3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA, ECSTASY) - PHARMACOLOGY AND TOXICOLOGY IN ANIMALS AND HUMANS

(+/-)3,4-Methylenedioxymethamphetamine (MDMA, ''Ecstasy''), a ring-sub stituted amphetamine derivative first synthesized in 1914, has emerged as a popular recreational drug of abuse over the last decade. Pharmac ological studies indicate that MDMA produces a mixture of central stim ulant and psychedelic effects, many of which appear to be mediated by brain monoamines, particularly serotonin and dopamine. In addition to its pharmacologic actions, MDMA has been found to possess toxic activi ty toward brain serotonin neurones. Serotonergic neurotoxicity after M DMA has been demonstrated in a variety of experimental animals (includ ing non-human primates). In monkeys, the neurotoxic dose of MDMA close ly approaches that used by humans. While the possibility that MDMA is also neurotoxic in humans is under investigation, other adverse effect s of MDMA in humans have been documented, including various systemic c omplications and a number of untoward neuropsychiatric sequelae. Notab ly, many of the adverse neuropsychiatric consequences noted after MDMA involve behavioral domains putatively influenced by brain serotonin ( e.g., mood, cognition and anxiety). Given the restricted status of MDM A use, retrospective clinical observations from suspecting clinicians will probably continue to be a primary source of information regarding MDMA's effects in humans. As such, this article is intended to famili arize the reader with the behavioral pharmacology and toxicology of MD MA, with the hope that improved recognition of MDMA-related syndromes will provide insight into the function of serotonin in the human brain , in health as well as disease.