Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview
Molecular Neurobiology June 1, 2009 João Paulo Capela, Helena Carmo, Fernando Remião et al.
MDMA (ecstasy) is a widely abused hallucinogenic drug that can damage nerve cells in both animals and humans. In rats and some mouse strains, it destroys serotonin-producing nerve endings and causes broader brain damage in areas like the cortex, hippocampus, and striatum. In human users, reduced serotonin markers correlate with lasting memory and learning problems. The neurotoxicity involves multiple factors: hyperthermia, metabolism by monoamine oxidase, dopamine oxidation, serotonin transporter activity, nitric oxide and peroxynitrite formation, glutamate excitotoxicity, serotonin 2A receptor activation, and toxic metabolites. This review summarizes the history, pharmacology, metabolism, and cellular/molecular mechanisms of MDMA neurotoxicity to aid development of treatments for long-term psychiatric complications.