A Kratom science breakthrough has just occurred. A peer reviewed scientific study titled ‘Metabolism of a kratom alkaloid metabolite in human plasma increases its opioid potency and efficacy‘ was published just a few days ago, and it found that a chemical reaction occurs in human blood which causes Kratom’s effects to become much more powerful.
Specifically, the Kratom alkaloid 7-hydroxymitragynine, which was previously believed to be the strongest natural Kratom alkaloid, is converted into Mitragynine Pseudoindoxyl in human blood. Mitragynine Pseudoindoxyl has a much higher binding affinity than 7-hydroxymitragynine for the mu-opioid receptors, making Mitragynine Pseudoindoxyl a much more potent opioid analgesic than even 7-hydroxymitragynine.
Essentially, opioid binding affinity is measured by a molecule’s dissociation constant at the receptor, and a lower dissociation constant equals higher binding affinity. Mitragynine has a dissociation constant of 230 at the mu-opioid receptor, 7-hydroxymitragynine has a dissociation constant of 37, and Mitragynine Psuedoindoxyl has a dissociation constant of just 0.8.
This means Mitragynine Pseudoindoxyl has by far the highest opioid binding affinity among the primary Kratom alkaloids. A previous scientific study has already confirmed that Mitragynine Pseudoindoxyl, as well as 7-hydroxymitragynine, has much more opioid analgesic efficacy than even Morphine.
Based on this data, the scientists who wrote this new study conclude that a significant amount of Kratom’s effects are due to Mitragynine Pseudoindoxyl.
Notably, the reason this wasn’t known until now is almost all previous studies conducted animal experiments, and it seems only human blood causes the conversion of 7-hydroxymitragynine into Mitragynine Pseudoindoxyl.
Zooming out, a previous study found that most of Kratom’s effects are due to the liver metabolizing Mitragynine into 7-hydroxymitragynine. Basically, the opioid effects of Mitragynine itself are weak, and the metabolization of Mitragynine into 7-hydroxymitragynine is what truly produces Kratom’s opioid effects.
With this new study this theory can now be taken a step further. Mitragynine is first metabolized into 7-hydroxymitragynine in the liver, and then in the blood the 7-hydroxymitragynine is converted into Mitragynine Pseudoindoxyl, and both of these transitions play a critical role in Kratom’s opioid effects.
Overall, this new data gives a much clearer idea of how Kratom works, and what causes Kratom’s effects. More than anything, it is incredibly interesting that Kratom’s effects are mostly produced due to the way the body breaks down and interacts with Mitragynine, and that Kratom wouldn’t be nowhere near as strong or as effective if it wasn’t for the chemistry which occurs within the body.