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Aims: To obtain damage/benefit assessments of eight commonly used addictive products and one addictive behaviour from French addiction experts and link these to overall evaluations., Design and Setting: Criteria-based evaluation by experts in addiction. Specific statistical modelling to estimate the relative contribution of various criteria to formulating expert general opinion on products., Participants: Forty-eight French experts in addiction., Measurements: Twelve criteria covering the whole spectrum of damages and benefits to users and to society evaluated using visual analogue scales (VAS). Direct measure of expert overall subjective opinions on products from user and from social perspectives., Findings: Damage scoring identified alcohol (damage score = 48.1), heroin (damage score = 44.9) and cocaine (damage score = 38.5) as the most harmful products to users and to society; gambling was considered the least harmful (score = 22.5), replicating previous results. Damage scoring correlated poorly with legal status or with overall subjective expert opinions of products. Benefit perception scores indicated alcohol as a clear outlier (benefit score = 45.5) followed by tobacco (benefit score = 34.3) and cannabis (benefit score = 31.1). Statistical modelling suggested that experts attributed 10 times more importance to benefit perception than to damages when making their subjective opinion from a user perspective and two times more importance to benefit perception than to damages in formulating their opinion from a social perspective., Conclusions: The perceived benefits of addictive products appear to have a major impact on the opinion of those products expressed by a number of French addiction experts., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

Baclofen, a γ-aminobutyric acid (GABA)-B receptor agonist, represents a promising drug in alcohol addiction management. Animal models have shown its action at various stages of the process of alcohol addiction. Moreover, initial open and randomized controlled trials have shown the efficacy of 30 mg/day baclofen on alcohol craving, intake, and relapse prevention. It may also decrease alcohol withdrawal symptoms. However, these initial studies were conducted by the same Italian team; 2 American studies, using a different methodology, did not confirm these effects. Following recent reports by an alcohol-dependent French physician who treated himself with high doses (120-270 mg/day), claiming prolonged suppression of alcohol craving and absence of dependence symptoms, baclofen has since received wide media exposure in France where it has been called "the treatment for alcoholism." An open-label French study supports these findings. In addition, baclofen seems to be particularly interesting because of its safety and tolerance, even in patients with cirrhosis. Thus, baclofen should benefit from further studies of its biobehavioral mechanisms, dose-response effect, and indications in various alcoholic patient profiles.

Amongst validated psychological treatments, brief intervention appears to be the best suited for primary care. It aims at increasing motivation for change after a screening for an alcohol use disorder. The first therapeutic step for an alcohol-dependent patient aiming at abstinence is alcohol detoxification. At this stage, benzodiazepines should be briefly prescribed if the patient manifests clinically significant withdrawal symptoms. The next step is relapse prevention, for which only three medications are currently validated in France, acamprosate, naltrexone, and disulfiram.

Designer drugs belong to a group of legally or illegally produced substances that are structurally and pharmacologically very similar to illicit drugs. In the past, designer drugs were often used during all-night dance parties, but they are now consumed in multiple settings from college bars to parks to private house parties. Most of these club drugs can be bought on legal websites and home-delivered for private parties. Recently, legal highs have once again become a burning media issue across the world. Our review will focus on GHB and synthetic cathinones. Literature searches were conducted for the period from 1975 to July 2010 using PubMed, EMBASE, PsycInfo, Internet underground and governmental websites using the following keywords alone or in combination: designer drugs, club drugs, party drugs, GHB, synthetic cathinones, mephedrone, methylone, flephedrone, MDAI, and MDVP. Available epidemiological, neurobiological, and clinical data for each compound are described. There is evidence that negative health and social consequences may occur in recreational and chronic users. The addictive potential of designer drugs is not weak. Non-fatal overdoses and deaths related to GHB/GBL or synthetic cathinones have been reported. Clinicians must be careful with GBL or synthetic cathinones, which are being sold and used as substitutes for GHB and MDMA, respectively. Interventions for drug prevention and harm reduction in response to the use of these drugs should be implemented on the Internet and in recreational settings. Prevention, Information, Action, and Treatment are the main goals that must be addressed for this new potentially addictive problem., (Copyright © 2010 John Wiley & Sons, Ltd.)

This discussion piece suggests that reliance on a Higher Power in drug abuse recovery programs is entertained among some addicts for its psychobiological effects. Prayer, meditation, early romantic love, and drug abuse may have in common activation of mesolimbic dopaminergic pathways of the brain and the generation of intense emotional states. In this sense, reliance on a Higher Power may operate as a substitute addiction, which replaces the psychobiological functions formerly served by drug use. Implications of this perspective are discussed.

