzyme-, macrophage- and in vivo-treated polymer films in a molecular weight-dependent manner. Overall, the molecular weight of surface-eroding PEC was identified as an essential parameter to control the spatial and temporal on-demand degradation and drug release from the employed delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

Psychotic Symptoms Associated with the use of Dopaminergic Drugs, in Patients with Cocaine Dependence or Abuse.

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Roncero, Carlos; Abad, Alfonso C; Padilla-Mata, Antonio; Ros-Cucurull, Elena; Barral, Carmen; Casas, Miquel; Grau-López, Lara

2017-01-01

In the field of dual diagnosis, physicians are frequently presented with pharmacological questions. Questions about the risk of developing psychotic symptoms in cocaine users who need treatment with dopaminergic drugs could lead to an undertreatment. Review the presence of psychotic symptoms in patients with cocaine abuse/dependence, in treatment with dopaminergic drugs. Systematic PubMed searches were conducted including December 2014, using the keywords: "cocaine", dopaminergic drug ("disulfuram-methylphenidate-bupropion-bromocriptine-sibutramineapomorphine- caffeine") and ("psychosis-psychotic symptoms-delusional-paranoia"). Articles in English, Spanish, Portuguese, French, and Italian were included. Articles in which there was no history of cocaine abuse/dependence, absence of psychotic symptoms, systematic reviews, and animal studies, were excluded. 313 papers were reviewed. 7 articles fulfilled the inclusion-exclusion criteria. There is a clinical trial including 8 cocaine-dependent patients using disulfiram in which 3 of them presented psychotic symptoms and 6 case-reports: disulfuram (1), methylphenidate (1), disulfiram with methylphenidate (2), and bupropion (2), reporting psychotic symptoms, especially delusions of reference and persecutory ideation. Few cases have been described, which suggests that the appearance of these symptoms is infrequent. The synergy of dopaminergic effects or the dopaminergic sensitization in chronic consumption are the explanatory theories proposed by the authors. In these cases, a relationship was found between taking these drugs and the appearance of psychotic symptoms. Given the low number of studies found, further research is required. The risk of psychotic symptoms seems to be acceptable if we compare it with the benefits for the patients but a closer monitoring seems to be advisable.

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

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Kutlu, Munir Gunes

2016-01-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. PMID:27634143

The Predictive Role of Difficulties in Emotion Regulation and Self-Control with Susceptibility to Addiction in Drug-Dependent Individuals

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Mahmoud Shirazi

2015-06-01

Full Text Available Objective: The present study aimed to examine the predictive role of difficulties in emotion regulation and self-control in potential for addiction among drug-dependent individuals. Method: This was a correlational study which falls within the category of descriptive studies. The statistical population of the current study included all patients under treatment in outpatient health centers in Bam, among whom 315 individuals were selected through cluster sampling method as the participants of the study. Difficulties in Emotion Regulation Scale, Self-Control Scale, and Addiction Susceptibility Questionnaire were used for data collection purposes. Results: The results indicated that difficulties engaging in goal directed behavior, impulse control difficulties, lack of emotional awareness, and lack of emotional clarity (dimensions of difficulties in emotion regulation had a significant positive correlation with potential for addiction. In addition, there was a negative significant relationship between self-control and potential for addiction among drug-dependent individuals. Conclusion: In addition to common methods of abstinence from drug dependence, teaching self-control and emotional control techniques to addicted patients can help them reduce their dependence.

Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner.

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Taubenfeld, Stephen M; Muravieva, Elizaveta V; Garcia-Osta, Ana; Alberini, Cristina M

2010-07-06

Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.

Role of the activation gate in determining the extracellular potassium dependency of block of HERG by trapped drugs.

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Pareja, Kristeen; Chu, Elaine; Dodyk, Katrina; Richter, Kristofer; Miller, Alan

2013-01-01

Drug induced long QT syndrome (diLQTS) results primarily from block of the cardiac potassium channel HERG (human-ether-a-go-go related gene). In some cases long QT syndrome can result in the lethal arrhythmia torsade de pointes, an arrhythmia characterized by a rapid heart rate and severely compromised cardiac output. Many patients requiring medication present with serum potassium abnormalities due to a variety of conditions including gastrointestinal dysfunction, renal and endocrine disorders, diuretic use, and aging. Extracellular potassium influences HERG channel inactivation and can alter block of HERG by some drugs. However, block of HERG by a number of drugs is not sensitive to extracellular potassium. In this study, we show that block of WT HERG by bepridil and terfenadine, two drugs previously shown to be trapped inside the HERG channel after the channel closes, is insensitive to extracellular potassium over the range of 0 mM to 20 mM. We also show that bepridil block of the HERG mutant D540K, a mutant channel that is unable to trap drugs, is dependent on extracellular potassium, correlates with the permeant ion, and is independent of HERG inactivation. These results suggest that the lack of extracellular potassium dependency of block of HERG by some drugs may in part be related to the ability of these drugs to be trapped inside the channel after the channel closes.

Relationships between self-reported unfair treatment and prescription medication use, illicit drug use, and alcohol dependence among Filipino Americans.

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Gee, Gilbert C; Delva, Jorge; Takeuchi, David T

2007-05-01

We examined associations between self-reported unfair treatment and prescription medication use, illicit drug use, and alcohol dependence. We used data from the Filipino American Community Epidemiological Survey, a cross-sectional investigation involving 2217 Filipino Americans interviewed in 1998-1999. Multinomial logistic and negative binomial regression analyses were used in assessing associations between unfair treatment and the substance use categories. Reports of unfair treatment were associated with prescription drug use, illicit drug use, and alcohol dependence after control for age, gender, location of residence, employment status, educational level, ethnic identity level, nativity, language spoken, marital status, and several health conditions. Unfair treatment may contribute to illness and subsequent use of prescription medications. Furthermore, some individuals may use illicit drugs and alcohol to cope with the stress associated with such treatment. Addressing the antecedents of unfair treatment may be a potential intervention route.

Improved Predictions of Drug-Drug Interactions Mediated by Time-Dependent Inhibition of CYP3A.

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Yadav, Jaydeep; Korzekwa, Ken; Nagar, Swati

2018-05-07

Time-dependent inactivation (TDI) of cytochrome P450s (CYPs) is a leading cause of clinical drug-drug interactions (DDIs). Current methods tend to overpredict DDIs. In this study, a numerical approach was used to model complex CYP3A TDI in human-liver microsomes. The inhibitors evaluated included troleandomycin (TAO), erythromycin (ERY), verapamil (VER), and diltiazem (DTZ) along with the primary metabolites N-demethyl erythromycin (NDE), norverapamil (NV), and N-desmethyl diltiazem (NDD). The complexities incorporated into the models included multiple-binding kinetics, quasi-irreversible inactivation, sequential metabolism, inhibitor depletion, and membrane partitioning. The resulting inactivation parameters were incorporated into static in vitro-in vivo correlation (IVIVC) models to predict clinical DDIs. For 77 clinically observed DDIs, with a hepatic-CYP3A-synthesis-rate constant of 0.000 146 min -1 , the average fold difference between the observed and predicted DDIs was 3.17 for the standard replot method and 1.45 for the numerical method. Similar results were obtained using a synthesis-rate constant of 0.000 32 min -1 . These results suggest that numerical methods can successfully model complex in vitro TDI kinetics and that the resulting DDI predictions are more accurate than those obtained with the standard replot approach.

Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

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Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

2017-09-01

The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

OpenAIRE

Kutlu, Munir Gunes; Gould, Thomas J.

2016-01-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In thi...

The psychological and neurochemical mechanisms of drug memory reconsolidation: implications for the treatment of addiction.

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Milton, Amy L; Everitt, Barry J

2010-06-01

Memory reconsolidation is the process by which memories, destabilised at retrieval, require restabilisation to persist in the brain. It has been demonstrated that even old, well-established memories require reconsolidation following retrieval; therefore, memory reconsolidation could potentially be exploited to disrupt, or even erase, aberrant memories that underlie psychiatric disorders, thereby providing a novel therapeutic target. Drug addiction is one such disorder; it is both chronic and relapsing, and one prominent risk factor for a relapse episode is the presentation of environmental cues that have previously been associated with drugs of abuse. This 'cue-induced relapse' can be accounted for in psychological terms by reinforcing memories of the pavlovian association between the cue and the drug, which can thus influence behaviour through at least three psychologically and neurobiologically dissociable mechanisms: conditioned reinforcement, conditioned approach and conditioned motivation. As each of these psychological processes could contribute to the resumption of drug-seeking following abstinence, it is important to develop treatments that can reduce drug-seeking re-established via influences on each or all of these pavlovian processes, in order to minimise the risk of a subsequent relapse. Investigation of the memory reconsolidation mechanisms of the memories underlying conditioned reinforcement, conditioned approach and conditioned motivation indicate that they depend upon different neurochemical systems, including the glutamatergic and adrenergic systems within limbic corticostriatal circuitry. We also discuss here the subsequent translation to the clinic of this preclinical work.

Pharmacological and genetic interventions in serotonin (5-HT)(2C) receptors to alter drug abuse and dependence processes

NARCIS (Netherlands)

Filip, Malgorzata; Spampinato, Umberto; McCreary, Andrew C.; Przegalinski, Edmund

2012-01-01

The present review provides an overview on serotonin (5-hydroxytryptamine; 5-HT)(2C) receptors and their relationship to drug dependence. We have focused our discussion on the impact of 5-HT2C receptors on the effects of different classes of addictive drugs, illustrated by reference to data using

Governor's Conference on Drug Dependence and Abuse. An Occasional Paper of the Honors College.

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Milliken, William G.; And Others

1970-01-01

Following Governor Milliken's address, Dr. Dana Farnsworth defines the problem in terms of who's involved, to what extent, and with which drugs. His presentation focuses primarily on the motives of affluent young people who experiment with or become dependent upon hallucinogens, marihuana and amphetamines. He deals extensively with the drastically…

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction.

Science.gov (United States)

Kutlu, Munir Gunes; Gould, Thomas J

2016-10-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. © 2016 Kutlu and Gould; Published by Cold Spring Harbor Laboratory Press.

Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence

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Murphy, Anna; Nestor, Liam J; McGonigle, John; Paterson, Louise; Boyapati, Venkataramana; Ersche, Karen D; Flechais, Remy; Kuchibatla, Shankar; Metastasio, Antonio; Orban, Csaba; Passetti, Filippo; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor; Robbins, Trevor W; Lingford-Hughes, Anne; Nutt, David J; Deakin, John FW; Elliott, Rebecca

2017-01-01

Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the Go/No-Go task (GNGT). A double-blind, placebo-controlled, crossover design approach was used in abstinent alcohol dependent, abstinent poly-drug dependent and healthy control volunteers. For the MIDT, there was evidence of blunted ventral striatal response to reward in the poly-drug-dependent group under placebo. GSK598809 normalized ventral striatal reward response and enhanced response in the DRD3-rich regions of the ventral pallidum and substantia nigra. Exploratory investigations suggested that the effects of GSK598809 were mainly driven by those with primary dependence on alcohol but not on opiates. Taken together, these findings suggest that GSK598809 may remediate reward deficits in substance dependence. For the GNGT, enhanced response in the inferior frontal cortex of the poly-drug group was found. However, there were no effects of GSK598809 on the neural network underlying response inhibition nor were there any behavioral drug effects on response inhibition. GSK598809 modulated the neural network underlying reward anticipation but not response inhibition, suggesting that DRD3 antagonists may restore reward deficits in addiction. PMID:28042871

Double Dissociation of Spike Timing-Dependent Potentiation and Depression by Subunit-Preferring NMDA Receptor Antagonists in Mouse Barrel Cortex

NARCIS (Netherlands)

Banerjee, A.; Meredith, R.M.; Rodriguez-Moreno, A.; Mierau, S.B.; Auberson, Y.P.; Paulsen, O.

2009-01-01

Spike timing-dependent plasticity (STDP) is a strong candidate for an N-methyl-D-aspartate (NMDA) receptor-dependent form of synaptic plasticity that could underlie the development of receptive field properties in sensory neocortices. Whilst induction of timing-dependent long-term potentiation

Personality Traits and Psychopathology in Nicotine and Opiate Dependents Using the Gateway Drug Theory

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Bahareh Amirabadi

2015-03-01

Full Text Available Objectives: According to the gateway drug theory, tobacco use is a predisposing factor for future substance abuse. This study was conducted to compare nicotine and opiate dependents to identify the differences between their personality traits and psychopathology that makes them turn to other substances after cigarette smoking. Methods: A causal-comparative study was conducted. Three groups were randomly selected: nicotine dependents, opiate dependents and ordinary individuals (non-dependent population. Cloninger’s Temperament and Character Inventory-Revised, the Fagerstrom Test for Nicotine Dependence, Maudsley Addiction Profile, the Beck Depression Inventory, and Beck Anxiety Inventory were used to collect data. Analysis of variance was used to analyze data. Results: Opiate dependents had higher ‘novelty seeking’ and lower ‘cooperativeness’ scores as compared to the other two groups. They also had higher anxiety and depression scores than the other two groups. Discussion: Higher ‘novelty seeking’ and lower ‘cooperativeness’ scores are important personality traits predicting

Ethical Implications in Vaccine Pharmacotherapy for Treatment and Prevention of Drug of Abuse Dependence.

Science.gov (United States)

Carfora, Anna; Cassandro, Paola; Feola, Alessandro; La Sala, Francesco; Petrella, Raffaella; Borriello, Renata

2018-03-01

Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. "Drug vaccines" aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, "cocaine and nicotine vaccines" have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway. However, although vaccines can become a reasonable treatment option for drugs of abuse, there are several disadvantages that must be considered. These include i) great individual variability in the formation of antibodies, ii) the lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice, and iii) the lack of an effect on the drug desire that may predispose an addict to relapse. In addition, a comprehensive overview of several crucial ethical issues has not yet been widely discussed in order to have not only a biological approach to immunotherapy of addiction. Overall, immunotherapy offers a range of possible treatment options: the pharmacological treatment of addiction, the treatment of overdoses, the prevention of toxicity to the brain or the heart, and the protection of the fetus during pregnancy. So far, the results obtained from a small-scale experiment using vaccines against cocaine and nicotine suggest that a number of important technical challenges still need to be overcome before such vaccines can be approved for clinical use.

Nanotechnology in dentistry: drug delivery systems for the control of biofilm-dependent oral diseases.

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de Sousa, Francisco Fabio Oliveira; Ferraz, Camila; Rodrigues, Lidiany K Arla de Azevedo; Nojosa, Jacqueline de Santiago; Yamauti, Monica

2014-01-01

Dental disorders, such as caries, periodontal and endodontic diseases are major public health issues worldwide. In common, they are biofilm-dependent oral diseases, and the specific conditions of oral cavity may develop infectious foci that could affect other physiological systems. Efforts have been made to develop new treatment routes for the treatment of oral diseases, and therefore, for the prevention of some systemic illnesses. New drugs and materials have been challenged to prevent and treat these conditions, especially by means of bacteria elimination. "Recent progresses in understanding the etiology, epidemiology and microbiology of the microbial flora in those circumstances have given insight and motivated the innovation on new therapeutic approaches for the management of the oral diseases progression". Some of the greatest advances in the medical field have been based in nanosized systems, ranging from the drug release with designed nanoparticles to tissue scaffolds based on nanotechnology. These systems offer new possibilities for specific and efficient therapies, been assayed successfully in preventive/curative therapies to the oral cavity, opening new challenges and opportunities to overcome common diseases based on bacterial biofilm development. The aim of this review is to summarize the recent nanotechnological developments in the drug delivery field related to the prevention and treatment of the major biofilm-dependent oral diseases and to identify those systems, which may have higher potential for clinical use.

The Effect of Health Education based on Health Belief Model on Preventive Actions of Synthetic Drugs Dependence in Male Students of Kerman, Iran

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Seyed Saeed Mazloomy Mahmoodabad

2017-06-01

Conclusion: Findings indicated that by increase of HBM components' average scores, the average score of synthetic drug dependence preventive actions increased too. Therefore, results of the research confirm the effect and efficiency of HBM in making preventive actions of drug dependence. 

Context-dependent memory: colour versus odour.

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Pointer, S C; Bond, N W

1998-06-01

An olfactory stimulus and a visual stimulus were employed in a context-dependent memory study using a prose passage as the to-be-remembered item. Ninety-five university students (aged 17-35 years) learned the passage of prose in the presence of one of the stimuli and were then asked to recall the passage with the original context either reinstated or not reinstated. The results revealed a significant context-dependent memory effect for the olfactory cue but not for the visual cue. They demonstrate support for the effectiveness of odours as context cues and it is suggested that context-dependent memory processes may underlie the formation and retrieval of odour-evoked autobiographical memories.

Chemical dependency and drug testing in the workplace.

OpenAIRE

Osterloh, J D; Becker, C E

1990-01-01

Urine testing for drug use in the workplace is now widespread, with the prevalence of positive drug tests in the work force being 0% to 15%. The prevalence of marijuana use is highest, and this can be reliably tested. Though it is prudent to rid the workplace of drug use, there is little scientific study on the relationship of drug use and workplace outcomes, such as productivity and safety. Probable-cause testing and preemployment testing are the most common applications. Random testing has ...

The potential impact of density dependent fecundity on the use of the faecal egg count reduction test for detecting drug resistance in human hookworms.

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Andrew C Kotze

Full Text Available Current efforts to control human soil-transmitted helminth (STH infections involve the periodic mass treatment of people, particularly children, in all endemic areas, using benzimidazole and imidothiazole drugs. Given the fact that high levels of resistance have developed to these same drugs in roundworms of livestock, there is a need to monitor drug efficacy in human STHs. The faecal egg count reduction test (FECRT, in which faecal egg output is measured pre- and post-drug treatment, is presently under examination by WHO as a means of detecting the emergence of resistance. We have examined the potential impact of density dependent fecundity on FECRT data. Recent evidence with the canine hookworm indicates that the density dependent egg production phenomenon shows dynamic properties in response to drug treatment. This will impact on measurements of drug efficacy, and hence drug resistance. It is likely that the female worms that survive a FECRT drug treatment in some human cases will respond to the relaxation of density dependent constraints on egg production by increasing their egg output significantly compared to their pre-treatment levels. These cases will therefore underestimate drug efficacy in the FECRT. The degree of underestimation will depend on the ability of the worms within particular hosts to increase their egg output, which will in turn depend on the extent to which their egg output is constrained prior to the drug treatment. As worms within different human cases will likely be present at quite different densities prior to a proposed FECRT, there is potential for the effects of this phenomenon on drug efficacy measurements to vary considerably within any group of potential FECRT candidates. Measurement of relative drug efficacy may be improved by attempting to ensure a consistent degree of underestimation in groups of people involved in separate FECRTs. This may be partly achieved by omission of cases with the heaviest infections

Effectiveness of Cognitive-Behavioral Therapy in the Improvement of Coping Strategies and Addiction Symptoms in Drug-Dependent Patients

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H BrockieMilan

2014-12-01

Full Text Available Objective: This study was carried out to determine the effectiveness of cognitive-behavioral therapy in improving coping strategies and symptoms of drug addiction patients. Method: In a quasi-experimental study, the number of 90drug-dependent patients referring to clinics to stop taking drugs existing in the city of Urmia were divided into two experimental (n=45 groups and control (n=45 using random sampling. The experimental group received 12 sessions of cognitive-behavioral treatment in Carroll style while the control group received only methadone and the physical pills. All the participants completed coping strategies questionnaire at the beginning, during (after three months, and three months after treatment (follow-up. As well, they were assessed for the rate of improvement in symptoms of addiction and process of addiction treatment using by Madzly’s addiction profile questionnaire. Findings: The results proved the effectiveness of cognitive-behavioral therapy and its survival. Conclusion: Cognitive behavioral therapy is very influential in the boost of coping strategies and the improvement of mental and physical health in drug-dependent patients.

Chemical dependency and drug testing in the workplace.

Science.gov (United States)

Osterloh, J D; Becker, C E

1990-05-01

Urine testing for drug use in the workplace is now widespread, with the prevalence of positive drug tests in the work force being 0% to 15%. The prevalence of marijuana use is highest, and this can be reliably tested. Though it is prudent to rid the workplace of drug use, there is little scientific study on the relationship of drug use and workplace outcomes, such as productivity and safety. Probable-cause testing and preemployment testing are the most common applications. Random testing has been less accepted owing to its higher costs, unresolved legal issues, and predictably poor test reliability. Legal issues have focused on the right to policy, discrimination, and the lack of due process. The legal cornerstone of a good program is a policy that is planned and agreed on by both labor and management, which serves both as a contract and as a procedure in which expectations and consequences are known. The National Institute on Drug Abuse is certifying laboratories doing employee drug testing. Testing methods when done correctly are less prone to error than in the past, but screening tests can be defeated by adulterants. Although the incidence of false-positive results is low, such tests are less reliable when the prevalence of drug abuse is also low.

[Stabilizing the social and health status of drug dependent patients with methadone. Long-term maintainance therapy--Vienna results].

Science.gov (United States)

Loimer, N; Werner, E; Hollerer, E; Pfersmann, V; Schmid-Siegel, B; Presslich, O

1991-01-01

On September 25th, 1987 methadone was legalized in Austria for therapeutic use in drug addiction treatment in case of: 1. Long-term drug addiction with intravenous application of the drug, and several unsuccessful withdrawal therapies and/or 2. opiate addiction through intravenous application of the drug along with an existing HIV-1 infection. Since than, 291 patients were treated with methadone at the drug-dependency outpatient clinic of the Psychiatric Clinic of the University of Vienna. In 1990, 96 patients treated for more than one year were investigated using a standardized questionnaire. The image in which crime, prostitution, poverty, ill health all merge was broken by this decriminalization. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society.

Social causation and neighborhood selection underlie associations of neighborhood factors with illicit drug-using social networks and illicit drug use among adults relocated from public housing.

Science.gov (United States)

Linton, Sabriya L; Haley, Danielle F; Hunter-Jones, Josalin; Ross, Zev; Cooper, Hannah L F

2017-07-01

Theories of social causation and social influence, which posit that neighborhood and social network characteristics are distal causes of substance use, are frequently used to interpret associations among neighborhood characteristics, social network characteristics and substance use. These associations are also hypothesized to result from selection processes, in which substance use determines where people live and who they interact with. The potential for these competing selection mechanisms to co-occur has been underexplored among adults. This study utilizes path analysis to determine the paths that relate census tract characteristics (e.g., economic deprivation), social network characteristics (i.e., having ≥ 1 illicit drug-using network member) and illicit drug use, among 172 African American adults relocated from public housing in Atlanta, Georgia and followed from 2009 to 2014 (7 waves). Individual and network-level characteristics were captured using surveys. Census tract characteristics were created using administrative data. Waves 1 (pre-relocation), 2 (1st wave post-relocation), and 7 were analyzed. When controlling for individual-level sociodemographic factors, residing in census tracts with prior economic disadvantage was significantly associated with illicit drug use at wave 1; illicit drug use at wave 1 was significantly associated with living in economically-disadvantaged census tracts at wave 2; and violent crime at wave 2 was associated with illicit drug-using social network members at wave 7. Findings from this study support theories that describe social causation and neighborhood selection processes as explaining relationships of neighborhood characteristics with illicit drug use and illicit drug-using social networks. Policies that improve local economic and social conditions of neighborhoods may discourage substance use. Future studies should further identify the barriers that prevent substance users from obtaining housing in less

Barriers to community-based drug dependence treatment: implications for police roles, collaborations and performance indicators

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Ma, Yi; Du, Chunhua; Cai, Thomas; Han, Qingfeng; Yuan, Huanhuan; Luo, Tingyan; Ren, Guoliang; Mburu, Gitau; Wang, Bangyuan; Golichenko, Olga; Zhang, Chaoxiong

2016-01-01

Introduction Worldwide, people who use drugs (PWUD) are among the populations at highest risk for HIV infection. In China, PWUD are primarily sentenced to compulsory detainment centres, in which access to healthcare, including HIV treatment and prevention services, is limited or non-existent. In 2008, China's 2008 Anti-Drug Law encouraged the development and use of community-based drug dependence rehabilitation, yet there is limited evidence evaluating the efficacy and challenges of this model in China. In this study, we explore these challenges and describe how cooperation between law enforcement and health departments can meet the needs of PWUD. Methods In 2015, we conducted semi-structured, in-depth interviews with all four staff members and 16 clients of the Ping An Centre No. 1 for community-based drug treatment, three local police officers and three officials from the local Centre for Disease Control. Interviews explored obstacles in implementing community-based drug dependence treatment and efforts to resolve these difficulties. Transcripts were coded and analyzed with qualitative data analysis software (MAXQDA 11). Results We identified three challenges to community-based drug treatment at the Ping An Centre No. 1: (1) suboptimal coordination among parties involved, (2) a divergence in attitudes towards PWUD and harm reduction between law enforcement and health officials and (3) conflicting performance targets for police and health officials that undermine the shared goal of treatment. We also identified the take-home methadone maintenance treatment model at the Ping An Centre No. 1 as an example of an early successful collaboration between the police, the health department and PWUD. Conclusions To overcome barriers to effective community-based drug treatment, we recommend aligning the goals of law enforcement and public health agencies towards health-based performance indicators. Furthermore, tensions between PWUD and police need to be addressed and trust

A dose-dependent relationship between exposure to a street-based drug scene and health-related harms among people who use injection drugs.

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Debeck, Kora; Wood, Evan; Zhang, Ruth; Buxton, Jane; Montaner, Julio; Kerr, Thomas

2011-08-01

While the community impacts of drug-related street disorder have been well described, lesser attention has been given to the potential health and social implications of drug scene exposure on street-involved people who use illicit drugs. Therefore, we sought to assess the impacts of exposure to a street-based drug scene among injection drug users (IDU) in a Canadian setting. Data were derived from a prospective cohort study known as the Vancouver Injection Drug Users Study. Four categories of drug scene exposure were defined based on the numbers of hours spent on the street each day. Three generalized estimating equation (GEE) logistic regression models were constructed to identify factors associated with varying levels of drug scene exposure (2-6, 6-15, over 15 hours) during the period of December 2005 to March 2009. Among our sample of 1,486 IDU, at baseline, a total of 314 (21%) fit the criteria for high drug scene exposure (>15 hours per day). In multivariate GEE analysis, factors significantly and independently associated with high exposure included: unstable housing (adjusted odds ratio [AOR] = 9.50; 95% confidence interval [CI], 6.36-14.20); daily crack use (AOR = 2.70; 95% CI, 2.07-3.52); encounters with police (AOR = 2.11; 95% CI, 1.62-2.75); and being a victim of violence (AOR = 1.49; 95 % CI, 1.14-1.95). Regular employment (AOR = 0.50; 95% CI, 0.38-0.65), and engagement with addiction treatment (AOR = 0.58; 95% CI, 0.45-0.75) were negatively associated with high exposure. Our findings indicate that drug scene exposure is associated with markers of vulnerability and higher intensity addiction. Intensity of drug scene exposure was associated with indicators of vulnerability to harm in a dose-dependent fashion. These findings highlight opportunities for policy interventions to address exposure to street disorder in the areas of employment, housing, and addiction treatment.

Chronic disease and recent addiction treatment utilization among alcohol and drug dependent adults

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Samet Jeffrey

2011-10-01

Full Text Available Abstract Background Chronic medical diseases require regular and longitudinal care and self-management for effective treatment. When chronic diseases include substance use disorders, care and treatment of both the medical and addiction disorders may affect access to care and the ability to focus on both conditions. The objective of this paper is to evaluate the association between the presence of chronic medical disease and recent addiction treatment utilization among adults with substance dependence. Methods Cross-sectional secondary data analysis of self-reported baseline data from alcohol and/or drug-dependent adults enrolled in a randomized clinical trial of a disease management program for substance dependence in primary care. The main independent variable was chronic medical disease status, categorized using the Katz Comorbidity Score as none, single condition of lower severity, or higher severity (multiple conditions or single higher severity condition, based on comorbidity scores determined from self-report. Asthma was also examined in secondary analyses. The primary outcome was any self-reported addiction treatment utilization (excluding detoxification in the 3 months prior to study entry, including receipt of any addiction-focused counseling or addiction medication from any healthcare provider. Logistic regression models were adjusted for sociodemographics, type of substance dependence, recruitment site, current smoking, and recent anxiety severity. Results Of 563 subjects, 184 (33% reported any chronic disease (20% low severity; 13% higher severity and 111 (20% reported asthma; 157 (28% reported any addiction treatment utilization in the past 3 months. In multivariate regression analyses, no significant effect was detected for chronic disease on addiction treatment utilization (adjusted odds ratio [AOR] 0.88 lower severity vs. none, 95% confidence interval (CI: 0.60, 1.28; AOR 1.29 higher severity vs. none, 95% CI: 0.89, 1.88 nor for

Cocaine Allergy in Drug-Dependent Patients and Allergic People.

Science.gov (United States)

Armentia, Alicia; Martín-Armentia, Blanca; Martín-Armentia, Sara; Ruiz-Muñoz, Pedro; Quesada, Jorge Martínez; Postigo, Idoia; Conde, Rosa; González-Sagrado, Manuel; Pineda, Fernando; Castillo, Miriam; Palacios, Ricardo; Tejedor, Jesús

Adverse reactions to local anesthetics (LAs), especially esters, are not uncommon, but true allergy is rarely diagnosed. To our knowledge, currently there is no reliable method of determining IgE-mediated hypersensitivity to LAs and cocaine. To assess the clinical value of allergy tests (prick, IgE, challenges, and arrays) in people suffering hypersensitivity reactions (asthma and anaphylaxis) during local anesthesia with cocaine derivatives and drug abusers with allergic symptoms after cocaine inhalation. We selected cocaine-dependent patients and allergic patients who suffered severe reactions during local anesthesia from a database of 23,873 patients. The diagnostic yield (sensitivity, specificity, and predictive value) of allergy tests using cocaine and coca leaf extracts in determining cocaine allergy was assessed, taking a positive challenge as the criterion standard. After prick tests, specific IgE, and challenge with cocaine extract, 41 of 211 patients (19.4%) were diagnosed as sensitized to cocaine. Prick tests and IgE to coca leaves (coca tea) had a good sensitivity (95.1% and 92.7%, respectively) and specificity (92.3 and 98.8%, respectively) for the diagnosis of cocaine allergy and LA-derived allergy. Cocaine may be an important allergen. Drug abusers and patients sensitized to local anesthesia and tobacco are at risk. Both prick tests and specific IgE against coca leaf extract detected sensitization to cocaine. The highest levels were related to severe clinical profiles. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner

NARCIS (Netherlands)

Gupta, V.K.; Scheunemann, L.; Eisenberg, T.; Mertel, S.; Bhukel, A.; Koemans, T.S.; Kramer, J.M.; Liu, K.S.; Schroeder, S.; Stunnenberg, H.G.; Sinner, F.; Magnes, C.; Pieber, T.R.; Dipt, S.; Fiala, A.; Schenck, A.; Schwaerzel, M.; Madeo, F.; Sigrist, S.J.

2013-01-01

Age-dependent memory impairment is known to occur in several organisms, including Drosophila, mouse and human. However, the fundamental cellular mechanisms that underlie these impairments are still poorly understood, effectively hampering the development of pharmacological strategies to treat the

Associations Between Family History of Substance Use, Childhood Trauma, and Age of First Drug Use in Persons With Methamphetamine Dependence.

Science.gov (United States)

Svingen, Leah; Dykstra, Rita E; Simpson, Jamie L; Jaffe, Anna E; Bevins, Rick A; Carlo, Gustavo; DiLillo, David; Grant, Kathleen M

2016-01-01

The current study examined the association among family history of substance use problems, childhood maltreatment, and age of first drug use in a sample of men and women seeking treatment for methamphetamine dependence. Various forms of childhood maltreatment were considered as mediators of the association between family history of substance use problems and age of first drug use. Participants (N = 99, 40% women, mean age 33) who were under treatment for methamphetamine dependence completed a baseline interview that obtained demographic information, past substance use by participants, history of drug/alcohol problems in their family of origin, and age at first use of any drug (excluding alcohol and tobacco). The Early Trauma Inventory Self-Report-Short Form was used to assess child maltreatment experiences before the age of 18. Family history of substance use problems and childhood physical (but not emotional or sexual) trauma significantly predicted age of first drug use. Further, childhood physical trauma mediated the association between family history of substance use problems and age of first drug use. These findings suggest that the experience of childhood physical abuse may be an important mechanism through which family history of substance use is associated with an earlier age of first drug use.

Influences of social reward experience on behavioral responses to drugs of abuse: Review of shared and divergent neural plasticity mechanisms for sexual reward and drugs of abuse.

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Beloate, Lauren N; Coolen, Lique M

2017-12-01

Different factors influence the development of drug addiction in humans, including social reward experiences. In animals, experience with social rewards, such as sexual behavior, pair bonding, social and environmental enrichment, can be protective. However, loss or lack of social rewards can lead to a vulnerability to drug-seeking behavior. The effects of social reward experience on drug-seeking behavior are associated with changes in the neural pathways that control drug-related behavior. This review will provide an introduction and overview of the mesolimbic pathway and the influence of social reward experience on drug-seeking behavior in rodents. Moreover, the research from our laboratory on effects of sexual experience and loss of sex reward on psychostimulant and opiate reward will be reviewed. Finally, we will review current knowledge of the neural mechanisms that underlie these interactions. Investigations of the neural underpinnings by which social and drug rewards interact contribute to improved understanding of the neural basis of vulnerability for drug addiction and reward-related behaviors in general. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes in psychiatric symptoms among persons with methamphetamine dependence predicts changes in severity of drug problems but not frequency of use.

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Polcin, Douglas L; Korcha, Rachael; Bond, Jason; Galloway, Gantt; Nayak, Madhabika

2016-01-01

Few studies have examined how changes in psychiatric symptoms over time are associated with changes in drug use and severity of drug problems. No studies have examined these relationships among methamphetamine (MA)-dependent persons receiving motivational interviewing within the context of standard outpatient treatment. Two hundred seventeen individuals with MA dependence were randomly assigned to a standard single session of motivational interviewing (MI) or an intensive 9-session model of MI. Both groups received standard outpatient group treatment. The Addiction Severity Index (ASI) and timeline follow-back (TLFB) for MA use were administered at treatment entry and 2-, 4-, and 6-month follow-ups. Changes in ASI psychiatric severity between baseline and 2 months predicted changes in ASI drug severity during the same time period, but not changes on measures of MA use. Item analysis of the ASI drug scale showed that psychiatric severity predicted how troubled or bothered participants were by their drug us, how important they felt it was for them to get treatment, and the number of days they experienced drug problems. However, it did not predict the number days they used drugs in the past 30 days. These associations did not differ between study conditions, and they persisted when psychiatric severity and outcomes were compared across 4- and 6-month time periods. Results are among the first to track how changes in psychiatric severity over time are associated with changes in MA use and severity of drug problems. Treatment efforts targeting reduction of psychiatric symptoms among MA-dependent persons might be helpful in reducing the level of distress and problems associated with MA use but not how often it is used. There is a need for additional research describing the circumstances under which the experiences and perceptions of drug-related problems diverge from frequency of consumption.

Prevention and treatment in prison law: women prisoners drug dependence in Spain

Directory of Open Access Journals (Sweden)

Francisco José del Pozo Serrano

2015-05-01

Full Text Available The penitentiary drug dependence treatment for women has been traditionally generic (applied for most masculine penitentiary and with few differentiating empiric studies in an spanish level.Based on a regulatory framework, this research focuses on the study of the main elements of risk and protection implied in the relation between the drug dependant female prisoners and the treatment programs, as well as the recovery processes, in order to propose specific actions.The research has a multimethod approach, inserted within the Project I+D+I named “Mujeres reclusas drogodependientes y su reinserción social. Estudio socioeducativo y propuestas de acción” [EDU2009-13408], with a national sample of second and third degree (Central Government and Community of Catalonia, corresponding to an estimate of 15% of the female prisoners nationally. 538 valid questionnaires, 61 semi-structured interviews has been obtained, in which informatic analytical methods, specific programs for quantitative data (SPSS, V. 15 y 20, and analytical content methods for qualitative data has been applied. The analysis has been developed before and after the internment, including four profiles of female prisioners (AA: Active addicted (8'20%, EX: ex addicted (EX: 67'21%, NA: non addicted (NA: 14.75% and PMM (9.84% addicted within methadone maintenance programs .Among the main results found, it is relevant to mention the elements of risk related to the absence of participation of ex addicted women in relapse prevention programs. In fact, this is a relevant issue since 70% of the women are ex addicted. There is a large number of women not receiving any treatment in prision and not participating in any program due to lack of information, mistrust and overlap with other activities. Aditionally, theres is a perception of gender discrimination towards the access and permanece of women in the programs, compared with men.  Also, within the main elements of protection, it has been

Homeless drug users and information technology: a qualitative study with potential implications for recovery from drug dependence.

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Neale, Joanne; Stevenson, Caral

2014-09-01

Having access to information and communication technologies (ICTs) is a prerequisite to meaningful participation in society. This paper seeks to: i. explore the engagement of homeless drug users (HDUs) with ICTs and ii. discuss the findings with reference to recovery from drug dependence. The study design was qualitative and longitudinal, involving data collected in 2012-13 via 52 semi-structured interviews with 30 homeless drug users (25 men; five women). Participants were recruited from 17 hostels in two English cities. Interview data were analyzed using Framework. HDUs had access to ICTs, used ICTs, and wanted to engage with them more. Experiences of digital exclusion were a function of participants' inability to afford ICTs, the relatively cheap and poor quality technology available to them, limited knowledge about ICTs, and lack of support in using them. That HDUs were often unable to take full advantage of technology because they had nobody to explain what their devices could do or to show them how they worked was ironic given that using ICTs to (re)establish and maintain relationships were functions of technology that HDUs particularly liked. The physical, human, cultural, and social capital of HDUs influenced their access to, and use of, ICTs. Equally, ICTs were themselves an important recovery resource. Services and others should endeavor to provide HDUs with easy access to good quality technology, as well as offers of support and education so that all individuals have the knowledge and confidence to make optimum use of the technology that is available to them.

Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction

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Engleman, Eric A.; Katner, Simon N.; Neal-Beliveau, Bethany S.

2016-01-01

Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH’s effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system–dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine

Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction.

Science.gov (United States)

Engleman, Eric A; Katner, Simon N; Neal-Beliveau, Bethany S

2016-01-01

Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH's effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system-dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine neurotransmission

The prediction of drug dependence from expectancy for hostility while intoxicated.

Science.gov (United States)

Walter, D; Nagoshi, C; Muntaner, C; Haertzen, C A

1990-10-01

Three hundred seventy-one male substance-abusing volunteers for drug studies were administered the Buss-Durkee Hostility Inventory (B-D). One hundred nineteen of these subjects were readministered the B-D with the instruction to answer the items in terms of their behavior while drinking alcohol, with 67 of these subjects also completing a heroin use condition. Expectancies for hostility under alcohol or heroin were generally uncorrelated with other measures of personality, psychopathology, antisocial personality, impulsiveness, or criminality; but expectancies for hostility under alcohol were predictive of diagnoses of alcohol, opioid, and marijuana abuse and dependence over and above the influence of these other measures.

Effects of chronic mild stress on the development of drug dependence in rats.

Science.gov (United States)

Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Litwa, Ewa; Willner, Paul

2014-09-01

There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

The importance of biological rhythms in drug treatment of hypertension and sex-dependent modifications

Directory of Open Access Journals (Sweden)

Lemmer B

2012-04-01

Full Text Available Björn LemmerInstitute of Experimental and Clinical Pharmacology and Toxicology, Ruprecht-Karls-University of Heidelberg, Mannheim, GermanyAbstract: The cardiovascular system is highly organized in time. Blood pressure, heart rate, peripheral resistance, pressure, and vasodilating hormones display pronounced circadian variations. New data presented here demonstrate also sex-dependent differences in vasodilating hormones, with higher NOχ excretion in females than males and a steeper early morning rise in norepinephrine in males, whereas the 24-hour blood pressure and heart-rate profiles were not different. Various antihypertensive drugs were investigated in crossover studies – morning versus evening dosing – in hypertensive patients; however, consistent data were only described for angiotensin-converting-enzyme (ACE inhibitors, calcium channel blockers, and angiotensin II type 1 (AT1 receptor blockers. Whereas in dippers ACE inhibitors had a superdipping effect when dosed at night, no difference in the blood pressure lowering effect or on the 24-hour blood pressure profile was found with calcium channel blockers after morning and evening dosing. In nondippers, the calcium channel blockers isradipine and amlodipine transformed nondippers into dippers, similar after evening dosing. The effects of AT1-receptor blockers are similar to those of ACE inhibitors. Also, diuretics are able to normalize non dipping behavior. Moreover, a circadian phase dependency in their pharmacokinetics has been demonstrated for various cardiovascular-active drugs, such as beta blockers, calcium channel blockers, oral nitrates, and ACE inhibitors, modified by the galenic formulation. There is evidence that in hypertensive dippers, antihypertensive drugs should be given during early morning hours, whereas in non dippers it can be necessary to add an evening dose or even to apply a single evening dose in order not only to reduce high blood pressure, but also to

Red blood cell aggregation changes are depended on its initial value: Effect of long-term drug treatment and short-term cell incubation with drug.

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Muravyov, A V; Tikhomirova, I A; Maimistova, A A; Bulaeva, S V; Mikhailov, P V; Kislov, N V

2011-01-01

This study was designed to investigate whether the red cell aggregation depends on its initial level under drug therapy or cell incubation with bioactive chemical compounds. Sixty six subjects were enrolled onto this study, and sub-divided into two groups: the first group of patients (n = 36) with cerebral atherosclerosis received pentoxifylline therapy (400 mg, thrice daily) for 4 weeks. The patients of the second group were initially treated with Epoetin beta 10,000 units subcutaneously thrice a week, for 4 weeks. The second group - adult anemic patients (n = 30) with the confirmed diagnosis of solid cancer (Hb treatment the red cell aggregation increased (p treatment with pentoxifylline reduced it markedly (p treatment 75% the anemic patients with initially high RBCA had an aggregation lowering. The drop of aggregation was about 34% (p treatment. The initially low red cell aggregation after incubation with epoetin-beta was markedly increased by 122% (p drugs depend markedly on the initial, pre-treatment aggregation status of the patients. These results demonstrate that the different red blood cell aggregation responses to the biological stimuli depend strongly on the initial, pre-treatment status of the subject and the most probably it is connected with the crosstalk between the adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism.

The role of emotional and behavioral disorders in the development of drug dependence in patients with medication-induced headache (review

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A. E. Shagbazyan

2016-01-01

Full Text Available Medication-induced headache (MIH is a variety of chronic daily headache (HA. MIH belongs to secondary (symptomatic HA, develops as a complication of pre-existing primary cephalgia, and is caused by the overuse of drugs to relieve HA. The role of drug dependence syndrome and behavioral and emotional disorders in the development of MIH, which may be associated with dysfunction of certain brain systems that control these functions, has been recently discussed. The paper reviews the literature dealing with studies of the role of behavioral and emotional disorders and orbitofrontal cortical dysfunction in the development of drug dependence syndrome in patients with MIH. The importance of analyzing these aspects of MIH is determined by the prospects for applying alternative approaches to managing these patients.

Cue reactivity is associated with duration and severity of alcohol dependence: an FMRI study.

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Zsuzsika Sjoerds

Full Text Available INTRODUCTION: With the progression of substance dependence, drug cue-related brain activation is thought to shift from motivational towards habit pathways. However, a direct association between cue-induced brain activation and dependence duration has not yet been shown. We therefore examined the relationship between alcohol cue-reactivity in the brain, cue-induced subjective craving and alcohol dependence duration and severity. Since alcohol dependence is highly comorbid with depression/anxiety, which may modulate brain responses to alcohol cues, we also examined the relation between comorbid depression/anxiety and cue-reactivity. METHODS: We compared 30 alcohol dependent patients with 15 healthy controls and 15 depression/anxiety patients during a visual alcohol cue-reactivity task using functional magnetic resonance imaging blood oxygenated level-dependent responses and subjective craving as outcomes. Within the alcohol dependent group we correlated cue-reactivity with alcohol dependence severity and duration, with cue-induced craving and with depression/anxiety levels. RESULTS: Alcohol dependent patients showed greater cue-reactivity in motivational brain pathways and stronger subjective craving than depression/anxiety patients and healthy controls. Depression/anxiety was not associated with cue-reactivity, but depression severity in alcohol dependent patients was positively associated with craving. Within alcohol dependence, longer duration of alcohol dependence was associated with stronger cue-related activation of the posterior putamen, a structure involved in habits, whereas higher alcohol dependence severity was associated with lower cue-reactivity in the anterior putamen, an area implicated in goal-directed behavior preceding habit formation. CONCLUSION: Cue-reactivity in alcohol dependence is not modulated by comorbid depression or anxiety. More importantly, the current data confirm the hypothesis of a ventral to dorsal striatal shift

Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals.

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Passamonti, Luca; Luijten, M; Ziauddeen, H; Coyle-Gilchrist, I T S; Rittman, T; Brain, S A E; Regenthal, R; Franken, I H A; Sahakian, B J; Bullmore, E T; Robbins, T W; Ersche, K D

2017-08-01

Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by drugs such as cocaine. We examined the potentially beneficial effects of the noradrenaline reuptake inhibitor atomoxetine in improving cognitive control during two tasks that used cocaine- and non-cocaine-related stimuli. A double-blind, placebo-controlled, and cross-over psycho-pharmacological design was employed. A single oral dose of atomoxetine (40 mg) was administered to 28 cocaine-dependent individuals (CDIs) and 28 healthy controls. All participants performed a pictorial attentional bias task involving both cocaine- and non-cocaine-related pictures as well as a verbal go/no-go task composed of cocaine- and food-related words. As expected, CDIs showed attentional bias to cocaine-related cues whilst controls did not. More importantly, however, atomoxetine, relative to placebo, significantly attenuated attentional bias in CDIs (F 26  = 6.73, P = 0.01). During the go/no-go task, there was a treatment × trial × group interaction, although this finding only showed a trend towards statistical significance (F 26  = 3.38, P = 0.07). Our findings suggest that atomoxetine reduces attentional bias to drug-related cues in CDIs. This may result from atomoxetine's modulation of the balance between tonic/phasic activity in the locus coeruleus and the possibly parallel enhancement of noradrenergic neurotransmission within the prefrontal cortex. Studying how cognitive enhancers such as atomoxetine influence key neurocognitive indices in cocaine addiction may help to develop reliable biomarkers for patient stratification in future clinical trials.

Stop Negative Thinking Effects for Drug Dependence

OpenAIRE

Windiarti, Sri Endang; Indriati, Indriati; Surachmi, Fajar

2013-01-01

The purpose of this study was to determine the effect of therapy stop thinking negatively against drug addiction in Rehabilitation Orphanage Rumah Damai Gunung Pati Semarang. This research is quasy experiment with pretest - posttes without the control group design. Thirty respondents were taken to the reseach sujects. Stop thinking negative therapy before and after thebehavior of drug addiction there are differences (t = 0.00), so it can be stated that the therapy stop thinking negatively inf...

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.

[Limitations of insulin-dependent drugs in the treatment of type 2 diabetes mellitus].

Science.gov (United States)

Valerón, Pino Fuente; de Pablos-Velasco, Pedro L

2013-09-01

In this study, we review the efficacy and safety limitations of insulin-dependent oral antidiabetic agents. In terms of efficiency, the main drawback of metformin, sulfonylureas, gliptins and -to a lesser extent-glitazones is durability. No drug per se is able to maintain stable blood glucose control for years. Metformin, sulfonylureas and gliptins have demonstrated safety. Experience with the first two drug groups is more extensive. The main adverse effect of metformin is gastrointestinal discomfort. Major concerns related to the use of sulfonylureas are hypoglycemia and weight gain. The use of pioglitazone has been associated with an increased risk of bladder cancer, edema, heart failure, weight gain, and distal bone fractures in postmenopausal women. The most common adverse reactions associated with glucagon-like peptide-1 agonists are gastrointestinal discomfort that sometimes leads to treatment discontinuation. Copyright © 2013 Elsevier España, S.L. All rights reserved.

From the ventral to the dorsal striatum: devolving views of their roles in drug addiction.

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Everitt, Barry J; Robbins, Trevor W

2013-11-01

We revisit our hypothesis that drug addiction can be viewed as the endpoint of a series of transitions from initial voluntarily drug use to habitual, and ultimately compulsive drug use. We especially focus on the transitions in striatal control over drug seeking behaviour that underlie these transitions since functional heterogeneity of the striatum was a key area of Ann Kelley's research interests and one in which she made enormous contributions. We also discuss the hypothesis in light of recent data that the emergence of a compulsive drug seeking habit both reflects a shift to dorsal striatal control over behaviour and impaired prefontal cortical inhibitory control mechanisms. We further discuss aspects of the vulnerability to compulsive drug use and in particular the impact of impulsivity. In writing this review we acknowledge the untimely death of an outstanding scientist and a dear personal friend. Copyright © 2013 Elsevier Ltd. All rights reserved.

The analysis of drug consumption, drug trafficking and the fight against drug trafficking at the present day

Directory of Open Access Journals (Sweden)

Borisenko M.V.

2017-04-01

Full Text Available the article discusses the current drug situation in Russia, Siberian Federal District and Novosibirsk Region relating to drug consumption and drug trafficking and the main reasons of deaths of drug-dependent people.

pH-Dependent solubility and permeability criteria for provisional biopharmaceutics classification (BCS and BDDCS) in early drug discovery.

Science.gov (United States)

Varma, Manthena V; Gardner, Iain; Steyn, Stefanus J; Nkansah, Paul; Rotter, Charles J; Whitney-Pickett, Carrie; Zhang, Hui; Di, Li; Cram, Michael; Fenner, Katherine S; El-Kattan, Ayman F

2012-05-07

The Biopharmaceutics Classification System (BCS) is a scientific framework that provides a basis for predicting the oral absorption of drugs. These concepts have been extended in the Biopharmaceutics Drug Disposition Classification System (BDDCS) to explain the potential mechanism of drug clearance and understand the effects of uptake and efflux transporters on absorption, distribution, metabolism, and elimination. The objective of present work is to establish criteria for provisional biopharmaceutics classification using pH-dependent passive permeability and aqueous solubility data generated from high throughput screening methodologies in drug discovery settings. The apparent permeability across monolayers of clonal cell line of Madin-Darby canine kidney cells, selected for low endogenous efflux transporter expression, was measured for a set of 105 drugs, with known BCS and BDDCS class. The permeability at apical pH 6.5 for acidic drugs and at pH 7.4 for nonacidic drugs showed a good correlation with the fraction absorbed in human (Fa). Receiver operating characteristic (ROC) curve analysis was utilized to define the permeability class boundary. At permeability ≥ 5 × 10(-6) cm/s, the accuracy of predicting Fa of ≥ 0.90 was 87%. Also, this cutoff showed more than 80% sensitivity and specificity in predicting the literature permeability classes (BCS), and the metabolism classes (BDDCS). The equilibrium solubility of a subset of 49 drugs was measured in pH 1.2 medium, pH 6.5 phosphate buffer, and in FaSSIF medium (pH 6.5). Although dose was not considered, good concordance of the measured solubility with BCS and BDDCS solubility class was achieved, when solubility at pH 1.2 was used for acidic compounds and FaSSIF solubility was used for basic, neutral, and zwitterionic compounds. Using a cutoff of 200 μg/mL, the data set suggested a 93% sensitivity and 86% specificity in predicting both the BCS and BDDCS solubility classes. In conclusion, this study identified

Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement.

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Griffiths, R R; Chausmer, A L

2000-11-01

Caffeine is an excellent model compound for understanding drugs of abuse/dependence. The results of self-administration and choice studies in humans clearly demonstrate the reinforcing effects of low and moderate doses of caffeine. Caffeine reinforcement has been demonstrated in about 45% of normal subjects with histories of moderate and heavy caffeine use. Recent studies provide compelling evidence that caffeine physical dependence potentiates the reinforcing effects of caffeine through the mechanism of withdrawal symptom avoidance. Tolerance to the subjective and sleep-disrupting effects of caffeine in humans has been demonstrated. Physical dependence as reflected in a withdrawal syndrome in humans has been repeatedly demonstrated in adults and recently demonstrated in children. Withdrawal severity is an increasing function of caffeine maintenance dose, with withdrawal occurring at doses as low as 100 mg per day. Increased cerebral blood flow may be the physiological mechanism for caffeine withdrawal headache. Case studies in adults and adolescents clearly demonstrate that some individuals meet DSM-IV diagnostic criteria for a substance dependence syndrome on caffeine, including feeling compelled to continue caffeine use despite desires and recommendations to the contrary. Survey data suggest that 9% to 30% percent of caffeine consumers may be caffeine dependent according to DSM-IV criteria.

Association between severity of illicit drug dependence and quality of life in a psychosocial care center in BRAZIL: cross-sectional study.

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Campêlo, Selva Rios; Barbosa, Maria Alves; Dias, Danilo Rocha; Caixeta, Camila Cardoso; Leles, Cláudio Rodrigues; Porto, Celmo Celeno

2017-11-17

Quality of life must be one of the main purposes for the treatment of drug users, requiring a better understanding of the association between the quality of life and the severity of dependency. This study aimed to investigate the correlation between severity of substance use in various areas of human functioning and quality of life of illicit drug users in a psychosocial care center for alcohol and drugs. This cross-sectional study included 60 participants - illicit drug users - treated at a psychosocial care center for alcohol and drugs. Participants were evaluated with the short version of World Health Organization Quality of Life (WHOQOL-Bref) instrument to measure the quality of life, the 6th version of Addiction Severity Index (ASI-6) to assess the severity of dependence in several areas and the Mini International Neuropsychiatric Interview (MINI) to identify the presence of psychiatric disorders. Pearson and Spearman correlation tests and linear regression were applied to verify the association between the severity of dependence and the quality of life, and Student's t-test to compare the mean quality of life between individuals with and without psychiatric comorbidities. Negative correlation was found between the severity of dependence on the drugs dimensions: alcohol, psychiatric, medical, legal, family/social support and family/social problems of ASI-6, and the quality of life domains measured by the WHOQOL-Bref. The evidence was strongest in the psychiatric and medical dimensions. There was a significant difference in the quality of life mean among participants presenting or not presenting psychiatric comorbidities, for the psychological domain in anxiety disorders, and for the physical and psychological domains in mood disorders. The quality of life decreased as the severity of dependence increased, with different results in the various areas of the participant's life. This result emphasizes the need for training the professional team which works in the

Drug Release Mechanism of Slightly Soluble Drug from ...

African Journals Online (AJOL)

theophylline (THP) as drug in drug to clay ratios of 1:2, 3:4 and 1:1. The formulations were characterized for drug release and loading. Dependent and independent kinetic models were employed to analyze the drug release data. Fourier transform infrared spectroscopy (FTIR) was used for the structural characterization of ...

Drug-Target Kinetics in Drug Discovery.

Science.gov (United States)

Tonge, Peter J

2018-01-17

The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

Brief report: the influence of dissociative experiences and alcohol/drugs dependence on Internet addiction

OpenAIRE

Roberta Biolcati; Giacomo Mancini; Elena Trombini

2017-01-01

The main aim of this study is to investigate the influence of dissociative experiences and alcohol/drugs dependence on Internet addiction. From a clinical point of view Internet addiction, an excessive or poorly controlled preoccupation, urges, and/or behaviors regarding Internet use, lead to emotional and social problems in several life domains. Moreover, the increased prevalence of Internet addiction among adolescents and young adults is cause of concerns. Data was collected on 441 undergra...

Effects of acute exercise on drug craving, self-esteem, mood and affect in adults with poly-substance dependence: Feasibility and preliminary findings.

Science.gov (United States)

Ellingsen, Maren Mikkelsen; Johannesen, Sunniva Launes; Martinsen, Egil W; Hallgren, Mats

2018-06-04

Novel treatments for substance use disorders are needed. Acute bouts of exercise can improve mood states in non-clinical populations, but effects in those with poly-substance dependence are understudied. We examined the feasibility and short-term effects of three types of exercise on drug cravings, self-esteem, mood and positive/negative affect in nine poly-drug-dependent inpatients. Using a cross-over design, changes in the four study outcomes were assessed immediately before exercise and on four separate occasions post-exercise (immediately after, then at 1, 2 and 4 h post-exercise) enabling patterns of change over time (analysis of covariance) to be observed. Participants were willing and able to engage in different non-laboratory based exercises. Football was associated with non-significant short-term reductions in drug cravings. A similar trend was seen for circuit-training, but not walking. Football and circuit-training were associated with brief improvements in mood and positive/negative affect. No adverse events were reported. Football, circuit training and walking are feasible therapeutic activities for inpatients with poly-substance dependence. Controlled trials are needed to determine the long-term effects of these activities. © 2018 Australasian Professional Society on Alcohol and other Drugs.

Drug development for neurodevelopmental disorders

DEFF Research Database (Denmark)

Berry-Kravis, Elizabeth M; Lindemann, Lothar; Jønch, Aia E

2018-01-01

Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal ge......, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches. These robust preclinical findings have led...... to the implementation of the most comprehensive drug development programme undertaken thus far for a genetically defined neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate receptor 5 (mGluR5) antagonists and a phase III trial of a GABAB receptor agonist. However, none of the trials has...... been able to unambiguously demonstrate efficacy, and they have also highlighted the extent of the knowledge gaps in drug development for FXS and other neurodevelopmental disorders. In this Review, we examine potential issues in the previous studies and future directions for preclinical and clinical...

Social policy and drug dependence: an historical case study.

Science.gov (United States)

Smart, C

1985-11-01

A detailed examination is presented of the background to the reports and policy developments concerning drug dependence which emerged in Britain during the 1960s. Analysis of documents and interviews with policy makers, officials and doctors involved in the events of the period, reveal that explanatory models in terms of 'moral panic' or 'power struggle' tend to oversimplify the complex processes involved. The role in policy formation of the media, government departments and groups within the medical profession is considered. The patterns of conflict and convergence are seen to overlap simple lines of 'interest'--we find conflict within the medical profession, convergence between the Home Office (legal) and elements of the medical professions (medical). The resulting legal and institutional framework involved only loose guidelines from the centre about treatment, and the shape of policy was determined by individual doctors in the new hospital treatment centres. The apparent re-run of the 1960s being staged in the 1980s will require detailed research in the future in order to avoid superficial comparisons.

Neurocognitive Predictors of Drug Relapse

NARCIS (Netherlands)

R. Marhe (Reshmi)

2013-01-01

textabstractWorldwide, about 35 million people, that is 0.8% of the world’s adult population, use heroin and/or cocaine and more than 10-13% of these drug users are or will become drug dependent (UNODC, World Drug Report, 2012). Drug dependency is characterized as a chronic relapsing disorder

On the Comparison of Impulsivity between HIV Positive Persons, Drug-Dependent Persons, and Healthy Counterparts

Directory of Open Access Journals (Sweden)

M Nikoogoftar

2015-02-01

Full Text Available Objective: This study was an attempt to compare impulsive decision-making between AIDS sufferers, people suffering substance abuse, and nonclinical populations. Method: This was a causal-comparative study which was conducted within the six months of 2011. In this study, 30 AIDS sufferers, 30 drug abusers, and 30 healthy subjects from nonclinical population in the 15-67 age range were selected through convenience sampling. The selected participants were matched in terms of age, education, and gender. Barratt Impulsiveness Scale (1997 were administered to the three groups. Results: The results showed that there was a significant difference among the three groups in impulsivity subscales. Conclusion: The results showed that there existed some degree of deficiency in decision-making processes in AIDS sufferers and drug dependent persons. It may be rooted in a number of personality traits neurological damage drug use the insufficiency of appropriate training in life skills, problem-solving, and decision-making the availability of emotions at paly and personal and cultural thoughts and beliefs around protective behaviors in sexual relationships.

Studying the factors in dependency to substances changing the mood and behavior and effective methods in drug addiction counseling

Directory of Open Access Journals (Sweden)

2004-05-01

Full Text Available Addicts to alcohol and other substances changing the mood and behavior attempt to stop their addiction and avoid its relapse because they suffer mental and physical problems, they are under the pressure of family members, employer and other individuals who influence over their life as well as negative effects of drug addiction on their performance in family, work and social relations. Since drug addicts experience physical pain when they are not using drugs, they refer, at first, to physicians and then to psychiatrists. Although emerging and applying non-medical and non-pharmaceutical approaches models is not too old, arising various addictive drugs and increasing the number of drug addicts as well as individual/social destructive consequences of drug addiction have caused that psychiatrists, psychologists and social workers to represent various non-pharmaceutical theories, models, methods and guidelines based on the conditions of their clients and their clinical experiences. The present article attempts to identify the reasons of drug addiction tendency, consumption patterns, models, theories of addiction to substances changing the mood and behavior, various methods of drug treatment, effective methods in drug addiction counseling and non-medical and non-pharmaceutical methods to give up drug addiction by using recent research findings. On this basis, the most effective methods to help those who suffer from alcohol and other drugs abuse and dependency are studied.

FUNCTIONAL GENOMICS IDENTIFIES TIS21-DEPENDENT MECHANISMS AND PUTATIVE CANCER DRUG TARGETS UNDERLYING MEDULLOBLASTOMA SHH-TYPE DEVELOPMENT

Directory of Open Access Journals (Sweden)

Giulia Gentile

2016-11-01

Full Text Available We have recently generated a novel medulloblastoma (MB mouse model with activation of the Shh pathway and lacking the MB suppressor Tis21 (Patched1+-Tis21KO.ts main phenotype is a defect of migration of the cerebellar granule precursor cells (GCPs. By genomic analysis of GCPs in vivo, we identified as drug target and major responsible of this defect the down-regulation of the promigratory chemokine Cxcl3. Consequently, the GCPs remain longer in the cerebellum proliferative area, and the MB frequency is enhanced. Here, we further analyzed the genes deregulated in a Tis21-dependent manner (Patched1+-is21 wild-type versus Ptch1+-Tis21 knockout, among which are a number of down-regulated tumor inhibitors and up-regulated tumor facilitators, focusing on pathways potentially involved in the tumorigenesis and on putative new drug targets.The data analysis using bioinformatic tools revealed: i a link between the Shh signaling and the Tis21-dependent impairment of the GCPs migration, through a Shh-dependent deregulation of the clathrin-mediated chemotaxis operating in the primary cilium through the Cxcl3-Cxcr2 axis; ii a possible lineage shift of Shh-type GCPs toward retinal precursor phenotype the neural cell type involved in group 3 MB; iii the identification of a subset of putative drug targets for MB, involved, among the others, in the regulation of Hippo signaling and centrosome assembly. Finally, our findings define also the role of Tis21 in the regulation of gene expression, through epigenetic and RNA processing mechanisms, influencing the fate of the GCPs.

Effectiveness of Gross Model-Based Emotion Regulation Strategies Training on Anger Reduction in Drug-Dependent Individuals and its Sustainability in Follow-up.

Science.gov (United States)

Massah, Omid; Sohrabi, Faramarz; A'azami, Yousef; Doostian, Younes; Farhoudian, Ali; Daneshmand, Reza

2016-03-01

Emotion plays an important role in adapting to life changes and stressful events. Difficulty regulating emotions is one of the problems drug abusers often face, and teaching these individuals to express and manage their emotions can be effective on improving their difficult circumstances. The present study aimed to determine the effectiveness of the Gross model-based emotion regulation strategies training on anger reduction in drug-dependent individuals. The present study had a quasi-experimental design wherein pretest-posttest evaluations were applied using a control group. The population under study included addicts attending Marivan's methadone maintenance therapy centers in 2012 - 2013. Convenience sampling was used to select 30 substance-dependent individuals undergoing maintenance treatment who were then randomly assigned to the experiment and control groups. The experiment group received its training in eight two-hour sessions. Data were analyzed using analysis of co-variance and paired t-test. There was significant reduction in anger symptoms of drug-dependent individuals after gross model based emotion regulation training (ERT) (P emotion regulation strategies training. Based on the results of this study, we may conclude that the gross model based emotion regulation strategies training can be applied alongside other therapies to treat drug abusers undergoing rehabilitation.

Drug addiction: An affective-cognitive disorder in need of a cure.

Science.gov (United States)

Fattore, Liana; Diana, Marco

2016-06-01

Drug addiction is a compulsive behavioral abnormality. In spite of pharmacological treatments and psychosocial support to reduce or eliminate drug intake, addiction tends to persist over time. Preclinical and human observations have converged on the hypothesis that addiction represents the pathological deterioration of neural processes that normally serve affective and cognitive functioning. The major elements of persistent compulsive drug use are hypothesized to be structural, cellular and molecular that underlie enduring changes in several forebrain circuits that receive input from midbrain dopamine neurons and are involved in affective (e.g. ventral striatum) and cognitive (e.g. prefrontal cortex) mechanisms. Here we review recent progress in identifying crucial elements useful to understand the pathophysiology of the disease and its treatments. Manipulation of neuropeptides brain systems and pharmacological targeting of κ-opioid receptors and/or drug metabolism may hold beneficial effects at affective and cognitive level. Non-pharmacological, highly innovative approaches such as Transcranial Magnetic Stimulation may reveal unsuspected potential and promise to be the first neurobiology-based therapeutics in addiction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroimaging Impaired Response Inhibition and Salience Attribution in Human Drug Addiction: A Systematic Review.

Science.gov (United States)

Zilverstand, Anna; Huang, Anna S; Alia-Klein, Nelly; Goldstein, Rita Z

2018-06-06

The impaired response inhibition and salience attribution (iRISA) model proposes that impaired response inhibition and salience attribution underlie drug seeking and taking. To update this model, we systematically reviewed 105 task-related neuroimaging studies (n > 15/group) published since 2010. Results demonstrate specific impairments within six large-scale brain networks (reward, habit, salience, executive, memory, and self-directed networks) during drug cue exposure, decision making, inhibitory control, and social-emotional processing. Addicted individuals demonstrated increased recruitment of these networks during drug-related processing but a blunted response during non-drug-related processing, with the same networks also being implicated during resting state. Associations with real-life drug use, relapse, therapeutic interventions, and the relevance to initiation of drug use during adolescence support the clinical relevance of the results. Whereas the salience and executive networks showed impairments throughout the addiction cycle, the reward network was dysregulated at later stages of abuse. Effects were similar in alcohol, cannabis, and stimulant addiction. Copyright © 2018 Elsevier Inc. All rights reserved.

Thiomers and thiomer-based nanoparticles in protein and DNA drug delivery.

Science.gov (United States)

Hauptstein, Sabine; Bernkop-Schnürch, Andreas

2012-09-01

Thanks to advances in biotechnology, more and more highly efficient protein- and DNA-based drugs have been developed. Unfortunately, these kinds of drugs underlie poor non-parental bioavailability. To overcome hindrances like low mucosal permeability and enzymatic degradation polymeric excipients are utilized as drug carrier whereat thiolated excipients showed several promising qualities in comparison to the analogical unmodified polymer. The article deals with the comparatively easy modification of well-established polymers like chitosan or poly(acrylates) to synthesize thiomers. Further, the recently developed "next generation" thiomers e.g. preactivated or S-protected thiomers are introduced. Designative properties like mucoadhesion, uptake and permeation enhancement, efflux pump inhibition and protection against enzymatic degradation will be discussed and differences between first and next generation thiomers will be pointed out. Additionally, nanoparticles prepared with thiomers will be dealt with regarding to protein and DNA drug delivery as thiomers seem to be a promising approach to avoid parenteral application. Properties of thiomers per se and results of in vivo studies carried out so far for peptide and DNA drugs demonstrate their potential as multifunctional excipients. However, further investigations and optimizations have to be done before establishing a carrier system ready for clinical approval.

Delay discounting of oral morphine and sweetened juice rewards in dependent and non-dependent rats.

Science.gov (United States)

Harvey-Lewis, Colin; Perdrizet, Johnna; Franklin, Keith B J

2014-07-01

Opioid-dependent humans are reported to show accelerated delay discounting of opioid rewards when compared to monetary rewards. It has been suggested that this may reflect a difference in discounting of consumable and non-consumable goods not specific to dependent individuals. Here, we evaluate the discounting of similar morphine and non-morphine oral rewards in dependent and non-dependent rats We first tested the analgesic and rewarding effects of our morphine solution. In a second experiment, we assigned rats randomly to either dependent or non-dependent groups that, 30 min after daily testing, received 30 mg/kg subcutaneous dose of morphine, or saline, respectively. Delay discounting of drug-free reward was examined prior to initiation of the dosing regimen. We tested discounting of the morphine reward in half the rats and retested the discounting of the drug-free reward in the other half. All tests were run 22.5 h after the daily maintenance dose. Rats preferred the morphine cocktail to the drug-free solution and consumed enough to induce significant analgesia. The control quinine solution did not produce these effects. Dependent rats discounted morphine rewards more rapidly than before dependence and when compared to discounting drug-free rewards. In non-dependent rats both reward types were discounted similarly. These results show that morphine dependence increases impulsiveness specifically towards a drug reward while morphine experience without dependence does not.

Time-dependent recovery of in vivo binding sites after drug dosing: A method for radiotracer evaluation

International Nuclear Information System (INIS)

Kilbourn, Michael R.

1997-01-01

The recovery of in vivo binding sites for (±)-α-[ 11 C]methoxytetrabenazine, a radioligand for the monoamine vesicular transporter (VMAT2), was determined in mouse brain at various times following a pharmacological dose of tetrabenazine. Concentrations of in vivo radioligand binding sites progressively increased and had reached control values by 8.5 h, and this recovery was consistent with the pharmacokinetics of the competing drug tetrabenazine and its active metabolite, dihydrotetrabenazine. This study demonstrates a simple experimental protocol of using a single dose of a reversible competing drug and time-dependent measurements of in vivo binding of a radioligand. This protocol is suitable for testing the sensitivity of an in vivo radiotracer for measurement of varying concentrations of in vivo binding sites

Sex differences and ovarian hormones in animal models of drug dependence.

Science.gov (United States)

Carroll, Marilyn E; Anker, Justin J

2010-06-01

Increasing evidence indicates the presence of sex differences in many aspects of drug abuse. Most studies reveal that females exceed males during the initiation, escalation, extinction, and reinstatement (relapse) of drug-seeking behavior, but males are more sensitive than females to the aversive effects of drugs such as drug withdrawal. Findings from human and animal research indicate that circulating levels of ovarian steroid hormones account for these sex differences. Estrogen (E) facilitates drug-seeking behavior, while progesterone (P) and its metabolite, allopregnanalone (ALLO), counteract the effects of E and reduce drug seeking. Estrogen and P influence other behaviors that are affiliated with drug abuse such as drug-induced locomotor sensitization and conditioned place preference. The enhanced vulnerability to drug seeking in females vs. males is also additive with the other risk factors for drug abuse (e.g., adolescence, sweet preference, novelty reactivity, and impulsivity). Finally, treatment studies using behavioral or pharmacological interventions, including P and ALLO, also indicate that females show greater treatment effectiveness during several phases of the addiction process. The neurobiological basis of sex differences in drug abuse appears to be genetic and involves the influence of ovarian hormones and their metabolites, the hypothalamic pituitary adrenal (HPA) axis, dopamine (DA), and gamma-hydroxy-butyric acid (GABA). Overall, sex and hormonal status along with other biological risk factors account for a continuum of addiction-prone and -resistant animal models that are valuable for studying drug abuse prevention and treatment strategies. Copyright 2009. Published by Elsevier Inc.

Neurotrophins in the ventral tegmental area: Role in social stress, mood disorders and drug abuse.

Science.gov (United States)

Nikulina, E M; Johnston, C E; Wang, J; Hammer, R P

2014-12-12

This review discusses the impact of neurotrophins and other trophic factors, including fibroblast growth factor and glial cell line-derived neurotrophic factor, on mood disorders, weight regulation and drug abuse, with an emphasis on stress- and drug-induced changes in the ventral tegmental area (VTA). Neurotrophins, comprising nerve growth factor, brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4/5 play important roles in neuronal plasticity and the development of different psychopathologies. In the VTA, most research has focused on the role of BDNF, because other neurotrophins are not found there in significant quantities. BDNF originating in the VTA provides trophic support to dopamine neurons. The diverse intracellular signaling pathways activated by BDNF may underlie precise physiological functions specific to the VTA. In general, VTA BDNF expression increases after psychostimulant exposures, and enhanced BDNF level in the VTA facilitates psychostimulant effects. The impact of VTA BDNF on the behavioral effects of psychostimulants relies primarily on its action within the mesocorticolimbic circuit. In the case of opiates, VTA BDNF expression and effects seem to be dependent on whether an animal is drug-naïve or has a history of drug use, only the latter of which is related to dopamine mechanisms. Social defeat stress that is continuous in mice or intermittent in rats increases VTA BDNF expression, and is associated with depressive and social avoidance behaviors. Intermittent social defeat stress induces persistent VTA BDNF expression that triggers psychostimulant cross-sensitization. Understanding the cellular and molecular substrates of neurotrophin effects may lead to novel therapeutic approaches for the prevention and treatment of substance use and mood disorders. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Drug: D10250 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available 08249]) ... Other ... DG01718 ... Drugs for addictive disorder ... DG01717 ... Drugs for opioid dependence ATC code: N07BC51 ... Treatment of opioid dependence ... PubChem: 163312281 ...

Drugs in breast milk.

Science.gov (United States)

Hervada, A R; Feit, E; Sagraves, R

1978-09-01

The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

Long-Term Synaptic Changes in Two Input Pathways into the Lateral Nucleus of the Amygdala Underlie Fear Extinction

Science.gov (United States)

Park, Junchol; Choi, June-Seek

2010-01-01

Plasticity in two input pathways into the lateral nucleus of the amygdala (LA), the medial prefrontal cortex (mPFC) and the sensory thalamus, have been suggested to underlie extinction, suppression of a previously acquired conditioned response (CR) following repeated presentations of the conditioned stimulus (CS). However, little is known about…

RNA-dependent RNA polymerase: Addressing Zika outbreak by a phylogeny-based drug target study.

Science.gov (United States)

Stephen, Preyesh; Lin, Sheng-Xiang

2018-01-01

Since the first major outbreak of Zika virus (ZIKV) in 2007, ZIKV is spreading explosively through South and Central America, and recent reports in highly populated developing countries alarm the possibility of a more catastrophic outbreak. ZIKV infection in pregnant women leads to embryonic microcephaly and Guillain-Barré syndrome in adults. At present, there is limited understanding of the infectious mechanism, and no approved therapy has been reported. Despite the withdrawal of public health emergency, the WHO still considers the ZIKV as a highly significant and long-term public health challenge that the situation has to be addressed rapidly. Non-structural protein 5 is essential for capping and replication of viral RNA and comprises a methyltransferase and RNA-dependent RNA polymerase (RdRp) domain. We used molecular modeling to obtain the structure of ZIKV RdRp, and by molecular docking and phylogeny analysis, we here demonstrate the potential sites for drug screening. Two metal binding sites and an NS3-interacting region in ZIKV RdRp are demonstrated as potential drug screening sites. The docked structures reveal a remarkable degree of conservation at the substrate binding site and the potential drug screening sites. A phylogeny-based approach is provided for an emergency preparedness, where similar class of ligands could target phylogenetically related proteins. © 2017 John Wiley & Sons A/S.

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

Sensorimotor simulations underlie conceptual representations: modality-specific effects of prior activation.

Science.gov (United States)

Pecher, Diane; Zeelenberg, René; Barsalou, Lawrence W

2004-02-01

According to the perceptual symbols theory (Barsalou, 1999), sensorimotor simulations underlie the representation of concepts. Simulations are componential in the sense that they vary with the context in which the concept is presented. In the present study, we investigated whether representations are affected by recent experiences with a concept. Concept names (e.g., APPLE) were presented twice in a property verification task with a different property on each occasion. The two properties were either from the same perceptual modality (e.g., green, shiny) or from different modalities (e.g., tart, shiny). All stimuli were words. There was a lag of several intervening trials between the first and second presentation. Verification times and error rates for the second presentation of the concept were higher if the properties were from different modalities than if they were from the same modality.

