- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02061293
A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence
Study Overview
Status
Conditions
Intervention / 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New Mexico
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Albuquerque, New Mexico, United States, 87131
- University of New Mexico Health Sciences Center
-
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New York
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New York, New York, United States, 10016
- Clinical and Translational Science Institute, NYU Langone Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Males and females age 25-65 with SCID (DSM-IV) diagnosis of alcohol dependence who
- Want to stop or decrease their drinking
- Are not participating in any formal treatment for alcohol dependence (12-step meetings are not considered treatment)
- Are able to provide voluntary informed consent
- Have at least 4 heavy drinking days in the past 30 days
- If female of childbearing potential, are willing to use approved form of contraception from screening until after the psilocybin administration sessions
- Have a family member or friend who can pick them up and stay with them overnight after the psilocybin administration sessions
- Are able to provide adequate locator information.
Exclusion Criteria:
- 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)
- 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)
- Cognitive impairment (Folstein Mini Mental State Exam score < 26)
- A family history of schizophrenia or schizoaffective disorder (first or second degree relatives), or bipolar disorder type 1 (first degree relatives)
- History of hallucinogen use disorder, or any use in the past 1 year, or >25 lifetime uses;
- Cocaine, psychostimulant, opioid, or cannabis dependence (past 12 months)
- Current non-medical use of cocaine, psychostimulants, or opioids (past 30 days)
- 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)
- Serious ECG abnormalities (e.g., evidence of ischemia, myocardial infarction, QTc prolongation [QTc > .045 for men, QTc > .047 for women])
- Serious abnormalities of complete blood count or chemistries
- Active legal problems with the potential to result in incarceration
- Pregnancy or lactation
- 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).
- Allergy or hypersensitivity to psilocybin or diphenhydramine.
- 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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Psilocybin
Psilocybin 25 mg/70 kg PO administered at week 4, 25-40 mg/70 kg PO administered at week 8.
|
Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.
|
Active Comparator: Diphenhydramine
Diphenhydramine 50 mg PO administered at week 4, 50-100 mg PO administered at week 8.
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Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent of Heavy Drinking Days
Time Frame: Screening (Week 0)
|
The Timeline Follow-back (TLFB) method is used to calculate the percent of heavy drinking days.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
Heavy drinking is defined as ≥4 drinks per day for women and ≥5 drinks per day for men.
|
Screening (Week 0)
|
Percent of Heavy Drinking Days
Time Frame: Baseline (Week 4)
|
The Timeline Follow-back (TLFB) method is used to calculate the percent of heavy drinking days.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
Heavy drinking is defined as ≥4 drinks per day for women and ≥5 drinks per day for men.
|
Baseline (Week 4)
|
Percent of Heavy Drinking Days
Time Frame: Follow Up (Weeks 5-36)
|
The Timeline Follow-back (TLFB) method is used to calculate the percent of heavy drinking days.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
Heavy drinking is defined as ≥4 drinks per day for women and ≥5 drinks per day for men.
|
Follow Up (Weeks 5-36)
|
Drinks Per Day
Time Frame: Screening (Week 0)
|
The Timeline Follow-back (TLFB) method is used to calculate drinks per day.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
|
Screening (Week 0)
|
Drinks Per Day
Time Frame: Baseline (Week 4)
|
The Timeline Follow-back (TLFB) method is used to calculate drinks per day.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
|
Baseline (Week 4)
|
Drinks Per Day
Time Frame: Follow Up (Weeks 5-36)
|
The Timeline Follow-back (TLFB) method is used to calculate drinks per day.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
|
Follow Up (Weeks 5-36)
|
Percent of Drinking Days
Time Frame: Screening (Week 0)
|
The Timeline Follow-back (TLFB) method is used to calculate the percentage of days that participants drank alcohol.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
|
Screening (Week 0)
|
Percent of Drinking Days
Time Frame: Baseline (Week 4)
|
The Timeline Follow-back (TLFB) method is used to calculate the percentage of days that participants drank alcohol.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
|
Baseline (Week 4)
|
Percent of Drinking Days
Time Frame: Follow Up (Weeks 5-36)
|
The Timeline Follow-back (TLFB) method is used to calculate the percentage of days that participants drank alcohol.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
|
Follow Up (Weeks 5-36)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Short Inventory of Problems (SIP-2R) Score
Time Frame: Baseline (Week 4)
|
15-item self-report questionnaire assessing problems related to alcohol use.
