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

January 27, 2023 updated by: Deepak C. D'Souza, Yale University

FAAH-Inhibitor for Cannabis Dependence

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Yale University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Marijuana Withdrawal Checklist (MWC)
Time Frame: 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.

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
Time Frame: 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.

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
Time Frame: 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.
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
Time Frame: 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).
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).

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feeling States
Time Frame: 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)
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)
Plasma Endocannabinoid Levels
Time Frame: 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
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Collaborators

National Institute on Drug Abuse (NIDA)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 12, 2012

Primary Completion (Actual)

March 11, 2016

Study Completion (Actual)

March 11, 2016

Study Registration Dates

First Submitted

June 5, 2012

First Submitted That Met QC Criteria

June 12, 2012

First Posted (Estimate)

June 13, 2012

Study Record Updates

Last Update Posted (Estimate)

February 23, 2023

Last Update Submitted That Met QC Criteria

January 27, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1202009714
  • U01DA033267 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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