A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Intervention: Psilocybin; Diphenhydramine; Motivational Enhancement and Taking Action (META)
Intervention description: Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.
Intervention MeSH terms: Diphenhydramine; Promethazine; Psilocybin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 95.0
Sex: All
Minimum age: 25 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      Several lines of evidence suggest that classic hallucinogens such as psilocybin can
      facilitate behavior change in addictions such as alcohol dependence. The proposed
      investigation is a multi-site, double-blind active-controlled trial (n = 180, 90 per group)
      contrasting the acute and persisting effects of psilocybin to those of diphenhydramine in the
      context of outpatient alcoholism treatment.
    

Eligibility 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:

          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).