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

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01618656
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 120
• Location: 1
• Arms: 2
• Actual Duration (Months): 41.9
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cannabis Dependence	Drug: PF-04457845; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: FAAH-Inhibitor for Cannabis Dependence
• Actual Study Start Date: Sep 12, 2012
• Actual Primary Completion Date: Mar 11, 2016
• Actual Study Completion Date: Mar 11, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Marijuana Withdrawal Checklist [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)]

   32-item checklist evaluating potential symptoms of cannabis withdrawal

2. Self reported cannabis use at the end of 4 weeks [Administered weekly for 4 weeks to assess change from baseline (Day 0)]

   Subject quantifies and reports frequency of cannabis use prior to study participation and during

3. THC-COOH Quantification at the end of 4 weeks [Samples obtained weekly for 4 weeks to assess change from baseline (Day 0)]

   Subjects provide urine samples to quantify levels of THC

Secondary Outcome Measures

1. Polysomnography [Two nights prior to study treatment, three nights during study treatment and two nights at the end of study treatment (four weeks later), to assess change from baseline (Day 0)]

   Measurement of sleeping patterns

2. Cognitive Testing [Once pre-treatment, twice during treatment (within 4 weeks) and once during the non-treatment follow up (within 8 weeks) to assess change from baseline (Day 0)]

   Various computerized tests of memory, attention and learning

Other Outcome Measures

1. Feeling States [Administered on Day 0, Day 1, Day 2, Day 3, and Day 4 (Once pre-treatment and during the inpatient phase 'acute abstinence') to assess change from baseline (Day 0)]

   Visual analog scale for feeling states (depression, anxiety, irritability)

2. Plasma endocannabinoid levels [Samples obtained at the following study visits: Day -1, Day 0, Day 2, Day 4, Week 2, Week 3, Week 4 to assess change from baseline (Day 0)]

   Measurement of circulating plasma Anandamide

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male

2. Ages 18-55 (inclusive)

3. Cannabis Dependence

Exclusion Criteria:

1. Allergies or intolerance to FAAH-Inhibitors

2. Current significant medical or other comorbidities

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University School of Medicine	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• Yale University
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Deepak C D'Souza, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Deepak C. D'Souza, Associate Professor of Psychiatry, Yale University
• ClinicalTrials.gov Identifier: NCT01618656
• Other Study ID Numbers: 1202009714; U01DA033267
• First Posted: Jun 13, 2012
• Last Update Posted: Feb 10, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Marijuana Abuse

Study Results

No Results Posted as of Feb 10, 2022