Chronic MDMA users show increased fractional anisotropy in white matter tracts, particularly the corpus callosum and corticospinal tracts, with some links to usage intensity. However, blood neurofilament light chain levels did not differ from controls. The absence of reduced fractional anisotropy and elevated NfL—typically seen in conditions with white matter lesions, such as stimulant and ketamine use disorders—suggests MDMA use is not associated with significant white matter damage. Thus, axonal degradation observed in animal models was not replicated in this human sample of 39 chronic users and 39 matched controls.
Chronic users of methamphetamine and MDMA show similar deficits in conflict control and emotional processing, rather than substance-specific differences. In an emotional face-word Stroop task with anger and happy faces, both user groups exhibited smaller behavioral effects of cognitive-emotional conflict and selective impairments in processing anger, compared to amphetamine-naïve controls. These deficits were accompanied by stronger P3 event-related potential modulations, indicating altered stimulus-response mapping and decision-making. The findings suggest that chronic use of substituted amphetamines may affect noradrenergic systems, which could underlie the observed similarities. Understanding noradrenaline's role in these processes is an important direction for future research.
Regular recreational use of MDMA (Ecstasy) is linked to verbal memory problems, and this study examined the brain changes underlying these deficits. Comparing 61 MDMA users with 61 matched non-users, the researchers found reduced grey matter volume in hippocampal regions and impaired verbal learning, short-term recall after interference, long-term recall, and recognition in users. Self-reported MDMA use over the past six months correlated with several memory scores. Hippocampal volume, especially in the CA1 subregion, was inversely related to verbal long-term memory and to MDMA use intensity measured by hair concentrations. Differences in grey matter between groups correlated with brain serotonin receptor densities, suggesting a serotonergic basis for the structural and memory changes.
The authors argue that the consequences of MDMA use cannot be easily separated from the effects of other drug use or lifestyle factors, highlighting the difficulty in attributing specific outcomes solely to MDMA.