Blood flow patterns underlie developmental heart defects.

Science.gov (United States)

Midgett, Madeline; Thornburg, Kent; Rugonyi, Sandra

2017-03-01

Although cardiac malformations at birth are typically associated with genetic anomalies, blood flow dynamics also play a crucial role in heart formation. However, the relationship between blood flow patterns in the early embryo and later cardiovascular malformation has not been determined. We used the chicken embryo model to quantify the extent to which anomalous blood flow patterns predict cardiac defects that resemble those in humans and found that restricting either the inflow to the heart or the outflow led to reproducible abnormalities with a dose-response type relationship between blood flow stimuli and the expression of cardiac phenotypes. Constricting the outflow tract by 10-35% led predominantly to ventricular septal defects, whereas constricting by 35-60% most often led to double outlet right ventricle. Ligation of the vitelline vein caused mostly pharyngeal arch artery malformations. We show that both cardiac inflow reduction and graded outflow constriction strongly influence the development of specific and persistent abnormal cardiac structure and function. Moreover, the hemodynamic-associated cardiac defects recapitulate those caused by genetic disorders. Thus our data demonstrate the importance of investigating embryonic blood flow conditions to understand the root causes of congenital heart disease as a prerequisite to future prevention and treatment. NEW & NOTEWORTHY Congenital heart defects result from genetic anomalies, teratogen exposure, and altered blood flow during embryonic development. We show here a novel "dose-response" type relationship between the level of blood flow alteration and manifestation of specific cardiac phenotypes. We speculate that abnormal blood flow may frequently underlie congenital heart defects. Copyright © 2017 the American Physiological Society.

Paradoxical dopaminergic drug effects in extraversion: Dose- and time-dependent effects of Sulpiride on EEG theta activity

Directory of Open Access Journals (Sweden)

Mira-Lynn eChavanon

2013-04-01

Full Text Available Dopaminergic drugs frequently produce paradoxical effects depending on baseline performance levels, genotype or personality traits. The present study for the first time aimed to specify the mechanisms underlying such opposite effects using the following recently reported scenario as an example: Depending on the personality trait agentic extraversion (aE; i.e. assertiveness, dominance, ambition, positive emotionality the selective dopamine D2 receptor antagonist sulpiride (200 mg had opposite effects on resting posterior versus anterior theta activity in the electroencephalogram (EEG. In order to better describe these opposite pharmaco-EEG effects and to generate hypotheses regarding the underlying mechanisms, we measured the EEG intermittently over five hours in 80 healthy male volunteers extremely high or low in aE who had received either placebo or one of three doses of sulpiride (50 mg, 200 mg, or 400 mg. The findings suggest a model postulating stronger pre- versus postsynaptic subreceptor effects in high aE individuals compared to low aE individuals. Future studies may now systematically apply the model to other examples of paradoxical dopaminergic drug effects and examine the molecular basis of individual differences in pre- versus postsynaptic dopamine D2 subreceptor sensitivities and densities.

[Are there any sex/gender differences in drug use and drug addiction?].

Science.gov (United States)

Mendrek, Adrianna

Drug use and drug addiction have been traditionally considered to be a male problem, however the gender gap has been decreasing over the past few decades. Thus, while the prevalence of alcohol, cannabis and nicotine dependence is still overall greater among men than among women, sex/gender differences in the abuse of stimulants and opiates seem to have disappeared. Moreover, women appear to be more prone to develop drug dependence, suffer more severe physical and psychological consequences of drug abuse, and have more difficulties quitting the habit. Numerous psychological, socio-cultural and biological factors have been implicated in these changing statistics. For example, while a large proportion of men initiate drug use to induce feelings of elation, energy or focus, women frequently start taking drugs to alleviate pre-existing mental health problems, including high levels of stress, feelings of alienation, depression, anxiety, or post-traumatic stress disorder. This maladaptive self-medication strategy often results in a faster transition to a habitual drug use and eventually a more severe dependence. In addition, the socio-cultural norms (particularly in the Western society) have changed dramatically over the past few decades. Thus, while there is still a more severe stigma and prejudice against women who use drugs (especially if they are pregnant of have children), overall there is much greater acceptance of women's drug use than it was several decades ago. Moreover, women have much greater access to various drugs of abuse than they used to have. Finally, over the past couple of decades new research started emerging pointing to some neurobiological factors that could also contribute to sex differences in drug addiction. Thus, there is now evidence that dopamine system, which for decades has been strongly implicated in drug reinforcement, is sexually dimorphic. The number of dopaminergic neurons, the density of the dopaminergic terminals, as well as

Vulnerability for cocaine dependence / Involvement of µ-opioid receptors

NARCIS (Netherlands)

Lesscher, Heidi Maria Bonifacio

2004-01-01

Drug dependence is a major health issue worldwide, which is characterised by its persistence and high rates of relapse. Individual differences exist in the vulnerability for drug dependence after first exposure to drugs of abuse like cocaine. A likely risk factor for drug dependence is the

The thalamus in drug addiction: from rodents to humans.

Science.gov (United States)

Huang, Anna S; Mitchell, Jameson A; Haber, Suzanne N; Alia-Klein, Nelly; Goldstein, Rita Z

2018-03-19

Impairments in response inhibition and salience attribution (iRISA) have been proposed to underlie the clinical symptoms of drug addiction as mediated by cortico-striatal-thalamo-cortical networks. The bulk of evidence supporting the iRISA model comes from neuroimaging research that has focused on cortical and striatal influences with less emphasis on the role of the thalamus. Here, we highlight the importance of the thalamus in drug addiction, focusing on animal literature findings on thalamic nuclei in the context of drug-seeking, structural and functional changes of the thalamus as measured by imaging studies in human drug addiction, particularly during drug cue and non-drug reward processing, and response inhibition tasks. Findings from the animal literature suggest that the paraventricular nucleus of the thalamus, the lateral habenula and the mediodorsal nucleus may be involved in the reinstatement, extinction and expression of drug-seeking behaviours. In support of the iRISA model, the human addiction imaging literature demonstrates enhanced thalamus activation when reacting to drug cues and reduced thalamus activation during response inhibition. This pattern of response was further associated with the severity of, and relapse in, drug addiction. Future animal studies could widen their field of focus by investigating the specific role(s) of different thalamic nuclei in different phases of the addiction cycle. Similarly, future human imaging studies should aim to specifically delineate the structure and function of different thalamic nuclei, for example, through the application of advanced imaging protocols at higher magnetic fields (7 Tesla).This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'. © 2018 The Author(s).

Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments.

Science.gov (United States)

Carroll, Marilyn E; Smethells, John R

2015-01-01

The purpose of this review is to discuss recent findings related to sex differences in behavioral dyscontrol that lead to drug addiction, and clinical implications for humans are discussed. This review includes research conducted in animals and humans that reveals fundamental aspects of behavioral dyscontrol. The importance of sex differences in aspects of behavioral dyscontrol, such as impulsivity and compulsivity, is discussed as major determinants of drug addiction. Behavioral dyscontrol during adolescence is also an important consideration, as this is the time of onset for drug addiction. These vulnerability factors additively increase drug-abuse vulnerability, and they are integral aspects of addiction that covary and interact with sex differences. Sex differences in treatments for drug addiction are also reviewed in terms of their ability to modify the behavioral dyscontrol that underlies addictive behavior. Customized treatments to reduce behavioral dyscontrol are discussed, such as (1) using natural consequences such as non-drug rewards (e.g., exercise) to maintain abstinence, or using punishment as a consequence for drug use, (2) targeting factors that underlie behavioral dyscontrol, such as impulsivity or anxiety, by repurposing medications to relieve these underlying conditions, and (3) combining two or more novel behavioral or pharmacological treatments to produce additive reductions in drug seeking. Recent published work has indicated that factors contributing to behavioral dyscontrol are an important target for advancing our knowledge on the etiology of drug abuse, intervening with the drug addiction process and developing novel treatments.

Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments

Science.gov (United States)

Carroll, Marilyn E.; Smethells, John R.

2016-01-01

The purpose of this review is to discuss recent findings related to sex differences in behavioral dyscontrol that lead to drug addiction, and clinical implications for humans are discussed. This review includes research conducted in animals and humans that reveals fundamental aspects of behavioral dyscontrol. The importance of sex differences in aspects of behavioral dyscontrol, such as impulsivity and compulsivity, is discussed as major determinants of drug addiction. Behavioral dyscontrol during adolescence is also an important consideration, as this is the time of onset for drug addiction. These vulnerability factors additively increase drug-abuse vulnerability, and they are integral aspects of addiction that covary and interact with sex differences. Sex differences in treatments for drug addiction are also reviewed in terms of their ability to modify the behavioral dyscontrol that underlies addictive behavior. Customized treatments to reduce behavioral dyscontrol are discussed, such as (1) using natural consequences such as non-drug rewards (e.g., exercise) to maintain abstinence, or using punishment as a consequence for drug use, (2) targeting factors that underlie behavioral dyscontrol, such as impulsivity or anxiety, by repurposing medications to relieve these underlying conditions, and (3) combining two or more novel behavioral or pharmacological treatments to produce additive reductions in drug seeking. Recent published work has indicated that factors contributing to behavioral dyscontrol are an important target for advancing our knowledge on the etiology of drug abuse, intervening with the drug addiction process and developing novel treatments. PMID:26903885

Segmental-dependent membrane permeability along the intestine following oral drug administration: Evaluation of a triple single-pass intestinal perfusion (TSPIP) approach in the rat.

Science.gov (United States)

Dahan, Arik; West, Brady T; Amidon, Gordon L

2009-02-15

In this paper we evaluate a modified approach to the traditional single-pass intestinal perfusion (SPIP) rat model in investigating segmental-dependent permeability along the intestine following oral drug administration. Whereas in the traditional model one single segment of the intestine is perfused, we have simultaneously perfused three individual segments of each rat intestine: proximal jejunum, mid-small intestine and distal ileum, enabling to obtain tripled data from each rat compared to the traditional model. Three drugs, with different permeabilities, were utilized to evaluate the model: metoprolol, propranolol and cimetidine. Data was evaluated in comparison to the traditional method. Metoprolol and propranolol showed similar P(eff) values in the modified model in all segments. Segmental-dependent permeability was obtained for cimetidine, with lower P(eff) in the distal parts. Similar P(eff) values for all drugs were obtained in the traditional method, illustrating that the modified model is as accurate as the traditional, throughout a wide range of permeability characteristics, whether the permeability is constant or segment-dependent along the intestine. Three-fold higher statistical power to detect segmental-dependency was obtained in the modified approach, as each subject serves as his own control. In conclusion, the Triple SPIP model can reduce the number of animals utilized in segmental-dependent permeability research without compromising the quality of the data obtained.

Risk factors in prevention of drug dependences

NARCIS (Netherlands)

Orosova, Ol'ga; Gajdosova, Beata; Madarasova-Geckova, Andrea; Van Dijk, Jitse P.

2007-01-01

The study presents the state-of-art of knowledge of risk factors of drug use as a form of risk behaviour in adolescents in individual, interpersonal, and environmental domain (family, school, society). The attention is paid to general deviation syndrome and to the construct of general tendency to

Brain Pathways to Recovery from Alcohol Dependence

Science.gov (United States)

Cui, Changhai; Noronha, Antonio; Warren, Kenneth; Koob, George F.; Sinha, Rajita; Thakkar, Mahesh; Matochik, John; Crews, Fulton T.; Chandler, L. Judson; Pfefferbaum, Adolf; Becker, Howard C.; Lovinger, David; Everitt, Barry; Egli, Mark; Mandyam, Chitra; Fein, George; Potenza, Marc N.; Harris, R. Adron; Grant, Kathleen A.; Roberto, Marisa; Meyerhoff, Dieter J.; Sullivan, Edith V.

2015-01-01

This article highlights the research presentations at the satellite symposium on “Brain Pathways to Recovery from Alcohol Dependence” held at the 2013 Society for Neuroscience Annual Meeting. The purpose of this symposium was to provide an up to date overview of research efforts focusing on understanding brain mechanisms that contribute to recovery from alcohol dependence. A panel of scientists from the alcohol and addiction research field presented their insights and perspectives on brain mechanisms that may underlie both recovery and lack of recovery from alcohol dependence. The four sessions of the symposium encompassed multilevel studies exploring mechanisms underlying relapse and craving associated with sustained alcohol abstinence, cognitive function deficit and recovery, and translational studies on preventing relapse and promoting recovery. Gaps in our knowledge and research opportunities were also discussed. PMID:26074423

COMPUTER DYNAMICS SIMULATION OF DRUG DEPENDENCE THROUGH ARTIFICIAL NEURONAL NETWORK: PEDAGOGICAL AND CLINICAL IMPLICATIONS

Directory of Open Access Journals (Sweden)

G. SANTOS

2008-05-01

Full Text Available To develop and to evaluate the efficiency of a software able to simulate a virtual patient at different stages of addition was the main goal and challenge of this work. We developed the software in Borland™ Delphi  5®  programming language. Techniques of artificial intelligence, neuronal networks and expert systems, were responsible for modeling the neurobiological structures and mechanisms of the interaction with the drugs used. Dynamical simulation and  hypermedia were designed to increase the software’s interactivity which was able to show graphical information from virtual instrumentation and from realistic functional magnetic resonance imaging display. Early, the program was designed to be used by undergraduate students to improve their neurophysiologic learn, based not only in an interaction of membrane receptors with drugs, but in such a large behavioral simulation. The experimental manipulation of the software was accomplished by: i creating a virtual patient from a normal mood to a behavioral addiction, increasing gradatively: alcohol, opiate or cocaine doses. ii designing an approach to treat the patient, to get total or partial remission of behavioral disorder by combining psychopharmacology and psychotherapy. Integration of dynamic simulation with hypermedia and artificial intelligence has been able to point out behavioral details as tolerance, sensitization and level of addiction to drugs of abuse and so on, turned into a potentially useful tool in the development of teaching activities on several ways, such as education as well clinical skills, in which it could assist patients, families and health care to improve and test their knowledge and skills about different faces supported by drugs dependency. Those features are currently under investigation.

Risk-taking in disorders of natural and drug rewards: neural correlates and effects of probability, valence, and magnitude.

Science.gov (United States)

Voon, Valerie; Morris, Laurel S; Irvine, Michael A; Ruck, Christian; Worbe, Yulia; Derbyshire, Katherine; Rankov, Vladan; Schreiber, Liana Rn; Odlaug, Brian L; Harrison, Neil A; Wood, Jonathan; Robbins, Trevor W; Bullmore, Edward T; Grant, Jon E

2015-03-01

Pathological behaviors toward drugs and food rewards have underlying commonalities. Risk-taking has a fourfold pattern varying as a function of probability and valence leading to the nonlinearity of probability weighting with overweighting of small probabilities and underweighting of large probabilities. Here we assess these influences on risk-taking in patients with pathological behaviors toward drug and food rewards and examine structural neural correlates of nonlinearity of probability weighting in healthy volunteers. In the anticipation of rewards, subjects with binge eating disorder show greater risk-taking, similar to substance-use disorders. Methamphetamine-dependent subjects had greater nonlinearity of probability weighting along with impaired subjective discrimination of probability and reward magnitude. Ex-smokers also had lower risk-taking to rewards compared with non-smokers. In the anticipation of losses, obesity without binge eating had a similar pattern to other substance-use disorders. Obese subjects with binge eating also have impaired discrimination of subjective value similar to that of the methamphetamine-dependent subjects. Nonlinearity of probability weighting was associated with lower gray matter volume in dorsolateral and ventromedial prefrontal cortex and orbitofrontal cortex in healthy volunteers. Our findings support a distinct subtype of binge eating disorder in obesity with similarities in risk-taking in the reward domain to substance use disorders. The results dovetail with the current approach of defining mechanistically based dimensional approaches rather than categorical approaches to psychiatric disorders. The relationship to risk probability and valence may underlie the propensity toward pathological behaviors toward different types of rewards.

Drug: D08669 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available 571 ... Nicotinic cholinergic receptor partial agonist Other ... DG01718 ... Drugs for addictive disorder ... DG01715 ... Drugs for nicotine depend...ence ATC code: N07BA03 Chemical group: DG00995 ... Nicotine withdrawal CHRNA4/CHRNB2

Drug: D10143 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available 1718 ... Drugs for addictive disorder ... DG01716 ... Drugs for alcohol dependence Chemical group: DG01756 ... opioid ...modulator Treatment of alcohol dependence ... CAS: 676501-25-0 PubChem: 135626861 ChEMBL: CHEMBL2103878 LigandBox: D10143 ...

Opponent appetitive-aversive neural processes underlie predictive learning of pain relief.

Science.gov (United States)

Seymour, Ben; O'Doherty, John P; Koltzenburg, Martin; Wiech, Katja; Frackowiak, Richard; Friston, Karl; Dolan, Raymond

2005-09-01

Termination of a painful or unpleasant event can be rewarding. However, whether the brain treats relief in a similar way as it treats natural reward is unclear, and the neural processes that underlie its representation as a motivational goal remain poorly understood. We used fMRI (functional magnetic resonance imaging) to investigate how humans learn to generate expectations of pain relief. Using a pavlovian conditioning procedure, we show that subjects experiencing prolonged experimentally induced pain can be conditioned to predict pain relief. This proceeds in a manner consistent with contemporary reward-learning theory (average reward/loss reinforcement learning), reflected by neural activity in the amygdala and midbrain. Furthermore, these reward-like learning signals are mirrored by opposite aversion-like signals in lateral orbitofrontal cortex and anterior cingulate cortex. This dual coding has parallels to 'opponent process' theories in psychology and promotes a formal account of prediction and expectation during pain.

Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

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Asuka Baba

2016-01-01

Full Text Available Background: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm, the absence of such changes by these drugs indicates their mast cell-stabilizing properties. Methods: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Relatively lower concentrations of tranilast (100, 250 µM and ketotifen (1, 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM and ketotifen (50, 100 µM almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. Conclusions: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

Drug: D01340 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available gif ... Analgesic ... DG01586 ... Opioid receptor antagonist Other ... DG01718 ... Drugs for addictive disorder ... DG01717 ... Drugs for opioid depend...ence Therapeutic category: 2219 ATC code: A06AH04 V03AB15 Chemical group: DG01155 ...

Sex differences in behavioral dyscontrol: Role in drug addiction and novel treatments

Directory of Open Access Journals (Sweden)

Marilyn E. Carroll

2016-02-01

Full Text Available The purpose of this review is to discuss recent findings related to sex differences in behavioral dyscontrol that lead to drug addiction, and clinical implications for humans are discussed. This review includes research conducted in animals and humans that reveals fundamental aspects of behavioral dyscontrol. The importance of sex differences in aspects of behavioral dyscontrol, such as impulsivity and compulsivity, are discussed as major determinants of drug addiction. Behavioral dyscontrol during adolescence is also an important consideration, as this is the time of onset for drug addiction. These vulnerability factors additively increase drug abuse vulnerability, and they are integral aspects of addiction that covary and interact with sex differences. Sex differences in treatments for drug addiction are also reviewed in terms of their ability to modify the behavioral dyscontrol that underlies addictive behavior. Customized treatments to reduce behavioral dyscontrol are discussed, such as: 1 using natural consequences such as nondrug rewards (e.g., exercise to maintain abstinence, or using punishment as a consequence for drug use, 2 targeting factors that underlie behavioral dyscontrol, such as impulsivity or anxiety, by repurposing medications to relieve these underlying conditions, and 3 combining two or more novel behavioral or pharmacological treatments to produce additive reductions in drug seeking. Recent published work has indicated that factors contributing to behavioral dyscontrol are an important target for advancing our knowledge on the etiology of drug abuse, intervening with the drug addiction process and developing novel treatments.

Addiction research centres and the nurturing of creativity: National Drug Dependence Treatment Centre, India--a profile.

Science.gov (United States)

Ray, Rajat; Dhawan, Anju; Chopra, Anita

2013-10-01

The National Drug Dependence Treatment Centre (NDDTC) is a part of the All India Institute of Medical Sciences, a premier autonomous medical university in India. This article provides an account of its origin and its contribution to the field of substance use disorder at the national and international levels. Since its establishment, the NDDTC has played a major role in the development of various replicable models of care, the training of post-graduate students of psychiatry, research, policy development and planning. An assessment of the magnitude of drug abuse in India began in the early 1990s and this was followed by a National Survey on Extent, Patterns and Trends of Drug Abuse in 2004. Several models of clinical care have been developed for population subgroups in diverse settings. The centre played an important role in producing data and resource material which helped to scale up opioid substitution treatment in India. A nationwide database on the profile of patients seeking treatment (Drug Abuse Monitoring System) at government drug treatment centres has also been created. The centre has provided valuable inputs for the Government of India's programme planning. Besides clinical studies, research has also focused on pre-clinical studies. Capacity-building is an important priority, with training curricula and resource material being developed for doctors and paramedical staff. Many of these training programmes are conducted in collaboration with other institutions in the country. The NDDTC has received funding from several national and international organizations for research and scientific meetings, and, most recently (2012), it has been designated as a World Health Organization Collaborating Centre on Substance Abuse. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Evaluating Dependence Criteria for Caffeine

OpenAIRE

Striley, Catherine L.W.; Griffiths, Roland R.; Cottler, Linda B.

2011-01-01

Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who re...

Parental rearing patterns and drug abuse. Preliminary report.

Science.gov (United States)

Kokkevi, A; Stefanis, C

1988-01-01

Results from a controlled study on a sample of 91 imprisoned drug dependents on perceived parental rearing practices using the EMBU and on parental family characteristics are presented. While few differences were observed between drug dependents and imprisoned controls-father less warm and mother more permissive in drug dependent group--comparisons of drug dependents with a general population sample revealed more differences between the two populations: drug dependents perceive both parents compared to the general population group as less rejective, very permissive, their mother as warmer and more overprotective and their father more inconsistent and less favouring them than siblings. Supportive evidence on the dependents' family psychopathology is provided by studying family characteristics. While our findings seem to support the prevailing view in the literature on the role of the mother of the drug dependent characterised by strong emotional bonds and overprotection as well as of the rather emotionally distant father, the question is raised on the contribution of other factors, such as psychopathic personality, on the above findings.

[Evaluation of the relapse prevention guidance for drug-dependent inmates: the intervention using self-teach workbook and group therapy in a "private finance initiative" prison--the first report].

Science.gov (United States)

Matsumoto, Toshihiko; Imamura, Fumie; Kobayashi, Ohji; Wada, Kiyoshi; Ozaki, Shiro; Takeuchi, Yoshio; Hasegawa, Masahiko; Imamura, Yoko; Tania, Yuko; Adachi, Yasumori

2011-04-01

In Japan, methamphetamine (MAP) abuse has been a serious problem for 60 years, and many of MAP abusers have been incarcerated in prisons as a violator of the Stimulant Control Law in Japan. The purpose of the present study is to evaluate effectiveness of the relapse prevention guidance for drug-dependent inmates using a self-teaching workbook for drug-abusing adolescents and group therapy, conducted in the Harima Rehabilitation Program Center, one of the new prisons which the Ministry of Justice founded cooperating private enterprises as a "Private Finance Initiative" project. We provided for 89 male drug-dependent inmates, incarcerated in the Harima Rehabilitation Program Center, with the relapse prevention guidance consisting of a self-teaching workbook and group therapy, and implement pre-and post-evaluations by the Self-efficacy Scale for Drug Dependence (SES) and the Stages of Change Readiness and Treatment Eagerness Scale, 8th version for Drug Dependence (SOCRATES-8D). After a waiting term, the participants were provided with a self-teaching program, subsequently with a group program. At the point of completing the waiting term, no significant changes were observed in the SES and SOCRATES-8D scores. However, at the point of completing the self-teaching program, the SES scores significantly fell, while the total SOCRATES-8D score and the scores of the two subscales, the "Recognition" and "Ambivalence," significantly rose. Further, at the point of completing the group program, the total scores of the SES and SOCRATES-8D, and the score of the two SOCRATES-8D subscales, the "Recognition" and "Taking Steps," significantly rose. The relapse prevention guidance consisting of a self-teaching workbook and group therapy, conducted in the Harima Rehabilitation Program Center, were supposed to bring same internal changes as the "Stage of Changes" model, proposed by Prochaska and DiClemente, to drug-dependent inmates.

Drug: D10144 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available HCl D10144.gif ... Other ... DG01718 ... Drugs for addictive disorder ... DG01716 ... Drugs for alcohol dependence Chem...ical group: DG01756 ... Treatment of alcohol dependence ... CAS: 1179819-25-0 PubChem: 135626862 ChEMBL: CHEMBL2105746 LigandBox: D10144 ...

Bio-Psycho-Spiritual Modeling in Drug Dependents and Compiling of Intervention Program for Promotion of Resiliency Based on Cognitive Narratology and Positive Psychology

Directory of Open Access Journals (Sweden)

Ezat ollah Kordmirza Nikoozadeh

2009-08-01

Full Text Available Introduction: Since the past few decades, the concentration of researches on drug abuse and drugs dependency have shift from risk factor to protective factors. In the past two decades, the concept of resiliency was increasingly considered by developmental psychology. The concentration shifted from risk to resiliency originates from disadvantage in emphasizing on identification of risk factors. Method: Target population was all volunteer addicts who referred to clinics in Tehran city. The group selected based on random cluster sampling. In total 319 persons (male composed of two groups, dependent to drug (150 persons and independent to drug (169 persons were participated in research and in general, 108 questionnaires of non-addicts and 126 of addicts were analyzed. In order to determine the fit model based on assumed variables in the research, by utilizing LISREL softwar99e, initially the relation between primary fundamental variables and final endogenous variables were reviewed. In continuation, the - relations between intermediary and endogenous variables were determined. Results: The results showed the fitting of predicted model of resiliency. Conclusion: In this research the program based on bio-psycho-spiritual model for instructional intervention in order to enhance of resiliency of addict people provided.

The risk of alcohol and drug dependence among healthcare workers as a result of excessive stress.

OpenAIRE

Chudá, Romana

2012-01-01

Charles University in Prague First Faculty of Medicine Department of Psychiatry, Center for Addictology School Year: 2007/2010 Abstract of the bachelor work Name: Romana Chudá Specialization: Adiktologie Matriculation year: 2007 Supervisor: MUDr. Petr Popov Opponent: MUDr. Dušan Randák Pages: 61 The title of the bachelor work: The risk of alcohol and drug dependence aminy healthcare workers as a result of excessive stress Abstract: The author has several times seen medical staff, who had been...

Hip mechanics underlie lower extremity power training-induced increase in old adults' fast gait velocity : The Potsdam Gait Study (POGS)

NARCIS (Netherlands)

Beijersbergen, Chantal M. I.; Granacher, Urs; Gäbler, Martijn; DeVita, Paul; Hortobagyi, Tibor

Background: Aging is associated with slowed gait and old compared with young adults generally walk with greater positive hip work (H1) and reduced positive ankle work (A2). The role of exercise interventions on old adults' gait mechanics that underlie training-induced improvements in gait velocity

Drug decriminalization and the price of illicit drugs.

Science.gov (United States)

Félix, Sónia; Portugal, Pedro

2017-01-01

This study is an empirical assessment of the impact of the drug decriminalization policy followed by Portugal in July 2001, on the price of illicit drugs. The analysis is performed using a difference-in-differences approach and the Synthetic Control Method in order to construct a synthetic control unit from a convex combination of countries. The results suggest that the prices of opiates and cocaine in the post-treatment period did not decrease in the sequence of the policy change. We conclude that the drug decriminalization policy seems to have caused no harm through lower illicit drugs prices, which would lead to higher drug usage and dependence. Copyright © 2016 Elsevier B.V. All rights reserved.

Examination of the causes of covariation between conduct disorder symptoms and vulnerability to drug dependence.

Science.gov (United States)

Button, Tanya M M; Hewitt, John K; Rhee, Soo Hyun; Young, Susan E; Corley, Robin P; Stallings, Michael C

2006-02-01

Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview--Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.

Drug Education: An Emphasis on Chemical Dependency.

Science.gov (United States)

Violette, Ronald W.

Efforts in the area of drug education have been less than successful over the years. The time has come to step back and reevaluate and reassess what it is we are trying to accomplish. Emphases in the past have certainly been well intentioned, but a new direction needs to be charted for the future. Health Educators and other professionals have…

Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels

Science.gov (United States)

Cui, Jianmin

2016-01-01

Gating of voltage-dependent cation channels involves three general molecular processes: voltage sensor activation, sensor-pore coupling, and pore opening. KCNQ1 is a voltage-gated potassium (Kv) channel whose distinctive properties have provided novel insights on fundamental principles of voltage-dependent gating. 1) Similar to other Kv channels, KCNQ1 voltage sensor activation undergoes two resolvable steps; but, unique to KCNQ1, the pore opens at both the intermediate and activated state of voltage sensor activation. The voltage sensor-pore coupling differs in the intermediate-open and the activated-open states, resulting in changes of open pore properties during voltage sensor activation. 2) The voltage sensor-pore coupling and pore opening require the membrane lipid PIP2 and intracellular ATP, respectively, as cofactors, thus voltage-dependent gating is dependent on multiple stimuli, including the binding of intracellular signaling molecules. These mechanisms underlie the extraordinary KCNE1 subunit modification of the KCNQ1 channel and have significant physiological implications. PMID:26745405

Brief report: the influence of dissociative experiences and alcohol/drugs dependence on Internet addiction

Directory of Open Access Journals (Sweden)

Roberta Biolcati

2017-05-01

Full Text Available The main aim of this study is to investigate the influence of dissociative experiences and alcohol/drugs dependence on Internet addiction. From a clinical point of view Internet addiction, an excessive or poorly controlled preoccupation, urges, and/or behaviors regarding Internet use, lead to emotional and social problems in several life domains. Moreover, the increased prevalence of Internet addiction among adolescents and young adults is cause of concerns. Data was collected on 441 undergraduate students (285 female, aging from 18 to 36, using an assessment self-reporting set consisting of the Young’s Internet Addiction Test, the Leeds Dependence Questionnaire and the Dissociative Experience Scale. Results converging for the three psychological phenomena involved are interrelated, corroborating the hypothesis of the search for an altered state of consciousness as their common underlying mechanism. Findings show that the tendency to escape from reality, through dissociation and substance abuse, are risk factors for Internet addiction in youngsters. The implications of these results are discussed in a preventive and clinical perspective.

Evaluating Dependence Criteria for Caffeine.

Science.gov (United States)

Striley, Catherine L W; Griffiths, Roland R; Cottler, Linda B

2011-12-01

Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who reported caffeine use in the last 7 days and also reported use of alcohol, nicotine, or illicit drugs within the past year ( n =167). Results: Thirty-five percent met the criteria for dependence when all seven of the adopted DSM dependence criteria were used. Rates of endorsement of several of the most applicable diagnostic criteria were as follows: 26% withdrawal, 23% desire to cut down or control use, and 44% continued use despite harm. In addition, 34% endorsed craving, 26% said they needed caffeine to function, and 10% indicated that they talked to a physician or counselor about problems experienced with caffeine. There was a trend towards increased caffeine dependence among those dependent on nicotine or alcohol. Within a subgroup that had used caffeine, alcohol, and nicotine in the past year, 28% fulfilled criteria for caffeine dependence compared to 50% for alcohol and 80% for nicotine. Conclusion: The present study adds to a growing literature suggesting the reliability, validity, and clinical utility of the caffeine dependence diagnosis. Recognition of caffeine dependence in the DSM-V may be clinically useful.

Drug: D05157 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D05157 Drug Nicotine polacrilex (USAN); Nicorette (TN) ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01715 ... Drugs for nicotine dependence Cyp substrate ... DG01638 ... CYP2A6 substrate Cy

The effects of exogenous progesterone on drug craving and stress arousal in cocaine dependence: impact of gender and cue type.

Science.gov (United States)

Fox, Helen C; Sofuoglu, Mehmet; Morgan, Peter T; Tuit, Keri L; Sinha, Rajita

2013-09-01

Exogenous progesterone has been shown to attenuate the rewarding effects of cocaine. However, its effects on provoked drug craving, stress arousal and cognitive performance has not been systematically investigated in cocaine dependent men and women. Thus, we conducted a double-blind placebo-controlled study assessing the efficacy of progesterone in reducing provoked drug craving, stress system arousal and improving cognitive performance in cocaine dependent men and women. Forty-two early abstinent treatment-seeking cocaine dependent individuals were randomly assigned to either daily doses of placebo (12M/9F) or micronized progesterone (12M/9F) (400 mg/day), for 7 days. Under experimental conditions, all subjects were exposed to three 5-min personalized guided imagery conditions (stress, cocaine cue, relaxing), one per day, consecutively in a random, counterbalanced order. Subjective craving, mood, hypothalamic-pituitary-adrenal (HPA) and cardiovascular output, and a cognitive measure of inhibitory control (Stroop Color Word Task) were assessed pre- and post imagery. Progesterone relative to placebo significantly decreased cue-induced craving and cortisol responses and increased cue-induced ACTH. In addition, women but not men receiving progesterone reported lower ratings of negative emotion and higher ratings of relaxed mood following stress exposure. Improved Stroop performance was observed in all participants receiving progesterone, across all conditions. Progesterone was selectively effective in reducing cocaine cue-induced but not stress-related cocaine craving as well as specific measures of the provoked arousal state. Findings suggest that progesterone's effects on drug craving and arousal are moderated by both the type of environmental cue exposure and gender. Copyright © 2013 Elsevier Ltd. All rights reserved.

mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse.

Science.gov (United States)

Neasta, Jeremie; Barak, Segev; Hamida, Sami Ben; Ron, Dorit

2014-07-01

The mammalian (or mechanistic) target of rapamycin (mTOR) complex 1 (mTORC1) is a serine and threonine kinase that regulates cell growth, survival, and proliferation. mTORC1 is a master controller of the translation of a subset of mRNAs. In the central nervous system mTORC1 plays a crucial role in mechanisms underlying learning and memory by controlling synaptic protein synthesis. Here, we review recent evidence suggesting that the mTORC1 signaling pathway promotes neuroadaptations following exposure to a diverse group of drugs of abuse including stimulants, cannabinoids, opiates, and alcohol. We further describe potential molecular mechanisms by which drug-induced mTORC1 activation may alter brain functions. Finally, we propose that mTORC1 is a focal point shared by drugs of abuse to mediate drug-related behaviors such as reward seeking and excessive drug intake, and offer future directions to decipher the contribution of the kinase to mechanisms underlying addiction. Recent studies suggesting that exposure to diverse classes of drugs of abuse as well as exposure to drug-associated memories lead to mTORC1 kinase activation in the limbic system. In turn, mTORC1 controls the onset and the maintenance of pathological neuroadaptions that underlie several features of drug addiction such as drug seeking and relapse. Therefore, we propose that targeting mTORC1 and its effectors is a promising strategy to treat drug disorders. © 2014 International Society for Neurochemistry.

[Treatment approaches for synthetic drug addiction].

Science.gov (United States)

Kobayashi, Ohji

2015-09-01

In Japan, synthetic drugs have emerged since late 2000s, and cases of emergency visits and fatal traffic accidents due to acute intoxication have rapidly increased. The synthetic drugs gained popularity mainly because they were cheap and thought to be "legal". The Japanese government restricted not only production and distribution, but also its possession and use in April 2014. As the synthetic drug dependent patients have better social profiles compared to methamphetamine abusers, this legal sanction may have triggered the decrease in the number of synthetic drug dependent patient visits observed at Kanagawa Psychiatric Center since July 2014. Treatment of the synthetic drug dependent patients should begin with empathic inquiry into the motives and positive psychological effects of the drug use. In the maintenance phase, training patients to trust others and express their hidden negative emotions through verbal communications is essential. The recovery is a process of understanding the relationship between psychological isolation and drug abuse, and gaining trust in others to cope with negative emotions that the patients inevitably would face in their subsequent lives.

[Development of a program of prevention of drug dependence in school children].

Science.gov (United States)

García Lerín, A; Calvo Trujillo, S; Sánchez-Porro Valadés, P

1997-03-15

To promote healthy habits of behaviour among school-children so that they reject drug-taking and learn to identify high-risk situations. Quasi-experimental study. The Amorós private school in Carabanchel, in Madrid's Health District XI. 45 pupils from the eighth year of basic, aged between 13 and 14. Quantitative and qualitative methods. Quantitative indicators were: number of students who attended the activities organised, their level of participation, the number of new terms, increase in knowledge. Qualitative indicators were the oral poll of class leaders, attainment of objectives, later evaluation of changes in attitude towards drug-takers and collages among the initiatives after the course. Drug-taking usually starts in the family context, leisure situations and peers. In this study isolated consumption was also detected. Most commonly consumed drugs were: caffeine, tobacco (mainly Virginia), alcohol occasionally, and cannabis. The type and form of drug-taking found is very similar to that of other, Spaniards of the same age. We found children who were not drug-takers, but were anxious about this because they "wanted to try out drugs".

Drug: D00123 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D00123 Drug Cyanamide (JP17); Cyanamide (TN) ... CH2N2 D00123.gif ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01716 ... Drugs for alcohol dependence Same as: C01566 Therapeutic category: 3

[Abuse, dependence and intoxication of substances].

Science.gov (United States)

Wada, Kiyoshi

2015-09-01

As for substance-related disorders, there were several differences between ICD-10 and DSM-IV, however, the concept of "dependence" had been essential for both criteria. DSM-5 published in 2013 had erased dependence. This confuses us. It is important to recognize dependence again. "Abuse" is the self-intake behavior of drug against the social norms. Repeated abuse results in dependence. Dependence is a state of loss of control against drug use due to craving. Abuse can produce "acute intoxication", and repeated abuse under dependence can produce "chronic intoxication". It is important to understand abuse, dependence and "intoxication" based on their relationship from the point of time course.

