A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence
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| ClinicalTrials.gov Identifier: NCT02061293 |
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Recruitment Status :
Completed
First Posted : February 12, 2014
Results First Posted : October 18, 2022
Last Update Posted : November 8, 2022
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Sponsor:
NYU Langone Health
Collaborators:
Heffter Research Institute
University of New Mexico
Information provided by (Responsible Party):
NYU Langone Health
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Alcohol Dependence | Drug: Psilocybin Drug: Diphenhydramine Behavioral: Motivational Enhancement and Taking Action (META) | Phase 2 |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 95 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence |
| Actual Study Start Date : | June 2014 |
| Actual Primary Completion Date : | July 30, 2021 |
| Actual Study Completion Date : | July 30, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Alcohol Use Disorder (AUD)
| Arm | Intervention/treatment |
|---|---|
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Experimental: Psilocybin
Psilocybin 25 mg/70 kg PO administered at week 4, 25-40 mg/70 kg PO administered at week 8.
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Drug: Psilocybin Behavioral: Motivational Enhancement and Taking Action (META) Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan. |
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Active Comparator: Diphenhydramine
Diphenhydramine 50 mg PO administered at week 4, 50-100 mg PO administered at week 8.
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Drug: Diphenhydramine Behavioral: Motivational Enhancement and Taking Action (META) Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan. |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
- 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.
- 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.
- Percentage of Participants Achieving Abstinence From Drinking [ Time Frame: From Week 33 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.
- 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.
- 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.
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
Information from the National Library of Medicine
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| Ages Eligible for Study: | 25 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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).
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02061293
Locations
| United States, New Mexico | |
| University of New Mexico Health Sciences Center | |
| Albuquerque, New Mexico, United States, 87131 | |
| United States, New York | |
| Clinical and Translational Science Institute, NYU Langone Medical Center | |
| New York, New York, United States, 10016 | |
Sponsors and Collaborators
NYU Langone Health
Heffter Research Institute
University of New Mexico
Investigators
| Principal Investigator: | Michael P Bogenschutz, MD | NYU Langone Health |
Study Documents (Full-Text)
Documents provided by NYU Langone Health:
Documents provided by NYU Langone Health:
Study Protocol and Statistical Analysis Plan [PDF] September 9, 2020
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | NYU Langone Health |
| ClinicalTrials.gov Identifier: | NCT02061293 |
| Other Study ID Numbers: |
14-00614 Heffter 113080-2 ( Other Grant/Funding Number: Heffter Research Institute ) |
| First Posted: | February 12, 2014 Key Record Dates |
| Results First Posted: | October 18, 2022 |
| Last Update Posted: | November 8, 2022 |
| Last Verified: | October 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Alcoholism Alcohol-Related Disorders Substance-Related Disorders Chemically-Induced Disorders Mental Disorders Diphenhydramine Promethazine Psilocybin Sleep Aids, Pharmaceutical Hypnotics and Sedatives Central Nervous System Depressants Physiological Effects of Drugs Anesthetics, Local Anesthetics Sensory System Agents |
Peripheral Nervous System Agents Antiemetics Autonomic Agents Gastrointestinal Agents Histamine H1 Antagonists Histamine Antagonists Histamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Anti-Allergic Agents Antipruritics Dermatologic Agents Hallucinogens Psychotropic Drugs |