The aim of the present work was to systematically review all association studies of cannabis receptor 1 (CNR1) polymorphisms with dependence syndrome and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the 'high risk' versus 'low risk' alleles in cases with dependence versus controls. Studies were analyzed by random-effects meta-analysis using pooled OR. Eleven full text articles met our eligibility criteria and nine meta-analyses were performed on three polymorphisms of CNR1: rs1049353, rs806379 and the AAT repeat. Of these, only the AAT polymorphism showed a significant association with illicit substance dependence but only in the Caucasian population samples and using a risk allele definition of ≥ 16 repeats. Our analysis showed a small effect size (OR = 1.55, P = 0.045), with strong heterogeneity (Q = 19.87, P < 0.01 with I² = 85%). In line with the polygenic model, our meta-analysis supports a minor implication for CNR1 AAT polymorphism in illicit substance dependence vulnerability. Further studies in well-phenotyped samples and using more polymorphisms are needed to conclude on the actual influence of cannabinoid receptor polymorphisms., (© 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.)

Opiate substitution therapies have largely contributed to improving outcomes in opiate dependent patients. Their impact has significantly diminished HIV transmission rates, decreased incidence of overdose and reduced delinquency due to heroin trafficking. Since then, some advances have been made in the formulations and dosing regimen of these treatments. They have also largely facilitated opiate withdrawal. However, concerning the maintenance of opiate abstinence, very few new treatments have been proposed. Despite considerable advances in our knowledge of the neurobiological mechanisms of opiate dependence, few clinical trials have been proposed to test new molecules both in accompanying opiate substitution and in maintaining abstinence from illicit opiate use. The objective of this article is to examine the evidence concerning the treatment of opiate dependent patients, especially new treatments and to examine the eventual gaps between currently knowledge, available treatment and demands.

Introduction: There is no specific and approved treatment, by regulatory authorities, for cocaine dependence. Therefore, developing new medications for the treatment of this disease continues to be a research priority. Recent advances in neurobiology and brain imaging studies have suggested several promising pharmacological approaches., Materials and Methods: Literature searches were conducted for the period from January 1990 to February 2011 using PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov, which are the main electronic sources of ongoing trials., Results: Recent controlled clinical studies have highlighted some very promising medications, especially glutamatergic (N-Acetylcysteine, modafinil, topiramate) and GABAergic (vigabatrin) agents, agonist replacement therapy (sustained-release methylphenidate, d-amphetamine) and dopamine agents (disulfiram). Additionally, immunotherapy is a new and promising pharmacological approach., Conclusion: Promising pharmacological approaches have emerged for the treatment of cocaine dependence, but larger, randomized, placebo-controlled studies are needed for some medications. Preclinical studies suggest new targets of interest in cocaine dependence. The optimal therapeutic platform is the combination of pharmacotherapies with behavioral therapies.

Switching from the concept of substance or alcohol dependence to that of addiction has profoundly modified our ways of approaching, treating and organizing the care of this disease. This more complex and subtle approach gives less importance to the substance and its effects and focuses more on the initiation of pathological behavior. It is important to keep in mind that the addictive process associates a substance (more or less addictive), an individual (more or less vulnerable) and an environment (more or less condoning). Today, it is no longer possible to consider that a drug acts on only one receptor or one system. Current understanding of inner regulation mechanisms integrates the interactions between the various stimulated brain pathways. Addiction treatments which should benefit from advances in genetics, neuropsychology and neuroimaging could be increasingly individualized in the years to come. The "addictology" approach has triggered thinking about other therapeutic approaches such as modification of therapeutic objectives toward "risk reductions" or applying this model to behavioral addictions (food, sex, sport, gaming...). This conceptual shift seems to enrich clinical analysis, the therapeutic possibilities and the avenues for research.

The aim of the present work was to systematically review all association studies of inflammation genes with alcohol dependence/alcohol abuse (AD/AA) and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the 'high-risk' versus 'low-risk' alleles in AD/AA cases versus controls. Data reported in at least three published studies were available for four genetic polymorphisms [TNF-α-238 (rs361525, G/A); TNF-α-308 (rs1800629, G/A); IL-1RA (VNTR [86 bp]n); IL-10-592 (rs1800896, C/A)]. In total, nine meta-analyses were performed. Of these, only the TNF-α-238 polymorphism showed a significant association with AD/AA (OR=1.36, 95% CI: 1.05-1.76). This risk remained significant and increased slightly when we considered only patients with advanced alcohol-related liver disease (AALD) (OR=1.5, 95% CI: 1.13-1.98) but not when we considered only patients without AALD (OR=1.08, 95% CI: 0.5-2.35). Sensitivity analysis showed that this genetic association is derived from the AALD phenotype rather than from AD. Our approach is limited by our phenotype definition; some studies included chronic heavy drinkers (minimal daily consumption of 80 g for a minimal duration of 10 years) but without a standardized psychiatric assessment., (Copyright © 2011 S. Karger AG, Basel.)

Tobacco dependence is a chronic disease that often requires repeated interventions and multiple attempts to quit. To date, three medications are FDA-approved for smoking cessation: nicotine replacement therapy, sustained-release bupropion, and varenicline. These treatments are effective across a broad range of populations, and are recommended for all smokers, including those with psychiatric or addictive comorbidity. Less is known however concerning the benefit-risk profile of these medications in pregnant women and adolescents. With these limitations in mind, clinicians should encourage and offer counseling and a prescription of pharmacotherapy to every patient willing to make a quit attempt. Despite the relative efficacy of first-line medications, many smokers relapse after one given quit attempt, and alternative pharmacotherapies are needed. Clonidine and nortriptyline have been proposed as second-line medications. In addition, this review indentifies a series of promising drugs that hopefully will be available to complete our current armory.

