Psilocybin on Brain Mechanisms of Motivation in OUD

NCT06810310 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 857697
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to test addiction-related brain circuitry (motivation/reward and inhibition) as well as neurocognitive circuitry prior to and following low or high dose psilocybin (PEX010 from Filament). Using fMRI, we will examine brain circuits relevant to drug relapse as well as neurocognitive flexibility circuits in individuals with opioid use disorder. We will randomize 24 males and females, aged 18 - 60, in the greater Philadelphia area, to either 1mg or 25 mg of psilocybin. Participants will

1. 1.come to our offices for screening visits - these are assessments, interviews, and some medical tests (such as a history and physical, as well as a fasting blood draw) to help us determine eligibility for our study.
2. 2.If not already in an inpatient setting, participants be admitted to an inpatient program for the duration of the psilocybin phases - about two weeks. During this time, they will be brought to our offices at 3535 Market Street in Philadelphia for about 7 visits. These visits include pre-dose psilocybin preparation therapy, baseline assessments and neuropsychological testing, psilocybin dosing, post dose therapy visits, and post dose assessments.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (2)

• Brain measure of GO domain

  Using fMRI, we will measure the brain response to 500ms evocative cues and 6 second drug-related videos that trigger drug desire

  One week pre dose and one week post dose

• Behavioral measure of GO domain

  Using a the Affect Bias behavioral task, we will measure the affective bias to opioid and other evocative visual cues.

  One week pre dose and one week post dose

Secondary Outcomes (2)

• Brain measure of STOP domain

  weeks 1 through 8 (outcomes phase)

• Behavioral measure of STOP domain

  One week pre dose and one week post dose

Study Arms (2)

Low dose psilobyin

ACTIVE COMPARATOR

1 mg PEX010 capsule, single dose

Drug: psilocybin (low dose)

High dose psilocybin

EXPERIMENTAL

25 mg PEX010 capsule, single dose

Drug: Psilocybin (high dose)

Interventions

Psilocybin (high dose) DRUG

PEX010 is the psilocybin produced by Filament

High dose psilocybin

psilocybin (low dose) DRUG

1mg psilocybin, produced by Filament

Low dose psilobyin

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.
• 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, this includes a history of hallucinogen-persistent perception disorder (HPPD)
• 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 significant hepatocellular injury as evidenced by elevated bilirubin levels (greater than 1.3), or, pulmonary (e.g., COPD), endocrine, cardiovascular, renal (creatinine clearance less than or equal to 60ml/min) or gastrointestinal disease (e.g., Crohn's 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). Patients with documented Gilbert's syndrome will be included regardless of bilirubin levels.
• 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.
• Needs treatment with any psychoactive (e.g., anti-depressants) medications (with the exception of Benadryl used sparingly, if necessary, for sleep).

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

Anna Rose Childress, PhD

CONTACT

215-746-1803; childress@pennmedicine.upenn.edu

Megan Ivey, MS

CONTACT

215-746-7712; megan.ivey@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Associate Professor, Department of Psychiatry

Study Record Dates

• First Submitted: January 30, 2025
• First Posted: February 5, 2025
• Study Start: December 22, 2025
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)