PERCEPTION AND PERFORMANCE OF THE INTERDISCIPLINARY TEAM IN SERVING DRUG DEPENDENTS IN SPECIALIZED NETWORK OF MENTAL HEALTH SINOP, MATO GROSSO

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P. V. C. Santos

2017-08-01

Full Text Available Chemical dependency is currently one of the most important public health problems in our country. The study deals with a quantitative and qualitative research, whose goal is to evaluate the perception and performance of the interdisciplinary team in serving drug dependents in specialized network of mental health Sinop, Mato Grosso. Applied a semi-structured questionnaire with objective and subjective questions with 11 professionals in health care at the Psychosocial Care Center (CAPS and Medical Specialties Center (EMC. The results reveal the importance of the preparation of these professionals to work in service to dependents and interdisciplinarity proved to be the best option to achieve a dignified and humane care

Grapefruit and drug interactions.

Science.gov (United States)

2012-12-01

Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

Pharmacogenetics of drug-drug interaction and drug-drug-gene interaction: a systematic review on CYP2C9, CYP2C19 and CYP2D6.

Science.gov (United States)

Bahar, Muh Akbar; Setiawan, Didik; Hak, Eelko; Wilffert, Bob

2017-05-01

Currently, most guidelines on drug-drug interaction (DDI) neither consider the potential effect of genetic polymorphism in the strength of the interaction nor do they account for the complex interaction caused by the combination of DDI and drug-gene interaction (DGI) where there are multiple biotransformation pathways, which is referred to as drug-drug-gene interaction (DDGI). In this systematic review, we report the impact of pharmacogenetics on DDI and DDGI in which three major drug-metabolizing enzymes - CYP2C9, CYP2C19 and CYP2D6 - are central. We observed that several DDI and DDGI are highly gene-dependent, leading to a different magnitude of interaction. Precision drug therapy should take pharmacogenetics into account when drug interactions in clinical practice are expected.

Drug: D03288 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D03288 Drug Calcium carbimide (INN) ... Ca. CN2 D03288.gif ... Other ... DG01718 ... Drugs f...or addictive disorder ... DG01716 ... Drugs for alcohol dependence Same as: C19113 ATC code: N07BB02 ... CAS: 1

Drug: D03365 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D03365 Drug Nicotine (USP); Habitrol (TN) ... C10H14N2 D03365.gif ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01715 ... Drugs for nicotine dependence Cyp substrate ... DG01892 ... CYP1A2 substra

Learning Recursion: Multiple Nested and Crossed Dependencies

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Meinou de Vries

2011-06-01

Full Text Available Language acquisition in both natural and artificial language learning settings crucially depends on extracting information from ordered sequences. A shared sequence learning mechanism is thus assumed to underlie both natural and artificial language learning. A growing body of empirical evidence is consistent with this hypothesis. By means of artificial language learning experiments, we may therefore gain more insight in this shared mechanism. In this paper, we review empirical evidence from artificial language learning and computational modeling studies, as well as natural language data, and suggest that there are two key factors that help deter-mine processing complexity in sequence learning, and thus in natural language processing. We propose that the specific ordering of non-adjacent dependencies (i.e. nested or crossed, as well as the number of non-adjacent dependencies to be resolved simultaneously (i.e. two or three are important factors in gaining more insight into the boundaries of human sequence learning; and thus, also in natural language processing. The implications for theories of linguistic competence are discussed.

The strength of aversive and appetitive associations and maladaptive behaviors

OpenAIRE

Itzhak, Yossef; Perez-Lanza, Daniel; Liddie, Shervin

2014-01-01

Certain maladaptive behaviors are thought to be acquired through classical Pavlovian conditioning. Exaggerated fear response, which can develop through Pavlovian conditioning, is associated with acquired anxiety disorders such as posttraumatic stress disorders (PTSD). Inflated reward-seeking behavior, which develops through Pavlovian conditioning, underlie some types of addictive behavior (e.g., addiction to drugs, food, gambling). These maladaptive behaviors are dependent on associative lear...

Drug: D00131 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D00131 Drug Disulfiram (JP17/USP/INN); Antabuse (TN) ... C10H20N2S4 D00131.gif ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01716 ... Drugs for alcohol dependence Cyp inhibitor ... DG01634 ... CY

Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity.

Science.gov (United States)

Moeller, Scott J; London, Edythe D; Northoff, Georg

2016-02-01

Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Expressive writing for high-risk drug dependent patients in a primary care clinic: A pilot study

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Wedgwood Lucinda

2006-11-01

Full Text Available Abstract Background Previous research has shown that expressive writing is beneficial in terms of both physical and emotional health outcomes. This study aimed to investigate the effectiveness and acceptability of a brief expressive writing intervention for high-risk drug dependent patients in a primary care clinic, and to determine the relationship between linguistic features of writing and health outcomes. Methods Participants completed four 15-minute expressive writing tasks over a week, in which they described their thoughts and feelings about a recent stressful event. Self-report measures of physical (SF-12 and psychological health (DASS-21 were administered at baseline and at a two-week follow-up. Fifty-three participants were recruited and 14 (26% completed all measures. Results No statistically significant benefits in physical or psychological health were found, although all outcomes changed in the direction of improvement. The intervention was well-received and was rated as beneficial by participants. The use of more positive emotion words in writing was associated with improvements in depression and stress, and flexibility in first person pronoun use was associated with improvements in anxiety. Increasing use of cognitive process words was associated with worsening depressive mood. Conclusion Although no significant benefits in physical and psychological health were found, improvements in psychological wellbeing were associated with certain writing styles and expressive writing was deemed acceptable by high-risk drug dependent patients. Given the difficulties in implementing psychosocial interventions in this population, further research using a larger sample is warranted.

Effectiveness of group cognitive therapy about opium addict complications on attitude of adolescents with drug dependent parents

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Kaveh Hojjat

2015-12-01

Full Text Available Background and Aim: Statistics show that 30% to 40 % of  opium addicted fathers’ children are prone to substance abuse in the future. The present study aimed at assessing the effectiveness of cognitive therapy approach  to attitude changing of adolescents with substance dependent fathers. Materials and Methods:  In this controlled. field-trail randomized study. .data collection tool was “attitude to addiction questionnaire”. The study population was all male students in the first grade of high school in Maneh - Samalghan city. . Six sessions of group cognitive therapy based on the effectiveness of drug side-effects in drug-addicted fathers’ adolescent children’s attitude were held. The above-mentioned questionnaire was filled out before and after intervention. The obtained data  was fed into SPSS software (V: 16 using. Independent t-test .and paired t-test were used for analysis and P<0.05 was taken as the significant level. Results:  There were no significant differences between the two groups in pre-test regarding their attitude about drug abuse (P=.20%. Mean score variance from pre-test to post-test in the intervention group decreased, but in the control group, it showed a slight increase. This means that the intervention reduced the positive attitude towards drugs, but the changes were not statistically significant (p=0.57. Besides, among ten factors decisive in an individual’s attitude about addiction, only group cognitive therapy  was able  to decrease mean points of an individual’s attitude about drug abuse .. Significantly (P = 0.04. Conclusion: It was found that group cognitive therapy education about opium  addict complicationsdidn`t have a significant effect on the attitude of the students with addicted fathers. Thus, a change of adolescents’ attitude requires more research.

Matrix Metalloproteinases Contribute to Neuronal Dysfunction in Animal Models of Drug Dependence, Alzheimer's Disease, and Epilepsy

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Hiroyuki Mizoguchi

2011-01-01

Full Text Available Matrix metalloproteinases (MMPs and tissue inhibitors of metalloproteinases (TIMPs remodel the pericellular environment by regulating the cleavage of extracellular matrix proteins, cell surface components, neurotransmitter receptors, and growth factors that mediate cell adhesion, synaptogenesis, synaptic plasticity, and long-term potentiation. Interestingly, increased MMP activity and dysregulation of the balance between MMPs and TIMPs have also been implicated in various pathologic conditions. In this paper, we discuss various animal models that suggest that the activation of the gelatinases MMP-2 and MMP-9 is involved in pathogenesis of drug dependence, Alzheimer's disease, and epilepsy.

Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration

NARCIS (Netherlands)

Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, Imc; Danhof, M; Meijer, J H; Burggraaf, J

2016-01-01

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in

On the Comparison of Interpersonal Sensitivity and Assertiveness between Drug-Dependent Persons and Ordinary People

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Babak Vojudi

2015-02-01

Full Text Available Objective: The present study was aimed at comparing interpersonal sensitivity and assertiveness between drug-dependent persons and ordinary people. Method: The research method was causal-comparative. The statistical population of the study consisted of all narcotic addicts of Tabriz City who referred to Addiction Treatment Centers while the research was being conducted. The number of 30 addicted persons was selected through cluster sampling and 30 ordinary persons as control group through convenience sampling method. Gmbryl & Ritchie’s assertiveness questionnaire (1975 and Boyce & Parker’s Interpersonal Sensitivity Measure (IPSM 1989 were used for data collection purposes. Results: The results showed that there was a statistically significant difference between two groups in terms of interpersonal sensitivity and assertiveness. The addicts showed less assertiveness and more interpersonal sensitivity in comparison with their healthy counterparts. Conclusion: The findings show that people who are unable to express themselves and exert sensitivity in interpersonal relationships are more likely at high risk of substance dependence. However, it is possible to prevent these persons from turning to addiction by teaching them these skills.

Procesos de estigma y exclusión en salud: Articulaciones entre estigmatización, derechos ciudadanos, uso de drogas y drogadependencia Processes of stigma and exclusion in health: Joints between stigmatization, civil rights, use of drugs and dependence of drugs

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Andrea Vázquez

2009-12-01

Full Text Available El objetivo del trabajo es establecer articulaciones entre la estigmatización, los derechos ciudadanos, el uso de drogas y la drogadependencia, como un caso particular de exclusión en salud. La estigmatización produce grupos de personas que ven condicionado su ejercicio de ciudadanía al negárseles el cumplimiento de derechos tales como el derecho a la salud. Uno de estos grupos, lo configuran los usuarios de drogas y los drogadependientes. Es relevante estudiar los procesos de estigma como barrera de accesibilidad a la atención en salud, para identificar componentes que disminuyan dicha exclusión (OPS/OMS, 2005. La reducción de la estigmatización y la discriminación del uso de drogas y la drogadependencia, es fundamental para la elaboración de políticas de inclusión desde una lógica de respeto por los derechos humanos.The aim of the work is to establish joints between the stigmatization, the civil rights, drugs use and dependence of drug, as a particular case of exclusion in health. The stigmatization produces groups of persons who have problems for the exercise of citizenship. These persons are refused in the fulfillment of rights such as the right to the health. One of these groups, it is formed by the users of drugs and the dependents of drugs. It´s relevant to study the processes of stigma as accessibility barrier to the attention in health, to identify components that diminish the above mentioned exclusion. (OPS/OMS,2005. The reduction of the stigmatization and the discrimination of the use of drugs and dependence of drug, it's fundamental for the elaboration of policies of incorporation from logic of respect for the human rights.

Characterization of Polyelectrolyte Complex Formation Between Anionic and Cationic Poly(amino acids) and Their Potential Applications in pH-Dependent Drug Delivery.

Science.gov (United States)

Folchman-Wagner, Zoë; Zaro, Jennica; Shen, Wei-Chiang

2017-06-30

Polyelectrolyte complexes (PECs) are self-assembling nano-sized constructs that offer several advantages over traditional nanoparticle carriers including controllable size, biodegradability, biocompatibility, and lack of toxicity, making them particularly appealing as tools for drug delivery. Here, we discuss potential application of PECs for drug delivery to the slightly acidic tumor microenvironment, a pH in the range of 6.5-7.0. Poly(l-glutamic acid) (E n ), poly(l-lysine) (K n ), and a copolymer composed of histidine-glutamic acid repeats ((HE) n ) were studied for their ability to form PECs, which were analyzed for size, polydispersity, and pH sensitivity. PECs showed concentration dependent size variation at residue lengths of E 51 /K 55 and E 135 /K 127 , however, no complexes were observed when E 22 or K 21 were used, even in combination with the longer chains. (HE) 20 /K 55 PECs could encapsulate daunomycin, were stable from pH 7.4-6.5, and dissociated completely between pH 6.5-6.0. Conversely, the E 51-dauno /K 55 PEC dissociated between pH 4.0 and 3.0. These values for pH-dependent particle dissociation are consistent with the p K a 's of the ionizable groups in each formulation and indicate that the specific pH-sensitivity of (HE) 20-dauno /K 55 PECs is mediated by incorporation of histidine. This response within a pH range that is physiologically relevant to the acidic tumors suggests a potential application of these PECs in pH-dependent drug delivery.

Protecting the Innocence of Youth: Moral Sanctity Values Underlie Censorship From Young Children.

Science.gov (United States)

Anderson, Rajen A; Masicampo, E J

2017-11-01

Three studies examined the relationship between people's moral values (drawing on moral foundations theory) and their willingness to censor immoral acts from children. Results revealed that diverse moral values did not predict censorship judgments. It was not the case that participants who valued loyalty and authority, respectively, sought to censor depictions of disloyal and disobedient acts. Rather, censorship intentions were predicted by a single moral value-sanctity. The more people valued sanctity, the more willing they were to censor from children, regardless of the types of violations depicted (impurity, disloyalty, disobedience, etc.). Furthermore, people who valued sanctity objected to indecent exposure only to apparently innocent and pure children-those who were relatively young and who had not been previously exposed to immoral acts. These data suggest that sanctity, purity, and the preservation of innocence underlie intentions to censor from young children.

Planning-related motor processes underlie mental practice and imitation learning.

Science.gov (United States)

Bach, Patric; Allami, Bassem Khalaf; Tucker, Mike; Ellis, Rob

2014-06-01

It is still controversial whether mental practice-the internal rehearsal of movements to improve later performance-relies on processes engaged during physical motor performance and, if so, which processes these are. We report data from 5 experiments, in which participants mentally practiced complex rhythms with either feet or hands while using the same or different body parts to respond to unrelated sounds. We found that responses were impaired for those body parts that were concurrently used in mental practice, suggesting a binding of body-part-specific motor processes to action plans. This result was found when participants mentally trained to memorize the rhythms, to merely improve their performance, when mental practice and execution directly followed one another and when separated by a different task. Finally, it was found irrespective of whether participants practiced on the basis of a symbolic rhythm description and when they practiced by watching somebody perform the rhythms (imitation learning). The effect was eliminated only when the requirement for mental practice was eliminated from the task while keeping visual stimulation identical. These data link mental practice not to execution but planning related motor processes and reveal that these planning processes underlie both mental practice and imitation learning. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Drug-induced urinary incontinence

NARCIS (Netherlands)

Tsakiris, Peter; Oelke, Matthias; Michel, Martin C.

2008-01-01

Physiological urinary continence depends on many factors that are potentially vulnerable to adverse drug effects, which may lead to incontinence. In principle, drugs could cause incontinence by lowering bladder outlet resistance and/or by increasing intravesical pressure, which disrupts the normal

New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis

Science.gov (United States)

2013-09-01

antagonist that inhibits stomach acid production. It is commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease ...situations where the maximal Epo-dependent output is not sufficient (hemolysis, sepsis, genetic bone marrow failure diseases such as Diamond Blackfan...2 These studies led us to generate two hypotheses that underlie the research supported by this grant. First, we proposed that combinations of

Drug Use, the Drug Environment, and Child Physical Abuse and Neglect.

Science.gov (United States)

Freisthler, Bridget; Wolf, Jennifer Price; Wiegmann, Wendy; Kepple, Nancy J

2017-08-01

Although drug use is considered a risk factor for child maltreatment, very little work has examined how the drug environment may affect physical abuse and neglect by parents. Utilizing information from a telephone survey with 2,597 respondents from 43 cities with valid police data on narcotics incidents, we analyzed the relationship between drug use, drug availability, and child maltreatment using multilevel models. City-level rates of drug abuse and dependence were related to more frequent physical abuse. Parents who use drugs in areas with greater availability of drugs reported more physical abuse and physical neglect. Emotional support was protective of all types of maltreatment. While most child welfare interventions focus on reducing parental drug use in order to reduce child abuse, these findings suggest environmental prevention or neighborhood strengthening approaches designed to reduce the supply of illicit drugs may also reduce child abuse through multiple mechanisms.

Excipient-mediated alteration in drug bioavailability in the rat depends on the sex of the animal.

Science.gov (United States)

Mai, Yang; Afonso-Pereira, Francisco; Murdan, Sudaxshina; Basit, Abdul W

2017-09-30

The pharmaceutical excipient, polyethylene glycol 400 (PEG 400), unexpectedly alters the bioavailability of the BCS class III drug ranitidine in a sex-dependent manner. As ranitidine is a substrate for the efflux transporter P-glycoprotein (P-gp), we hypothesized that the sex-related influence could be due to interactions between PEG 400 and P-gp. In this study, we tested this hypothesis by: i) measuring the influence of PEG 400 on the oral bioavailability of another P-gp substrate (ampicillin) and of a non-P-gp substrate (metformin); and ii) measuring the effect of PEG 400 on drug bioavailability in the presence of a P-gp inhibitor (cyclosporine A) in male and female rats. We found that PEG 400 significantly increased (pbioavailability of ampicillin (the P-gp substrate) in male rats, but not in female ones. In contrast, PEG 400 had no influence on the bioavailability of the non-P-gp substrate, metformin in male or female rats. Inhibition of P-gp by oral pre-treatment with cyclosporine A increased the bioavailability of the P-gp substrates (ampicillin and ranitidine) in males and females (pbioavailability of metformin in either male or female rats. These results prove the hypothesis that the sex-specific effect of PEG 400 on the bioavailability of certain drugs is due to the interaction of PEG 400 with the efflux transporter P-gp. Copyright © 2017 Elsevier B.V. All rights reserved.

Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

Science.gov (United States)

Pei, Xin-Yan; Dai, Yun; Felthousen, Jessica; Chen, Shuang; Takabatake, Yukie; Zhou, Liang; Youssefian, Leena E; Sanderson, Michael W; Bodie, Wesley W; Kramer, Lora B; Orlowski, Robert Z; Grant, Steven

2014-01-01

The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

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Xin-Yan Pei

Full Text Available The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

[Dependent patient and interpersonal dependency: psychotherapeutic strategies].

Science.gov (United States)

Versaevel, C

2012-04-01

This article is a review of psychotherapies for patients suffering from dependent personality and interpersonal dependency. We synthesized articles making reference to this question, notably those written by Bornstein, author who refers to the dependent personality. We highlighted the psychotherapies that have been the object of an evaluation. The research on the subject is sparse: only eight studies permitting assessment of psychotherapies in this indication in 2005. Besides these psychotherapies, we detailed other approaches which are used by practitioners in these indications. The therapy does not aim at autonomy "at all costs", but that the patient finds a dependence "adapted" to his/her environment. Before starting a therapy, an evaluation is useful to specify the type of dependence. First of all, is there a "pathological" dependence? Is the suffering of the patient secondary to his personality or not supportive enough? Does insight exist? What is the reaction of the patient if we suggest the hypothesis of a dependence on his/her part? Does he/she consider this idea or reject it? Finally, is the dependence primary or secondary? For that purpose, it is necessary to study the biography of the patient and the appearance of the comorbidity over time. The primary dependence is seen in childhood and precedes the other psychological disorders. The secondary dependence follows after the comorbidity and events of life that alter self-esteem (depression, for example). Various therapeutic strategies arise from various currents. The therapies of analytical inspiration recommend replaying the relationship of object and explicitly evoking the transfer. The behavioural and cognitive psychotherapies aim at making the patient identify the cognitions which underlie the dependence, then leading the patient to modify his/her cognition and to behave in a more autonomous way, using the theory of learning. The humanist therapies aim at a therapeutic relationship of acceptance and

Drug-Abuse Nanotechnology: Opportunities and Challenges.

Science.gov (United States)

Mahmoudi, Morteza; Pakpour, Sepideh; Perry, George

2018-05-31

Opioid drug abuse and dependence/addiction are complex disorders regulated by a wide range of interacting networks of genes and pathways that control a variety of phenotypes. Although the field has been extensively progressed since the birth of the National Institute on Drug Abuse in 1974, the fundamental knowledge and involved mechanisms that lead to drug dependence/addiction are poorly understood, and thus, there has been limited success in the prevention of drug addiction and development of therapeutics for definitive treatment and cure of addiction disease. The lack of success in both identification of addiction in at-risk populations and the development of efficient drugs has resulted in a serious social and economic burden from opioid drug abuse with global increasing rate of mortality from drug overdoses. This perspective aims to draw the attention of scientists to the potential role of nanotechnologies, which might pave the way for the development of more practical platforms for either drug development or identification and screening of patients who may be vulnerable to addiction after using opioid drugs.

Comparison of health care needs of child family members of adults with alcohol or drug dependence versus adults with asthma or diabetes.

Science.gov (United States)

Ray, G Thomas; Mertens, Jennifer R; Weisner, Constance

2014-05-01

To compare the health problems, preventive care utilization, and medical costs of child family members (CFMs) of adults diagnosed with alcohol or drug dependence (AODD) to CFMs of adults diagnosed with diabetes or asthma. Child family members of adults diagnosed with AODD between 2002 and 2005 and CFMs of matched adults diagnosed with diabetes or asthma were followed up to 7 years after diagnosis of the index adult. Logistic regression was used to determine whether the CFMs of AODD adults were more likely to be diagnosed with medical conditions, or get preventive care, than the CFMs of adults with asthma or diabetes. Children's health services use was compared using multivariate models. In Year 5 after index date, CFMs of adults with AODD were more likely to be diagnosed with depression and AODD than CFMs of adults with asthma or diabetes and were less likely to be diagnosed with asthma, otitis media, and pneumonia than CFMs of adults with asthma. CFMs of AODD adults were less likely than CFMs of adult asthmatic patients to have annual well-child visits. CFMs of AODD adults had similar mean annual total health care costs to CFMs of adults with asthma but higher total costs ($159/yr higher, confidence interval, $56-$253) than CFMs of adult diabetic patients. CFMs of adults with AODD had higher emergency department, higher outpatient alcohol and drug program, higher outpatient psychiatry, and lower primary care costs than CFMs of either adult asthmatic patients or diabetic patients. Children in families with an alcohol- or drug-dependent adult have unique patterns of health conditions, and differences in the types of health services used, compared to children in families with an adult asthmatic or diabetic family member. However, overall cost and utilization for health care services is similar or only somewhat higher. This is the first study of its kind, and the results have implications for the reduction of parental alcohol or drug dependence stigma by health care

[Drug induced diarrhea].

Science.gov (United States)

Morard, Isabelle; Hadengue, Antoine

2008-09-03

Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

Drug: D02102 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available gonist ... DG01563 ... mu-Opioid receptor agonist Analgesic ... DG01984 ... Opioid analgesics Other ... DG01718 ... Drugs for... addictive disorder ... DG01717 ... Drugs for opioid dependence Cyp substrate ... DG01633

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner.

Science.gov (United States)

Cannady, Reginald; Fisher, Kristen R; Graham, Caitlin; Crayle, Jesse; Besheer, Joyce; Hodge, Clyde W

2017-05-01

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here, we show that low-dose alcohol (0.6 g/kg/30 minutes) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared with behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol-reinforced but not sucrose-reinforced responding and was ineffective following intra-AcbC infusion. Because GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor myristolated autocamtide-2-related inhibitory peptide (m-AIP) dose-dependently reduced alcohol self-administration. A subthreshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use

Genes and (Common) Pathways Underlying Drug Addiction

Science.gov (United States)

Li, Chuan-Yun; Mao, Xizeng; Wei, Liping

2008-01-01

Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction. PMID:18179280

Genes and (common pathways underlying drug addiction.

Directory of Open Access Journals (Sweden)

Chuan-Yun Li

2008-01-01

Full Text Available Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn, the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.

Mediating the distal crime-drug relationship with proximal reactive criminal thinking.

Science.gov (United States)

Walters, Glenn D

2016-02-01

This article describes the results of a study designed to test whether reactive criminal thinking (RCT) does a better job of mediating the crime → drug relationship than it does mediating the drug → crime relationship after the direct effects of crime on drug use/dependency and of drug use/dependency on crime have been rendered nonsignificant by control variables. All 1,170 male members of the Pathways to Desistance study (Mulvey, 2012) served as participants in the current investigation. As predicted, the total (unmediated) effects of crime on substance use/dependence and of substance use/dependence on crime were nonsignificant when key demographic and third variables were controlled, although the indirect (RCT-mediated) effect of crime on drug use was significant. Proactive criminal thinking (PCT), by comparison, failed to mediate either relationship. The RCT continued to mediate the crime → drug relationship and the PCT continued to not mediate either relationship when more specific forms of offending (aggressive, income) and substance use/dependence (drug use, substance-use dependency symptoms) were analyzed. This offers preliminary support for the notion that even when the total crime-drug effect is nonsignificant the indirect path from crime to reactive criminal thinking to drugs can still be significant. Based on these results, it is concluded that mediation by proximal reactive criminal thinking is a mechanism by which distal measures of crime and drug use/dependence are connected. (c) 2016 APA, all rights reserved).

Di/tri-peptide transporters as drug delivery targets

DEFF Research Database (Denmark)

Nielsen, C U; Brodin, Birger

2003-01-01

-dependent, and the transporters thus belong to the Proton-dependent Oligopeptide Transporter (POT)-family. The transporters are not drug targets per se, however due to their uniquely broad substrate specificity; they have proved to be relevant drug targets at the level of drug transport. Drug molecules such as oral active beta....../tri-peptide transporters from vesicular storages 3) changes in gene transcription/mRNA stability. The aim of the present review is to discuss physiological, patho-physiological and drug-induced regulation of di/tri-peptide transporter mediated transport....

TGI Monday?: Drug-Dependent Outpatients Report Lower Stress and More Happiness at Work than Elsewhere

Science.gov (United States)

Epstein, David H.; Preston, Kenzie L.

2013-01-01

In the general population, experience-sampling studies show that work is the aspect of daily life most associated with momentary unhappiness and a desire to be elsewhere. We assessed whether this holds true for urban outpatients in treatment for heroin and cocaine dependence. In a 25-week natural-history study, 79 employed methadone-maintained misusers of heroin and cocaine carried electronic diaries on which mood and behavior were assessed up to five times per day. Being at work was associated with lower stress, greater happiness, and lower drug craving. Work accounted for 14% of the variance in stress, 30% of the variance in happiness, and 50% of the variance in cocaine craving. Participants with skilled jobs reported more positive and less negative mood states (and lower cocaine craving) at all times compared to participants with semi/unskilled jobs, although the latter reported greater mood improvement at work. In all participants, mood improvements occurred specifically in the presence of coworkers (not other companions). Our seemingly unusual findings might be specific to substance-disorder patients (for whom work may be a respite from drug-using companions), but might also hold for other urban dwellers of similar socioeconomic backgrounds (for whom work may be a respite from environmental stressors). PMID:22494220

Rational polypharmacology: systematically identifying and engaging multiple drug targets to promote axon growth

Science.gov (United States)

Al-Ali, Hassan; Lee, Do-Hun; Danzi, Matt C.; Nassif, Houssam; Gautam, Prson; Wennerberg, Krister; Zuercher, Bill; Drewry, David H.; Lee, Jae K.; Lemmon, Vance P.; Bixby, John L.

2016-01-01

Mammalian Central Nervous System (CNS) neurons regrow their axons poorly following injury, resulting in irreversible functional losses. Identifying therapeutics that encourage CNS axon repair has been difficult, in part because multiple etiologies underlie this regenerative failure. This suggests a particular need for drugs that engage multiple molecular targets. Although multi-target drugs are generally more effective than highly selective alternatives, we lack systematic methods for discovering such drugs. Target-based screening is an efficient technique for identifying potent modulators of individual targets. In contrast, phenotypic screening can identify drugs with multiple targets; however, these targets remain unknown. To address this gap, we combined the two drug discovery approaches using machine learning and information theory. We screened compounds in a phenotypic assay with primary CNS neurons and also in a panel of kinase enzyme assays. We used learning algorithms to relate the compounds’ kinase inhibition profiles to their influence on neurite outgrowth. This allowed us to identify kinases that may serve as targets for promoting neurite outgrowth, as well as others whose targeting should be avoided. We found that compounds that inhibit multiple targets (polypharmacology) promote robust neurite outgrowth in vitro. One compound with exemplary polypharmacology, was found to promote axon growth in a rodent spinal cord injury model. A more general applicability of our approach is suggested by its ability to deconvolve known targets for a breast cancer cell line, as well as targets recently shown to mediate drug resistance. PMID:26056718

Age-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters

Directory of Open Access Journals (Sweden)

Seok Kyu eKang

2015-05-01

Full Text Available Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB, with NKCC1 antagonist bumetanide (BTN as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in postnatal day 7, 10 and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

[Club drugs].

Science.gov (United States)

Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

2011-01-01

Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.

Chloroquine uptake, altered partitioning and the basis of drug resistance: evidence for chloride-dependent ionic regulation.

Science.gov (United States)

Martiney, J A; Ferrer, A S; Cerami, A; Dzekunov, S; Roepe, P

1999-01-01

The biochemical mechanism of chloroquine resistance in Plasmodium falciparum remains unknown. We postulated that chloroquine-resistant strains could alter ion fluxes that then indirectly control drug accumulation within the parasite by affecting pH and/or membrane potential ('altered partitioning mechanism'). Two principal intracellular pH-regulating systems in many cell types are the amiloride-sensitive Na+/H+ exchanger (NHE), and the sodium-independent, stilbene-sensitive Cl-/HCO3- antiporter (AE). We report that under physiological conditions (balanced CO2 and HCO3-) chloroquine uptake and susceptibility are not altered by amiloride analogues. We also do not detect a significant difference in NHE activity between chloroquine-sensitive and chloroquine-resistant strains via single cell photometry methods. AE activity is dependent on the intracellular and extracellular concentrations of Cl- and HCO3- ions. Chloroquine-resistant strains differentially respond to experimental modifications in chloride-dependent homeostasis, including growth, cytoplasmic pH and pH regulation. Chloroquine susceptibility is altered by stilbene DIDS only on chloroquine-resistant strains. Our results suggest that a Cl(-)-dependent system (perhaps AE) has a significant effect on the uptake of chloroquine by the infected erythrocyte, and that alterations of this biophysical parameter may be part of the mechanism of chloroquine resistance in P. falciparum.

[Caffeine: a nutrient, a drug or a drug of abuse].

Science.gov (United States)

Pardo Lozano, Ricardo; Alvarez García, Yolanda; Barral Tafalla, Diego; Farré Albaladejo, Magí

2007-01-01

Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be explained by variations in its metabolism. The main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse.

The Predictive Role of Difficulties in Emotion Regulation and Self-Control with Susceptibility to Addiction in Drug-Dependent Individuals

OpenAIRE

Mahmoud Shirazi; Monavar Janfaza

2015-01-01

Objective: The present study aimed to examine the predictive role of difficulties in emotion regulation and self-control in potential for addiction among drug-dependent individuals. Method: This was a correlational study which falls within the category of descriptive studies. The statistical population of the current study included all patients under treatment in outpatient health centers in Bam, among whom 315 individuals were selected through cluster sampling method as the participants of t...

Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals

NARCIS (Netherlands)

Passamonti, L. (Luca); M. Luijten (Maartje); Ziauddeen, H.; I. Coyle-Gilchrist (Ian); Rittman, T.; Brain, S.A.E.; Regenthal, R.; I.H.A. Franken (Ingmar); Sahakian, B.J.; Bullmore, E.T.; Robbins, T.W.; Ersche, K.D.

2017-01-01

textabstractRationale: Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by

Cocaine impairs serial-feature negative learning and blood-brain barrier integrity.

Science.gov (United States)

Davidson, Terry L; Hargrave, Sara L; Kearns, David N; Clasen, Matthew M; Jones, Sabrina; Wakeford, Alison G P; Sample, Camille H; Riley, Anthony L

2018-05-10

Previous research has shown that diets high in fat and sugar [a.k.a., Western diets (WD)] can impair performance of rats on hippocampal-dependent learning and memory problems, an effect that is accompanied by selective increases in hippocampal blood brain barrier (BBB) permeability. Based on these types of findings, it has been proposed that overeating of a WD (and its resulting obesity) may be, in part, a consequence of impairments in these anatomical substrates and cognitive processes. Given that drug use (and addiction) represents another behavioral excess, the present experiments assessed if similar outcomes might occur with drug exposure by evaluating the effects of cocaine administration on hippocampal-dependent memory and on the integrity of the BBB. Experiment 1 of the present series of studies found that systemic cocaine administration in rats also appears to have disruptive effects on the same hippocampal-dependent learning and memory mechanism that has been proposed to underlie the inhibition of food intake. Experiment 2 demonstrated that the same regimen of cocaine exposure that produced disruptions in learning and memory in Experiment 1 also produced increased BBB permeability in the hippocampus, but not in the striatum. Although the predominant focus of previous research investigating the etiologies of substance use and abuse has been on the brain circuits that underlie the motivational properties of drugs, the current investigation implicates the possible involvement of hippocampal memory systems in such behaviors. It is important to note that these positions are not mutually exclusive and that neuroadaptations in these two circuits might occur in parallel that generate dysregulated drug use in a manner similar to that of excessive eating. Copyright © 2018 Elsevier Inc. All rights reserved.

Etiology of Drug Abuse: A Narrative Analysis

Directory of Open Access Journals (Sweden)

Nadjme Jadidi

2014-01-01

Full Text Available Introduction and Aim. Further gains in the prevention of drug abuse disorders require in-depth and holistic understanding of the risk factors of addiction from different perspectives. Lay persons and experts have different concepts of risk which could complement each other. The purpose of this study was to elaborate drug abuse risk factors through the story of individuals who had become drug dependent. Design and Methods. In this qualitative research, 33 individuals attending treatment centres for drug abuse were interviewed about the story of their addiction in Kerman, Iran. Interview questions were around the story of the participants. Results. All participants were male and in the age range of 18–40 years. Narrative analysis identified five themes as the main risk factors: family factors, peer pressure, the effect of gateway drugs (especially waterpipe, individual characteristics, and the community factors. More emphasis was placed upon the role of family factors, peer influence, and gateway effect. Discussion and Conclusion. This study elicited information from drug dependent subjects regarding the risk factors of drug abuse. According to drug dependent individuals’ views, more attention should be devoted to family and peer influences by policy makers, in developing culture-based preventive strategies.

Will growth in cryptomarket drug buying increase the harms of illicit drugs?

Science.gov (United States)

Aldridge, Judith; Stevens, Alex; Barratt, Monica J

2018-05-01

Cryptomarkets-on-line, anonymous market-places for illicit goods and services that specialize mainly in drugs-account for a small but rapidly growing share of the illicit drug market in many countries. Policy responses so far are based generally on the assumption that their rise will only increase drug harms. In this contribution for debate, we question this assumption. We provide a narrative review of the emerging literature connected to drug cryptomarkets. We use MacCoun & Reuter's formula to understand the effect of population-level increases in use on total harm as depending on the level of harm associated with each unit of use. We then consider the potential for cryptomarkets to increase or decrease the harms and benefits related to each unit of drug use, with specific attention to the quality of drugs sold and the non-drug-related harms and benefits for customers. It is likely that cryptomarkets will increase both the amount and the range of substances that are sold. However, we argue that the effects on harms will depend upon whether cryptomarkets also increase the quality and safety of products that are sold, provide harm-reducing information to consumers and reduce transactional conflict involved in drug purchasing. There is an emerging and rapidly growing evidence base connected to the macro and micro harms and benefits of cryptomarkets for drug users. Future researchers should use appropriately matched comparative designs to establish more firmly the differential harms and benefits of sourcing drugs both on- and off-line. While it is unlikely that the on-line drug trade can be eradicated completely, cryptomarkets will respond to regulation and enforcement in ways that have complex, and sometimes unanticipated, effects on both harms and benefits. © 2017 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Drug: D07810 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available gonist ... DG01563 ... mu-Opioid receptor agonist Analgesic ... DG01984 ... Opioid analgesics Other ... DG01718 ... Drugs for... addictive disorder ... DG01717 ... Drugs for opioid dependence ATC code: N07BC06 Chem

6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization.

Science.gov (United States)

Agrawal, Vineet; Paul, Manash K; Mukhopadhyay, Anup K

2005-01-01

This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.

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

Science.gov (United States)

Swedberg, Michael D B

2016-01-01

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

Genetic Defects Underlie the Non-syndromic Autosomal Recessive Intellectual Disability (NS-ARID

Directory of Open Access Journals (Sweden)

Saleha Shamim

2017-05-01

Full Text Available Intellectual disability (ID is a neurodevelopmental disorder which appears frequently as the result of genetic mutations and may be syndromic (S-ID or non-syndromic (NS-ID. ID causes an important economic burden, for patient's family, health systems, and society. Identifying genes that cause S-ID can easily be evaluated due to the clinical symptoms or physical anomalies. However, in the case of NS-ID due to the absence of co-morbid features, the latest molecular genetic techniques can be used to understand the genetic defects that underlie it. Recent studies have shown that non-syndromic autosomal recessive (NS-ARID is extremely heterogeneous and contributes much more than X-linked ID. However, very little is known about the genes and loci involved in NS-ARID relative to X-linked ID, and whose complete genetic etiology remains obscure. In this review article, the known genetic etiology of NS-ARID and possible relationships between genes and the associated molecular pathways of their encoded proteins has been reviewed which will enhance our understanding about the underlying genes and mechanisms in NS-ARID.

Factors Associated with the Transition from Drug Abuse to Initiation of Injection Drug Use

Directory of Open Access Journals (Sweden)

Mosayeb Yarmohamadi Vasel

2015-06-01

Full Text Available Objectives: Drug injection carries with it many risks and therefore it is important to understand the initiating factors of injection and its origins. Thus,  the purpose of this study was to identify factors associated with the initiation of injection drug use among substance abusers. Methods:  Study method was a cross-sectional study. The research statistics universe constitutes all people suffering from a substance dependence disorder with a pattern of injection use in Tehran and Hamedan. This study was conducted among 216 individuals with substance dependence disorders who were selected from harm reduction centers in Tehran and Hamedan. The sampling selection method was simply random. The instruments used for data collection included: demographic information, patterns of drug use and initiation of injection scales.  Results: In this study, the average age of initiation to injections was 22.5 years. Factors associated with initiation of drug injection included: acquired more pleasure, easier use, faster effect of injection, ineffective previous use method, curiosity, peer pressure, lack of availability of the drug, poverty, and low quality drugs. Discussion: Results of this study indicate that initiation factors to drug injection are multifaceted (Psychological, Social, Economic and Environmental, therefore, injection interventionists should consider all these factors for prevention, treatment and harm reduction.

