Outpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder

Inclusion criteria

• Age 21-70 years
• Have given written informed consent
• Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for OUD
• No antidepressant medications for approximately 5 half-lives prior to enrollment
• Willing to undergo buprenorphine induction or has undergone buprenorphine induction in the past 3 weeks
• Reports previous buprenorphine maintenance
• Urine toxicology positive for an opioid
• Has access to stable housing
• Can read, write, and speak English fluently
• Be judged by study team clinicians to be at low risk for suicidality
• Have limited recent use of classic psychedelics (no use in the past year).
• Expresses a desire for sustained recovery from disordered opioid use.

Exclusion criteria

• General medical exclusion criteria:
• Women who are pregnant, nursing, or not practicing an effective means of birth control
• Cardiovascular conditions: hypertension with resting blood pressure systolic \>139 or diastolic \>89, angina, heart rate \> 99, a clinically significant ECG abnormality (e.g., atrial fibrillation, QTc \> 450), transient ischemic attack (TIA) in the last 6 months, stroke, peripheral or pulmonary vascular disease, cardiac valvulopathy
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• Currently taking on a daily basis any medications (including herbal substances and supplements) with a central nervous system effect on serotonin, including serotonin-reuptake inhibitors and monoamine oxidase (MAO) inhibitors.
• For individuals who have intermittent or as needed (PRN) use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
• Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, or UDP-glucuronosyltransferase (UGT)1A9 inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag.
• Currently taking methadone or naltrexone.
• Currently on longstanding buprenorphine maintenance (3+ weeks post-induction)
• Naïve to buprenorphine
• Reports of significant adverse events (severe withdrawal, medical complications, hospitalization) during previous buprenorphine induction(s).
• Unable or unwilling to discontinue acid-reducing agents or major metabolizing enzyme inhibitors for 5-half lives prior to the experimental dosing session.
• Have a seizure disorder, multiple sclerosis, history of significant head trauma, central nervous system (CNS) tumor, movement disorders or any neurodegenerative condition.
• Morbidly obese (\>100 lbs above ideal body weight, or Body Mass Index (BMI) \>=40, or BMI \>=35 with high blood pressure or diabetes)
• Body weight \< 45 kg
• Be judged by a study team clinician to be at risk for moderate or severe alcohol or benzodiazepine withdrawal.
• Allergic to buprenorphine
• For blood samples, the following lab values will be exclusionary: transaminases greater than x2 the upper limit of normal lab reference range, hemoglobin less than 11 g/d, and creatinine clearance \< 40 ml/min using the Cockraft and Gault equation. Psychiatric Exclusion Criteria:
• Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), Bipolar I or II Disorder or Major Depression with psychotic features.
• Have a first or second degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I or II disorder.