Memory deficits of MDMA users are linked to cortical thinning related to 5-HT receptor densities
Rebecca C Coray, Vincent Beliveau, Josua Zimmermann, Katrin H. Preller, Michael D. Wunderli, Markus R Baumgartner, Erich Seifritz, Ann-Kathrin Stock, Christian Beste, David M. Cole, Boris B. Quednow
Brain October 19, 2025 DOI: 10.1093/brain/awaf391 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 122 |
| Population | MDMA users and matched MDMA-naive controls |
| Topics | MDMA Serotonin |
| Keywords | Grey matter Mnemonic Hippocampal formation Recall Episodic memory Hippocampus Verbal memory Cognitive psychology Cognition |
| Citations | 1 |
| Key findings | MDMA users showed reduced hippocampal grey matter volume and impaired verbal memory, with structural differences linked to serotonin receptor densities and MDMA use intensity. |
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 to controls. Self-reported MDMA use in the past six 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 behavior, possibly via influences on brain grey matter structures.
Comparable studies
Other observational and cohort studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subjective Reports of the Effects of MDMA in a Clinical Setting Individuals who took MDMA in a clinical setting | 1986 | Observational study | |
| Memory impairment in abstinent MDMA ("Ecstasy") users Abstinent MDMA users | 1998 | Observational cohort | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| The Psychological and Physiological Effects of MDMA on Normal Volunteers Older, more educated, drug-experienced individuals | 1986 | Observational cohort | |
| Cognitive performance in recreational users of MDMA or 'ecstasy': evidence for memory deficits Young people who were regular or novice MDMA users, or non-users | 1998 | Observational cohort | n = 30 |