Goran.Hrsak
Holofractale de l'hypervérité
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- 30/3/06
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MDMA: neurotoxicity
No compelling evidence exists that taking a single c.125mg dose of MDMA a few times or so a year is likely to cause any long-term harm to the user's mental or physical health. Nevertheless, even pharmaceutical-grade MDMA taken at moderate doses in optimal conditions is not a wholly benign drug. The problem isn't (just) the toxic adulterants used by dance-floor pharmacologists or the botched syntheses of bathtub chemists. Deceptively, and in contrast to most other recreationally used drugs, ingesting pure MDMA can sometimes leave the user feeling better than normal the next day, albeit tired and slightly spaced-out. Beyond warm memories, this afterglow may in part be explained by MDMA's residual amphetamine metabolic by-products: MDMA itself has a long, c.8-9 hour elimination half-life from the blood; and its main metabolite's longer-acting, less stimulating (-)-MDA enantiomer has 5-HT2A activating effects resembling low-grade LSD. But two days or so after taking MDMA, most users experience the serotonin dip. The dip ranges from the almost imperceptible to the markedly unpleasant. The functional deficit the dip reflects may last ten days or more - in some cases possibly weeks or months. A biphasic post-E serotonin profile in the user has been reported: users' serotonin levels - though hard to measure and interpret - apparently fall 3-6 hours after taking the drug, then recover to nearly normal levels after around 24 hours, and then decline again.
Excessive MDMA intake triggers oxidative damage to the user's serotonergic nerve cell fine axon terminal lipids and proteins via the production of toxic free radicals. However, the threshold dose for any lasting MDMA-induced toxicity is unknown; and the identity and precise mechanism of the chemical(s) causing the oxidative stress is unclear. The issue is also controversial. Currently the three leading candidates for guilty agent are:
1] toxic metabolites of MDMA
2] toxic metabolites of dopamine
3] impaired cellular energetics
No compelling evidence exists that taking a single c.125mg dose of MDMA a few times or so a year is likely to cause any long-term harm to the user's mental or physical health. Nevertheless, even pharmaceutical-grade MDMA taken at moderate doses in optimal conditions is not a wholly benign drug. The problem isn't (just) the toxic adulterants used by dance-floor pharmacologists or the botched syntheses of bathtub chemists. Deceptively, and in contrast to most other recreationally used drugs, ingesting pure MDMA can sometimes leave the user feeling better than normal the next day, albeit tired and slightly spaced-out. Beyond warm memories, this afterglow may in part be explained by MDMA's residual amphetamine metabolic by-products: MDMA itself has a long, c.8-9 hour elimination half-life from the blood; and its main metabolite's longer-acting, less stimulating (-)-MDA enantiomer has 5-HT2A activating effects resembling low-grade LSD. But two days or so after taking MDMA, most users experience the serotonin dip. The dip ranges from the almost imperceptible to the markedly unpleasant. The functional deficit the dip reflects may last ten days or more - in some cases possibly weeks or months. A biphasic post-E serotonin profile in the user has been reported: users' serotonin levels - though hard to measure and interpret - apparently fall 3-6 hours after taking the drug, then recover to nearly normal levels after around 24 hours, and then decline again.
Excessive MDMA intake triggers oxidative damage to the user's serotonergic nerve cell fine axon terminal lipids and proteins via the production of toxic free radicals. However, the threshold dose for any lasting MDMA-induced toxicity is unknown; and the identity and precise mechanism of the chemical(s) causing the oxidative stress is unclear. The issue is also controversial. Currently the three leading candidates for guilty agent are:
1] toxic metabolites of MDMA
2] toxic metabolites of dopamine
3] impaired cellular energetics
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