Studies of MDMA-induced neurotoxicity in nonhuman primates: a basis for evaluating long-term effects in humans.

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Abstract

The results of the studies reviewed here show that the neurotoxic effects of MDMA generalize to the primate. Further, they indicate that monkeys are considerably more sensitive than rats to the serotonin-depleting effects of MDMA, and that the dose-response curve of MDMA in the monkey is much steeper than in the rat. Perhaps as a consequence of this, the toxic effects of MDMA in the monkey involve serotonergic nerve fibers as well as cell bodies, whereas in the rat, only nerve fibers are affected. The present studies also show that the toxic dose of MDMA in the monkey (5 mg/kg) closely approaches the dose typically used by humans (1.7 to 2.7 mg/kg). This finding heightens concern that MDMA may be neurotoxic in humans, particularly since the steepness of the dose-response curve of MDMA in the primate suggests a narrow margin of safety. Finally, preclinical studies in monkeys have shown that CSF 5-HIAA can be used to detect MDMA-induced serotonergic damage in the primate CNS. Studies now underway in MDMA-exposed humans should help determine if MDMA exerts long-term toxic effects on serotonergic neurons in the human brain.

Original languageEnglish (US)
Pages (from-to)306-322
Number of pages17
JournalNIDA research monograph
Volume94
StatePublished - 1989

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N-Methyl-3,4-methylenedioxyamphetamine
Primates
Haplorhini
Poisons
Nerve Fibers
Serotonin Agents
Serotonergic Neurons
Hydroxyindoleacetic Acid
Safety
Neurons

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

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title = "Studies of MDMA-induced neurotoxicity in nonhuman primates: a basis for evaluating long-term effects in humans.",
abstract = "The results of the studies reviewed here show that the neurotoxic effects of MDMA generalize to the primate. Further, they indicate that monkeys are considerably more sensitive than rats to the serotonin-depleting effects of MDMA, and that the dose-response curve of MDMA in the monkey is much steeper than in the rat. Perhaps as a consequence of this, the toxic effects of MDMA in the monkey involve serotonergic nerve fibers as well as cell bodies, whereas in the rat, only nerve fibers are affected. The present studies also show that the toxic dose of MDMA in the monkey (5 mg/kg) closely approaches the dose typically used by humans (1.7 to 2.7 mg/kg). This finding heightens concern that MDMA may be neurotoxic in humans, particularly since the steepness of the dose-response curve of MDMA in the primate suggests a narrow margin of safety. Finally, preclinical studies in monkeys have shown that CSF 5-HIAA can be used to detect MDMA-induced serotonergic damage in the primate CNS. Studies now underway in MDMA-exposed humans should help determine if MDMA exerts long-term toxic effects on serotonergic neurons in the human brain.",
author = "George Ricaurte",
year = "1989",
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pages = "306--322",
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AU - Ricaurte, George

PY - 1989

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N2 - The results of the studies reviewed here show that the neurotoxic effects of MDMA generalize to the primate. Further, they indicate that monkeys are considerably more sensitive than rats to the serotonin-depleting effects of MDMA, and that the dose-response curve of MDMA in the monkey is much steeper than in the rat. Perhaps as a consequence of this, the toxic effects of MDMA in the monkey involve serotonergic nerve fibers as well as cell bodies, whereas in the rat, only nerve fibers are affected. The present studies also show that the toxic dose of MDMA in the monkey (5 mg/kg) closely approaches the dose typically used by humans (1.7 to 2.7 mg/kg). This finding heightens concern that MDMA may be neurotoxic in humans, particularly since the steepness of the dose-response curve of MDMA in the primate suggests a narrow margin of safety. Finally, preclinical studies in monkeys have shown that CSF 5-HIAA can be used to detect MDMA-induced serotonergic damage in the primate CNS. Studies now underway in MDMA-exposed humans should help determine if MDMA exerts long-term toxic effects on serotonergic neurons in the human brain.

AB - The results of the studies reviewed here show that the neurotoxic effects of MDMA generalize to the primate. Further, they indicate that monkeys are considerably more sensitive than rats to the serotonin-depleting effects of MDMA, and that the dose-response curve of MDMA in the monkey is much steeper than in the rat. Perhaps as a consequence of this, the toxic effects of MDMA in the monkey involve serotonergic nerve fibers as well as cell bodies, whereas in the rat, only nerve fibers are affected. The present studies also show that the toxic dose of MDMA in the monkey (5 mg/kg) closely approaches the dose typically used by humans (1.7 to 2.7 mg/kg). This finding heightens concern that MDMA may be neurotoxic in humans, particularly since the steepness of the dose-response curve of MDMA in the primate suggests a narrow margin of safety. Finally, preclinical studies in monkeys have shown that CSF 5-HIAA can be used to detect MDMA-induced serotonergic damage in the primate CNS. Studies now underway in MDMA-exposed humans should help determine if MDMA exerts long-term toxic effects on serotonergic neurons in the human brain.

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