Abstract
BackgroundThe compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals. MethodsIn 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. ResultsMarked 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. ConclusionsThe 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.
Highlights
The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals
When hippocampal resting state functional connectivity (RSFC) after MDMA administration was contrasted against hippocampal RSFC after placebo administration, significant increases in RSFC were observed in the dorsal ACC, right amygdala, and right middle frontal gyrus
When amygdala RSFC after MDMA administration was contrasted against amygdala RSFC after placebo administration, significant increases in RSFC were observed in the brainstem and bilaterally in the anterior parahippocampal gyrus
Summary
This was a within-subjects, double-blind, randomized, placebocontrolled study. Participants were scanned twice, 7 days apart —once after MDMA and once after placebo. The study was approved by the National Research Ethics Service West London Research Ethics Committee, Joint Compliance and Research Office of Imperial College London, Research Ethics Committee of Imperial College London, Head of the Department of Medicine of Imperial College London, Imanova Centre for Imaging Science, and Faculty of Medicine of Imperial College London. The study was conducted in accordance with Good Clinical Practice guidelines. A Home Office Licence was obtained for the storage and handling of a Schedule 1 drug.
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