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Commins and
colleagues [n32] have proposed that MDMA and related compounds destroy
serotonergic neurons by releasing large amounts of serotonin and inducing
endogenous formation of 5, 6-dihydroxytryptamine, a well-known serotonergic
neurotoxin.

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It is not yet known whether the effects of MDMA on serotonergic neurons in
the primate are permanent or reversible. Under some circumstances,
regeneration of serotonergic nerve fibers in the central nervous system can
take place. [n26] However, for axon regrowth to occur, the cell body must be
preserved. It remains to be determined if serotonin-containing cell bodies
in the dorsal raphe nucleus of the MDMA -treated primate survive beyond two
weeks. If they do, and if regeneration of nerve fibers takes place, it is
still not certain that the new fibers would establish normal connections.

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Multiple doses of MDMA also produced large depletions
of serotonin in the caudate nucleus, putamen, hippocampus, hypothalamus, and
thalamus of the monkey (Table 2). One of the most severely affected areas was
the cerebral cortex (Table 2), where the lowest dose (2.5 mg/kg) of MDMA
produced a 44% depletion of serotonin (Table 1).

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MDMA does produce long-lasting changes to the serotonergic system at some doses. These long-term changes include decreases in brain concentrations of the neurotransmitter serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA). Levels of tryptophan hydroxylase (TPH), the enzyme that begins the synthesis of 5-HT within the serotonergic nerve cell are decreased. There are also decreases in the density of the serotonin reuptake transporter (SERT), the protein on the membrane of serotonergic neurons that recycles released 5-HT by pulling it back into the cell. Most studies suggest that MDMA primarily causes long-term changes in serotonergic axons that have their cell bodies in an area of the brainstem called the dorsal raphe nucleus.

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Long-lasting decreases in these serotonergic markers suggest that either (a) some type of "down regulation" has occurred, meaning the nerve cell is making and maintaining less of the markers, or (b) that serotonergic axons are permanently lost.

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The sustained acute pharmacological effects of MDMA may exhaust neuronal energy sources and antioxidant defenses, leading to damage. Metabolites of MDMA are another possible source of oxidative stress. Very few behavioral correlates of MDMA exposure have been found in drug-free laboratory animals, despite dramatic serotonergic changes, alterations in neurofunctioning, and changes in response to drugs. A growing number of studies describe differences between ecstasy users and nonusers. These studies have serious limitations, but suggest that some ecstasy users experience serotonergic changes and cognitive alterations.

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>> I also heard if you take SSRIs it could prevent any brain damage occuring on the same sites cause the ssris will bind and prevent damage?

MDMA's neurotoxicity occurs when dopamine, in the absence of sertonin, binds to the 5-HTR transporter and is deposited into the synaptic vesicle. Once deposited, an enzyme called monoamine oxidase attemps to break dopamine down, producing H2O2, or hydrogen peroxide, which oxidizes brain cells and causes their disintegration. This is called oxidative stress.

SSRI's have greater affinity for the 5-HTR receptor site than both serotonin and dopamine. Theoretically, taking an SSRI just as the acute effects of MDMA are beginning to disappear will both prolong the experience as well as block dopamine from binding to the 5-HTR transporter, eliminating the potential for oxidative stress. Studies proving this have thus far only been carried out on mice, and there is no way of knowing how well this method of prophylaxis translates to humans.

Beacuse of it's schedule one status, there has not been sufficient study to determine the risks surrounding MDMA-induced oxidative stress, or precise data detailing the doses of MDMA necessary to make an individual particularly vulnerable to the effects of oxidative stress. Regardless, oxidative stress does occur, and is a well-documented side effect of MDMA use. The risk is quite real and should not be ignored.

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