Methamphetamine is the second illicit drug used after cannabis in North America, Asia, Oceania. It also becomes a prominent part of the European drug scene, especially in East European countries such as Czech Republic and Slovakia. Methamphetamine addiction is a serious worldwide public health problem with many consequences and complications. Significant morbidity, including cardiovascular, infectious, pulmonary, dental diseases and other systems complications are associated with methamphetamine acute or chronic use. Cognitive disorders, psychotic and mood disorders have been reported. There is also substantial evidence that methamphetamine has an adverse impact on social relationships. Treatment of methamphetamine complications is primarily supportive and need a multidisciplinary approach. It can serve as a target to initiate a treatment for the addiction problem. The use of behavioral therapies and pharmacological agents are the best therapeutic approach., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Consumption of cannabis in young adults has continued to increase in recent years. Cannabis arteritis was first described in the 1960s, but the number of cases has continued to increase. We reviewed current knowledge of the different types of cannabis arteritis in young adults and found 70 cases of cannabis arteritis in the literature. We discuss physiopathological arguments in favor of cannabis vascular toxicity per se, although we did not find sufficient evidence to identify cannabis arteritis as a specific diagnostic entity. Many factors suggest a link between cannabis consumption and arteritis in young adults, but it is difficult to say whether this type of arteritis is similar to thromboangiitis obliterans. We were unable to demonstrate a formal association between cannabis smoking and the development of thromboangiitis obliterans, because most case reports showed associated tobacco smoking (97%) and the number of years cannabis had been smoked by the participants was mostly unknown. Cannabis consumption would however seems to be an aggravating factor, together with tobacco, in arteritis, which occurs in young adults.

Cocaine remains the second most used illicit drug in Europe, after cannabis, though levels of use vary between countries. This psychostimulant has become a noticeable part of the European drug scene. Cocaine dependence, a chronic, relapsing and multifactorial disorder, is a significant worldwide public health problem with somatic, legal, social, cognitive and psychological complications. The relationship between clinical psychotic symptoms and use of specific substances other than cannabis has received minimal attention in the literature. Psychotic symptoms and experience of paranoia and suspiciousness are reported during the use and the withdrawal of cocaine. Furthermore, although psychotic symptoms were found to be common among substance users, the risk for development of chronic psychotic disorder was found. In the light of recent epidemiological data stating that there is an increased cocaine use, that there is an increased number of patients entering drug treatment for primary cocaine use in Europe for several years and that cocaine users are an heterogeneous group, we made a review on the specific topic of cocaine-induced psychotic disorders. This review is based on Medline, EMBASE, PsycINFO and Google Scholar searches of English and French-language articles published between 1969 and February, 2010.

Aims: Inquiry regarding the relationship between passionate love and addiction has long been a topic of intense debate. Recent advances in neurobiology now allow for an examination between these two states., Methods: After describing the clinical distinctions between "love passion," "love addiction," and "sex addiction," we compare clinical, neuropsychological, neurobiological, and neuroimaging data on love, passion, pathological gambling (PG) and substance dependence., Results: There are no recognized definitions or diagnostic criteria for "love addiction," but its phenomenology has some similarities to substance dependence: euphoria and unrestrained desire in the presence of the love object or associated stimuli (drug intoxication); negative mood, anhedonia, and sleep disturbance when separated from the love object (drug withdrawal); focussed attention on and intrusive thoughts about the love object; and maladaptive or problematic patterns of behavior (love relation) leading to clinically significant impairment or distress, with pursuit despite knowledge of adverse consequences. Limited animal and human studies suggest that brain regions (e.g., insula, anterior cingulated [ACC], orbitofrontal [OFC]) and neurotransmitters (dopamine) that mediate substance dependence may also be involved with love addiction (as for PG). Ocytocin (OT), which is implicated in social attachment and mating behavior, may also be involved in substance dependence. There are no data on the epidemiology, genetics, co-morbidity, or treatment of love addiction., Conclusion: There are currently insufficient data to place some cases of "love passion" within a clinical disorder, such as "love addiction," in an official diagnostic nomenclature or to firmly classify it as a behavioral addiction or disorder of impulse control. Further clinical and scientific studies are needed to improve our understanding and treatment of this condition. For these studies, we propose new criteria for evaluating addiction to love.

Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double-blind placebo-controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d-amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research.

