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MDMA May Be Neurotoxic to Dopamine Neurons

The authors of this Science article retracted its publication on September 12, 2003.

Ecstasy ([±]3,4-methylenedioxymethamphetamine; MDMA), a common drug of abuse in the U.S. and elsewhere, has been shown to be a serotonin neurotoxin in rodent and nonhuman primate studies. In this 3-part, nonhuman primate study, researchers examined the effects of MDMA at a dosage that mimicked recreational use.

MDMA (3 doses of 2 mg/kg at 3-hour intervals) was injected into 5 squirrel monkeys. One monkey developed an unsteady gait and was not given the third dose; another developed malignant hyperthermia and died soon after the last dose. Two weeks after MDMA exposure, researchers assessed markers of the integrity of brain serotonergic and dopaminergic neurons in the 3 remaining animals and in 3 saline-treated controls. In addition to exhibiting serotonin toxicity, the MDMA-exposed monkeys showed greater dopamine toxicity, with significant reductions in various markers of striatal dopaminergic axon terminals. Similar findings were reported 6 weeks after MDMA exposure in the monkey that received only 2 doses.

To determine whether these findings were species-specific, the researchers conducted similar studies in 5 baboons. One MDMA-exposed baboon died of malignant hyperthermia, and another received only 2 doses because of side effects. Although measures of norepinephrine and norepinephrine transporters were unaffected, a profound loss of striatal dopaminergic axonal markers was observed.

To study the risk for parkinsonism in 3 MDMA-exposed monkeys, the researchers reduced brain dopamine levels with alphamethyl-paratyrosine (AMPT) 1 week before and 1 week after MDMA exposure. After receiving MDMA, the monkeys were considerably more sensitive to the effects of AMPT-induced motor dysfunction.

Comment: These results suggest that recreational MDMA users may be at risk for Parkinson's disease and may sustain long-lasting destruction of brain dopamine neurons.

— Charles Nemeroff, MD, PhD

Published in Journal Watch Psychiatry November 21, 2002

Citation(s):

Ricaurte GA et al. Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA ("ecstasy"). Science 2002 Sep 27; 297:2260-3.

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Ricaurte GA et al. Retraction. Science 2003 Sep 12; 301:1479.

Holden C. Retraction: Paper on toxic party drug is pulled over vial mix-up. Science 2003 Sep 12; 301:1454.