The investigational fatty acid amide hydrolase inhibitor (FAAH) PF-04457845 may decrease cannabis withdrawal symptoms and dependence in men, according to phase 2 study results published in Lancet Psychiatry.

Researchers conducted a double-blind placebo-controlled parallel group trial of 46 men between age 18 and 55 who were diagnosed with cannabis dependence using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria. Study patients were randomly assigned in a 2:1 ratio to receive either 4 mg daily of PF-04457845 or placebo by means of a fixed block size of 6 patients, stratified according to degree and willingness to cease cannabis use. The co-primary end points were the difference in withdrawal symptoms after 4 weeks of therapy in addition to self-reported cannabis use and urine THC-COOH measures.

After statistical analysis, the investigators found that compared with placebo therapy with PF-04457845 was associated with a significant reduction in cannabis withdrawal and accompanying mood symptoms (mean symptom score difference, 4.96; 95% CI, 0.71-9.21; P =.048) after treatment day 1. In addition, participants in the PF-04457845 arm saw a significant reduction in self-reported cannabis use after 4 weeks of treatment (mean joints per day difference, 0.88; 95% CI, 0.29-1.46; P =.0003) and lower urinary THC-COOH concentrations (mean difference of 657.92 ng/mL; 95% CI, 17.55-767.18; P =.009) .

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The primary study limitation was the enrollment of only male patients, which limited the generalizability of results.

“Treatment with an FAAH inhibitor reduced cannabis withdrawal symptoms, cannabis use, and sleep disturbance in men, and was well tolerated,” the researchers wrote.

“Future studies in a larger sample of treatment-seeking individuals and women, and in an outpatient setting that is more ecologically valid will be important to [determining] safe and efficacious treatments for a large and growing clinical problem,” they concluded.


D’Souza DC, Cortes-Briones J, Creatura G, et al. 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;6(1):35-45.