Psilocybin vs Ketamine Psychotherapy for Alcoholism

Not currently recruiting at 1 trial location

Overseen By Lindsay E Golden

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Peggy C Nopoulos

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

Disqualifiers: Psychotic disorders, Substance use, 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: 10

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how two treatments—psilocybin and ketamine—can aid individuals struggling with alcohol use. Researchers aim to assess how each treatment, combined with talk therapy, affects drinking habits. Participants will be assigned to one of two groups: one will receive psilocybin sessions, and the other will have ketamine sessions. This trial suits English-speaking men who have experienced at least four heavy drinking days in the last month and meet specific health criteria. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

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

Yes, you may need to stop taking certain medications. The trial excludes participants using medications that could interact with the study drugs, such as antidepressants, antipsychotics, psychostimulants, treatments for addictions, and other dopaminergic or serotonergic agents. Check with the study investigators for specific guidance.

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

Research has shown that psilocybin-assisted therapy is generally safe for people with alcohol use disorder (AUD). Studies indicate that a single 25 mg dose of psilocybin, combined with therapy, can effectively reduce alcohol consumption. Participants found this treatment acceptable and manageable, with no serious safety issues reported.

Evidence suggests that ketamine can help treat AUD by reducing cravings and alcohol use. Most people tolerate ketamine well, though some might experience side effects like memory problems or slowed breathing, especially if mixed with alcohol. However, when used correctly in a clinical setting, ketamine is considered safe.

Both treatments have been studied in people with AUD, and while side effects can occur, they are generally well-tolerated when used as directed in a controlled environment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because both psilocybin and ketamine offer unique approaches to treating alcoholism. Unlike traditional treatments that often rely on counseling and medications like naltrexone or acamprosate, psilocybin is a psychedelic that can potentially create profound, mind-altering experiences, which may lead to significant behavioral changes and insights into addiction. Ketamine, typically used as an anesthetic, acts rapidly and can alter brain chemistry in a way that might reduce cravings and depressive symptoms associated with alcoholism. These drugs offer new hope by targeting the brain in novel ways, which could lead to more effective and quicker treatments for those struggling with alcohol dependency.

What evidence suggests that this trial's treatments could be effective for alcoholism?

This trial will compare the effects of psilocybin and ketamine in treating alcoholism. Studies have shown that psilocybin, when combined with therapy, can significantly reduce heavy drinking days for individuals with alcohol problems. Some research even suggests it outperforms other treatments. However, results vary, and not all studies report a substantial decrease in alcohol use. Meanwhile, ketamine has effectively reduced alcohol cravings and consumption, helping individuals maintain sobriety longer than usual treatments. Overall, both treatments appear promising, but results can differ depending on the individual. Participants in this trial will be assigned to either the Psilocybin Group or the Ketamine Group to evaluate these effects. ^{1 2 6 7 8}

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 adults with moderate to severe Alcohol Use Disorder who've had multiple heavy drinking days recently, are not in formal alcohol treatment, and have no serious health issues like heart disease or uncontrolled diabetes. Participants must be fluent in English, psilocybin and ketamine naive, without a history of certain mental health conditions.

Inclusion Criteria

I have never had a stroke, asthma, or severe alcohol withdrawal.

I do not have seizures, heart disease, uncontrolled high blood pressure, or insulin-dependent diabetes.

I have someone to take me home and watch over me after my treatment.

Exclusion Criteria

My heart, blood, and liver tests do not show serious problems.

MRI contraindication (pacemaker, etc.)

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 including cocaine, psychostimulant, or opioid use disorder within past 12 months and/or any use within past 30 days, 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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline and Randomization

Participants are consented, randomized into one of the two arms, complete psychiatric and medical evaluations, and undergo an MRI scan

1 week

1 visit (in-person)

Treatment

Participants receive 4 psychotherapy sessions, including a psilocybin or ketamine-assisted therapy session, with integration of experiences and MRI scans

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored weekly for safety and effectiveness after treatment, with a final MRI scan and assessment

4 weeks

4 visits (in-person)

Open-label extension (optional)

Participants in the ketamine group are offered a psilocybin-assisted therapy session and two follow-up/integration sessions, with an additional 4 weeks of follow-up

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Psilocybin

Trial Overview The study compares the effects of two types of assisted psychotherapy: one using psilocybin and the other using ketamine. It aims to see which helps more with alcohol use disorder by measuring changes in participants' drinking behavior.

How Is the Trial Designed?

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

receives individual psychotherapy sessions plus a (25 mg) psilocybin session.

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

receives individual psychotherapy sessions plus a (200 mg) ketamine session with open-label access option at the end of their study involvement.

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Peggy C Nopoulos

Lead Sponsor

Trials

2

Recruited

420+

Published Research Related to This Trial

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

Psilocybin, a naturally occurring compound from certain fungi, has shown significant clinical efficacy in reducing symptoms of depression and anxiety in multiple clinical trials, indicating its potential as a treatment for psychiatric disorders.

