Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder (PAP-AUD)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Alcoholism; Alcohol Use Disorder
• Intervention / Treatment: Drug: Psilocybin

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kaitlin O'Grady; Phone Number: 587-893-0257; Email: pactlab@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Recruiting
      • University of Calgary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meets DSM-5 AUD criteria of at least moderate severity
• Meets heavy drinking requirements (heavy drinking days, number of drinks) in past 30 days
• Desire to decrease alcohol consumption
• Limited lifetime hallucinogen use

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
Cognitive flexibility	Berg Card Sorting Task	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
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
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

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Johns Hopkins University; University of Maryland; Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Leah Mayo, PhD, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: August 9, 2023
• First Submitted That Met QC Criteria: August 9, 2023
• First Posted (Actual): August 16, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: REB23-0666

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No