Clinical trial NCT02061293: A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence
Official title: A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcohol Dependence
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: Heffter Research Institute
name: University of New Mexico
First posted: 2014-02-12
Enrollment: 95
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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).

Primary outcomes:
measure: Percent of Heavy Drinking Days
timeFrame: Screening (Week 0)
measure: Percent of Heavy Drinking Days
timeFrame: Baseline (Week 4)
measure: Percent of Heavy Drinking Days
timeFrame: Follow Up (Weeks 5-36)
measure: Drinks Per Day
timeFrame: Screening (Week 0)
measure: Drinks Per Day
timeFrame: Baseline (Week 4)
measure: Drinks Per Day
timeFrame: Follow Up (Weeks 5-36)
measure: Percent of Drinking Days
timeFrame: Screening (Week 0)
measure: Percent of Drinking Days
timeFrame: Baseline (Week 4)
measure: Percent of Drinking Days
timeFrame: Follow Up (Weeks 5-36)
Secondary outcomes:
measure: Short Inventory of Problems (SIP-2R) Score
timeFrame: Baseline (Week 4)
measure: Short Inventory of Problems (SIP-2R) Score
timeFrame: Week 36
measure: Percentage of Participants Achieving Abstinence From Drinking
timeFrame: From Week 5 (1 week after first drug administration) up to Week 36
measure: Percentage of Participants Achieving Abstinence From Drinking
timeFrame: From Week 33 up to Week 36
measure: Percent of Participants Achieving No Heavy Drinking Days
timeFrame: From Week 5 (1 week after first drug administration) up to Week 36
measure: Percent of Participants Achieving No Heavy Drinking Days
timeFrame: From Week 33 Up to Week 36
measure: Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level
timeFrame: From Week 5 (1 week after first drug administration) up to Week 36
measure: Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level
timeFrame: From Week 33 Up to Week 36
measure: Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels
timeFrame: From Week 5 (1 week after first drug administration) up to Week 36
measure: Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels
timeFrame: From Week 33 Up to Week 36
measure: Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels
timeFrame: From Week 5 (1 week after first drug administration) up to Week 36
measure: Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels
timeFrame: From Week 33 up to Week 36
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: New York
country: United States
facility: Clinical and Translational Science Institute, NYU Langone Medical Center
state: New York
Study officials:
affiliation: NYU Langone Health
name: Michael P Bogenschutz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, Mennenga SE, O'Donnell K, Owens LT, Podrebarac S, Rotrosen J, Tonigan JS, Worth L. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Oct 1;79(10):953-962. doi: 10.1001/jamapsychiatry.2022.2096.
citation: Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015 Mar;29(3):289-99. doi: 10.1177/0269881114565144. Epub 2015 Jan 13.