Background: Normative misperceptions have been widely documented for alcohol use among U.S. college students. There is less research on other substances or European cultural contexts. This study explores which factors are associated with alcohol, tobacco and cannabis use misperceptions among French college students, focusing on substance use., Methods: 12 classes of second-year college students (n = 731) in sociology, medicine, nursing or foreign language estimated the proportion of tobacco, cannabis, alcohol use and heavy episodic drinking among their peers and reported their own use., Results: Peer substance use overestimation frequency was 84% for tobacco, 55% for cannabis, 37% for alcohol and 56% for heavy episodic drinking. Cannabis users (p = 0.006), alcohol (p = 0.003) and heavy episodic drinkers (p = 0.002), are more likely to overestimate the prevalence of use of these consumptions. Tobacco users are less likely to overestimate peer prevalence of smoking (p = 0.044). Women are more likely to overestimate tobacco (p < 0.001) and heavy episodic drinking (p = 0.007) prevalence. Students having already completed another substance use questionnaire were more likely to overestimate alcohol use prevalence (p = 0.012). Students exposed to cannabis prevention campaigns were more likely to overestimate cannabis (p = 0.018) and tobacco use (p = 0.022) prevalence. Other identified factors are class-level use prevalences and academic discipline., Conclusions: Local interventions that focus on creating realistic perceptions of substance use prevalence could be considered for cannabis and alcohol prevention in French campuses.

Cannabis is the most frequently used illegal drug in France. In 2007, the average age for a first use was 15.1 years. Most teenagers will limit their use to a few experiences or controlled use. However, for those who do become dependent, the lapse between the first use and dependence is brief (approximately 18 months) with an average of 28 months compared to tobacco (3-5 years) and alcohol (5-9 years). In light of this brief delay, it is crucial to quickly recognize adolescents who have problem cannabis use and to educate parents to warning signs and to teach them how to efficiently discuss the subject with their teenager. Multidimensional Family Therapy, Cognitive and Behavioral Family Therapy and Brief Strategic Family Therapy have shown their efficacy in clinical trials. Improving family dynamics represents not only a motivational opportunity to help the adolescent to adhere to drug dependence treatment, but may also facilitate reintegration into a drug-free social environment and maintenance in a drug-free existence. Family interventions have been shown to be even more effective when community family assistance relations (social workers, educational counselors) are optimized. Family therapy should also be combined with personal empowerment and life planning interventions which enable the adolescent to increase his self-esteem through scholastic and professional achievement., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Although the term workaholism is widely used, there is very little consensus about its meaning. Since the seventies, workaholism has been described as a work addiction such as drug or alcohol addiction. Similarities with other addictions include craving, withdrawal, tolerance, progressive involvement, and denial. Although considerable attention has been devoted to the concept of workaholism in recent years, little empirical research has been undertaken to further the understanding of this phenomenon. The existence of different types of workaholism has been described. Questionnaires were developed to assess this concept. This heterogeneous disease has negative health, personal, family relationships and professional consequences. Many therapeutic interventions are possible for this unknown addictive trouble. The objective of this paper is to gain a better understanding and knowledge regarding the phenomenon of workaholism. Data obtained for this review are based on a Medline, EMBASE, PsycINFO, Google Scholar search of English- and French-language articles published between 1968 and 2009.

Background: The effect of normative perceptions (social norms) on heavy episodic drinking (HED) behavior is well known in the U.S. college setting, but little work is available in other cultural contexts. The objective of this study is therefore to assess whether social norms of alcohol use are related to HED in France, taking account of other influential predictors., Methods: A cross-sectional survey was carried out among 731 second-year university students in the Paris region to explore the role of 29 potential alcohol use risk factors. The probability of heavy episodic drinking and the frequency of HED among heavy episodic drinkers were modeled independently. Monthly alcohol consumption was also assessed., Results: Of the students, 56% overestimate peer student prevalence of HED (37% for alcohol drinking prevalence). HED frequency rises with perceived peer student prevalence of HED. Other social norms associated with HED are perceived friends' approval of HED (increasing both HED probability and HED frequency) and perceived friend prevalence of alcohol drinking (increasing HED probability only). Cannabis and tobacco use, academic discipline, gender, and the number of friends are also identified as being associated with HED., Conclusions: Overestimation of peer student prevalence is not uncommon among French university students. Furthermore, perceived peer student prevalence of HED is linked to HED frequency, even after adjusting for other correlates. Interventions correcting misperceived prevalences of HED among peer students have therefore the potential to reduce the frequency of HED in this population.

Prolonged cannabis use has a significant impact on health and well-being. Genetic factors are known to influence cannabis dependence, but few specific genetic markers have been identified. ABCB1 polymorphisms are known to modify drug pharmacokinetics but have yet to be studied for their role in generating and maintaining cannabis dependence. The objective of this study is to determine if ABCB1 C3435T polymorphism may represent an independent genetic marker for cannabis dependence risk. An open bi-centric association study was conducted in two French Addiction Centres. Caucasian patients diagnosed with isolated cannabis dependence were compared with healthy age-matched controls for socio-demographic, clinical and genetic data using chi-square test, Fisher's exact test, or Mann-Whitney U test. Independent association between ABCB1 C3435T SNP marker and cannabis dependence was evaluated using multiple logistic regression analysis. Versus controls (n=40), patients with cannabis dependence (n=40) had a significantly higher 3435C allele frequency (62.5% versus 43.8% respectively, P=0.017) and CC genotype (50% versus 20%, P=0.005, OR=4.00 [1.50-10.60]). Multiple logistic regression analysis of the C3435T SNP and variables identified in univariate analyses indicated that the CC genotype was independently associated with cannabis dependence (P=0.045, OR=6.61 [1.05-46.58]). This is the first time a significant specific genetic marker has been shown in cannabis dependence. ABCB1 polymorphisms may alter Delta9THC distribution, its psychoactive effects and individual vulnerability to dependence. These results pave the way to a new pharmacogenetic hypothesis in cannabis dependence.

