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White matter alterations in chronic MDMA use: Evidence from diffusion tensor imaging and neurofilament light chain blood levels


Zimmermann, Josua; Friedli, Nicole; Bavato, Francesco; Stämpfli, Philipp; Coray, Rebecca; Baumgartner, Markus R; Grandgirard, Denis; Leib, Stephen L; Opitz, Antje; Seifritz, Erich; Stock, Ann-Kathrin; Beste, Christian; Cole, David M; Quednow, Boris B (2022). White matter alterations in chronic MDMA use: Evidence from diffusion tensor imaging and neurofilament light chain blood levels. NeuroImage: Clinical, 36:103191.

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.

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
04 Faculty of Medicine > Institute of Legal Medicine
04 Faculty of Medicine > Psychiatric University Hospital Zurich > Department of Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Radiology, Nuclear Medicine and Imaging
Life Sciences > Neurology
Health Sciences > Neurology (clinical)
Life Sciences > Cognitive Neuroscience
Uncontrolled Keywords:Cognitive Neuroscience, Neurology (clinical), Neurology, Radiology, Nuclear Medicine and imaging
Language:English
Date:1 January 2022
Deposited On:10 Oct 2022 15:00
Last Modified:27 Apr 2024 01:40
Publisher:Elsevier
ISSN:2213-1582
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.nicl.2022.103191
PubMed ID:36126513
Project Information:
  • : FunderSNSF
  • : Grant ID310030_189136
  • : Project TitleShedding light on the pathophysiology of pneumococcal and listeric meningitis by complementary disease models and non- invasive methods to evaluate novel therapeutics
  • : FunderSNSF
  • : Grant ID320030L_179450
  • : Project TitleComparative 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
  • : FunderDFG
  • : Grant IDBE4045/34-1
  • : Project Title
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)