Comment · Thu, December 27, 2012
How long prior to MDMA should you take your pre-load? (multivitamins, magnesium and antioxidants)
Original post in this thread
[deleted] · 18 points
I have several vitamins, antioxidants and magnesiun supplements but I wonder when I should take them. 1h prior? 30mins prior?
What they were answering
yayblah · -1 points
Where are you getting that 10% of MDMA -> MDA via CYP3A4?
And also - how is MDA neurotoxic? I am curious because I have taken it before, or at least it was advertised as such. Only was able to test with Marquis
u/MisterYouAreSoDumb
Metabolism of MDMA to MDA in humans is anywhere from 5% to 18%, depending on dosage, re-dosing schedule, body temperature, and a couple other factors.
Rats metabolize much more to MDA, due to their CYP2D1 (Their CYP3A4 equivalent), being the primary metabolic pathway. Our primary pathway is CYP2D6, with CYP3A4 being secondary. I have a bunch of studies on the matter on my computer.
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And yes, MDA is much more neurotoxic to 5-HT neurons.
MDMA (5 mg kg-1, i.p.) was without effect on brain 5-HT content. A single dose of MDA (5 mg kg-1, i.p.) produced a major (approximately 40%) loss of 5-HT content of cortex and hippocampus 7 days later.
So a 5mg/kg dosage of MDMA showed no loss in 5-HT in the brain after 7 days. The same dose of MDA showed a 40% loss! It is significantly more neurotoxic.
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Also from another study:
>Indeed,
5-(N-acetylcystein-S-yl)-R-MeDA is more than 2 orders
of magnitude more potent than 5-(glutathion-S-yl)-RMeDA
(14, 15). Intrastriatal administration of 5-(Nacetylcystein-
S-yl)-R-MeDA, **at a dose as low as 7 nmol,
produces a 50% reduction in striatal 5-HT concentrations**,
approximately equivalent to the effects of 23.25 ímol
MDA (93 ímol/kg s.c. in rats weighing 250 g).
5-(Nacetylcystein- S-yl)-R-MeDA is referring to a conjugate of HHA or alpha-methyldopamine. Remember from my post what creates HHA? Metabolism of MDA. If it were the direct metabolite of MDMA, it would be HHMA, not HHA. So a known product of MDA metabolism, at a very low concentration equivalent to .03% of the MDA dose, caused a 50% decrease in 5-HT. See where my theory makes sense?
Keep in mind that the doses I quoted are in rats. The equivalent human dose to the first study I linked is .8mg/kg. That would only be a 65mg dose for me. These are not high doses we are talking about here. MDA is very neurotoxic to 5-HT neurons.