Experimental studies on 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and its potential to damage brain serotonin neurons
by
Ricaurte GA, McCann UD.
Departments of Neurology and Psychiatry Behavioral Sciences,
Johns Hopkins Medical Institutions,
Baltimore, MD 21224, USA.
Neurotox Res. 2001 Jan;3(1):85-99


ABSTRACT

A number of drugs that fall into the broad category of "ring-substituted amphetamines" have been found to be neurotoxic toward brain monoamine neurons in animals. Several of these drugs, including 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") and methamphetamine ("speed") and fenfluramine ("Pondimin") have been used or abused by humans. A growing body of evidence indicates that humans, like animals, are susceptible to substituted amphetamine-induced neurotoxic injury, and that consequences of this injury can be subtle. This article will review the effects of ring-substituted amphetamine analogs on brain monoamine neurons, using MDMA as the prototype. Studies documenting MDMA neurotoxic potential toward brain serotonin (5-HT) neurons in animals are summarized first. Human MDMA studies are then discussed, beginning with a consideration of methodological challenges in evaluating the status of 5-HT neurons in the living human brain. Recent findings indicating possible functional alterations in brain serotonergic systems in humans with a history of extensive MDMA exposure are then presented, including some new findings on sleep and personality in abstinent MDMA users.

Long-term brain damage?
Toxic metabolites of MDMA?
MDMA and sympathetic activity
A toxic intraneuronal metabolite of serotonin?
Electrophysiological evidence of 5-HT damage
Non-neurotoxic and neurotoxic serotonin-releasers
Ecstasy-induced toxicity and the dopamine transporter
5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine


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