Evidence for altered neural activity patterns after MDMA-assisted therapy in adults with chronic and severe post-traumatic stress disorder: a pilot study
S. P. Singleton, J. B. Wang, M. Mithoefer, Colleen Hanlon, M. George, A. Mithoefer, Oliver Mithoefer, Allison R. Coker, B. Yazar-Klosinski, A. Emerson, R. Doblin, Amy Kuceyeski
medRxiv May 27, 2022 preprint DOI: 10.1101/2022.05.25.22275473 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Pilot study |
|---|---|
| Sample size | 9 |
| Population | Veterans and first-responders with PTSD |
| Intervention | MDMA-assisted therapy |
| Duration | Two-month follow-up |
| Topics | MDMA PTSD |
| Key findings | MDMA-AT increased amygdala-hippocampal resting-state functional connectivity and reduced amygdala-precuneus connectivity during neutral autobiographical memory recall, with the latter change co-varying with PTSD severity reduction. |
Abstract
3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) for post-traumatic stress disorder (PTSD) has demonstrated promise in multiple clinical trials. MDMA is hypothesized to facilitate the therapeutic process, in part, by decreasing fear response during fear memory processing while increasing extinction learning retention. The acute administration of MDMA in healthy controls modifies recruitment of brain regions involved in the hyperactive fear response in PTSD such as the amygdala and hippocampus. However, to date there have been no neuroimaging studies aimed at directly elucidating the neural impact of MDMA-AT in PTSD patients. We analyzed brain activity and connectivity via functional MRI during both rest and autobiographical memory (trauma and neutral) response before and two-months after MDMA-AT for PTSD in nine veterans and first-responders. We find that MDMA-AT (i) increases amygdala-hippocampal resting-state functional connectivity, and (ii) reduces amygdala-precuneus functional connectivity during neutral autobiographical memory recall in a manner that co-varies with reduction of PTSD severity. These findings compliment previous research indicating that amygdala-hippocampal functional connectivity is a potential target of MDMA-AT and highlights other regions of interest related to memory processes. More research is necessary to determine if these findings are specific to MDMA-AT compared to other types of treatment for PTSD.
Comparable studies
Other observational and cohort studies on MDMA for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| MDMA-Assisted Psychotherapy Using Low Doses in a Small Sample of Women with Chronic Posttraumatic Stress Disorder Women with chronic PTSD secondary to sexual assault | 2008 | Observational cohort | n = 6 |
| Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder. Veterans and first-responders with chronic PTSD of 6 months or more | 2022 | Observational cohort | n = 9 |
| Self-reported PTSD is associated with increased use of MDMA in adolescents with substance use disorders German adolescent patients with a substance use disorder | 2021 | Observational cohort | n = 121 |
| The Nova Protocol: a comprehensive multimodal longitudinal study among civilian survivors of a mass trauma event. Survivors of the 7 October 2023 Nova music festival attack and a sociocultural... | 2026 | Longitudinal observational study protocol |
Citations in the library
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- The psychedelic-peptide paradox: a hormetic hypothesis. Comprehensive Psychoneuroendocrinology June 2, 2025
- The association between study design and antidepressant effects in psychedelic-assisted therapy: A meta-analysis. Journal of Affective Disorders January 15, 2025
- Exploring the therapeutic convergence of meditation, psychedelics, and MDMA Journal of Psychedelic Studies April 17, 2025
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