A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Two to four sites will participate in this study. Aims of the study are 1) to characterize
      the acute effects of PO psilocybin 25 mg/70 kg, 30 mg/70 kg, and 40 mg/70 kg in alcohol
      dependent patients; 2) to evaluate the effect of psilocybin treatment on drinking outcomes
      for 32 weeks after the first administration, relative to diphenhydramine control; 3) to test
      whether or not characteristics of the drug administration session experiences mediate effects
      of psilocybin on short-term (1 week) persisting effects and post-session drinking behavior,
      4) to evaluate the explanatory value of changes in alcohol craving, self-efficacy,
      motivation, and other psychological domains in accounting for the observed experimental
      effect of psilocybin relative to diphenhydramine control, and 5) to evaluate pre-post changes
      in drinking in participants after they receive psilocybin in the third session.

      The total duration of psychosocial treatment in the double-blind period will be 12 weeks, and
      double-blind drug administration sessions will occur after 4 and 8 weeks. In the first
      psilocybin session, a dose of 25 mg/70 kg will be administered. Depending on the response in
      the first session, the dose for the second session may be increased to 30 mg/70 kg or 40
      mg/70 kg, or held at 25mg/70kg. The dose of diphenhydramine will start at 50 mg, and may be
      increased to 100 mg or held at 50 mg in the second session, depending on response in the
      first session. Following completion of the double-blind period (34 weeks after randomization)
      all participants who meet interim safety criteria will be offered an additional session in
      which psilocybin will be administered. The drug will be administered during 8-hour sessions
      in an outpatient setting under close medical and psychiatric monitoring. The drug
      administration sessions will occur in the context of an extended version of Motivational
      Enhancement Therapy (Motivational Enhancement and Taking Action, META) with the addition of
      standardized preparation before and debriefing and follow-up after the psilocybin
      administration sessions. Extensive screening and baseline assessment will be completed,
      including thorough safety screening and assessment of participant characteristics that could
      potentially moderate treatment response. Within-session and short-term persisting effects
      will be assessed. Drinking outcomes and changes in several potential mediators of treatment
      effect, including motivation, self-efficacy, craving, depression, anxiety, and spiritual
      dimensions of the experience, will be measured until 50 weeks after the first drug
      administration session, for a total of 54 weeks from the initiation of treatment.
    

Intervention name(s): Psilocybin; Diphenhydramine; Motivational Enhancement and Taking Action (META)
Intervention type(s): Drug; Drug; Behavioral
Intervention description(s): Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.
Intervention MeSH terms: Diphenhydramine; Promethazine; Psilocybin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment