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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether small, regular doses of psilocybin, a compound in magic mushrooms, can ease emotional distress in people with serious illnesses. The trial aims to test the safety and potential benefits of this treatment for improving depression, anxiety, and general well-being. Suitable candidates include those in palliative care for an advanced illness who experience significant emotional distress. Participants will take psilocybin capsules at home for four weeks and provide feedback on their experiences. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to explore its potential benefits.

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.

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

Research has shown that psilocybin, the active ingredient in "magic mushrooms," has been tested in several studies for its safety and effects. One study found that psilocybin was generally well-tolerated, even at higher doses like 10mg and 25mg. Some people experienced mild side effects, such as headaches and nausea, but these were neither severe nor long-lasting.

In another study on treatment-resistant depression, patients who took psilocybin reported some side effects, usually mild. There were no reports of serious harm or life-threatening reactions. This suggests that psilocybin, even in controlled doses, is safe when used under medical supervision.

These studies suggest that taking very small amounts of psilocybin, known as microdosing, is likely to be even more tolerable. However, since microdosing has been studied less, the upcoming trial will provide more specific information on its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Psilocybin is unique because it taps into the power of psychedelics to potentially alleviate emotional distress, a departure from traditional treatments like antidepressants and therapy. Unlike standard medications that typically alter neurotransmitter levels over weeks, psilocybin targets serotonin receptors directly, potentially offering rapid relief in just a few doses. Researchers are excited about psilocybin's novel approach, as it may provide a new, effective option for those who don't respond well to conventional treatments. Additionally, the microdosing regimen being studied could minimize side effects while still delivering therapeutic benefits.

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

Research has shown that psilocybin, a substance in certain mushrooms, might help reduce depression and anxiety. Some studies found that a single larger dose of psilocybin can significantly lower depression levels, with effects lasting several weeks. In this trial, participants will receive psilocybin microdosing, which involves taking smaller amounts regularly, with the hope of achieving similar benefits over time. Psilocybin affects serotonin in the brain, a chemical that regulates mood. While more research is needed, early results suggest it might offer a new way to manage emotional distress, especially for those with serious illnesses. ^{1 3 5 6 7}

Who Is on the Research Team?

James Downar, MDCM, MSc

Principal Investigator

The Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Bruyère Health Research Institute.

Collaborator

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+

Published Research Related to This Trial

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]

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 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 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]

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 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, 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]

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]

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 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, 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]

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]

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. 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 Journal ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12226623/

Psilocybin therapy for treatment resistant depression MADRS score change at week 3 was the primary outcome of the study though a large reduction in depressive symptoms was evident on the day following psilocybin ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724020494

The role of the psychedelic experience in psilocybin ... Several exploratory trials have suggested that an exemplar, psilocybin, can reduce symptoms of major depressive disorder (MDD), including in ...

5. columbiapsychiatry.org columbiapsychiatry.org/news/psilocybin-found-rapidly-improve-depression-clinical-trial

Psilocybin Found to Rapidly Improve Depression in ... A single dose of psilocybin, combined with psychological support, generated a rapid response and significant reduction in depressive symptoms that lasted up to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05624268

Efficacy, Safety, and Tolerability of COMP360 in ... Psychological therapies cannot have been initiated within 30 days prior to Screening; Exposure to COMP360 psilocybin therapy prior to Screening. Ages Eligible ...

7. psychiatrictimes.com psychiatrictimes.com/view/comp360-psilocybin-for-treatment-resistant-depression-positive-phase-3-efficacy-data

COMP360 Psilocybin for Treatment-Resistant Depression COMP360 showed a statistically significant reduction in TRD symptom severity compared to placebo, with a clinically meaningful MADRS score ...