Ecstasy to Alleviate SEvere Chronic Neuropathic Pain Trial

NCT07301632 | Recruiting Phase 2

• 1 other identifier: EASE Pain P-006
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Health Canada regulated internal pilot study designed to assess the feasibility, tolerability, and preliminary efficacy of 3, 4-methylenedioxymethamphetamine hydrochloride capsules-AT for chronic neuropathic pain to inform a larger, fully powered multi-center study. This is an interventional, randomized, 2-arm parallel, triple blinded study. The total study duration is 2 years. Participants will receive preparatory psychotherapy session during week 2 and week 4 followed by a combined single dosing session with psychotherapy during week 6. Integrative psychotherapy will follow at weeks 6, 8, 12, and 16. Follow up for primary clinical endpoint at week 16; final follow up for secondary clinical endpoint at 16-weeks. Participants will be asked to complete adjunctive home psychotherapy in the form of online modules. Data collected will be entered in electronic case report form (REDCap Academic).

Conditions

Chronic Neuropathic Pain

Keywords

3, 4-methylenedioxymethamphetamine hydrochloride; Chronic Neuropathic Pain

Outcome Measures

Primary Outcomes (6)

• The primary outcome of this pilot trial is to determine feasibility of a large-scale, multi-center trial.

  Average Monthly recruitment of \>1 participant per center means that the full trial should meet recruitment requirements within 12 months.

  16 weeks

• Secondary feasibility outcome

  Data completion rate (of primary clinical outcome)≥ 80%

  16 weeks

• Participant Retention

  Retention of ≥80% of participants at the reported primary outcome point of 16 weeks after the experimental session should minimize attrition bias in the definitive trial's primary outcome data (e.g. withdrawal due to side-effects)

  16 weeks

• Blinding

  Blinding Integrity (≤80% of participants in both arms correctly guess their treatment allocation (Note: 50% of participants would be expected to correctly guess treatment allocation due to chance alone)

  16 weeks

• Adverse Events

  ≤3 serious drug-related adverse events

  16 weeks

• Secondary Feasibility Outcome

  identification of patient, clinician and researcher-identified trial barriers using qualitative methods (e.g. interviews at the end of the study with participants who provides consent )

  16 weeks

Secondary Outcomes (9)

• The Patient-Reported Outcomes Measurement Information System (PROMIS) pain Intensity, Pain Interference and Physical Function Scale

  Week 1, Week 7, Week 11 and Week 16

• Patient Health Questionnaire (PHQ-9)

  Week 1, Week 7, Week 11 and Week 16

• Generalized Anxiety Disorder 7-Item (GAD-7) Questionnaire

  Week 1, Week 7, Week 11 and Week 16

• The Post traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual for Mental Disorder-5 (PCL-5)

  Week 1, Week 7, Week 11 and Week 16

• Health Questionnaire (EQ-5D-5L)

  Week 1, Week 7, Week 11 and Week 16

Study Arms (2)

3,4-Methylenedioxymethamphetamine

ACTIVE COMPARATOR

Treatment Arm: 3,4-Methylenedioxymethamphetamine 120mg (3 x 40mg capsule) PO single dose plus psychological support; optional 40mg supplemental dose at 2hr mark if there are no tolerability issues reported, patient consents and lead physician deems appropriate. (Maximum dose 160mg)

Drug: 3,4-Methylenedioxymethamphetamine

Methylphenidate

PLACEBO COMPARATOR

Placebo arm: Methylphenidate 30mg (3 x 10mg capsule) PO single dose plus psychological support; optional 10mg supplemental dose at 2hr mark if there are no tolerability issues reported, patient consents and lead physician deems appropriate. (Maximum dose of 40 mg)

Drug: Methylphenidate

Interventions

Methylphenidate DRUG

Placebo arm: Methylphenidate 30mg (3 x 10mg capsule) PO single dose plus psychological support; optional 10mg supplemental dose at 2hr mark if there are no tolerability issues reported, patient consents and lead physician deems appropriate. (Maximum dose of 40 mg)

Also known as: MDP

Methylphenidate

3,4-Methylenedioxymethamphetamine DRUG

Treatment arm: 3,4-Methylenedioxymethamphetamine 120mg (3 x 40mg capsule) PO single dose plus psychological support; optional 40mg supplemental dose at 2hr mark if there are no tolerability issues reported, patient consents and lead physician deems appropriate. (Maximum dose 160mg)

