Psilocybin for Emotional Distress

Recruiting at 1 trial location

Overseen By James Downar, MDCM, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Lithium, Tramadol, MAOIs, Antipsychotics

Disqualifiers: Psychotic disorder, Bipolar, Dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this multi-centre phase I/II open-label, single-arm study is to determine the safety, feasibility, therapeutic dose, and preliminary efficacy of psilocybin microdosing to treat psychological distress among patients with advanced illness. Forty patients will receive psilocybin drug product (1-3mg per day, Mon-Fri) for 4 weeks to be administered via oral capsules by the participant. Feasibility (recruitment rate, rate of intervention and follow-up completion), safety (rate of adverse events), dosing, and preliminary efficacy (depression, anxiety, overall well-being, and global impression of change) will be measured.

Will I have to stop taking my current medications?

You may need to stop or adjust some medications. If you're taking lithium, tramadol, certain antidepressants, or antipsychotics, you might need to stop or switch them. If you're on an SSRI or antipsychotic, your dose must stay the same during the trial. You also can't take any other psychedelic substances and must avoid benzodiazepines or antipsychotics within 12 hours of taking psilocybin.

What data supports the effectiveness of the drug psilocybin for emotional distress?

Research shows that psilocybin has been studied in clinical trials for various psychiatric disorders, including depression and anxiety, with results indicating it is well tolerated and can lead to significant long-term improvements even in patients with treatment-resistant conditions. ^{1 2 3 4 5}

Is psilocybin generally safe for human use?

Psilocybin, found in magic mushrooms, can cause rapid effects on the central nervous system, including hallucinations and physical symptoms like ataxia (loss of control of body movements) and hyperkinesis (increased movement). While some studies suggest it may be safe under controlled conditions, especially in lower doses, there are risks, particularly for those with heart conditions or when used in high concentrations. ^{3 6 7 8 9}

How is the drug psilocybin unique in treating emotional distress?

Psilocybin, found in 'magic mushrooms', is unique because it acts on the brain's serotonin system, potentially improving perception and mental skills, which is different from traditional treatments for emotional distress. It is known for inducing rapid effects, such as hallucinations, within 0.5-1 hour after ingestion, and its therapeutic potential is still being explored. ^{5 6 10 11 12}

Research Team

James Downar, MDCM, MSc

Principal Investigator

The Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for adults over 18 with advanced illnesses and a life expectancy of less than 12 months, who are under palliative care and experiencing significant psychological distress. Participants must be able to communicate in English or French.

Inclusion Criteria

You must be able to understand and speak English or French.

My doctor expects I have less than 12 months to live and I am receiving palliative care.

I am feeling very anxious, depressed, or unwell.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive psilocybin microdosing (1-3mg per day, Mon-Fri) for 4 weeks

4 weeks

Daily self-administration (Mon-Fri)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

1 day, 2 week, 4 week, 12 week, 24 week follow-up

Treatment Details

Interventions

• Psilocybin

Trial Overview The study tests the safety and initial effectiveness of microdosing psilocybin (1-3mg daily) for four weeks to alleviate psychological distress in palliative care patients. It's an open-label, single-arm phase I/II trial involving forty participants.

Participant Groups

Group I: Psilocybin Microdosing Experimental Treatment 1 Intervention

Participants will receive a 4-week psilocybin microdosing intervention (1-3mg/day, Monday-Friday for up to 4 weeks; start at 1mg with opportunity to increase dose each week)

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?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

CHU de Quebec-Universite Laval

Collaborator

Trials

177

Recruited

110,000+

St. Joseph's Healthcare Hamilton

Collaborator

Trials

203

Recruited

26,900+

The Ottawa Hospital

Collaborator

Trials

97

Recruited

64,000+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Kingston Health Sciences Centre

Collaborator

Trials

32

Recruited

34,400+

Bruyere Research Institute

Collaborator

Trials

35

Recruited

2,024,000+

William Osler Health System

Collaborator

Trials

11

Recruited

36,100+

Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Collaborator

Trials

64

Recruited

33,600+

Findings from Research

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, 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]

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 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-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]

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]

Psychoactive compounds from fungi, like psilocin and muscimol, have been associated with both potential therapeutic benefits and significant neurotoxicity, raising concerns about their safety in medical applications.

Recent studies suggest that while hallucinogens may impair cognitive functions, substances like psilocin could also enhance perception and mental skills, complicating their use in therapy and increasing the risk of misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fungal hallucinogens psilocin, ibotenic acid, and muscimol: analytical methods and biologic activities. Stebelska, K.[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]

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]

References

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

Psilocybin in Palliative Care: An Update. [2023]

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. England pubmed.ncbi.nlm.nih.gov

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

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

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

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

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

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

Fungal hallucinogens psilocin, ibotenic acid, and muscimol: analytical methods and biologic activities. [2016]

11. England pubmed.ncbi.nlm.nih.gov

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

12. 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]