Adjunctive Effects of Psilocybin and a Formulation of Buprenorphine

Inclusion Criteria: * Aged 21 to 65 years * Able to read, speak, and understand spoken and written English * Diagnosis of moderate or severe opioid use disorder (OUD) * Current opioid misuse, with misuse occurring on at least 10 of the last 30 days (at least 5 of last 30 days if already on buprenorphine/naloxene. See exclusion #1). Misuse will be defined as either: 1. Use of illicit opioids, such as heroin or street fentanyl; or use of a prescription opioid (such as oxycodone, morphine, or hydrocodone) through a route (e.g. nasal, injected) other than FDA approved , and/or 2. Use of a prescription opioid for a purpose (e.g. intoxication, anxiety relief) other than that for which it was prescribed. * Able to achieve stable daily dose of a buprenorphine-naloxone formulation that controls opioid withdrawal symptoms * Persons of childbearing potential must agree to practice an effective means of contraception throughout their participation in the study, beginning at screening and throughout follow-up * Ability and willingness to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and evaluations * Healthy kidney function * Able to provide contact information for a local support person. This person must be available during both 24-hour treatment and observation periods, and willing to provide the participant social/emotional support the day after each treatment and as needed during the dosing day and/or overnight observation period. Exclusion Criteria: * Currently prescribed and has taken buprenorphine or buprenorphine formulation (e.g., Suboxone®) for over four months immediately prior to initial study contact * Currently receiving pharmacotherapy of any duration with methadone * Current participation in a drug treatment court program or other legal supervision. Individuals who are under legal supervision will be advised that participating in this study could potentially violate terms of probation, parole, or extended supervision. Contact information for the individual's community supervision officer must be collected to confirm whether study participation may impact the potential participant's status on probation or parole * Inadequately treated hypertension * Current acute coronary syndrome or angina * Evidence of ischemic disease, cardiac conduction defects, and/or ventricular arrhythmias on screening ECG * History of heart transplant * Current insulin dependence, due to Type I or Type II diabetes * Urine drug test containing non-prescribed drugs of abuse * Any finding(s), based on the screening process, that the PI feels makes the study unsuitable for the participant