Psilocybin for Neuropathic Pain

(PEACE-PAIN Trial)

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

Trial Summary

What is the purpose of this trial?

This is a feasibility study to examine the use of use of Psilocybin (magic mushrooms) to alleviate pain in chronic neuropathic pain. While theoretical mechanisms demonstrate promise, there is no clinical evidence. This vacuum of clinical evidence has been occupied by a "psychedelic hype bubble" with media communications touting psychedelics as a 'miracle cures'. The mismatch between evidence and perception creates an urgent need for RCT to fill this significant gap. This trial aims to address this gap by conducting a pilot trial assessing the feasibility, tolerability, and preliminary efficacy of psilocybin for chronic neuropathic pain to inform a future larger, multi-centre study. The purpose is to conduct a randomized control double-blinded trial of psilocybin and active placebo (dextromethorphan). At this time, the aim of the trial is to recruit 30 participants from St. Michael's Hospital, to learn whether it will be feasible to plan a larger study in the future.

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.

What evidence supports the effectiveness of the drug psilocybin for treating neuropathic pain?

While there is no direct evidence for psilocybin's effectiveness in treating neuropathic pain, research has shown that psilocybin can significantly reduce depression and anxiety, which are often associated with chronic pain conditions. Additionally, psilocybin has shown promising results in treating addiction and mood disorders, suggesting potential benefits for other conditions involving the nervous system. ^{1 2 3 4 5}

Is psilocybin safe for human use?

Psilocybin is generally considered safe when used in controlled settings, but it can cause challenging psychological experiences, especially at higher doses or without proper support. Some people may experience temporary psychological distress, and in rare cases, there can be lasting psychological effects. It is important to use psilocybin under professional supervision to minimize risks. ^{5 6 7 8 9}

How does the drug psilocybin differ from other treatments for neuropathic pain?

Psilocybin is unique because it is a psychedelic compound that may work by altering brain function and perception, unlike traditional pain medications that target specific pain pathways. While other treatments like cannabis and opioids focus on direct pain relief, psilocybin's potential lies in its ability to modulate the brain's response to pain, offering a novel approach for those with treatment-resistant neuropathic pain. ^{10 11 12 13 14}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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, 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]

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]

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]

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]

References

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

Psilocybin in Palliative Care: An Update. [2023]

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

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

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

Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy. [2022]

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

Analysis of Psilocybin-Assisted Therapy in Medicine: A Narrative Review. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

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

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

7. 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]

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

The pharmacology of psilocybin. [2016]

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

Intravenous mushroom poisoning. [2019]

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

Low-dose vaporized cannabis significantly improves neuropathic pain. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Decreased basal endogenous opioid levels in diabetic rodents: effects on morphine and delta-9-tetrahydrocannabinoid-induced antinociception. [2013]

12. England pubmed.ncbi.nlm.nih.gov

Herbal medicinal products or preparations for neuropathic pain. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Natural Products and some Semi-synthetic Analogues as Potential TRPV1 Ligands for Attenuating Neuropathic Pain. [2022]

14. New Zealand pubmed.ncbi.nlm.nih.gov

A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis. [2020]