Psilocybin for Enhanced Analgesia in Chronic nEuropathic PAIN

NCT06731335 | Recruiting Phase 2

• 1 other identifier: P-005
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Chronic Neuropathic Pain; Pain Management

Keywords

chronic pain; neuropathic pain; psychodelics; psilocybin; chronic neuropathic pain

Outcome Measures

Primary Outcomes (1)

• Feasibility to recruit 30 participants into a trial of psilocybin and active placebo to prepare for a larger multicentre trial

  Recruitment rate and withdrawal rate (Acceptability and feasibility study)

  18 months

Secondary Outcomes (2)

• Change in pain intensity from baseline to one month after interventions

  one month

• Change in pain interference from baseline to one month after interventions

  one month

Study Arms (2)

Intervention Arm with Psilocybin

EXPERIMENTAL

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

Drug: Psilocybin

Placebo

PLACEBO COMPARATOR

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

Drug: Active Placebo

Interventions

Psilocybin DRUG

PSILOCYBIN (PEX010) 25 mg PO single dose

Also known as: Psychotherapy

Intervention Arm with Psilocybin

Active Placebo DRUG

Dextromethorphan 400 mg PO single dose

Also known as: Psychotherapy

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• Diagnosis of chronic neuropathic pain as determined by a pain specialist
• Moderate-to-severe neuropathic pain determined by Patient Reported Outcomes Measurement Information System (PROMIS)
• Previous trials of at least two medications recommended in the Canadian consensus guidelines on the management of neuropathic pain with no self-reported meaningful improvement in symptoms
• Sufficient command of English to participate in psychotherapy
• For participants of childbearing potential, use of a highly effective or double-barrier methods of contraception.

You may not qualify if:

• History of Dextromethorphan addiction or abuse.
• Enzyme CYP2D6 deficient as shown on the pharmacogenetic test.
• Underlying psychiatric conditions: lifetime or family history of a primary psychotic disorder, bipolar disorder, borderline personality disorder, paranoid personality disorder, current suicidal ideation, and substance use disorder within the past 12 months as assessed by history and confirmed by the Mini International Neuropsychiatric Interview (MINI)
• Medications that interact with study drugs
• Medical condition that is unstable or inadequately controlled, including cardiovascular disease, liver disease, or end-stage renal disease
• Previous lifetime use of a serotonergic psychedelic drug
• Nursing or pregnant women.
• Any other clinically significant medical illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (2)

St. Michael's Hospital. Unity Health Toronto

Toronto, Ontario, M5B 1W8, Canada

NOT YET RECRUITING

St. Michael's Hospital. Unity Health Toronto

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

Related Publications (11)

• Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology (Berl). 2011 Dec;218(4):649-65. doi: 10.1007/s00213-011-2358-5. Epub 2011 Jun 15.

  PMID: 21674151 BACKGROUND

• Carbonaro TM, Bradstreet MP, Barrett FS, MacLean KA, Jesse R, Johnson MW, Griffiths RR. Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. J Psychopharmacol. 2016 Dec;30(12):1268-1278. doi: 10.1177/0269881116662634. Epub 2016 Aug 30.

  PMID: 27578767 BACKGROUND

• Yaden DB, Potash JB, Griffiths RR. Preparing for the Bursting of the Psychedelic Hype Bubble. JAMA Psychiatry. 2022 Oct 1;79(10):943-944. doi: 10.1001/jamapsychiatry.2022.2546.

  PMID: 36044208 BACKGROUND

• Glynos NG, Pierce J, Davis AK, McAfee J, Boehnke KF. Knowledge, Perceptions, and Use of Psychedelics among Individuals with Fibromyalgia. J Psychoactive Drugs. 2023 Jan-Mar;55(1):73-84. doi: 10.1080/02791072.2021.2022817. Epub 2022 Jan 10.

  PMID: 35001856 BACKGROUND

• Ramachandran V, Chunharas C, Marcus Z, Furnish T, Lin A. Relief from intractable phantom pain by combining psilocybin and mirror visual-feedback (MVF). Neurocase. 2018 Apr;24(2):105-110. doi: 10.1080/13554794.2018.1468469. Epub 2018 May 15.

  PMID: 29764303 BACKGROUND

• Bornemann J, Close JB, Spriggs MJ, Carhart-Harris R, Roseman L. Self-Medication for Chronic Pain Using Classic Psychedelics: A Qualitative Investigation to Inform Future Research. Front Psychiatry. 2021 Nov 12;12:735427. doi: 10.3389/fpsyt.2021.735427. eCollection 2021.

  PMID: 34867525 BACKGROUND

• Bondesson E, Larrosa Pardo F, Stigmar K, Ringqvist A, Petersson IF, Joud A, Schelin MEC. Comorbidity between pain and mental illness - Evidence of a bidirectional relationship. Eur J Pain. 2018 Aug;22(7):1304-1311. doi: 10.1002/ejp.1218. Epub 2018 Apr 16.

  PMID: 29577509 BACKGROUND

• Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci. 2017 Jan 20;18(2):113. doi: 10.1038/nrn.2017.5. No abstract available.

  PMID: 28704354 BACKGROUND

• Carhart-Harris RL, Leech R, Hellyer PJ, Shanahan M, Feilding A, Tagliazucchi E, Chialvo DR, Nutt D. The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Hum Neurosci. 2014 Feb 3;8:20. doi: 10.3389/fnhum.2014.00020. eCollection 2014.

  PMID: 24550805 BACKGROUND

• Castellanos JP, Woolley C, Bruno KA, Zeidan F, Halberstadt A, Furnish T. Chronic pain and psychedelics: a review and proposed mechanism of action. Reg Anesth Pain Med. 2020 Jul;45(7):486-494. doi: 10.1136/rapm-2020-101273. Epub 2020 May 4.

  PMID: 32371500 BACKGROUND

• MacCallum CA, Lo LA, Pistawka CA, Deol JK. Therapeutic use of psilocybin: Practical considerations for dosing and administration. Front Psychiatry. 2022 Dec 1;13:1040217. doi: 10.3389/fpsyt.2022.1040217. eCollection 2022.

  PMID: 36532184 BACKGROUND

MeSH Terms

Conditions

Agnosia; Chronic Pain; Neuralgia

Interventions

Psilocybin; Psychotherapy

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pain; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Behavioral Disciplines and Activities

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Feasibility trial

Study Record Dates

• First Submitted: November 28, 2024
• First Posted: December 12, 2024
• Study Start: March 5, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)