Also known as: MDMA

3,4-Methylenedioxymethamphetamine

Eligibility Criteria

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

You may qualify if:

• Consenting adults 18 years and older.
• Diagnosis of chronic neuropathic pain (greater than 3 months in duration) by a clinician with specialized training in chronic pain, confirmed with the standardized Leeds Assessment of Neuropathic Symptoms and Signs questionnaire.
• Suffering from moderate-to-severe pain as defined by
• Baseline Patient Reported Outcomes Measurement System - Pain Interference (PROMIS-PI) score of greater than or equal to 60
• An average pain intensity of greater than or equal to 5 on a 0-10 numeric rating scale,43
• Treatment-refractory pain as defined by a failure of ≥2 medications recommended in the Canadian consensus guidelines on the management of CNP to generate self-reported meaningful improvement in symptoms.
• For participants of childbearing potential, use of a highly effective or double-barrier methods of contraception. Abstinence is acceptable if it is the preferred and usual lifestyle of the participant.
• Sufficient English skills to participate in psychotherapy.

You may not qualify if:

• Past or current history of a psychotic disorder, mania, hypomania, bipolarity, current suicidal ideation, stimulant use disorder (i.e., cocaine, amphetamine, methamphetamine, MDMA, methylphenidate (Ritalin), etc , and any other substance use disorder within the past 12 months assessed by history and confirmed the Mini-International Neuropsychiatric Interview \[MINI\]. Other secondary psychiatric comorbidities (e.g., anxiety disorders, trauma related disorders, other personality disorders. etc.) will not be excluded
• Participants with a history of suicide attempts are not excluded unless a significant risk of suicidal behavior is present at the time of screening as determined by the CRSS (Columbia suicide rating scale)
• History of prior MDMA use (excluded to maintain blinding integrity)
• Long QT syndrome, measured by an ECG with a QTc more than 450 ms for males, and 470 ms for females.
• Presence of a relative or absolute contraindication to MDMA or Methylphenidate:
• Pre-existing cardiovascular disorders evidenced in clinical records or disclosed on patient self-report, such as: uncontrolled hypertension (sustained blood pressure ≥160/100 mmHg), angina (ongoing angina at rest, recent hospitalization for acute coronary syndrome within the past 3 months, or a history of revascularization (e.g., stenting or bypass surgery) within the past 6 months), arterial occlusive disease; heart failure, hemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction (within the past 6 months), potentially life-threatening arrhythmias (new-onset within the last 3 months), arrhythmias causing hemodynamic instability (SBP \< 90 mm Hg), or requiring urgent intervention (e.g., atrial fibrillation with rapid ventricular response or ventricular tachycardia), channelopathies, aneurysmal vascular disease (e.g., thoracic and/or abdominal aorta, intracranial, and peripheral arterial vessels), advanced arteriosclerosis
• Cerebrovascular conditions: acute stroke or recent history of intracerebral hemorrhage (ischemic or hemorrhagic stroke occurring within the past 6 months)
• Conditions at risk of elevation of blood pressure and increase heart rate, such as glaucoma, tension, agitation, thyrotoxicosis, pheochromocytoma
• Motor tics and/or family history or diagnosis of Tourette's syndrome
• Moderate to severe chronic kidney disease or kidney failure, such as requiring dialysis, significant treatment adjustments for kidney function, or regular nephrologist follow-up)
• Moderate to severe liver disease, such as cirrhosis, a history of significant jaundice unrelated to temporary illness, or any liver condition requiring regular monitoring by a specialist).
• Current treatment with selective serotonin reuptake inhibitors (SSRI's) and serotonin-norepinephrine reuptake inhibitors (SNRI's), tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans) and 5-HT3 receptor antagonist antiemetics (risk of Serotonin Syndrome)
• Hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (methylphenidate contains lactose)
• Seizure disorders
• Pregnancy, or breastfeeding

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

MeSH Terms

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Methylphenidate

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Akash Goel, MD,MPH,FRCPC

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Akash Goel, MD,MPH,FRCPC

CONTACT

4168645071; Akash.Goel@unityhealth.to

Study Design

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

Model Details: Preparatory psychotherapy from week 1 to 5; a single dosing session with psychotherapy at week 6 and integrative psychotherapy at weeks 7 to 16. Follow up for primary clinical endpoint and final follow up at week 16.

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: December 24, 2025
• Study Start: January 30, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 13, 2026

Record last verified: 2025-10

Locations

CA (1)