Psilocybin Therapy for Alcoholism

(PAP-AUD Trial)

Overseen By Kaitlin O'Grady

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Disqualifiers: Substance use disorder, Schizophrenia, Bipolar, 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

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

Compensation: Varies

Number of Visits: 8

Duration: 5 weeks

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a single dose of psilocybin (a psychedelic compound), combined with motivational enhancement therapy (MET), can reduce heavy drinking in individuals with alcohol use disorder (AUD). Participants will be divided into two groups, receiving either a high dose (25mg) or a low dose (1mg) of psilocybin before beginning therapy sessions. The trial seeks participants who have been drinking heavily in the past month and wish to reduce their intake, but have limited experience with hallucinogens. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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 and well-tolerated. One study found that patients who had recently stopped drinking alcohol and had other health issues managed psilocybin therapy well and found it acceptable. Most participants handled the treatment without serious side effects.

A review of several studies found that using psilocybin with therapy significantly reduced alcohol use. Importantly, these studies did not report major safety concerns, suggesting that psilocybin can be used safely in these settings.

While individual responses can vary, the overall evidence supports the safety of using psilocybin in controlled therapy settings. ^{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 involve behavioral therapies and medications like naltrexone or acamprosate, psilocybin is derived from psychedelic compounds found in certain mushrooms. Researchers are excited about this treatment because psilocybin acts on serotonin receptors in the brain, potentially leading to profound changes in perception and behavior after just a single dose. Additionally, psilocybin's potential to rapidly reduce alcohol cravings and promote long-term behavioral change offers a promising new avenue compared to the gradual effects of current therapies. This novel approach could revolutionize how we address addiction by providing faster and potentially more enduring results.

What evidence suggests that psilocybin might be an effective treatment for alcoholism?

Research shows that psilocybin significantly impacts alcohol use disorder (AUD). In earlier studies, participants who took psilocybin reported fewer cravings and reduced alcohol consumption. Psilocybin affects brain areas linked to mood and behavior, aiding in addiction treatment. This trial will administer either a high dose (25mg) or a low dose (1mg) of psilocybin to participants. Combining psilocybin with therapy has shown promise in improving treatment outcomes. These findings suggest that psilocybin could effectively reduce heavy drinking in individuals with AUD. ^{6 7 8 9 10}

Who Is on the Research Team?

Leah Mayo, PhD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for adults who want to cut down on heavy drinking, meet the criteria for a moderate or severe alcohol use disorder, and have had multiple heavy drinking days recently. They should not be frequent users of hallucinogens, pregnant, or trying to become pregnant. People with certain mental health conditions or serious substance abuse issues other than alcohol are not eligible.

Inclusion Criteria

Limited lifetime hallucinogen use (less than 10 times total, none in past 6 months)

At least 5 heavy drinking days in past 30 days

I have consumed 24 or more drinks weekly in the last month.

Exclusion Criteria

I have been diagnosed with schizophrenia or bipolar disorder, or have a close family member who has.

I have not had serious thoughts or attempts of suicide in the last 3 years.

Currently pregnant, nursing, or trying to become pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete clinical, behavioral, and neuroimaging measures

1 week

Treatment

Single dose of psilocybin administered followed by 5 weekly MET sessions

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

3 visits (in-person) at 1-, 4-, and 12-weeks post-dosing

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study is testing whether a single dose of psilocybin combined with motivational enhancement therapy can help reduce excessive alcohol consumption in individuals diagnosed with an alcohol use disorder.

How Is the Trial Designed?

Group I: High Dose (25mg) Experimental Treatment 1 Intervention

PEX010 (Oral Psilocybin), 25mg; single dose administered 24hrs prior to first of 5 weekly MET sessions

Group II: Low dose (1mg) Active Control 1 Intervention

PEX010 (Oral Psilocybin), 1mg; single dose administered 24hrs prior to first of 5 weekly MET 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?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Bloom Psychedelic Therapy and Research Institute

Collaborator

Trials

1

Recruited

130+

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-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, 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]

Psilocybin, a compound found in certain mushrooms, is being studied for its potential therapeutic effects in treating conditions like addiction, anxiety, and depression, primarily through its active metabolite psilocin, which interacts with the 5HT2A receptor.

While psilocybin shows promise as a treatment agent in neuropsychiatry, careful consideration of its safety and potential for harm is necessary to determine its clinical use, highlighting the need for a responsible approach in this research area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy. Dodd, S., Norman, TR., Eyre, HA., et al.[2022]

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]

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]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

Psilocybin, found in 'magic mushrooms', shows promise as a non-addictive alternative for treating mental health disorders like major depressive disorder and addiction, potentially addressing the urgent need for new therapies amid rising addiction and suicide rates.

Current research indicates that psilocybin may offer therapeutic benefits without the overdose risks associated with traditional mind-altering substances, suggesting a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. Kargbo, RB.[2021]

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 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]

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. 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.

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. sciencedirect.com sciencedirect.com/topics/immunology-and-microbiology/psilocybin

Psilocybin - an overview Psilocybin is a substance that causes an altered state of consciousness, which is phenomenologically similar to acute psychosis.

6. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2795625

Percentage of Heavy Drinking Days Following Psilocybin ... Valid drinking outcome data were obtained for 717 of 744 months (96.4%) in the 8-month follow-up period for the 93 participants receiving ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9577917/

Psilocybin-assisted therapy for reducing alcohol intake in ... Psilocybin-assisted therapy will cause a larger reduction in alcohol consumption measured as percentage of heavy drinking days compared with placebo-assisted ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149763425001630

Efficacy and safety of psilocybin for the treatment ... Psilocybin-assisted psychotherapy showed significant reductions in alcohol use and high smoking cessation rates. · Among 16 studies, most were open-label or ...

9. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00081-1/fulltext

Psilocybin-assisted therapy for relapse prevention in ... Therefore, the current data reveal no significant impact of psilocybin-assisted therapy on abstinence or alcohol use levels after alcohol ...

10. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/add.70152

Psilocybin in alcohol use disorder and comorbid ... Conclusions. Psilocybin-assisted psychotherapy appears feasible, acceptable, and safe in recently detoxified patients with comorbid alcohol use ...