Comment · Thu, April 25, 2013
MDMA: The 'Dont Re-dose' advice?
Original post in this thread
KosherDev · 25 points
So this came up in another thread and people suggested I make my way over here for a more specific answer.
We've all heard the general advice of not re-dosing on mdma to minimize any potential harmful after effects. It makes sense but is it the act of just 'taking more' that could cause issues, or is it the actual time separation?
So the example. You take an initial 120mg dose, and then a subsequent 60mg dose an hour or so later for a grand total of 180mg.
Vs.
One initial dose of 180mg.
Are they equally 'bad' or does the subsequent dosage cause more complications than one large initial dose? If so, why?
What they were answering
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb
It all has to do with the non-linear pharmacodynamics of MDMA metabolism. The predominant theory of nonlinear pharmacokinetics of MDMA and HMMA is mechanism-based inactivation of CYP2D6 by MDMA. This means that initial doses inhibit the primary metabolic pathway, CYP2D6, and cause a greater amount to be metabolized by the secondary pathway, CYP3A4.
The thing is, large doses do the same thing, just over a different time scale. The reason for the time scale difference is body temperature. When body temperature rises, the metabolic characteristics change. The higher your body temperature gets, the more toxic metabolites get created. Since your body temperature starts rising after the first dose, and that first dose has already inhibited your CYP2D6 enzyme, the subsequent dose is going to lead to more metabolism by CYP3A4 than a singe high dose would. Then once the inhibition from the first dose wears off, the O-demethylation will continue. However, now we are O-demethylating more MDA than we normally would have with a single dose. Since MDA's metabolites are much more neurotoxic than MDMA's direct metabolites, this leads to higher 5-HT system damage.
The best way to combat this is to inhibit your CYP3A4 enzyme throughout your roll, then increase your urinary acidity enough to pee out the unmetabolized MDMA before the initial CYP2D6 inhibition wears off. I have even thought that adding a CYP2D6 inhibitor late in the roll might help as well. The goal is to get the MDMA out of your system as fast as possible, with as little metabolism as possible.
Re-dosing can be done safely, and I do most times I roll. However, I never re-dose after 1.5hrs after the first drop, and never more than half the initial dose. Also, I always inhibit my CYP3A4 enzyme, and start increasing my urinary acidity after I re-dose. It usually leads to me having to pee many times before the morning, but it works.