USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder.

The risk of developing drug addiction is strongly influenced by the epigenetic landscape and chromatin remodeling. While histone modifications such as methylation and acetylation have been studied in the ventral tegmental area and nucleus accumbens (NAc), the role of H2A monoubiquitination remains unknown. Our investigations, initially focused on the scaffold protein melanoma-associated antigen D1 (Maged1), reveal that H2A monoubiquitination in the paraventricular thalamus (PVT) significantly contributes to cocaine-adaptive behaviors and transcriptional repression induced by cocaine. Chronic cocaine use increases H2A monoubiquitination, regulated by Maged1 and its partner USP7. Accordingly, Maged1 specific inactivation in thalamic Vglut2 neurons, or USP7 inhibition, blocks cocaine-evoked H2A monoubiquitination and cocaine locomotor sensitization. Additionally, genetic variations in MAGED1 and USP7 are linked to altered susceptibility to cocaine addiction and cocaine-associated symptoms in humans. These findings unveil an epigenetic modification in a non-canonical reward pathway of the brain and a potent marker of epigenetic risk factors for drug addiction in humans.

Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers.

Background: Cannabidiol (CBD) is a cannabinoid of potential interest for the treatment of substance use disorders. Our aim was to review the outcome measures, surrogate endpoints, and biomarkers in published and ongoing randomized clinical trials. Methods: We conducted a search in PubMed, Web of Science, PMC, PsycINFO, EMBASE, CENTRAL Cochrane Library, "clinicalTrials.gov," "clinicaltrialsregister.eu," and "anzctr.org.au" for published and ongoing studies. Inclusion criteria were randomized clinical trials (RCTs) examining the use of CBD alone or in association with other cannabinoids, in all substance use disorders. The included studies were analyzed in detail and their qualities assessed by a standardized tool (CONSORT 2010). A short description of excluded studies, consisting in controlled short-term or single administration in non-treatment-seeking drug users, is provided. Findings: The screening retrieved 207 published studies, including only 3 RCTs in cannabis use disorder. Furthermore, 12 excluded studies in cannabis, tobacco, and opioid use disorders are described. Interpretation: Primary outcomes were validated withdrawal symptoms scales and drug use reduction in the three RCTs. In the short-term or crossover studies, the outcome measures were visual analog scales for subjective states; self-rated scales for withdrawal, craving, anxiety, or psychotomimetic symptoms; and laboratory tasks of drug-induced craving, effort expenditure, attentional bias for substance, impulsivity, or anxiety to serve as surrogate endpoints for treatment efficacy. Of note, ongoing studies are now adding peripheral biomarkers of the endocannabinoid system status to predict treatment response. Conclusion: The outcome measures and biomarkers assessed in the ongoing CBD trials for substance use disorders are improving.

Clustering suicidal phenotypes and genetic associations with brain-derived neurotrophic factor in patients with substance use disorders.

Suicide attempts (SA), especially recurrent SA or serious SA, are common in substance use disorders (SUD). However, the genetic component of SA in SUD samples remains unclear. Brain-derived neurotrophic factor (BDNF) alleles and levels have been repeatedly involved in stress-related psychopathology. This investigation uses a within-cases study of BDNF and associated factors in three suicidal phenotypes ('any', 'recurrent', and 'serious') of outpatients seeking treatment for opiate and/or cocaine use disorder. Phenotypic characterization was ascertained using a semi-structured interview. After thorough quality control, 98 SNPs of BDNF and associated factors (the BDNF pathway) were extracted from whole-genome data, leaving 411 patients of Caucasian ancestry, who had reliable data regarding their SA history. Binary and multinomial regression with the three suicidal phenotypes were further performed to adjust for possible confounders, along with hierarchical clustering and compared to controls (N = 2504). Bayesian analyses were conducted to detect pleiotropy across the suicidal phenotypes. Among 154 (37%) ever suicide attempters, 104 (68%) reported at least one serious SA and 96 (57%) two SA or more. The median number of non-tobacco SUDs was three. The BDNF gene remained associated with lifetime SA in SNP-based (rs7934165, rs10835210) and gene-based tests within the clinical sample. rs10835210 clustered with serious SA. Bayesian analysis identified genetic correlation between 'any' and 'serious' SA regarding rs7934165. Despite limitations, 'serious' SA was shown to share both clinical and genetic risk factors of SA-not otherwise specified, suggesting a shared BDNF-related pathophysiology of SA in this population with multiple SUDs.

