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Comment · Tue, January 14, 2014

Another MDMA re-dose/redose question [first and second time MDMA experience inside]

Original post in this thread

YouKnowNothingJohn · 8 points

Although having read plenty of information on reddit and MDMA forums/sites, I still have a couple of questions regarding the dosing and specifically re-dosing of MDMA. I am familiar with the reasons behind the advise to only re-dose once shortly into your roll. Let me first give you some background.

Warning, long post, skip to bottom if not interested

*****
##Background

Our group uses MDMA at home and on festivals, the usage is quite low since we strictly keep three or more months between each use. No crazy amounts of MDMA are taken either. Living in the country we live in, we fortunately have access to high quality xtc pills and government testing facilities. At the moment we have some 100% clean pills with 205mg of pure MDMA inside.

For me personally I have used MDMA two times, both at festivals, and we will do a home session within one month's time. The last time we used I had already purchased some vitamin C and magnesium supplements to try to make the roll a bit safer.

Everyone in the group was into the idea of doing MDMA as safe as we could. I started reading a lot on how MDMA works and made my own supplement list based on different sources but mainly posts by Miste…

What they were answering

YouKnowNothingJohn · 1 points

Makes sense. I think for the next home session we will make a quick planning how much to take at what times. Also making sure that we don't eat a fatty dinner and have too much acid drinks.

Then we have a baseline for our group and can adjust from there. Maybe we can find a right dose after all without spacing the dosages too much (no pun intended).

If I am correct, the way the MDMA is delayed should have no effect on the increased neurotoxicity right? Be it absorption issues, spread dosage or a timed release, in every case the primary metabolic pathway will be inhibited by the first MDMA dose. So whatever caused the spread in MDMA dosage, the effect will be the same: more MDA metabolites?

Drinking grapefruit juice and taking grape seed extract will inhibit the CYP3A4 enzyme reducing the formed MDA metabolites. This should help protect against later re-dosing but this is of course dependent on the success of inhibition, which you cannot be sure off.

Would you go so far to agree with me that considering the supplements suggested in the OP and our spread rolls, a possible second re-dose should be okay? Of course I will try to use the baseline we set next time we roll and the advice given here to figure out if we can use a single re-dose.

u/MisterYouAreSoDumb

If I am correct, the way the MDMA is delayed should have no effect on the increased neurotoxicity right?

Well that is complicated, since MDMA's pharmacodynamics are complex. If the Cmax is lower, but the AUC is the same, then some aspects of the neurotoxicity will be lower. Namely that would be the excitotoxic risks, as the lower peak plasma levels would lead to lower extracellular glutamate levels. However, the reactive oxygen damage is more complex. The longer MDMA is in your system, the more likely your body is going to O-demethylate and N-demthylate it into the various toxic metabolites. Then there is ring-hydroxylation, which will happen regardless of how much you inhibit your liver enzymes. That is why re-dosing is so bad. It extends the time your body has to create the toxic metabolites, and extends the time you body has to deal with the oxidative substances.

That being said, Na-R-ALA is a very good antioxidant. Pair it with CoQ10, vitamin C and E, EGCG, and resveratrol, and it can handle a lot of reactive oxygen species. Then take into account the CYP3A4 inhibition, which is already lowering the amount of toxic metabolites they will have to deal with, and you should be pretty good. I am never going to say that multiple re-dosings are safe. However, my supplementation regimen will give your body the best defense against the risk.

There is also the possibility of inhibiting CYP2D6 as well, to even further limit the toxic metabolites being created. However, you would have to be careful with dosages, as that will most definitely lead to higher serum levels.

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