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

MDMA (Ecstasy) is a brain serotonergic neurotoxin in animals, including nonhuman primates. Recreational doses overlap with those causing serotonin neurotoxicity in animals. Human MDMA users show selective decreases in cerebrospinal fluid 5-hydroxyindoleacetic acid and brain serotonin transporters, similar to neurotoxicity seen in nonhuman primates. Functional abnormalities possibly related to serotonin injury include cognitive deficits, altered sleep architecture, altered neuroendocrine function, altered behavioral responses to serotonin-selective drugs, and increased impulsivity. Further animal, longitudinal, and epidemiological studies are needed to confirm these findings and assess whether users face increased risk of neuropsychiatric illness with age.

Study at a glance

Abstract

(±)3,4-Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) is a brain serotonergic neurotoxin in experimental animals, including nonhuman primates. It is also an increasingly popular recreational drug of abuse, and doses of MDMA that are used recreationally overlap with those that produce serotonin (5-HT) neurotoxicity in animals. Studies in human MDMA users probing for evidence of brain serotonergic neurotoxicity indicate that some MDMA users may incur MDMA-related 5-HT neural injury and, possibly, functional sequelae. In particular, MDMA users have selective decrements in cerebrospinal fluid 5-hydroxyindoleacetic acid and brain 5-HT transporters, similar to nonhuman primates with documented MDMA-induced neurotoxicity. Functional abnormalities seen in MDMA users that may be related to 5- HT injury include cognitive deficits, altered sleep architecture, altered neuroendocrine function, altered behavioral responses to 5-HT selective drugs, and increased impulsivity. Additional studies in animals, as well as longitudinal and epidemiological studies in MDMA users, are required to confirm and extend the present data, and to determine whether MDMA users are at increased risk for developing neuropsychiatric illness as they age.