Altered insula connectivity under MDMA

This within-subjects, double-blind, randomized, placebo-controlled study (n=25) investigated the effects of MDMA (100mg) on brain connectivity, and found that it decreased functional connectivity insula/salience network, which was also correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA.

Abstract

Introduction: Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap.

Methods: To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired.

Results: There was decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA.

Discussion: The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations–both of which are known to be associated with insular functioning.

Authors: Ishan C. Walpola,Timothy Nest, Leor Roseman, David Erritzoe, Amanda Feilding, David J Nutt & Robin L Carhart-Harris

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