Dronabinol and Epidiolex (Cannabidiol) for Uncontrolled Residual Symptoms of Buprenorphine Initiation (Demure Trial)

About This Grant

ABSTRACT Opioid use disorder (OUD) and opioid overdose deaths remain shockingly high, fueled by fentanyl. Buprenorphine is an effective treatment for OUD, but successful treatment of people who use fentanyl has been hampered by protracted opioid withdrawal symptoms which can last even 6 months. There is evidence that Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) each could improve protracted opioid withdrawal symptoms and OUD outcomes in POUD who use fentanyl. However, using them separately has downsides—THC alone can cause intolerable side effects, and using CBD alone does not address as many symptoms as when it is used together with dronabinol. Dronabinol (synthetic THC) and Epidiolex (CBD) are two FDA approved cannabinoids that are pharmaceutical grade and are ideal products to test the effectiveness and safety of THC and CBD as an adjunct to buprenorphine in improving retention in OUD treatment and reducing opioid use. We will enroll 40 POUD early in treatment with buprenorphine with continued opioid use or cravings in a 12-week pilot randomized trial of dronabinol + Epidiolex (vs. placebo). Our primary outcome variable is retention in OUD treatment and secondary outcomes are opioid use, opioid withdrawal symptoms, pain severity and adverse events (panic, anxiety, and poor cognition). Finally, we will explore the mechanism by which cannabinoids improve OUD outcomes in POUD. Findings from this pilot study will inform the design, implementation, and power calculations for a future R01 which will examine the efficacy of dronabinol + Epidiolex as an adjunct to buprenorphine and rigorously examine potential mechanisms of opioid withdrawal symptoms, including cravings and pain.