Alcohol Dependence
Conditions
Brief summary
Several lines of evidence suggest that classic hallucinogens such as psilocybin can facilitate behavior change in addictions such as alcohol dependence. The proposed investigation is a multi-site, double-blind active-controlled trial (n = 180, 90 per group) contrasting the acute and persisting effects of psilocybin to those of diphenhydramine in the context of outpatient alcoholism treatment.
Detailed description
Two to four sites will participate in this study. Aims of the study are 1) to characterize the acute effects of PO psilocybin 25 mg/70 kg, 30 mg/70 kg, and 40 mg/70 kg in alcohol dependent patients; 2) to evaluate the effect of psilocybin treatment on drinking outcomes for 32 weeks after the first administration, relative to diphenhydramine control; 3) to test whether or not characteristics of the drug administration session experiences mediate effects of psilocybin on short-term (1 week) persisting effects and post-session drinking behavior, 4) to evaluate the explanatory value of changes in alcohol craving, self-efficacy, motivation, and other psychological domains in accounting for the observed experimental effect of psilocybin relative to diphenhydramine control, and 5) to evaluate pre-post changes in drinking in participants after they receive psilocybin in the third session. The total duration of psychosocial treatment in the double-blind period will be 12 weeks, and double-blind drug administration sessions will occur after 4 and 8 weeks. In the first psilocybin session, a dose of 25 mg/70 kg will be administered. Depending on the response in the first session, the dose for the second session may be increased to 30 mg/70 kg or 40 mg/70 kg, or held at 25mg/70kg. The dose of diphenhydramine will start at 50 mg, and may be increased to 100 mg or held at 50 mg in the second session, depending on response in the first session. Following completion of the double-blind period (34 weeks after randomization) all participants who meet interim safety criteria will be offered an additional session in which psilocybin will be administered. The drug will be administered during 8-hour sessions in an outpatient setting under close medical and psychiatric monitoring. The drug administration sessions will occur in the context of an extended version of Motivational Enhancement Therapy (Motivational Enhancement and Taking Action, META) with the addition of standardized preparation before and debriefing and follow-up after the psilocybin administration sessions. Extensive screening and baseline assessment will be completed, including thorough safety screening and assessment of participant characteristics that could potentially moderate treatment response. Within-session and short-term persisting effects will be assessed. Drinking outcomes and changes in several potential mediators of treatment effect, including motivation, self-efficacy, craving, depression, anxiety, and spiritual dimensions of the experience, will be measured until 50 weeks after the first drug administration session, for a total of 54 weeks from the initiation of treatment.
Interventions
DRUGPsilocybin
DRUGDiphenhydramine
BEHAVIORALMotivational Enhancement and Taking Action (META)
Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.
Sponsors
Heffter Research Institute
University of New Mexico
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females age 25-65 with SCID (DSM-IV) diagnosis of alcohol dependence who 2. Want to stop or decrease their drinking 3. Are not participating in any formal treatment for alcohol dependence (12-step meetings are not considered treatment) 4. Are able to provide voluntary informed consent 5. Have at least 4 heavy drinking days in the past 30 days 6. If female of childbearing potential, are willing to use approved form of contraception from screening until after the psilocybin administration sessions 7. Have a family member or friend who can pick them up and stay with them overnight after the psilocybin administration sessions 8. Are able to provide adequate locator information.