Alterations in nicotinic receptor alpha5 subunit gene differentially impact early and later stages of cocaine addiction: a translational study in transgenic rats and patients.

Cocaine addiction is a chronic and relapsing disorder with an important genetic component. Human candidate gene association studies showed that the single nucleotide polymorphism (SNP) rs16969968 in the α5 subunit (α5SNP) of nicotinic acetylcholine receptors (nAChRs), previously associated with increased tobacco dependence, was linked to a lower prevalence of cocaine use disorder (CUD). Three additional SNPs in the α5 subunit, previously shown to modify α5 mRNA levels, were also associated with CUD, suggesting an important role of the subunit in this pathology. To investigate the link between this subunit and CUD, we submitted rats knockout for the α5 subunit gene (α5KO), or carrying the α5SNP, to cocaine self-administration (SA) and showed that the acquisition of cocaine-SA was impaired in α5SNP rats while α5KO rats exhibited enhanced cocaine-induced relapse associated with altered neuronal activity in the nucleus accumbens. In addition, we observed in a human cohort of patients with CUD that the α5SNP was associated with a slower transition from first cocaine use to CUD. We also identified a novel SNP in the ß4 nAChR subunit, part of the same gene cluster in the human genome and potentially altering CHRNA5 expression, associated with shorter time to relapse to cocaine use in patients. In conclusion, the α5SNP is protective against CUD by influencing early stages of cocaine exposure while CHRNA5 expression levels may represent a biomarker for the risk to relapse to cocaine use. Drugs modulating α5 containing nAChR activity may thus represent a novel therapeutic strategy against CUD.

BNP worsens 12 days after alcohol cessation while other cardiovascular risk biomarkers improve: An observational study.

Subjects with alcohol use disorder (AUD) display a high prevalence of cardiovascular risk factors (CRFs), and a high incidence of cardiovascular diseases associated with an earlier mortality. Abstinence has long-term cardiovascular and global health benefits. However, few studies have examined the short-term effect of alcohol cessation on cardiac function and key CRFs. The aim of the study was to assess brain natriuretic peptide (BNP) and other CRFs on admission for alcohol cessation and 12 days later, in inpatients with AUD. A retrospective chart review of inpatients hospitalized for alcohol cessation was conducted. Patients who did not relapse at day 12 were included. We compared, at entry and at day 12, BNP and other CRFs: hemodynamic and electromyographic variables, lipid, homocysteine level, and liver enzymes at entry and at day 12. Wilcoxon, Student tests, and repeated-measures ANOVA were conducted. Fifty-five patients were included (38 males, mean age 50.5 years, alcohol per day 60 g-750 g, 44 current tobacco smokers). BNP was significantly increased (11.8 pg/mL [±16.2] to 35.5 pg/mL [±47.6], p < 0.001). Repeated-measure ANOVA showed a significant between-subject effect (p = 0.024), but no significant interaction between BNP variation and having a BNP at entry >10 pg/mL (p = 0.092). In contrast, a significant improvement on 8 of 13 other CRFs and liver enzymes measures was observed (p ≤ 0.05). A rapid improvement of several CRFs was confirmed. However, the increase of BNP at day 12 supports its investigation as a possible relevant biomarker of cardiac function in alcohol withdrawal.

COPD Positive Screening with Spirometry Increases Motivation to Quit Tobacco Smoking in an Addiction Treatment Center.

Providing an on-site immediate diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and lung age in tobacco smokers could be a motivational tool for smoking cessation. Our aim was to investigate the effects of an abnormal spirometry results on motivational change and subsequent smoking cessation. We conducted a retrospective analysis of smoking status after 3 months of tobacco counseling. Patients were recruited in an addiction outpatient center. Spirometry results were obtained with a portable device during the first visit. The sample was thus divided in 3 groups: COPD, subthreshold-group (no COPD but abnormal lung age) and normal spirometry. Among the three groups, we compared the immediate motivation change, difference in Q-MAT motivation scale score after minus before spirometry (Kruskal-Wallis test) and the smoking status after 3 months (Fisher test). We included 48 patients (37 males, median age 44 years, median cigarette-per-day 20). Spirometry results divided the sample in COPD (N = 13), subthreshold (N = 11) and normal group (N = 24). Mean Q-MAT score change after spirometry was different between groups (p = 0.019), greater in COPD (4.62 ± 3.38) than normal group (1.46 ± 3.11), and lower in patient with a co-occuring hazardous alcohol use (p = 7.6 × 10-3). Three-months smoking status was different between spirometry results groups (p = 0.0021). COPD (5/13, 38.5%) and subthreshold patients (6/10, 60.0%) had stopped more frequently than patients from the normal-group (2/22, 9.1%). The effect of immediate spirometry results on motivation to quit varies according to the screened pulmonary damages and hazardous alcohol use. It could be a useful tool in addiction treatment centers.