According to available information, GHB and its precursors--gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD)--are used especially in a nightlife scene characterized by the search for amplified sensations through the combination of electronic music, marathon dancing, and substance abuse. Evidence indicates that GHB/GHL is used particularly in some subpopulations and in places, such as in gay nightclubs. Commonly known as Gorliquid ecstasy, it was misused in the 1980s for its bodybuilding effects and in the 1990s as a recreational drug at music venues. In the same period, media coverage of the use of GHB in sexual assault (often referred to as date rape) brought the drug into the spotlight. GHB/GHL addiction is a recognized clinical entity evidenced by severe withdrawal symptoms when the drug is abruptly discontinued after regular or chronic use. There is evidence that negative health and social consequences may occur in recreational and chronic users. Nonfatal overdoses and deaths related to GHB have been reported. These undesirable effects and especially the deaths appear to have prompted campaigns to limit the use of GHB. Clinicians must also be aware of GBL, which is being sold and used as a substitute for GHB.

Prior studies have associated 677C-T Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with decreased enzymatic activity and modified homocysteine regulation. This study determines and compares MTHFR 677C-T distribution and examines its consequences on homocysteine metabolism and alcohol dependence in alcoholic patients classified according to the Babor and Lesch typologies. MTHFR TT genotype was more prevalent in AD patients with milder alcohol dependence (Babor type A) and with Lesch type 3, associated with depression. MTHFR TT was also associated with hyperhomocysteinemia. Determining MTHFR 677C-T genotype, folate and vitamin B12 levels could assist physicians in identifying type 3 patients and improve addictions management.

Introduction: Tobacco is an important source of somatic diseases and causes high mortality. It is associated with cognitive disorders which tend to maintain addictive mechanisms. In the short term, the nicotine contained in tobacco enhances attention and memory., Method: To realize this review, we made a research, we made a research on Medline, Embase, PsycInfo, Google Scholar using the single or combined key-words "tobacco", "nicotine", "addiction", "dependence", "cognitive disorders", "executive function", "memory", "attention", "neuropsychological". We selected English or French articles from 1987 to 2008 by privileging controlled studies., Results: This effect can be observed in smokers (with or without withdrawal symptoms), non-smokers and in patients suffering from cognitive disorders. In the long term, tobacco accelerates dementia processes. It is associated with an increased risk of cognitive deterioration. This deterioration concerns mainly memory and processing speed. These results were reported in prospective studies. They contradict early reports, that suggested smoking could actually be protective against certain central neural system disorders. These early results relayed on case-control studies, which were certainly biased by a "healthy survival effect". Further studies are required to evaluate nicotine's long term effect and its potential efficacy in treating and preventing cognitive disorders or dementia.

Even though uncomplicated alcoholics may likely have episodic memory deficits, discrepancies exist regarding to the integrity of brain regions that underlie this function in healthy subjects. Possible relationships between episodic memory and 1) brain microstructure assessed by magnetic resonance diffusion tensor imaging (DTI), 2) brain volumes assessed by voxel-based morphometry (VBM) were investigated in uncomplicated, detoxified alcoholics.Diffusion and morphometric analyses were performed in 24 alcohol dependent men without neurological or somatic complications and in 24 healthy men. The mean apparent coefficient of diffusion (ADC) and grey matter volumes were measured in the whole brain. Episodic memory performance was assessed using a French version of the Free and Cued Selective Reminding Test (FCSRT). Correlation analyses between verbal episodic memory, brain microstructure, and brain volumes were carried out using SPM2 software.In those with alcohol dependence, higher ADC was detected mainly in frontal, temporal and parahippocampal regions, and in the cerebellum. In alcoholics, regions with higher ADC typically also had lower grey matter volume. Low verbal episodic memory performance in alcoholism was associated with higher mean ADC in parahippocampal areas, in frontal cortex and in the left temporal cortex; no correlation was found between regional volumes and episodic memory scores. Regression analyses for the control group were not significant.These findings support the hypothesis that regional microstructural but no macrostructural alteration of the brain might be responsible, at least in part, for episodic memory deficits in alcohol dependence.

Cocaine has become an essential part of the French drug scene and is the most commonly abused stimulant worldwide. The principal routes of cocaine administration are intranasal ("snorting"), intravenous ("injecting"), and inhalation ("smoking" freebase or crack cocaine). Distinct classes of primary cocaine users were identified in the literature. Cocaine dependence is a multifactorial disorder, variable in its manifestations, and heritable. It comprises distinct clinical phenomena that drive a cycle of addiction: cocaine-induced euphoria, acute withdrawal, cue-induced craving (people, places, things), loss of control with poor decision making, cocaine seeking behaviour with multiple risks taken and cocaine administration.

