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

NCT02061293 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 14-00614Heffter 113080-2
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 2

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.

Conditions

Alcohol Dependence

Outcome Measures

Primary Outcomes (9)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Follow Up (Weeks 5-36)

Secondary Outcomes (12)

• Short Inventory of Problems (SIP-2R) Score

  Baseline (Week 4)

• Short Inventory of Problems (SIP-2R) Score

  Week 36

• Percentage of Participants Achieving Abstinence From Drinking

  From Week 5 (1 week after first drug administration) up to Week 36

• Percentage of Participants Achieving Abstinence From Drinking

  From Week 33 up to Week 36

• Percent of Participants Achieving No Heavy Drinking Days

  From Week 5 (1 week after first drug administration) up to Week 36

Study Arms (2)

Psilocybin

EXPERIMENTAL

Psilocybin 25 mg/70 kg PO administered at week 4, 25-40 mg/70 kg PO administered at week 8.

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.

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

Interventions

Psilocybin DRUG

Psilocybin

Diphenhydramine DRUG

Diphenhydramine

Motivational Enhancement and Taking Action (META) BEHAVIORAL

Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.

Diphenhydramine; Psilocybin

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)
• 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).

Sponsors & Collaborators

• NYU Langone Health: lead
• Heffter Research Institute: collaborator
• University of New Mexico: collaborator

Study Sites (2)

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87131, United States

Location

Clinical and Translational Science Institute, NYU Langone Medical Center

New York, New York, 10016, United States

Location

Related Publications (5)

• 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.

  PMID: 38326432 DERIVED

• 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.

  PMID: 37276086 DERIVED

• 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.

  PMID: 36332827 DERIVED

• 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.

  PMID: 36001306 DERIVED

• 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.

  PMID: 25586396 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Psilocybin; Diphenhydramine

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Samantha Podrebarac, MSc
• Organization: NYU Langone Health

Samantha.Podrebarac@nyulangone.org

212-263-0912

Study Officials

• Michael P Bogenschutz, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2014
• First Posted: February 12, 2014
• Study Start: June 1, 2014
• Primary Completion: July 30, 2021
• Study Completion: July 30, 2021
• Last Updated: November 8, 2022
• Results First Posted: October 18, 2022

Record last verified: 2022-10

Locations

US (2)