Association between coffee, tobacco, and alcohol daily consumption and sleep/wake cycle: an actigraphy study in euthymic patients with bipolar disorders.

Individuals with bipolar disorder (BD) have higher than average rates of coffee, tobacco and alcohol use. These substances may have deleterious effects on sleep quality and quantity, which may destabilize sleep/wake cycles and negatively impact the clinical course and prognosis of BD. The use of these substances may also be perceived as a self-medication attempt, for example, to induce sleep or to increase vigilance during the day. The objective of the current study was to investigate associations between the self-reported daily use of coffee, tobacco, and alcohol, and objective measures of sleep and activity patterns in adult individuals with BD. A sample of 147 euthymic individuals with BD were assessed for daily coffee, tobacco and alcohol consumption and 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and daytime activity were compared between groups classified as coffee+/coffee-, tobacco+/tobacco- and alcohol+/alcohol-, defined according to their current daily use. Then, we examined potential correlations between sleep/wake cycle parameters and the amount of daily consumption of each substance. Multivariable analyses identified associations between the use of coffee, tobacco, and alcohol and several sleep and activity parameters, such as between coffee, alcohol, and the relative amplitude of activity (respectively, p = .003 and p = .005), between alcohol and M10 onset (onset time of the 10 most active hours during the 24-h cycle) (p = .003), and between coffee and sleep duration (p = .047). This study supports the hypothesis that there is a relationship, whose direction would be bidirectional, between the daily use of these substances and the sleep/wake cycle in euthymic individuals with BD. These preliminary results require replications in other retrospective and prospective samples. They may have a clinical impact on psycho-education strategies to be proposed to individuals with BD.

Post-GWAS analysis of six substance use traits improves the identification and functional interpretation of genetic risk loci.

BACKGROUND: Little is known about the functional mechanisms through which genetic loci associated with substance use traits ascertain their effect. This study aims to identify and functionally annotate loci associated with substance use traits based on their role in genetic regulation of gene expression. METHODS: We evaluated expression Quantitative Trait Loci (eQTLs) from 13 brain regions and whole blood of the Genotype-Tissue Expression (GTEx) database, and from whole blood of the Depression Genes and Networks (DGN) database. The role of single eQTLs was examined for six substance use traits: alcohol consumption (N = 537,349), cigarettes per day (CPD; N = 263,954), former vs. current smoker (N = 312,821), age of smoking initiation (N = 262,990), ever smoker (N = 632,802), and cocaine dependence (N = 4,769). Subsequently, we conducted a gene level analysis of gene expression on these substance use traits using S-PrediXcan. RESULTS: Using an FDR-adjusted p-value <0.05 we found 2,976 novel candidate genetic loci for substance use traits, and identified genes and tissues through which these loci potentially exert their effects. Using S-PrediXcan, we identified significantly associated genes for all substance traits. DISCUSSION: Annotating genes based on transcriptomic regulation improves the identification and functional characterization of candidate loci and genes for substance use traits.

QT length during methadone maintenance treatment: gene × dose interaction.

Methadone is known to be a risk factor for sudden death by enlarging ECG QT corrected (QTc) interval. For other medical conditions, QTc lengthening has been described as the result of interactions between pharmacological treatments and genetic factors. Former heroin-dependent subjects under methadone maintenance treatment in remission for at last 3 months were recruited. We studied the association between QTc length (Bazett formula) and 126 SNPs located on five genes (KCNE1, KCNQ1, KCNH2, NOS1AP and SCN5A) previously associated with drug-induced QT prolongation. Both SNP-based and gene-based approaches were used, and we tested also the interaction of the top SNP with methadone dosage to predict the QTc length. In our sample of 154 patients, current methadone daily dose was associated with QTc length (rPearson  = 0.26; P = 10-3 ). Only one SNP, rs11911509 on KCNE1, remained significantly associated with QT length after correction for multiple testing (P = 3.84 × 10-4 ; pcorrected  = 0.049). Using a gene-based approach, KCNE1 was also significantly associated with QTc length (pempirical  = 0.02). We found a significant interaction between methadone dosage and rs11911509 minor allele count (allele A vs. C; P = 0.01). Stratified analysis revealed that the correlation between QTc length and methadone dosage was restricted only to AA carriers of this top SNP. Patients' genetic background should be taken into account in the case of clinically relevant QT enlargement during methadone maintenance treatment.

