This is the big question on my mind lately, and I'm curious to hear people's thoughts.
The question is based on the assumption that one would want to maximize the positive effects and duration of the leaf, aka "potentiation". I've been doing a lot of forum digging and reading lately on this, as a long time daily user it's always of interest. Onward...

I've read that mitragynine and 7-OH are the major active alkaloids believed to be responsible for most of the leaf's effects. They are not often referred to as prodrugs that need to be metabolized into actives, but rather are active themselves. CYP Enzymes metabolize and eliminate the alkaloids from the body. In that case you'd think to inhibit the enzymes to keep the alkaloids active longer. A lot of potentiation threads deal with this, things like Valerian and GJF, cimetidine, etc. to inhibit CYP enzymes and slow metabolism and breakdown of alkaloids into inactives.

However, I've read this study recently that concludes that mitragynine is processed into 7-OH in vitro and in vivo via enzyme CYP3A4 and that 7-OH is mostly responsible for the analgesic effects. Study Here Highly recommended read as it is very recent and addresses a lot of previous studies as well as the topic in question.
They found that mitragynine itself had very little affinity for MOR (mu receptors) and that 7-HOM was an in vivo metabolite of mitragynine via CYP3A4 and caused analgesia through MOR activity. (Also touches on how safe m. speciosa is with regards to respiratory depression among other interesting info)

If that's the case, which it seems to be based on that fairly conclusive study, one would want to induce CYP3A4Wiki and maximize it's efficiency. There's a nice categorized list of inducers and inhibitors on that wiki page.


submitted by /u/cirespieler
[link] [comments]