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Home/Research/MDMA/Chronic Pain

MDMA for Chronic Pain

12 papers and 3 clinical trials exploring mdma as a treatment for chronic pain.

Compoundempathogen

MDMA

MDMA is a synthetic empathogen that enhances monoamine release, producing prosocial and anxiolytic effects without frank hallucinosis. Two Phase III trials demonstrated significant PTSD symptom reductions, though FDA review raised concerns about blinding, durability, and safety characterisation.

Full MDMA profile
IndicationOver 1.5 billion worldwide.

Chronic Pain

Chronic pain is increasingly recognised as a multifaceted condition that may respond to psychedelic therapies, which are gaining attention in clinical settings for their potential efficacy in pain management. Recent research indicates that compounds such as psilocybin and MDMA are entering clinical trials aimed at exploring their therapeutic effects on chronic pain syndromes.

Full Chronic Pain profile

Academic Research

12 papers
Open Accessindividual

Psychedelic-assisted therapy: a survey on the clinical methods of Swiss physicians

This survey study (n=41) examined how Swiss physicians provide psychedelic-assisted therapy under legal exemptions, mainly for depression, anxiety, PTSD and chronic pain. It found wide variation in practice, with psilocybin, MDMA and LSD commonly used, music often played during sessions, and adverse effects usually including disorientation, feeling cold, anxiety and nausea.

Published
May 20, 2026
Journal
Therapeutic Advances in Psychopharmacology
Authors
Beichmann, K., Catzeflis, P., Aicher, H. D., Seragnoli, F., Calder, A., Amrani, A., Hasler, G.
Open Accessindividual

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD A Randomized Clinical Trial

In a multicentre, double‑blind, placebo‑controlled phase 2 trial of 65 adults with chronic PTSD, once‑weekly oral TSND‑201 produced significantly greater reductions in clinician‑rated PTSD severity (CAPS‑5; LS mean difference 9.64, P = .01) and improvements in self‑reported symptoms, functioning and depression versus placebo. TSND‑201 was generally well tolerated — common adverse events included headache, decreased appetite, nausea, dizziness and transient blood‑pressure increases — supporting its potential as a rapid‑acting, durable treatment for PTSD.

Published
February 18, 2026
Journal
JAMA Psychiatry
Authors
Jones, A., Warner-Schmidt, J., Kwak, H., Stogniew, M., Mandell, B., Ching, T. H., Stein, M. B., Kelmendi, B.
Open Accessindividual

MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder

In an exploratory analysis of 32 participants from a Phase 2 open‑label trial of manualised MDMA‑assisted therapy for PTSD, 84% reported chronic pain and 75% reported pain‑related disability. MDMA‑AT was associated with significant reductions in pain intensity, disability and overall Chronic Pain Grade Scale severity in the high‑pain subgroup and reduced pain intensity in the medium‑pain subgroup, supporting further investigation of MDMA‑AT for comorbid chronic pain.

Published
November 3, 2022
Journal
Frontiers in Psychiatry
Authors
Christie, D., Yazar-Klosinski, B., Nosova, E., Kryskow, P., Siu, W. O., Lessor, D., Argento, E.
Open Accessmeta

Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review

This mixed-methods systematic review of 44 clinical studies (598 patients) found serotonergic psychedelics and MDMA to be generally well tolerated but noted that adverse events were poorly defined and likely underreported. Common acute AEs were nausea, headache and anxiety, late AEs included fatigue and low mood, one serious MDMA-related cardiac event occurred, and qualitative data suggest challenging psychological experiences can also have therapeutic value, underlining the need for systematic, detailed AE assessment in future trials.

Published
August 26, 2022
Journal
Journal of Psychopharmacology
Authors
Breeksema, J. J., Kuin, B. W., Kamphuis, J., Van Den Brink, W., Vermetten, E., Schoevers, R. A.
Open Accessmeta

Hallucinogenic Persisting Perception Disorder: A Case Series and Review of the Literature

This retrospective series of 13 patients and review of 24 case reports found that HPPD commonly causes visual snow, floaters, palinopsia, photophobia and nyctalopia despite normal ophthalmic and neurological investigations, producing a phenotype that overlaps substantially with Visual Snow Syndrome. The authors argue DSM‑5 diagnostic criteria should be expanded to include these symptoms, that VSS patients be screened for prior hallucinogen use, and that controlled studies compare primary and secondary VSS to clarify pathophysiology and treatment.

