Inpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder

NCT ID: NCT06005662

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2027-04-30
• Study Completion Date: 2028-07-31

Brief Summary

This study will examine the effect of a single high dose of psilocybin therapy (30 mg) versus a very low dose (1 mg) as an adjunctive therapy to individuals undergoing standard-of-care buprenorphine treatment for Opioid use disorder (OUD). Effects of adjunctive psilocybin will be determined for longitudinal outcomes of opioid abstinence, compliance with buprenorphine maintenance, quality of life, and mood.

Detailed Description

The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis. Use of buprenorphine follow standard of care, and the investigators are investigating the additive power of adjunctive psilocybin to enhance opioid abstinence, treatment adherence, quality of life, and mood.

The study will consist of a brief (6-8 day) inpatient phase for standard buprenorphine induction as well as experimental psilocybin administration, an 8-week outpatient phase involving standard buprenorphine maintenance and experimental follow-up meetings, and long-term follow-up sessions for 4 months after. During the inpatient phase, participants will be inducted onto sublingual (SL) buprenorphine (using a buprenorphine/naloxone combination product) while admitted to the Bayview Clinical Research Unit. During this time, participants will also undergo 2-3 preparatory sessions, and will undergo an experimental drug administration session under supportive conditions, during which the participants will receive either a very low dose (1 mg) or a single high (30mg) oral dose of psilocybin under double-blind conditions. At the end of the inpatient phase, participants will be discharged to complete the 8-week outpatient phase, during which participants will undergo visits at 1, 2, 3, 4, 6, and 8 weeks post-dosing session for monitoring of adverse events, clinical status, treatment adherence, and to receive a weekly supply of buprenorphine. All buprenorphine procedures will be open label and will follow standard-of-care practices.

This trial utilizes a Bayesian sequential methodology, employing a maximum sample size of 90 participants and calculating Bayes factors (starting at 20 participants and assessed after each 10) to assess evidence for the null and experimental hypotheses, enabling potential early stopping for efficacy or futility based on predetermined thresholds (Bayes factor of 6 and 1/6). This will be calculated for the primary outcome of opioid abstinence at 8-weeks

Conditions

Opioid Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High-dose psilocybin + buprenorphine

High-dose psilocybin (30 mg) session following standard-of-care buprenorphine induction

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis

Very low-dose psilocybin + buprenorphine

Very low dose psilocybin session (1 mg) following standard-of-care buprenorphine induction

Group Type: ACTIVE_COMPARATOR

Psilocybin

Intervention Type: DRUG

The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis

Interventions

Psilocybin

The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis

Intervention Type: DRUG

Other Intervention Names

Buprenorphine

Eligibility Criteria

Inclusion Criteria

• 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.

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 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
• 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.
• 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)
• Body weight < 45 kilograms
• Be judged by a study team clinician to be at risk for moderate or severe alcohol or benzodiazepine withdrawal.
• Allergic to buprenorphine or hydromorphone
• 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.

• 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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandeep Nayak, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins School of Medicine

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

IRB00344281

Identifier Type: -

Identifier Source: org_study_id