Psilocybin for Opioid Use Disorder in Two Adults Stabilized on Buprenorphine: A Technical Report on Study Modifications and Preliminary Findings

Background: Psilocybin has demonstrated promising clinical outcomes for nicotine and alcohol use disorders, yet its potential clinical utility in the treatment of opioid use disorder (OUD) remains unreported in modern literature. This technical report presents methodological considerations and preliminary data from a safety-feasibility trial examining the interaction between psilocybin and buprenorphine in two adults diagnosed with OUD. Procedures: Two adults meeting eligibility criteria for long-term stabilization of buprenorphine/naloxone (≥6 months) enrolled and underwent two psilocybin dosing sessions in a supportive setting. Preliminary data pertaining to the safety, clinical outcomes, and subjective effects of psilocybin were collected. Main Findings: Two participants received psilocybin and completed all study visits. Feasibility considerations were identified, including limitations in provider-based recruitment strategies, participant accessibility, flexibility of the study schedule, and initial eligibility criteria. There were no serious adverse events or significant baseline changes on measures of opioid craving or withdrawal, and the subjective effects associated with psilocybin were consistent with previous studies. Principal Conclusions: Coadministration of psilocybin and buprenorphine was safely tolerated and did not demonstrate contraindicating effects vis-à-vis effectiveness of buprenorphine or the subjective effects of psilocybin. Challenges in feasibility led to modifications in the sample population and eligibility criteria and strategies to improve accessibility, minimize burden, and enhance overall generalizability.clinicaltrials.gov ID: NCT05242029.