Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder

Study Overview
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Brief Summary
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The aim of this study is to determine if a single dose of psilocybin administered with motivational enhancement therapy (MET) can reduce heavy drinking in patients with an alcohol use disorder (AUD).

Detailed Description
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The primary objective of this study is to determine if psilocybin administered with a standardized psychotherapeutic intervention, motivational enhancement therapy (MET), can reduce heavy drinking in a patient population with an alcohol use disorder (AUD). Patients with an AUD will be randomly allocated to either a high dose (25mg; active treatment) or a low dose (1mg; active control) psilocybin arm. All participants will receive 5 sessions of MET, starting at 24hrs post-dosing. Heavy drinking will be assessed as percent heavy drinking days using the Time Line Follow Back (TLFB) at baseline and 1-, 4-, and 12-weeks post-dosing. A total of 128 male and female patients between the ages of 22-65 with a moderate to severe AUD diagnosis will be recruited from the community. Participants will undergo a thorough screening procedure and eligible participants will be randomly allocated to the high (N=64) or low (N=64) psilocybin doses. All participants will complete a baseline session consisting of clinical, behavioral, and neuroimaging measures. Following the single dosing session, participants will complete 5 weekly MET sessions. Neuroimaging measures will be assessed again at 1-week post-doing. Clinical and behavioral outcomes will be measured at 1-, 4-, and 12-weeks post-dosing

Official Title
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Mechanisms Supporting Psilocybin-assisted Psychotherapy for Alcohol Use Disorder: A Randomized, Controlled Clinical Trial

Conditions
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Alcohol Use Disorder, Alcoholism

Intervention / Treatment
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* Drug: Psilocybin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets DSM-5 AUD criteria of at least moderate severity At least 5 heavy drinking days in past 30 days At least 18 (females) or 24 (males) drinks per week in past 30 days Desire to decrease alcohol consumption Limited lifetime hallucinogen use (less than 10 times total, none in past 6 months) Exclusion Criteria: Severe or moderate substance use disorder other than alcohol or nicotine in past 6 months Diagnosis of schizophrenia, bipolar disorders or first-degree relative with diagnosis Active suicidal ideation or serious attempt within past 3 years Currently pregnant, nursing, or trying to become pregnant Any notable abnormality on ECG, physical exam, or routine medical blood laboratory test

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose (25mg)<br>PEX010 (Oral Psilocybin), 25mg; single dose administered 24hrs prior to first of 5 weekly MET sessions | Drug: Psilocybin<br>* Single dosing session followed by 5 MET weekly sessions starting 24hrs after dosing<br>* Other names: PEX010;|
| Active Comparator: Low dose (1mg)<br>PEX010 (Oral Psilocybin), 1mg; single dose administered 24hrs prior to first of 5 weekly MET sessions | Drug: Psilocybin<br>* Single dosing session followed by 5 MET weekly sessions starting 24hrs after dosing<br>* Other names: PEX010;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heavy drinking | Percent heavy drinking days (TLFB) | Change from baseline to 1-, 4-, and 12-weeks post-dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abstinence | Days abstinent (TLFB) | Change from baseline to 1-, 4-, and 12-weeks post-dosing | 
| Biomarkers of alcohol consumption | Phosphatidylethanol (Peth) | Change from baseline to 1-, 4-, and 12-weeks post-dosing | 
| Alcohol cue reactivity | Alcohol urge questionnaire (AUQ) | Change from baseline to 1-, 4-, and 12-weeks post-dosing | 
| Cognitive flexibility | Berg Card Sorting Task | Change from baseline to 1-, 4-, and 12-weeks post-dosing | 
| Depression | The Montgomery-Åsberg Depression Rating Scale (MADRS) | Change from baseline to 1-, 4-, and 12-weeks post-dosing | 
| Anxiety | The General Anxiety Disorder 7 (GAD-7) scale | Change from baseline to 1-, 4-, and 12-weeks post-dosing | 
| Quality of life | The World Health Organization Quality of Life (WHOQOL) scale | Change from baseline to 1-, 4-, and 12-weeks post-dosing | 
| Glutamate levels | MR spectroscopy of glutamate levels in the anterior cingulate cortex | Change from baseline to 1-week post-dosing | 
| GABA levels | MR spectroscopy of GABA levels in the anterior cingulate cortex | Change from baseline to 1-week post-dosing | 
| Resting state functional connectivity |  | Change from baseline to 1-week post-dosing |