This will be a randomized, double-blind, placebo controlled, study of cannabidiol (CBD) (600 mg/day) as an adjunctive therapy to buprenorphine + naloxone or methadone in patients who have Opioid Use Disorder and are receiving residential behavioral therapy, including cognitive behavioral therapy. The primary endpoint will be safety and tolerability of CBD in these patients, as indicated by the incidence of treatment-emergent adverse events (n/% per group). Participants will be evaluated via measurement of cardiovascular parameters (heart rate, blood pressure, and cardiac rhythm and conduction on EKG), other vital signs, liver enzymes, pulse oximetry, adverse events, and pharmacokinetics. Secondary measures will include cue-induced craving, reductions in spontaneous craving, opioid withdrawal, and negative affective states.
Patients will be recruited from the Tarzana Treatment Center (TTC) in the San Fernando Valley, where buprenorphine + naloxone or methadone (as part of their treatment) and CBD (as part of this protocol) will be administered. Tarzana Treatment Centers, Inc. is a community-based, private non-profit behavioral healthcare organization located in Southern California with several agency sites, including the one in the San Fernando Valley, where this protocol will be conducted. TTC delivers drug and alcohol use treatment, has been accredited by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) since 1987, and has a workforce that includes physicians, psychologists, and nurses. TTC's substance use treatment approach includes residential programs that are overseen by a Program Director and are staffed by a clinical supervisor, operations supervisor, counselors, interns, nursing staff and 24/7 technicians. Groups and services include an education group, process group, 12-step, family group, mental health services and recreation skills. Cognitive-behavioral treatment is used in both individual and group therapy to address craving and relapse issues and in the treatment of mental health problems.
Up to 75 participants who meet all eligibility criteria will be invited to complete baseline assessments (blood and urine tests, questionnaires), and will be assigned randomly to receive CBD or placebo, corresponding to two groups of up to 30 participants each. Within each group, participants will be randomized by baseline buprenorphine plasma level (either below or ≥ 2 ng/ml).
The study will comprise three periods: 1) a screening period (\~7-14-days) while participants are stabilized on buprenorphine + naloxone; 2) a 4-week treatment period when study medication will be administered; and 3) a 4-week follow-up period after termination of treatment with the study medication. Cue-induced craving sessions will be conducted at three times: Day 0 (baseline), Day 7 (when a steady state of CBD should have been reached; half-life of CBD after oral administration is 18-32 h), and Day 28 (end of treatment).
Adherence to medication in the trial will be assured as the participant will take the test medication (CBD or placebo) under supervision daily. Blood samples will be collected to determine plasma concentrations of CBD, buprenorphine, and laboratory assessments of safety. Cue-induced craving and other measures of craving and affect will be collected repeatedly during the study.
