Issues with dosing for MDMA supplementation

Well to start off, my post over 3 years ago was meant to be a starting place for a discussion to help elucidate the best manner in which to protect oneself from MDMA-induced neurotoxicity. I never meant it to be considered gospel, or to be taken as clinically proven. I had hoped it would spur some intelligent discussion, and perhaps people would pick apart the individual components and hypotheses in it, and improve it. While some intelligent discussion has happened, and it certainly has spurred an interest in a lot of people on the dangers of MDMA, the picking apart of the specifics regarding it has not really happened; save for some recent skepticism. Hundreds of people have written me now having used the regimen, and even modified it a bit, with great effects. Anecdotally the regimen works to reduce the subjective adverse effects of MDMA use. However, no formal studies have been run to assess just how effective it is. I probably get 3-5 people PMing me a week since I wrote it. Many of them say it spurred an interest in pharmacology, and got them to realize that MDMA is not as safe as some people make it out to be. So in that respect, it has served its purpose well. Scientifically it still leaves a lot to be desired, and more questions that need to be answered.

Regarding your issue with the ALA dosing, we just don't have the comparable data between ALA and MDMA in rats and humans to make a conclusion. They gave rats 100mg/kg in those studies. However, they did not assess whether lower dosages would achieve the same protection. Then you have to scale between the species, which is not an exact science. They also gave MDMA at 20mg/kg IP. They were trying to assess whether or not ALA affected MDMA-induced neurotoxicity, not what the ideal dosage for that effect is. So it could very well be that 1/10 of the dosage has the same effect. Then you have to take into account the form of ALA used. AUC in humans after a 200mg and 600mg dose of racemic ALA was 46 and 157 mcg x min/ml. When you supplement in humans with Na-R-ALA, or the sodium salt of R-ALA, the AUC of a 600mg dose becomes 441mcg x min/ml. So the sodium salt of R-ALA is much more biovailable than either racemic or regular R-ALA. Also, S-ALA has been shown to competitively inhibit the binding of R-ALA, which makes judging dose/effect amounts harder to compare between the forms. We know the mechanism of ALA to protect against MDMA-induced neurotoxicity is there. The question then becomes: what dosage do we need in humans, and in what form? I always suggest Na-R-ALA for the improved bioavailability and pharmacodymics. The other question is: will taking Na-R-ALA during a roll hurt anything, even if we are not reaching the dosage level to absolutely protect from all 5-HT system damage? While the answer to that is not scientifically settled, I find it very unlikely that it would hurt anything.

On the same token, ALCAR was given to rats at 100mg/kg IP as well. We run into the same scaling issues we did with ALA. Again, they were not attempting to assess the ideal dosage to reach the protection, but rather trying to see if it did at all. Further studies would need to be done to assess what the lowest effective dose of ALCAR is in rats that gives the protection, the AUC achieved by those doses, then another study to assess what dosage in humans it would take to reach a similar AUC. The same question should be asked here that we did about ALA: will taking 500mg ALCAR with your roll hurt anything, even if the dosages are not high enough to reach the same effect at the aforementioned rat study? You can bring up the same questions, and make the same arguments, for the vitamin C issue as well. Using rat studies that are attempting to elucidate whether or not a compound affects MDMA-induced neurotoxicity, to determine an exact human dosage to reach the same effect, is not really a sound method. Studies never use small dosages of things to try and prove a statistically significant effect. Once you prove the effect exists, you need further studies to assess relative effects at differing dosages. Those have not happened, so all we have to go on is the fact that the mechanisms work in theory, and the anecdotes of people that have tried varying dosages. It's not an exact science, and should not be used as gospel. However, the main question really is: does taking reasonable dosages of Na-R-ALA, ALCAR, and Vitamin C cause more damage when taken with MDMA, than taking MDMA by itself? If not, and the anecdotes report favorable results with the combo, then there is merit in looking into it further.

So please, do not take my posts a few years ago to be settled science. It's far from it. This is a debate that needs many people involved, and more funding for studies, to really get the answers. While many people have used the regimen I posted with good effect, and many people have even used it as a reasoning to limit or stop their MDMA use, it should not be taken as the end all and be all of MDMA protection. Anyone that comes to me asking if the regimen can help them do MDMA more often, or in higher dosages, gets the same cautionary answer I give everyone. Do not use MDMA in high dosages, or in high frequencies, as the only reliable way to protect yourself long-term is to limit use and keep your body temperatures down. MDMA should be respected, and it's risks should be known. The fact of the matter is that many of the people who read my posts from years ago, are those that were under the impression that MDMA was safe, and they could take it all the time. Even if the science behind protection is not settled, sparking conversation in the populace who thinks MDMA is harmless, is a good thing. The key takaway is that MDMA can certainly be neurotoxic to humans when abused, and care should be taken when using it.