Clinical TrialOpioid Use Disorder (OUD)PsilocybinPsilocybinRecruiting

Psilocybin on Brain Mechanisms of Motivation in OUD

Randomised, quadruple-masked Phase II trial (n=24) comparing single low (1 mg) vs high (25 mg) PEX010 psilocybin doses to study motivation/reward and cognitive flexibility circuits in people with opioid use disorder.

Target Enrollment
24 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This parallel, randomized study will assign 24 participants with opioid use disorder to a single oral low (1 mg) or high (25 mg) dose of PEX010 (psilocybin, Filament) to probe addiction-related brain circuitry and cognitive flexibility using fMRI.

Participants will undergo screening assessments, be resident in a treatment facility for the psilocybin phases (~two weeks), and attend approximately seven study visits including preparation therapy, baseline neuropsychological testing, dosing, post-dose therapy visits, and follow-up assessments.

Primary outcomes focus on fMRI measures of motivation/reward and inhibition circuits; secondary measures include cognitive flexibility and clinical assessments relevant to relapse risk.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Therapeutic Protocol

support

Study Arms & Interventions

Low dose

active comparator

1 mg PEX010 capsule, single dose

Interventions

  • Psilocybin1 mg
    via Oral• single dose• 1 doses total

    PEX010 (Filament) low dose

High dose

experimental

25 mg PEX010 capsule, single dose

Interventions

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

    PEX010 (Filament) high dose

Participants

Ages
18 – 60
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 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) confirmed prescription for BUP-NX in a drug monitoring program and stable dose ≥1 week and plan to continue BUP-NX ≥12 weeks; or 2) received Sublocade® injection within past month; or 3) currently on methadone maintenance therapy on a consistent dose ≥1 week. Urine must be buprenorphine-positive (for BUP-NX) or methadone-positive (for methadone) at screening.
  • Physically healthy males and females, aged 18–60, meeting DSM-5 criteria for opioid use disorder and voluntarily seeking treatment.
  • Females must be non-pregnant and non-lactating; those of childbearing potential must agree to use acceptable contraception during study participation.
  • Subject must read at or above eighth grade level and speak, understand, and write in English.
  • IQ ≥80.

Exclusion Criteria

  • Exclusion Criteria:
  • Participation in clinical trial and receipt of investigational drug(s) during 30 days prior, except as approved by PI.
  • Current DSM-5 moderate to severe SUD for any substance other than cocaine, alcohol, marijuana or nicotine. Any prior use of psilocybin is exclusionary. Comorbid AUD accepted if not requiring medicated detoxification.
  • Current or lifetime DSM-5 criteria for schizophrenia or any psychotic disorder, organic mental disorder, or first-degree family history of these disorders; includes HPPD.
  • Current DSM-5 criteria for bipolar disorder.
  • Meets current DSM-5 criteria for severe Major Depressive Disorder (mild/moderate MDD and stable remission allowed if no suicidal risk and no ongoing antidepressant therapy).
  • Current or past month active suicidal ideation or lifetime history of serious suicidal attempt.
  • Current or past significant trauma with elevated PTSD symptoms at PI discretion.
  • Any other psychiatric disorder that in the PI's opinion interferes with completion or increases risk.
  • Evidence of significant hepatocellular injury (bilirubin >1.3) or pulmonary, endocrine, cardiovascular, renal (creatinine clearance ≤60 ml/min) or gastrointestinal disease, current HIV infection, or AST/ALT >3.5x ULN (Gilbert's syndrome exempt for bilirubin).
  • History of serious head trauma with loss of consciousness >3 minutes or associated skull fracture/intracranial bleeding or abnormal MRI.
  • Seizure disorder or history of seizures not related to withdrawal (excluding childhood febrile seizures).
  • Presence of magnetically active prosthetics incompatible with MRI unless radiologist confirms safe; x-ray may be required.
  • Claustrophobia or other condition preventing lying in MRI for ~60 minutes.
  • Non-removable skin patches (PI discretion).
  • Receipt of medication that could interact adversely with psilocybin within time of administration per Medical Director.
  • Need for treatment with psychoactive medications (exception: occasional Benadryl for sleep).
  • Significant cardiovascular conditions including coronary artery disease, congenital long QT, hypertrophy, ischemia, CHF, prior MI, tachycardia >100 bpm, clinically significant ECG abnormality (QTcF >450 ms considered significant), artificial heart valve, or other conditions judged unsuitable by Medical Director.
  • Elevated blood pressure at screening or baseline as defined in protocol.

Study Details

Locations

University of Pennsylvania — Philadelphia, Pennsylvania, United States

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