Dronabinol and Epidiolex to Manage Uncontrolled Residual Symptoms of Buprenorphine Initiation Trial

The goal of this pilot study is to test novel, adjunctive pharmacotherapy for patients with opioid use disorder (POUD) who may be at risk for overdose and other poor opioid use disorder (OUD) outcomes even after initiating buprenorphine. The investigator team proposes to test the effectiveness of combined dronabinol (synthetic delta-9-tetrahydrocannabinol \[THC\]) and Epidiolex (cannabidiol \[CBD\]) - two FDA-approved cannabinoids - to improve retention in buprenorphine treatment and reduce opioid use among POUD who are early in treatment. POUD who are early in treatment are at a critical juncture-a moment of opportunity and motivation, but also of high risk of return to opioid use and loss to follow up.

Inclusion Criteria: * Fluency in English and Spanish * The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of OUD * Newly initiated on buprenorphine within 21 days * Positive urine toxicology for opioids other than buprenorphine in the past week OR opioid withdrawal symptoms in the past week based on the Clinical Opioid Withdrawal Scale (COWS) \>=5 * Any cannabis use in the past at or after the age of 18 years based on self-report Exclusion Criteria: * Urine toxicology positive for cannabinoids * Inability to provide informed consent * Liver tests (AST or ALT) \>3 times the upper limit of normal, or a history of liver disease * Pregnancy or breast/chest feeding * Unstable cardiac disease, history of hypotension or syncope * Psychotic disorder, or history of suicidal behavior and/or ideation * Progressive neurological conditions, frequent falls, or history of epileptic seizures * Severe alcohol use disorder, benzodiazepine use disorder or stimulant use disorder * Other serious medical conditions that would be a contraindication to THC or CBD use