Adjunctive Cannabidiol in Inpatient Buprenorphine Treatment for Opioid Use Disorder: A Pilot Randomized Trial.

Abstract

Despite the efficacy of medications for opioid use disorder (MOUD), return to illegal opioid use remains common. Cannabidiol (CBD) may reduce craving and improve outcomes. This pilot trial evaluated the safety and preliminary efficacy of CBD as adjunctive therapy to buprenorphine in an inpatient setting. Adults (≥18 years), who met DSM-5 criteria for opioid use disorder and were admitted to an inpatient addiction treatment center between May 2022 and March 2024, were enrolled in a randomized, double-blind, placebo-controlled trial. Participants received oral CBD (600 mg/day) or placebo for 28 days alongside buprenorphine. Primary outcomes were safety and tolerability, monitored via adverse events and clinical laboratory tests. Efficacy was assessed as effects on opioid craving and withdrawal, and affective symptoms (anxiety, negative affect, and positive affect). Of 35 enrolled participants, 30 received at least one dose of study medication (CBD: n=18; placebo: n=12) and were included in the safety analysis. CBD was well tolerated; no serious adverse events or deaths occurred. Gastrointestinal symptoms occurred in both groups and were the most common adverse event. No significant pharmacokinetic interaction was observed between CBD and buprenorphine. Both groups showed reductions in opioid craving and negative affect over time, with mixed group-by time interactions (most favoring placebo, but cue-induced craving trending toward greater improvement with CBD). Adjunctive CBD was safe and well tolerated in combination with buprenorphine. No clear advantage over placebo was observed. Larger trials are needed to determine clinical utility in MOUD treatment.