How might schools influence young people's drug use? Development of theory from qualitative case-study research.

Science.gov (United States)

Fletcher, Adam; Bonell, Chris; Sorhaindo, Annik; Strange, Vicki

2009-08-01

To explore young people's experiences of school and drug use, generate hypotheses regarding the pathways through which schools may influence students' drug use, and examine how these may vary according to students' sociodemographic characteristics. Qualitative data were collected through semistructured interviews with 30 students (aged 14-15) and 10 teachers in two case-study schools. Students were purposively sampled to encompass variations in socioeconomic status, gender, ethnicity, and school engagement. Techniques associated with thematic content analysis and grounded theory were used to analyze the data and generate hypotheses. Three potential pathways via which school effects on drug use may occur were identified: (1) peer-group sorting and drug use as a source of identity and bonding among students who are disconnected from the main institutional markers of status; (2) students' desire to "fit in" at schools perceived to be unsafe and drug use facilitating this; and/or (3) drug use as a strategy to manage anxieties about school work and escape unhappiness at schools lacking effective social support systems. Various pathways may plausibly underlie school effects on drug use. These support the idea of "whole-school" interventions to reduce drug use through: recognizing students' varied achievements and promoting a sense of belonging, reducing bullying and aggression, and providing additional social support for students. Such interventions should be piloted and evaluated in a range of settings to examine effects on students' drug use. Broader policies relating to secondary school targets, curricula, assessment, and streaming may also influence rates of adolescent drug use.

RAS - Screens & Assays - Drug Discovery

Science.gov (United States)

The RAS Drug Discovery group aims to develop assays that will reveal aspects of RAS biology upon which cancer cells depend. Successful assay formats are made available for high-throughput screening programs to yield potentially effective drug compounds.

Drug: D00836 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D00836.gif ... Analgesic ... DG01984 ... Opioid analgesics ... DG01586 ... Opioid receptor antagonist Other ... DG01718 ... Drugs... for addictive disorder ... DG01717 ... Drugs for opioid dependence Therapeutic category: 1149 ATC code: N02AE0

Drug: D02104 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available gesic ... DG01586 ... Opioid receptor antagonist ... DG01587 ... Opioid receptor agonist/antagonist Other ... DG01718 ... Drugs... for addictive disorder ... DG01716 ... Drugs for alcohol dependence ATC code: N07BB05 Chemical group: DG00998 ...

Drug: D06282 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available C4H6O6 D06282.gif ... Neuropsychiatric agent ... DG01571 ... Nicotinic cholinergic receptor partial agonist Other ... DG01718 ... Drugs... for addictive disorder ... DG01715 ... Drugs for nicotine dependence Therapeutic category: 7990 A

[Relevance of drug use in clinical manifestations of schizophrenia].

Science.gov (United States)

Arias Horcajadas, F; Sánchez Romero, S; Padín Calo, J J

2002-01-01

To study the association between drugs use with schizophrenia clinical manifestations. The sample consists of 82 out-patients with schizophrenia, between 18 and 45 years old. They were evaluated with Addiction Severity Index (ASI) and with Positive and Negative Syndrome Scale (PANSS). A 6 months follow up was carried out. 37,8% patients had lifetime drug dependence (including alcohol and others drugs except for tobacco). The prevalence of dependence for the different drugs were: opioids 9,8%, cocaine 11%, alcohol 29,3%, cannabis 24,4%, tobacco 68,3%, caffeine 15,9%. Drug dependent had more family and legal problems. At the multiple regression analysis it was observed that cannabis and tobacco dependence was associated with a decrease in the PANSS negative symptoms subscale, and on the contrary, alcohol dependence produces a similar intensity increase at that scoring. We don't detect any clinical relevance effects over positive symptoms. Cannabis and tobacco may improve schizophrenia negative symptoms or neuroleptic secondary effects or patients with few negative symptoms may have more predisposition to the use, on the contrary alcohol use can impairment those symptoms.

Effect of training the communication skills with cognitive-behavioral model to drug dependent couples on communication patterns and recurrent relapse

OpenAIRE

M. Rahbarian; R. Hossein zadeh; P. Doosti

2016-01-01

Background: One of the main challenges in methadone maintenance treatment is relapse and lack of sustainability on treatment. Therefore, considering the effective factors in this regard and reducing it through psychological interventions as an adjunct to medication is necessary. Objective: The current study aimed to determine the effectiveness of communication skill training based on cognitive-behavioral model on communication patterns and recurrent relapse in drug dependent couples. Me...

Self-efficacy and social networks after treatment for alcohol or drug dependence and major depression: disentangling person and time-level effects.

Science.gov (United States)

Worley, Matthew J; Trim, Ryan S; Tate, Susan R; Roesch, Scott C; Myers, Mark G; Brown, Sandra A

2014-12-01

Proximal personal and environmental factors typically predict outcomes of treatment for alcohol or drug dependence (AODD), but longitudinal treatment studies have rarely examined these factors in adults with co-occurring psychiatric disorders. In adults with AODD and major depression, the aims of this study were to: (a) disaggregate person-and time-level components of network substance use and self-efficacy, (b) examine their prospective effects on posttreatment alcohol/drug use, and (c) examine whether residential environment moderated relations between these proximal factors and substance use outcomes. Veterans (N = 201) enrolled in a trial of group psychotherapy for AODD and independent MDD completed assessments every 3 months during 1 year of posttreatment follow-up. Outcome variables were percent days drinking (PDD) and using drugs (PDDRG). Proximal variables included abstinence self-efficacy and social network drinking and drug use. Self-efficacy and network substance use at the person-level prospectively predicted PDD (ps effects of social networks predicted future PDD (ps social network effects (ps network and posttreatment drinking and drug use. Both individual differences and time-specific fluctuations in proximal targets of psychosocial interventions are related to posttreatment substance use in adults with co-occurring AODD and MDD. More structured environmental settings appear to alleviate risk associated with social network substance use, and may be especially advised for those who have greater difficulty altering social networks during outpatient treatment.

Student understanding of time dependence in quantum mechanics

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Paul J. Emigh

2015-09-01

Full Text Available [This paper is part of the Focused Collection on Upper Division Physics Courses.] The time evolution of quantum states is arguably one of the more difficult ideas in quantum mechanics. In this article, we report on results from an investigation of student understanding of this topic after lecture instruction. We demonstrate specific problems that students have in applying time dependence to quantum systems and in recognizing the key role of the energy eigenbasis in determining the time dependence of wave functions. Through analysis of student responses to a set of four interrelated tasks, we categorize some of the difficulties that underlie common errors. The conceptual and reasoning difficulties that have been identified are illustrated through student responses to four sets of questions administered at different points in a junior-level course on quantum mechanics. Evidence is also given that the problems persist throughout undergraduate instruction and into the graduate level.

Drug: D05111 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available ... DG01586 ... Opioid receptor antagonist ... DG01587 ... Opioid receptor agonist/antagonist Other ... DG01718 ... Drugs for... addictive disorder ... DG01716 ... Drugs for alcohol dependence Same as: C08027 ATC code: N07BB05 Chemical group

Drug: D02780 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available )2. Ca D02780.gif ... Neuropsychiatric agent ... DG01498 ... NMDA receptor antagonist Other ... DG01718 ... Drugs for add...ictive disorder ... DG01716 ... Drugs for alcohol dependence Therapeutic category: 1190 ATC code: N07BB03 Chemica

The Effects of Psychotropic Drugs.

Science.gov (United States)

Bonnardeaux, Jef-Louis

1984-01-01

Presents information on psychotropic drugs for individuals who are not specialists in pharmacology. Discusses: alcohol and barbituates; dependence and withdrawal; central nervous system depressors (anaesthetics, narcotic analgesics, sedatives and hypnotic drugs, tranquilizers), central nervous stimulants (amphetamines, cocaine, tobacco, caffeine),…

Drug Pricing Reforms

DEFF Research Database (Denmark)

Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas

2015-01-01

Reference price systems for prescription drugs have found widespread use as cost containment tools. Under such regulatory regimes, patients co-pay a fraction of the difference between pharmacy retail price of the drug and a reference price. Reference prices are either externally (based on drug...... prices in other countries) or internally (based on domestic drug prices) determined. In a recent study, we analysed the effects of a change from external to internal reference pricing in Denmark in 2005, finding that the reform led to substantial reductions in prices, producer revenues, and expenditures...... for patients and the health insurance system. We also estimated an increase in consumer welfare but the size effect depends on whether or not perceived quality differences between branded and other drugs are taken into account....

Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate)

DEFF Research Database (Denmark)

Bohr, Adam; Wang, Yingya; Harmankaya, Necati

2017-01-01

.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half......Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough...... to control the spatial and temporal on-demand degradation and drug release from the employed delivery system....

Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

Science.gov (United States)

Kim, Albert H.; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin

2014-01-01

MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22−23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ∼1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. PMID:24899699

Predicting Inpatient Detoxification Outcome of Alcohol and Drug Dependent Patients: The Influence of Sociodemographic Environment, Motivation, Impulsivity, and Medical Comorbidities

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Yvonne Sofin

2017-01-01

Full Text Available Aims. This prospective study aims to identify patient characteristics as predictors for treatment outcome during inpatient detoxification treatment for drug and alcohol dependent patients. Methods. A mixed gender sample of 832 consecutively admitted drug and alcohol dependent patients were interviewed by an experienced physician. The impact of a variety of factors concerning social environment, therapy motivation, impulsivity related variables, medical history, and addiction severity on treatment outcome was examined. Results. 525 (63.1% of the patients completed detoxification treatment whereas 307 (36.9% dropped out prematurely. Being female, living in a partnership, having children, being employed, and having good education were predictive for a positive outcome. Family, health, the fear of losing the job, prosecution, and emergency admission were significant motivational predictors for treatment outcome. Being younger, history of imprisonment, and the number of previous drop-outs were predictive for a negative outcome. Conclusions. Variables concerning social environment and the number of previous drop-outs have been identified as best predictors for treatment outcome. Socially stable patients benefit from the current treatment setting and treatment shall be adapted for patients with negative predictors. Treatment may consequently be tailored with respect to intervention type, duration, and intensity to improve the outcome for those patients that fulfil criteria with negative impact on treatment retention.

Contextualization of drug-mediator relations using evidence networks.

Science.gov (United States)

Tran, Hai Joey; Speyer, Gil; Kiefer, Jeff; Kim, Seungchan

2017-05-31

Genomic analysis of drug response can provide unique insights into therapies that can be used to match the "right drug to the right patient." However, the process of discovering such therapeutic insights using genomic data is not straightforward and represents an area of active investigation. EDDY (Evaluation of Differential DependencY), a statistical test to detect differential statistical dependencies, is one method that leverages genomic data to identify differential genetic dependencies. EDDY has been used in conjunction with the Cancer Therapeutics Response Portal (CTRP), a dataset with drug-response measurements for more than 400 small molecules, and RNAseq data of cell lines in the Cancer Cell Line Encyclopedia (CCLE) to find potential drug-mediator pairs. Mediators were identified as genes that showed significant change in genetic statistical dependencies within annotated pathways between drug sensitive and drug non-sensitive cell lines, and the results are presented as a public web-portal (EDDY-CTRP). However, the interpretability of drug-mediator pairs currently hinders further exploration of these potentially valuable results. In this study, we address this challenge by constructing evidence networks built with protein and drug interactions from the STITCH and STRING interaction databases. STITCH and STRING are sister databases that catalog known and predicted drug-protein interactions and protein-protein interactions, respectively. Using these two databases, we have developed a method to construct evidence networks to "explain" the relation between a drug and a mediator.  RESULTS: We applied this approach to drug-mediator relations discovered in EDDY-CTRP analysis and identified evidence networks for ~70% of drug-mediator pairs where most mediators were not known direct targets for the drug. Constructed evidence networks enable researchers to contextualize the drug-mediator pair with current research and knowledge. Using evidence networks, we were

Levofloxacin?Induced QTc Prolongation Depends on the Time of Drug Administration

OpenAIRE

Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, IMC; Danhof, M; Meijer, JH; Burggraaf, J

2016-01-01

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in which 12 healthy male subjects received levofloxacin at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00. Using a pharmacokinetic-pharmacodynamic (PK-PD) modeling approach to account for variations in ...

The Effect of Race on Provider Decisions to Test for Illicit Drug Use in the Peripartum Setting

Science.gov (United States)

KUNINS, HILLARY VEDA; BELLIN, ERAN; CHAZOTTE, CYNTHIA; DU, EVELYN; ARNSTEN, JULIA HOPE

2010-01-01

Background Testing for illicit drugs may expose women who test positive to severe legal and social consequences. It is unknown whether racial disparities in drug testing practices underlie observed disparities in legal and social consequences of positive tests. Methods Using administrative hospital and birth certificate data, we analyzed factors associated with both receipt and results of illicit drug testing among women with live births during 2002–2003. We assessed the independent association of race and other sociodemographic factors with both receipt of a drug test by the mother or her newborn infant and positive maternal or neonatal toxicology results, after controlling for obstetrical conditions and birth outcomes associated with maternal substance abuse. Results Of the 8487 women with live births, 244 mother-newborn pairs (3%) were tested for illicit drug use. Black women and their newborns were 1.5 times more likely to be tested for illicit drugs as nonblack women in multivariable analysis. However, race was not independently associated with a positive result. Conclusions We identified racial differences in rates of testing for illicit drug use between black and nonblack women. We found equivalent positivity rates among tested black and nonblack women. The prevalence of drug use among untested women is unknown, however, so although tested women had equivalent rates of substance use detected, whether black and nonblack substance users are equally likely to be identified in the course of peripartum care remains uncertain. PMID:17388741

Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment.

Science.gov (United States)

Marchand, Kirsten; Oviedo-Joekes, Eugenia; Guh, Daphne; Marsh, David C; Brissette, Suzanne; Schechter, Martin T

2012-01-25

Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months). A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. NCT00175357.

Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment

Directory of Open Access Journals (Sweden)

Marchand Kirsten

2012-01-01

Full Text Available Abstract Background Substitution with opioid-agonists (e.g., methadone has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. Methods Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI, conducted in Vancouver and Montreal (Canada between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months. Results A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. Conclusions After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. Trial Registration NCT00175357.

The Effectiveness of Cognitive Behavioral Therapy on Increasing of Self-Efficacy and Improving of Addiction Symptoms among Drug Dependency Patients

OpenAIRE

Hamid Kamarzarin; Hosin Zaree; Hosin Brouki, M

2012-01-01

Introduction: The aim of this study was to determine the effectiveness of cognitive behavior therapy on increasing of self efficacy and improving of addiction symptoms among drug dependency patients. Method: For this purpose, 90 substance abusers were selected of private addiction center, Central Prison and drop in center by using of random sampling, and they were divided into two experimental (45 subjects) and witness groups (45 subjects) randomly. The members of experimental group were unde...

Clinical pharmacokinetics of non-opiate abused drugs.

Science.gov (United States)

Busto, U; Bendayan, R; Sellers, E M

1989-01-01

The present review discusses the available data on the kinetic properties of non-opiate abused drugs including psychomotor stimulants, hallucinogens and CNS-depressants. Some of the drugs of abuse reviewed here are illicit drugs (e.g. cannabis, cocaine), while others are effective pharmacological agents but have the potential to be abused (e.g. benzodiazepines). Although some of the drugs mentioned in this review have been in use for centuries (e.g. caffeine, nicotine, cocaine, cannabis), knowledge of their kinetics and metabolism is very recent and in some cases still incomplete. This is partially due to the difficulties inherent in studying drugs of abuse in humans, and to the complex metabolism of some of these drugs (e.g. cannabis, caffeine) which has made it difficult to develop sensitive assays to determine biological pathways. Although drugs of abuse may have entirely different intrinsic pharmacological effects, the kinetic properties of such drugs are factors contributing to abuse and dependence. The pharmacokinetic properties that presumably contribute to self-administration and drug abuse include rapid delivery of the drug into the central nervous system and high free drug clearance. Kinetic characteristics also play an important role in the development of physical dependence and on the appearance of a withdrawal syndrome: the longer the half-life, the greater the likelihood of the development of physical dependence; the shorter the half-life, the earlier and more severe the withdrawal. The balance between these 2 factors, which has not yet been carefully studied, will also influence abuse patterns. The clinical significance of kinetic characteristics with respect to abuse is discussed where possible.

Perfil clínico e demográfico de médicos com dependência química Clinical and demographical aspects of alcohol and drug dependent physicians

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Hamer Nastasy P. Alves

2005-06-01

Full Text Available OBJETIVO: Traçar o perfil clínico e demográfico de uma amostra de médicos em tratamento por dependência química, avaliar comorbidades psiquiátricas e conseqüências associadas ao consumo. MÉTODOS: Foram coletados dados de 198 médicos em tratamento ambulatorial por uso nocivo e dependência química, através de questionário elaborado pelos autores. RESULTADOS: A maioria de indivíduos foi do sexo masculino (87,8%, casados (60,1%, com idade média de 39,4 anos (desvio padrão=10,7 anos. Sessenta e seis por cento já tinham sido internados por causa do uso de álcool e/ou drogas. Setenta e nove por cento possuía residência médica e as especialidades mais envolvidas foram: clínica médica, anestesiologia e cirurgia. Comorbidade psiquiátrica foi diagnosticada em 27,7% (Eixo I do DSM-IV¹ e em 6% (Eixo II do DSM-IV¹. Quanto às substâncias consumidas, o mais freqüente foi uso associado de álcool e drogas (36,8%, seguido por uso isolado de álcool (34,3% e uso isolado de drogas (28,3%. Observou-se o intervalo de 3,7 anos em média entre a identificação do uso problemático de substâncias e a procura de tratamento. Quanto à busca por tratamento, 30,3% o fizeram voluntariamente. Quanto aos problemas sociais e legais observou-se: desemprego no ano anterior em quase 1/3 da amostra; problemas no casamento ou separação (52%, envolvimento em acidentes automobilísticos (42%, problemas jurídicos (19%, problemas profissionais (84,8% e 8,5% tiveram problemas junto aos Conselhos Regionais de Medicina. CONCLUSÃO: Os autores recomendam medidas assistenciais e preventivas para o problema.The misuse of alcohol and drugs among physicians is a common cause of malpractice, absenteeism and complaints to the Medical Councils. This problem demands more attention, because it entails risks to the population and to the physicians themselves. AIMS: To describe the clinical and demographic profile of a sample of physicians in treatment for alcohol

[Present status and future of hypnotic drug treatment for insomnia].

Science.gov (United States)

Uchiyama, Makoto; Konno, Michiko

2012-07-01

Pharmacological treatments of insomnia have become safer since the first benzodiazepine receptor agonist (BzRA) hypnotic was introduced in the 1960's. Though BzRAs could hardly cause a fatal condition even in cases of overdosing, they had inherited the arguments on addiction and withdrawal from the prior studies of barbiturate hypnotics that indicated they are strongly addictive. In the 2000s, it was repeatedly demonstrated that insomnia as well as sleep deprivation underlie the development and deterioration of comorbid diseases such as hypertension, cardiovascular diseases, diabetes and depression, and that the proper use of hypnotic drugs is unlikely to cause tolerance, addiction nor rebound phenomena, but likely to be associated with improvement of QOL. Thus, the 2005's consensus report on chronic insomnia by NIH has recommended general physicians to facilitate insomnia treatment to prevent the development of physical and/or mental disorders. The author reviewed in this article the efficacy and side effects of BzRA hypnotics, a hypnotic drug therapy combined with cognitive and behavioral interventions, uses of melatonin receptor agonist in general and sleep medicine practices, and future utilization of newly-developed orexin antagonists for insomnia treatment.

Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion.

Science.gov (United States)

Williams, Hywel D; Anby, Mette U; Sassene, Philip; Kleberg, Karen; Bakala-N'Goma, Jean-Claude; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Carrière, Frédéric; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

2012-11-05

The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout. In general, increasing NaTDC concentrations increased the digestion of the most lipophilic LBFs and promoted lipid (and drug) trafficking from poorly dispersed oil phases to the aqueous colloidal phase (AP(DIGEST)). High NaTDC concentrations showed some capacity to reduce drug precipitation, although, at NaTDC concentrations ≥3 mM, NaTDC effects on either digestion or drug solubilization were modest. In contrast, increasing drug load had a marked impact on drug solubilization. For LBFs containing long-chain lipids, drug precipitation was limited even at drug loads approaching saturation in the formulation and concentrations of solubilized drug in AP(DIGEST) increased with increased drug load. For LBFs containing medium-chain lipids, however, significant precipitation was evident, especially at higher drug loads. Across all formulations a remarkably consistent trend emerged such that the likelihood of precipitation was almost entirely dependent on the maximum supersaturation ratio (SR(M)) attained on initiation of digestion. SR(M) defines the supersaturation "pressure" in the system and is calculated from the maximum attainable concentration in the AP(DIGEST) (assuming zero precipitation), divided by the solubility of the drug in the colloidal phases formed post digestion. For LBFs where phase separation of oil phases did not occur, a

Drug: D08248 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available [veterinary] (TN) ... C19H21NO3. HCl D08248.gif ... Analgesic ... DG01586 ... Opioid receptor antagonist Other ... DG01718 ... Drugs... for addictive disorder ... DG01717 ... Drugs for opioid dependence ATC code: V03AB02 Chemical group: DG0

Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters.

Science.gov (United States)

Kang, Seok Kyu; Markowitz, Geoffrey J; Kim, Shin Tae; Johnston, Michael V; Kadam, Shilpa D

2015-01-01

Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB), with NKCC1 antagonist bumetanide (BTN) as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in post-natal day 7, 10, and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs) quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

Diameter-dependent release of a cisplatin pro-drug from small and large functionalized carbon nanotubes

Science.gov (United States)

Muzi, Laura; Ménard-Moyon, Cécilia; Russier, Julie; Li, Jian; Chin, Chee Fei; Ang, Wee Han; Pastorin, Giorgia; Risuleo, Gianfranco; Bianco, Alberto

2015-03-01

The use of platinum-based chemotherapeutic drugs in cancer therapy still suffers from severe disadvantages, such as lack of appropriate selectivity for tumor tissues and insurgence of multi-drug resistance. Moreover, drug efficacy can be attenuated by several mechanisms such as premature drug inactivation, reduced drug uptake inside cells and increased drug efflux once internalized. The use of functionalized carbon nanotubes (CNTs) as chemotherapeutic drug delivery systems is a promising strategy to overcome such limitations due to their ability to enhance cellular internalization of poorly permeable drugs and thus increase the drug bioavailability at the diseased site, compared to the free drug. Furthermore, the possibility to encapsulate agents in the nanotubes' inner cavity can protect the drug from early inactivation and their external functionalizable surface is useful for selective targeting. In this study, a hydrophobic platinum(iv) complex was encapsulated within the inner space of two different diameter functionalized multi-walled CNTs (Pt(iv)@CNTs). The behavior of the complexes, compared to the free drug, was investigated on both HeLa human cancer cells and RAW 264.7 murine macrophages. Both CNT samples efficiently induced cell death in HeLa cancer cells 72 hours after the end of exposure to CNTs. Although the larger diameter CNTs were more cytotoxic on HeLa cells compared to both the free drug and the smaller diameter nanotubes, the latter allowed a prolonged release of the encapsulated drug, thus increasing its anticancer efficacy. In contrast, both Pt(iv)@CNT constructs were poorly cytotoxic on macrophages and induced negligible cell activation and no pro-inflammatory cytokine production. Both CNT samples were efficiently internalized by the two types of cells, as demonstrated by transmission electron microscopy observations and flow cytometry analysis. Finally, the platinum levels found in the cells after Pt(iv)@CNT exposure demonstrate that they can

Smoking and Illicit Drug Use.

Science.gov (United States)

Gold, Mark S., Ed.

The biological mechanisms of nicotine dependence are described, the prevalence of tobacco dependency among those using other mood-altering drugs is examined, and the most efficacious way to address this dependency is discussed. New data on the relationship of smoking addiction to other addictions are examined. Topics include: (1) "Tobacco…

Neural Tuning Functions Underlie Both Generalization and Interference.

Directory of Open Access Journals (Sweden)

Ian S Howard

Full Text Available In sports, the role of backswing is considered critical for generating a good shot, even though it plays no direct role in hitting the ball. We recently demonstrated the scientific basis of this phenomenon by showing that immediate past movement affects the learning and recall of motor memories. This effect occurred regardless of whether the past contextual movement was performed actively, passively, or shown visually. In force field studies, it has been shown that motor memories generalize locally and that the level of compensation decays as a function of movement angle away from the trained movement. Here we examine if the contextual effect of past movement exhibits similar patterns of generalization and whether it can explain behavior seen in interference studies. Using a single force-field learning task, the directional tuning curves of both the prior contextual movement and the subsequent force field adaptive movements were measured. The adaptation movement direction showed strong directional tuning, decaying to zero by 90° relative to the training direction. The contextual movement direction exhibited a similar directional tuning, although the effect was always above 60%. We then investigated the directional tuning of the passive contextual movement using interference tasks, where the contextual movements that uniquely specified the force field direction were separated by ±15° or ±45°. Both groups showed a pronounced tuning effect, which could be well explained by the directional tuning functions for single force fields. Our results show that contextual effect of past movement influences predictive force compensation, even when adaptation does not require contextual information. However, when such past movement contextual information is crucial to the task, such as in an interference study, it plays a strong role in motor memory learning and recall. This work demonstrates that similar tuning responses underlie both generalization of

Inhibition of time-dependent enhancement of amino acid transport by leukemic leukocytes: a possible index of the sensitivity of cells to drugs

Energy Technology Data Exchange (ETDEWEB)

Frengley, P A; Peck, W A; Lichtman, M A

1975-01-01

Leukemic leukocytes increase their rates of alpha aminoisobutyric acid (AIB) accumulation when incubated for prolonged periods in amino acid deficient media. The time-dependent increase was prevented by concurrent exposure of cells to cycloheximide or actinomycin D in vitro. In addition, the increase in AIB uptake was not present in leukemic blasts studied in vitro when the cells were obtained from subjects with acute myeloblastic leukemia who had received antileukemic therapy. Cortisol added to cell suspensions in vitro inhibited the development of time-dependent increases in AIB uptake in lymphoid cells, but accentuated the process slightly in myeloblasts. Cortisol administered to a subject with CLL by infusion reduced the time-dependent increase in AIB uptake by CLL cells subsequently studied in vitro. These data indicate that the time-dependent increase in AIB uptake may be a means of testing the sensitivity of leukemic cells to drugs.

Reliability and validity of the Severity of Dependence Scale for detecting cannabis dependence in frequent cannabis users

NARCIS (Netherlands)

van der Pol, P.; Liebregts, N.; de Graaf, R.; Korf, D.J.; van den Brink, W.; van Laar, M.

2013-01-01

The Severity of Dependence Scale (SDS) measures with five items the degree of psychological dependence on several illicit drugs, including cannabis. Its psychometric properties have not yet been examined in young adult frequent cannabis users, an eminently high-risk group for cannabis dependence.

Drug- not carrier-dependent haematological and biochemical changes in a repeated dose study of cyclosporine encapsulated polyester nano- and micro-particles: Size does not matter

International Nuclear Information System (INIS)

Venkatpurwar, V.P.; Rhodes, S.; Oien, K.A.; Elliott, M.A.; Tekwe, C.D.; Jørgensen, H.G.; Kumar, M.N.V. Ravi

2015-01-01

Highlights: • The particulate delivery allows an increase in dose range without accrual of toxicities. • The altered haematological and biochemical changes are drug, but not particle dependent. • PLGA nano/microparticles are safe on subacute peroral dosing over 28 days. • Nano-toxicology, drug needs to be considered. - Abstract: Biodegradable nanoparticles are being considered more often as drug carriers to address pharmacokinetic/pharmacodynamic issues, yet nano-product safety has not been systematically proven. In this study, haematological, biochemical and histological parameters were examined on 28 day daily dosing of rats with nano- or micro-particle encapsulated cyclosporine (CsA) to confirm if any changes observed were drug or carrier dependent. CsA encapsulated poly(lactide-co-glycolide) [PLGA] nano- (nCsA) and micro-particles (mCsA) were prepared by emulsion techniques. CsA (15, 30, 45 mg/kg) were administered by oral gavage to Sprague Dawley (SD) rats over 28 days. Haematological and biochemical metrics were followed with tissue histology performed on sacrifice. Whether presented as nCsA or mCsA, 45 mg/kg dose caused significant loss of body weight and lowered food consumption compared to untreated control. Across the doses, both nCsA and mCsA produce significant decreases in lymphocyte numbers compared to controls, commensurate with the proprietary product, Neoral ® 15. Dosing with nCsA showed higher serum drug levels than mCsA presumably owing to the smaller particle size facilitating absorption. The treatment had no noticeable effects on inflammatory/oxidative stress markers or antioxidant enzyme levels, except an increase in ceruloplasmin (CP) levels for high dose nCsA/mCsA group. Further, only subtle, sub-lethal changes were observed in histology of nCsA/mCsA treated rat organs. Blank (drug-free) particles did not induce changes in the parameters studied. Therefore, it is extremely important that the encapsulated drug in the nano-products is

MDMA: interactions with other psychoactive drugs.

Science.gov (United States)

Mohamed, Wael M Y; Ben Hamida, Sami; Cassel, Jean-Christophe; de Vasconcelos, Anne Pereira; Jones, Byron C

2011-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most widely abused illegal drugs. Some users self-report euphoria and an increased perception and feeling of closeness to others. When taken in warm environments, MDMA users may develop acute complications with potential fatal consequences. In rodents, MDMA increases locomotor activity and, depending on ambient temperature, may produce a dose-dependent, potentially lethal hyperthermia. Like most other recreational drugs, MDMA is frequently taken in combination with other substances including tobacco, EtOH, marijuana, amphetamines, cocaine and, caffeine. Although polydrug use is very common, the understanding of the effects of this multiple substance use, as well as the analysis of consequences of different drug-drug associations, received rather little attention. The purpose of this review is to summarize our current knowledge about the changes on MDMA-related behavior, pharmacology, and neurotoxicity associated with co-consumption of other drugs of abuse and psychoactive agents. Copyright © 2011 Elsevier B.V. All rights reserved.

Timing of specimen collection is crucial in urine screening of drug dependent mothers and newborns.

Science.gov (United States)

Halstead, A C; Godolphin, W; Lockitch, G; Segal, S

1988-01-01

We compared results of urine drug analysis with clinical data and history to test the usefulness of peripartum drug screening and to establish guidelines for optimal testing. Urine from 28 mothers and 52 babies was analysed. Drugs not suspected by history were found in 10 mothers and six babies. Results assisted in the management of neonatal withdrawal in three babies. Drugs suspected by history were not found in 11/22 mothers and 23/35 babies. About half of these results were associated with delayed urine collection. In 12/28 mothers, drugs administered in hospital could have confused interpretation of screen results. We conclude that urine drug screening without strict protocols for specimen collection is of limited usefulness for management of drug abuse in pregnancy and neonatal drug withdrawal. We favour testing of maternal urine obtained before drugs are administered in hospital. Neonatal urine, if used, should be collected in the first day of life.

Predictors of illicit drug/s use among university students in Northern Ireland, Wales and England.

Science.gov (United States)

El Ansari, Walid; Vallentin-Holbech, Lotte; Stock, Christiane

2014-12-16

The use of illicit drug/s among university students is a public health concern. Nevertheless, many UK studies investigated a narrow spectrum of variables to explore their association/s with illicit drug/s use. We assessed the associations between a wide range of socio-demographic, health and wellbeing variables (independent variables) and having used illicit drug/s regularly, occasionally or never in life (dependent variables). Data (3706 students) were collected from seven universities in England, Wales, and Northern Ireland, using a self-administered questionnaire. About 5% of the sample had regularly used illicit drug/s, 25% occasionally, and 70% never. Regular drug use (RDU) was significantly more likely among males aged 21-29 years, daily smokers, those with heavy episodic drinking or possible alcohol dependency (CAGE test), and those who perceived their academic performance better than their peers. RDU was less likely among students with high health awareness and those living with parents. The predictors of occasional drug use (ODU) were similar to those of RDU. However, in addition, students with higher perceived stress were less likely, and students who felt financial burden/s were more likely to report ODU, while no association with academic performance was found. Never use of illicit drug/s was inversely associated with most of the variables listed above, and was positively associated with religiosity. Illicit drug/s use goes along with other substance use (alcohol and smoking). The finding that illicit drug/s use was higher among students reporting good academic performance was surprising and raises the question of whether illicit drug/s may be used as performance enhancing drugs. The factors identified with illicit drug/s use in this study could be utilized to develop appropriate public health policies and preventive measures for the health of students. Multilevel, value based, comprehensive, and strategic long-term intervention plans are required. This

Hyperactivity, drugs and attention deficit.

Science.gov (United States)

Pozzi, M; Hartley, L

1984-09-01

Thirty-two hyperactive children who were under imipramine or methylphenidate medication took part in the experiment. The children were asked to learn a set of paired associate pictures containing a salient, central, figure and a secondary figure below. Free recall of all pictures was scored both immediately and seven days later. The children were subdivided into four groups according to the classical state-dependent learning paradigm. Group 1 was withdrawn from medication on both trials, groups 2 and 3 were withdrawn from medication on the first or second trial and group 4 received medication on both trials. No drug effects were found in immediate total recall. Delayed free recall was improved when original learning was under the drug state. This result was related to the proposal that arousing words are better remembered in delayed recall. Delayed recall of the secondary stimuli was particularly improved by the drugs during learning. Drug state dependency of the children's memory was also shown.

Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence

Science.gov (United States)

Yang, Cheng; Chen, Yan; Tang, Lei

2011-01-01

Previous studies from our laboratory and others have implicated a critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, inhibited CaMKII, which led us to hypothesize that haloperidol can attenuate opioid tolerance and dependence by inhibiting CaMKII. The hypothesis was tested in two rodent models of opioid tolerance and dependence. Pretreatment with haloperidol (0.2–1.0 mg/kg i.p.) prevented the development of morphine tolerance and dependence in a dose-dependent manner. Short-term treatment with haloperidol (0.06–0.60 mg/kg i.p.) dose-dependently reversed the established morphine-antinociceptive tolerance and physical dependence. Correlating with behavioral effects, pretreatment or short-term treatment with haloperidol dose-dependently inhibited morphine-induced up-regulation of supraspinal and spinal CaMKIIα activity. Moreover, haloperidol given orally was also effective in attenuating morphine-induced CaMKIIα activity, antinociceptive tolerance, and physical dependence. Taken together, these data suggest that haloperidol attenuates opioid tolerance and dependence by suppressing CaMKII activity. Because haloperidol is a clinically used drug that can be taken orally, we propose that the drug may be of use in attenuating opioid tolerance and dependence. PMID:21436292

The rationale for consuming cognitive enhancement drugs in university students and teachers.

Directory of Open Access Journals (Sweden)

Sebastian Sattler

Full Text Available Cognitive enhancement (CE is the pharmaceutical augmentation of mental abilities (e.g., learning or memory without medical necessity. This topic has recently attracted widespread attention in scientific and social circles. However, knowledge regarding the mechanisms that underlie the decision to use CE medication is limited. To analyze these decisions, we used data from two online surveys of randomly sampled university teachers (N = 1,406 and students (N = 3,486. Each respondent evaluated one randomly selected vignette with regard to a hypothetical CE drug. We experimentally varied the characteristics of the drugs among vignettes and distributed them among respondents. In addition, the respondent's internalization of social norms with respect to CE drug use was measured. Our results revealed that students were more willing to enhance cognitive performance via drugs than university teachers, although the overall willingness was low. The probability of side effects and their strength reduced the willingness to use CE drugs among students and university teachers, whereas higher likelihoods and magnitudes of CE increased this propensity. In addition, the internalized norm against CE drug use influenced decision making: Higher internalization decreased the willingness to use such medications. Students' internalized norms more strongly affected CE abstinence compared with those of university teachers. Furthermore, internalized norms negatively interacted with the instrumental incentives for taking CE medication. This internalization limited the influence of and deliberation on instrumental incentives. This study is the first to provide empirical evidence regarding the importance of social norms and their influence on rational decision making with regard to CE. We identified previously undiscovered decision-making patterns concerning CE. Thus, this study provides insight into the motivators and inhibitors of CE drug use. These findings have

The rationale for consuming cognitive enhancement drugs in university students and teachers.

