Repeated intermittent administration of 3,4-methylenedioxymethamphetamine mitigates demyelination in the brain from cuprizone-treated mice.
Mingming Zhao, Akifumi Eguchi, Rumi Murayama, Dan Xu, Tingting Zhu, Biao Xu, Guiling Liu, Chisato Mori, Jianjun Yang, Kenji Hashimoto
European Journal of Pharmacology March 15, 2025 DOI: 10.1016/j.ejphar.2025.177345 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Cuprizone-treated mice |
| Intervention | MDMA |
| Dose | 10 mg/kg |
| Duration | 6 weeks |
| Topics | MDMA |
| Keywords | Demyelination Gut microbiota Metabolites Psychedelic medicine Gut-brain axis Drug research Medical breakthrough |
| Citations | 6 |
| Key points | Intermittent MDMA administration reduced demyelination in the corpus callosum of cuprizone-treated mice, with associated changes in gut microbiota and metabolites. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA), commonly known as a recreational drug, may also offer therapeutic benefits for mental health. Population-based studies suggest that MDMA users have a lower risk of demyelinating diseases, such as depression. Given the role of the gut microbiota in mediating MDMA's effects, we hypothesized that MDMA might confer mental health benefits via the gut-brain axis. Cuprizone (CPZ) induces demyelination by chelating copper, which leads to oligodendrocyte death and subsequent myelin loss. This study investigated the impact of MDMA on brain demyelination in CPZ-treated mice, focusing on the gut-brain axis. Repeated intermittent MDMA administration (10 mg/kg, three times weekly for 6 weeks) significantly reduced demyelination in the corpus callosum (CC) of CPZ-treated mice. Gut microbiota and non-targeted metabolomics analyses revealed notable differences in specific gut bacteria and plasma (β-D-allose and L-sorbose) or fecal metabolite (carnitine) levels between MDMA-treated and vehicle-treated CPZ-exposed mice. Negative correlations were found between the levels of metabolites (β-D-allose, L-sorbose, and carnitine) and the relative abundance of Romboutsia and Romboutsia timonensis. These findings suggest that intermittent MDMA administration may alleviate demyelination in the CC of CPZ-treated mice via the gut-brain axis. Further research is needed to elucidate the roles of gut microbiota and metabolites in MDMA's effects on brain demyelination and to investigate other demyelination models.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 19
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
- A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy Frontiers in Psychiatry March 20, 2019
- Agony and ecstasy: a review of MDMA effects and toxicity European Psychiatry August 1, 2000
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
and 14 more in the library