Items are ranked on a 4-point Likert scale ranging from 0 (never) to 3 (daily or almost daily).
The total score range is 0-45; the higher the score, the more problems related to alcohol use.
|
Baseline (Week 4)
|
Short Inventory of Problems (SIP-2R) Score
Time Frame: Week 36
|
15-item self-report questionnaire assessing problems related to alcohol use.
Items are ranked on a 4-point Likert scale ranging from 0 (never) to 3 (daily or almost daily).
The total score range is 0-45; the higher the score, the more problems related to alcohol use.
|
Week 36
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Percentage of Participants Achieving Abstinence From Drinking
Time Frame: From Week 5 (1 week after first drug administration) up to Week 36
|
The Timeline Follow-back (TLFB) method is used in calculating abstinence from drinking.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
Abstinence is defined as zero drinks of alcohol over the target period.
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From Week 5 (1 week after first drug administration) up to Week 36
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Percentage of Participants Achieving Abstinence From Drinking
Time Frame: From Week 33 up to Week 36
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The Timeline Follow-back (TLFB) method is used in calculating abstinence from drinking.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
Abstinence is defined as zero drinks of alcohol over the target period.
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From Week 33 up to Week 36
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Percent of Participants Achieving No Heavy Drinking Days
Time Frame: From Week 5 (1 week after first drug administration) up to Week 36
|
The Timeline Follow-back (TLFB) method is used in calculating the number of heavy drinking days.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
Heavy drinking is defined as ≥4 drinks per day for women and ≥5 drinks per day for men.
|
From Week 5 (1 week after first drug administration) up to Week 36
|
Percent of Participants Achieving No Heavy Drinking Days
Time Frame: From Week 33 Up to Week 36
|
The Timeline Follow-back (TLFB) method is used in calculating the number of heavy drinking days.
The TLFB is a method for assessing the number of drinks of alcohol on a daily basis over the previous 30 days.
For each day in the recall period, the participant indicates the number of drinks of alcohol they consumed.
The TLFB provides a calendar prompt and number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to facilitate accurate recall of drug use during the target period.
Heavy drinking is defined as ≥4 drinks per day for women and ≥5 drinks per day for men.
|
From Week 33 Up to Week 36
|
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level
Time Frame: From Week 5 (1 week after first drug administration) up to Week 36
|
For men, WHO low risk drinking (level 1) is defined as >0 grams of alcohol/day (g/d) to 40 g/d; moderate risk (level 2) as >40 g/d to 60 g/d; high risk (level 3) as >60 g/d to 100 g/d; and very high risk (level 4) as >100 g/d.
For women, low risk (level 1) is defined as >0 g/d to 20 g/d; moderate risk (level 2) as >20 g/d to 40 g/d; high risk (level 3) as >40 g/d to 60 g/d; and very high risk (level 4) as >60 g/d.
Abstinence was defined as no risk (level 0).
|
From Week 5 (1 week after first drug administration) up to Week 36
|
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level
Time Frame: From Week 33 Up to Week 36
|
For men, WHO low risk drinking (level 1) is defined as >0 grams of alcohol/day (g/d) to 40 g/d; moderate risk (level 2) as >40 g/d to 60 g/d; high risk (level 3) as >60 g/d to 100 g/d; and very high risk (level 4) as >100 g/d.