Addiction is a chronic relapsing disorder characterized by repetitive and compulsive drug-seeking behavior and drug abuse despite negative health or social consequences. Cocaine addiction is a significant worldwide public health problem, which has somatic, psychological, psychiatric, socio-economic and judicial complications. Some of the most frequent complications are cardiovascular effects (acute coronary syndrome, cardiac arrhythmias, increased blood pressure); respiratory effects (fibrosis, interstitial pneumonitis, pulmonary hypertension, alveolar haemorrhage, asthma exacerbation; emphysema), neurological effects (strokes, aneurysms, seizures, headaches); risk for contracting HIV/AIDS, hepatitis B and C, sexual transmitted disease and otolaryngologic effects. Other complications are not discussed here. The vast majority of studies indicate that there are cognitive deficits induced by cocaine addiction. Attention, visual and working memories, executive functioning are affected in cocaine users. Psychiatric complications found in clinical practice are major depressive disorders, cocaine-induced paranoia, cocaine-induced compulsive foraging and panic attacks.

Recent advances in neurobiology, genetics, neuropsychology and brain imaging research have identified various physiopathological mechanisms implicated in cocaine addiction and suggested several promising pharmacological approaches. Clinical targets of the pharmacological treatments are cocaine-induced euphoria and craving. Currently, there is no specific pharmacological therapy with established efficacy for the treatment of cocaine dependence, nor is any medication approved by regulatory authorities for such treatment. However, recent controlled clinical trials have highlighted the promise of several medications, especially N-acetylcysteine, modafinil, topiramate, GABAergic agents, disulfiram, agonist replacement therapy (methylphenidate LP, d-amphetamine). Partial agonists at the dopamine D2 receptor and anticocaine vaccines are other promising treatment approaches. It is important to clearly differentiate the detoxification treatment and the relapse prevention treatment phases.

Background: Neuroimaging studies showed clear evidence of alcoholism-related damage to the frontal lobes and cerebellum. Although these regions have been involved in language processing, language skills are relatively spared in alcoholics. Here, we aimed at identifying neural substrates associated with the preserved mechanisms of language processing in alcoholics. We hypothesized that alcoholics would show a different pattern of neural activity compared with the controls., Methods: Alcoholic and nonalcoholic subjects performed an auditory language task while receiving a functional magnetic resonance imaging (fMRI) scan in a 1.5 T magnet. This task has been previously shown to solicit the comprehension processing in healthy controls, with reliable fMRI response in the left frontal and temporal/parietal lobes., Results: Behavioral results showed comparable performance (error rates, response time) between the alcoholics and the matched controls. However, analysis of the functional data revealed that the alcoholics exhibited greater fMRI response in the left middle frontal gyrus (pars triangularis), the right superior frontal gyrus, and the cerebellar vermis relative to the controls., Conclusions: These findings suggest that frontocerebellar neural activity, supporting the comprehension processing of the auditory language task, may require compensatory mechanisms in alcoholics in order to maintain the same level of performance as the controls.

A prospective study assessed the outcome in a sample of 122 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol-dependent patients in primary care. Standardized questionnaires collected clinical, social, and management data during 875 visits over an 18-month follow-up. A time-event analysis identified outcome predictors. Forty-three percent of patients attempted at least one detoxification during follow-up, one out of three in a hospital. Despite a very high relapse rate (83%), only 14% of the patients attempted a repeated abstinence. Longest and cumulative durations of abstinence appeared to be very close, corresponding to 29% of the follow-up time. The frequency of visits (risk ratio [RR] = 1.08) and visits addressing alcohol consumption (RR = 1.73) significantly lead to detoxification. In this French sample, management by the general practitioners appears to be a positive predictor of outcome in alcohol dependence. Future research could (a) enlighten the relationship between detoxification and frequency or circumstances of the visits and (b) tell whether formal planned follow-up by general practice physicians could improve outcome in alcohol dependence.

Background: Knowledge of the correlates of smoking is a first step to successful prevention interventions. The social norms theory hypothesises that students' smoking behaviour is linked to their perception of norms for use of tobacco. This study was designed to test the theory that smoking is associated with perceived norms, controlling for other correlates of smoking., Methods: In a pencil-and-paper questionnaire, 721 second-year students in sociology, medicine, foreign language or nursing studies estimated the number of cigarettes usually smoked in a month. 31 additional covariates were included as potential predictors of tobacco use. Multiple imputation was used to deal with missing values among covariates. The strength of the association of each variable with tobacco use was quantified by the inclusion frequencies of the variable in 1000 bootstrap sample backward selections. Being a smoker and the number of cigarettes smoked by smokers were modelled separately., Results: We retain 8 variables to predict the risk of smoking and 6 to predict the quantities smoked by smokers. The risk of being a smoker is increased by cannabis use, binge drinking, being unsupportive of smoke-free universities, perceived friends' approval of regular smoking, positive perceptions about tobacco, a high perceived prevalence of smoking among friends, reporting not being disturbed by people smoking in the university, and being female. The quantity of cigarettes smoked by smokers is greater for smokers reporting never being disturbed by smoke in the university, unsupportive of smoke-free universities, perceiving that their friends approve of regular smoking, having more negative beliefs about the tobacco industry, being sociology students and being among the older students., Conclusion: Other substance use, injunctive norms (friends' approval) and descriptive norms (friends' smoking prevalence) are associated with tobacco use.University-based prevention campaigns should take multiple substance use into account and focus on the norms most likely to have an impact on student smoking.