Use of the Fagerström test to assess differences in the degree of nicotine dependence in smokers from five ethnic groups: The HELIUS study.

BACKGROUND: The prevalence of smoking varies across ethnic groups in developed countries, but little is known about ethnic variations in specific aspects of nicotine dependence (ND). We conducted item-response analyses in current smokers to compare ND factors across five ethnic groups. METHODS: Data were obtained from a population-based, multi-ethnic cohort study conducted in the Netherlands. The Fagerström Test for Nicotine Dependence (FTND) was assessed in 1147 Dutch, 991 South-Asian Surinamese, 1408 African Surinamese, 1396 Turkish, and 584 Moroccan smokers (N = 5526). We tested whether the factorial structure of the FTND was invariant across ethnic groups using a multi-group confirmatory factor analysis. FTND item and total scores and factor means were compared across groups. RESULTS: The two-factor model representing "morning smoking" and "smoking patterns" provided an adequate fit. The items "Cigarettes smoked daily" and "Time until first cigarette" showed differential item functioning (DIF) as a function of ethnicity. Three out of four ethnic minority groups scored significantly higher on both factors compared to the Dutch origin group (all p < 0.001) before and after taking DIF into account, while the African Surinamese scored higher only on "morning smoking" when DIF was accounted for. DISCUSSION: The factor structure of the FTND is not measurement invariant across ethnic groups in this population-based sample. Accounting for DIF affecting the nicotine dependence factor scores, although South-Asian Surinamese, Turkish, and Moroccan groups showed higher levels of dependence than the Dutch origin group, genetic as well as environmental factors may account for the observed differences.

Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use.

BACKGROUND: Alcohol and tobacco use are heritable phenotypes. However, only a small number of common genetic variants have been identified, and common variants account for a modest proportion of the heritability. Therefore, this study aims to investigate the role of low-frequency and rare variants in alcohol and tobacco use. METHODS: We meta-analyzed ExomeChip association results from eight discovery cohorts and included 12,466 subjects and 7432 smokers in the analysis of alcohol consumption and tobacco use, respectively. The ExomeChip interrogates low-frequency and rare exonic variants, and in addition a small pool of common variants. We investigated top variants in an independent sample in which ICD-9 diagnoses of "alcoholism" (N = 25,508) and "tobacco use disorder" (N = 27,068) had been assessed. In addition to the single variant analysis, we performed gene-based, polygenic risk score (PRS), and pathway analyses. RESULTS: The meta-analysis did not yield exome-wide significant results. When we jointly analyzed our top results with the independent sample, no low-frequency or rare variants reached significance for alcohol consumption or tobacco use. However, two common variants that were present on the ExomeChip, rs16969968 (p = 2.39 × 10-7) and rs8034191 (p = 6.31 × 10-7) located in CHRNA5 and AGPHD1 at 15q25.1, showed evidence for association with tobacco use. DISCUSSION: Low-frequency and rare exonic variants with large effects do not play a major role in alcohol and tobacco use, nor does the aggregate effect of ExomeChip variants. However, our results confirmed the role of the CHRNA5-CHRNA3-CHRNB4 cluster of nicotinic acetylcholine receptor subunit genes in tobacco use.

[Temporary approval for intranasal naloxone: Setting up in a French addiction center]. / Pratique de l'ATU de cohorte de la naloxone intranasale (Nalscue®) : mise en place dans un CSAPA parisien.

Intranasal naloxone aims at preventing opioid overdose related deaths in active drug users. In France, it has been available since July 2016 through a temporary approval which requires a hospital-based pharmacy and a nominative registration of each patient. We present the characteristics of the first patients who could receive this prescription in our hospital-based addiction center and how they used naloxone during follow-up. Results favor a larger dispensing of naloxone. Patients' as well as peers' and families' education is needed.

