Psilocybin for Neuropathic Pain

(PEACE-PAIN Trial)

Overseen By Karim Ladha, MD MSc FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Unity Health Toronto

Must not be taking: Serotonergic psychedelics

Disqualifiers: Psychotic disorder, Bipolar, Cardiovascular, others

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: 6

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests psilocybin, a substance found in magic mushrooms, to determine its effectiveness for chronic neuropathic pain. The study compares psilocybin with an active placebo to assess its efficacy and safety. Individuals with moderate-to-severe neuropathic pain who have not found relief with at least two other treatments might be suitable candidates for this trial. The goal is to determine whether a larger study should be conducted in the future. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking pain management research.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those on medications that interact with the study drugs. It's best to discuss your current medications with the trial team to see if they might interact.

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

Research has shown that psilocybin, the main ingredient in magic mushrooms, is usually safe for humans. In one study, participants took a single 25 mg dose of psilocybin, and no serious side effects occurred. This suggests that the treatment can be safe when used in a controlled environment. It is important to note that in this study, both the researchers and participants knew what was being given, which can sometimes affect the results.

Psilocybin has also been tested in people with depression that doesn't respond to other treatments, and it showed promise without causing major side effects. While researchers are studying psilocybin for other conditions like chronic pain, more research is needed to confirm its safety and effectiveness for these new uses.

Joining a trial like this can help gather more information on how well the treatment is tolerated. Current data suggests that psilocybin can be safe for human use in certain situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuropathic pain?

Psilocybin is unique because it offers a novel approach to treating neuropathic pain by targeting serotonin receptors in the brain, which is different from traditional pain medications like opioids or anticonvulsants. Unlike these standard treatments, psilocybin has the potential to alter the perception of pain and improve mood, which could provide a dual benefit for patients. Researchers are excited about psilocybin because it could offer rapid pain relief and mental health support in a single dose, potentially reducing the need for long-term medication use.

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

This trial will compare the effects of psilocybin with an active placebo for treating neuropathic pain. Research suggests that psilocybin, the active ingredient in magic mushrooms, might help treat long-lasting nerve pain. Psilocybin affects certain brain areas related to mood and perception, potentially reducing pain. Although clinical proof for nerve pain is not yet available, studies have shown it could help with conditions like depression and anxiety, which often share causes with chronic pain. Therefore, researchers hope psilocybin could provide relief for people with this type of pain. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals suffering from chronic neuropathic pain, including conditions like Ilioinguinal Neuralgia. Participants will be recruited from St. Michael's Hospital to determine if a larger study is feasible.

Inclusion Criteria

Previous trials of at least two medications recommended in Canadian consensus guidelines with no self-reported meaningful improvement

Sufficient command of English to participate in psychotherapy

Use of highly effective or double-barrier methods of contraception for participants of childbearing potential

Exclusion Criteria

History of Dextromethorphan addiction or abuse

Previous lifetime use of a serotonergic psychedelic drug

I am not pregnant or nursing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Psilocybin or Dextromethorphan with psychological support

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

5 visits (in-person) on days 1, 7, 14, 30, and 90

What Are the Treatments Tested in This Trial?

Interventions

• Active Placebo
• Psilocybin

Trial Overview The study tests the effectiveness of Psilocybin (found in magic mushrooms) against an active placebo (dextromethorphan) in managing chronic neuropathic pain through a randomized control double-blinded trial.

How Is the Trial Designed?

Group I: Intervention Arm with Psilocybin Experimental Treatment 1 Intervention

Intervention Arm with Psilocybin 25 mg single dose PO + psychological support

Group II: Placebo Placebo Group 1 Intervention

Placebo (Active) Dextromethorphan 400 mg single dose PO + psychological support

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?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Published Research Related to This Trial

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 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]

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 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 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]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[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]

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/medicine-and-dentistry/psilocin

Psilocin - an overview | ScienceDirect Topics Psilocin causes anxiety, disorientation, depersonalization, psychosis, and hallucinations. Other adverse effects include severe nausea, vomiting, ...

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

COMP360 Psilocybin for Treatment-Resistant Depression This study aims to compare the safety and efficacy of 2 fixed doses, taken 3 weeks apart, of 25 mg COMP360 to 10 mg COMP360 and 1 mg COMP360. “ ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12030455/

The Emergence of Psilocybin in Psychiatry and Neuroscience The results demonstrated that psilocybin significantly improved psychological flexibility, mindfulness, and values-based living. These psychological ...

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/20/NCT06518720/Prot_SAP_000.pdf

Treatment with Psilocybin for Chronic Neuropathic Pain ... Research has shown that co-morbid pain and MDD confers worse outcomes than either disease alone (Dhanju et al., 2019). Patients with pain and co-morbid MDD ...

9. ir.compasspathways.com ir.compasspathways.com/News--Events-/news/news-details/2025/Compass-Pathways-Announces-Publication-of-Results-from-Phase-2-Study-of-COMP360-Psilocybin-for-Post-Traumatic-Stress-Disorder/default.aspx

News Details Open-label Phase 2 study shows a single 25 mg COMP360 psilocybin dose was well tolerated, with no serious adverse events observed, ...

10. theeducatedpatient.com theeducatedpatient.com/view/psilocybin-shows-promise-for-hard-to-treat-depression-in-new-study

Psilocybin Shows Promise for Hard-to-Treat Depression in ... A single dose of COMP360 psilocybin significantly reduced depression symptoms in people with treatment-resistant depression, according to new ...