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

Condition(s) targeted: Alcohol Dependence

Intervention: Psilocybin (Drug); Diphenhydramine (Drug); Motivational Enhancement and Taking Action (META) (Behavioral)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of New Mexico

Official(s) and/or principal investigator(s):
Michael P Bogenschutz, MD, Principal Investigator, Affiliation: University of New Mexico Health Sciences Center

Overall contact:
Lindsay Worth, MPA, Phone: 505-925-7474, Email: lindsayw@salud.unm.edu

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. Two to four sites will participate. 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 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 4) to test whether or not characteristics of the drug administration session experiences and short term (1 week) persisting effects mediate effects of psilocybin on post-session drinking behavior. 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. 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 32 weeks after the first drug administration session, for a total of 36 weeks from the initiation of treatment.

Official title: A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: percent heavy drinking days

Secondary outcome:

Changes in vital signs

adverse events

Percent days abstinent

drinks per drinking day

days to first drinking day

Days to first heavy drinking day

consequences of drinking

craving

self efficacy

Motivation to change drinking behavior

Minimum age: 25 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Males and females age 25-65 with Structured Clinical Interview for 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, uncontrolled hypertension, history of cerebrovascular accident, severe obesity (BMI greater than 35), 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. A family history of schizophrenia or schizoaffective disorder (first or second degree relatives), or bipolar disorder type 1 (first degree relatives) 4. Lifetime history of hallucinogen use on more than 10 occasions, or any use in the past 5 years; 5. Cocaine, psychostimulant, opioid, or cannabis dependence (past 12 months) 6. Current non-medical use of cocaine, psychostimulants, or opioids (past 30 days) 7. 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) 8. Serious ECG abnormalities (e. g., evidence of ischemia, QTc prolongation) 9. Serious abnormalities of complete blood count or chemistries 10. Active legal problems with the potential to result in incarceration 11. Pregnancy or lactation 12. 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). 13. Allergy or hypersensitivity to psilocybin or diphenhydramine. 14. 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).

Lindsay Worth, MPA, Phone: 505-925-7474, Email: lindsayw@salud.unm.edu

University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, United States; Recruiting
Michael P Bogenschutz, M.D., Phone: 505-272-8428, Email: mbogenschutz@salud.unm.edu
Michael P Bogenschutz, M.D., Principal Investigator
Alyssa A Forcehimes, Ph.D., Sub-Investigator
Claire Wilcox, M.D., Sub-Investigator
Jessica Pommy, B.A., Sub-Investigator
Linda Schenkel, CCRC, CphT, Sub-Investigator
Robert Voloshin, MD, Sub-Investigator
Lindsay Worth, MPA, Sub-Investigator

Clinical and Translational Science Institute, NYU Langone Medical Center, New York, New York, United States; Not yet recruiting
Gabrielle Agin-Liebes, Phone: 646-501-4206, Email: gabrielle.agin-liebes@nyumc.org
Stephen Ross, MD, Principal Investigator
John Rotrosen, MD, Sub-Investigator
Tara Malone, Sub-Investigator
Gabrielle Agin-Liebes, Sub-Investigator

Starting date: June 2014
Last updated: September 15, 2014