(±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals

MDMA, or 'Ecstasy', is a potent and selective neurotoxin for brain serotonin neurons in animals, as shown by neurochemical, neuroanatomical, and functional measures. New data indicate that MDMA reduces levels of the type 2 vesicular monoamine transporter, further supporting its serotonin neurotoxic potential. Using interspecies scaling, the authors demonstrate that dosages of MDMA known to be neurotoxic in animals fall squarely within the range used by recreational human users, countering the argument that animal dosages are too high to be relevant.

Study at a glance

Abstract

The popular recreational drug, (±)3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) is a potent and selective brain serotonin (5-HT) neurotoxin in animals. MDMA-induced 5-HT neurotoxicity can be demonstrated using a variety of neurochemical, neuroanatomical and, more recently, functional measures of 5-HT neurons. Although the neurotoxic effects of MDMA in animals are widely accepted, the relevance of the animal data to human MDMA users has been questioned, largely because dosages of drugs used in animals are perceived as being much higher than those used by humans. In the present paper, we review the extensive body of data demonstrating that MDMA produced toxic effects on brain 5-HT neurons in animals and present new data indicating that levels of the type 2 vesicular monoamine transporter are reduced in MDMA-treated animals, providing further indication of MDMA’s 5-HT neurotoxic potential. Further, we demonstrate, using principles of interspecies scaling, that dosages of MDMA known to be neurotoxic in animals fall squarely in the range of dosages used typically by recreational MDMA users.