For women, low risk (level 1) is defined as >0 g/d to 20 g/d; moderate risk (level 2) as >20 g/d to 40 g/d; high risk (level 3) as >40 g/d to 60 g/d; and very high risk (level 4) as >60 g/d.
Abstinence was defined as no risk (level 0).
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From Week 33 Up to Week 36
|
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels
Time Frame: From Week 5 (1 week after first drug administration) up to Week 36
|
For men, WHO low risk drinking (level 1) is defined as >0 grams of alcohol/day (g/d) to 40 g/d; moderate risk (level 2) as >40 g/d to 60 g/d; high risk (level 3) as >60 g/d to 100 g/d; and very high risk (level 4) as >100 g/d.
For women, low risk (level 1) is defined as >0 g/d to 20 g/d; moderate risk (level 2) as >20 g/d to 40 g/d; high risk (level 3) as >40 g/d to 60 g/d; and very high risk (level 4) as >60 g/d.
Abstinence was defined as no risk (level 0).
|
From Week 5 (1 week after first drug administration) up to Week 36
|
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels
Time Frame: From Week 33 Up to Week 36
|
For men, WHO low risk drinking (level 1) is defined as >0 grams of alcohol/day (g/d) to 40 g/d; moderate risk (level 2) as >40 g/d to 60 g/d; high risk (level 3) as >60 g/d to 100 g/d; and very high risk (level 4) as >100 g/d.
For women, low risk (level 1) is defined as >0 g/d to 20 g/d; moderate risk (level 2) as >20 g/d to 40 g/d; high risk (level 3) as >40 g/d to 60 g/d; and very high risk (level 4) as >60 g/d.
Abstinence was defined as no risk (level 0).
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From Week 33 Up to Week 36
|
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels
Time Frame: From Week 5 (1 week after first drug administration) up to Week 36
|
For men, WHO low risk drinking (level 1) is defined as >0 grams of alcohol/day (g/d) to 40 g/d; moderate risk (level 2) as >40 g/d to 60 g/d; high risk (level 3) as >60 g/d to 100 g/d; and very high risk (level 4) as >100 g/d.
For women, low risk (level 1) is defined as >0 g/d to 20 g/d; moderate risk (level 2) as >20 g/d to 40 g/d; high risk (level 3) as >40 g/d to 60 g/d; and very high risk (level 4) as >60 g/d.
Abstinence was defined as no risk (level 0).
|
From Week 5 (1 week after first drug administration) up to Week 36
|
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels
Time Frame: From Week 33 up to Week 36
|
For men, WHO low risk drinking (level 1) is defined as >0 grams of alcohol/day (g/d) to 40 g/d; moderate risk (level 2) as >40 g/d to 60 g/d; high risk (level 3) as >60 g/d to 100 g/d; and very high risk (level 4) as >100 g/d.
For women, low risk (level 1) is defined as >0 g/d to 20 g/d; moderate risk (level 2) as >20 g/d to 40 g/d; high risk (level 3) as >40 g/d to 60 g/d; and very high risk (level 4) as >60 g/d.
Abstinence was defined as no risk (level 0).
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From Week 33 up to Week 36
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Michael P Bogenschutz, MD, NYU Langone Health
Publications and helpful links
General Publications
- 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. Erratum In: JAMA Psychiatry. 2022 Sep 14;:
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Alcohol-Related Disorders
- Substance-Related Disorders
- Alcoholism
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Sensory System Agents
- Anesthetics
- Antiemetics
- Gastrointestinal Agents
- Dermatologic Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Anesthetics, Local
- Anti-Allergic Agents
- Sleep Aids, Pharmaceutical
- Histamine H1 Antagonists
- Histamine Antagonists
- Histamine Agents
- Antipruritics
- Hallucinogens
- Diphenhydramine
- Promethazine
- Psilocybin
Other Study ID Numbers
- 14-00614
- Heffter 113080-2 (Other Grant/Funding Number: Heffter Research Institute)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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