Proof-of-concept trial of PP-01 for mitigating cannabis withdrawal syndrome in participants with cannabis use disorder.

BACKGROUND AND OBJECTIVES: Cannabis withdrawal symptoms can be severe and protracted, significantly impeding the ability to abstain from cannabis use, resulting in failed quit attempts and relapse. This clinical trial evaluated safety and efficacy of PP-01, a novel dual‑mechanism of action, investigational agent, for mitigating cannabis withdrawal symptoms in patients with cannabis use disorder (CUD). METHODS: This Phase 1b/2a randomized, double-blind, placebo-controlled, crossover, 5-night, inpatient study evaluated efficacy and safety of PP-01 (nabilone and gabapentin) in 14 adults with moderate to severe CUD. Participants with daily/near daily use of ≥1 gram/day of cannabis and a history of cannabis withdrawal were randomized to PP-01 or placebo. Severity and bothersomeness of withdrawal symptoms were evaluated by patient daily diary. Mixed model repeated measures analysis of variance was used to compare mean differences between PP-01 and placebo. RESULTS: PP-01 significantly reduced severity (p = .0222) and bothersomeness (p = .0063) of cannabis withdrawal symptoms within 10 and 4 h post-first dose of PP-01, respectively. Sleep quality and cannabis cravings significantly improved following first dose through discharge. Objective withdrawal measures also statistically significantly improved. PP-01 was well tolerated; adverse events (AEs) were mild in severity with no serious AEs. DISCUSSION AND CONCLUSIONS: Investigational PP-01 mitigated cannabis withdrawal symptoms in participants with moderate to severe CUD, was safe and well-tolerated in this proof-of-concept study. SCIENTIFIC SIGNIFICANCE: PP-01 is intended as a potential treatment for cannabis withdrawal syndrome (CWS)/CUD, a serious and unmet need for which there is no Food and Drug Administration (FDA)-approved medication.