I have no personal experience with this disorder but I believe G6PD deficiency could cause problems with the metabolism of many drugs, including MDMA.
Glucose-6-phosphate-dehydrogenase is an enzyme serving several roles. G6P can be metabolized either by the glycolysis pathway via phosphofructokinase-1, or by the enzyme G6PD via the pentose phosphate pathway. Both PFK-1 and G6PD are regulatory enzymes. Different endogenous processes affect these pathways, and the products of both enzymes are needed in other bio-pathways.
The G6PD regulated pentose-phosphate pathway produces an important endogenous chemical, NADPH. This is the reduced form of nicotinamide adenine dineucleotide phosphate, termed the “energy carrier” as it provides energy for many rate limiting reactions. In this role NADPH is involved in the biosynthesis of fatty acids and steroids, and is found in adipose (fat) tissue.
Organs where NADPH is particularly active include the mammary gland, adrenal cortex and the liver. It is the role in the liver that strikes most concern with drug use. Cytochromes are mixed function oxidases involved in the metabolism of many drugs, poisons and even bio products from natural pathways.
When cytochromes are involved in metabolism, they co-depend upon either flavin (e.g. FMNH2) nucleotides or as in the case of P450, with NADPH as the co-substrate.
P450 is a cytochromes involved in the metabolism of MDMA and many other recreational drugs. Several cytochromes can be involved with a single substance, but there is usually a preference for one. Preference to a particular cytochromes/ co-enzyme/ cosubstrate combination e.g. P450/ P450 reductase/ NADPH with MDMA metabolism, is dependant upon availability of all components. Another, perhaps more toxic pathway may be chosen if first choice cytochromes and cofactors are otherwise employed or low in number due to deficiency.
RH (drug) + P450 [Fe-S] reductase (oxidised ) + P450 (reduced) + NADPH + O2 =
ROH (drug metabolite) + P450 reductase (reduced) + P450 (oxidised ) + NADP+ + H2O
With a low availability of NADPH, it may be possible that the drug could cause serious toxic reactions. Please proceed very carefully and speak to a hepatologist or specialist in the area of this disorder before taking any new drug.
