clinical trial of n-acetylcysteine versus placebo efficacy in the cannabis withdrawal

Conditions: Cannabis Dependence; Cannabis Abuse

Summary: the primary purpose is to assess the efficacy in human of n-acetylcysteine versus placebo during 4 weeks in cannabis withdrawal.

introduction:there are few clinical trials on pharmacotherapies in marijuana dependence. there is no randomized and double-blind trial on n-acetylcysteine efficacy in marijuana withdrawal.aims:the first aim is to assess the efficacy in human (n=150 outpatients) of n-acetylcysteine versus placebo during 4 weeks in cannabis withdrawal.the secondary aims are:a-assessing the abstinence during the next 5 months of follow-up.b-assessing the correlations between genetic characteristics: cytochrome cyp2c9 and cyp3a4, cnr1 receptor, fatty amide hydroxylase (faah), dopamine dat transporters and catechol-o-méthyltransférase (comt); and three phenotypes : 1. cannabis level consumption, 2. cannabis abuse and dependence (dsm-iv), and 3. cannabis withdrawal.c-assessing tobacco consumption (fagerström test), nicotinique receptor chra3 and cannabis quitting success.subjects:150 cannabis outpatients, seeking treatment in lariboisiere hospital cannabis setting, to cut down their cannabis use.inclusion criteria: \> 18 year old, not pregnant or breast feeding, cannabis abuse or dependence diagnosis (dsm-iv), acceptance of the trial and consent signed, validated by ethic committee.methods:randomized and double-blind trial.visit 0: clinical assessment and trial presentation, validate inclusion and non- inclusion criteria.visit 1: consent signed. blood and urine analysis. questionnaires assessing cannabis and tobacco's craving.nac and placebo doses will be increased if craving decreases \<25% compared to previous visit. the doses start at 200 mg x 4/24h to 800 mg x 4/24h.visit 2 to 5: medication safety and cannabis craving and withdrawal assessment during 4 weeks.visit 5: blood and urine analysis.visit 6 to 8: abstinence assessment during 5 months.goals:efficacy assessment of n-acetylcysteine in cannabis withdrawal and abstinence compared to placebo. assessment of nac efficacy in cannabis craving. the length of the study is 6 months to evaluate abstinence persistence. evaluation of clinical, biological and genetic factors associated with abstinence success.statistic :sample size : a two group continuity corrected c2 test with a 0.050 two-sided significance level will have 80% power to detect the difference between a group 1 proportion, p1, of 0.250 and a group 2 proportion, p2, of 0.500 (odds ratio of 3.000) when the sample size in each group is 66. taking into account a rate of lost of follow-up around 15 % the total sample size of the study has been fixed at n= 150 patients.main criterion and binary secondary criteria will be analysed by chi-square tests or fisher's exact probability test. relationships between genotype and phenotypes will be analysed by multivariate logistic models

Eligibility criteria:
inclusion criteria: * \> 18 year old * not pregnant or breast feeding * cannabis abuse or dependence diagnosis (dsm-iv) * acceptance of the trial and consent signed, validated by ethic committee * patient affiliated to social insurance care exclusion criteria: * contraindication to n-acetylcystein : allergic to n-acetylcystein, severe allergic illness, phenylcetonuria, lactose intolerance, gastro-duodenal ulcer. * severe somatic disease not stabilized : diabetes, epilepsia, recent myocardial infarcts, asthma. * severe mental disease not stabilized : schizophrenia.

Keywords: cannabis n-acetylcystein dependence abuse craving genetic