Psilocybin or Ketamine for Alcohol Use Disorder: An Active Comparator Trial (Psi or Ket)

Psilocybin vs Ketamine for Alcohol Use Disorder

This study will collect data that measures the effects of a psychedelic intervention on patients struggling with alcohol use disorder (AUD). The study design will be a double blind, randomized, active-comparator trial with two study arms. Subjects randomized to Arm 1 (n=40) will receive individual psychotherapy sessions plus a 30 mg dose of psilocybin. Arm 2 subjects (n=40) will receive individual psychotherapy sessions and a 0.75 mg/kg dose of ketamine.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Dependence; Alcohol Use Disorder; Alcohol Abuse
• Intervention / Treatment: Drug: Psilocybin; Drug: Ketamine

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peggy C Nopoulos, MD; Phone Number: 319-356-1144; Email: peggy-nopoulos@uiowa.edu
• Study Contact Backup: Name: Lindsay E Golden, BS; Phone Number: 319-384-5243; Email: lindsay-golden@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52240
      • Recruiting
      • University of Iowa Health Care
      • Contact: Lindsay E Golden; Email: lindsay-golden@uiowa.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Weight between 50kg and 150kg
• No known allergies to rescue medication
• For people capable of becoming pregnant, not pregnant and using contraception
• Not currently breastfeeding
• Meets criteria for DSM-V moderate to severe AUD.
• Have at least 4 heavy drinking days (5 or more standard drinks in a day) in the past 30 days.
• Not currently participating in formal treatment for AUD.
• No history of a of cerebrovascular accident, asthma, or significant alcohol withdrawal history
• No seizure disorder, coronary artery disease, heart failure, uncontrolled hypertension, insulin-dependent diabetes, pancreatitis, liver disease
• No hallucinogen or ketamine use in past 12 months
• No self-reported, personal, or familial history of specific psychotic disorders/episodes.
• No serious traumatic brain injury (TBI) in the past 2 years
• No substance use disorder other than AUD over the past 12 months
• If taking a GLP-1 agonist, stable dosage for past 3 months
• Family member/friend for pick-up, overnight post-drug session monitoring.
• No MRI contraindications

Exclusion Criteria:

Drug/medication assessment that yields: nonprescription medication use, nutritional supplement, or herbal supplement (except when approved by the study investigators), medically unstable, current medication use that has significant potential to interact with study drug (e.g., antidepressants, antipsychotics, psychostimulants, treatments for addictions, other dopaminergic or serotonergic agents, lithium, anticonvulsants, or benzodiazepines).

Psychiatric assessment that yields:1) history of severe suicide attempt, 2) current suicidality 3) first-degree relative with schizophrenia or schizoaffective disorder, 4) comorbid substance use disorder including cocaine, psychostimulant, or opioid use disorder within past 12 months 5) history of co-occurring psychotic episode/diagnosis including schizophrenia, schizoaffective disorder, schizophreniform, substance-induced psychosis, delusional disorder, or psychosis not otherwise specified, 6) high risk of adverse emotional or behavioral reaction based on the medical monitor's clinical evaluation that may also yield evidence of serious current stressors, a lack of meaningful social support, antisocial behavior, and/or serious personality disorders amongst other conditions.

Medical assessment that yields: serious ECG abnormalities (evidence of ischemia, myocardial infarction, QTc prolongation [QTc > .045]), serious abnormalities of complete blood count or chemistries, medical conditions that would preclude safe participation (significantly impaired liver function), or pregnancy.

MRI contraindication (pacemaker, etc.)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin Group (Arm 1); receives individual psychotherapy sessions plus a (30 mg) psilocybin session.	Drug: Psilocybin; 30 mg single dose
Active Comparator: Ketamine Group (Arm 2); receives individual psychotherapy sessions plus a (0.75 mg/kg) ketamine session	Drug: Ketamine; 0.75 mg/kg weight-based single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Timeline Follow-Back for Alcohol to assess change	Quantifies daily alcohol use	Weekly, over the course of 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T1rho	Measures biological changes in the brain	Twice (before intervention, post intervention): at week 1 and week 16
Resting state fMRI	Measures biological changes in brain resting state global functional connectivity	Twice (before intervention, post intervention):: at week 1 and week 16
EEG- signal complexity	Measures electrical signal change	Twice (before drug administration and at peak of drug experience) during week 3

Collaborators and Investigators

• Sponsor: University of Iowa
• Investigators: Principal Investigator: Peggy C Nopoulos, MD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: May 2, 2024
• First Submitted That Met QC Criteria: May 6, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: ketamine; psilocybin; psychedelic
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Ketamine; Psilocybin
• Other Study ID Numbers: 202404714

Drug and device information, study documents

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