Psilocybin for Alcoholism

Recruiting at 1 trial location

Overseen By Gillian Monty

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: Psychiatric medications

Disqualifiers: Pregnancy, Seizure disorder, Cardiovascular disease, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a double-blind, randomized, placebo-controlled Phase 2 mechanistic clinical trial designed to evaluate the therapeutic neural mechanisms of psilocybin in patients with alcohol use disorder (AUD), and to determine whether further studies are warranted to study the relationship of any such effects to clinical improvement in AUD symptoms. The primary aims are to evaluate the effects of psilocybin on AUD; measures will include 1) fMRI neural activation and functional connectivity, using a well-validated task to characterize neural and subjective response to negative affective and alcohol visual stimuli; 2) alcohol use data (self-report and blood biomarkers); and 3) self-report measures related the NE, IS, and EF domains.

Will I have to stop taking my current medications?

The trial requires participants to stop taking any prohibited medications and supplements for at least 5 elimination half-lives or 14 days, whichever is longer, before starting the study. However, psychiatric medications will not be discontinued or changed for study participation.

What evidence supports the effectiveness of the drug psilocybin for treating alcoholism?

Psilocybin has shown promise in clinical trials for treating various psychiatric disorders, including substance use disorders, where patients sometimes experience significant, long-term improvements after just one or a few sessions. However, more research is needed to confirm its effectiveness specifically for alcoholism. ^{1 2 3 4 5}

Is psilocybin safe for human use?

Psilocybin has been studied for safety in humans, showing that while it can cause challenging experiences, the risk of lasting harm is low when used in controlled settings with proper support. In a study with healthy adults, escalating doses were generally well-tolerated, and most participants reported benefits despite some difficult experiences. ^{3 6 7 8 9}

How is the drug psilocybin unique in treating alcoholism?

Psilocybin is unique in treating alcoholism because it works by disrupting the reconsolidation of alcohol-related memories, which may help reduce alcohol-seeking behavior. Unlike traditional treatments, psilocybin acts on serotonin receptors in the brain, potentially offering a novel approach for those who do not respond to existing therapies. ^{3 6 10 11 12}

Research Team

Michael Bogenschutz, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for individuals with alcohol use disorder (AUD). Participants should be willing to undergo MRI scans and provide self-reports on their alcohol consumption. Details about specific inclusion and exclusion criteria are not provided, but typically these would cover health status, age range, severity of AUD, and other factors relevant to the study.

Inclusion Criteria

Have at least 4 heavy drinking days (4 or more drinks per day for a woman, 5 or more drinks per day for a man) in the 30 days prior to admission to SHH

Have a negative pregnancy test at screening, Baseline, Day 0 (pre-IP administration); and Day 2.

I agree to use birth control during the trial if I can become pregnant or father a child.

Exclusion Criteria

I do not have any health conditions that would make it unsafe for me to join the study.

Pregnancy or lactation

Have any of the following DSM-5 psychiatric disorders, as determined by the MINI and Psychiatric History at the Screening Visit: Lifetime history of schizophrenia spectrum or other psychotic disorder, current alcohol withdrawal, history of mania, active suicidal ideation with intent, made a medically significant suicide attempt within the past 12 months, family history of certain psychiatric disorders, history of hallucinogen use disorder, history of hallucinogen persisting perceptual disorder, any use of classic psychedelics in the past 1 year, > 25 lifetime uses of classic psychedelics, incarcerated or have pending legal action that could prevent participation in study activities, court-mandated to complete residential treatment at SHH, unable or unwilling to discontinue taking any protocol-prohibited medications and supplements, known allergy or hypersensitivity to psilocybin or any of the materials contained in the IP used in the study, allergy, hypersensitivity, or other contraindication that would preclude safe treatment of acute hypertension, anxiety, or psychotic symptoms if necessary during or immediately after the IP Administration Session, have any other medical, psychiatric, or psychosocial disorder, symptom, condition, or situation that is likely to interfere with the establishment of rapport, adherence to study requirements, or safe administration of psilocybin or fMRI scanning, inability to safely complete fMRI sessions, any history of severe traumatic brain injury.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single IP administration session of psilocybin or placebo and three supportive therapy sessions

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of alcohol use and neural activity

24 weeks

Regular follow-up visits

Treatment Details

Interventions

• Psilocybin

Trial Overview The trial is testing whether psilocybin can help treat AUD compared to an inactive placebo. All participants will receive supportive therapy sessions. The effects will be measured using brain imaging (fMRI), blood tests for alcohol biomarkers, and questionnaires assessing emotional response and drinking behavior.

Participant Groups

Group I: Oral high-dose of psilocybin Experimental Treatment 2 Interventions

Participants will receive a single IP administration session of psilocybin (30 mg total) and three supportive therapy sessions.

Group II: Placebo control Placebo Group 2 Interventions

Participants will receive a single IP administration session of matching placebo capsules and three supportive therapy sessions.

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

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

Psilocybin is primarily a pro-drug that converts to the active compound psilocin in the body, which then interacts with serotonin receptors to produce its hallucinogenic effects.

The metabolism of psilocybin and psilocin varies significantly among individuals, affecting their dose-response and potential toxicity, highlighting the need for personalized approaches in therapeutic settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Dinis-Oliveira, RJ.[2018]

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

Psilocybin shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., et al.[2023]

In a study involving eight volunteers, psilocybin was administered, and its metabolite, psilocin, was found to peak in urine concentrations up to 870 microg/L within 2-4 hours after ingestion, indicating a rapid metabolism.

About 3.4% of the psilocybin dose was excreted as free psilocin within 24 hours, and using beta-glucuronidase to treat urine samples significantly increased detectable levels of psilocin, suggesting that enzymatic processes can enhance the detection of this metabolite.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man. Hasler, F., Bourquin, D., Brenneisen, R., et al.[2019]

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]

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]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

Psilocybin, a prodrug for psilocin, shows strong agonist activity at the serotonin 5-HT2A receptor, which is responsible for its psychedelic effects, and has been shown to have nanomolar affinity for various serotonin receptor subtypes in both in vitro and in vivo studies.

In mouse experiments, psilocybin and related compounds induced head twitch responses, a sign of psychedelic activity, which were blocked by a 5-HT2A antagonist, confirming the involvement of this receptor in their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. Glatfelter, GC., Pottie, E., Partilla, JS., et al.[2023]

Research on four species of Psilocybe mushrooms revealed the presence of β-carbolines, such as harmane and harmine, which are derived from l-tryptophan and contribute to the mushrooms' psychoactive effects.

These β-carbolines act as potent inhibitors of monoamine oxidases, which not only affect the degradation of psilocybin but also suggest a complex interaction of natural compounds that enhance the pharmacological effects of the mushrooms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Production of Psilocybin and a Cocktail of β-Carboline Monoamine Oxidase Inhibitors in "Magic" Mushrooms. Blei, F., Dörner, S., Fricke, J., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

Simultaneous Production of Psilocybin and a Cocktail of β-Carboline Monoamine Oxidase Inhibitors in "Magic" Mushrooms. [2021]