Safety and Efficacy of a FAAH-Inhibitor to Treat Cannabis Withdrawal

Study Overview
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Brief Summary
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Cannabis dependence is associated with changes in the brain's cannabinoid system. When cannabis dependent individuals try to quit using cannabis, some of them experience problems that make it difficult for them to achieve and maintain abstinence. Therefore, reducing the problems related to quitting cannabis may facilitate abstinence. One way to do this is by harnessing the brain's capacity to make its own cannabis-like substances - endocannabinoids. One of the main endocannabinoids is anandamide. The study is based on the hypothesis that the problems related to quitting cannabis use will be reduced by increasing the brain levels of anandamide. Furthermore, by reducing the problems related to quitting cannabis, people will be less likely to relapse. Brain anandamide levels will be increased by blocking the breakdown of anandamide using a fatty acid amide hydrolase inhibitor (FAAH-I). The effects of a novel FAAH-I cannabis withdrawal and relapse in cannabis dependent subjects will be studied in a double-blind, randomized, controlled, proof-of-concept study. Cannabis-dependent subjects will receive placebo or the FAAH-inhibitor PF-04457845 in a 2:1 randomization. The trial consists of a 1 week inpatient stay to achieve abstinence, a 3 week outpatient treatment phase. Cannabis withdrawal will be measured during the inpatient phase. Cannabis use and urinary THC-COOH levels will be measured during the entire study. The treatment phase will be followed by a safety follow up phase of 8 weeks.

Official Title
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FAAH-Inhibitor for Cannabis Dependence

Conditions
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Cannabis Dependence

Intervention / Treatment
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* Drug: PF-04457845
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Ages 18-55 (inclusive) Cannabis Dependence Exclusion Criteria: Allergies or intolerance to FAAH-Inhibitors Current significant medical or other comorbidities

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

Sexes Eligible for Study
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Male

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PF-04457845<br>2/3 of subjects will be randomized to fatty acid amide hydrolase (FAAH) inhibitor 4mg | Drug: PF-04457845<br>* Study medication will be administered at 4mg by mouth daily for four weeks.<br>|
| Placebo Comparator: Placebo (sugar pill)<br>1/3 of subjects will be randomized to placebo | Drug: Placebo<br>* Sugar pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Marijuana Withdrawal Checklist (MWC) | 32-item checklist evaluating potential symptoms of cannabis withdrawal, lower values reflect lesser severity of withdrawal symptoms (lower scores represent a better outcome). Min: 0 Max: 96 | The MWC was administered on Day 0, Day 1, Day 2, Day 3, and Day 4 (during the inpatient phase when withdrawal peaks) to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm. | 
| Change in Self Reported Cannabis Use at the End of 4 Weeks | Subject quantifies and reports frequency of cannabis use prior to study participation and during the 4 week period. Lower scores reflect less cannabis usage, while higher scores reflect more frequent usage. Min: 0 Max: undeterminable, varies per patient and their usage. | Administered weekly for 4 weeks to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm. | 
| Change in THC-COOH Quantification at the End of 4 Weeks | Subjects provide urine samples to quantify levels of THC. | Samples obtained weekly for 4 weeks to assess change from baseline (Day 0). The results from each time point and subject were calculated to report the mean score for each arm. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Polysomnography | Polysomnography (PSG) is a comprehensive reading of biophysiological changes that occur during sleep, including identification of sleep stage. A mean and standard deviation of their data points during sleep stages were calculated to determine change from baseline to the end of study treatment. | Polysomnography was collected two nights prior to baseline visit, for three nights during study treatment and two nights after four weeks of study treatment. A mean was calculated to assess change from baseline (Day 0). |