Comment · Wed, January 15, 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
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##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
I very much appreciate your detailed explanations! If you wouldn't mind I'd like to ask a few more questions regarding the details behind the neurotoxic risk involved with taking MDMA.
As far as I know there are roughly three important systems at work:
* In the intestines and liver, MDMA is broken down by CYP3A4 into MDA and CYP2D6 then creates the neurotoxic metabolite HHA. This then gets taken up into the blood stream and does its damage in our brain? Do you know where exactly and how? If HHA is formed inside the liver, I would assume it will be transported out to your bladder, does this mean that the neurotoxic effects of HHA in the liver are small/nonexistent? Also, you mentioned that the first dose of MDMA inhibits the primary metabolic pathway, CYP2D6, so why then is HHA still a problem if this metabolite is also created by the CYP2D6 enzyme? I guess this has to do with the ring-hydroxylation, which occurs even with enzyme inhibition so this must happen via some other pathway?
* When MDMA enters the axon via the uptake transporters it causes the release of serotonin and dopamine into the synapse. After a while the uptake transporters remove the serotonin from the synapse bit by bit. The serotonin is broken down by monoamine oxidase or some of it may return to the vesicles. This process continues until the synapse is depleted of most of the serotonin. The dopamine, howe…
u/MisterYouAreSoDumb
HHA itself is not toxic. It has to conjugate with gluthatione before it can pass the blood brain barrier and cause oxidative damage to your neurons. So it's kind of ironic that your body's natural defense system is needed to actually create the very thing that damages it. HHM is also toxic, but is limited to the periphery. It is most definitely hepatotoxic, so vitamin C is a must to protect your liver. Then you also have the ring-hydroxylated metabolites THA and THM. Those damage you body's enzymes that create catecholamines; namely tryptophan hydroxylase. This is why your serotonin levels fall in the days following MDMA use. The actual roll only lowers stores 10-20%. It's the disruption of the enzymes that leads to lack of serotonin a few days later.
The dopamine issue is definitely a factor. However, it is not the primary factor. Your body's natural antioxidant systems can handle the excess hydrogen peroxide created when MAO-A breaks down dopamine in the neuron. However, when your body's antioxidant systems are already depleted and taxed from the toxic metabolites, dopamine just presents extra ROS that need to be scavenged. Late in a roll with no supplementation, it can and does get overwhelmed.
Excitotoxicicity happens when excess calcium enters a neuron either through the AMPA or NMDA receptor channels. This is caused by excess glutamate, causing the channels to open too often, or for too long. Magnesium is your body's natural blockage of the NMDA channels. Since most people are deficient in magnesium as it is, that system is easily overwhelmed when glutamate levels rise. This is why a good magnesium supplement is a must, and why supplements like memantine are also a good idea when taking stimulants.
So you have the general premise down. We want to slow the metabolism of MDMA into its toxic metabolites by inhibiting the liver enzymes that O-demethylate and N-demethylate the molecule. Then we also want to supply the body with the necessary central and peripheral antioxidants to help with the ROS that do get created; whether that be from toxic metabolites conjugated with gluthathione, or from dopamine uptaked into the neurons. Then we also want to provide the body the things it needs to prevent excess calcium influx into the neuron, and to provide the protein pumps the energy they need to pump the excess back out again.