Science.gov (United States)

Sattler, Sebastian; Sauer, Carsten; Mehlkop, Guido; Graeff, Peter

2013-01-01

Cognitive enhancement (CE) is the pharmaceutical augmentation of mental abilities (e.g., learning or memory) without medical necessity. This topic has recently attracted widespread attention in scientific and social circles. However, knowledge regarding the mechanisms that underlie the decision to use CE medication is limited. To analyze these decisions, we used data from two online surveys of randomly sampled university teachers (N = 1,406) and students (N = 3,486). Each respondent evaluated one randomly selected vignette with regard to a hypothetical CE drug. We experimentally varied the characteristics of the drugs among vignettes and distributed them among respondents. In addition, the respondent's internalization of social norms with respect to CE drug use was measured. Our results revealed that students were more willing to enhance cognitive performance via drugs than university teachers, although the overall willingness was low. The probability of side effects and their strength reduced the willingness to use CE drugs among students and university teachers, whereas higher likelihoods and magnitudes of CE increased this propensity. In addition, the internalized norm against CE drug use influenced decision making: Higher internalization decreased the willingness to use such medications. Students' internalized norms more strongly affected CE abstinence compared with those of university teachers. Furthermore, internalized norms negatively interacted with the instrumental incentives for taking CE medication. This internalization limited the influence of and deliberation on instrumental incentives. This study is the first to provide empirical evidence regarding the importance of social norms and their influence on rational decision making with regard to CE. We identified previously undiscovered decision-making patterns concerning CE. Thus, this study provides insight into the motivators and inhibitors of CE drug use. These findings have implications for

The Rationale for Consuming Cognitive Enhancement Drugs in University Students and Teachers

Science.gov (United States)

Sattler, Sebastian; Sauer, Carsten; Mehlkop, Guido; Graeff, Peter

2013-01-01

Cognitive enhancement (CE) is the pharmaceutical augmentation of mental abilities (e.g., learning or memory) without medical necessity. This topic has recently attracted widespread attention in scientific and social circles. However, knowledge regarding the mechanisms that underlie the decision to use CE medication is limited. To analyze these decisions, we used data from two online surveys of randomly sampled university teachers (N = 1,406) and students (N = 3,486). Each respondent evaluated one randomly selected vignette with regard to a hypothetical CE drug. We experimentally varied the characteristics of the drugs among vignettes and distributed them among respondents. In addition, the respondent’s internalization of social norms with respect to CE drug use was measured. Our results revealed that students were more willing to enhance cognitive performance via drugs than university teachers, although the overall willingness was low. The probability of side effects and their strength reduced the willingness to use CE drugs among students and university teachers, whereas higher likelihoods and magnitudes of CE increased this propensity. In addition, the internalized norm against CE drug use influenced decision making: Higher internalization decreased the willingness to use such medications. Students’ internalized norms more strongly affected CE abstinence compared with those of university teachers. Furthermore, internalized norms negatively interacted with the instrumental incentives for taking CE medication. This internalization limited the influence of and deliberation on instrumental incentives. This study is the first to provide empirical evidence regarding the importance of social norms and their influence on rational decision making with regard to CE. We identified previously undiscovered decision-making patterns concerning CE. Thus, this study provides insight into the motivators and inhibitors of CE drug use. These findings have implications

Aspectos familiares de meninas adolescentes dependentes de álcool e drogas Family aspects of alcohol and drug-dependent adolescent girls

Directory of Open Access Journals (Sweden)

Ana Beatriz Pedriali Guimarães

2009-01-01

Full Text Available CONTEXTO: O consumo de drogas entre adolescentes tem sido alvo de várias pesquisas nos últimos anos. Sabe-se que a família pode ser um fator tanto de proteção quanto de risco para o uso de substâncias nessa fase. OBJETIVO: O presente artigo é uma revisão da literatura sobre o tema família de adolescentes abusadoras e/ou dependentes de substâncias psicoativas, a fim de levantar quais dados a literatura já dispõe sobre esse assunto com o intuito de capacitar profissionais da área da saúde na atuação clínica bem como na prevenção desta síndrome. MÉTODOS:Revisão bibliográfica no sistema MedLine (Index Medicus, ScieLO, PubMed, a partir das seguintes palavras-chave: adição, abuso de drogas, meninas, adolescência e família. RESULTADOS:Observou-se que essas famílias em sua maioria possuem características disfuncionais como laços familiares conflitivos, pouca proximidade entre os membros, falta de uma hierarquia bem definida e pais que não dão exemplo positivo quanto ao uso de drogas. Diferenças entre gêneros também são apontadas: meninas necessitam maior apoio familiar que os meninos como fator protetor do envolvimento com grupo de pares desviantes. As meninas também são tão sensíveis ao abuso psicológico quanto ao físico, diferentemente dos meninos que consideram pior o abuso físico. Destaca-se ainda que a presença de relações de apoio com irmãs mais velhas é fator protetor para o abuso de substâncias em meninas. Outros temas, como transmissão transgeracional e estilo parental, também são abordados. CONCLUSÕES:Conclui-se que este tema é pouco explorado na literatura, principalmente no que se refere a estudos que abordem isoladamente a relação entre meninas e dependência.BACKGROUND: Drug use among adolescents has been investigated in several recent studies. Family is recognizably both a protective and a risk factor for substance use during adolescence. OBJECTIVE:This present article is a

Genotype distribution and treatment response among incarcerated drug-dependent patients with chronic hepatitis C infection.

Directory of Open Access Journals (Sweden)

Chun-Han Cheng

Full Text Available The prevalence of hepatitis C virus (HCV infection is disproportionately high among prisoners, especially among those who are drug-dependent. However, current screening and treatment recommendations are inconsistent for this population, and appropriate care is not reliably provided. To address these problems, the present study aimed to identify unique characteristics and clinical manifestations of incarcerated patients with HCV infection. We included incarcerated patients who received treatment with pegylated-interferon combined with ribavirin at Mackay Memorial Hospital in Taitung and were serving sentences at either the Taiyuan Skill Training Institute or the Yanwan Training Institute. HCV genotypes 1 (41.4%, 3 (25.9%, and 6 (24.1% were the most prevalent in the incarcerated patients. During the study period, we analyzed treatment response among 58 incarcerated patients and compared obtained results with treatment response among 52 patients who were living in the community. Higher sustained virological response rate was observed among patients with incarceration and HCV genotype other than 1. The odds ratios (corresponding 95% confidence intervals for incarceration and genotype 1 were 2.75 (1.06-7.11 and 0.37 (0.14-0.99, respectively. Better treatment compliance among incarcerated patients might partially explain these results. The results of this study suggest that treatment of prisoners with HCV infection is feasible and effective. More appropriate and timely methods are needed to prevent HCV transmission among injection drug users inside prisons.

"Up yours": smuggling illicit drugs into prison.

Science.gov (United States)

George, Sanju; Clayton, Steve; Namboodiri, Vasudevan; Boulay, Sylvie

2009-01-01

A significant proportion of patients who are heroin-dependant and receiving treatment in the community serve prison sentences at some point in their lives, meaning their treatment continues "on the inside". Although prison inmates are promised the same quality of care as they would get "on the outside", this is not always the case. Some drawbacks of the drug treatments offered in prisons can lead to people smuggling drugs into prisons. The present work describes how a patient, who is heroin dependant and attending a community drug and alcohol team for methadone maintenance treatment, smuggled methadone and heroin into prison, his reasons for doing that, his personal description of the extent of drug use in prisons and finally what can be done to stop it from treatment and policy perspectives. Drug misuse is common in prisons. Much more can be done at treatment and policy levels to prevent people smuggling drugs into prison.

Motives for using: a comparison of prescription opioid, marijuana and cocaine dependent individuals.

Science.gov (United States)

Hartwell, Karen J; Back, Sudie E; McRae-Clark, Aimee L; Shaftman, Stephanie R; Brady, Kathleen T

2012-04-01

Identification of the motives for drug use is critical to the development of effective interventions. Furthermore, consideration of the differences in motives for drug use across substance dependent populations may assist in tailoring interventions. To date, few studies have systematically compared motives for substance use across drug classes. The current study examined motives for drug use between non-treatment seeking individuals with current prescription opioid, marijuana, or cocaine dependence. Participants (N=227) completed the Inventory of Drug-Taking Situations (IDTS; Annis, Turner & Sklar,1997), which contains eight subscales assessing motives for drug use. The findings revealed that prescription opioid dependent individuals scored significantly higher than all other groups on the Physical Discomfort, Testing Personal Control and Conflict with Others subscales. Both the prescription opioid and cocaine dependent groups scored significantly higher than the marijuana group on the Urges or a Temptation to Use subscale. In contrast, marijuana dependent individuals scored highest on the Pleasant Emotions and Pleasant Times with Others subscales. The marked differences revealed in motives for drug use could be used in the development and implementation of specific treatment interventions for prescription opioid, marijuana and cocaine dependent individuals. Published by Elsevier Ltd.

Personality of mothers of substance-dependent patients

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David Baron

2010-04-01

Full Text Available David Baron1, Samir AbolMagd2, Salwa Erfan2, Mona El Rakhawy21Temple University School of Medicine, Philadelphia, PA, USA; 2University of Cairo School of Medicine, Cairo, EgyptAbstract: Drug addicts often come from dysfunctional families. The prevailing view in the literature is that mothers of drug-dependent patients can be characterized by strong emotional bonds and overprotection. Studies suggest that maternal rejection could be a major risk factor of developing drug addiction. This work is a continuation of our previous study of childhood parenting experiences of substance-dependent patients. The aims were to compare the personality profile of mothers of substance-dependent patients and that of mothers of matched control subjects; and to examine the relation between the personality of mothers of addicts, and severity of their offspring’s addiction. The study group consisted of 20 mothers of substance-dependent patients and a control group of 35 mothers of non-dependent subjects; mothers of both groups were age matched. Patients were diagnosed according to DSM IV criteria. Personalities of mothers of both groups were assessed using the Minnesota Multiphasic Personality Inventory (MMPI. Substance-dependent patients (sons were administered the Addiction Severity Index (ASI. The mean scores of the MMPI Scales were higher for mothers of dependent patients compared to mothers of non-dependent subjects. Scores on the depression, hysteria and paranoia scales were significantly higher for mothers of patients (P = 0.03, 0.02, and 0.03, respectively. There was a significant positive correlation between scores of hysteria, and psychopathic deviance and the ASI (P = 0.03 and 0.01, respectively. There were significant negative correlations between scores of social introversion and the ASI drug/alcohol use status (P = 0.007, and family history dimensions (P = 0.003. Mothers of substance-dependent patients showed disturbances in aspects of personalities

Sexual addiction in drug addicts: The impact of drug of choice and poly-addiction.

Science.gov (United States)

Antonio, Nelson; Diehl, Alessandra; Niel, Marcelo; Pillon, Sandra; Ratto, Lilian; Pinheiro, Maria Carolina; Silveira, Dartiu; Otani, Thais Zelia; Otani, Victor; Cordeiro, Quirino; Ushida, Ricardo

2017-05-01

To compare the risk of comorbid sexual addiction in a sample of individuals with a diagnosis of substance dependence, stratifying the sample by drug of choice as well as by mono versus polysubstance addiction. All data were collected at Santa Casa de São Paulo, Brazil. The study sample comprised all alcohol or drug dependents admitted to the Addiction Treatment Unit between November 2013 and August 2014. A generalized linear model with a binomial distribution was performed to compare the odds of having a Sexual Addiction Screening Test (SAST) score greater than 6 points in the subgroups analyzed. A total of 133 participants were included in our analysis, all reporting cocaine/crack and/or alcohol as drug of choice. Polysubstance addicts had a significant higher risk of a positive screening for sexual addiction compared to monosubstance addicts, age-sex adjusted odds ratios of sexual addiction being respectively 2.72 (95CI 1.1-6.71) and 0.37 (95CI 0.15-0.91). The odds of a SAST score greater than 6 was not statistically different between the cocaine/crack and alcohol groups, respectively 0.38 (95CI 0.14-1.02) and 2.67 (95CI 0.98-7.25). We found a significant relation between stronger drug addiction and greater levels of sexual addiction in the cocaine/crack group (p=0.0012), but not in the alcohol group. Our study reinforces the importance of assessing sexual behavior of drug addicts in clinical practice, especially considering users of multiple substances or with severe dependence.

Comorbidade entre transtorno de estresse pós-traumático e abuso e dependência de álcool e drogas: uma revisão da literatura Comorbidity of post traumatic stress disorder (PTSD with alcohol and drug abuse and dependency: a literature review

Directory of Open Access Journals (Sweden)

Heloisa de Souza Dantas

2008-01-01

Full Text Available CONTEXTO: Pesquisas revelam uma alta comorbidade entre o transtorno de estresse pós-traumático (TEPT e o abuso e dependência de álcool e drogas (ADAD. OBJETIVOS: Descrever a natureza da associação entre TEPT e ADAD, as diferenças entre os gêneros feminino e masculino, bem como os principais tratamentos utilizados. MÉTODOS: Pesquisa bibliográfica entre os anos de 1995 e 2007 no PubMed, utilizando os termos "trauma" AND "alcohol", "trauma" AND "substance abuse", "trauma" AND "dependence", "trauma" AND "drugs", "posttraumatic stress" AND "alcohol", posttraumatic stress" AND "substance abuse", "posttraumatic stress" AND "dependence", "posttraumatic stress" AND "drugs". RESULTADOS: As seguintes hipóteses foram identificadas: 1 o abuso de substâncias aumenta os riscos para a ocorrência de TEPT em virtude de estilos de vida que expõem mais o sujeito à ocorrência de traumas e pelo fato de as drogas potencializarem as seqüelas do trauma; 2 o TEPT levaria ao aumento do uso de álcool e drogas acompanhado de possível abuso com o objetivo de aliviar sintomas decorrentes do transtorno. Conclusões: A identificação precoce da comorbidade entre o TEPT e o ADAD é fundamental para o bom prognóstico do paciente, bem como o atendimento adequado às vítimas de situações traumáticas para que sejam minimizadas as chances da ocorrência do TEPT.BACKGROUND: The literature reveals high comorbidity rates between post traumatic stress disorder (PTSD and substance abuse and dependence (SAD. OBJECTIVES: This paper seeks to describe the relationship between the two disorders; the gender differences; and the primary treatments used to reduce PTSD as well as SAD symptoms. METHODS: A review of the literature between 1995 and 2007. A PubMed search was used to find articles with the key words: "trauma" AND "alcohol", "trauma" AND "substance abuse", "trauma" AND "dependence", "trauma" AND "drugs", "post traumatic stress" AND "alcohol", post traumatic

Drugs and having babies: an exploration of how a specialist clinic meets the needs of chemically dependent pregnant women.

Science.gov (United States)

Morris, Michelle; Seibold, Carmel; Webber, Ruth

2012-04-01

to explore the extent to which a specialist clinic meets the needs of chemically dependent women. a critical ethnography informed by theorists such as Habermas and feminists' interpretation of Foucault. a specialist antenatal clinic for chemically dependent pregnant women at a major metropolitan women's hospital in Melbourne, Australia. a purposive sample of twenty (20) chemically dependent pregnant women who attended the clinic. Data collection and analysis included three taped interviews (two preceding the birth and one post birth), observation of the interactions between the women and the clinic staff over a 25-month period and chart audits. similar to other studies there were multiple factors influencing development and maintenance of chemical dependency in this group of women, including family instability, family history of drug and alcohol abuse, childhood sexual abuse, having a chemically dependent partner and having a dual diagnosis of both drug addiction and mental illness. Initially there was considerable variation between the women and the clinic staff's expectations with regard to attending for antenatal care and conforming to a set regime as the women struggled with the contradictions inherent in their lifestyle and that of the 'normal' expectant mother. Aspects of that struggle included their belief that their opinions and knowledge of their lives was largely ignored, leading to episodes of resistance. Several women alleged the clinics staff's relationship with them was influenced by a belief that the women were 'hopeless addicts in need of expert medical and midwifery care' and that the clinic staff exercised control in an authoritarian manner. However, as they explored possibilities for collaboration, they realised they could exercise power and work towards a more equal relationship with staff. The quality of relationships in most instances improved over time, and if not always strictly collaborative, was situated at various points along a continuum

Rational drug design paradigms: the odyssey for designing better drugs.

Science.gov (United States)

Kellici, Tahsin; Ntountaniotis, Dimitrios; Vrontaki, Eleni; Liapakis, George; Moutevelis-Minakakis, Panagiota; Kokotos, George; Hadjikakou, Sotiris; Tzakos, Andreas G; Afantitis, Antreas; Melagraki, Georgia; Bryant, Sharon; Langer, Thierry; Di Marzo, Vincenzo; Mavromoustakos, Thomas

2015-01-01

Due to the time and effort requirements for the development of a new drug, and the high attrition rates associated with this developmental process, there is an intense effort by academic and industrial researchers to find novel ways for more effective drug development schemes. The first step in the discovery process of a new drug is the identification of the lead compound. The modern research tendency is to avoid the synthesis of new molecules based on chemical intuition, which is time and cost consuming, and instead to apply in silico rational drug design. This approach reduces the consumables and human personnel involved in the initial steps of the drug design. In this review real examples from our research activity aiming to discover new leads will be given for various dire warnings diseases. There is no recipe to follow for discovering new leads. The strategy to be followed depends on the knowledge of the studied system and the experience of the researchers. The described examples constitute successful and unsuccessful efforts and reflect the reality which medicinal chemists have to face in drug design and development. The drug stability is also discussed in both organic molecules and metallotherapeutics. This is an important issue in drug discovery as drug metabolism in the body can lead to various toxic and undesired molecules.

Discovery of genomic intervals that underlie nematode responses to benzimidazoles.

Science.gov (United States)

Zamanian, Mostafa; Cook, Daniel E; Zdraljevic, Stefan; Brady, Shannon C; Lee, Daehan; Lee, Junho; Andersen, Erik C

2018-03-01

Parasitic nematodes impose a debilitating health and economic burden across much of the world. Nematode resistance to anthelmintic drugs threatens parasite control efforts in both human and veterinary medicine. Despite this threat, the genetic landscape of potential resistance mechanisms to these critical drugs remains largely unexplored. Here, we exploit natural variation in the model nematodes Caenorhabditis elegans and Caenorhabditis briggsae to discover quantitative trait loci (QTL) that control sensitivity to benzimidazoles widely used in human and animal medicine. High-throughput phenotyping of albendazole, fenbendazole, mebendazole, and thiabendazole responses in panels of recombinant lines led to the discovery of over 15 QTL in C. elegans and four QTL in C. briggsae associated with divergent responses to these anthelmintics. Many of these QTL are conserved across benzimidazole derivatives, but others show drug and dose specificity. We used near-isogenic lines to recapitulate and narrow the C. elegans albendazole QTL of largest effect and identified candidate variants correlated with the resistance phenotype. These QTL do not overlap with known benzimidazole target resistance genes from parasitic nematodes and present specific new leads for the discovery of novel mechanisms of nematode benzimidazole resistance. Analyses of orthologous genes reveal conservation of candidate benzimidazole resistance genes in medically important parasitic nematodes. These data provide a basis for extending these approaches to other anthelmintic drug classes and a pathway towards validating new markers for anthelmintic resistance that can be deployed to improve parasite disease control.

Effectiveness of Hope Therapy on Reducing Depressive Symptoms and Preventing of Relapse in Cure-Seeker Women with Dependency to Narcotic Drugs

OpenAIRE

Akram S Raesian; Mahmood Golzari; Ahmad Borjali

2011-01-01

Introduction: The aim of the present research was the investigation of the effectiveness of hope therapy on reduction of the degree of depression symptoms and prevention of relapse in cure-seeker women with dependency to narcotic drugs. Method: In semi-experimental research method 20 clients who diagnosed as substance abuse disorder that completed detoxification period successfully, and they were scored more than 14 in depression symptoms (Beck depression questionnaire, second edition) select...

Drug-, dose- and sex-dependent effects of chronic fluoxetine, reboxetine and venlafaxine on open-field behavior and spatial memory in rats.

Science.gov (United States)

Gray, Vanessa C; Hughes, Robert N

2015-03-15

In an effort to address the need to include both sexes in studies of effects of the SSRI fluoxetine, the NRI reboxetine and the SNRI venlafaxine on anxiety-related behavior and memory along with the use of chronic drug administration, male and female PVG/c rats were fed diets containing two doses of each drug for 21 days. The rats' anxiety level was then assessed in an open field. Short-term spatial memory for a brightness change in a Y maze was also measured. While there was little evidence of anxiolytic effects of any of the drugs, both fluoxetine and, to a lesser extent, venlafaxine appeared to be mainly anxiogenic in their action depending on both dose and sex. Reboxetine was relatively ineffective in this respect. Ability to locate the Y-maze arm that had changed (from white to black) seemed to be impaired for male (but not female) rats by both fluoxetine and venlafaxine and, to a much lesser extent, by reboxetine. Given the relative ineffectiveness of reboxetine in either test, it is possible that the effects of the other two drugs on both anxiety and memory were mainly due to their serotonin reuptake inhibiting properties. The differences that occurred between males and females in responsiveness to all three drugs supported the long-held view that both sexes should be investigated in studies of this sort, especially in view of reports of sex differences in effects of clinically prescribed antidepressants. Copyright © 2014 Elsevier B.V. All rights reserved.

Recent Advances in Drug-Induced Angioedema

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Naoko Inomata

2012-01-01

Full Text Available Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life- threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs in the causation of life- threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin- dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

Reproduction (I): Sex, Drug and Ethics

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Mann, Thaddeus

1970-01-01

Reviews the evidence of drug effects on the unborn, the chromosomal constituency of intersexuality, and the relationships between drug dependence and sexual inadequacy. The sexual effects of alcohol and smoking are discussed. Considers ethical and legal problems raised by the research. (AL)

Drug: D08247 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D08247 Drug Nalorphine (INN); Nalorphine serb (TN) ... C19H21NO3 D08247.gif ... Analgesic ... DG01586 ... Opioid receptor antagonist Other ... DG01718 ... Drugs for addictive disorder ... DG01717 ... Drugs for opioid dependence Same as: C11787 ATC code: V03AB02 Chemical group: DG01151 ... CAS: 62-67-9 PubChem: 96024935 ChEBI: 7458 ChEMBL: CHEMBL415284 LigandBox: D08247 NIKKAJI: J4.825I ...

Bibliography [On Drugs].

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National Association of Student Personnel Administrators, Detroit, MI.

A bibliography of materials on drugs is presented. The book and paper back entries are annotated. Selected technical references are listed under these major findings: (1) dependency, (2) barbiturates, (3) amphetamines, and (4) general pharmacology. (PS)

Recreational drugs of abuse.

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Albertson, Timothy E

2014-02-01

The use of recreational drugs of abuse continues to expand without limitations to national boundaries, social status, race, or education. Beyond the prevalence of illicit drug use and dependence, their contribution to the global burden of disease and death are large and troubling. All medical providers should be aware of the evolving drugs of abuse and their medical and social consequences. In addition to heroin and stimulants such as cocaine and methamphetamine, new designer stimulants called "bath salts" and cannabinoids called "spice," along with the abuse of prescription drugs and volatile substances, are now widely recognized problems in many societies. The wide variety and continuingly expanding clinical manifestations of toxicity of recreational drugs of abuse is not widely appreciated by clinicians. This edition attempts to summarize six major classes of drugs of abuse and their clinical effects with special emphasis on their immunological and respiratory effects.

Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence

NARCIS (Netherlands)

Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M; Kreek, Mary Jeanne

2016-01-01

BACKGROUND: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence.

Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence

NARCIS (Netherlands)

Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R.; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M.; Kreek, Mary Jeanne

2016-01-01

Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Genetic

Gender Comparisons Among Asian American and Pacific Islander Patients in Drug Dependency Treatment.

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Han, Yun; Lin, Veronique; Wu, Fei; Hser, Yih-Ing

2016-05-11

Few studies have focused on Asian Americans and Pacific Islanders (AAPIs), despite indications of increasing substance abuse among AAPIs in recent years. This prospective longitudinal study examined gender differences among AAPIs in treatment. The study included 567 (177 women, 390 men) AAPI patients drawn from two prior studies, one with 32 community treatment programs in 13 California counties (CalTOP, 3, 9 months), and another project including 36 treatment sites in 5 California counties (TSI, 3, 12 months). Baseline and follow-up assessments utilized the Addiction Severity Index(ASI). A subset of patients was assessed at 3 and 9/12 months (n = 106). Significant gender-related differences were observed at baseline: fewer women than men were employed or never married. More women were living with someone having alcohol and drug problems. Methamphetamine was the primary drug for women and men, followed by alcohol and heroin. Compared to AAPI men, AAPI women reported greater problem severity in family/social relationships (0.18 vs. 0.11, p drug, and legal domains for both genders, and in mental health for men only. Compared to AAPI men, AAPI women demonstrated significantly greater improvements in drug problems (ΔASI = 0.07, p drug use problems for AAPI men.

Drug Loading and Release Behavior Depending on the Induced Porosity of Chitosan/Cellulose Multilayer Nanofilms.

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Park, Sohyeon; Choi, Daheui; Jeong, Hyejoong; Heo, Jiwoong; Hong, Jinkee

2017-10-02

The ability to control drug loading and release is the most important feature in the development of medical devices. In this research, we prepared a functional nanocoating technology to incorporate a drug-release layer onto a desired substrate. The multilayer films were prepared using chitosan (CHI) and carboxymethyl cellulose (CMC) polysaccharides by the layer-by-layer (LbL) method. By using chemical cross-linking to change the inner structure of the assembled multilayer, we could control the extent of drug loading and release. The cross-linked multilayer film had a porous structure and enhanced water wettability. Interestingly, more of the small-molecule drug was loaded into and released from the non-cross-linked multilayer film, whereas more of the macromolecular drug was loaded into and released from the cross-linked multilayer film. These results indicate that drug loading and release can be easily controlled according to the molecular weight of the desired drug by changing the structure of the film.

Host-guest chemistry of dendrimer-drug complexes. 6. Fully acetylated dendrimers as biocompatible drug vehicles using dexamethasone 21-phosphate as a model drug.

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Yang, Kun; Weng, Liang; Cheng, Yiyun; Zhang, Hongfeng; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen

2011-03-17

Fully acetylated poly(amidoamine) (PAMAM) dendrimer was proposed as a biocompatible drug vehicle using dexamethasone 21-phosphate (Dp21) as a model drug. NMR techniques including (1)H NMR and 2D NOE NMR were used to characterize the host-guest chemistry of acetylated dendrimer/Dp21 and cationic dendrimer/Dp21 complexes. The pH-dependent micellization, complexation, and inclusion behaviors of Dp21 were observed in the presence of acetylated and cationic PAMAM dendrimers. Acetylated dendrimer only encapsulates Dp21 at acidic conditions, while cationic dendrimer can host Dp21 at both acidic and neutral conditions. The orientation of Dp21 molecules in the dendrimer cavities depends on the quaternization degree of tertiary amine groups of dendrimer and the protonation ratio of phosphate group of Dp21. A distinctive pH-dependent release behavior of Dp21 from the acetylated and nonacetylated dendritic matrix was observed: Dp21 exhibits a much slower release rate from acetylated dendrimer at lower pH conditions and a much faster release rate from nonacetylated dendrimer with decreasing pH values. Cytotoxicity studies further confirmed the biocompatibility of acetylated dendrimers, which are much safer in the delivery of therapeutics for the treatment of various diseases than nonacetylated dendrimers. The dendrimer-drug binding and release mechanisms provide a new insight for the design and optimization of biocompatible dendrimer-based drug delivery systems. © 2011 American Chemical Society

Anti-diabetes drug pioglitazone ameliorates synaptic defects in AD transgenic mice by inhibiting cyclin-dependent kinase5 activity.

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Jinan Chen

Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a serine/threonine kinase that is activated by the neuron specific activators p35/p39 and plays many important roles in neuronal development. However, aberrant activation of Cdk5 is believed to be associated with the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Here in the present study, enhanced Cdk5 activity was observed in mouse models of AD; whereas soluble amyloid-β oligomers (Aβ, which contribute to synaptic failures during AD pathogenesis, induced Cdk5 hyperactivation in cultured hippocampal neurons. Inhibition of Cdk5 activity by pharmacological or genetic approaches reversed dendritic spine loss caused by soluble amyloid-β oligomers (Aβ treatment. Interestingly, we found that the anti-diabetes drug pioglitazone could inhibit Cdk5 activity by decreasing p35 protein level. More importantly, pioglitazone treatment corrected long-term potentiation (LTP deficit caused by Aβ exposure in cultured slices and pioglitazone administration rescued impaired LTP and spatial memory in AD mouse models. Taken together, our study describes an unanticipated role of pioglitazone in alleviating AD and reveals a potential therapeutic drug for AD curing.

Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny

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Jane Alcorn

2010-10-01

Full Text Available Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20. Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age.

The current status of community drug testing via the analysis of drugs and drug metabolites in sewage

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Malcolm J. Reid

2011-12-01

Full Text Available Over the past few years the analysis of drug residues in sewage has been promoted as a means of estimating the level of drug use in communities. Measured drug residue concentrations in the sewage are used to determine the load (total mass of the drug being used by the entire community. Knowledge of the size or population of the community then allows for the calculation of drug-use relative to population (typically drug-mass/day/1000 inhabitants which facilitates comparisons between differing communities or populations. Studies have been performed in many European countries, including Norway, as well as in the US and Australia. The approach has successfully estimated the use of cocaine, amphetamine, methamphetamine, MDMA, cannabis, nicotine and alcohol. The analysis of biomarkers of drug use in sewage has great potential to support and complement existing techniques for estimating levels of drug use, and as such has been identified as a promising development by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA; www.emcdda.europa.eu/wastewater-analysis. The approach is not without its challenges, and ongoing collaboration across Europe aims at agreeing upon best-practice and harmonising the methods being used. In Norway development is being performed through the NFR RUSMIDDEL funded DrugMon (www.niva.no/drugmon project that has led to the development of many new techniques, significantly improved our understanding of the uncertainties associated with the approach and allowed the coordination of Europe wide collaboration which has included all important intercalibration exercises. Application of the technique can provide evidence-based and real-time estimates of collective drug use with the resulting data used to improve the much needed estimates of drug use and dependency.

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

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

2016-06-01

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

Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls.

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Leininger, Elizabeth C; Kelley, Darcy B

2013-04-07

Independent or convergent evolution can underlie phenotypic similarity of derived behavioural characters. Determining the underlying neural and neuromuscular mechanisms sheds light on how these characters arose. One example of evolutionarily derived characters is a temporally simple advertisement call of male African clawed frogs (Xenopus) that arose at least twice independently from a more complex ancestral pattern. How did simplification occur in the vocal circuit? To distinguish shared from divergent mechanisms, we examined activity from the calling brain and vocal organ (larynx) in two species that independently evolved simplified calls. We find that each species uses distinct neural and neuromuscular strategies to produce the simplified calls. Isolated Xenopus borealis brains produce fictive vocal patterns that match temporal patterns of actual male calls; the larynx converts nerve activity faithfully into muscle contractions and single clicks. In contrast, fictive patterns from isolated Xenopus boumbaensis brains are short bursts of nerve activity; the isolated larynx requires stimulus bursts to produce a single click of sound. Thus, unlike X. borealis, the output of the X. boumbaensis hindbrain vocal pattern generator is an ancestral burst-type pattern, transformed by the larynx into single clicks. Temporally simple advertisement calls in genetically distant species of Xenopus have thus arisen independently via reconfigurations of central and peripheral vocal neuroeffectors.

Experiences to be a family caregiver of dependent elderly in the home environment

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Alcimar Marcelo do Couto

2016-02-01

Full Text Available Objective: to understand the experience of caring for dependent elderly in the home environment, from the perspective of family caregivers that present burden and emotional distress. Methods: this is a qualitative research with a contribution in the Theory Grounded in Data. There were home visits for observation and semi-structured interviews with nine relatives of dependent elderly in self-care. Results: with the coding and analysis of empirical data, one can understand the daily cares in the care relationship with their elderly dependent relatives. The consolidated experiences underlie on positive experiences, such as solidarity by the established interaction and the maintenance of self-esteem, and negative as changes in daily routine and health, with stress identification related to the caregiver role. Conclusion: in the understanding of the family, their experiences as a caregiver in the home context varied between positive and negative aspects, which respectively minimize and maximize the feeling of burden and emotional distress.

Cross-generational effects on gender differences in psychoactive drug abuse and dependence.

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Holdcraft, Laura C; Iacono, William G

2004-05-10

Studies of patients with cocaine and heroin use disorders have shown gender differences in prevalence, course, and outcome. These differences may be decreasing in successive generations. Less is known about gender differences in course and symptomatology for other illicit drug use disorders, especially in community samples. Participants (1323 men and 1384 women) who were biological or step-parents of twins and born in the 1940-1960s, from the Minnesota Twin-Family Study (MTFS) were divided into two cohorts based on the median birth year. A structured interview was used to assess DSM-III-R cannabis, amphetamine, cocaine and hallucinogen use disorders. There was a higher prevalence of each of these drug disorders and earlier onset of cannabis and amphetamine use disorders in later-born participants. For most drug use disorder categories, men and women were similar with respect to age of onset and severity of disorder but women had a shorter course of drug use disorders. Women with amphetamine disorders were atypical with respect to having a higher frequency of use but similar number of lifetime uses compared to men, and more emotional effects of amphetamine intoxication than men. In addition, women with amphetamine disorders were more likely to have anorexia nervosa than those without amphetamine disorders. These results have several implications for prevention, etiology and treatment.

Kinetics of drug release from ointments: Role of transient-boundary layer.

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Xu, Xiaoming; Al-Ghabeish, Manar; Krishnaiah, Yellela S R; Rahman, Ziyaur; Khan, Mansoor A

2015-10-15

In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time. Published by Elsevier B.V.

Temperament and character modify risk of drug addiction and influence choice of drugs.

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Milivojevic, Dragan; Milovanovic, Srdjan D; Jovanovic, Minja; Svrakic, Dragan M; Svrakic, Nenad M; Svrakic, Slobodan M; Cloninger, C Robert

2012-01-01

Drug addiction and alcoholism involve a complex etiopathogenesis with a variable degree of risk contributions from the host (person), environment, and addictive substances. In this work, temperament and character features of individuals addicted to opiates or alcohol are compared with normal controls to study personality factors in the overall risk for drug addiction. The study was done in a permissive environment, with easy access to alcohol and heroin, which facilitated analyses of personality factors in drug choice. Participants included 412 consecutive patients (312 opiate addicts, 100 alcohol addicts) treated at the Specialized Hospital for Chemical Dependency in Belgrade, Serbia, and a community sample of 346 controls. Opiate addicts manifested antisocial temperament configuration (high Novelty Seeking, low Reward Dependence) coupled with high Self-transcendence (ie, susceptibility to fantasy and imagination). Alcohol addicts manifested sensitive temperament configuration (high Novelty Seeking coexisting with high Harm Avoidance). Immature personality was observed far more frequently in opiate addicts than in alcoholics or normals. Novelty Seeking appears to be a general risk factor for drug addiction. High Harm Avoidance appears to channel individuals with high Novelty Seeking towards alcoholism. Immature character traits and probable Personality Disorder increase the risk of illegal drugs. Based on equivalent research in nonpermissive environments, at least a portion of our opiate addicts could have developed alcoholism instead in environments with more limited access to opiates. Personality factors provide useful guidelines for preventive work with young individuals with personality risk factors for drug addiction. Copyright © American Academy of Addiction Psychiatry.

Seeing through the public health smoke-screen in drug policy.

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Csete, Joanne; Wolfe, Daniel

2017-05-01

In deliberations on drug policy in United Nations fora, a consensus has emerged that drug use and drug dependence should be treated primarily as public health concerns rather than as crimes. But what some member states mean by "public health approach" merits scrutiny. Some governments that espouse treating people who use drugs as "patients, not criminals" still subject them to prison-like detention in the name of drug-dependence treatment or otherwise do not take measures to provide scientifically sound treatment and humane social support to those who need them. Even drug treatment courts, which the U.S. and other countries hold up as examples of a public health approach to drug dependence, can serve rather to tighten the hold of the criminal justice sector on concerns that should be addressed in the health sector. The political popularity of demonisation of drugs and visibly repressive approaches is an obvious challenge to leadership for truly health-oriented drug control. This commentary offers some thoughts for judging whether a public health approach is worthy of the name and cautions drug policy reformers not to rely on facile commitments to health approaches that are largely rhetorical or that mask policies and activities not in keeping with good public health practise. Copyright © 2017 Elsevier B.V. All rights reserved.

“Up yours”: smuggling illicit drugs into prison

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George, Sanju; Clayton, Steve; Namboodiri, Vasudevan; Boulay, Sylvie

2009-01-01

A significant proportion of patients who are heroin-dependant and receiving treatment in the community serve prison sentences at some point in their lives, meaning their treatment continues “on the inside”. Although prison inmates are promised the same quality of care as they would get “on the outside”, this is not always the case. Some drawbacks of the drug treatments offered in prisons can lead to people smuggling drugs into prisons. The present work describes how a patient, who is heroin dependant and attending a community drug and alcohol team for methadone maintenance treatment, smuggled methadone and heroin into prison, his reasons for doing that, his personal description of the extent of drug use in prisons and finally what can be done to stop it from treatment and policy perspectives. Drug misuse is common in prisons. Much more can be done at treatment and policy levels to prevent people smuggling drugs into prison. PMID:21954402

Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

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Burke, Andrew R.; Miczek, Klaus A.

2014-01-01

Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

Co-Option and De Novo Gene Evolution Underlie Molluscan Shell Diversity

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Aguilera, Felipe; McDougall, Carmel

2017-01-01

Abstract Molluscs fabricate shells of incredible diversity and complexity by localized secretions from the dorsal epithelium of the mantle. Although distantly related molluscs express remarkably different secreted gene products, it remains unclear if the evolution of shell structure and pattern is underpinned by the differential co-option of conserved genes or the integration of lineage-specific genes into the mantle regulatory program. To address this, we compare the mantle transcriptomes of 11 bivalves and gastropods of varying relatedness. We find that each species, including four Pinctada (pearl oyster) species that diverged within the last 20 Ma, expresses a unique mantle secretome. Lineage- or species-specific genes comprise a large proportion of each species’ mantle secretome. A majority of these secreted proteins have unique domain architectures that include repetitive, low complexity domains (RLCDs), which evolve rapidly, and have a proclivity to expand, contract and rearrange in the genome. There are also a large number of secretome genes expressed in the mantle that arose before the origin of gastropods and bivalves. Each species expresses a unique set of these more ancient genes consistent with their independent co-option into these mantle gene regulatory networks. From this analysis, we infer lineage-specific secretomes underlie shell diversity, and include both rapidly evolving RLCD-containing proteins, and the continual recruitment and loss of both ancient and recently evolved genes into the periphery of the regulatory network controlling gene expression in the mantle epithelium. PMID:28053006

Drugs and taste aversion

International Nuclear Information System (INIS)

Rondeau, D.B.; Jolicoeur, F.B.; Merkel, A.D.; Wayner, M.J.

1981-01-01

The literature on the effects of drugs on the acquisition and the magnitude of taste aversion is reviewed and discussed. Then, the results of a series of experiments on the effects of phenobarbital and related drugs on taste aversion are reported. A standard taste aversion model was used in all experiments; test drugs were injected prior to drinking in a one bottle situation on the first test day following the taste aversion treatment. Phenobarbital in doses ranging from 20 to 80 mg/kg significantly attenuated taste aversion induced by lithium chloride (LiCl) and x-radiation, the maximal effect occurred with the 60 mg/kg dose. The attenuating effect was found to be dependent upon the magnitude of the aversion to the sapid solution. Phenobarbital completely abolished aversion produced by 0.375 mEq LiCl while the attenuation effect decreased linearly with higher doses of LiCl. Results also indicate that phenobarbital's attenuating effect cannot be solely attributed to its dipsogenic characteristic or to its state dependent learning effect. Attenuation of LiCl aversion to a saccharin solution was also observed following single doses of amobarbital, 30 mg/kg, pentobarbital, 15 mg/kg, and chloropromazine, 0.75 mg/kg. Taste aversion was not affected by other doses of those drugs or by hexobarbital, barbital, and chlordiazepoxide. Phenobarbital's attenuating effect on taste aversion is discussed in relation to other known behavioral and neurophysiological effects of the drug

Consistency of psychotropic drug-drug interactions listed in drug monographs.

