Effects of MDMA on the Human Nervous System

(±)3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a synthetic ring-substituted amphetamine analog that produces a unique blend of stimulant and psychedelic effects. Considerable research demonstrates that MDMA has the potential to damage brain serotonin (5-HT)-containing neurons in animals, and a growing body of data indicates that MDMA is also a 5-HT neurotoxin in humans. This chapter begins with a review of the history of MDMA's origins and early use practices, its emergence as a "party drug" in the 1990s, and its more recent reemergence as a potential psychotherapeutic adjunct in insight-oriented therapy. The major focus of this chapter addresses MDMA's effects on the human nervous system. To this end, MDMA's mechanism of action and its effects on the sympathetic nervous system are first detailed. The ensuing discussion addresses MDMA's effects on the central nervous system, including its pharmacological and neurotoxic effects, relying on information from preclinical models, when appropriate. Studies in humans that have attempted to identify lasting functional consequences of MDMA-induced 5-HT injury on cognitive function, sleep, neuroendocrine control, and pain function are reviewed, and evidence that MDMA may precipitate acute or lasting neuropsychiatric disorders is discussed. Finally, limitations of existing data in humans are discussed, and suggested directions for future research are provided.