White matter alterations in chronic MDMA use: Evidence from diffusion tensor imaging and neurofilament light chain blood levels
Josua Zimmermann, Nicole Friedli, Francesco Bavato, Philipp Stämpfli, Rebecca Coray, Markus R. Baumgartner, Denis Grandgirard, Stephen L. Leib, Antje Opitz, Erich Seifritz, Ann-Kathrin Stock, Christian Beste, David M. Cole, Boris B. Quednow
NeuroImage: Clinical September 19, 2022 Peer reviewed DOI: 10.1016/j.nicl.2022.103191 via DOAJ
Summary
Chronic MDMA users showed increased fractional anisotropy in several white matter tracts, particularly in the corpus callosum and corticospinal tracts, which correlated with MDMA use intensity. However, there were no significant differences in neurofilament light chain levels between MDMA users and healthy controls. These findings suggest that MDMA use does not lead to significant white matter lesions in humans, contrasting with animal studies that indicated axonal degeneration.
Study at a glance
| Sample size | 78 |
|---|---|
| Population | 39 chronic MDMA users and 39 matched MDMA-naïve healthy controls |
| Key finding | MDMA use is not associated with significant white matter lesions in humans. |
Abstract
3,4–Methylenedioxymethamphetamine (MDMA, “Ecstasy”) is a serotonin- and noradrenaline-releasing substance, currently among the most widely used illicit substances worldwide. In animal studies, repeated exposure to MDMA has been associated with dendritic but also axonal degeneration in the brain. However, translation of the axonal findings, specifically, to humans has been repeatedly questioned and the few existing studies investigating white matter alterations in human chronic MDMA users have yielded conflicting findings. In this study, we combined whole-brain diffusion tensor imaging and neurofilament light chain (NfL) analysis in blood to reveal potential MDMA-induced axonal neuropathology. To this end, we assessed 39 chronic MDMA users and 39 matched MDMA-naïve healthy controls. MDMA users showed increased fractional anisotropy in several white matter tracts, most prominently in the corpus callosum as well as corticospinal tracts, with these findings partly related to MDMA use intensity. However, the NfL levels of MDMA users were not significantly different from those of controls. We conclude that MDMA use is not associated with significant white matter lesions due to the absence of reduced fractional anisotropy and increased NfL levels commonly observed in conditions associated with white matter lesions, including stimulant and ketamine use disorders. Hence, the MDMA-induced axonal degradation demonstrated in animal models was not observed in this human study of chronic MDMA users.