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 DOI: 10.1016/j.nicl.2022.103191 via DOAJ
Summary
AI-generated from the abstractChronic 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.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 78 |
| Population | Chronic MDMA users and matched MDMA-naïve healthy controls |
| Topics | MDMA |
| Keywords | Neurotoxicity Axonal neuropathology White matter Dti |
| Citations | 14 |
| Key finding | Chronic MDMA use is not associated with significant white matter lesions, as evidenced by increased fractional anisotropy and normal neurofilament light chain levels. |
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.