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 via PubMed
Summary
AI-generated from the abstractIntermittent MDMA administration (10 mg/kg, three times weekly for 6 weeks) reduced demyelination in the corpus callosum of mice treated with cuprizone, a chemical that induces myelin loss. The effect appears linked to changes in gut bacteria and metabolites, including β-D-allose, L-sorbose, and carnitine, which correlated negatively with specific microbes such as Romboutsia. These findings suggest MDMA may influence brain demyelination through the gut-brain axis, though further research is needed to clarify the roles of gut microbiota and metabolites.
Study at a glance
| 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 Neuroscience |
| Citations | 6 |
| Key finding | 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.