Clinical TrialOpioid Use Disorder (OUD)PsilocybinRecruiting

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

Single-group study (n=12) of a single oral psilocybin dose (20–25 mg, weight-based) assessing synaptotrophic effects with pre/post [11C]-UCB-J PET and fMRI in detoxified individuals with opioid use disorder (OUD).

Target Enrollment
12 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

Single-center, single-group (n=12) study at Yale evaluating synaptic density changes after a single oral psilocybin dose with paired [11C]-UCB-J PET and resting-state fMRI pre- and 1-2 weeks post-dosing.

Participants are medically healthy, detoxified inpatients with opioid use disorder who receive inpatient detoxification, baseline PET, psilocybin administration (20 mg if <70 kg; 25 mg if ≥70 kg), overnight observation and may be discharged the day after dosing with outpatient urine toxicology twice weekly prior to the second PET.

Outcomes include changes in [11C]-UCB-J PET measures of synaptic density, resting-state connectivity on fMRI, and exploratory behavioural correlations; imaging performed at the Yale PET Center with anatomical MRI for registration and partial volume correction.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Study Arms & Interventions

Psilocybin

experimental

Single-group study: single oral psilocybin dose (weight-based 20 or 25 mg) with pre/post [11C]-UCB-J PET and fMRI.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    20 mg if <70 kg; 25 mg if ≥70 kg. [11C]-UCB-J radiotracer administered IV for PET; arterial line may be used.

Participants

Ages
21 – 55
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 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.

Exclusion Criteria

  • Exclusion Criteria:
  • 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.)
  • Arterial Line Exclusion: Blood donation within eight weeks of the start of the study
  • Arterial Line Exclusion: History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto)
  • 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).

Study Details

  • Status
    Recruiting
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment12 participants
  • Timeline
    Start: 2024-01-01
    End: 2027-01-31
  • Compound
    Psilocybin
  • Topic
    Opioid Use Disorder (OUD)

Locations

Yale University — New Haven, Connecticut, United States

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