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The Mechanism of MDMA Neurotoxicity
by Erowid
November 2001

"the MDMA-induced depletion of brain 5-HT and the functional consequences thereof appear to involve the induction of oxidative stress resulting from an increased generation of free radicals and diminished antioxidant capacity of the brain."
Shankaran M, Yamamoto BK, Gudelsky GA. 2001. "Ascorbic Acid Prevents 3,4- Methylenedioxymethamphetamine (MDMA)-Induced Hydroxyl Radical Formation and the Behavioral and Neurochemical Consequences of the Depletion of Brain 5-HT" Synapse 40:55-64.

"damage occurs when endogenous free radical scavenging mechanisms become overwhelmed or exhausted."
O'Shea E, Granados R, Esteban B, Colado MI, Green AR. 1998. "The relationship between the degree of neurodegeneration of rat brain 5-HT nerve terminals and the dose and frequency of administration of MDMA ('ecstasy')" Neuropharmacology 37(7):919-26.

"The exhaustion of energy in 5-HT nerve terminals compromised all energy-requiring endogenous mechanisms involved in the regulation of transmembrane-ion exchange, internal Ca(++)-homeostasis, prevention of oxidative stress, detoxification, and repair. Above a critical threshold the failure of these self-protective mechanisms will lead to the degeneration of the 5-HT axon Unterminals."
Huether G, Zhou D, Ruther E. 1997. "Causes and consequences of the loss of serotonergic presynapses elicited by the consumption of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and its congeners" J Neural Transm 104(8-9):771-94.

Role of Oxidative Stress in MDMA Neurotoxicity - Baggott Local File