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Liu, Xinyue; Hatton, Randy C; Zhu, Yanmin; Hincapie-Castillo, Juan M; Bussing, Regina; Barnicoat, Marie; Winterstein, Almut G

With an increasing prevalence of psychotropic polypharmacy, clinicians depend on drug-drug interaction (DDI) references to ensure safe regimens, but the consistency of such information is frequently questioned. To evaluate the consistency of psychotropic DDIs documented in Clinical Pharmacology (CP), Micromedex (MM), and Lexicomp (LC) and summarize consistent psychotropic DDIs. In May 2016, we extracted severe or major psychotropic DDIs for 102 psychotropic drugs, including central nervous system (CNS) stimulants, antidepressants, an antimanic agent (lithium), antipsychotics, anticonvulsants, and anxiolytics-sedatives-hypnotics from CP, MM, and LC. We then summarized the psychotropic DDIs that were included in all 3 references and with evidence quality of "excellent" or "good" based on MM. We identified 1496, 938, and 1006 unique severe or major psychotropic DDIs from CP, MM, and LC, respectively. Common adverse effects related to psychotropic DDIs include increased or decreased effectiveness, CNS depression, neurotoxicity, QT prolongation, serotonin syndrome, and multiple adverse effects. Among these interactions, only 371 psychotropic DDIs were documented in all 3 references, 59 of which had "excellent" or "good" quality of evidence based on MM. The consistency of psychotropic DDI documentation across CP, MM, and LC is poor. DDI documentations need standards that would encourage consistency among drug information references. The list of the 59 DDIs may be useful in the assessment of psychotropic polypharmacy and highlighting DDI alerts in clinical practice. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Confirming therapeutic target of protopine using immobilized β2 -adrenoceptor coupled with site-directed molecular docking and the target-drug interaction by frontal analysis and injection amount-dependent method.

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Liu, Guangxin; Wang, Pei; Li, Chan; Wang, Jing; Sun, Zhenyu; Zhao, Xinfeng; Zheng, Xiaohui

2017-07-01

Drug-protein interaction analysis is pregnant in designing new leads during drug discovery. We prepared the stationary phase containing immobilized β 2 -adrenoceptor (β 2 -AR) by linkage of the receptor on macroporous silica gel surface through N,N'-carbonyldiimidazole method. The stationary phase was applied in identifying antiasthmatic target of protopine guided by the prediction of site-directed molecular docking. Subsequent application of immobilized β 2 -AR in exploring the binding of protopine to the receptor was realized by frontal analysis and injection amount-dependent method. The association constants of protopine to β 2 -AR by the 2 methods were (1.00 ± 0.06) × 10 5 M -1 and (1.52 ± 0.14) × 10 4 M -1 . The numbers of binding sites were (1.23 ± 0.07) × 10 -7 M and (9.09 ± 0.06) × 10 -7 M, respectively. These results indicated that β 2 -AR is the specific target for therapeutic action of protopine in vivo. The target-drug binding occurred on Ser 169 in crystal structure of the receptor. Compared with frontal analysis, injection amount-dependent method is advantageous to drug saving, improvement of sampling efficiency, and performing speed. It has grave potential in high-throughput drug-receptor interaction analysis. Copyright © 2017 John Wiley & Sons, Ltd.

Determinants of nonmedical use, abuse or dependence on prescription drugs, and use of substance abuse treatment.

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Bali, Vishal; Raisch, Dennis W; Moffett, Maurice L; Khan, Nasreen

2013-01-01

Previous studies have found a negative association between health insurance and nonmedical use of prescription drugs (NMUPD), and abuse or dependence on prescription drugs (ADPD); and mixed associations between health insurance and use of substance abuse treatment (SAT). However, effect of health insurance in the specific subgroups of population is largely unknown. To estimate the relationship between health insurance and (1) NMUPD, (2) ADPD, and (3) use of SAT services among 12-64 years old, noninstitutionalized individuals and to see if these relationships are different in different subgroups of population. This study used cross-sectional survey data from 2007 National Survey on Drug Use and Health. Bivariate and multiple logistic regression analyses were conducted. In 2007, self-reported prevalence of NMUPD was approximately 10% (N=15,509,703). In multivariate analysis, NMUPD was negatively associated with health insurance, age, race other than non-Hispanic White, education, marital status, and income ($40,000-$74,999). Past year use of tobacco and alcohol were positively associated with NMUPD. Among those with private health insurance, Hispanics and individuals with family income less than $20,000 and $40,000-$74,999 were more likely prone to NMUPD than others. High school graduates with public health insurance were less likely prone to NMUPD. Approximately, 13% of nonmedical users reported ADPD (N=2,011,229). Health insurance and age were negatively associated with ADPD. However, people who were unmarried, reported fair/poor health, and used tobacco were more likely to report ADPD. Lastly, the use of substance abuse treatment programs was approximately 73% and 76% between NMUPD and ADPD population, respectively. Health insurance was not associated with use of substance abuse treatment. Individuals with high school education were 2.6 times more likely to use substance abuse treatment than the college graduates. Additionally, no significant interaction effects

Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform

International Nuclear Information System (INIS)

Li Yanan; An Feifei; Zhang Xiaohong; Yang Yinlong; Liu Zhuang; Zhang Xiujuan

2013-01-01

A one-dimensional drug delivery system (1D DDS) is highly attractive since it has distinct advantages such as enhanced drug efficiency and better pharmacokinetics. However, drugs in 1D DDSs are all encapsulated in inert carriers, and problems such as low drug loading content and possible undesirable side effects caused by the carriers remain a serious challenge. In this paper, a novel, carrier-free, pure drug nanorod-based, tumor-targeted 1D DDS has been developed. Drugs are first prepared as nanorods and then surface functionalized to achieve excellent water dispersity and stability. The resulting drug nanorods show enhanced internalization rates mainly through energy-dependent endocytosis, with the shape-mediated nanorod (NR) diffusion process as a secondary pathway. The multiple endocytotic mechanisms lead to significantly improved drug efficiency of functionalized NRs with nearly ten times higher cytotoxicity than those of free molecules and unfunctionalized NRs. A targeted drug delivery system can be readily achieved through surface functionalization with targeting group linked amphipathic surfactant, which exhibits significantly enhanced drug efficacy and discriminates between cell lines with high selectivity. These results clearly show that this tumor-targeting DDS demonstrates high potential toward specific cancer cell lines. (paper)

Gastrointestinal Complications Depending on the Selectivity of Non-Steroidal Anti-Inflammatory Drug

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G.V. Dzyak

2013-02-01

Full Text Available The article deals with the problem of gastrointestinal complications during administration of nonsteroidal anti-inflammatory drugs, commonly used to treat a range of conditions, particularly rheumatic diseases. The results of own researches, which served to define the characteristics of changes in the state of gastric secretory function in patients receiving non-selective and selective anti-inflammatory agent and their comparative analysis, are provided. The data obtained demonstrated a certain contribution to the understanding of the mechanism of development of complications from the gastrointestinal tract when taken drugs of above group.

Patterns of drug use among a sample of drug users and injecting drug users attending a General Practice in Iran

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Shakeshaft Anthony

2006-01-01

Full Text Available Abstract Aim This study aimed to examine drug use, drug treatment history and risk behaviour among a sample of Iranian drug users seeking treatment through a general practice clinic in Iran. Methods Review of medical records and an intake questionnaire at a large general practice in Marvdasht, Iran, with a special interest in drug dependence treatment. Records from a random sample of injecting drug users (IDU, non-injecting drug users (DU and non-drug using patients were examined. Results 292 records were reviewed (34% IDU, 31% DU and 35% non-drug users. Eighty-three percent were males; all females were non-drug users. The mean age of the sample was 30 years. Of the IDU sample, 67% reported sharing a needle or syringe, 19% of these had done so in prison. Of those who had ever used drugs, being 'tired' of drug use was the most common reason for seeking help (34%. Mean age of first drug use was 20 years. The first drugs most commonly used were opium (72%, heroin (13% and hashish/ other cannabinoids (13%. Three quarters reported having previously attempted to cease their drug use. IDU were more likely than DU to report having ever been imprisoned (41% vs 7% and 41% to have used drugs in prison. Conclusion This study has shown that there is a need for general practice clinics in Iran to treat drug users including those who inject and that a substantial proportion of those who inject have shared needles and syringes, placing them at risk of BBVI such as HIV and hepatitis C. The expansion of services for drug users in Iran such as needle and syringe programs and pharmacotherapies are likely to be effective in reducing the harms associated with opium use and heroin injection.

Frequency of 5+/4+ drinks as a screener for drug use and drug-use disorders.

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Dawson, Deborah A; Compton, Wilson M; Grant, Bridget F

2010-09-01

The objective of this study was to test the ability of a question on frequency of drinking 5+ (for men) or 4+ (for women) drinks to screen for drug use and drug-use disorders (DUDs) in a general population sample. Using data collected in 2001-2002 from a representative U.S. adult population sample (N= 43,093), including a subsample of those with past-year emergency-department use (n = 8,525), past-year frequency of drinking 5+/4+ drinks was evaluated as a screener for drug use and DUDs for four categories of illicit drugs. Sensitivities and specificities of the 5+/4+ drinks screener were 72.4% and 76.6% for any drug dependence, 71.9% and 77.3% for any DUD, and 63.3% and 78.9% for any drug use in the general population. Sensitivities and specificities were higher for marijuana and cocaine/crack and lowest for illicit prescription drugs. Optimal screening cut-points were once a month or more for cocaine/crack dependence, either once or more a month or seven or more times a year for cocaine/crack DUDs, seven or more times a year for cocaine/crack use, and once or more a year for the other drug use and DUD measures. Sensitivity and specificity were similar among adults who had visited an emergency department in the past year, and the optimal screening cutpoints were identical. Past-year frequency of drinking 5+/4+ drinks was quite accurate as a screener for past-year marijuana and cocaine/crack use and DUDs, but it was less accurate for illicit prescription drug use and DUDs. Its drug-screening potential can be thought of as "added value" from an item already likely to be asked in the interest of detecting problem drinking. Future work may consider using the alcohol consumption screener as a starting point, with follow-up questions to assess illicit drug use among those who screen positive.

Kv4 channels underlie the subthreshold-operating A-type K+-current in nociceptive dorsal root ganglion neurons

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Thanawath R Na Phuket

2009-07-01

Full Text Available The dorsal root ganglion (DRG contains heterogeneous populations of sensory neurons including primary nociceptive neurons and C-fibers implicated in pain signaling.  Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K+ channels; however, the molecular correlate of the corresponding A-type K+ current (IA has remained hypothetical.  Kv4 channels may underlie the IA in DRG neurons.  We combined electrophysiology, molecular biology (whole-tissue and single-cell RT-PCR and immunohistochemistry to investigate the molecular basis of the IA in acutely dissociated DRG neurons from 7-8 day-old rats.  Whole-cell recordings demonstrate a robust tetraethylammonium-resistant (20 mM and 4-aminopyridine-sensitive (5 mM IA.  Matching Kv4 channel properties, activation and inactivation of this IA occur in the subthreshold range of membrane potentials and the rate of recovery from inactivation is rapid and voltage-dependent.  Among Kv4 transcripts, the DRG expresses significant levels of Kv4.1 and Kv4.3 mRNAs.  Also, single small-medium diameter DRG neurons (~30 mm exhibit correlated frequent expression of mRNAs encoding Kv4.1 and Nav1.8, a known nociceptor marker.  In contrast, the expressions of Kv1.4 and Kv4.2 mRNAs at the whole-tissue and single-cell levels are relatively low and infrequent.  Kv4 protein expression in nociceptive DRG neurons was confirmed by immunohistochemistry, which demonstrates colocalization of Kv4.3 and Nav1.8, and negligible expression of Kv4.2.  Furthermore, specific dominant-negative suppression and overexpression strategies confirmed the contribution of Kv4 channels to IA in DRG neurons.  Contrasting the expression patterns of Kv4 channels in the central and peripheral nervous systems, we discuss possible functional roles of these channels in primary sensory neurons.

Effects of yohimbine and drug cues on impulsivity and attention in cocaine-dependent men and women and sex-matched controls.

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Moran-Santa Maria, M M; Baker, N L; McRae-Clark, A L; Prisciandaro, J J; Brady, K T

2016-05-01

Deficits in executive function have been associated with risk for relapse. Data from previous studies suggest that relapse may be triggered by stress and drug-paired cues and that there are significant sex differences in the magnitude of these responses. The aim of this study was to examine the impact of the pharmacological stressor and alpha-2 adrenergic receptor antagonist yohimbine and cocaine cues on executive function in cocaine-dependent men and women. In a double-blind placebo controlled cross-over study, cocaine-dependent men (n=12), cocaine-dependent women (n=27), control men (n=31) and control women (n=25) received either yohimbine or placebo prior to two cocaine cue exposure sessions. Participants performed the Connors' Continuous Performance Test II prior to medication/placebo administration and immediately after each cue exposure session Healthy controls had a significant increase in commission errors under the yohimbine condition [RR (95% CI)=1.1 (1.0-1.3), χ(2)1=2.0, p=0.050]. Cocaine-dependent individuals exhibited a significant decrease in omission errors under the yohimbine condition [RR (95% CI)=0.6 (0.4-0.8), χ(2)1=8.6, p=0.003]. Cocaine-dependent women had more omission errors as compared to cocaine-dependent men regardless of treatment [RR (95% CI)=7.2 (3.6-14.7), χ(2)1=30.1, pwomen exhibited a slower hit reaction time as compared to cocaine-dependent men [Female 354 ± 13 vs. Male 415 ± 14; t89=2.6, p=0.012]. These data add to a growing literature demonstrating significant sex differences in behaviors associated with relapse in cocaine-dependent individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

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Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

2013-09-01

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

Ventricular configuration and cerebral growth in infants born to drug-dependent mothers

International Nuclear Information System (INIS)

Pasto, M.E.; Deiling, J.M.; Kurtz, A.B.; Goldberg, B.; Graziani, L.J.; Tunis, S.L.; Finnegan, L.P.

1985-01-01

Cranial ultrasound examinations were performed during the first 3 days of life and at age 1 month on 22 infants with the neonatal abstinence syndrome. The results were compared to those obtained in 15 control infants who were not exposed to narcotic drugs in utero. The ultrasound images were examined for ventricular configuration, intracranial hemidiameters, area of thalami, and width of temporal lobes. At 24 to 72 h and at 1 month of age, significantly more drug-exposed than control infants had a slit-like ventricular configuration. The intracranial hemidiameter was significantly smaller in the drug-exposed than in the control infants. All cerebral measurements except the right temporal lobe demonstrated significant growth over the first month of life in both groups of infants. By means of ancillary examinations (computerized tomography and transfontanel pressure measurements) the pathogenesis of the slit-like ventricles was found not to be related to edema or to increased intracranial pressure. Whether or not the ventricles remain small and brain growth remains parallel after the period of abstinence awaits further investigation. (orig.)

Albumin-based drug delivery

DEFF Research Database (Denmark)

Larsen, Maja Thim; Kuhlmann, Matthias; Hvam, Michael Lykke

2016-01-01

The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand...... binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent...... conjugation, genetic fusions, association or ligand-mediated association. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform....

Attitudes of Students Living in Dormitories of Zahedan University of Medical Sciences Towards the Causes of Drug Addiction.

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Mir Lotfi, Parvizreza; Javadimehr, Mani; Adrome, Mahdiye

2015-06-01

Health-threatening behavior is one of the most challenges of social and mental health, that most countries are involved somehow in it, and as a result widespread and severe problems are imposed on communities. The aim of this study was to assess the attitudes of students living in dormitories of Zahedan University of Medical Sciences towards causes of drug addiction. In this study, 100 students (60 boys and 40 girls) living in dormitories (Kooser and Misagi) of Zahedan University of Medical Sciences were selected using the simple random sampling method. Data were collected by oral interview and participants were asked demographic, geographic and economic oral questions about their attitude towards causes of drug addiction. The interview was conducted by psychology experts and respondents' answers were recorded on tape recorder and then transcribed on papers, and finally the data were analyzed by SPSS (15). Different percentages of participants expressed different views about the causes of drug addiction. Results showed that 75%, 65%, 55.5% 90%, 40% and 85%, of participants believed being away from their parents, curiosity, unconsidered friendships, smoking, using drug at home, and easy accessibility were as major contributing factors involved in drug addiction, respectively, and the same factors underlie the student's involvement in addiction. Many contributing factors of drug abuse obtained in this study can influence on tendency towards drug use for new students. It is evident that the period of residency in dormitories is one of the most critical periods in students' life. Thus, the concerned authorities take necessary measures to overcome the students' mental and social problems.

Radiation and platinum drug interaction

International Nuclear Information System (INIS)

Nias, A.H.W.

1985-01-01

The ideal platinum drug-radiation interaction would achieve radiosensitization of hypoxic tumour cells with the use of a dose of drug which is completely non-toxic to normal tissues. Electron-affinic agents are employed with this aim, but the commoner platinum drugs are only weakly electron-affinic. They do have a quasi-alkylating action however, and this DNA targeting may account for the radiosensitizing effect which occurs with both pre- and post-radiation treatments. Because toxic drug dosage is usually required for this, the evidence of the biological responses to the drug and to the radiation, as well as to the combination, requires critical analysis before any claim of true enhancement, rather than simple additivity, can be accepted. The amount of enhancement will vary with both the platinum drug dose and the time interval between drug administration and radiation. Clinical schedules may produce an increase in tumour response and/or morbidity, depending upon such dose and time relationships. (author)

Transcriptional changes common to human cocaine, cannabis and phencyclidine abuse.

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Elin Lehrmann

2006-12-01

Full Text Available A major goal of drug abuse research is to identify and understand drug-induced changes in brain function that are common to many or all drugs of abuse. As these may underlie drug dependence and addiction, the purpose of the present study was to examine if different drugs of abuse effect changes in gene expression that converge in common molecular pathways. Microarray analysis was employed to assay brain gene expression in postmortem anterior prefrontal cortex (aPFC from 42 human cocaine, cannabis and/or phencyclidine abuse cases and 30 control cases, which were characterized by toxicology and drug abuse history. Common transcriptional changes were demonstrated for a majority of drug abuse cases (N = 34, representing a number of consistently changed functional classes: Calmodulin-related transcripts (CALM1, CALM2, CAMK2B were decreased, while transcripts related to cholesterol biosynthesis and trafficking (FDFT1, APOL2, SCARB1, and Golgi/endoplasmic reticulum (ER functions (SEMA3B, GCC1 were all increased. Quantitative PCR validated decreases in calmodulin 2 (CALM2 mRNA and increases in apolipoprotein L, 2 (APOL2 and semaphorin 3B (SEMA3B mRNA for individual cases. A comparison between control cases with and without cardiovascular disease and elevated body mass index indicated that these changes were not due to general cellular and metabolic stress, but appeared specific to the use of drugs. Therefore, humans who abused cocaine, cannabis and/or phencyclidine share a decrease in transcription of calmodulin-related genes and increased transcription related to lipid/cholesterol and Golgi/ER function. These changes represent common molecular features of drug abuse, which may underlie changes in synaptic function and plasticity that could have important ramifications for decision-making capabilities in drug abusers.

Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs

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Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

2006-05-01

Mats of PVA nanofibres were successfully prepared by the electrospinning process and were developed as carriers of drugs for a transdermal drug delivery system. Four types of non-steroidal anti-inflammatory drug with varying water solubility property, i.e. sodium salicylate (freely soluble in water), diclofenac sodium (sparingly soluble in water), naproxen (NAP), and indomethacin (IND) (both insoluble in water), were selected as model drugs. The morphological appearance of the drug-loaded electrospun PVA mats depended on the nature of the model drugs. The 1H-nuclear magnetic resonance results confirmed that the electrospinning process did not affect the chemical integrity of the drugs. Thermal properties of the drug-loaded electrospun PVA mats were analysed by differential scanning calorimetry and thermogravimetric analysis. The molecular weight of the model drugs played a major role on both the rate and the total amount of drugs released from the as-prepared drug-loaded electrospun PVA mats, with the rate and the total amount of the drugs released decreasing with increasing molecular weight of the drugs. Lastly, the drug-loaded electrospun PVA mats exhibited much better release characteristics of the model drugs than drug-loaded as-cast films.

Applied metabolomics in drug discovery.

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Cuperlovic-Culf, M; Culf, A S

2016-08-01

The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs. This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads.

Horizonte de racionalidade acerca da dependência de drogas nos serviços de saúde: implicações para o tratamento The horizon of rationality about drug dependency in health services: implications to the treatments

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Daniela Ribeiro Schneider

2010-05-01

Full Text Available O artigo refere-se à discussão de pesquisa baseada em metodologia de análise de conteúdo, cuja meta é explicitar o horizonte de racionalidade dos serviços de atenção aos usuários de álcool e outras drogas na Região da Grande Florianópolis, objetivando contribuir no estabelecimento de parâmetros qualitativos na avaliação de serviços de saúde. Verificou-se a existência de concepção hegemônica acerca do fenômeno da dependência de drogas e do modo de intervenção no fenômeno, síntese de racionalidades diversas e, algumas vezes, contraditórias entre si. Tal concepção centra seu modelo na noção de doença, na meta da abstinência, no busca do controle sobre a adição, operando dispositivos médico-terapêuticos e morais. Nas raízes desta concepção, encontra-se uma perspectiva subjetivista, moralista e psicopatologizante, constituindo-se em visão ahistórica e pouco crítica da produção social em torno do uso de drogas, pautada numa racionalidade de predomínio metafísico, ainda que mesclado com outras racionalidades como a científica. Discute-se a importância de correlacionar o "horizonte de racionalidade" dos serviços de saúde com a problemática da eficácia e eficiência dos tratamentos na área da dependência de drogas.This article refers to the research discussion based on methodology of content analysis, which aims at making explicit the horizon of rationality of the services provided for alcohol users and other drugs in the Great Florianópolis region, to contribute to the establishment of qualitative parameters in the evaluation of health services. It was verified that there is a hegemonic conception about the drugs dependence phenomenon as well as the way to intervene in this phenomenon, synthesis of different and, sometimes, contradictory rationalities. The model of this conception is based on the notion of disease, on the pursue for abstinence, on the struggle to control de addiction, operating

Cytogenetic risks and possible adverse health effects by narcotic substances dependent.

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Movafagh, Abolfazl; Haeri, Ali; Kolahi, Ali Asghar; Hassani-Moghadam, Hossein

2012-09-01

Illicit drug abuse has crossed social, economic, and geographical borders, and remains one of the major health problems that modern society is facing worldwide. The role of multiple drug abuse as a basic for chromosome damage has been overlooked and it is important to determine its possible adverse health effects. This study aimed to compare the frequency of chromosomal damages between drug addicts and free drug controls. Cytogenetic study was obtained from 146 illicit drug-users and 200 free drug controls. Subjects were grouped into three categories depending on main drug of dependence. Cytogenetic studies on cultured lymphocytes showed an increase the frequency of chromosomal damages among addicts including opiate (5.89%), heroin (7.65%), and crystal (4.9%) when compared with drug free controls (1.45%). The frequency of chromosomal abnormalities was breaks, gaps, marker, and acentric, respectively. Our findings are also important as they are among the first to suggest here, illicit drug addiction continue to be significant public health problems in Iran.

Abnormal Brain Dynamics Underlie Speech Production in Children with Autism Spectrum Disorder.

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Pang, Elizabeth W; Valica, Tatiana; MacDonald, Matt J; Taylor, Margot J; Brian, Jessica; Lerch, Jason P; Anagnostou, Evdokia

2016-02-01

A large proportion of children with autism spectrum disorder (ASD) have speech and/or language difficulties. While a number of structural and functional neuroimaging methods have been used to explore the brain differences in ASD with regards to speech and language comprehension and production, the neurobiology of basic speech function in ASD has not been examined. Magnetoencephalography (MEG) is a neuroimaging modality with high spatial and temporal resolution that can be applied to the examination of brain dynamics underlying speech as it can capture the fast responses fundamental to this function. We acquired MEG from 21 children with high-functioning autism (mean age: 11.43 years) and 21 age- and sex-matched controls as they performed a simple oromotor task, a phoneme production task and a phonemic sequencing task. Results showed significant differences in activation magnitude and peak latencies in primary motor cortex (Brodmann Area 4), motor planning areas (BA 6), temporal sequencing and sensorimotor integration areas (BA 22/13) and executive control areas (BA 9). Our findings of significant functional brain differences between these two groups on these simple oromotor and phonemic tasks suggest that these deficits may be foundational and could underlie the language deficits seen in ASD. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

Negative consequences associated with dependence in daily cannabis users

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Earleywine Mitch

2007-01-01

Full Text Available Abstract Background Cannabis is the most widely consumed illicit substance in America, with increasing rates of use. Some theorists tend to link frequency of use with cannabis dependence. Nevertheless, fewer than half of daily cannabis users meet DSM-IV-TR criteria for cannabis dependence. This study seeks to determine whether the negative aspects associated with cannabis use can be explained by a proxy measure of dependence instead of by frequency of use. Results Over 2500 adult daily cannabis users completed an Internet survey consisting of measures of cannabis and other drug use, in addition to measures of commonly reported negative problems resulting from cannabis use. We compared those who met a proxy measure of DSM-IV-TR criteria for cannabis dependence (N = 1111 to those who did not meet the criteria (N = 1770. Cannabis dependent subjects consumed greater amounts of cannabis, alcohol, and a variety of other drugs. They also had lower levels of motivation, happiness, and satisfaction with life, with higher levels of depression and respiratory symptoms. Conclusion Although all of our subjects reported daily use, only those meeting proxy criteria for cannabis dependence reported significant associated problems. Our data suggest that dependence need not arise from daily use, but consuming larger amounts of cannabis and other drugs undoubtedly increases problems.

Membrane-Dependent Effects of a Cytoplasmic Helix on the Structure and Drug Binding of the Influenza Virus M2 Protein

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Cady, Sarah; Wang, Tuo; Hong, Mei

2011-01-01

The influenza A M2 protein forms a proton channel for virus infection and also mediates virus assembly and budding. The minimum protein length that encodes both functions contains the transmembrane (TM) domain (roughly residues 22 to 46) for the amantadine-sensitive proton-channel activity and an amphipathic cytoplasmic helix (roughly residues 45 to 62) for curvature induction and virus budding. However, structural studies involving the TM domain with or without the amphipathic helix differed on the drug-binding site. Here we use solid-state NMR spectroscopy to determine the amantadine binding site in the cytoplasmic-helix-containing M2(21–61). 13C-2H distance measurements of 13C-labeled protein and 2H-labeled amantadine showed that in DMPC bilayers, the first equivalent of drug bound S31 inside the M2(21–61) pore, similar to the behavior of M2TM in DMPC bilayers. The non-specific surface site of D44 observed in M2TM is disfavored in the longer peptide. Thus, the pharmacologically relevant drug-binding site in the fully functional M2(21–61) is S31 in the TM pore. Interestingly, when M2(21–61) was reconstituted into a virus-mimetic membrane containing 30% cholesterol, no chemical shift perturbation was observed for pore-lining residues, while M2TM in the same membrane exhibited drug-induced chemical shift changes. Reduction of the cholesterol level and the use of unsaturated phospholipids shifted the conformational equilibrium of M2TM fully to the bound state, but did not rescue drug binding to M2(21–61). These results suggest that the amphipathic helix, together with cholesterol, modulates the ability of the TM helices to bind amantadine. Thus, the M2 protein interacts with the lipid membrane and small-molecule inhibitors in a complex fashion, and a careful examination of the environmental dependence of the protein conformation is required to fully understand the structure-function relation of this protein. PMID:21661724

Application of three-dimensional printing for colon targeted drug delivery systems.

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Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M

2017-01-01

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

The Effectiveness of Cognitive Behavioral Therapy on Increasing of Self-Efficacy and Improving of Addiction Symptoms among Drug Dependency Patients

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Hamid Kamarzarin

2012-08-01

Full Text Available Introduction: The aim of this study was to determine the effectiveness of cognitive behavior therapy on increasing of self efficacy and improving of addiction symptoms among drug dependency patients. Method: For this purpose, 90 substance abusers were selected of private addiction center, Central Prison and drop in center by using of random sampling, and they were divided into two experimental (45 subjects and witness groups (45 subjects randomly. The members of experimental group were under 12 sessions of cognitive behavioral therapy by Carol method, and control group only have taken Methadone and other physical drugs. All participants at the beginning of research, during the study (after three months and three months after treatment completed self-efficacy questionnaire and Maudsley addiction profile (Map by a psychologist were assessed. The symptoms of addiction recovery and addiction treatment process. Results: Analysis of covariance indicated the treatment effectiveness and its maintenance on increasing of efficacy and reducing of the symptoms of Maudsley addiction profile. Conclusion: Cognitive behavior therapy is effective to increase self-efficacy and improve symptoms in substance abusers.

Metabonomics and drug development.

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Ramana, Pranov; Adams, Erwin; Augustijns, Patrick; Van Schepdael, Ann

2015-01-01

Metabolites as an end product of metabolism possess a wealth of information about altered metabolic control and homeostasis that is dependent on numerous variables including age, sex, and environment. Studying significant changes in the metabolite patterns has been recognized as a tool to understand crucial aspects in drug development like drug efficacy and toxicity. The inclusion of metabonomics into the OMICS study platform brings us closer to define the phenotype and allows us to look at alternatives to improve the diagnosis of diseases. Advancements in the analytical strategies and statistical tools used to study metabonomics allow us to prevent drug failures at early stages of drug development and reduce financial losses during expensive phase II and III clinical trials. This chapter introduces metabonomics along with the instruments used in the study; in addition relevant examples of the usage of metabonomics in the drug development process are discussed along with an emphasis on future directions and the challenges it faces.

Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence.

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Coller, Janet K; Hutchinson, Mark R

2012-05-01

In the past two decades a trickle of manuscripts examining the non-neuronal central nervous system immune consequences of the drugs of abuse has now swollen to a significant body of work. Initially, these studies reported associative evidence of central nervous system proinflammation resulting from exposure to the drugs of abuse demonstrating key implications for neurotoxicity and disease progression associated with, for example, HIV infection. However, more recently this drug-induced activation of central immune signaling is now understood to contribute substantially to the pharmacodynamic actions of the drugs of abuse, by enhancing the engagement of classical mesolimbic dopamine reward pathways and withdrawal centers. This review will highlight the key in vivo animal, human, biological and molecular evidence of these central immune signaling actions of opioids, alcohol, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). Excitingly, this new appreciation of central immune signaling activity of drugs of abuse provides novel therapeutic interventions and opportunities to identify 'at risk' individuals through the use of immunogenetics. Discussion will also cover the evidence of modulation of this signaling by existing clinical and pre-clinical drug candidates, and novel pharmacological targets. Finally, following examination of the breadth of central immune signaling actions of the drugs of abuse highlighted here, the current known common immune signaling components will be outlined and their impact on established addiction neurocircuitry discussed, thereby synthesizing a common neuroimmune hypothesis of addiction. Copyright © 2012 Elsevier Inc. All rights reserved.

Evaluations of in vitro metabolism, drug-drug interactions mediated by reversible and time-dependent inhibition of CYPs, and plasma protein binding of MMB4 DMS.

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Hong, S Peter; Lusiak, Bozena D; Burback, Brian L; Johnson, Jerry D

2013-01-01

1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) dimethanesulfonate (DMS) is a bisquaternary pyridinium aldoxime that reactivates acetylcholinesterase inhibited by organophosphorus nerve agent. Drug metabolism and plasma protein binding for MMB4 DMS were examined using various techniques and a wide range of species. When (14)C-MMB4 DMS was incubated in liver microsomes, 4-pyridine aldoxime (4-PA) and an additional metabolite were detected in all species tested. Identity of the additional metabolite was postulated to be isonicotinic acid (INA) based on liquid chromatography with a tandem mass spectrometry analysis, which was confirmed by comparison with authentic INA. Formation of INA was dependent on species, with the highest level found in monkey liver microsomes. The MMB4 DMS exhibited reversible inhibition in a concentration-dependent manner toward cytochrome P450 1A2 (CYP1A2), CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in human liver microsomes showing the highest inhibition for CYP2D6. Human recombinant CYPs were used to evaluate inhibitory curves more adequately and determine detailed kinetic constants for reversible inhibition and potential time-dependent inhibition (TDI). The MMB4 DMS exhibited reversible inhibition toward human-recombinant CYP2D6 with an inhibition constant (K i) value of 66.6 µmol/L. Based on the k inact/K I values, MMB4 DMS was found to exhibit the most potent TDI toward CYP2D6. The MMB4 DMS at 5 different concentrations was incubated in plasma for 5 hours using an equilibrium dialysis device. For all species tested, there were no concentration-dependent changes in plasma protein binding, ranging from 10% to 17%. These results suggest that MMB4 was not extensively bound to plasma protein, and there were no overt species-related differences in the extent of MMB4 bound to plasma protein.

Street Drugs and Pregnancy

Science.gov (United States)

... help you quit. Or contact: National Council on Alcoholism and Drug Dependence (800) 622-2255 Substance Abuse Treatment Facility Locator (800) 662-4357 Last reviewed: November, 2016 Pregnancy Is it safe? Other Pregnancy topics ') document.write(' ...

Docetaxel-induced polyploidization may underlie chemoresistance and disease relapse.

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Ogden, Angela; Rida, Padmashree C G; Knudsen, Beatrice S; Kucuk, Omer; Aneja, Ritu

2015-10-28

Although docetaxel significantly improves survival in a variety of malignancies, its clinical utility is severely restricted by acquired chemoresistance and disease relapse. To uncover the mechanisms underlying these all too common occurrences, an abundance of research has focused on mutations and gene expression patterns; however, these findings are yet to translate into improved outcomes for patients being administered this drug. These analyses have overlooked a promising lead in the quest to discern key mediators of resistance and relapse following docetaxel therapy: polyploidization. This process is manifested following docetaxel-mediated mitotic arrest by the appearance of giant, multinucleated cells, which slipped from mitosis without undergoing cytokinesis. Polyploid cells generally possess supernumerary centrosomes, are chromosomally instable, and resist chemotherapy. We thus suspect that chemoresistance and relapse following treatment with docetaxel might be combatted by co-administration of centrosome declustering drugs, which could selectively destroy polyploid cells given that normal cells do not possess amplified centrosomes, an intriguing paradigm that warrants further investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A rationale and model for addressing tobacco dependence in substance abuse treatment

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Richter Kimber P

2006-08-01

Full Text Available Abstract Most persons in drug treatment smoke cigarettes. Until drug treatment facilities systematically treat their patients' tobacco use, millions will flow through the drug treatment system, overcome their primary drug of abuse, but die prematurely from tobacco-related illnesses. This paper reviews the literature on the health benefits of quitting smoking for drug treatment patients, whether smoking causes relapse to other drug or alcohol abuse, the treatment of tobacco dependence, and good and bad times for quitting smoking among drug treatment patients. It also presents a conceptual model and recommendations for treating tobacco in substance abuse treatment, and provides references to internet and paper-copy tools and information for treating tobacco dependence. At present, research on tobacco treatment in drug treatment is in its infancy. Although few drug treatment programs currently offer formal services, many more will likely begin to treat nicotine dependence as external forces and patient demand for these services increases. In the absence of clear guidelines and attention to quality of care, drug treatment programs may adopt smoking cessation services based on cost, convenience, or selection criteria other than efficacy. Because research in this field is relatively new, substance abuse treatment professionals should adhere to the standards of care for the general population, but be prepared to update their practices with emerging interventions that have proven to be effective for patients in drug treatment.

Psychoactive drug consumption: performance-enhancing behaviour and pharmacodependence in workers.

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Ngoundo-Mbongue, T B; Niezborala, M; Sulem, P; Briant-Vincens, D; Bancarel, Y; Jansou, P; Chastan, E; Montastruc, J L; Lapeyre-Mestre, M

2005-02-01

The aim of this study was to investigate factors associated to psychoactive medication use and dependence in working environment during a 1-year period. We performed a 1-year-follow-up cohort study including workers from Toulouse metropolitan area. During their annual compulsory examination to assess their aptitude to work, subjects were asked to fill in an anonymous questionnaire at 1 year interval, in May 2000 and May-June 2001. Among a study sample of 1273 subjects (47.4% of men, mean age 39.2 +/- 9.2 years), the prevalence of psychoactive medication use at baseline was 9.1% (4.3% anxiolytic, 1.9% hypnotic, 1.7% antidepressant, 2.1% opiate analgesic and 0.5% antipsychotic drugs, according to ATC classification). Dependence on these drugs was found in 3.5% of workers. This consumption was associated with professional categories (higher in employees versus senior executive, Odds Ratio: 1.80; 95% Confidence Interval [1.04-3.11]), low job satisfaction and outside workplace (1.92; [1.30-2.84] and 3.40; [2.27-5.09] respectively), and patterns of medication use at workplace: for sleeping disorders related to job (18.27; [11.81-28.26]), for enhancing performance at work (28.13; [12.00-65.92]), for relieving unpleasant symptoms at work (22.98; [9.59-55.01]). The risk of psychoactive medication chronic use (psychoactive drug users in 2000 and 2001), and dependence at 1 year were both strongly associated with nicotine dependence (5.99 and 6.23, respectively) and performance-enhancing behaviour with drugs and/or alcohol (8.35 and 3.32 respectively), whereas current use (psychoactive drug users only in 2001) was strongly associated with performance-enhancing behaviour. Among workers using psychoactive drugs, one out of three are dependent on psychoactive medications. Performance-enhancing behaviour and coping strategies might be a determinant of psychoactive drug use and could lead to dependence in the workplace.