Components of the corticocerebellar circuit and the midbrain individually play a central role in addictive processes and have been associated with altered volumes and impairment of cognitive flexibility in alcohol-dependent subjects. The microstructure of white matter bundles composing the corticocerebellar network and passing through the midbrain was studied using diffusion tensor imaging in a group of detoxified alcohol-dependent men (n=20) and a group of healthy men (n=24). The relationship between properties of these white matter bundles and cognitive flexibility performance was investigated in alcohol-dependent subjects. Bundles connecting two regions of interest were analyzed using a fiber-tracking quantitative approach, which provided estimates of the fractional anisotropy and the apparent diffusion coefficient, as well as the number of tracked fibers normalized by the volume of regions of interest. Within the bundles running between the midbrain and pons, a mean of 18% fewer fibers per unit volume were tracked in alcohol-dependent men than in healthy controls. In addition, the normalized number of these fibers correlated with the performance in the Trail-Making Test part-B. Even though the alcohol-dependent subjects were detoxified and apparently neurologically intact, their earlier excessive use of alcohol seems to be associated with altered neural microstructure of mesencephalic white matter bundles, which may contribute to their cognitive flexibility impairment.

Background: Axis I psychiatric disorders (PD) and substance use disorders (SUD) are common in prison, but only few studies have focused on their association in this setting. Dual diagnosis (DD) (the co-occurrence of a SUD and any axis I disorder) is known to have a poorer prognosis and to require more intense supportive care., Objectives: The objectives of this study were (1) to describe prisoners with DD (prevalence and characteristics); (2) to compare DD prisoners with 3 other groups of prisoners: no diagnosis (ND), SUD alone, or other isolated PD; and (3) to evaluate the impact of DD on suicide risk in prison., Method: A random stratified strategy was used to select 23 various types of prisons and 998 prisoners. Diagnoses were assessed using a unique procedure, each prisoner being evaluated by 2 psychiatrists, 1 junior, using a structured interview (MINI 5 plus), and 1 senior, using an open clinical interview. Following interviews, clinicians met to establish a list of diagnoses. Cloninger's temperament and character inventory was also used., Results: Of the prisoners, 26.3% had a DD. DD prevalence was almost 80% in prisoners with SUD, while only one-third of the prisoners with an axis I PD had co-morbid SUD. No significant differences were observed in drug use patterns between DD and SUD without co-morbid PDs. DD showed the strongest association with suicide risk [OR = 5.7 (1.7-4.6)]., Conclusion: DD is very frequent in prison and is a major risk factor for suicide. Systematic psychiatric/SUD screening of prisoners with either a SUD or an axis I PD should be encouraged.

P-glycoprotein (P-gp) plays a major role in drug efflux. All the transported substrates are more or less hydrophobic and amphiphatic in nature. Being lipophilic, Delta(9) tetrahydrocannabinol (THC), the main cannabis component, could be a potential P-gp substrate. The aim of this project was to determine the contribution of the mdr1a gene product to THC disposition. Therefore, oral THC and digoxin (substrate test for P-gp) pharmacokinetics have been investigated in the intestinal epithelium and in the brain capillary endothelium of CF1 mdr1a-/- mice (mice naturally deficient in P-gp). These pharmacokinetics were compared to THC and digoxin oral pharmacokinetics in wild type mice mdr1a+/+ (not P-gp deficient). The application of Bailer's method showed that THC total exposure measured by the area under the plasma concentration time curve was 2.17-fold higher in CF1 mice naturally deficient in P-gp than in wild type mice after oral administration of 25 mg/kg of THC, and 2.4-fold higher after oral administration of 33 microg/kg of digoxin. As a consequence, the oral bioavailability of THC and digoxin was higher in naturally P-gp-deficient mice. We concluded that P-gp limits THC oral uptake and mediates direct drug excretion from the systemic circulation into the intestinal lumen.

Background: Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, in particularly in those with marked withdrawal symptoms. The common C677T transition on the methylenetetrahydrofolate reductase (MTHFR) gene influences homocysteinemia. Our objective was to study the prevalence of the MTHFR C677T polymorphism in alcohol-dependent subjects and the influence of this polymorphism on symptoms associated with alcoholism., Methods: MTHFR C677T polymorphism was determined in 93 control subjects and 242 alcohol-dependent subjects. Serum homocysteine, folate and vitamin B12 levels together with hepatic biological parameters were determined in the control and alcohol-dependent subjects., Results: Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, particularly in those with marked withdrawal symptoms. Alcohol-dependent subjects showed a significant decrease in MTHFR 677TT prevalence (9%, 21/242) compared to controls (18%, 17/93) (p<0.02). The relative risk estimated as an odds ratio for alcoholism in subjects with the TT genotype is 0.42 (odd ratio 95% confidence interval, 0.21-0.83). Moreover, drinkers with TT genotype presented lower values for markers of alcohol misuse (p<0.05), better liver function tests, a lower frequency of relapses and no marked withdrawal symptoms as assessed by the Lesch typology., Conclusion: MTHFR 677TT genotype could play a protective role against alcohol dependence. Moreover, when subjects with MTHFR 677TT genotype become dependent to alcohol, they seem to constitute a subgroup of alcoholic patients with a decreased risk for developing neurotoxic withdrawal symptoms and hepatic toxicity.