There have been no significant adverse clinical events or recorded deaths associated with psilocybin use, suggesting it may be a safe option; however, larger studies are needed before it can be approved for widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Psilocybin in the Treatment of Psychiatric Disorders with Attention to Relative Safety Profile: A Systematic Review. Hodge, AT., Sukpraprut-Braaten, S., Narlesky, M., et al.[2023]

Psilocybin, a compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

Psilocybin has shown promise in reducing symptoms of depression and anxiety, particularly in cancer patients, with effects lasting for at least six months after a single treatment, based on three controlled studies.

In small pilot studies, psilocybin has also demonstrated potential effectiveness in treating addiction to alcohol and cigarettes, suggesting its versatility as a therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Therapeutic Effects of Psilocybin: A Systematic Review. Goel, DB., Zilate, S.[2022]

S-ketamine, known for its rapid antidepressant effects, can cause neurotoxicity in the retrosplenial cortex, as indicated by the presence of heat shock protein 70 (HSP70) in treated rats.

In contrast, psilocybin did not show similar neurotoxic effects in the retrosplenial cortex, suggesting it may be a safer alternative for clinical use compared to S-ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin does not induce the vulnerability marker HSP70 in neurons susceptible to Olney's lesions. Iorgu, AM., Vasilescu, AN., Pfeiffer, N., et al.[2023]

In a study examining the effects of Psilocybe cubensis and Panaeolus cyanescens mushrooms on heart cells, the extracts did not worsen hypertrophy caused by endothelin-1 and provided protection against TNF-α-induced cell injury.

The findings suggest that these mushroom extracts can be safely used in controlled conditions for potential therapeutic benefits in heart disease, although caution is advised with higher concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. Nkadimeng, SM., Steinmann, CML., Eloff, JN.[2021]

Psychedelic substances like psilocybin, DMT, LSD, and MDMA are being researched for their potential therapeutic effects on psychiatric disorders, which are a leading cause of global disability.

The review highlights ongoing and recently completed clinical trials, indicating a renewed interest in the safety and efficacy of these compounds, especially in combination with psychotherapeutic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders. Rhee, TG., Davoudian, PA., Sanacora, G., et al.[2023]

A ketamine-assisted therapy program evaluated in a community of practice model showed significant improvements in mental health outcomes for 94 patients, with 91% reporting reduced anxiety, 79% reporting reduced depression, and 86% of PTSD patients screening negative after treatment.

The program demonstrated clinically significant enhancements in work/life functionality, with 92% of participants experiencing improvements, highlighting ketamine's potential as an effective treatment for those with treatment-resistant mental health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cohort-Based Case Report: The Impact of Ketamine-Assisted Therapy Embedded in a Community of Practice Framework for Healthcare Providers With PTSD and Depression. Dames, S., Kryskow, P., Watler, C.[2022]

A scoping review of 77 studies on serotonergic psychedelics (including LSD, ayahuasca, DMT, ibogaine, and mescaline) found that while these substances may improve mood, anxiety, and substance use, the evidence for their safety and efficacy is low-level compared to psilocybin.

Serious adverse events, including homicide and suicide, were reported in studies involving LSD, highlighting potential risks associated with these psychedelic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond Psilocybin: Reviewing the Therapeutic Potential of Other Serotonergic Psychedelics in Mental and Substance Use Disorders. Wong, S., Yu, AY., Fabiano, N., et al.[2023]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

Esketamine has shown a significant reduction in depressive symptoms and suicidal thoughts shortly after intake and after one month of treatment, outperforming standard antidepressants in many studies.

Psilocybin demonstrated its antidepressant effects starting one day after intake, with benefits lasting up to 6-8 months, and in some cases, it was found to be comparable or superior to traditional treatments like escitalopram.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esketamine and Psilocybin-The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review. Psiuk, D., Nowak, EM., Dycha, N., et al.[2022]

In a proof-of-concept study involving 10 alcohol-dependent participants, psilocybin administration led to a significant increase in abstinence rates after treatment, with effects maintained for up to 36 weeks.

Participants experienced no significant adverse events, suggesting that psilocybin is safe for use in this context, and the intensity of the psilocybin effects predicted positive changes in drinking behavior and cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Bogenschutz, MP., Forcehimes, AA., Pommy, JA., et al.[2022]

Citations

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Therapeutic potential of ketamine for alcohol use disorder Overall, KAP had a significant positive effect on primary outcome measures compared to controls, however, the data is mixed. The study examining KAP for TRD ...

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Home | SAMHSA - Substance Abuse and Mental Health ... SAMHSA leads efforts to advance behavioral health across the U.S., offering resources for mental health, substance use, and community well-being.

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8. americanaddictioncenters.org americanaddictioncenters.org/ketamine-abuse/mixing-alcohol

Dangers of Mixing Ketamine and Alcohol Individuals who mix ketamine and alcohol may be at increased risk of urinary tract issues, memory loss, slowed breathing, coma, and even death.