Exclusion criteria
1. Medical conditions that would preclude safe participation in the trial (e.g., seizure disorder, significantly impaired liver function, coronary artery disease, heart failure, uncontrolled hypertension (above 165/95 mmHg at screening), history of cerebrovascular accident, asthma, hyperthyroidism, narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, or bladder-neck obstruction) 2. Exclusionary psychiatric conditions (schizophrenia, schizoaffective disorder, bipolar disorder, current major depressive episode, current post-traumatic stress disorder, current suicidality or history of medically serious suicide attempt) 3. Cognitive impairment (Folstein Mini Mental State Exam score \< 26) 4. A family history of schizophrenia or schizoaffective disorder (first or second degree relatives), or bipolar disorder type 1 (first degree relatives) 5. History of hallucinogen use disorder, or any use in the past 1 year, or \>25 lifetime uses; 6. Cocaine, psychostimulant, opioid, or cannabis dependence (past 12 months) 7. Current non-medical use of cocaine, psychostimulants, or opioids (past 30 days) 8. Significant alcohol withdrawal (CIWA-Ar score greater than 7. Patients presenting at screening in withdrawal may be referred for detoxification and reassessed within 30 days) 9. Serious ECG abnormalities (e.g., evidence of ischemia, myocardial infarction, QTc prolongation \[QTc \> .045 for men, QTc \> .047 for women\]) 10. Serious abnormalities of complete blood count or chemistries 11. Active legal problems with the potential to result in incarceration 12. Pregnancy or lactation 13. Need to take medication with significant potential to interact with study medications (e.g., antidepressants, antipsychotics, psychostimulants, treatments for addictions, other dopaminergic or serotonergic agents, lithium, anticonvulsants). 14. Allergy or hypersensitivity to psilocybin or diphenhydramine. 15. High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Heavy Drinking Days | 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. |
| Drinks Per Day | 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. |
| Percent of Drinking Days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level | 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). |
| Short Inventory of Problems (SIP-2R) Score | 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. |
| Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels | 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 | 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). |
| Percentage of Participants Achieving Abstinence From Drinking | 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. |
| Percent of Participants Achieving No Heavy Drinking Days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Psilocybin Psilocybin 25 mg/70 kg PO administered at week 4, 25-40 mg/70 kg PO administered at week 8.
Motivational Enhancement and Taking Action (META): Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan. | 48 |
| Diphenhydramine Diphenhydramine 50 mg PO administered at week 4, 50-100 mg PO administered at week 8.
Motivational Enhancement and Taking Action (META): Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan. | 45 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Elevated Blood Pressure | 1 | 1 |
Baseline characteristics
| Characteristic | Psilocybin | Total | Diphenhydramine |
|---|---|---|---|
| Age, Continuous | 46.94 years STANDARD_DEVIATION 10.91 | 45.59 years STANDARD_DEVIATION 11.53 | 44.24 years STANDARD_DEVIATION 12.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 14 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 79 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 12 Participants | 7 Participants |
| Race (NIH/OMB) White | 37 Participants | 73 Participants | 36 Participants |
| Region of Enrollment United States | 48 Participants | 93 Participants | 45 Participants |
| Sex: Female, Male Female | 20 Participants | 41 Participants | 21 Participants |
| Sex: Female, Male Male | 28 Participants | 52 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 45 |
| other Total, other adverse events | 37 / 48 | 29 / 45 |
| serious Total, serious adverse events | 0 / 48 | 2 / 45 |
Outcome results
Primary
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.
Time frame: Screening (Week 0)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Drinks Per Day | 5.2 drinks per day | Standard Deviation 2.81 |
| Diphenhydramine | Drinks Per Day | 4.38 drinks per day | Standard Deviation 2.39 |
Primary
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.
Time frame: Follow Up (Weeks 5-36)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Drinks Per Day | 1.17 drinks per day | Standard Deviation 1.99 |
| Diphenhydramine | Drinks Per Day | 2.26 drinks per day | Standard Deviation 2.02 |
Primary
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.
Time frame: Baseline (Week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Drinks Per Day | 2.77 drinks per day | Standard Deviation 2.3 |
| Diphenhydramine | Drinks Per Day | 2.19 drinks per day | Standard Deviation 1.98 |
Primary
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.
Time frame: Follow Up (Weeks 5-36)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Percent of Drinking Days | 29.39 percentage of days | Standard Deviation 32.86 |
| Diphenhydramine | Percent of Drinking Days | 42.83 percentage of days | Standard Deviation 33.43 |
Primary
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.
Time frame: Screening (Week 0)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Percent of Drinking Days | 78.03 percentage of days | Standard Deviation 27.02 |
| Diphenhydramine | Percent of Drinking Days | 71.68 percentage of days | Standard Deviation 28.98 |
Primary
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.
