Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms.
Methylenedioxymethamphetamine (MDMA, Ecstasy) is a very popular drug of abuse. This has led to new intense concerns relevant to its nefarious neuropsychiatric effects. These adverse events might be related to the neurotoxic effects of the drug. Although the mechanisms of MDMA-induced neurotoxicity remain to be fully characterized, exposure to the drug can cause acute and long-term neurotoxic effects in animals and nonhuman primates. Recent studies have also documented possible toxic effects in the developing fetus. Nevertheless, there is still much debate concerning the effects of the drug in humans and how to best extrapolate animal and nonhuman primate data to the human condition. Herein, we review the evidence documenting the adverse effects of the drug in some animal models. We also discuss possible mechanisms for the development of MDMA neurotoxicity. Data supporting deleterious effects of this drug on the developing fetus are also described. Much remains to be done in order to clarify the molecular and biochemical pathways involved in the long-term neuroplastic changes associated with MDMA abuse.
Lyles
Johnalyn
J
Molecular Neuropsychiatry Branch, National Institutes of Health/National Institute on Drug Abuse Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Cadet
Jean Lud
JL
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects; D006213:Hallucinogens / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D023421:Models, Animal; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism
D006213:Hallucinogens; D018377:Neurotransmitter Agents; D011985:Receptors, Serotonin; D009569:Nitric Oxide; D018817:N-Methyl-3,4-methylenedioxyamphetamine