Alcohol DependencePhase 2NCT02061293

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

A Phase 2 study testing Psilocybin, Diphenhydramine and Motivational Enhancement and Taking Action (META) in people with Alcohol Dependence, run by NYU Langone Health at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 25 to 65 years
Conditions the study is for: Alcohol Dependence
What is being tested?: Psilocybin, Diphenhydramine and Motivational Enhancement and Taking Action (META)
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 95 participants
Where: 2 sitesUnited States
Study dates: Jun 2014to 30 Jul 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 25 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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)

Show all 15Show fewer

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).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

University of New Mexico Health Sciences Center
Albuquerque, New Mexico, 87131
Clinical and Translational Science Institute, NYU Langone Medical Center
New York, New York, 10016

Other trials in United States

About this study

Read the 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.

Conditions: Alcohol Dependence
Being tested: Psilocybin, Diphenhydramine, Motivational Enhancement and Taking Action (META)
Medical subject headings: Alcoholism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PsilocybinDrug
DiphenhydramineDrug
Motivational Enhancement and Taking Action (META)Behavioural
Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.

Study groups in NCT02061293
Study group	Role	What they receive
Psilocybin	Experimental	Psilocybin 25 mg/70 kg PO administered at week 4, 25-40 mg/70 kg PO administered at week 8. Receives: Drug: Psilocybin; Behavioral: Motivational Enhancement and Taking Action (META)
Diphenhydramine	Active comparator	Diphenhydramine 50 mg PO administered at week 4, 50-100 mg PO administered at week 8. Receives: Drug: Diphenhydramine; Behavioral: Motivational Enhancement and Taking Action (META)

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent of Heavy Drinking Days
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.
Measured: Screening (Week 0)
Percent of Heavy Drinking Days
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.
Measured: Baseline (Week 4)
Percent of Heavy Drinking Days
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.
Measured: Follow Up (Weeks 5-36)
Drinks Per Day
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.
Measured: Screening (Week 0)
Drinks Per Day
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.
Measured: Baseline (Week 4)
Drinks Per Day
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.
Measured: Follow Up (Weeks 5-36)
Percent of Drinking Days
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.
Measured: Screening (Week 0)
Percent of Drinking Days
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.
Measured: Baseline (Week 4)
Percent of Drinking Days
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.
Measured: Follow Up (Weeks 5-36)

Secondary outcomes (12)

Short Inventory of Problems (SIP-2R) Score
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.
Measured: Baseline (Week 4)
Short Inventory of Problems (SIP-2R) Score
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.
Measured: Week 36
Percentage of Participants Achieving Abstinence From Drinking
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.
Measured: From Week 5 (1 week after first drug administration) up to Week 36
Percentage of Participants Achieving Abstinence From Drinking
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.
Measured: From Week 33 up to Week 36
Percent of Participants Achieving No Heavy Drinking Days
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.
Measured: From Week 5 (1 week after first drug administration) up to Week 36
Percent of Participants Achieving No Heavy Drinking Days
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.
Measured: From Week 33 Up to Week 36
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level
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).
Measured: 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
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).
Measured: From Week 33 Up to Week 36
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels
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).
Measured: 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
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).
Measured: From Week 33 Up to Week 36
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels
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).
Measured: 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
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).
Measured: From Week 33 up to Week 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201430 Jul 2021

