Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder.

TitleAltered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder.
Publication TypeJournal Article
Year of Publication2022
AuthorsS Singleton P, Wang JB, Mithoefer M, Hanlon C, George MS, Mithoefer A, Mithoefer O, Coker AR, Yazar-Klosinski B, Emerson A, Doblin R, Kuceyeski A
JournalFront Psychiatry
Volume13
Pagination947622
Date Published2022
ISSN1664-0640
Abstract

INTRODUCTION: 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. 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, hippocampus, and insula. However, to date there have been no neuroimaging studies aimed at directly elucidating the neural impact of MDMA-AT in PTSD patients.

METHODS: 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 in nine veterans and first-responders with chronic PTSD of 6 months or more.

RESULTS: We hypothesized that MDMA-AT would increase amygdala-hippocampus resting-state functional connectivity, however we only found evidence of a trend in the left amygdala-left hippocampus (t = -2.91, uncorrected p = 0.0225, corrected p = 0.0901). We also found reduced activation contrast (trauma > neutral) after MDMA-AT in the cuneus. Finally, the amount of recovery from PTSD after MDMA-AT correlated with changes in four functional connections during autobiographical memory recall: the left amygdala-left posterior cingulate cortex (PCC), left amygdala-right PCC, left amygdala-left insula, and left isthmus cingulate-left posterior hippocampus.

DISCUSSION: Amygdala-insular functional connectivity is reliably implicated in PTSD and anxiety, and both regions are impacted by MDMA administration. These findings compliment previous research indicating that amygdala, hippocampus, and insula 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.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02102802, identifier NCT02102802.

DOI10.3389/fpsyt.2022.947622
Alternate JournalFront Psychiatry
PubMed ID36713926
PubMed Central IDPMC9879604
Grant ListRF1 MH123232 / MH / NIMH NIH HHS / United States
Related Institute: 
Brain Health Imaging Institute (BHII)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065