{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:24:54Z","timestamp":1786443894775,"version":"build-2736575974"},"reference-count":24,"publisher":"Royal College of Psychiatrists","issue":"5","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-sa\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec id=\"S0007125025103206_as1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy (MDMA-AT) has shown promising safety and efficacy in phase 3 studies of post-traumatic stress disorder, but has not been investigated for a primary diagnosis of major depressive disorder (MDD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025103206_as2\">\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>We aimed to explore the proof of principle and safety as a first study with MDMA-AT for MDD, and to provide preliminary efficacy data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025103206_as3\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Twelve participants (7 women, 5 men) with moderate to severe MDD received MDMA in 2 open-label sessions 1 month apart, along with psychotherapy before, during and after the MDMA sessions, between January 2023 and May 2024. The primary outcome measure was mean change in Montgomery\u2013Asberg Depression Rating Scale (MADRS), and the secondary outcome measure was mean change in functional impairment as measured with the Sheehan Disability Scale (SDS), both from baseline to 8 weeks following the second MDMA session. We used descriptive statistics and the two-tailed Wilcoxon signed-rank test to compare baseline and outcome scores. Repeated measures were analysed by a mixed-effects model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025103206_as4\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline MADRS was 29.6 (s.d. 4.9). Feasibility was demonstrated with sufficient recruitment and retention. MADRS scores were significantly reduced post treatment compared with baseline (mean difference \u201319.3, s.e. 2.4, CI \u201314.8 to \u201323.8,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). SDS scores significantly decreased from baseline (mean difference \u201311.7, s.e. 2.2, CI \u20137.5 to \u201315.9,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.001). There were no adverse events of special interest, and no unexpected or serious adverse events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025103206_as5\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study met the primary objectives of safety and feasibility, and provided indications of efficacy for MDMA-AT for MDD. Further studies with a randomised design are required to confirm these findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025103206_as6\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>EudraCT no. 2021-000805-26.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1192\/bjp.2025.10320","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T05:49:08Z","timestamp":1752212948000},"page":"783-789","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":9,"title":["MDMA-assisted therapy as a treatment for major depressive disorder: proof of principle study"],"prefix":"10.1192","volume":"227","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3354-1511","authenticated-orcid":false,"given":"Tor-Morten","family":"Kvam","sequence":"first","affiliation":[{"name":"University of Oslo"},{"name":"\u00d8stfold Hospital Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7656-625X","authenticated-orcid":false,"given":"Ivar W.","family":"Goks\u00f8yr","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Rog","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger-Tove Jentoft","family":"van de Vooren","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8429-2869","authenticated-orcid":false,"given":"Lowan Han","family":"Stewart","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Autran","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4894-7263","authenticated-orcid":false,"given":"Mark","family":"Berthold-Losleben","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust"},{"name":"Norwegian University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"M\u00f8rch-Johnsen","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust"},{"name":"\u00d8stfold Hospital Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Holst","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingmar","family":"Clausen","sequence":"additional","affiliation":[{"name":"\u00d8stfold Hospital Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4461-3568","authenticated-orcid":false,"given":"Ole A.","family":"Andreassen","sequence":"additional","affiliation":[{"name":"University of Oslo"},{"name":"Oslo University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"170","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"S0007125025103206_ref23","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(23)00363-2"},{"key":"S0007125025103206_ref8","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1075-9"},{"key":"S0007125025103206_ref24","unstructured":"24 Mithoefer, MC. A Manual for MDMA-assisted Psychotherapy in the Treatment of Posttraumatic Stress Disorder. Version 8.1. Multidisciplinary Association for Psychedelic Studies (MAPS), 2017 (https:\/\/maps.org\/wp-content\/uploads\/2022\/05\/MDMA-Assisted-Psychotherapy-Treatment-Manual-V8.1-22AUG2017.pdf)."},{"key":"S0007125025103206_ref20","volume-title":"Open Label Study of MDMA-assisted Psychotherapy for Treatment of PTSD with Optional fMRI Sub-Study","year":"2025"},{"key":"S0007125025103206_ref6","doi-asserted-by":"publisher","DOI":"10.1007\/s002130000648"},{"key":"S0007125025103206_ref4","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.65.5.513"},{"key":"S0007125025103206_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32802-7"},{"key":"S0007125025103206_ref1","unstructured":"1 World Health Organization. Depressive Disorder (Depression). WHO, 2018 (https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/depression)."},{"key":"S0007125025103206_ref17","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01336-3"},{"key":"S0007125025103206_ref19","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.954388"},{"key":"S0007125025103206_ref9","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00650"},{"key":"S0007125025103206_ref3","doi-asserted-by":"publisher","DOI":"10.1037\/a0013075"},{"key":"S0007125025103206_ref14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75706-1"},{"key":"S0007125025103206_ref22","unstructured":"22 Weathers, FW , Litz, BT , Keane, TM , Palmieri, PA , Marx, BP , Schnurr, PP. The PTSD Checklist for DSM-5 (PCL-5) \u2013 Standard Scale. US Department of Veterans Affairs, 2013 (www.ptsd.va.gov)."},{"key":"S0007125025103206_ref13","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-018-5010-9"},{"key":"S0007125025103206_ref12","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-019-05249-5"},{"key":"S0007125025103206_ref10","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2015.1094156"},{"key":"S0007125025103206_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2015.04.007"},{"key":"S0007125025103206_ref7","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(00)00126-3"},{"key":"S0007125025103206_ref15","doi-asserted-by":"publisher","DOI":"10.1177\/0269881121991792"},{"key":"S0007125025103206_ref16","first-page":"315","article-title":"MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study","volume":"21","author":"Mitchell","year":"2023","journal-title":"Focus (Am Psychiatr Publ)"},{"key":"S0007125025103206_ref5","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(99)00148-7"},{"key":"S0007125025103206_ref21","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02565-4"},{"key":"S0007125025103206_ref11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0295926"}],"updated-by":[{"DOI":"10.1192\/bjp.2026.10579","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000}}],"container-title":["The British Journal of Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0007125025103206","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T02:43:53Z","timestamp":1785206633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0007125025103206\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,11]]},"references-count":24,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["S0007125025103206"],"URL":"https:\/\/doi.org\/10.1192\/bjp.2025.10320","relation":{},"ISSN":["0007-1250","1472-1465"],"issn-type":[{"value":"0007-1250","type":"print"},{"value":"1472-1465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,11]]},"assertion":[{"value":"\u00a9 The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution-ShareAlike licence (https:\/\/creativecommons.org\/licenses\/by-sa\/4.0\/), which permits re-use, distribution, and reproduction in any medium, provided the same Creative Commons licence is used to distribute the re-used or adapted article and the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}