Psilocybin for Heart Function

Overseen By Christina Behlke, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Usona Institute

Must not be taking: Psychedelics, MDMA, Ketamine

Disqualifiers: Cardiovascular, Psychiatric, Gastrointestinal, others

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

Compensation: Varies

Number of Visits: 6

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, affects the heart's electrical activity and how food influences its processing in the body. The study has two parts: one examines the heart effects of a high dose of psilocybin, and the other investigates how eating or fasting affects its absorption. Individuals who are generally healthy and have not recently taken psilocybin or similar psychedelics may be suitable candidates. As a Phase 1 trial, this research aims to understand how psilocybin works in people, offering participants the opportunity to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you should not have taken psilocybin or other psychedelics in the 28 days before starting the study.

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

Research shows that psilocybin, the main compound tested in this trial, has some safety data from earlier studies. Psilocybin, a psychedelic substance found in certain mushrooms, has been shown in previous studies to be generally safe for healthy adults when used in controlled settings.

Most reported side effects have been mild and temporary, such as feelings of anxiety, mood changes, and increased heart rate. These effects typically resolve on their own after a short time. This trial will test both regular and higher doses of psilocybin, so careful monitoring is essential.

This trial is in an early stage, focusing mainly on understanding safety and how the body processes psilocybin. Always consult a healthcare professional before deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Psilocybin is unique because it's a psychedelic compound derived from certain mushrooms, offering a novel approach to mental health conditions compared to traditional medications like SSRIs or benzodiazepines. Unlike these standard treatments, which often take weeks to show effectiveness and primarily target neurotransmitter levels, psilocybin acts on serotonin receptors in the brain and can induce profound changes in perception and mood relatively quickly. Researchers are excited about its potential to provide rapid mood enhancements and long-lasting effects after just a single dose, which could revolutionize how we treat conditions like depression or PTSD. Additionally, this trial is investigating how psilocybin affects the heart's electrical activity and how food influences its absorption, which could provide critical insights for safe and effective treatment protocols.

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

Research has shown that psilocybin, when used in controlled amounts, may help treat depression. One study found that a single 25 mg dose of psilocybin significantly reduced depression symptoms over three weeks compared to a smaller dose. The positive effects appeared to last longer, with improvements observed for up to 52 weeks. These findings suggest psilocybin might help maintain a longer-lasting antidepressant effect. In this trial, participants will receive various doses and conditions of psilocybin, including therapeutic and supratherapeutic doses, as well as placebo controls. While the current trial tests these different doses and conditions, past results offer hope that psilocybin could effectively improve mood and mental health. ^{6 7 8 9 10}

Who Is on the Research Team?

Charles Raison, MD

Principal Investigator

Usona Institute

Are You a Good Fit for This Trial?

Inclusion Criteria

Provision of signed and dated informed consent form (ICF)

Stated willingness to comply with all study procedures and availability for the duration of the study

Healthy adult male or female

Exclusion Criteria

History of significant hypersensitivity to psilocybin or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs

Presence of out-of-range cardiac interval (PR < 110 msec, PR > 200 msec, QRS < 60 msec, QRS >110 msec and QTcF > 450 msec for males and > 470 for females) on the ECG at screening or other clinically significant ECG abnormalities, unless deemed non-significant by an Investigator

Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Treatment

Participants receive a single dose of psilocybin or placebo in a crossover design to evaluate cardiac repolarization

Up to 24 hours per treatment period

4 treatment periods with multiple ECG assessments

Part 2: Treatment

Participants receive a single dose of psilocybin under fed or fasted conditions to evaluate pharmacokinetics

Up to 24 hours per treatment period

2 treatment periods with pharmacokinetic assessments

Follow-up

Participants are monitored for treatment-related adverse events

Up to 30 days post-dose for Part 1 and 15 days post-dose for Part 2

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

How Is the Trial Designed?

Group I: Part 2: IP at Therapeutic Dose (Fed Conditions) Experimental Treatment 1 Intervention

A single therapeutic dose of psilocybin under fed conditions.

Group II: Part 2: IP at Therapeutic Dose (Fasted Conditions) Experimental Treatment 1 Intervention

A single therapeutic dose of psilocybin administered under fasted conditions.

