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

NCT01618656 | Completed Phase 2 Results DMC

• 2 other identifiers: 1202009714U01DA033267
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Cannabis Dependence

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Change in Polysomnography

  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 Outcomes (2)

• 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)

• 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)

Study Arms (2)

PF-04457845

ACTIVE COMPARATOR

2/3 of subjects will be randomized to fatty acid amide hydrolase (FAAH) inhibitor 4mg

Drug: PF-04457845

Placebo (sugar pill)

PLACEBO COMPARATOR

1/3 of subjects will be randomized to placebo

Drug: Placebo

Interventions

PF-04457845 DRUG

Study medication will be administered at 4mg by mouth daily for four weeks.

PF-04457845

Placebo DRUG

Sugar pill

Placebo (sugar pill)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male
• Ages 18-55 (inclusive)
• Cannabis Dependence

You may not qualify if:

• Allergies or intolerance to FAAH-Inhibitors
• Current significant medical or other comorbidities

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Yale University School of Medicine

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

• 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.

  PMID: 30528676 DERIVED

MeSH Terms

Conditions

Marijuana Abuse

Interventions

N-pyridazin-3-yl-4-(3-((5-(trifluoromethyl)pyridin-2-yl)oxy)benzylidene)piperidine-1-carboxamide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Deepak Cyril D'Souza, MD
• Organization: Yale University School of Medicine

deepak.dsouza@yale.edu

203-932-5711

Study Officials

• Deepak C D'Souza, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: June 5, 2012
• First Posted: June 13, 2012
• Study Start: September 12, 2012
• Primary Completion: March 11, 2016
• Study Completion: March 11, 2016
• Last Updated: February 23, 2023
• Results First Posted: February 23, 2023

Record last verified: 2023-01

Locations

US (1)