MDMA and Seizures: A Dangerous Liaison?

Repeated small doses of MDMA produce a lasting pro-convulsant effect that lowers the threshold for limbic seizures and increases metabolic hyperexcitability in mice, even before structural changes like mossy fiber sprouting appear. While clinical seizures after MDMA use are often attributed to acute effects such as hyponatremia and hyperthermia, additional mechanisms involving monoaminergic systems may also contribute. Chronic effects of MDMA on seizure threshold have been underexplored, and this review presents preliminary data showing that seizure susceptibility emerges early, without accompanying mossy fiber sprouting.

Study at a glance

Abstract

Abstract: In the past decades, there was a massive increase in the abuse of methylenedioxymethamphetamine (MDMA) in the Western countries. Seizure onset after MDMA is considered to be related mainly to its acute systemic effects (e.g., hyponatremia and hyperthermia). However, additional mechanisms might concur to it as well. Experiments aimed at disclosing the basis for such an acute effect have the advantage of profiting of controlled conditions and the “pure” compounds, as opposed to the limits of clinical data which are biased by several confounding factors. Amphetamines exert profound effect on different monoaminergic systems, which might participate to lowering of seizure threshold. Chronic effects of MDMA abuse on seizure threshold have not been explored in detail so far. Recent data showed that in mice receiving small, repeated doses of MDMA, a persisting pro‐convulsant effect toward limbic seizures and metabolic hyperexcitability can be observed. In the present article, we reviewed these studies and we report our preliminary experimental data documenting the lack of mossy fiber sprouting at short time intervals following MDMA, when seizure susceptibility is already present.