The effects of acutely administered 3, 4-methylenedioxymethamphetamine on spontaneous brain function in healthy volunteers measured with arterial spin labeling and blood oxygen level–dependent resting state functional connectivity

This study (n=25) investigated how the subjective effects of MDMA are related to its neural effects. fMRI scans during MDMA use showed changes in cerebral blood flow in the right medial temporal lobe, thalamus, inferior visual cortex, somatosensory cortex, right amygdala and hippocampus, as well as decreased resting-state functional connectivity (RSFC) between midline cortical regions, the medial prefrontal cortex, and the medial temporal lobe. They increased RSFC between the amygdala and hippocampus.

Abstract

“Background: The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.

Methods: In a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level–dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.

Results: Marked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.

Conclusions: The MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity.”

Authors: Robin L. Carhart-Harris, Kevin Murphy, Robert Leech, David Erritzoe, Matthew B. Wall, Bart Ferguson, Luke T.J. Williams, Leor Roseman, Stefan Brugger, Ineke De Meer, Mark Tanner, Robin Tyacke, Kim Wolff, Ajun Sethi, Michael A.P. Bloomfield, Tim M. Williams, Mark Bolstridge, Lorna Stewart, Celia Morgan, Rexford D. Newbould, Amanda Feilding, H. Valerie Curran & David J. Nutt