CNSPulse
T50

PSILOCYBIN TREATMENT FOR CHRONIC NEUROPATHIC PAIN AND DEPRESSION

Jordana Kazdan — Karim Ladha2, Venkat Bhat2, Daniel Blumberger1, Hance Clarke2, Akash Goel2, Brett Jones1, Tyler Kaster1, Joel Katz3, Paul Ritvo3, Daphne Voineskos2, Wei Wang1, Duminda Wijeysundera2, Ishrat Husain1 1Centre for Addiction and Mental Health, University of Toronto, 2University of Toronto, 3York University

2026 ASCP Annual Meeting

Background

Chronic neuropathic pain and Major Depressive Disorder (MDD) are two debilitating conditions with high rates of treatment resistance. Over 65% of individuals living with neuropathic pain also experience depressive symptoms, yet existing treatments do not adequately address both conditions simultaneously. Recent evidence suggests that psilocybin (the active ingredient in ‘magic mushrooms’), combined with supportive therapy, produces rapid antidepressant effects in adults with MDD. Given that neuropathic pain and depression share several mechanisms, psilocybin presents a promising therapeutic alternative for this comorbidity. However, this has not yet been translated into clinical evidence. Before a large-scale RCT can be conducted, the feasibility of conducting such study needs to be explored, along with its tolerability and therapeutic effects in this population.

Purpose

To address this important gap, this study aims to 1) determine the feasibility and safety of administering psilocybin therapy (25 mg) in adults with comorbid chronic neuropathic pain and MDD, and 2) provide preliminary evidence on whether psilocybin therapy can improve pain and depression symptom severity from baseline to 1-week posttreatment.

Methods

In this phase II open-label trial, 16 adults (aged > 18) with chronic neuropathic pain and DSM-5 MDD will receive one oral dose of psilocybin (25 mg) combined with supportive therapy. Eligible participants must have demonstrated treatment resistance, defined by an inadequate response to conventional therapies per the Canadian guidelines for neuropathic pain and the Antidepressant Treatment History Form. Two trained therapists will provide manualized psychotherapy before, during, and after the psilocybin dosing session. Feasibility outcomes include recruitment, adherence, and retention throughout the 3-month follow-up period. Safety outcomes include the number and severity of adverse events at all time points. Clinical outcomes include pain intensity and interference as determined by Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires, and depressive symptoms as determined by the Montgomery–Åsberg Depression Rating Scale (MADRS). Given the pilot nature of this study, clinical outcomes will be analyzed on an intention-to-treat basis and summarized descriptively. To date, 1 of 16 participants has completed the study intervention.

Results

Enrolment is ongoing, and analyses presented will reflect early-stage data prior to study completion. Findings will focus on feasibility and safety outcomes, including recruitment processes, protocol adherence, and adverse event reporting.

Importance: This is the first registered clinical trial systematically assessing the feasibility, safety, and preliminary efficacy of administering psilocybin treatment to individuals with chronic neuropathic pain and MDD. Results are expected to inform the design of future largescale trials needed to confirm treatment-related effects. This research could lead to new and innovative treatment pathways for medically complex patients who are often left underserved. ClinicalTrials.gov Identifier: NCT06518720.