An Evaluation of Psilocybin's Effect on Cardiac Repolarization and the Effect of Food on Psilocybin's Pharmacokinetics

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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the effects of psilocybin, a compound from certain mushrooms, on heart function and its absorption with food. Healthy adults are tested to see how it changes brain function and perception. Psilocybin is a naturally occurring substance found in certain mushrooms, known for its hallucinogenic effects and potential therapeutic benefits.

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.

What evidence supports the effectiveness of the drug psilocybin?

Psilocybin has shown potential therapeutic benefits in palliative care, helping patients manage psychological distress. It works by activating serotonin receptors in the brain, which can lead to altered states of consciousness and potentially improve mood and well-being. ^{1 2 3 4 5}

Is psilocybin generally safe for human use?

Psilocybin, found in magic mushrooms, has been studied for its effects on the brain and body. While it can cause hallucinations and other effects, studies suggest it can be safe under controlled conditions. However, caution is advised, especially for people with heart conditions, as its safety in such cases is not fully known. ^{2 6 7 8 9}

How does this drug differ from other treatments for the condition?

This drug, containing psilocybin, is unique because it works by activating serotonin receptors in the brain, which can lead to psychedelic effects. Unlike traditional treatments, it offers a novel approach by potentially altering perception and mood, which may be beneficial for mental health conditions like depression and PTSD. ^{10 11 12 13 14}

Research Team

Charles Raison, MD

Principal Investigator

Usona Institute

Eligibility Criteria

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

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

Treatment Details

Interventions

• Psilocybin

Participant Groups

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+

Findings from Research

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, 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 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]

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]

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]

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]

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]

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]

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]

References

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

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

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

The pharmacology of psilocybin. [2016]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. [2022]

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

Psilocybin in Palliative Care: An Update. [2023]

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

[Hallucinogenic mushrooms]. [2018]

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

Intravenous mushroom poisoning. [2019]

8. England 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. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. Germany pubmed.ncbi.nlm.nih.gov

Genetic Survey of Psilocybe Natural Products. [2022]

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

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

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

DNA Authentication and Chemical Analysis of Psilocybe Mushrooms Reveal Widespread Misdeterminations in Fungaria and Inconsistencies in Metabolites. [2023]

13. United States 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. [2016]

14. England pubmed.ncbi.nlm.nih.gov

Magic truffles or Philosopher's stones: a legal way to sell psilocybin? [2019]