First posted12 Feb 2014 (estimated)
Study startJun 2014
Primary completion30 Jul 2021
Study completion30 Jul 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Alcohol DependenceStudies of the same condition, open and under way.
More trials run by NYU Langone HealthThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 95 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02061293
Sponsor's protocol ID: 14-00614
Other IDs: Heffter 113080-2
Status last verified: Oct 2022
First submitted: 7 Feb 2014
Last updated: 8 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Pagni BA, Ross S, Mennenga S, Bhatt S, Zeifman RJ, Petridis PD, Carrithers BM, Worth L, Podrebarac S, Owens LT, O'Donnell K, Roberts DE, Kim Y, Bogenschutz MP. Safety and efficacy of psilocybin-assisted therapy for alcohol use disorder: Open-label extension of a phase II randomized controlled trial. Drug Alcohol Depend. 2026 Oct 15;288:113387. doi: 10.1016/j.drugalcdep.2026.113387. Online ahead of print.
PubMed 42913354
Pagni BA, Zeifman RJ, Mennenga SE, Carrithers BM, Goldway N, Bhatt S, O'Donnell KC, Ross S, Bogenschutz MP. Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial. Am J Psychiatry. 2025 Jan 1;182(1):114-125. doi: 10.1176/appi.ajp.20230887.
PubMed 39741446
Pagni BA, Petridis PD, Podrebarac SK, Grinband J, Claus ED, Bogenschutz MP. Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: an fMRI pilot study. Sci Rep. 2024 Feb 7;14(1):3159. doi: 10.1038/s41598-024-52967-8.
PubMed 38326432
Agin-Liebes G, Nielson EM, Zingman M, Kim K, Haas A, Owens LT, Rogers U, Bogenschutz M. Reports of self-compassion and affect regulation in psilocybin-assisted therapy for alcohol use disorder: An interpretive phenomenological analysis. Psychol Addict Behav. 2024 Feb;38(1):101-113. doi: 10.1037/adb0000935. Epub 2023 Jun 5.
PubMed 37276086
O'Donnell KC, Mennenga SE, Owens LT, Podrebarac SK, Baron T, Rotrosen J, Ross S, Forcehimes AA, Bogenschutz MP. Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial. Contemp Clin Trials. 2022 Dec;123:106976. doi: 10.1016/j.cct.2022.106976. Epub 2022 Nov 2.
PubMed 36332827
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.
PubMed 36001306
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.
PubMed 25586396

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence
ClinicalTrials.gov ID: NCT02061293
Acronym / sponsor ID: 14-00614
Conditions: Alcohol Dependence
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 95 participants (actual)
Lead sponsor: NYU Langone HealthUniversity, hospital or other
Collaborators: Heffter Research Institute, University of New Mexico
Study start: Jun 2014 (actual)
Primary completion: 30 Jul 2021 (actual)
Study completion: 30 Jul 2021 (actual)
First posted: 12 Feb 2014 (estimated)
Results: Posted 18 Oct 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Psilocybin	Experimental	Drug: Psilocybin, Behavioral: Motivational Enhancement and Taking Action (META)Psilocybin 25 mg/70 kg PO administered at week 4, 25-40 mg/70 kg PO administered at week 8.
Diphenhydramine	Active comparator	Drug: Diphenhydramine, Behavioral: Motivational Enhancement and Taking Action (META)Diphenhydramine 50 mg PO administered at week 4, 50-100 mg PO administered at week 8.

Who may qualify

Ages: 25 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (15 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Psilocybin	Drug	Psilocybin
Diphenhydramine	Drug	Diphenhydramine
Motivational Enhancement and Taking Action (META)Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.	Behavioural	Diphenhydramine, Psilocybin

Primary outcome

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.
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.
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.
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.
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.
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.
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.
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.
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.

12 secondary outcomes

Short Inventory of Problems (SIP-2R) Score
Time frame: Baseline (Week 4)
Short Inventory of Problems (SIP-2R) Score
Time frame: Week 36
Percentage of Participants Achieving Abstinence From Drinking
Time frame: From Week 5 (1 week after first drug administration) up to Week 36
Percentage of Participants Achieving Abstinence From Drinking
Time frame: From Week 33 up to Week 36
Percent of Participants Achieving No Heavy Drinking Days
Time frame: 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
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
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level
Time frame: 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
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels
Time frame: 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
Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels
Time frame: From Week 33 up to Week 36