TLR4 gene polymorphism associated with lifetime cigarette smoking in bipolar disorder.

Bipolar disorder (BD) is associated with an increased risk of tobacco dependence, the leading addictive substance worldwide. Toll-like receptor 4, a sensor of pathogens and of products of cellular stress and damage, is a major innate immune molecule and logical candidate gene for tobacco dependence in BD because (i) the involvement of TLR4 molecules in several substance use disorders has been suggested, (ii) and the association between the TLR4 gene and BD. We analysed herein the potential association between six TLR4 polymorphisms and lifetime tobacco smoking in 514 BD patients. Significant association between tobacco smoking and rs10759932 was found (genotype, Cochrane Armitage trend test, p=0.008, pcorrected=0.040 and alleles, p=0.008; pcorrected=0.040), where the C minor allele is associated with a protective effect, even after adjusting for confounding factors (OR=1.54 [1.04-2.30], p=0.03). Our results suggest that TLR4 gene polymorphism may act as an intermediate factor for the association between tobacco smoking addiction and BD.

Anxiety disorders are associated with early onset of heroin use and rapid transition to dependence in methadone maintained patients.

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity.

AIMS: Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid-dependent responder patients. METHODS: Eighty-one stable patients (60 men and 21 women, 43.7 ± 8.1 years old, 63.1 ± 50.9 mg day(-1) methadone), divided into quartiles with respect to the median daily dose, were enrolled and underwent clinical examination, treatment history and determination of liver/intestinal cytochrome P450 (CYP) 3A4 activity measured by the midazolam test, R,S-methadone trough concentration and clinically significant polymorphisms of the OPRM1, DRD2, COMT, ABCB1, CYP2B6, CYP3A5, CYP2C19 and CYP2D6 genes. RESULTS: Methadone maintenance dose was correlated to the highest dose ever used (r(2) = 0.57, P < 0.0001). Fractioned methadone intake (odds ratio 4.87, 95% confidence interval 1.27-18.6, P = 0.02), bodyweight (odds ratio 1.57, 95% confidence interval 1.01-2.44, P = 0.04), history of cocaine dependence (80 vs. 44 mg day(-1) in never-addict patients, P = 0.005) and ethnicity (Asian > Caucasian > African, P = 0.04) were independently associated with high-dose methadone in multiple regression analysis. A modest correlation was observed between liver/intestinal CYP3A4 activity and methadone dose at steady state (Spearman rank correlation coefficient [rs ] = 0.21, P = 0.06) but not with highest dose ever used (rs = 0.15, P = 0.18) or dose-normalized R,S-methadone trough concentrations (rs = -0.05, P = 0.64). Concomitant CYP3A4 inhibitors only affected the relationship between methadone dose and R,S-methadone trough concentration. None of the genetic polymorphisms explored was predictive of the methadone maintenance dose. CONCLUSIONS: Methadone maintenance dose was predicted by sociodemographic and clinical variables rather than genetic polymorphisms or liver/intestinal CYP3A4 activity in stable patients.

Anxiety and substance use disorders: co-occurrence and clinical issues.

The co-occurrence of substance use disorders (SUDs) and anxiety disorders has been now well established. This association is frequent and can be explained by three models: the shared vulnerability factors model, the self-medication model, and the substance-induced model. General population epidemiological studies provide strong evidence of the frequency of the association for the most used substances: tobacco, alcohol, cannabis, and to a lesser extent sedatives, opiates, and cocaine. For substances that are less commonly used in the general population, the frequency of the co-occurrence can more precisely be studied in clinical samples. We provide the most recent literature results on the association of SUDs and anxiety, and evidence for one explicative model or the other when available. For substances with sedative properties (alcohol, benzodiazepines, cannabis, opioids), both evidence for a self-medication and for a toxic effect exist. For substances with psychostimulant properties (tobacco, cocaine, and amphetamines), the literature favors the toxic hypothesis to explain the association with anxiety disorders. We give practical steps for the recognition of these dual diagnoses and present therapeutic issues, although the strategies are rarely evidence based.

KCNH2 polymorphism and methadone dosage interact to enhance QT duration.