Aims: Using Cloninger's model of personality, we aimed to specify the relative influence of the more biologically determined variables, temperament and character and more environmentally driven influence, childhood adversity in the development of addiction; and to compare patterns found among alcoholics with those found among drug addicts., Methods: We studied a group of prisoners, at a high risk of substance abuse and past history of childhood adversity. Using a stratified random strategy we selected (i) 23 prisons among the different types of prison in France, (ii) 998 prisoners. Each prisoner was assessed by two psychiatrists--one junior, using a structured interview (MINI 5 plus), and one senior, completing the procedure with an open clinical interview. At the end of the interview the clinicians met and agreed on a list of diagnoses. Cloninger's Temperament and Character Inventory was used to measure personality. Structural equations models, which have been advocated to disentangle the respective influence of complex risk factors, were used., Results: The "novelty seeking" temperament was a crucial vulnerability factor, for both alcoholics and drug addicts, in the same proportion. Character and childhood adversity played a significant part only in the development of drug abuse., Conclusions: In a prison population, a common biological loaded factor, novelty seeking is found both at the core of alcohol- and drug-related disorder whereas environmentally loaded factors play a greater role in drug problems.

Cocaine, already a significant drug problem in North and South America, has become a more prominent part of the European drug scene. Cocaine dependence has major somatic, psychological, psychiatric, socio-economic, and legal implications. No specific effective pharmacological treatment exists for cocaine dependence. Recent advances in neurobiology have identified various neuronal mechanisms implicated in cocaine addiction and suggested several promising pharmacological approaches. Data were obtained from Medline, EMBASE, and PsycINFO searches of English-language articles published between 1985 and June 2007 using the key words: cocaine, addiction, cocaine dependence, clinical trials, pharmacotherapy(ies) singly and in combination. Large well-controlled studies with appropriate statistical methods were preferred. Pharmacological agents such as GABA agents (topiramate, tiagabine, baclofen and vigabatrin) and agonist replacement agents (modafinil, disulfiram, methylphenidate) seem to be the most promising in treatment of cocaine dependence. The results from trials of first- and second-generation neuroleptics are largely negative. Aripiprazole, a partial dopaminergic agonist that may modulate the serotonergic system, shows some promise. Preliminary results of human studies with anti-cocaine vaccine, N-acetylcysteine, and ondansetron, are promising, as are several compounds in preclinical development. While no medication has received regulatory approval for the treatment of cocaine dependence, several medications marketed for other indications have shown efficacy in clinical trials. An anti-cocaine vaccine and several compounds in preclinical development have also shown promise. Findings from early clinical trials must be confirmed in larger, less selective patient populations.

Cocaine is more and more used and abused in France. Cocaine dependence is quite serious and is associated with numerous adverse health consequences. No effective pharmacotherapy for cocaine dependence is yet available. Recent advances in neurobiology, brain imaging and some clinical trials suggest that certain medications that modulate GABAergic, dopaminergic, and glutamatergic systems, as well as immunotherapy, show promise in the treatment of cocaine addiction. Recent controlled clinical studies have tested some of these drugs, which act on the various neurobiological circuits modified by cocaine exposure and clinically improve patients' symptoms. Pharmacological agents such as modafinil, GABAergic agents (baclofen, topiramate, tiagabin, and vigabatrin), disulfiram, aripiprazole, N-acetylcysteine and cocaine vaccine seem very promising in the treatment of cocaine dependence. However, this must be confirmed in larger patient populations.

Cannabis has long been perceived as a drug causing questionable dependence. Only recently has a clinically recognized withdrawal syndrome been described, thus laying the foundations for specific treatment evaluations. Six different pharmacotherapies have been studied in cannabis withdrawal. Of these, only oral tetrahydrocannabinol, and perhaps mirtazapine, have shown some promise in the specific treatment of withdrawal symptoms. In cannabis dependence, rimonabant, and perhaps buspiron, have shown promising results. Clinical trials of oral tetrahydrocannabinol were less convincing. Cognitive and behavioral therapies and motivational enhancement therapies have proven their efficacy in several randomized controlled trials. Brief therapies have also been associated with good compliance and efficacy. Combinations with voucher incentives in certain populations have been associated with improved treatment compliance and reduced cannabis use. Only two studies have analyzed the cost-efficacy of psychotherapies. It would seem that brief combined cognitive and behavioral therapies, and motivational enhancement therapies are the most cost effective. For the moment, it is uncertain whether the additional treatment costs associated with voucher incentives are proportional to the accrued abstinence duration.