Group III: Part 1: Treatment B (IP at Supratherapeutic Dose) Experimental Treatment 1 Intervention

A single supratherapeutic dose of psilocybin.

Group IV: Part 1: Treatment A (IP at Therapeutic Dose) Experimental Treatment 1 Intervention

A single therapeutic dose of psilocybin.

Group V: Part 1: Treatment D (Placebo - Positive Control) Active Control 1 Intervention

A single 400 mg dose of moxifloxacin.

Group VI: Part 1: Treatment C (Placebo - Negative Control) Placebo Group 1 Intervention

A single dose of placebo-to-match psilocybin MCC capsules.

Who Is Running the Clinical Trial?

Usona Institute

Lead Sponsor

Trials

18

Recruited

1,100+

Published Research Related to This Trial

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]

The study developed highly sensitive and accurate methods using liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS-MS) to effectively distinguish between psilocin and psilocybin, two active compounds in magic mushrooms.

Detection limits for these compounds were extremely low, ranging from 1 to 25 picograms, and the methods demonstrated high precision with low variability, making them suitable for analyzing psilocin and psilocybin content in various samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid chromatography-mass spectrometric and liquid chromatography-tandem mass spectrometric determination of hallucinogenic indoles psilocin and psilocybin in "magic mushroom" samples. Kamata, T., Nishikawa, M., Katagi, M., et al.[2016]

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]

This study found that the binding of serotonin 2A receptors (5-HT2AR) in the brain can predict how long the peak effects of psilocybin last and how quickly individuals return to normal consciousness after its effects wear off.

Higher levels of 5-HT2AR binding were associated with lower scores on the Mystical Experience Questionnaire, suggesting that individual differences in receptor availability may influence the subjective experience of psilocybin, which could have implications for its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. Stenbæk, DS., Madsen, MK., Ozenne, B., et al.[2022]

Genomic analysis of five species of Psilocybe mushrooms revealed a much greater metabolic diversity than previously understood, indicating potential for discovering new compounds beyond psilocybin and psilocin.

Two species, P. cyanescens and P. mexicana, were identified as producers of aeruginascin, along with other metabolites like lumichrome and verpacamide A, which may help explain the pharmacological and toxicological effects associated with these mushrooms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic Survey of Psilocybe Natural Products. Dörner, S., Rogge, K., Fricke, J., et al.[2022]

A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quickly and accurately measure the levels of psilocybin and psilocin in magic truffles, with high precision and reliability (r² > 0.99).

The study found that only psilocybin was present in the examined Psilocybe sclerotia, with concentrations ranging from 59.3 to 167.8 µg per 100 mg of fresh truffles, indicating variability in psilocybin content.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magic truffles or Philosopher's stones: a legal way to sell psilocybin? Pellegrini, M., Rotolo, MC., Marchei, E., 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]

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 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 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 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 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206443

Single-Dose Psilocybin for a Treatment-Resistant Episode ... Psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40047545/

Results From a Long-Term Observational Follow-Up Study ... Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg.

3. compasspathways.com compasspathways.com/our-work/comp360-psilocybin-treatment-in-trd/

COMP360 psilocybin treatment in TRD This trial assessed the safety and efficacy of COMP360 psilocybin treatment in three doses: 1mg, 10mg, 25mg. The results, published in the New England ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05624268

Efficacy, Safety, and Tolerability of COMP360 in ... This is a phase III, international, multi-centre, randomised, parallel group, fixed single-dose, double-blind, placebo-controlled study.

5. ir.compasspathways.com ir.compasspathways.com/News--Events-/news/news-details/2025/Compass-Pathways-Announces-Publication-of-Results-from-COMP004-Study-on-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx

Compass Pathways Announces Publication of Results from ... 52-week observational follow-up study from Phase 2b reveals single 25 mg COMP360 psilocybin dose offers longer-term antidepressant effects ...

6. 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 ...

7. 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 ...

8. 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.

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

Psilocybine - the NIST WebBook Psilocybine's formula is C12H17N2O4P, molecular weight is 284.2481, CAS number is 520-52-5, and also known as Psilocybin.

10. zfin.org zfin.org/CHEBI:8614

ZFIN ChEBI: psilocybin A tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic alkaloid isolated ...