Psychedelic-assisted therapies (Psilocybin and MDMA) for treatment-resistant psychiatric disorders
Maria Luiza Góes Gurgel, Ana Luísa Carrijo Ferreira, Luisa da Costa Mello, Amanda Comandolli Caldato, Sofia Zaher Do Canto, Pietra Brossi Camilotti, Manuela Ruela Folino Silva, Raissa Assalin Gomes, Beatriz Bomfim Wiltembürg, Giulia Spadone Perini, Manoela Rosa Bertipaglia, Rafaella Barcelos de Matos, Enzo Seletti Orsi, Fernanda Oliveira Nacle, Gabriela Fernandes Daniel Ribeiro
International Health Sciences Review November 10, 2026 DOI: 10.70164/ihsr.v2i6.268 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Randomized Peer reviewed |
|---|---|
| Intervention | MDMA-assisted psychotherapy |
| Topics | MDMA Psilocybin Psychedelic-assisted therapy |
| Key findings | Psilocybin-assisted therapy produced moderate reductions in depressive symptoms (pooled Hedges' g = 0.66), and MDMA-assisted psychotherapy reduced PTSD severity in two phase 3 trials with favorable response and remission rates. The authors argue that blinding difficulties, expectancy bias, uncertain long-term efficacy, limited population diversity, and safety concerns in people with pre-existing neuropsychiatric conditions warrant clinical caution and further research before broader use. |
Abstract
Objective: To describe the pharmacological mechanisms, clinical efficacy, and safety of psilocybin- and MDMA-assisted therapies for depression and post-traumatic stress disorder (PTSD), while critically examining the methodological limitations of current evidence.
Methods: This narrative, non-systematic literature review was conducted between September and November 2026. PubMed/MEDLINE was searched for publications from January 2016 to November 2026. Randomized clinical trials, systematic reviews, meta-analyses, and studies addressing mechanisms of action and safety were considered. Twelve references were selected and qualitatively synthesized.
Results: Psilocybin demonstrated significant reductions in depressive symptoms, with a moderate pooled effect size (Hedges' g = 0.66). Evidence specifically concerning treatment-resistant depression remains limited. MDMA-assisted psychotherapy showed significant reductions in PTSD severity in two phase 3 trials, with favorable response and remission rates. Both interventions presented acceptable tolerability under controlled clinical conditions, although transient adverse effects were frequent. Serious adverse events were reported particularly among individuals with pre-existing neuropsychiatric conditions. Major limitations included difficulties with blinding, expectancy bias, uncertain long-term efficacy, and limited population diversity.
Conclusion: Psychedelic-assisted therapies represent promising investigational approaches in psychiatry. However, methodological limitations and safety uncertainties warrant clinical caution and further rigorous research before broader therapeutic implementation.
Comparable studies
Other narrative reviews on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Human Pharmacology of MDMA | 2004 | Review | |
| Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research | 2001 | Review | |
| 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans | 1994 | Review | |
| (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals | 2000 | Review | |
| Amphetamine toxicities | 2010 | Review |