Psilocybin for Opioid Use Disorder (OUD)

NCT06796062 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 24-011201UG3DA062088-01
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 5

Brief Summary

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

Opioid Use Disorder

Outcome Measures

Primary Outcomes (9)

• Stage 1: The number of weeks during the 24 week follow-up period with no illicit opioid use

  Subject reports no illicit opioid use and provides a urine drug screen (UDS) negative for all classes of opioids other than methadone or other legally prescribed opioids.

  Up to 24 weeks

• Stage 1: Number of adverse events

  Up to 24 weeks

• Stage 1: Change in QTc during drug administration session

  Up to 24 weeks

• Stage 2: The number of weeks during the 24 week follow-up period with no illicit opioid use

  Up to 24 weeks

• Stage 2: Number of adverse events

  Up to 24 weeks

• Stage 2: Change in QTc during drug administration session

  Up to 24 weeks

• Stage 2: Total score on the Penn Craving Scale for Opioids

  The Penn Alcohol Craving Scale (PACS) is a 5-item questionnaire that measures an individual's craving to drink alcohol in the past week. The self-report measure includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week. Each question is scaled from 0 to 6. Low score (below 15) indicates minimal to no reported alcohol craving. Moderate score (15-20) suggests a moderate level of alcohol craving. High score (above 20) represents a high level of alcohol craving, potentially warranting further assessment and treatment

  Up to 24 weeks

• Stage 2: Score on the Negative Affect subscale of the Positive and Negative Affect Scale

  The Positive and Negative Affect Schedule (PANAS) is a self-report questionnaire that consists of two 10-item scales to measure both positive and negative affect. Each item is rated on a 5-point verbal frequency scale of 1 (not at all) to 5 (very much). Scores range from 10 - 50 for both sets of items. For the total negative score, a lower score indicates less of a negative affect.

  Up to 24 weeks

• Stage 2: Total score on the 20-item version of the Short Urgency, Premeditation, Perseverance, Sensation seeking, and Positive urgency (UPPS-P) Impulsive Behavior Scale (SUPPS-P)

  The 20-item version of the UPPS-P Impulsive Behavior Scale, also known as the SUPPS-P, is a shortened questionnaire that assesses five different dimensions of impulsivity: negative urgency, positive urgency, lack of perseverance, lack of premeditation, and sensation seeking; with four items dedicated to each dimension, totaling 20 questions in total. Responses are rated on a Likert scale (e.g., strongly disagree to strongly agree), with higher scores generally indicating a greater tendency towards impulsive behavior.

  Up to 24 weeks

Secondary Outcomes (2)

• Stage 2: Time to opioid relapse

  Up to 24 weeks

• Stage 2: Time to first illicit opioid use

  Up to 24 weeks

Study Arms (5)

Stage 1: Psilocybin 30 mg (high dose)

EXPERIMENTAL

Participants will receive a single IP administration (30 mg) session and remain under supervision at the facility for 8 hours.

Drug: Psilocybin

Stage 1: Psilocybin 20 mg (medium dose)

EXPERIMENTAL

Participants will receive a single IP administration (20 mg) session and remain under supervision at the facility for 8 hours.

Drug: Psilocybin

Psilocybin 1 mg (control)

ACTIVE COMPARATOR

Participants will receive a single IP administration (1 mg) session and remain under supervision at the facility for 8 hours.

Drug: Psilocybin

Stage 2: Psilocybin 30 mg (high dose)

EXPERIMENTAL

Participants will receive a single IP administration (30 mg) session and remain under supervision at the facility for 8 hours.

Drug: Psilocybin

Stage 2: Psilocybin 20 mg (medium dose)

EXPERIMENTAL

Participants will receive a single IP administration (20 mg) session and remain under supervision at the facility for 8 hours.

Drug: Psilocybin

Interventions

Psilocybin DRUG

One capsule (1 mg, 20 mg, or 30 mg) administered once orally

Psilocybin 1 mg (control); Stage 1: Psilocybin 20 mg (medium dose); Stage 1: Psilocybin 30 mg (high dose); Stage 2: Psilocybin 20 mg (medium dose); Stage 2: Psilocybin 30 mg (high dose)

Eligibility Criteria

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

You may qualify if:

