Treatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND)

NCT06518720 | Recruiting Phase 2

• 1 other identifier: 179-2023
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. The purpose of this study is to assess the feasibility, tolerability, and preliminary efficacy of psilocybin therapy for adults with chronic neuropathic pain and co-morbid treatment resistant depression.

Conditions

Treatment Resistant Depression; Chronic Pain

Keywords

Psilocybin; Psychedelics; Clinical Trial; Chronic Pain; Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• Percentage of participants recruited, enrolled and retained (feasibility) and the number of serious adverse events and serious adverse drug reactions associated with administration of 25 mg of psilocybin (safety).

  Percentage of participants recruited, enrolled and retained over 24 months. Number of serious adverse events and serious adverse drug reactions associated with psilocybin 25 mg.

  24 Months

Secondary Outcomes (1)

• Change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from Baseline to 1-week post-treatment.

  Baseline (Visit 2, Day 0) to 1-week post-treatment (Visit 4, Day 7).

Other Outcomes (2)

• Change in Patient Reported Outcomes Measurement Information System-Pain Intensity Scale (PROMIS-PI) from Baseline to 1-week post-treatment.

  Baseline (Visit 2, Day 0) to 1-week post-treatment (Visit 4, Day 7).

• Change in Patient Reported Outcomes Measurement Information System- Pain Interference Scale (PROMIS-Interference) from Baseline to 1-week post-treatment.

  Baseline (Visit 2, Day 0) to 1-week post-treatment (Visit 4, Day 7).

Study Arms (1)

Psilocybin (25 mg)

EXPERIMENTAL

One capsule of psilocybin 25 mg will be taken orally with a glass of water.

Drug: Psilocybin 25 mg

Interventions

Psilocybin 25 mg DRUG

The psilocybin used in this study meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of psilocybin. The psilocybin will be administered once during the trial in combination with supportive therapy.

Also known as: PEX010

Psilocybin (25 mg)

Eligibility Criteria

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

You may qualify if:

• Adults 18 to 65 years old;
• Are outpatients;
• Must be deemed to have capacity to provide informed consent;
• Must sign and date the informed consent form;
• Stated willingness to comply with all study procedures;
• Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;
• Primary DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the Structured Clinical Interview for DSM-5 (SCID-5) administered at the first screening visit;
• Participants diagnosed with treatment-resistant depression defined as individuals with a baseline HamD-17 score \> 14 and that have not responded to two or more separate trials of antidepressants at an adequate dosage and duration (an antidepressant resistance rating score of three or more is considered an adequate trial) based on the Antidepressant Treatment History Form (ATHF) (Sackeim \& Sackeim, 2001); there is no upper limit on the number of treatment failures;
• Diagnosis of chronic neuropathic pain as determined by a pain specialist and confirmed with the standardized Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire25
• Moderate-to-severe neuropathic pain determined by Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference score of \> 6026, as well as mean pain intensity scores \> 5 on a numeric rating scale27
• 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
• Ability to take oral medication;
• Individuals with an eGFR above 40mL/min/1.73m2 and all blood work on clinical laboratory tests assessed as not clinically significant by study delegate physician at Screening (V1)
• Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation;
• Individuals who are willing to taper off current antidepressant and antipsychotic medications for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so; and

You may not qualify if:

• Pregnant as assessed by a urine pregnancy test at Screening (V1) or individual's that intend to become pregnant during the study or are breastfeeding;
• Treatment with another investigational drug or other intervention within 30 days of Screening (V1);
• Have initiated psychotherapy in the preceding 12 weeks prior to Screening (V1);
• Have a DSM-5 diagnosis of substance use disorder (recreational use of tobacco, alcohol, cannabis and prescribed opioids are permitted) within the preceding 6 months;
• Have active suicidal ideation with intent and plan as determined by item 3 of the HamD-17;
• Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; obsessive-compulsive disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview;
• Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant;
• Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment.
• Presence of baseline prolonged QTc or Torsade de Pointes as measured by the ECG or a history of long QTc syndrome or related risk factors;
• Individuals who are currently taking methadone, buprenorphine or \> 100 milligrams of morphine (or morphine equivalents).
• Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent 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

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J1H4, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Chronic Pain

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Muhammad Ishrat Husain, MBBS, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Muhammad Ishrat Husain, MBBS, MD

CONTACT

4165358501; ishrat.husain@camh.ca

Alexandria Coles, MSc.

CONTACT

4165358501; alexandria.coles@camh.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist, Temerty Centre for Therapeutic Brain Intervention

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: July 24, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)