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

• ClinicalTrials.gov Identifier: NCT01618656
• Recruitment Status: Completed
• First Posted: June 13, 2012
• Results First Posted: February 23, 2023
• Last Update Posted: February 23, 2023
• Sponsor: Yale University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Deepak C. D'Souza, Yale University

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 (Clinical Trial)
• Actual Enrollment: 70 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: September 12, 2012
• Actual Primary Completion Date: March 11, 2016
• Actual Study Completion Date: March 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. 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

2. 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.

3. 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.

Secondary Outcome Measures :

1. 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.

Other Outcome Measures:

1. 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)
2. 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

Eligibility Criteria

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

Criteria

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

United States, Connecticut

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

D'Souza DC, Cortes-Briones J, Creatura G, Bluez G, Thurnauer H, Deaso E, Bielen K, Surti T, Radhakrishnan R, Gupta A, Gupta S, Cahill J, Sherif MA, Makriyannis A, Morgan PT, Ranganathan M, Skosnik PD. Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial. Lancet Psychiatry. 2019 Jan;6(1):35-45. doi: 10.1016/S2215-0366(18)30427-9. Epub 2018 Dec 6.

• Responsible Party: Deepak C. D'Souza, Associate Professor of Psychiatry, Yale University
• ClinicalTrials.gov Identifier: NCT01618656
• Other Study ID Numbers: 1202009714; U01DA033267 ( U.S. NIH Grant/Contract )
• First Posted: June 13, 2012
• Results First Posted: February 23, 2023
• Last Update Posted: February 23, 2023
• Last Verified: January 2023

Additional relevant MeSH terms:

Marijuana Abuse; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders