Clinical TrialAlcohol Use Disorder (AUD)PsilocybinPlaceboCompleted

A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence

Several lines of evidence suggest that classic hallucinogens such as psilocybin can facilitate behaviour change in addictions such as alcohol dependence. The investigation is a multi-site, double-blind, active-controlled trial (n=95, 47 per group) contrasting the acute and persisting effects of psilocybin to those of diphenhydramine (placebo) in the context of outpatient alcoholism treatment.

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

Detailed Description

Randomized, quadruple-blind, parallel-group Phase II trial comparing psilocybin-assisted therapy to diphenhydramine control in participants with alcohol dependence; manualized Motivational Enhancement and Taking Action (META) therapy provided across the double-blind period.

Psilocybin is given in two 8-hour outpatient dosing sessions at weeks 4 and 8 (initial dose 25 mg/70 kg; second session may be 25, 30, or 40 mg/70 kg). Diphenhydramine comparator given 50 mg (may increase to 100 mg) on the same schedule. Outcomes include drinking behavior up to 50 weeks after first administration (total follow-up ~54 weeks), craving, self-efficacy, motivation, mood, and spiritual measures.

Extensive screening, medical safety monitoring, and post-session debriefing/integration are included; participants meeting interim safety criteria may be offered an additional open-label psilocybin session after the double-blind period.

Study Protocol

Preparation

sessions

Dosing

2 sessions
480 min each

Integration

sessions

Therapeutic Protocol

mi

Study Arms & Interventions

Psilocybin

experimental

Oral psilocybin administered in two blinded dosing sessions (week 4 and week 8) plus manualized META psychosocial therapy.

Interventions

  • Psilocybin25 - 40 mg
    via Oral• two sessions• 2 doses total

    Dose expressed per 70 kg; initial 25 mg/70 kg at session 1, second session may be 25, 30, or 40 mg/70 kg.

  • Compound
    via Other• two sessions

    Motivational Enhancement and Taking Action (META) psychosocial intervention: preparation, debriefing and follow-up.

Diphenhydramine

active comparator

Oral diphenhydramine administered in two blinded dosing sessions plus META psychosocial therapy.

Interventions

  • Placebo50 - 100 mg
    via Oral• two sessions• 2 doses total

    Diphenhydramine 50 mg at session 1, may be increased to 100 mg at session 2 (encoded as placebo reference for compound list).

  • Compound
    via Other• two sessions

    Motivational Enhancement and Taking Action (META) psychosocial intervention: preparation, debriefing and follow-up.

Participants

Ages
25 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Males and females age 25-65 with SCID (DSM-IV) diagnosis of alcohol dependence who
  • 2. Want to stop or decrease their drinking
  • 3. Are not participating in any formal treatment for alcohol dependence (12-step meetings are not considered treatment)
  • 4. Are able to provide voluntary informed consent
  • 5. Have at least 4 heavy drinking days in the past 30 days
  • 6. If female of childbearing potential, are willing to use approved form of contraception from screening until after the psilocybin administration sessions
  • 7. Have a family member or friend who can pick them up and stay with them overnight after the psilocybin administration sessions
  • 8. Are able to provide adequate locator information.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Medical conditions that would preclude safe participation in the trial (e.g., seizure disorder, significantly impaired liver function, coronary artery disease, heart failure, uncontrolled hypertension (above 165/95 mmHg at screening), history of cerebrovascular accident, asthma, hyperthyroidism, narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, or bladder-neck obstruction)
  • 2. Exclusionary psychiatric conditions (schizophrenia, schizoaffective disorder, bipolar disorder, current major depressive episode, current post-traumatic stress disorder, current suicidality or history of medically serious suicide attempt)
  • 3. Cognitive impairment (Folstein Mini Mental State Exam score < 26)
  • 4. A family history of schizophrenia or schizoaffective disorder (first or second degree relatives), or bipolar disorder type 1 (first degree relatives)
  • 5. History of hallucinogen use disorder, or any use in the past 1 year, or >25 lifetime uses;
  • 6. Cocaine, psychostimulant, opioid, or cannabis dependence (past 12 months)
  • 7. Current non-medical use of cocaine, psychostimulants, or opioids (past 30 days)
  • 8. Significant alcohol withdrawal (CIWA-Ar score greater than 7. Patients presenting at screening in withdrawal may be referred for detoxification and reassessed within 30 days)
  • 9. Serious ECG abnormalities (e.g., evidence of ischemia, myocardial infarction, QTc prolongation [QTc > .045 for men, QTc > .047 for women])
  • 10. Serious abnormalities of complete blood count or chemistries
  • 11. Active legal problems with the potential to result in incarceration
  • 12. Pregnancy or lactation
  • 13. Need to take medication with significant potential to interact with study medications (e.g., antidepressants, antipsychotics, psychostimulants, treatments for addictions, other dopaminergic or serotonergic agents, lithium, anticonvulsants).
  • 14. Allergy or hypersensitivity to psilocybin or diphenhydramine.
  • 15. High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support).

Study Details

Locations

University of New Mexico Health Sciences Center — Albuquerque, New Mexico, United States
Clinical and Translational Science Institute, NYU Langone Medical Center — New York, New York, United States

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