MDMA-assisted therapy for major depressive disorder: A seven-month follow-up proof of principle trial
The findings of a new study indicate that MDMA-AT which combines psychoactive drug experience with psychotherapy could potentially offer long-lasting relief for depression, beyond what’s often seen with conventional antidepressants
This is the first study to explore MDMA-assisted therapy for Major Depressive Disorder.
Twelve participants with MDD and an ongoing moderate to severe depressive episode received MDMA-AT in two MDMA dosing sessions one month apart, integrated with nine psychotherapy sessions. Clinical assessments were done before MDMA-AT (baseline), after the final psychotherapy session (post-treatment), and at follow-up seven months after baseline. The primary and secondary outcome measures were the Montgomery-Asberg Depression Rating Scale (MADRS) and Sheehan Disability Scale (SDS), respectively. Suicidality was tracked with the Columbia-Suicide Severity Rating Scale. Exploratory outcomes included self-reported assessments of functional impairment, depression, generalized anxiety, insomnia, and PTSD symptoms. We used a mixed-effects model and multinomial logistic regression for analysis of repeated measures.
All twelve participants attended the follow-up visit. At follow-up, there was a significant reduction of MADRS (p < 0.001) and SDS (p = 0.001) scores compared with baseline, along with significant improvements in all exploratory outcome measures. There were no significant changes in any measures from the post-treatment visit. Neither the mean suicidal ideation (SI) score nor the SI intensity rating exceeded pre-study levels.
This long-term follow-up study of MDMA-AT provides preliminary evidence supporting sustained treatment effects and long-term safety in MDD. However, further validation in larger, controlled trials is needed.
This was the first clinical investigation of MDMA-assisted therapy (MDMA-AT) in people with a primary diagnosis of Major Depressive Disorder (MDD), rather than the more common use for trauma-related disorders.
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The trial enrolled 12 participants (7 women, 5 men) with moderate to severe MDD.
Each participant underwent two open-label MDMA dosing sessions, about one month apart, paired with a course of psychotherapy (preparation, integration) before, during, and after dosing.
At the “post-treatment” visit (about 8 weeks after the second MDMA session), 9 of 12 participants (75%) met the study’s responder criterion (≥ 50% reduction in depression via the Montgomery–Åsberg Depression Rating Scale, MADRS) and also 75% (9/12) met the study’s remission criterion (MADRS ≤ 12).
At 7-month follow-up, the group as a whole maintained significantly lower depression severity (MADRS) and lower functional impairment (Sheehan Disability Scale) than at baseline. Depression severity was reduced at post-treatment and sustained at follow-up.
Exploratory measures (e.g. self-report scales for anxiety, insomnia, PTSD symptoms, general depression) also improved from baseline to follow-up
Tor-Morten Kvam, Ivar W. Goksøyr, Justyna Rog, Inger-Tove Jentoft van de Vooren, Lowan Han Stewart, Ingrid Autran, Mark Berthold-Losleben, Lynn Mørch-Johnsen, René Holst, Jan Ivar Røssberg, Ingmar Clausen, Ole A. Andreassen, MDMA-assisted therapy for major depressive disorder: A seven-month follow-up proof of principle trial, Journal of Psychiatric Research, Volume 193, 2026, Pages 302-308, Paper access
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