MDMA and brain activity during neurocognitive performance: An overview of neuroimaging studies with abstinent ‘Ecstasy’ users

Introduction

MDMA (3,4-methylenedioxymethamphetamine, commonly 'Ecstasy') has returned to prominence with rising prevalence among young adults and higher-strength tablets/powders in recent years. Preclinical studies have shown that repeated high-dose MDMA exposure reduces central serotonin function and may cause loss of serotonergic terminals; early human molecular imaging likewise reported reduced serotonin transporter (SERT) availability in several brain regions. At the same time, human neuropsychological studies report inconsistent neurocognitive findings: some show deficits (notably in verbal memory and other aspects of memory/executive function) while others do not, and it remains uncertain which factors (dose, polydrug use, abstinence duration, task selection) determine observed impairments. Roberts and colleagues set out to review empirical human neuroimaging studies that examined brain activity during neurocognitive performance in abstinent recreational MDMA/ecstasy users. The review covers molecular imaging (PET, SPECT), haemodynamic functional imaging (fMRI, fNIRS), and electrophysiological measures (EEG/ERPs, sensory-evoked potentials), with the goal of relating imaging-indexed serotonergic or metabolic changes to performance on cognitive tasks and to identify common patterns and gaps in the literature.