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Home/Research/MDMA/Treatment-Resistant Depression (TRD)

MDMA for Treatment-Resistant Depression (TRD)

11 papers and 0 clinical trials exploring mdma as a treatment for treatment-resistant depression (trd).

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
Indication30% of individuals with depression experience treatment-resistant depression.

Treatment-Resistant Depression (TRD)

Research into psychedelics as a treatment for Treatment-Resistant Depression (TRD) is advancing rapidly, with compounds like psilocybin showing particular promise. Approximately 30% of depression sufferers experience TRD, which reflects a significant unmet need in mental health treatment.

Full Treatment-Resistant Depression (TRD) profile

Academic Research

11 papers
Open Accessmeta

Psychedelic medicine: mechanisms, evidence, and translation to practice

This review (2026) summarises the rapidly growing evidence for psychedelic-assisted therapies, finding the strongest support for psilocybin in treatment-resistant depression (TRD) and MDMA in post-traumatic stress disorder (PTSD). It also highlights that while these treatments are generally well tolerated in controlled settings, major challenges remain around unclear mechanisms, trial limitations, scalability, and translation into routine practice.

Published
February 23, 2026
Journal
BMJ
Authors
Jacobs, E., Zahid, Z., Hinkle, J., Nayak, S., Yaden, D. B.
Open Accessindividual

Psilocybin with psychotherapeutic support for treatment-resistant depression: a pilot clinical trial

An open‑label pilot trial of two 25 mg psilocybin sessions with preparatory and integration psychotherapy for treatment‑resistant depression produced a clinically meaningful reduction in self‑rated depressive symptoms at three weeks (Hedges’ g = −1.27) that was maintained at 20 weeks, although individual responses varied (two sustained responders, three relapses, two non‑responders). Exploratory analyses linked pre‑dosing mindset, spiritual experiences and perceptual shifts to outcome trajectories, with adverse events consistent with prior studies and no serious adverse events.

Published
October 2, 2025
Journal
Therapeutic Advances in Psychopharmacology
Authors
Meikle, S., Carter, O., Liknaitzky, P., Johansen, L., Iyer, R., Strauss, N., Williams, M., Castle, D., Rossell, S. L., Ids, O.
Open Accessmeta

The Australia story: Current status and future challenges for the clinical applications of psychedelics

This review (2024) examines the recent approval by the Australian Therapeutic Goods Administration (TGA) of psilocybin for treatment-resistant depression (TRD) and MDMA for PTSD, effective 1 July 2023. It highlights the campaign led by Mind Medicine Australia and supported by leading researchers and institutions, as well as implications for future approvals and psychedelic drug development pathways.

Published
December 19, 2024
Journal
British Journal of Clinical Pharmacology
Authors
Nutt, D. J., Hunt, P., Schlag, A. K., Fitzgerald, P. B.
Paywallmeta

Quality of reporting on psychological interventions in psychedelic treatments: a systematic review

This systematic review (s=45) on psychedelic-assisted psychotherapy for mental disorders finds that psychological interventions are reported with low completeness and high heterogeneity. It also finds that MDMA studies are more homogeneous, with greater procedural detail.

Published
December 9, 2024
Journal
Lancet
Authors
Seybert, C., Schimmers, N., Silva, L., Breeksema, J. J., Veraart, J. K. E., Bessa, B. S., d'Orsi, D., Schoevers, R. A., Dinis-Oliveira, R. J.
Open Accessmeta

Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies

This systematic review (2024) and meta-analysis (s=131) examines the incidence of psychedelic-induced psychosis, focusing on individuals with schizophrenia. It finds an incidence of 0.002% in population studies, 0.2% in UCTs, and 0.6% in RCTs, with 3.8% of UCT participants with schizophrenia developing long-lasting psychotic symptoms. It also reports that 13.1% of those with psychedelic-induced psychosis later developed schizophrenia.

Published
November 27, 2024
Journal
Molecular Psychiatry
Authors
Sabé, M., Sulstarova, A., Glangetas, A., De Pieri, M., Mallet, L., Curtis, L., Richard-Lepouriel, H., Penzenstadler, L., Seragnoli, F., Thorens, G., Zullino, D., Preller, K., Böge, K., Leucht, S., Correll, C. U., Solmi, M., Kaiser, S., Kirschner, M.
Paywallindividual

Set and setting predict psychopathology, wellbeing and meaningfulness of psychedelic experiences: a correlational study

This survey (n=1022) investigated the correlation between set and setting variables in psychedelic therapy with psychopathology, well-being, and personality. Findings suggest that growth motivations, natural settings, and the presence of significant others predict positive outcomes. In contrast, problematic motivations are associated with greater psychopathology and lower well-being.

Published
December 20, 2023
Journal
Expert Review of Clinical Pharmacology
Authors
Borkel, L. F., Rojas-Hernández, J., Henríquez-Hernández, L. A., Del Pino, A. S., Quintana-Hernández, D. J.

Clinical Trials

0 trials

No clinical trials have been tagged with both MDMA and Treatment-Resistant Depression (TRD) yet.

Trials are continuously being added as new studies are registered.

Explore further

Search all MDMA papers Search all Treatment-Resistant Depression (TRD) trials Full MDMA profile Full Treatment-Resistant Depression (TRD) profile