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 C 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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 Neurofilament light chain |
| Citations | 14 |
| Key findings | 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.
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 |
Citations in the library
Cited by 7
- Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings Neural Regeneration Research February 22, 2024
- Neural correlates of treatment response to ketamine for treatment-resistant depression: A systematic review of MRI-based studies. Psychiatry Research October 1, 2024
- Chemical cousins with contrasting behavioural profiles: MDMA users and methamphetamine users differ in social-cognitive functions and aggression. European Neuropsychopharmacology June 1, 2024
- The functional connectome of 3,4‐methyldioxymethamphetamine‐related declarative memory impairments Human Brain Mapping August 2, 2023
- Differential alterations in peripheral tryptophan pathways in methamphetamine versus MDMA users are linked to their contrasting psychiatric symptoms. Translational Psychiatry May 21, 2026
and 2 more in the library
Cites 30
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
- Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Journal of Neuroscience June 15, 1999
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
and 25 more in the library