Ecstasy to Alleviate SEvere Chronic Neuropathic Pain Trial

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).

Primary objective: To demonstrate the feasibility of conducting the full EASE Pain trial by achieving targets in recruitment, data completion rate, blinding integrity, minimal serious drug-related adverse events, and by identifying barriers and facilitators to the full trial. Secondary objectives (full trial): To evaluate whether a 120 mg dose of oral 3,4-methylenedioxymethamphetamine with an optional 40mg supplementary dose leads to meaningful improvements in pain interference at 16-weeks in patients with moderate-to-severe chronic neuropathic pain compared to active-placebo, and assess changes in physical function, physical activity, emotional function, overall rating of improvement, and adverse events over 16 weeks. Study type: Intervention trial Allocation: Randomized Intervention model: 2-Arm Parallel Group Primary purpose: Feasibility Phase: Phase II Blinding: Triple blinded (patient- outcome assessor- and psychotherapist-blinded) Total study duration: 2 years Duration for each subject: 16 weeks. 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. Dosage regimen: 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) 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) Treatment/ assessment visits: Week -1: Screening Week 1: Baseline data collection, psychotherapy workbook 1 (preparation) Week 2: Psychotherapy preparatory session 1 Week 3: Psychotherapy workbook 2 (preparation) Week 4: Psychotherapy preparation session 2 Week 5: Psychotherapy workbook 3 (preparation) Week 6: (Day 0): Randomization to drug and experimental session with in-person psychotherapy (Day 1) Psychotherapy integration session 1 Week7: Psychotherapy workbook 4 (integration). Questionnaire and AE follow up Week 8: Psychotherapy integration session 2 Week 9 to 11 Psychotherapy workbook 5 (integration) Week 10: Questionnaire and AE follow up Week 12: Psychotherapy integration session 3 Week 13 to 15: Psychotherapy workbook 6 (integration) Week 16: Psychotherapy integration session 4. Primary clinical end point (Questionnaires and Adverse Event (AE) follow up)