D'Souza DC, et al. - Via conducting a double-blind, placebo-controlled, parallel group phase 2a trial, researchers tested the efficacy and safety of the fatty acid amide hydrolase (FAAH)-inhibitor PF-04457845 in reduction of cannabis withdrawal and cannabis use in men who were daily cannabis users. Outcomes suggest PF-04457845 as effective in reducing cannabis withdrawal symptoms and cannabis use in men. Hence it seems to be an effective and safe approach for the treatment of cannabis use disorder.

Methods

• The men aged 18–55 years with cannabis dependence according to DSM-IV criteria (equivalent to cannabis use disorder in DSM-5) were included.
• After baseline assessments, researchers randomly assigned participants (2:1) to receive PF-04457845 (4 mg per day) or placebo using a fixed block size of six participants, stratified by severity of cannabis use and desire to quit.
• To achieve abstinence and precipitate cannabis withdrawal, they admitted the participants to hospital for 5 days (maximum 8 days); after this, discharge was done to continue the remaining 3 weeks of treatment as outpatients.
• Treatment-related differences in cannabis withdrawal symptoms during hospital admission, and week 4 (end of treatment) self-reported cannabis use and urine THC-COOH concentrations in the intention-to-treat population were assessed as the primary endpoints.

Results

• Researchers randomly assigned 46 men to PF-04457845 and 24 to placebo between Sept 12, 2012, and Jan 18, 2016.
• Video-calling and pill count confirmed 88% adherence to study medication; the findings were corroborated by corresponding drug and anandamide concentrations in blood.
• Compared to placebo, treatment with PF-04457845 was noted to be associated with reduced symptoms of cannabis withdrawal (first day of treatment mean symptom score 11·00 [95% CI 7·78–15·57] vs 6·04 [4·43–8·24]; difference 4·96 [0·71–9·21]; p _adj=0·048; second day of treatment 11·74 [8·28–16·66] vs 6·02 [4·28–8·47]; difference 5·73 [1·13–10·32]; p _adj=0·035) and related mood symptoms during the inpatient phase.
• In addition, lower self-reported cannabis use at 4 weeks (mean 1·27 joints per day [95% CI 0·82–1·97] vs 0·40 [0·25–0·62]; difference 0·88 [0·29–1·46]; p=0·0003) and lower urinary THC-COOH concentrations (mean 657·92 ng/mL [95% CI 381·60–1134·30] vs 265·55 [175·60–401·57]; difference 392·37 [17·55–767·18)]; p=0·009) were noted in association with treatment with PF-04457845.
• During the treatment period, discontinuation was noted in eight (17%) patients in the PF-04457845 group and four (17%) in the placebo group .
• An adverse event was reported in 20 (43%) of 46 participants in the PF-04457845 group and 11 (46%) of 24 participants in the placebo group during the 4-week treatment phase.
• No serious adverse events were evident.