Mechanistic and Structural Insights Into the Unique TetR-Dependent Regulation of a Drug Efflux Pump in Mycobacterium abscessus.

Science.gov (United States)

Richard, Matthias; Gutiérrez, Ana Victoria; Viljoen, Albertus J; Ghigo, Eric; Blaise, Mickael; Kremer, Laurent

2018-01-01

Mycobacterium abscessus is an emerging human pathogen causing severe pulmonary infections and is refractory to standard antibiotherapy, yet few drug resistance mechanisms have been reported in this organism. Recently, mutations in MAB_4384 leading to up-regulation of the MmpS5/MmpL5 efflux pump were linked to increased resistance to thiacetazone derivatives. Herein, the DNA-binding activity of MAB_4384 was investigated by electrophoretic mobility shift assays using the palindromic sequence IR S5/L5 located upstream of mmpS5/mmpL5 . Introduction of point mutations within IR S5/L5 identified the sequence requirements for optimal binding of the regulator. Moreover, formation of the protein/IR S5/L5 complex was severely impaired for MAB_4384 harboring D14N or F57L substitutions. IR S5/L5 /lacZ reporter fusions in M. abscessus demonstrated increased β-galactosidase activity either in strains lacking a functional MAB_4384 or in cultures treated with the TAC analogs. In addition, X-ray crystallography confirmed a typical TetR homodimeric structure of MAB_4384 and unraveled a putative ligand binding site in which the analogs could be docked. Overall, these results support drug recognition of the MAB_4384 TetR regulator, alleviating its binding to IR S5/L5 and steering up-regulation of MmpS5/MmpL5. This study provides new mechanistic and structural details of TetR-dependent regulatory mechanisms of efflux pumps and drug resistance in mycobacteria.

Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs

Science.gov (United States)

Li, Xuanwen; Fries, Susanne; Li, Ruizhi; Lawson, John A.; Propert, Kathleen J.; Diamond, Scott L.; Blair, Ian A.; FitzGerald, Garret A.; Grosser, Tilo

2014-01-01

The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug–drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug–drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk. PMID:25385584

Extensive molecular differences between anterior- and posterior-half-sclerotomes underlie somite polarity and spinal nerve segmentation

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Keynes Roger J

2009-05-01

Full Text Available Abstract Background The polarization of somite-derived sclerotomes into anterior and posterior halves underlies vertebral morphogenesis and spinal nerve segmentation. To characterize the full extent of molecular differences that underlie this polarity, we have undertaken a systematic comparison of gene expression between the two sclerotome halves in the mouse embryo. Results Several hundred genes are differentially-expressed between the two sclerotome halves, showing that a marked degree of molecular heterogeneity underpins the development of somite polarity. Conclusion We have identified a set of genes that warrant further investigation as regulators of somite polarity and vertebral morphogenesis, as well as repellents of spinal axon growth. Moreover the results indicate that, unlike the posterior half-sclerotome, the central region of the anterior-half-sclerotome does not contribute bone and cartilage to the vertebral column, being associated instead with the development of the segmented spinal nerves.

Algorithms for optimizing drug therapy

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Martin Lene

2004-07-01

Full Text Available Abstract Background Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet. Methods One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface and JavaScript (program logic. Results Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs

An endocannabinoid hypothesis of drug reward and drug addiction.

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Onaivi, Emmanuel S

2008-10-01

Pharmacologic treatment of drug and alcohol dependency has largely been disappointing, and new therapeutic targets and hypotheses are needed. There is accumulating evidence indicating a central role for the previously unknown but ubiquitous endocannabinoid physiological control system (EPCS) in the regulation of the rewarding effects of abused substances. Thus an endocannabinoid hypothesis of drug reward is postulated. Endocannabinoids mediate retrograde signaling in neuronal tissues and are involved in the regulation of synaptic transmission to suppress neurotransmitter release by the presynaptic cannabinoid receptors (CB-Rs). This powerful modulatory action on synaptic transmission has significant functional implications and interactions with the effects of abused substances. Our data, along with those from other investigators, provide strong new evidence for a role for EPCS modulation in the effects of drugs of abuse, and specifically for involvement of cannabinoid receptors in the neural basis of addiction. Cannabinoids and endocannabinoids appear to be involved in adding to the rewarding effects of addictive substances, including, nicotine, opiates, alcohol, cocaine, and BDZs. The results suggest that the EPCS may be an important natural regulatory mechanism for drug reward and a target for the treatment of addictive disorders.

Drug use among homeless young people in Los Angeles and Melbourne.

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Rosenthal, Doreen; Mallett, Shelley; Milburn, Norweeta; Rotheram-Borus, Mary Jane

2008-09-01

To examine the effect of time spent homeless on young people's substance use and use of drug and alcohol services in two countries with contrasting policy and service environments. A crossnational survey was conducted of recently homeless and experienced homeless young people in Melbourne (N = 674) and Los Angeles (N = 620). Questions were asked about alcohol and drug use in the past 3 months, frequency of use, injecting drug use, drug dependency, and perceived need for, and use of, drug and alcohol services. Data were analyzed using logistic regression. Substantial numbers of young people reported use of alcohol and drugs. More Australians than Americans and more experienced than newly homeless reported drug use, although there were no differences in frequency of use in the past 3 months. Polydrug use was common, as were injecting drugs and responses that signified drug dependency. All were more common among Australians and experienced homeless young people. A substantial number of young people had "ever" taken part in a drug or alcohol program, but only a minority believed that they needed help from services. Of these, only a minority had sought help. This was particularly so among those who were classified as drug dependent. Reasons for failure to seek help varied. Substance use is alarmingly high compared to national samples of young people, especially among those who had been homeless for longer periods. Programs to reduce substance use must take account of the prevailing drug cultures, as well as different subgroups of the population.

Inhibitory effects of drugs on the metabolic activity of mouse and human aldehyde oxidases and influence on drug-drug interactions.

Science.gov (United States)

Takaoka, Naoki; Sanoh, Seigo; Okuda, Katsuhiro; Kotake, Yaichiro; Sugahara, Go; Yanagi, Ami; Ishida, Yuji; Tateno, Chise; Tayama, Yoshitaka; Sugihara, Kazumi; Kitamura, Shigeyuki; Kurosaki, Mami; Terao, Mineko; Garattini, Enrico; Ohta, Shigeru

2018-04-17

As aldehyde oxidase (AOX) plays an emerging role in drug metabolism, understanding its significance for drug-drug interactions (DDI) is important. Therefore, we tested 10 compounds for species-specific and substrate-dependent differences in the inhibitory effect of AOX activity using genetically engineered HEK293 cells over-expressing human AOX1, mouse AOX1 or mouse AOX3. The IC 50 values of 10 potential inhibitors of the three AOX enzymes were determined using phthalazine and O 6 -benzylguanine as substrates. 17β-Estradiol, menadione, norharmane and raloxifene exhibited marked differences in inhibitory effects between the human and mouse AOX isoforms when the phthalazine substrate was used. Some of the compounds tested exhibited substrate-dependent differences in their inhibitory effects. Docking simulations with human AOX1 and mouse AOX3 were conducted for six representative inhibitors. The rank order of the minimum binding energy reflected the order of the corresponding IC 50 values. We also evaluated the potential DDI between an AOX substrate (O 6 -benzylguanine) and an inhibitor (hydralazine) using chimeric mice with humanized livers. Pretreatment of hydralazine increased the maximum plasma concentration (C max ) and the area under the plasma concentration-time curve (AUC 0-24 ) of O 6 -benzylguanine compared to single administration. Our in vitro data indicate species-specific and substrate-dependent differences in the inhibitory effects on AOX activity. Our in vivo data demonstrate the existence of a DDI which may be of relevance in the clinical context. Copyright © 2018 Elsevier Inc. All rights reserved.

pH-Dependent Solubility and Dissolution Behavior of Carvedilol--Case Example of a Weakly Basic BCS Class II Drug.

Science.gov (United States)

Hamed, Rania; Awadallah, Areeg; Sunoqrot, Suhair; Tarawneh, Ola; Nazzal, Sami; AlBaraghthi, Tamadur; Al Sayyad, Jihan; Abbas, Aiman

2016-04-01

The objective of this study was to investigate the pH-dependent solubility and dissolution of weakly basic Biopharmaceutical Classification Systems (BCS) class II drugs, characterized by low solubility and high permeability, using carvedilol, a weak base with a pK a value of 7.8, as a model drug. A series of solubility and in vitro dissolution studies was carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH range of the GI from 1.2 to 7.8. The effect of ionic strength, buffer capacity, and buffer species of the dissolution media on the solubility and dissolution behavior of carvedilol was also investigated. The study revealed that carvedilol exhibited a typical weak base pH-dependent solubility profile with a high solubility at low pH (545.1-2591.4 μg/mL within the pH range 1.2-5.0) and low solubility at high pH (5.8-51.9 μg/mL within the pH range 6.5-7.8). The dissolution behavior of carvedilol was consistent with the solubility results, where carvedilol release was complete (95.8-98.2% released within 60 min) in media simulating the gastric fluid (pH 1.2-5.0) and relatively low (15.9-86.2% released within 240 min) in media simulating the intestinal fluid (pH 6.5-7.8). It was found that the buffer species of the dissolution media may influence the solubility and consequently the percentage of carvedilol released by forming carvedilol salts of varying solubilities. Carvedilol solubility and dissolution decreased with increasing ionic strength, while lowering the buffer capacity resulted in a decrease in carvedilol solubility and dissolution rate.

Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts.

Science.gov (United States)

Duicu, Oana M; Privistirescu, Andreea; Wolf, Adrian; Petruş, Alexandra; Dănilă, Maria D; Raţiu, Corina D; Muntean, Danina M; Sturza, Adrian

2017-11-01

Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox drug with reported protective effects mainly on brain mitochondria. The purpose of the present study was to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H 2 O 2 production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats. Mitochondrial respiratory function was assessed by high-resolution respirometry. H 2 O 2 production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μmol·L -1 ) elicited an increase in oxygen consumption of mitochondria energized with complex I and II substrates in both normal and diseased mitochondria. Interestingly, methylene blue elicited a significant increase in H 2 O 2 release in the presence of complex I substrates (glutamate and malate), but had an opposite effect in mitochondria energized with complex II substrate (succinate). No changes in the calcium retention capacity of healthy or diabetic mitochondria were found in the presence of methylene blue. In conclusion, in cardiac mitochondria isolated from diabetic and nondiabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production.

[Drug addiction and social exclusion].

Science.gov (United States)

Solal, J F; Schneider, M C

1996-10-01

Destitute drug addicts have not deliberately chosen to be socially excluded; it's more the consequence of a sanitary and social policy which has given a greater importance to the treatment of addiction than to the drug addict's health. Facing Aids, physicians, with their pragmatic attitude, have reversed this drift. On the streets, the drug addict holds handicaps concurrently; medicinal addiction leads to harder sevrance and substitution. Having access to social rights allows to regain an identity, compulsory for an access to health care; but public hospitals have to make casier both the admission and the stay of patients whose therapeutic observance is dependent on a preliminary substitution. Drug addiction and precarity represent a double social challenge that a democratic society must take up without any segregation.

Attention deficit hyperactivity disorder and drug addiction rehabilitation patients

OpenAIRE

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

2016-01-01

ABSTRACT Objective 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. Methods The presence and severity of ADHD and substance use were evaluated through questionnaires in 80 adult patients in therapeutic communities. Results No difference in drug use or dependence prevalence between ADHD and non-ADHD patients was found. However, ADHD p...

Reinforcement magnitude modulation of rate dependent effects in pigeons and rats.

Science.gov (United States)

Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, R J

2011-08-01

Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32-5.6 mg/kg] and cocaine [0.32-10 mg/kg]) and two sedatives (chlordiazepoxide [1.78-32 mg/kg] and pentobarbital [1.0-17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32-3.2 mg/kg] and pentobarbital [1.8-10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45 mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval. (c) 2011 APA, all rights reserved.

Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

International Nuclear Information System (INIS)

Volkow, N.D.; Fowler, J.; Wang, G.J.; Telang, F.; Logan, J.; Jayne, M.; Ma, Y.; Pradhan, K.; Wong, C.T.; Swanson, J.M.

2010-01-01

Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 ± 3, post 6 ± 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 ± 2, post 3 ± 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

Energy Technology Data Exchange (ETDEWEB)

Volkow, N.D.; Fowler, J.; Wang, G.J.; Telang, F.; Logan, J.; Jayne, M.; Ma, Y.; Pradhan, K.; Wong, C.T.; Swanson, J.M.

2010-01-01

Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 {+-} 3, post 6 {+-} 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 {+-} 2, post 3 {+-} 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

Drugs: The portuguese fallacy and the absurd medicalization of Europe

Directory of Open Access Journals (Sweden)

Manuel Pinto Coelho

2015-08-01

Full Text Available Drug decriminalization in Portugal is a failure, despite several published articles claiming exactly the opposite. This paper will show that there is an illogical campaign supporting the Portuguese drug policy and an unacceptable manipulation of factual information. A book written by Glenn Greenwald, a lawyer fluent in Portuguese, suggests the opposite of what the research data demonstrates. He claims that Portugal is a success.  Mr. Greenwald is a member of the Cato Institute, an American libertarian think-tank that has been advocating for drug legalization for many years. This complex issue has been broadcast worldwide by the press, both Portuguese and international, boosting the proliferation of the ‘good news’ about the Portuguese drug policy and distorting the real analysis of what is going on in this country. This is happening to an extent that Anand Grover, the United Nations Special Rapporteur on the Right of Everyone to the Highest Attainable Standard of Physical and Mental Health, working in the area of drug dependence did invite the world to ‘reflect about human rights in drug use’ and ‘place health at the core of drug policy’. In their report, he highlighted two core issues, ‘health’ and ‘human rights.’ Could this be used to  justify the approach of legalization of drugs, at any price? Have they laid down their arms and are dangerously opening the way to the medicalization of drug dependency? Surprisingly, the two recent 2010 and 2011 EMCDDA (European Monitoring Centre for Drugs and Drug Addiction Reports, which emphasized the use of substitution drugs as a main tool to tackle opioid dependence, show clearly that Europe looks eager to follow this path.Is this the right path?

The discovery of drug-induced illness.

Science.gov (United States)

Jick, H

1977-03-03

The increased use of drugs (and the concurrent increased risks of drug-induced illness) require definition of relevant research areas and strategy. For established marketed drugs, research needs depend on the magnitudes of risk of an illness from a drug and the base-line risk. With the drug risk high and the base-line risk low, the problem surfaces in premarketing studies or through the epidemic that develops after marketing. If the drug adds slightly to a high base-line risk, the effect is undetectable. When both risks are low, adverse effects can be discovered by chance, but systematic case-referent studies can speed discovery. If both risks are high, clinical trials and nonexperimental studies may be used. With both risks intermediate, systematic evaluations, especially case-referent studies are needed. Newly marketed drugs should be routinely evaluated through compulsory registration and follow-up study of the earliest users.

Drugs of abuse--opiates.

OpenAIRE

Ling, W; Wesson, D R

1990-01-01

Treating opiate-dependent patients can be difficult for many physicians because the patients' life-styles, values, and beliefs differ from those of the physicians. Primary care physicians, however, are often involved in the treatment of the medical complications of opiate abuse, and physicians must often manage a patient's opiate dependence until appropriate referral to a drug abuse treatment program can be arranged. Treatment is guided by an understanding of the patient's addictive disease, ...

Neuropharmacological Consequences of Variant Drugs

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Mahnoor Amjad Butt

2017-11-01

Full Text Available Neuropharmacological effects deals with the influence of drugs on nervous system which harvest the changes in mood, behavioral action of an individual. The drugs are characterized by the chemical substances that communicate with the neurons which have different impacts on nervous system. It may either conducts the abusive or pleasure response which depends on the neural chemicals activity and concerns with the licit and illicit drugs. The elucidation of drugs via LC/MS shows its exertion on the brain components. The computational model helps in the identification of signaling pathways that trigger or inhibit the neurotransmitters. The licit drugs have indisputable responses on CNS. It imparts neuroprotection by either stimulating or inhibiting the receptor, by down regulation yield antinociceptors. However, the illicit drugs have negative acknowledgment on the body as in nicotine the fewer amounts provides benefits but in higher amount mimics the activity of brain receptors and replaces it. Many other drugs induce neurodegenerative disorders. Due to advances in field of neuropharmacology innumerable drugs are available for feasible treatment. The main objective of this review is neuropharmacological consequences in correlation to licit and illicit drugs that what type of responses generated by using these drugs, the neurodegenerative disorders, and their restoration via current treatment.

Is physician adherence to prescription guidelines a general trait of health care practices or dependent on drug type?--a multilevel logistic regression analysis in South Sweden.

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Ohlsson, Henrik; Merlo, Juan

2009-08-01

Therapeutic traditions at health care practices (HCPs) influence physicians' adherence to prescription guidelines for specific drugs, however, it is not known if such traditions affect all kinds of prescriptions or only specific types of drug. Our goal was to determine whether adherence to prescription guidelines is a common trait of HCPs or dependent on drug type. We fitted separate multi-level logistic regression models to all patients in the Skåne region who received a prescription for a statin drug (ATC: C10AA, n = 6232), an agent acting on the renin-angiotensin system (ATC: C09, n = 7222) or a proton pump inhibitor (ATC: A02BC, n = 11 563) at 198 HCPs from July 2006 to December 2006. There was a high clustering of adherence to prescription guidelines at HCPs for the different drug types (MOR(agents acting on the renin-angiotensin system) = 4.72 [95% CI: 3.90-5.92], MOR(Statins) = 2.71 [95% CI: 2.23-3.39] and MOR(Proton pump inhibitors) = 2.16 [95% CI: 1.95-2.45]). Compared with HCPs with low adherence to guidelines in two drug types, those HCPs with the highest level of adherence for these two drug types also showed a higher probability of adherence for the third drug type. Physicians' decisions to follow prescription guidelines seem to be influenced by therapeutic traditions at the HCP. Moreover, these therapeutic traditions seem to affect all kinds of prescriptions. This information can be used as basis for interventions to support rational and cost-effective medication use. Copyright 2009 John Wiley & Sons, Ltd.

Antilipolytic drug boosts glucose metabolism in prostate cancer

DEFF Research Database (Denmark)

Andersen, Kim Francis; Divilov, Vadim; Koziorowski, Jacek

2013-01-01

The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts.......The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts....

Alcohol dependence: international policy implications for prison populations.

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Jones, Gail Yvonne; Hoffmann, Norman G

2006-11-08

In light of the emphasis on drug abuse, this study explored the relative prevalence of substance use disorders among United Kingdom (UK) prison inmates in the context of findings from a general inmate population in the United States (US). The lead author of the report conducted a structured diagnostic interview with 155 new admissions to one of two prisons in the UK using the CAAPE (Comprehensive Addiction And Psychological Evaluation), a structured diagnostic interview, to ensure consistent assessments. The US sample consisted of 6,881 male inmates in a state prison system evaluated with an automated version of the SUDDS-IV (Substance Use Disorder Diagnostic Schedule-IV) interview. Alcohol dependence emerged as the most prevalent substance use disorder in both UK prisons and in the US sample. Relative frequencies of abuse and dependence for alcohol and other drugs revealed that dependence on a given substance was more prevalent than abuse ad defined by the current diagnostic criteria. Despite the emphasis on drugs in correctional populations, alcohol dependence appears to be the most prominent substance use disorder among the incarcerated in both the US and UK and must be considered in developing treatment programs and policy priorities.

Drug repurposing based on drug-drug interaction.

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Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

2015-02-01

Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

Effect of training the communication skills with cognitive-behavioral model to drug dependent couples on communication patterns and recurrent relapse

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M. Rahbarian

2016-12-01

Full Text Available Background: One of the main challenges in methadone maintenance treatment is relapse and lack of sustainability on treatment. Therefore, considering the effective factors in this regard and reducing it through psychological interventions as an adjunct to medication is necessary. Objective: The current study aimed to determine the effectiveness of communication skill training based on cognitive-behavioral model on communication patterns and recurrent relapse in drug dependent couples. Methods: This study was a quasi-experimental intervention with pretest-posttest and control group in 2013 which carried on 40 couple referred to public addiction treatment center of Qazvin city. These people had troubled communication patterns and were selected using convenience sampling and were divided into two groups of intervention and control, randomly. Two groups were assessed by relapse prediction scale (RPS and structured clinical interview for DSM (SCID-I for men and communication pattern questionnaire (CPQ for couples in pre and post-test. Intervention group received 9 two hours sessions of communication skill training based on cognitive-behavioral model. Data were analyzed using Levin and Box tests and multivariate analysis of covariance (MANCOVA. Findings: The difference between the intervention and control groups in the constructive communication pattern with 51% (p<0/05, in mutual avoidance pattern with 61% (p<0/0001 and in the demand / withdraw pattern with 45% (p<0/05 was statistically significant. Also, the difference between the two groups in the rate of relapse with 64% (p<0/0001 was statistically significant. Conclusion: According to the findings it seems group training of communication skill based on cognitive-behavioral model can improve the communication patterns in drug-dependent couples, as well as prevents relapse in men.

The role of alcohol and drugs in homicides in England and Wales.

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Shaw, Jenny; Hunt, Isabelle M; Flynn, Sandra; Amos, Tim; Meehan, Janet; Robinson, Jo; Bickley, Harriet; Parsons, Rebecca; McCann, Kerry; Burns, James; Kapur, Nav; Appleby, Louis

2006-08-01

The annual number of homicide convictions in England and Wales is increasing. Previous studies have highlighted the aetiological role of alcohol and drugs in homicide. To examine rates of alcohol and drug misuse and dependence in people convicted of homicide; the role of alcohol and drugs in the offence; the social and clinical characteristics of alcohol- and drug-related homicides; and the social and clinical characteristics of patients with dual diagnosis who commit homicide. A national clinical survey based on a 3-year (1996-9) consecutive sample of people convicted of homicide in England and Wales. Information on rates of alcohol and drug misuse/dependence, the role of alcohol and drugs in the offence and social and clinical characteristics of perpetrators were collected from psychiatric reports prepared for the court in homicide convictions. Detailed clinical information was gathered from questionnaires completed by mental health teams for those in contact with mental health services. Of the 1594 homicide perpetrators, more than one-third (42%) occurred in people with a history of alcohol misuse or dependence and 40% in people with a history of drug misuse or dependence. Alcohol or drug misuse played a contributory role in two-fifths of homicides. Alcohol played a major role in 52 (6%) and a minor role in 364 (39%) homicides. Drugs played a major role in six (1%) and a minor role in 138 (14%) homicides. Forty-two homicides (17%) were committed by patients with severe mental illness and substance misuse. Alcohol- and drug-related homicides were generally associated with male perpetrators who had a history of violence, personality disorders, mental health service contact and with stranger victims. Substance misuse contributes to the majority of homicides in England and Wales. A public health approach to homicide would highlight alcohol and drugs before severe mental illness.

Autonomous and Non-autonomous Defects Underlie Hypertrophic Cardiomyopathy in BRAF-Mutant hiPSC-Derived Cardiomyocytes

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Rebecca Josowitz

2016-09-01

Full Text Available Germline mutations in BRAF cause cardio-facio-cutaneous syndrome (CFCS, whereby 40% of patients develop hypertrophic cardiomyopathy (HCM. As the role of the RAS/MAPK pathway in HCM pathogenesis is unclear, we generated a human induced pluripotent stem cell (hiPSC model for CFCS from three patients with activating BRAF mutations. By cell sorting for SIRPα and CD90, we generated a method to examine hiPSC-derived cell type-specific phenotypes and cellular interactions underpinning HCM. BRAF-mutant SIRPα+/CD90− cardiomyocytes displayed cellular hypertrophy, pro-hypertrophic gene expression, and intrinsic calcium-handling defects. BRAF-mutant SIRPα−/CD90+ cells, which were fibroblast-like, exhibited a pro-fibrotic phenotype and partially modulated cardiomyocyte hypertrophy through transforming growth factor β (TGFβ paracrine signaling. Inhibition of TGFβ or RAS/MAPK signaling rescued the hypertrophic phenotype. Thus, cell autonomous and non-autonomous defects underlie HCM due to BRAF mutations. TGFβ inhibition may be a useful therapeutic option for patients with HCM due to RASopathies or other etiologies.

Mutation mechanisms that underlie turnover of a human telomere-adjacent segmental duplication containing an unstable minisatellite.

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Hills, Mark; Jeyapalan, Jennie N; Foxon, Jennifer L; Royle, Nicola J

2007-04-01

Subterminal regions, juxtaposed to telomeres on human chromosomes, contain a high density of segmental duplications, but relatively little is known about the evolutionary processes that underlie sequence turnover in these regions. We have characterized a segmental duplication adjacent to the Xp/Yp telomere, each copy containing a hypervariable array of the DXYS14 minisatellite. Both DXYS14 repeat arrays mutate at a high rate (0.3 and 0.2% per gamete) but linkage disequilibrium analysis across 27 SNPs and a direct crossover assay show that recombination during meiosis is suppressed. Therefore instability at DXYS14a and b is dominated by intra-allelic processes or possibly conversion limited to the repeat arrays. Furthermore some chromosomes (14%) carry only one copy of the duplicon, including one DXYS14 repeat array that is also highly mutable (1.2% per gamete). To explain these and other observations, we propose there is another low-rate mutation process that causes copy number change in part or all of the duplicon.

Chinese Herbal Medicine for the Treatment of Drug Addiction.

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Zhu, Weili; Zhang, Yinan; Huang, Yingjie; Lu, Lin

2017-01-01

This chapter summarizes recent developments in preclinical and clinical research on Chinese herbal medicines and their neurochemical mechanism of action for the treatment of drug addiction. We searched Chinese and English scientific literature and selected several kinds of Chinese herbal medicines that have beneficial effects on drug addiction. Ginseng (Renshen) may be clinically useful for the prevention of opioid abuse and dependence. Rhizoma Corydalis (Yanhusuo) may be used to prevent relapse to chronic drug dependence. Alkaloids of Uncaria rhynchophylla (Gouteng) appear to have positive effects on methamphetamine and ketamine addiction. Both Salvia miltiorrhiza (Danshen) and Radix Pueraiae (Gegen) have beneficial inhibitory effects on alcohol intake. Sinomenine has been shown to have preventive and curative effects on opioid dependence. l-Stepholidine, an alkaloid extract of the Chinese herb Stephania intermedia (Rulan), attenuated the acquisition, maintenance, and reacquisition of morphine-induced conditioned place preference and antagonized the heroin-induced reinstatement of heroin seeking. Traditional Chinese herbal medicines may be used to complement current treatments for drug addiction, including withdrawal and relapse. As the molecular mechanisms of action of traditional Chinese herbal medicines are elucidated, further advances in their use for the treatment of drug addiction are promising. © 2017 Elsevier Inc. All rights reserved.

Research on drug abuse and addiction treatment in prisons

OpenAIRE

Kljajević Srđan

2017-01-01

The causes of drug abuse and criminal behavior are closely linked. Not surprisingly, there is a high percentage of prisoners who during sentence execution abuse or are dependent on drugs. Antisocial personality disorder can be considered a common predictor of committing criminal offenses and drug abuse. A review of studies has revealed a high prevalence of inmates who use drugs while serving a sentence. Also, prison environment represents only a new context of the continuum of drug abuse by i...

Metabolic activation of hepatotoxic drug (benzbromarone) induced mitochondrial membrane permeability transition

Energy Technology Data Exchange (ETDEWEB)

Shirakawa, Maho; Sekine, Shuichi; Tanaka, Ayaka [The Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba (Japan); Horie, Toshiharu [Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo (Japan); Ito, Kousei, E-mail: itokousei@chiba-u.jp [The Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba (Japan)

2015-10-01

The risk of drug-induced liver injury (DILI) is of great concern to the pharmaceutical industry. It is well-known that metabolic activation of drugs to form toxic metabolites (TMs) is strongly associated with DILI onset. Drug-induced mitochondrial dysfunction is also strongly associated with increased risk of DILI. However, it is difficult to determine the target of TMs associated with exacerbation of DILI because of difficulties in identifying and purifying TMs. In this study, we propose a sequential in vitro assay system to assess TM formation and their ability to induce mitochondrial permeability transition (MPT) in a one-pot process. In this assay system, freshly-isolated rat liver mitochondria were incubated with reaction solutions of 44 test drugs preincubated with liver microsomes in the presence or absence of NADPH; then, NADPH-dependent MPT pore opening was assessed as mitochondrial swelling. In this assay system, several hepatotoxic drugs, including benzbromarone (BBR), significantly induced MPT in a NADPH-dependent manner. We investigated the rationality of using BBR as a model drug, since it showed the most prominent MPT in our assay system. Both the production of a candidate toxic metabolite of BBR (1′,6-(OH){sub 2} BBR) and NADPH-dependent MPT were inhibited by several cytochrome P450 (CYP) inhibitors (clotrimazole and SKF-525A, 100 μM). In summary, this assay system can be used to evaluate comprehensive metabolite-dependent MPT without identification or purification of metabolites. - Highlights: • We constructed a sequential assay system for toxic metabolite induced MPT in one pot. • 14 drugs (e.g. benzbromarone (BBR)) induced toxic metabolite dependent MPT. • Both the production of toxic metabolite and MPT could be inhibited by CYP inhibitors. • This system could evaluate the comprehensive MPT without purification of metabolites.

Legal Drugs Are Good Drugs And Illegal Drugs Are Bad Drugs

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Dina Indrati

2011-07-01

Full Text Available ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing setting and dual diagnosis.Key words: Legal, good drugs, illegal, bad drugs.

Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans.

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Nunes, Amanda A; Dos Santos, Rafael G; Osório, Flávia L; Sanches, Rafael F; Crippa, José Alexandre S; Hallak, Jaime E C

2016-01-01

Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders. We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results. The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the β-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.

[Salivary flow and psychoactive drug consumption in elderly people].

Science.gov (United States)

Cabrera, Marcos Aparecido Sarria; Mesas, Arthur Eumann; Rossato, Luiz Angelo; Andrade, Selma Maffei de

2007-01-01

To analyze the association between low saliva flow rates and the use of psychoactive drugs among the elderly. A cross-sectional study was carried out with 267 elderly people from 60 to 74 years of age who lived in a borough of the city of Londrina, Paraná State, Brazil. Individuals with high functional dependence or restricted to bed were excluded. Saliva flow rate was the dependent variable with values under the first tercile being considered as low flow rates (less than 0.44 ml/min). The continuous use of psychoactive drugs (antidepressant, antiepileptic, sedative, antipsychotic, hypnotic or sedative-hypnotic drugs) was the independent variable. Multivariate analysis was performed taking into account gender, age and smoking status. The majority of the elderly were women (80.5%), with a mean age of 66.5 years. Use of psychoactive drugs was observed among 31 elderly (11.6%). Mean saliva flow rate was 0.76 ml/min, lower among users of psychoactive drugs (0.67 ml/min). In the multivariate analysis, use of psychoactive drugs was associated with low saliva flow rates (psychoactive drugs and low saliva flow rates in this group of independent and non-institutionalized elderly. These conclusions stress the need of a rational use of these drugs, particularly among the elderly.

Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

OpenAIRE

Indrati, Dina; Prasetyo, Herry

2011-01-01

ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery.

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LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

2014-11-01

The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. © 2013 Society for the Study of Addiction.

Patterns of alcohol, cigarette, and caffeine and other drug use in two drug abusing populations.

Science.gov (United States)

Kozlowski, L T; Henningfield, J E; Keenan, R M; Lei, H; Leigh, G; Jelinek, L C; Pope, M A; Haertzen, C A

1993-01-01

Relationships were explored among the frequencies of use of various drugs by a sample of drug-abusing clients of the Addiction Research Foundation (ARF) in Toronto and by drug abusers volunteering to participate in research at the Addiction Research Center (ARC) in Baltimore. The two groups of drug-abusing individuals differed in a number of characteristics. Those from ARF were admitted primarily for diagnosis and possible treatment for alcohol and non-opioid drug problems, whereas those from the ARC were admitted for participation in research on other drugs of abuse, primarily involving opioids. Patterns of use of certain drugs tended to covary in both groups. Of particular interest was the finding that severity of alcoholism was directly related to various measures of tobacco and caffeinated beverage use. In contrast, there was little correlation between the frequency of use among other drugs of abuse (e.g., heroin, cannabis, glue) and the use of tobacco and caffeine. These findings suggest that dependence on nicotine, caffeine, and alcohol may be governed by the same factors and possibly should be considered jointly in the treatment of alcoholic persons. Frequency of use of other drugs examined may be controlled by other factors than those which determine level of use of tobacco and caffeine.

Drug-perturbation-based stratification of blood cancer

Science.gov (United States)

Dietrich, Sascha; Lu, Junyan; Wu, Bian; Hüllein, Jennifer; da Silva Liberio, Michelle; Walther, Tatjana; Wagner, Lena; Rabe, Sophie; Ghidelli-Disse, Sonja; Bantscheff, Marcus; Słabicki, Mikołaj; Mock, Andreas; Oakes, Christopher C.; Wang, Shihui; Oppermann, Sina; Lukas, Marina; Kim, Vladislav; Sill, Martin; Jauch, Anna; Sutton, Lesley Ann; Rosenquist, Richard; Liu, Xiyang; Jethwa, Alexander; Lee, Kwang Seok; Lewis, Joe; Putzker, Kerstin; Lutz, Christoph; Rossi, Davide; Oellerich, Thomas; Herling, Marco; Nguyen-Khac, Florence; Plass, Christoph; von Kalle, Christof; Ho, Anthony D.; Hensel, Manfred; Dürig, Jan; Ringshausen, Ingo; Huber, Wolfgang

2017-01-01

As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care. PMID:29227286

Mental Disorders in Substance Dependent Individuals as Compared to Non-Substance Dependent People in Hamadan, Iran

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A. Heidari Pahlavian

2011-10-01

Full Text Available Introduction & Objective: There are several close links between substance dependency and mental disorders. Many people who regularly abuse drugs are also diagnosed with psychiatric disorders and vice versa. The high prevalence of this comorbidity has been documented in several studies, although most of the research has been carried out in only a few countries and the cultural validity of the data is unknown. Thus the aim of this study was the comparative investigation of mental disorders in drug dependent and non drug dependent persons in city of Hamadan.Materials & Methods: This study was a descriptive comparative research. 106 men aged 18 to 51 who sought treatment at addiction rehabilitation department of Hamadan were recruited in this study. Also 106 men in the same age range were matched with the first group. Data were collected through structured clinical interview for DSM-IV-TR and SCL 90-R questionnaire. Data were analyzed using t-test and correlation coefficient test.Results: The rate and severity of mental disorders in 9 studied Categories of disorders—phobia, anxiety, somatization, psychotism, depression, paranoid thoughts, aggression, interpersonal sensitivity and obsession-compulsion—were significantly higher among the addicts than the normal group.The level of severity was higher in depression, paranoid thoughts and interpersonal sensitivity than the other disorders. 63.5% of addicts suffered from some psychological disorders while the figures for no addicts were 28.8%. The prevalence of co-morbid psychiatric disorders varied with the pattern of addicts.Conclusion: This study showed that persons with substance dependence display more signs of psycho pathology and mental disorders in comparison with non- substance dependent people.(Sci J Hamadan Univ Med Sci 2011;18(3:22-28

Light-regulated leaf expansion in two Populus species: dependence on developmentally controlled ion transport.

Science.gov (United States)

Stiles, Kari A; Van Volkenburgh, Elizabeth

2002-07-01

Leaf growth responses to light have been compared in two species of Populus, P. deltoides and P. trichocarpa. These species differ markedly in morphology, anatomy, and dependence on light during leaf expansion. Light stimulates the growth rate and acidification of cell walls in P. trichocarpa but not in P. deltoides, whereas leaves of P. deltoides maintain growth in the dark. Light-induced growth is promoted in P. deltoides when cells are provided 50-100 mM KCl. In both species, light initially depolarizes, then hyperpolarizes mesophyll plasma membranes. However, in the dark, the resting E(m) of mesophyll cells in P. deltoides, but not in P. trichocarpa, is relatively insensitive to decade changes in external [K+]. Results suggest that light-stimulated leaf growth depends on developmentally regulated cellular mechanisms controlling ion fluxes across the plasma membrane. These developmental differences underlie species-level differences in growth and physiological responses to the photoenvironment.

Theoretical and experimental investigation of drug-polymer interaction and miscibility and its impact on drug supersaturation in aqueous medium.

Science.gov (United States)

Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J

2016-10-01

Amorphous solid dispersions (ASDs) have the potential to offer higher apparent solubility and bioavailability of BCS class II drugs. Knowledge of the solid state drug-polymer solubility/miscibility and their mutual interaction are fundamental requirements for the effective design and development of such systems. To this end, we have carried out a comprehensive investigation of various ASD systems of dipyridamole and cinnarizine in polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) at different drug loadings. Theoretical and experimental examinations (by implementing binary and ternary Flory-Huggins (F-H) theory) related to drug-polymer interaction/miscibility including solubility parameter approach, melting point depression method, phase diagram, drug-polymer interaction in the presence of moisture and the effect of drug loading on interaction parameter were performed. The information obtained from this study was used to predict the stability of ASDs at different drug loadings and under different thermal and moisture conditions. Thermal and moisture sorption analysis not only provided the composition-dependent interaction parameter but also predicted the composition dependent miscibility. DPM-PVP, DPM-PAA and CNZ-PAA systems have shown molecular level mixing over the complete range of drug loading. For CNZ-PVP, the presence of a single Tg at lower drug loadings (10, 20 and 35%w/w) indicates the formation of solid solution. However, drug recrystallization was observed for samples with higher drug weight fractions (50 and 65%w/w). Finally, the role of polymer in maintaining drug supersaturation has also been explored. It has been found that drug-polymer combinations capable of hydrogen-bonding in the solution state (DPM-PVP, DPM-PAA and CNZ-PAA) are more effective in preventing drug crystallization compared to the drug-polymer systems without such interaction (CNZ-PVP). The DPM-PAA system outperformed all other ASDs in various stability conditions (dry-state, in