Outpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder

NCT06067737 | Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB00399750
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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 outpatient buprenorphine treatment for Opioid use disorder (OUD). The participants will have previously undergone buprenorphine induction before. Effects of adjunctive psilocybin will be determined for longitudinal outcomes of opioid abstinence, compliance with outpatient buprenorphine maintenance, quality of life, and mood.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (4)

• Number of Participants Abstinent from Opioid Use

  Non-buprenorphine opioid abstinence as verified by urine toxicology at each visit and Timeline Follow Back (TLFB). These will be combined to assess opioid abstinence for each participant. These will be assessed at the 8-week timepoint for the previous 3-weeks. Missing values will be presumed positive. Timeline Follow Back (TLFB) for Opioids: This is a self-report of drug use per day. This procedure asks participants to retrospectively quantitate their use of drugs. Greater numbers indicate more days using a substance, smaller numbers or zeros mean less or no days using a substance Urine toxicology: Urine samples will be collected at each study visit and screened broadly for illicit drug use including opioids via an outside medical laboratory. Quantitative buprenorphine levels will also be collected following induction to gauge whether buprenorphine is being taken. Participants must meet both criteria to be considered abstinent.

  Up to 8 weeks

• Treatment retention

  Treatment retention at 8 weeks, as indicated by participants making all follow-up visits, indicating they are taking buprenorphine and with urine toxicology positive for buprenorphine.

  8 weeks

• Number of Days Illicit Opioids Used

  Number of Days Illicit Opioids Used, as indicated by participant self-report and urine toxicology results

  8 weeks

• Number of Negative Urine Toxicologies

  Number of Negative Urine Toxicologies, as indicated by results from weekly urine toxicologies collected for eight weeks

  Weekly up to 8 weeks

Secondary Outcomes (4)

• Quality of Life as assessed by the World Health Organization Quality of Life Brief Version (WHOQOL-BREF)

  8 weeks

• Depression as assessed by the Beck Depression Inventory II (BDII)

  8 weeks

• Anxiety as assessed by the State-Trait Anxiety Inventory (STAI)

  8 weeks

• Number of Participants Abstinent from Other Drug Substances

  8 weeks

Study Arms (2)

High-dose psilocybin + buprenorphine

EXPERIMENTAL

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

Drug: Psilocybin

Very low-dose psilocybin + buprenorphine

ACTIVE COMPARATOR

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

Drug: Psilocybin

Interventions

Psilocybin DRUG

High-dose psilocybin (30 mg) session will be administered following standard-of-care outpatient buprenorphine induction to evaluate its effect on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis.

Also known as: buprenorphine

High-dose psilocybin + buprenorphine

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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 (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

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Center for Psychedelic and Consciousness Research

Baltimore, Maryland, 21224, United States

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Psilocybin; Buprenorphine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Sandeep Nayak, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew L Gaddis, MD

CONTACT

410-550-0048; gaddis@jhmi.edu

Sandeep Nayak, MD

CONTACT

410-550-0048; smn@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and study team will be masked/blinded to intervention.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 outpatient buprenorphine induction

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 5, 2023
• Study Start: February 8, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)