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

Abstract

Introduction3,4-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.MethodsWe 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.ResultsWe 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.DiscussionAmygdala—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 registrationhttps://clinicaltrials.gov/ct2/show/NCT02102802, identifier NCT02102802.

Functional brain changes after pharmacological interventions in post-traumatic stress disorder: A systematic review of clinical trials

“…In addition, the interpretation of the findings mentioned above are limited by the heterogeneous research methods used, including the types of tasks, as well as the way drugs were administered (e.g., intranasal versus oral administration). Other recent studies using ketamine 59, 60 or psychedelics 61 were not included as they did not compared patients with PTSD to groups of TEC or HCs. An important limitation is the exclusion of studies of PTSD patients showing severe comorbid disorders; although this would represent a more ecological group, it could also hinder the effects of the studied pharmacological agents on brain function solely associated with PTSD.…”

“…Other recent studies using ketamine 59,60 or psychedelics 61 were not included as they did not compared patients with PTSD to groups of TEC or HCs. An important limitation is the exclusion of studies of PTSD patients showing severe comorbid disorders; although this would represent a more ecological group, it could also hinder the effects of the studied pharmacological agents on brain function solely associated with PTSD.…”

Psychedelic Therapy: A Primer for Primary Care Clinicians—3,4-Methylenedioxy-methamphetamine (MDMA)

“…34 Meanwhile, neuroimaging studies on humans have discovered that MDMA decreases cerebral blood flow, a measure of brain activity, in the amygdala. 35 In addition, MDMA elevates functional connectivity between the amygdala and hippocampus 35,36 (note that the second study only found a trend-level effect), a region that supports the encoding and retrieval of memories. 37 Taken together, these findings from both humans and rodents seem to be consistent with the clinical observation that MDMA-assisted therapy facilitates access to traumatic memories that were previously repressed.…”

MDMA-gestützte Therapie

“…Zudem wird davon ausgegangen, dass MDMA durch die Erhöhung der Konnektivität zwischen Amygdala und Hippocampus die Aufarbeitung traumatischer Erinnerungen im Rahmen des therapeutischen Prozesses begünstigen kann [7]. Eine fMRT-Studie konnte nach einer MDMA-gestützten Therapie eine Veränderung in Gehirnregionen nachweisen, welche mit Angst, PTBS und autobiografischen Gedächtnisprozessen assoziiert sind [8]. Zusätzlich sollte erwähnt werden, dass alle klinische Studien mit dem MDMA-Razemat durchgeführt worden sind.…”