Clinical and Neurobiological Effects of Cannabis Dependence in Young Adults

Study Overview
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Brief Summary
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The purpose of this study is to find out more about cognitive functioning in people who are cannabis dependent, relative to people who do not use cannabis, and how their brains process information after one month of not using cannabis. An additional goal is to characterize the severity of cannabis dependence using precipitated and naturalistic withdrawal with a double blind, placebo controlled, single administration of rimonabant. Research assessments occur bi-weekly throughout this 28 day study.

Official Title
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Translational Center on the Clinical Neurobiology of Cannabis Addiction

Conditions
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Cannabis Dependence, Cannabis Withdrawal

Intervention / Treatment
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* Drug: rimonabant
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Cannabis Dependent Subjects: Inclusion Criteria: males or females 21-30 years of age meets Diagnostic and Statistical Manual (DSM-IV) diagnosis of Cannabis Dependence willing to be abstinent for 28 days during study smokes < 10 cigarettes per day drinks < 1 (female) or < 2 (male) per day Exclusion Criteria: active suicide ideation meets DSM-IV diagnosis for dependence on other substances other than cannabis significant medical disorders pregnant women meets DSM-IV diagnosis for a major Axis I disorder other than cannabis dependence currently taking psychoactive medication

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabis-dependent rimonabant<br>Cannabis dependent young adults administered rimonabant 90 mg at Day 0 and followed for 28 days post. | Drug: rimonabant<br>* double blind, placebo controlled, single 90 mg dose<br>* Other names: CB1 receptor antagonist;|
| Placebo Comparator: Cannabis-dependent placebo<br>Cannabis dependent young adults administered matched placebo at Day 0 and followed for 28 days post. | Drug: placebo<br>* matched placebo<br>|
| No Intervention: Non-cannabis using control<br>Non-cannabis using demographically similar young adults followed for 28 days. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Withdrawal Symptom Severity on the Marijuana Withdrawal Checklist (MWC) at 28 Days Following Single Dose Administration of Rimonabant or Placebo, or Commencement of Monitoring, During the Double-Blind Period | The MWC is a 28-item instrument that is used to assess the severity of frequently reported cannabis withdrawal symptoms. Each item on the measure is recorded as a severity rating between 0-3 where a zero indicates not present and a three indicates severe. The severity rating of each item was summed to obtain a single marijuana withdrawal severity score ranging between 0- 84. A lower score indicates less severe withdrawal. | Day 28 | 
| Plasma Norepinephrine | Blood samples were obtained and plasma concentrations were determined using validated enzyme-linked immunosorbent assay (ELISA) techniques at 28 days following single dose administration of rimonabant or placebo, or commencement of monitoring, during the double-blind period. | Day 28 | 
| Plasma Cortisol | Blood samples were obtained and plasma concentrations were determined using validated enzyme-linked immunosorbent assay (ELISA) techniques at 28 days following single dose administration of rimonabant or placebo, or commencement of monitoring, during the double-blind period. | Day 28 | 
| Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Strategy Score at Day 28 | The CANTAB SWM task is a validated computer-based testing instrument assessing the memory component of executive function. Strategy Score is an estimate of use of the most efficient strategy to complete the task. Scores range from 8-56; higher scores equate to poor use of the most efficient strategy. Change = (Day 28 Score - Day 0 Score). A more negative result indicates greater improvement. | Day 0 and Day 28 | 
| Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Total Errors at Day 28 | The CANTAB SWM task is a validated computer-based testing instrument assessing the memory component of executive function. Total Errors are a measure of performance and are unbounded. Change = (Day 28 Score - Day 0 Score). A more negative result indicates greater improvement. | Day 0 and Day 28 | 
| Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Mean Time To First Response at Day 28 | The CANTAB SWM task is a validated computer-based testing instrument assessing the memory component of executive function. Mean Time To First Response is a measure of latency and is unbounded. Change = (Day 28 Time - Day 0 Time). A more negative result indicates greater improvement. | Day 0 and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rimonabant, Cannabis Dependence, Marijuana Dependence, Cannabis Withdrawal, cannabinoid receptor type 1 (CB1) inverse agonist, Neuropsychology, functional magnetic resonance imaging (fMRI), Endocannabinoids, Cortisol