Psilocybin versus ketamine for reducing heavy drinking in alcohol use disorder
Psilocybin vs Ketamine for Alcohol Use Disorder
This trial will test whether a single 30 mg dose of psilocybin or a weight-based 0.75 mg/kg dose of ketamine, each given with individual psychotherapy, can reduce heavy drinking in adults with moderate to severe alcohol use disorder.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 80 (estimated) |
| Ages | 21 Years to 65 Years |
| Sex | All |
| Sponsor | University of Iowa Academic / other |
| Locations | 1 site (Iowa City, Iowa) |
| Trial ID | NCT06405607 on ClinicalTrials.gov |
What this trial studies
This is a randomized, double-blind, active-comparator Phase 2 trial with two arms of 40 participants each comparing psilocybin (30 mg) versus ketamine (0.75 mg/kg) delivered alongside individual psychotherapy. Eligible participants are adults meeting DSM-5 criteria for moderate to severe alcohol use disorder who have had at least four heavy drinking days in the past 30 days and who meet medical and psychiatric inclusion/exclusion criteria. Key exclusions include recent hallucinogen or ketamine use, personal or family history of psychotic disorders, significant cardiac, neurologic, hepatic, or seizure disorders, pregnancy or breastfeeding, and ongoing formal AUD treatment. The study will collect clinical and behavioral measures of alcohol use and related outcomes over follow-up to compare the effects of the two interventions.
Who should consider this trial
Good fit: Adults with moderate to severe alcohol use disorder who have had at least four heavy drinking days in the past 30 days, are not currently in formal AUD treatment, and who meet the listed medical and psychiatric eligibility criteria are the best candidates.
Not a fit: People with a history of psychotic disorders, recent hallucinogen or ketamine use, uncontrolled cardiac, seizure, liver or other excluded medical conditions, pregnant or breastfeeding individuals, or those in current AUD treatment are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, this approach could offer a new medication-assisted option that helps reduce heavy drinking and supports recovery for people with alcohol use disorder.
How similar studies have performed: Early-phase studies of psilocybin and ketamine for substance use and mood disorders have shown promising signals, but definitive head-to-head evidence specifically for alcohol use disorder is limited.
Eligibility criteria
Show full inclusion / exclusion criteria
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.)
Where this trial is running
Iowa City, Iowa
- University of Iowa Health Care — Iowa City, Iowa, United States (Recruiting)
Study contacts
- Principal investigator: Peggy C Nopoulos, MD — University of Iowa
- Study coordinator: Lindsay E Golden, BS
- Email: lindsay-golden@uiowa.edu
- Phone: 319-384-5243
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.