Psilocybin vs Ketamine for Alcoholism

(Psi or Ket Trial)

Overseen By Peggy C Nopoulos, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Iowa

Must not be taking: Antidepressants, Antipsychotics, Benzodiazepines, others

Disqualifiers: Seizure disorder, Heart failure, Psychotic disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether psilocybin (a psychedelic compound) or ketamine (an anesthetic and potential antidepressant), combined with therapy, can help individuals with alcohol use disorder (AUD) reduce their drinking. Participants will receive either psilocybin or ketamine during therapy sessions to determine which treatment proves more effective. It targets those with at least four heavy drinking days in the past month who are not currently receiving treatment for AUD. The trial excludes individuals with certain medical conditions, such as heart issues, or those who have recently used hallucinogens. Participants should have someone available to assist with transportation and supervision after treatment sessions. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings in AUD treatment.

Do I have to stop taking my current medications to join the trial?

The trial requires that you stop taking certain medications that could interact with the study drugs, like antidepressants, antipsychotics, and others. If you're on a GLP-1 agonist, your dosage must have been stable for the past 3 months. It's best to discuss your specific medications with the study investigators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both psilocybin and ketamine could help treat alcohol use disorder and are generally safe for people.

For psilocybin, studies have found it to be safe and well-tolerated. One study found that a single 25 mg dose was safe for people with alcohol use disorder and helped reduce their alcohol consumption. Another review of several studies supports that psilocybin, when used with therapy, is safe and effective in lowering alcohol use.

Ketamine also has a good safety record. Research indicates that low doses of ketamine are safe and can help with alcohol withdrawal symptoms. In one study, patients with alcohol use disorder received three ketamine infusions, which were well-tolerated. Most studies report few serious safety concerns with ketamine in these situations.

Overall, both treatments have shown promising safety results in past studies, suggesting they may be suitable for further testing in clinical trials for alcohol use disorder. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for alcoholism focus on therapy and medications like disulfiram, naltrexone, or acamprosate that reduce cravings or the effects of alcohol. But psilocybin and ketamine offer new angles. Psilocybin, a compound found in certain mushrooms, may reset brain circuits related to addiction, offering potential for profound mental shifts that standard medications don't provide. Ketamine, traditionally an anesthetic, has rapid-acting antidepressant effects and might quickly reduce cravings or withdrawal symptoms. Researchers are excited because these treatments could provide faster and more effective relief for individuals struggling with alcoholism, targeting the brain in novel ways.

What evidence suggests that this trial's treatments could be effective for alcohol use disorder?

This trial will compare the effects of psilocybin and ketamine on alcohol use disorder (AUD). Research has shown that both psilocybin and ketamine may help treat AUD. Participants in the Psilocybin Group (Arm 1) will receive individual psychotherapy sessions plus a psilocybin session. Studies have found that psilocybin, when combined with therapy, can greatly reduce the number of days people drink heavily. Participants also reported fewer cravings for alcohol and felt more motivated to change their drinking habits. Meanwhile, participants in the Ketamine Group (Arm 2) will receive individual psychotherapy sessions plus a ketamine session. Ketamine has been shown to lower alcohol use and cravings, and it might help people stay sober for longer periods. Both treatments have proven effective in helping individuals with AUD drink less alcohol. ^{1 2 3 6 7}

Who Is on the Research Team?

Peggy C Nopoulos, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for men with moderate to severe alcohol use disorder, who've had at least 4 heavy drinking days in the past month. Participants must not have certain health conditions like heart disease, uncontrolled high blood pressure, or diabetes; no hallucinogen or ketamine use in the last 3 years; weigh between 50-150kg and have no history of psychotic disorders.

Inclusion Criteria

Not currently participating in formal treatment for AUD

No self-reported, personal, or familial history of specific psychotic disorders/episodes

No known allergies to rescue medication

Exclusion Criteria

MRI contraindication (pacemaker, etc.)

I am not taking any medication or supplements that could interfere with the study drug.

I have a history or current issues with severe mental health conditions or substance use.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive individual psychotherapy sessions and either a 30 mg dose of psilocybin or a 0.75 mg/kg dose of ketamine

16 weeks

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Psilocybin

Trial Overview The study compares psilocybin (30 mg) and ketamine (0.75 mg/kg), each paired with psychotherapy, to see which helps more with alcoholism. It's a double-blind trial where neither participants nor researchers know who gets which drug until after the results are collected.

How Is the Trial Designed?

Group I: Psilocybin Group (Arm 1) Experimental Treatment 1 Intervention

receives individual psychotherapy sessions plus a (30 mg) psilocybin session.

Group II: Ketamine Group (Arm 2) Active Control 1 Intervention

receives individual psychotherapy sessions plus a (0.75 mg/kg) ketamine session

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10237681/

Ketamine Treatment for Alcohol Use Disorder: A Systematic ... The data revealed reductions in weekly alcohol consumption across all three groups [F(1,81.684)=12.677, p = 0.001], with no statistically ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S037687162200343X

Efficacy of ketamine intervention to decrease alcohol use ... Recent evidence suggests that ketamine may be an effective intervention to treat alcohol use disorder and alcoholic withdrawal.

3. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2021.21030277

Adjunctive Ketamine With Relapse Prevention–Based ... This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10172666/

The therapeutic use and efficacy of ketamine in alcohol ... Ketamine used in AUD was beneficial in reducing cravings, alcohol consumption and longer abstinence rates when compared to treatment as usual.

5. ascpjournal.biomedcentral.com ascpjournal.biomedcentral.com/articles/10.1186/s13722-022-00345-y

Single-dose intravenous ketamine or intramuscular naltrexone ... Ketamine may be particularly well-tolerated among patients with physiologic alcohol tolerance, lacking the dysphoric symptoms that can be ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40773768/

Safety and efficacy of ketamine for the treatment of patients ... Five of them reported favorable effects of adjunctive ketamine treatment on a range of different alcohol-related outcomes such as abstinence ...

7. tandfonline.com tandfonline.com/doi/full/10.1080/00952990.2025.2535559?src=

Safety and efficacy of ketamine for the treatment of patients ... Multiple clinical studies have suggested a positive role for ketamine in treating people with AUD by reducing alcohol cravings, frequency of heavy drinking days ...