Exploration of Synaptotrophic Effects of Psilocybin in Opioid Use Disorder (OUD)

NCT06160284 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2000036178P30DA046345
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the synaptotrophic effects of psilocybin among medically healthy, detoxified OUD subjects. Eligible OUD participants will undergo pre- and post- psilocybin administration PET scans with the \[11C\]-UCB-J radiotracer while inpatient.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (4)

• Change in Synaptic Density

  Change in synaptic density pre- and post- psilocybin administration will be measured using \[11C\]-UCB-J PET (volume of distribution \[VT\] and binding potential \[BPND\]) among OUD. The regions of interest (ROI) will be subregions of the prefrontal cortex identified by preclinical and preliminary clinical studies.

  baseline and 1-2 weeks post treatment

• Association between VT and BPND

  Association between VT and BPND assessed to determine whether changes in VT are associated with changes in BPND.

  up to 12 weeks

• Time to relapse

  Mean number of days to relapse assessed by self- report

  up to 12 weeks

• Urine toxicology post treatment

  The mean number of positive urine tests post treatment will be assessed. Urine samples will be tested for the presence of opioids. A positive test indicates opioid usage in the last 2 weeks.

  up to 12 weeks

Secondary Outcomes (11)

• Change in vital signs- heart rate (HR)

  immediately prior to psilocybin treatment with and up to 5 hours+ post treatment

• Change in vital signs- respiratory rate (RR)

  immediately prior to psilocybin treatment with and up to 5 hours+ post treatment

• Change in vital signs- oxygen saturation

  immediately prior to psilocybin treatment with and up to 5 hours+ post treatment

• Change in vital signs- systolic blood pressure

  immediately prior to psilocybin treatment with and up to 5 hours+ post treatment

• Change in vital signs- diastolic blood pressure

  immediately prior to psilocybin treatment with and up to 5 hours+ post treatment

Study Arms (1)

Current OUD diagnosis + psilocybin

EXPERIMENTAL

All participants will receive a \[11C\]-UCB-J PET scan and fMRI with in 1-2 weeks pre and post treatment with one dose of Psilocybin. Intravenous lines will be used for phlebotomy and administration of the \[11C\]-UCB-J radiotracer. On the PET scanning day, a radial arterial catheter may be inserted.

Drug: Psilocybin

Interventions

Psilocybin DRUG

Participants will receive a single dose of psilocybin administered in 20 mg or 25 mg doses depending on the participant's weight: 20 mg (among participants \< 70 kg) or 25 mg (among participants \>70 kg). Participants will be administered psilocybin at CNRU, within 1-2 weeks of the baseline \[11C\]-UCB-J PET.

Current OUD diagnosis + psilocybin

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Voluntary, written, informed consent;
• Physically healthy by medical history, physical, neurological, ECG, and laboratory examinations;
• DSM-5 criteria for Opioid Use Disorder;
• Documented evidence (by urine toxicology) of opioid use (upon screening);
• Inpatient verified \> 1 week of abstinence;
• For females, a negative serum pregnancy (beta-HCG) test.

You may not qualify if:

• DSM-5 criteria for other substance use disorders (e.g., alcohol, cocaine, sedative hypnotics), except for nicotine (concurrent alcohol or drug use is allowed if it does not meet criteria for a substance use disorder and does not take place during inpatient stay)
• A primary DSM-5 Axis I diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or major depression, as determined by psychiatric history (Mini International Neuropsychiatric Interview, MINI), or another disorder that may interfere with the study's primary outcomes in the view of PI
• Immediate (first-degree relative) family history of formally diagnosed schizophrenia or other psychotic disorders (e.g., delusional disorder, schizoaffective disorder), or bipolar I/II disorder
• A history of significant and/or uncontrolled medical or neurological illness
• Hypertension at screening defined as: systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg;
• History of cardiovascular disease, including but not limited to clinically significant coronary artery disease, cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction, angina pectoris, coronary artery bypass graft or artificial heart valve, stroke, transient ischemic attack, or any clinically significant arrhythmia
• Any clinically significant abnormal electrocardiogram (ECG) finding, such as findings suggestive of ischemia or infarct, complete bundle branch block, atrial fibrillation or other symptomatic arrhythmia, or predominantly non-sinus rhythm, at screening
• Resting QT interval with Fridericia's correction (QTcF) ≥ 450 msec (male) or ≥ 470 msec (female) at Screening, or inability to determine QTcF interval
• Presence of risk factors for torsades de pointes, including: long QT syndrome, uncontrolled hypokalemia or hypomagnesemia, history of cardiac failure, history of clinically significant/symptomatic bradycardia, family history of idiopathic sudden death or congenital long QT syndrome, or concomitant use of a torsadogenic medication
• Current use of psychotropic and/or potentially psychoactive prescription medications considered to the investigators are likely to interfere clinically with human subject's safety (i.e., contraindicated drug-drug interactions with psilocybin) or scientifically (i.e., likely to influence or alter outcomes of the study)
• Medical contraindications to MRI procedures (e.g., ferromagnetic implants/foreign bodies, claustrophobia, etc.)
• Participation in other research studies involving ionizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits followed by the Yale PET Center (21CFR361.1).

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, 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

• Gustavo Angarita, MD, MHS

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gustavo Angarita, MD, MHS

CONTACT

(203) 974-7536; gustavo.angarita@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be medically healthy females and males with OUD.

Study Record Dates

• First Submitted: November 28, 2023
• First Posted: December 7, 2023
• Study Start: May 28, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)