Psilocybin for Alcoholism

Not yet 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how psilocybin, a compound in certain mushrooms, might help people with alcohol use disorder (AUD) reduce their drinking. Researchers aim to determine if psilocybin affects brain activity and connections, and whether these changes can alleviate AUD symptoms. Participants will receive either a high-dose psilocybin capsule or a placebo, along with supportive therapy sessions. This trial suits those diagnosed with moderate to severe AUD who have experienced at least four days of heavy drinking in the past month. As a Phase 2 trial, this research measures how well psilocybin works in an initial, smaller group, offering participants a chance to contribute to groundbreaking treatment development.

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.

Is there any evidence suggesting that psilocybin is likely to be safe for humans?

Research shows that psilocybin, a substance found in certain mushrooms, is usually safe for people. Most studies report only mild to moderate side effects, such as temporary anxiety, nausea, or dizziness. Serious side effects are rare but have occurred in some cases. Psilocybin is tested in controlled environments with medical professionals present, ensuring any side effects can be managed safely. While psilocybin remains under study, its use in past research for conditions like depression provides some understanding of its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcoholism?

Unlike the standard treatments for alcoholism, which often include medications like disulfiram or naltrexone that work to reduce cravings or create aversion, psilocybin represents a novel approach by acting on serotonin receptors in the brain. This psychedelic compound is thought to potentially create profound changes in perception and consciousness that could help patients address the root psychological issues contributing to their addiction. Researchers are excited about psilocybin because it might offer a new pathway to recovery, helping individuals gain insights and motivation to change their drinking behavior through just a single high-dose session, potentially leading to lasting effects.

What evidence suggests that psilocybin might be an effective treatment for alcohol use disorder?

Research shows that psilocybin, a substance found in certain mushrooms, may help treat alcohol use disorder (AUD). In this trial, one group of participants will receive a high dose of psilocybin, while another group will receive a placebo. Studies suggest that psilocybin can reduce cravings and alcohol consumption by affecting parts of the brain related to mood and behavior. Some early findings also indicate it helps people change their perspective on alcohol and their relationship with it. While more research is needed, these initial results offer promise for those seeking new treatments for AUD. ^{1 2 3 4 5}

Who Is on the Research Team?

Michael Bogenschutz, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. en.wikipedia.org en.wikipedia.org/wiki/Psilocybin

Psilocybin Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in ...

2. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Psilocybin

Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIH Psilocybin is a tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic ...

3. webbook.nist.gov webbook.nist.gov/cgi/cbook.cgi?ID=520-52-5

Psilocybine - the NIST WebBook Formula · C12H17N2O4P ; Molecular weight · 284.2481 ; Permanent link for this species. Use this link for bookmarking this species for future reference.

4. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/psilocybine

Definition of psilocybine - NCI Drug Dictionary A tryptamine alkaloid, isolated from various genera of fungi including the genus Psilocybe, with hallucinogenic, anxiolytic, and psychoactive activities.

5. en.wikipedia.org en.wikipedia.org/wiki/Psilocin

Psilocin Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic.