Psilocybin for Opioid Use Disorder (OUD)

Conditions

• Opioid Use Disorder

Eligibility Criteria

Sex

ALL

Age

18 Years - 65 Years

Healthy Volunteers

Not accepted

Interventions

• Psilocybin — DRUG
  One capsule (1 mg, 20 mg, or 30 mg) administered once orally

Study Details

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.

Key Dates

Start date

Dec 17, 2025

Status verified

Dec 2025

Primary completion

Feb 28, 2029

Completion

Feb 28, 2029

Study Design

Enrollment

480 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Stage 1: Psilocybin 30 mg (high dose)
  Participants will receive a single IP administration (30 mg) session and remain under supervision at the facility for 8 hours.
• Experimental: Stage 1: Psilocybin 20 mg (medium dose)
  Participants will receive a single IP administration (20 mg) session and remain under supervision at the facility for 8 hours.
• Active Comparator: Psilocybin 1 mg (control)
  Participants will receive a single IP administration (1 mg) session and remain under supervision at the facility for 8 hours.
• Experimental: Stage 2: Psilocybin 30 mg (high dose)
  Participants will receive a single IP administration (30 mg) session and remain under supervision at the facility for 8 hours.
• Experimental: Stage 2: Psilocybin 20 mg (medium dose)
  Participants will receive a single IP administration (20 mg) session and remain under supervision at the facility for 8 hours.

Primary Outcome Measure

Stage 1: The number of weeks during the 24 week follow-up period with no illicit opioid use [ Time Frame: Up to 24 weeks ]

Central Contacts

• Michael Bogenschutz, MD
  646-501-4026
  [email protected]

Locations (5)

Find similar trials in Albuquerque, NM

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