Results and safety

Results posted to the registry on 18 Oct 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Psilocybin	49	48
Diphenhydramine	46	45

Primary outcome: Percent of Heavy Drinking Days

Time frame: Screening (Week 0). Mean (Standard Deviation). Unit: percentage of days

Measure	Psilocybin n = 48	Diphenhydramine n = 45
Value	56.48 (31.77)	48.57 (28.73)

Primary outcome: Percent of Heavy Drinking Days

Time frame: Baseline (Week 4). Mean (Standard Deviation). Unit: percentage of days

Measure	Psilocybin n = 48	Diphenhydramine n = 45
Value	24.11 (26.29)	21.31 (20.14)

Primary outcome: Percent of Heavy Drinking Days

Time frame: Follow Up (Weeks 5-36). Mean (Standard Deviation). Unit: percentage of days

Measure	Psilocybin n = 48	Diphenhydramine n = 45
Value	9.71 (26.21)	23.57 (26.67)

Primary outcome: Drinks Per Day

Time frame: Screening (Week 0). Mean (Standard Deviation). Unit: drinks per day

Measure	Psilocybin n = 48	Diphenhydramine n = 45
Value	5.2 (2.81)	4.38 (2.39)

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: After first medication administration (week 4) through week 36.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Psilocybin	0 of 48 (0%)	37 of 48 (77.1%)	0 of 48
Diphenhydramine	2 of 45 (4.4%)	29 of 45 (64.4%)	0 of 45

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42913354Pagni BA, Ross S, Mennenga S, Bhatt S, Zeifman RJ, Petridis PD, Carrithers BM, Worth L, Podrebarac S, Owens LT, O'Donnell K, Roberts DE, Kim Y, Bogenschutz MP. Safety and efficacy of psilocybin-assisted therapy for alcohol use disorder: Open-label extension of a phase II randomized controlled trial. Drug Alcohol Depend. 2026 Oct 15;288:113387. doi: 10.1016/j.drugalcdep.2026.113387. Online ahead of print.
Derived from this study: PubMed 39741446Pagni BA, Zeifman RJ, Mennenga SE, Carrithers BM, Goldway N, Bhatt S, O'Donnell KC, Ross S, Bogenschutz MP. Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial. Am J Psychiatry. 2025 Jan 1;182(1):114-125. doi: 10.1176/appi.ajp.20230887.
Derived from this study: PubMed 38326432Pagni BA, Petridis PD, Podrebarac SK, Grinband J, Claus ED, Bogenschutz MP. Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: an fMRI pilot study. Sci Rep. 2024 Feb 7;14(1):3159. doi: 10.1038/s41598-024-52967-8.
Derived from this study: PubMed 37276086Agin-Liebes G, Nielson EM, Zingman M, Kim K, Haas A, Owens LT, Rogers U, Bogenschutz M. Reports of self-compassion and affect regulation in psilocybin-assisted therapy for alcohol use disorder: An interpretive phenomenological analysis. Psychol Addict Behav. 2024 Feb;38(1):101-113. doi: 10.1037/adb0000935. Epub 2023 Jun 5.
Derived from this study: PubMed 36332827O'Donnell KC, Mennenga SE, Owens LT, Podrebarac SK, Baron T, Rotrosen J, Ross S, Forcehimes AA, Bogenschutz MP. Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial. Contemp Clin Trials. 2022 Dec;123:106976. doi: 10.1016/j.cct.2022.106976. Epub 2022 Nov 2.
Derived from this study: PubMed 36001306Bogenschutz 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.
Derived from this study: PubMed 25586396Bogenschutz 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael P Bogenschutz, MD principal investigator

NYU Langone Health

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Psilocybin, Diphenhydramine and Motivational Enhancement and Taking Action (META) in people with Alcohol Dependence, run by NYU Langone Health at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent of Heavy Drinking Days (time frame: Screening (Week 0)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02061293, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.