Psilocybin for Opioid Use Disorder (OUD)

This double-blind, adaptive, two-stage, multi-site, Phase II randomised controlled trial (n=240) will evaluate the effects of moderate and high-dose psilocybin (20-30mg), relative to a low-dose control (1mg), in patients with opioid use disorder (OUD) who continue to use illicit opioids despite adherence to methadone treatment.

Sponsored by NYU Langone Health, the study aims to assess the safety and efficacy of psilocybin as an adjunctive treatment for OUD. Participants will be randomly assigned to receive a single oral dose of either 30 mg (high dose), 20 mg (medium dose), or 1 mg (control condition). An interim statistical analysis will determine whether the study proceeds to Stage 2, retaining only the most effective active dose(s).

The primary outcomes include safety assessments and opioid abstinence, measured through biologically verified markers over 24 weeks. Secondary objectives involve evaluating psilocybin’s impact on OUD-related neuropsychopathology and identifying predictors of treatment response using machine learning. The trial will take place across multiple sites in New York and New Mexico, with an estimated completion date of September 2029.

Trial 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. 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.

Trial Number NCT06796062

Data attribution

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