Time frame: Baseline (Week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Percent of Drinking Days | 52.98 percentage of days | Standard Deviation 31.78 |
| Diphenhydramine | Percent of Drinking Days | 45.99 percentage of days | Standard Deviation 30.4 |
Primary
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.
Time frame: Screening (Week 0)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Percent of Heavy Drinking Days | 56.48 percentage of days | Standard Deviation 31.77 |
| Diphenhydramine | Percent of Heavy Drinking Days | 48.57 percentage of days | Standard Deviation 28.73 |
Primary
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.
Time frame: Follow Up (Weeks 5-36)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Percent of Heavy Drinking Days | 9.71 percentage of days | Standard Deviation 26.21 |
| Diphenhydramine | Percent of Heavy Drinking Days | 23.57 percentage of days | Standard Deviation 26.67 |
Primary
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.
Time frame: Baseline (Week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Percent of Heavy Drinking Days | 24.11 percentage of days | Standard Deviation 26.29 |
| Diphenhydramine | Percent of Heavy Drinking Days | 21.31 percentage of days | Standard Deviation 20.14 |
Secondary
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.
Time frame: From Week 33 up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percentage of Participants Achieving Abstinence From Drinking | 47.9 Percentage of participants |
| Diphenhydramine | Percentage of Participants Achieving Abstinence From Drinking | 24.4 Percentage of participants |
Secondary
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.
Time frame: From Week 5 (1 week after first drug administration) up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percentage of Participants Achieving Abstinence From Drinking | 22.9 Percentage of participants |
| Diphenhydramine | Percentage of Participants Achieving Abstinence From Drinking | 8.9 Percentage of participants |
Secondary
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.
Time frame: From Week 5 (1 week after first drug administration) up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percent of Participants Achieving No Heavy Drinking Days | 33.3 Percentage of participants |
| Diphenhydramine | Percent of Participants Achieving No Heavy Drinking Days | 11.1 Percentage of participants |
Secondary
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.
Time frame: From Week 33 Up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percent of Participants Achieving No Heavy Drinking Days | 62.5 Percentage of participants |
| Diphenhydramine | Percent of Participants Achieving No Heavy Drinking Days | 40 Percentage of participants |
Secondary
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).
Time frame: From Week 33 Up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level | 89.6 Percentage of participants |
| Diphenhydramine | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level | 64.4 Percentage of participants |
Secondary
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).
Time frame: From Week 5 (1 week after first drug administration) up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level | 83.3 Percentage of participants |
| Diphenhydramine | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 1 Level | 71.1 Percentage of participants |
Secondary
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).
Time frame: From Week 5 (1 week after first drug administration) up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels | 60.4 Percentage of participants |
| Diphenhydramine | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels | 40 Percentage of participants |
Secondary
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).
Time frame: From Week 33 Up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels | 60.4 Percentage of participants |
| Diphenhydramine | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 2 Levels | 40 Percentage of participants |
Secondary
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).
Time frame: From Week 33 up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels | 37.5 Percentage of participants |
| Diphenhydramine | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels | 17.8 Percentage of participants |
Secondary
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).
Time frame: From Week 5 (1 week after first drug administration) up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Psilocybin | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels | 29.92 Percentage of participants |
| Diphenhydramine | Percent of Participants Achieving WHO Risk Drinking Level Decrease of at Least 3 Levels | 13.3 Percentage of participants |
Secondary
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.
Time frame: Baseline (Week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Short Inventory of Problems (SIP-2R) Score | 20.26 score on a scale | Standard Deviation 8.89 |
| Diphenhydramine | Short Inventory of Problems (SIP-2R) Score | 21.6 score on a scale | Standard Deviation 9.61 |
Secondary
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.
Time frame: Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psilocybin | Short Inventory of Problems (SIP-2R) Score | 6.59 score on a scale | Standard Deviation 8.8 |
| Diphenhydramine | Short Inventory of Problems (SIP-2R) Score | 13 score on a scale | Standard Deviation 10.48 |