Clinical Trial of N-acetylcysteine Versus Placebo Efficacy in the Cannabis Withdrawal

Study Overview
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Brief Summary
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The primary purpose is to assess the efficacy in human of N-acetylcysteine versus placebo during 4 weeks in cannabis withdrawal.

Detailed Description
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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

Official Title
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Randomized and Double-blind Clinical Trial of N-acetylcysteine Versus Placebo Efficacy in the Cannabis Withdrawal

Conditions
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Cannabis Dependence, Cannabis Abuse

Intervention / Treatment
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* Drug: N-acetylcystein


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental : N-acetylcystein<br>N-acetylcystein and placebo doses will be increased if craving decreases <25% compared to the previous visit. The doses start at 200 mg x 4/24h to 800 mg x 4/24h | Drug: N-acetylcystein<br>* Visit 1: Consent signed. Blood and urine analysis. Questionnaires assessing cannabis and tobacco's craving.N-acetylcystein 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.<br>|
| Placebo Comparator: Placebo Comparator<br>N-acetylcystein and placebo doses will be increased if craving decreases <25% compared to the previous visit. The doses start at 200 mg x 4/24h to 800 mg x 4/24h | Drug: N-acetylcystein<br>* Visit 1: Consent signed. Blood and urine analysis. Questionnaires assessing cannabis and tobacco's craving.N-acetylcystein 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate of withdrawal defined by a reduction of at least 50% of the rate of urinary carboxy-THC |  | at 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The success rate of withdrawal defined by a declarative reduction of at least 50% of the cannabis |  | at 2, 3 and 6 months | 
| The retention rate of withdrawal |  | at 6 months | 
| The rate of complete cessation of cannabis use | Declarative clinical criteria by the patient and validated at D28 by the decrease of at least 50% of the report of the dosage of the report CarboxyTHC / creatinine | at 4 weeks and 2, 3 and 6 months. | 
| Phenotypic profile (3 major types) | The amount of cannabis and THC consumed with use of the upper quartile to define a high consumption and the lowest quartile to define the weak consumer Dependence and abuse according to DSM IV criteria; Withdrawal syndrome in dependent patients according to DSM IV and the scale of MJQQ Gorelick. | at Day 28 (end of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabis, N-Acetylcystein, Dependence, Abuse, Craving, Genetic