Wellcome Leap Psilocybin for OUD

NCT06786325 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 856720
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators will recruit 36 individuals on MAT for OUD for a double-blind, placebo-controlled design to determine whether PEX010 (25-mg/d) shows preliminary efficacy on neural correlates of neurocognition and on clinical outcomes. Participants will be randomized to either (single dose) 25-mg (PEX010-25 group) or 1-mg (PPEX010-1 group) PEX010 in a 2:1 ratio. Brain and behavioral testing sessions will precede Psilocybin (PSI) dosing day by 24-48 hours and will follow PSI dosing by 1 week. After an initial 6 phases, participants will come into the lab to submit a urine screen 2x/week and to complete a short survey in order to collect data on drug use, MAT adherence, and mental health symptoms. The investigators hypothesize the PEX010-25 (vs. PEX010-1) group will have better clinical outcomes (e.g., lower average percent positive urine drug screens, more late relapses, higher MAT adherence). There are research follow ups every three months out to one year post dose.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (2)

• Percent of patients in each arm having urine drug screens positive for opioids

  Urine drug screen (UDS), percent positive illicit opioids (e.g., fentanyl) during the 8-week outpatient phase, calculated by taking number of positive detections by total number of opportunities to submit UDS (2 per week for 8 weeks equals 16 opportunities). This variable will be a single, continuous variable measured as a percentage. As well as self-reported drug use via TLFB.

  weeks 1 through 8 (outcomes phase)

• MAT adherence as recorded by self report and corroborated POC UDS tests during the twicely weekly outcomes phase visits

  Self-reported use of prescribed MAT for OUD via TLFB; MAT metabolites (e.g., buprenorphine, methadone) will be detectable in twice-weekly urine drug screens, calculated by taking number of positive detections of MAT metabolites divided by the number of opportunities to submit a UDS

  weeks 1 through 8 outpatient phase

Study Arms (2)

High Dose Psilocybin

EXPERIMENTAL

25 mg PEX010 capsule, single dose

Drug: Psilocybin

Low Dose Psilocybin

ACTIVE COMPARATOR

1 mg PEX010 capsule, single dose

Drug: Psilocybin

Interventions

Psilocybin DRUG

PEX010 is the Psilocybin produced by Filament

Also known as: PEX010

High Dose Psilocybin; Low Dose Psilocybin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• An informed consent document voluntarily signed and dated by the subject.
• Voluntary enrollment in the residential addiction treatment facility
• Intention on residing within residential addiction treatment facility for the duration of the Pre/Post PSI dosing period.
• Either 1) have a confirmed prescription for BUP-NX in a drug monitoring program database, have been on a stable dose of BUP-NX for at least one week, and plan to continue taking BUP-NX for at least 12 weeks or 2) have received an injection of Sublocade® within the past month, or 3) are currently on methadone maintenance therapy and on a consistent dose for at least a week. Subject must provide a urine that is buprenorphine-positive (for subjects taking buprenorphine) or methadone-positive (for subjects taking methadone), during screening.
• Physically healthy males and females, aged 18-60 years old, who meet criteria for opioid use disorder (based on DSM-5 criteria) as their primary diagnosis and are voluntarily seeking treatment.
• Females must be non-pregnant and non-lactating. Additionally, for females with childbearing potential (i.e., have not undergone sterilization via hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year post-menopausal) participants must agree to use an acceptable form of contraception (e.g. abstinence, intrauterine device, hormonal injection, hormonal implant, hormonal patch/ring/pill, condoms (male or female), etc.) during study participation and to continue its use for the duration of the study
• Subject must read at or above eighth grade level and speak, understand, and write in English.
• IQ score of greater than or equal to 80.

You may not qualify if:

• Participation in clinical trial and receipt of investigational drug(s) during 30 days prior to the research study, except as explicitly approved by the Principal Investigator.
• Currently meets DSM-5 criteria for moderate to severe substance use disorder for any substance other than cocaine, alcohol, marijuana or nicotine as determined by the semi-structured interview. Patients with comorbid Alcohol Use Disorder will be accepted if their alcohol use disorder is not severe enough to require a medicated alcohol detoxification.
• Meets current or lifetime DSM-5 criteria for schizophrenia or any psychotic disorder, or organic mental disorder or has a first-degree family history of these disorders
• Meets current DSM-5 criteria for bipolar disorder
• Meets current DSM-5 criteria for severe Major Depressive Disorder (mild and moderate MDD as well as in stable remission are allowed if no suicidal risk and no ongoing antidepressant therapy).
• Current or past significant trauma exposure with elevated Post-Traumatic Stress symptoms at the discretion of the PI.
• Presence of any another psychiatric disorder that in the opinion of the PI will interfere with completion of the study or place the patient at heightened risk through participation in the study.
• Current or past month active suicidal ideations or lifetime history of serious suicidal attempt.
• Has evidence of a history of significant active hepatitis, significant hepatocellular injury as evidenced by elevated bilirubin levels (greater than 1.3), or, pulmonary, endocrine, cardiovascular, renal (creatinine clearance less than or equal to 60ml/min) or gastrointestinal disease, or current HIV infection, and/or clinically significant levels (over 3.5x upper limit of normal) of aspartate aminotransferase (AST), and serumalanine aminotransferase (ALT).
• History of serious head trauma or injury causing loss of consciousness that lasted more than 3 minutes and/or associated with skull fracture or intracranial bleeding or abnormal MRI.
• Seizure disorder or history of seizures not related to drug or alcohol withdrawal (excluding childhood febrile seizure).
• Presence of magnetically active prosthetics, plates, pins, broken needles, permanent retainer, bullets, etc. in patient's body (unless a radiologist confirms that its presence is unproblematic). An x-ray may be obtained to determine eligibility.
• Claustrophobia or other medical condition that disables the participant from lying in the MRI for approximately 60 minutes.
• Non-removable skin patches, at discretion of PI.
• Has received medication that could interact adversely with psilocybin within the time of administration of study agent based on the Medical Director's guidance.

Sponsors & Collaborators

• Anna Rose Childress, Ph.D.: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, 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

Central Study Contacts

Megan Ivey, MS

CONTACT

2157467712; megan.ivey@pennmedicine.upenn.edu

Paul Regier, PhD

CONTACT

2157463706; pregier@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Professor

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: January 22, 2025
• Study Start: October 7, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)