MDMA induces a release of extracellular glutamate in the hippocampus. Glutamate is the body's primary excitatory neurotransmitter. It binds to NMDA receptor sites, along with glycine, opening the ion channels and allowing calcium to enter the neuron. This is how the brain sends cascading electrical signals. When the ion channels open for too long or too frequently, calcium concentrations can become too high in the neuron. This can lower the effectiveness of your ion channels, or can even cause neuronal death. Magnesium is the substance your body uses to block the channel in a voltage-dependent manner. This means that the ion channel will not allow Ca2+ to pass, even if glutamate and glycine are bound to their receptor sites. However, once the neuronal membrane's electrical potential rises to an excited state, the Mg molecule will clear the channel and allow for normal operation. Most people are deficient in magnesium as it is. Supplementing a highly bioavailable magnesium supplement will give your body the substance it needs to naturally protect itself from excitotoxicity (this is when nerve cells are damaged or killed by excessive stimulation). There are a number of different types of magnesium supplements. Some are not absorbed very well. Others are. The most common form, oxide, is one of the worst. This is where the concept of chelation comes into play. Magnesium is a substance that readily binds to insoluble salts in the stomach and intestines, which makes it hard to absorb. However, if you chelate the magnesium molecule to a soluble amino acid, it prevents it's binding to insoluble salts, as well as opening up the possibilities for active transport. This means that fully chelated magnesium is absorbed much better by the body. Magnesium Glycinate is Mg chelated to a glycine molecule.
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Grape Seed Extract is a supplement high in vitamin E and flavonoids. Vitamin E deficiency has been shown to increase the severity of MDMA induced neurotoxicity. Also, flavonoids are potent antioxidants that will help protect against lipid oxidation and reactive oxygen species.
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Acetyl-L-carnitine synergises with Alpha Lipoic Acid and protects against oxidative stress. It has been shown to prevent MDMA induced neurotoxicity.
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5-HTP is the direct precursor to serotonin (5-HT). It is created from tryptophan in your diet using the enzyme tryptophan hydroxylase (TPH). MDMA can reduce TPH levels for weeks after use. This will make it harder for your body to produce the necessary 5-HT from normal dietary sources alone. Since 5-HTP does not need TPH, supplementing it the few days following your roll will help you body restore it's 5-HT levels. 5-HTP can pass your blood brain barrier, while 5-HT cannot. This means that when you supplement 5-HTP, you want to make sure it gets converted to 5-HT in your brain and not your periphery. The enzyme that converts 5-HTP to 5-HT is aromatic L-amino acid decarboxylase. It is found in your stomach and periphery, as well as your brain. This means that we have to inhibit it, so that your 5-HTP has time to pass your blood brain barrier. EGCG is an inhibitor of L-amino acid decarboxylase (Also known as DOPA decarboxylase). ALWAYS take EGCG with your 5-HTP to ensure that your brain is getting the serotonin, and not your periphery.
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When your NMDA receptors open and allow Ca2+ to influx into the neuron, that calcium must then be pumped back out of the neuron to bring it back down to resting potential. Protein pumps are what force the Ca2+ back into the extracellular space. To do this, they need andenosine triphosphate (ATP). CoQ10 is used by your body to synthesize ATP, which will allow your protein pumps to be able to expel the excess Ca2+ more efficiently. This will protect your neurons from excitotoxicity.