Inpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder

Who can take part

• Age 21-70 years
• Have given written informed consent
• Meet diagnostic criteria for OUD
• No antidepressant medications for approximately 5 half-lives prior to enrollment
• Not currently taking methadone, buprenorphine or naltrexone
• 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

Who cannot take part

• 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 inhibitors; o For individuals who have intermittent or as needed 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 medicines such as phenytoin, regorafenib, eltrombopag
• Currently taking buprenorphine, methadone, or naltrexone
• Unable or unwilling to discontinue acid-reducing agents or major metabolizing enzyme inhibitors for 5-half lives prior to the experimental dosing session
• Cardiovascular conditions: hypertension with resting blood pressure systolic >139 or diastolic >89, angina, heart rate > 99, a clinically significant electrocardiogram abnormality (e.g., atrial fibrillation), Transient Ischemic Attack or Stroke in the last 6 months, peripheral or pulmonary vascular disease, cardiac valvulopathy
• Epilepsy
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• Have a seizure disorder, multiple sclerosis, history of significant head trauma, nervous system tumor, movement disorders or any neurodegenerative condition
• Morbidly obese (>100 pounds above ideal body weight, or Body Mass Index (BMI) >=40, or BMI >=35 with high blood pressure or diabetes)
• Allergic to buprenorphine or hydromorphone
• Current or past history of meeting diagnostic 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
• 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; Psychiatric Exclusion Criteria:
• General medical exclusion criteria:
• Women who are pregnant, nursing, or not practicing an effective means of birth control
• Body weight < 45 kilograms
• Be judged by a study team clinician to be at risk for moderate or severe alcohol or benzodiazepine withdrawal