BACKGROUND: Many drugs increase the duration of the QT interval of patients, potentially leading to harmful effects such as polymorphic ventricular arrhythmias. Most of these drugs do so by inhibiting the rapid component IKr of the delayed rectifier potassium current IK. Methadone is the most prescribed heroin maintenance treatment and is known to inhibit the cardiac potassium channel hERG, which recapitulates IKr. In order to evaluate if any polymorphism of potassium channels' genes could explain some of the "idiosyncratic" QT prolongations observed in patients treated with methadone, we tested the association between KCNE1, KCNE2, and KCNH2 polymorphism and the QT interval prolongation in those patients, controlling for other variables associated with a decrease of the repolarizing reserve. METHODS: A cohort of 82 patients treated with stable dosage of methadone (mean dosage 65 mg/d) for at least three months was genotyped for five polymorphisms in KCNE1, KCNE2 and KCNH2 genes and had their corrected QT (QTc) assessed. RESULTS: The mean QTc interval was 415±34ms. In a linear regression model, longer QTc interval was associated with methadone dosage and with one genetic factor. Each copy of a Lys allele at codon 897 of KCNH2, the gene that encodes the cardiac potassium voltage-gated channel hERG, was associated with a 15.4ms longer QTc (95% CI [4.6-26.2]; p=0.001). CONCLUSION: KCNH2 genotyping may be relevant in the analysis of cumulative risk factors for QT prolongation in patients on methadone maintenance treatment.

[When and how to detoxify clients from methadone maintenance treatment?]. / Stratégies d'arrêt du traitement de substitution par méthadone.

BACKGROUND: Methadone is prescribed in France as a maintenance treatment for heroin dependence since 1969. Nevertheless, the optimal duration of methadone maintenance treatment and how detoxification from methadone at the end of the treatment should be performed is still discussed. OBJECTIVE: To conduct a literature review on when and how detoxify clients from methadone maintenance treatment and to collect the opinion of experts in the field. DOCUMENTARY SOURCES: We searched the PubMed, Embase, Cochrane Library and PsycINFO databases on the 1966-2011 period using the keywords "methadone", "maintenance", "detoxification", "tapering", "cessation", "withdrawal". We also searched data in other addictive journals in French that are not available in those databases. We also collected the opinion of the physician in charge of the oldest methadone program in France (1969). STUDIES SELECTION: We excluded studies that used methadone as short time treatment of heroin withdrawal and thus selected 23 articles. RESULTS: There is a consensus on when methadone maintenance treatment should be stopped, defined by the client's will to stop, the judgement from the physician that the client has been stable for a period of time that is long enough, but also the client's motivation to live his life without maintenance treatment. There is also a majority, among articles on how methadone treatment should be stopped, recommending ambulatory, practical approaches using slow tapering of the dose, with the ability to go back to the previous dose if needed, namely in case of relapse to heroin use, heavy withdrawal or psychiatric symptoms. LIMITS: There are few articles addressing the subject, especially comparing prospectively different cessation strategies. CONCLUSION: Methadone maintenance treatment should not necessarily be maintained all life long and can be stopped within its prescription setting, including medical, psychological and social evaluation.

Reliability and validity of the French version of the tobacco craving questionnaire.

OBJECTIVES: (1) To assess the factorial structure, reliability and validity of the French language version of the Tobacco Craving Questionnaire (TCQ), a multidimensional, self-report instrument evaluating tobacco craving, to allow its use in French-speaking populations. (2) To compare the two different language versions of the same instrument in 2 independent samples from 2 cultures in 2 distinct time periods. METHODS: The French TCQ was administered to 226 current cigarette smokers after at least 2 h of abstinence. RESULTS: Despite the substantial difference in population characteristics between the French and American samples of smokers, both exploratory and confirmatory factor analyses indicated that the French version was best described by a 4-factor solution, similar to the original English version. Reliability estimates were 0.83, 0.79, 0.69 and 0.66 for the French and 0.82, 0.70, 0.75 and 0.48 for the English version for 'emotionality' (factor 1), 'expectancy' (factor 2), 'compulsivity' (factor 3) and 'purposefulness' (factor 4), respectively. The 4 factors accounted for 11.6, 17.1, 9.0, and 9.5% of the total variance in emotionality, expectancy, compulsivity, and purposefulness, respectively, for the French compared to 14.2, 12.5, 14.4 and 5% of the total variance for the English version, respectively. CONCLUSION: The French version of the TCQ is as valid and reliable instrument as the original English version and assesses the same 4 dimensions of craving for tobacco.