Memory deficits of MDMA users are linked to cortical thinning related to 5-HT receptor densities
Year: 2025
Type: article
Study design: Observational Study
Abstract: Regular recreational use of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') has been consistently linked to verbal memory dysfunctions, whose neurobiological origins remain unclear. Although neurochemical, structural and functional alterations resulting from repeated MDMA intake have been identified in user populations, only limited knowledge exists regarding potential interrelationships among these components and their implications for mnemonic functions. The present study, thus, first examined the association of MDMA use with grey matter volume and cortical thickness. Subsequently, structural brain alterations were related to verbal memory performance and atlas-derived cerebral serotonin (5-HT) receptor expression patterns. Our data, involving 122 participants (61 MDMA users, 61 age-, sex- and education-matched MDMA-naive controls), revealed a robust reduction of grey matter volume within hippocampal regions and impaired verbal learning, short-term recall after interference, long-term recall and recognition performance in MDMA users compared with controls. Self-reported MDMA use in the past 6 months correlated with several memory performance scores. A moderate inverse correlation across all participants was observed between hippocampal volumes and verbal long-term memory. Correspondingly, hippocampal CA1 grey matter volume was related to MDMA use intensity in the last months as indicated by MDMA hair concentrations. The extent of cortical and subcortical grey matter differences between groups correlated with atlas-based 5-HT1A, 5-HT2A and 5-HT4 receptor densities, suggesting a serotonergic basis for mnemonic and structural alterations in MDMA users. Together, these findings highlight a multidimensional origin of memory dysfunction in MDMA users, where alterations in the chemoarchitecture of the brain may affect behaviour, possibly via influences on brain grey matter structures.
Source: Brain
Institutions: University of Zurich, ETH Zurich, University Hospital Zurich, Psychiatrische Universitätsklinik Zürich, Innsbruck Medical University, Universität Innsbruck, Copenhagen University Hospital, Rigshospitalet, Technische Universität Dresden, University of Basel, Universitäre Psychiatrische Kliniken Basel
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $5,570
Awards: Neurosocial consequences of cocaine use: a longitudinal investigation, G2551127468, G2944974243, Comparative neuropsychopharmacology of methamphetamine (“Crystal Meth”) and MDMA (“Ecstasy”) on facets of cognitive control and impulsive behavior in social and non-social contexts: integrating behavior, psychophysiology, and neurochemistry, G3360777551, G4675219560, Neurosocial consequences of cocaine use: a longitudinal investigation
OpenAlex ID: W4415408355