Tryp, you know I love your posts, and find you to be one of the most learned members of the forum about a variety of subjects, but especially nutrition. I have to ask you again about 5htp.
My understanding is that after MDMA use, the enzyme TDH is destroyed and takes about a couple of weeks to be restored. During that time, some users (and this has been confirmed by animal and human studies) will have low levels or extremely low levels of serotonin. The only way to restore levels without TDH is to use 5htp, with ECGC to prevent peripheral conversion, again not for long term use, but for the short term as Krazy proposes. I love your niacimide recommondation, but it won't result in restored serotonin levels without TDH. Am I on the right track?
Please correct me where I am misunderstanding.
--Kooch
MDMA research usually consists of supraphysioloical dosages of MDMA given to environmentally deprived and functionally malnourished rats or mice, accompanied by transparent assertions by the authors that the supposed findings are somehow equivalent to human dosages a tiny fraction of their size under vastly different conditions. Far more often than not the inter-species comparisons give no meaningful data relevant to human use of the drug, and as a result people tend to assume the worst (or else ignore the risks entirely).
I consider the depression of tyrosine hydroxylase activity (which is a reversible inhibition, not a destruction, and occurs in rats but not mice) and more generally the sustained decrease in serotonergic tone produced by MDMA, to be one of its the lasting beneficial effects. It would be very interesting to test whether the long-term therapeutic benefits of MDMA (ie, in PTSD sufferers) correspond (or can be influenced by) changes in serotonergic activity. in brief, the function of serotonin is to restrict our range of behaviors, in the same way that it constricts the smooth muscle in our blood vessels or our gut, or lowers the energy levels of an animal preparing for hibernation. Blood or brain serotonin found to be elevated in many disease conditions, and in laboratory animals predicts the development of 'learned helplessness'. MDMA (and to varying extents other indole or indolizable psychedelics) can help loosen the 'grip' of serotonin on our behavior, worldview, and blood vessels.
Flunarizine blocks the decrease in tryptophan hydroxylase activity induced by 3, methylenedioxymethamphetamine
Quote
Coadministration of FLU with METH further reduced tryptophan hydroxylase activity to 40~ of control; cotreatment of FLU with MDMA provided significant protection from the MDMA-induced decrease in tryptophan hydroxylase activity as enzyme activity was lowered to only 78~; of control. The administration of FLU alone did not alter tryptophan hydroxylase activity.
--
This study indicated that the inhibition of tyrosine hydroxylase was due to excess calcium influx, as most of it could be preveted by a 'calcium channel blocker'. Sufficient vitamin K and magesium intake should have a similar effect (although of course no one will publish a study on that).
MDMA can be used safely - if you have a largely raw fruit diet and sufficient supplementation, limit your doses, and avoid becoming dependent on it. In humans by far the major risk of MDMA use is hypothermia, resulting from an overheated environment, alcohol use, lack or excess of water, and the indiscriminate consumption of excessive dosages.
EGCG is fine, but your body absolutely does not need 5-HTP. Supplementing 5-HTP itself inhibits tryptophan hydroxylase, 'shunting' the tryptophan towards niacin synthesis. Niacin synthesis passes through several potentially neurotoxic kynurenine intermediates, whose toxicity is exacerbated by, among other things, vitamin deficiency. Only about 5% of tryptophan ultimately becomes serotonin. Therefore if, as I assert, the benefits of tryptophan supplementation are due increased niacin synthesis, niacin or niacinamide should be taken to avoid subjecting yourself to higher levels of the kynurenines.
The tryptophan requirement of the rat as affected by niacin and level of dietary nitrogen
Quote
Niacin had a marked tryptophan-sparing effect. With adequate niacin in the diet, the tryptophan required for normal growth at dietary protein levels of 9, 10, or 10.8% of protein were respectively 0.10, 0.12, and 0.13% of the diet. When niacin was omitted from the diet, the tryptophan required for normal growth at a 10.8% level of dietary protein increased to 0.19% of the diet.
When the level of dietary protein was increased to 19–20% by the addition of gelatin or casein hydrolyzate, the tryptophan requirement was increased to 0.17% of the diet in the presence of adequate niacin. Without supplementary niacin and with casein used as the source of tryptophan, the tryptophan requirement for normal growth was 0.30% of the diet.
On a related note - the supposed dietary 'essentiality' of tryptophan, is due in large part to its role as a precursor for niacin. The 'protein-calorie malnutrition' which is maintained in 'underdeveloped' countries by widespread consumption of rice and other nutrient-poor 'staples', is largely (perhaps primarily) a niacin deficiency, which is dishonestly portrayed as a tryptophan deficiency in order to promote the consumption of 'tryptophan-rich foods' such as muscle meat and most types of seeds.
