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

Abstract
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 per formed at baseline before CBD administration, and was repeated after 3 days of CBD. Secondary outcomes in cluded 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