Published
May 6, 2022
Journal
Frontiers in Neurology
Authors
Van Der Walt, A., Ford, H., Fraser, C. L., Solly, E., Clough, M., Fielding, J., White, O.
Paywallindividual

Lifetime use of MDMA/ecstasy and psilocybin is associated with reduced odds of major depressive episodes

In a nationally representative sample of 213,437 US adults, lifetime MDMA/ecstasy use was associated with lower odds of lifetime (aOR 0.84), past‑year (aOR 0.84) and past‑year severe (aOR 0.82) major depressive episodes, and psilocybin use was associated with modestly reduced odds of past‑year (aOR 0.90) and past‑year severe (aOR 0.87) MDEs. Other substances were either unrelated or linked to increased MDE odds, and the authors call for experimental studies to test causality and therapeutic potential.

Published
January 5, 2022
Journal
Journal of Psychopharmacology
Authors
Jones, G. M., Nock, M. K.

Clinical Trials

3 trials
RecruitingPhase I

Acute Analgesic Effects of MDMA on Experimentally Induced Acute Pain, Hyperalgesia and Allodynia in Healthy Participants

This Phase I, randomised, triple-masked, crossover trial (n=20) will assess the acute analgesic effects of oral MDMA in healthy adults aged 18 to 75 years. It will compare MDMA 25 mg, 75 mg and 125 mg with placebo to evaluate whether MDMA reduces experimentally induced acute nociceptive pain, hyperalgesia and allodynia. Participants will receive the study drug by mouth during a validated electrical stimulation pain model in which repeated small electrical pulses are applied under the skin to produce moderate pain and secondary pain phenomena. The main outcome is periprocedural pain measured with the numerical rating scale, with the highest MDMA dose compared against the lower doses and placebo.

Started
March 9, 2026
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT07494214
RecruitingPhase II

Ecstasy to Alleviate SEvere Chronic Neuropathic Pain Trial

This Phase II, randomised, triple-blinded, parallel trial (n=40) will evaluate the feasibility, tolerability and preliminary efficacy of a single oral dose of MDMA for adults with moderate-to-severe chronic neuropathic pain. The primary purpose is to determine feasibility for a larger multi-centre trial by assessing recruitment, data completion, blinding integrity and drug-related adverse events, while secondary aims include preliminary assessment of pain interference and other clinical outcomes at 16 weeks. Participants are randomised to a treatment arm receiving MDMA 120 mg (3 × 40 mg capsule) orally as a single dose with psychological support and an optional 40 mg supplemental dose at 2 hours (maximum 160 mg), or to an active-placebo arm receiving methylphenidate 30 mg (3 × 10 mg capsule) orally with an optional 10 mg supplemental dose at 2 hours (maximum 40 mg). Preparatory psychotherapy is delivered in the weeks before dosing, the combined dosing and psychotherapy session occurs at week 6, and integrative psychotherapy follows through weeks 7–16; adjunctive home psychotherapy modules are also used. Key outcomes include feasibility metrics and clinical measures such as PROMIS Pain Interference (primary clinical signal at 16 weeks), pain intensity, physical function, emotional function, overall improvement ratings and adverse events; each participant is followed for 16 weeks and the total study duration is 2 years.

Started
January 30, 2026
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT07301632
RecruitingPhase I

MDMA-assisted Therapy for Fibromyalgia

This single-arm open-label trial (n=20) will assess the efficacy of MDMA-assisted psychotherapy for fibromyalgia patients.

Started
March 1, 2024
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT06066853

Explore further

Search all MDMA papers Search all Chronic Pain trials Full MDMA profile Full Chronic Pain profile