Cannabidiol Effect on Cue-Induced Craving for Individuals with Opioid Use Disorder Treated with Buprenorphine: A Small Proof-of-Concept Open-Label Study.

Background: Opioid use disorder (OUD) remains a major public health concern. Despite the use of medications for OUD such as buprenorphine, the current gold-standard treatment, relapse in the context of increased craving remains common. Cannabidiol (CBD) has been shown to reduce cue-induced craving in individuals with OUD, but among those who were not receiving any buprenorphine treatment. This small proof-of-concept open-label study sought to evaluate the effect of CBD on cue-induced craving among individuals with OUD who were being actively treated with buprenorphine.

Methods: Participants (n = 5) received CBD (Epidiolex^®) 600 mg once daily for 3 consecutive days in an open-label manner. Primary outcome was cue-induced craving measured on a visual analog scale of 0 to 10, calculated as the difference in craving in response to drug-related versus neutral cues. The cue-reactivity paradigm was performed at baseline before CBD administration, and was repeated after 3 days of CBD. Secondary outcomes included scores on depression, anxiety, pain, opioid withdrawal, and side effects.

Results: All participants were actively taking buprenorphine for an average of 37.8 months (range 1-120 months). Cue-induced craving was significantly lower after CBD dosing compared with baseline (0.4 vs. 3.2, paired t-test, p = 0.0046). No significant changes in scores for depression, anxiety, pain, or opioid withdrawal were noted. CBD was well tolerated, although one participant experienced moderate sedation; otherwise, no other adverse effects were reported.

Conclusions: Given the high risk for bias in a small uncontrolled open label study such as this, results must be interpreted with caution. A larger adequately powered trial with a suitable control group is needed to confirm the finding that CBD may help to reduce cue-induced craving among individuals with OUD currently on buprenorphine treatment. Research should further evaluate whether adjunctive use of CBD can improve clinical outcomes for individuals with OUD maintained on buprenorphine. ClinicalTrials.gov (NCT04192370).