• Are able to provide voluntary informed consent.
• Have a breath alcohol concentration ≤ 0.01% at Screening Part 2, as determined by a breath alcohol reading from a calibrated breath alcohol sensor. (Note: this criterion may be re-evaluated within the 30-day screening period. This criterion will also be reassessed at Baseline and on Day 0 (prior to IP administration). Those not meeting the criterion may be rescheduled once within 14 days if the criterion is likely to resolve within 14 days in the judgement of the Investigator).
• Are able to read, speak, and understand English, as documented during the informed consent process.
• a. Non-English speaking subjects will be excluded because the study is using only validated English-language versions of of assessment instruments.
• Are 18 to 65 years old, inclusive, at Screening Part 2.
• Have Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM 5) diagnosis of OUD, based on an evaluation performed by trained study staff using the Mini-International Neuropsychiatric Interview (MINI).
• Want to stop their use of illicit opioids.
• Are in treatment at one of participating Opioid Treatment Programs (OTPs) for at least 6 months at the time of Screening Part 2.
• Are currently prescribed a methadone dose of at least 60 mg per day.
• Methadone dosage has changed by no more than 20 mg in the past month
• Have taken methadone at least 25 out of the last 30 days
• Have had at least one urine drug screen positive for non-prescribed opioids in the past 30 days at the time of Screening Part 2
• Report using opioids by insufflation, injection, or smoking
• Are able and willing to adhere to all study requirements, including attending all study visits and treatment sessions, and completing all assessments.
• Are able to provide at least one drug screen negative for illicit opioids, cocaine, and amphetamine-type stimulants during the screening period. (Note: this criterion may be re-evaluated within the 30-day screening period. This criterion will be reassessed at Day 0 \[prior to IP administration\]. Those not meeting the criterion on Day 0 may be rescheduled within 14 days if the criterion is likely to resolve in the judgement of the Investigator.)

You may not qualify if:

• Have any medical condition that would preclude safe participation in the study, including the following, as determined by medical history review, physical examination, electrocardiogram (ECG), and clinical laboratory tests:
• Seizure disorder
• Significantly impaired liver function, defined as 1) alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 5 × upper limit of normal (ULN); 2) ALT or AST \> 3 × ULN with concomitant total bilirubin \> 2.0 × ULN; or 3) ALT or AST ≥ 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia.
• Cardiovascular disease including coronary artery disease, angina, history of arrhythmia (unless a successful ablation has been performed), heart failure, history of heart valve replacement, and history of cerebrovascular accident or transient ischemic attack.
• Uncontrolled hypertension with systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg. (Note: subjects who otherwise qualify at Screening Part 2 will have 3 opportunities to produce 1 blood pressure reading ≤ 140/90 mmHg (each reading will be collected at least 15 minutes apart). If blood pressure is consistently elevated \> 140/90 mmHg across all 3 attempts, subjects may be referred to their primary care provider for management of hypertension. Upon management of blood pressure, subjects will have an opportunity to return once within the 30 day screening window to make 3 additional attempts at a blood pressure reading ≤ 140/90 mmHg. Subjects will be considered eligible upon registering 1 blood pressure reading ≤ 140/90 mmHg during the screening period. Blood pressure will be reassessed on Day 0 prior to dosing, and must be less than or equal to 140 systolic, 90 diastolic, with resting pulse ≤ 100 (ascertained within 20 minutes of drug administration in order for the participant to receive study medication.)
• Serious ECG abnormalities present on the ECG obtained on Day -65 (e.g., evidence of ischemia, myocardial infarction, QT interval corrected for heart rate \[QTc\] prolongation (QTc \> 0.45 seconds), arrhythmia, or conduction abnormalities that increase the risk of arrhythmia.
• Hyperthyroidism
• Insulin-dependent diabetes
• Any other medical condition which precludes safe participation in the study in the medical opinion of the Investigator.
• (Note: medical history will be updated and ECG will be repeated on Day 0, prior to dosing. Those not meeting the criterion will not be randomized but may be rescheduled once within 14 days if the criterion is likely to resolve within 14 days in the judgement of the Investigator.)
• Have any of the following DSM-5 psychiatric disorders, as determined by the MINI, Psychiatric History and Psychosis Screening Questionnaire at Screening Part 2: (Note: psychiatric history will be re-evaluated on Day 0, but the MINI will not be re-administered on Day 0)
• Lifetime history of schizophrenia spectrum or other psychotic disorder.
• Lifetime history of bipolar disorder.
• Current severe major depression (based on a MINI diagnosis of major depression, current, and a MADRS score \>34 at Screening)
• Alcohol use disorder including alcohol withdrawal.

Sponsors & Collaborators

• NYU Langone Health: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (5)

Duke City Recovery Toolbox

Albuquerque, New Mexico, 87102, United States

RECRUITING

University of New Mexico

Albuquerque, New Mexico, 87106, United States

RECRUITING

StartCare

Brooklyn, New York, 11206, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

VIP Community Services, Inc

The Bronx, New York, 10457, United States

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Psilocybin

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

Study Officials

• Michael Bogenschutz, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Bogenschutz, MD

CONTACT

646-501-4026; Michael.bogenschutz@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: January 28, 2025
• Study Start: December 17, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: January 23, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Access to subject level datasets submitted and stored in the The National Institute of Mental Health (NIMH) Data Archive (NDA) will only be provided for research purposes through the completion of the NDA Data Use Certification: Office of Management and Budget (OMB) Control Number: 0925-0667. For the majority of the data available in the NDA, Data Use Certifications will only be accepted from researchers who are sponsored by an institution registered in the NIH's Electronic Research Administration (eRA) Commons with an active Federal-wide Assurance issued through the Office for Human Research Protections (OHRP). Additionally, the application must include a reason for access related to scientific investigation, scholarship or teaching, or other form of research. A Data Access Committee (DAC) composed of NIH staff with relevant expertise reviews the Data Use Certification and makes decisions about whether to grant access to subject level data.

Locations

US (5)