Actively Recruiting

Phase 2
Age: 18Years - 65Years
All Genders
NCT06796062

Psilocybin for Opioid Use Disorder (OUD)

Led by NYU Langone Health · Updated on 2026-01-23

480

Participants Needed

5

Research Sites

163 weeks

Total Duration

On this page

Sponsors

N

NYU Langone Health

Lead Sponsor

N

National Institute on Drug Abuse (NIDA)

Collaborating Sponsor

AI-Summary

What this Trial Is About

This is a double-blind, adaptive, 2-stage, multi-site, phase 2 randomized controlled clinical trial designed to evaluate effects of moderate and high dose psilocybin, relative to low-dose psilocybin control, in OUD patients who continue to use illicit opioids in spite of adherence to standard-of-care treatment with methadone. Up to 480 participations will be consented to yield 240 randomized participants. This study is part of the NIH HEAL Initiative (https://heal.nih.gov/). In Stage 1, subjects will be randomly assigned to one of three groups: psilocybin 30 mg (high dose), psilocybin 20 mg (medium dose), and psilocybin 1 mg (control condition). By the end of Stage 1, an interim statistical analysis will be performed. The study will proceed to Stage 2 if at least one of the active dosages of psilocybin demonstrates 1) acceptable safety, based on analysis of safety data from Stage 1; and 2) conditional power of at least 25%, based on effect size estimates for the primary opioid use outcome (weeks of biologically-verified abstinence during 24 weeks of follow-up). Using a priori decision rules, the interim analysis will determine which of the active treatment groups (30 mg, 20 mg, or both) will be retained in Stage 2 of the trial. Stage 2 will continue the study, using the same treatment and assessment protocols, but retaining only the active dosage or dosages with a high probability of demonstrating efficacy relative to the psilocybin 1 mg control condition. The primary aims are to 1) Evaluate safety and efficacy outcomes in Stage 1 subjects in order to optimize design of the Stage 2, 2) Determine whether treatment with a single high (30 mg) or medium (20 mg) dose of psilocybin improves OUD treatment outcomes, relative to psilocybin 1 mg (control condition), in patients who continue to use illicit opioids despite adherence to methadone treatment, 3) Evaluate the effects of high-dose psilocybin and medium dose psilocybin on self-reported OUD-related neuropsychopathology, and 4) Identify likely responders to psilocybin treatment by using machine learning to model post-treatment OUD outcomes, based on pretreatment characteristics including all relevant clinical data, evaluations, and questionnaires.

CONDITIONS

Official Title

Psilocybin for Opioid Use Disorder (OUD)

Who Can Participate

Age: 18Years - 65Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Able to give voluntary informed consent
  • Breath alcohol concentration at or below 0.01% at screening and baseline
  • Able to read, speak, and understand English
  • Between 18 and 65 years old at screening
  • Diagnosed with Opioid Use Disorder using MINI evaluation
  • Want to stop using illicit opioids
  • In treatment at a participating Opioid Treatment Program for at least 6 months
  • Currently prescribed methadone dose of at least 60 mg per day
  • Methadone dose changed by no more than 20 mg in past month
  • Taken methadone at least 25 of the last 30 days
  • At least one urine drug screen positive for non-prescribed opioids in past 30 days
  • Use opioids by insufflation, injection, or smoking
  • Able and willing to follow all study requirements and visits
  • Able to provide at least one negative drug screen for illicit opioids, cocaine, and stimulants during screening
  • Agree to avoid non-prescribed psychotropic substances or illicit drugs for 72 hours before dosing, with some exceptions
  • Agree to avoid non-prescription medications and supplements for 1 week before dosing unless approved
  • Able to swallow capsules
  • Agree to practice effective contraception as specified
  • Have a family member or friend to assist with transportation and daily activities after dosing
  • Able to provide adequate contact information
Not Eligible

You will not qualify if you...

  • Medical conditions that prevent safe participation, including seizure disorder, severe liver impairment, cardiovascular disease, uncontrolled high blood pressure, serious ECG abnormalities, hyperthyroidism, insulin-dependent diabetes, or other conditions judged unsafe
  • DSM-5 psychiatric disorders such as schizophrenia spectrum, bipolar disorder, severe major depression, alcohol use disorder, or more than mild opioid withdrawal
  • Active suicidal thoughts with intent or suicide attempt within past 12 months
  • Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type 1
  • History of hallucinogen use disorder or persisting perception disorder
  • Hallucinogen use within past year
  • More than 25 lifetime uses of classic psychedelics
  • Currently incarcerated or pending legal actions preventing study participation
  • Taking prohibited medications or supplements that have not been stopped as required
  • Known allergy or hypersensitivity to psilocybin or study materials
  • Allergy or contraindication preventing safe treatment of acute symptoms during dosing session
  • Any other medical, psychiatric, or social condition likely to interfere with study adherence or safety as judged by the investigator

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 5 locations

1

Duke City Recovery Toolbox

Albuquerque, New Mexico, United States, 87102

Actively Recruiting

2

University of New Mexico

Albuquerque, New Mexico, United States, 87106

Actively Recruiting

3

StartCare

Brooklyn, New York, United States, 11206

Actively Recruiting

4

NYU Langone Health

New York, New York, United States, 10016

Actively Recruiting

5

VIP Community Services, Inc

The Bronx, New York, United States, 10457

Actively Recruiting

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Research Team

M

Michael Bogenschutz, MD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

DOUBLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

5

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Psilocybin for Opioid Use Disorder (OUD) | DecenTrialz