How All Kratom Works: A Revised Theory of One Alkaloid

[Love_Redz]

I do feel it is dose dependent for me for sure but I also feel that some of the other alkaloids help with some effects some how just not that noticeable

[pray4peace4]

I'd be interested to know if you just found this only in the McCurdy. It is an interesting theory and you very well may be onto something.

However, mitragynine pseudoindoxyl effective concentration is nearly equivalent to 100 fold to mitragynine in many respects, 7ohm is only 10 fold. In other words, at 0.01% mitragynine pseudoindoxyl is getting the equivalent to 1% mitragynine for ease of explanation. In saying, at even a tiny dose, this could make a huge difference in the effects. Not to mention that the rate at which the body metabolizes mitragynine into mitragynine pseudoindoxyl and 7ohm compounding this. In this case, I would agree that there is a sweet spot, in that everyone's metabolism is very different and highly dependent on a number of variables. But overall, I don't think this theory would hold with more research into mitragynine pseudoindoxyl and the liver. The McCurdy study did not go into this this variable at all, so I would not be able to say it is mitragynine alone.

Here's the science:
https://doi.org/10.1016/S0306-3623(98)00265-1
https://chemrxiv.org/articles/preprint/ ... e=14304335

To my knowledge, there's only one lab in the US that test consistently the concentration of mitragynine pseudoindoxyl to those low of levels to be viable to make claims/research, but at this time it is perhaps cost prohibitive to conduct further research on it.

My theory would be that mitragynine pseudoindoxyl, combined with the rate at which the body produces the two more powerful metabolites is what is more important than the mitragynine. Because mitragynine and the other alkaloids are metabolized in the liver through drug oxidation, reduction and hydrolysis, concentrations change entirely with how the liver prioritizes each. I think it's less a matter of which have the priority on the receptors (if the mitragynine is converted before it gets to the receptors, then it won't have prioritization). Though the effect of mitragynine on receptors is prioritized over 7ohm, what is the priority with mitragynine pseudoindoxy? I don't think I've seen a study on it. Additionally, If the liver processes the 7ohm and/or mitragynine pseudoindoxyl first, then there would be less of the concentration of mitragynine, as some would pass renal over time. If the mitrgynine is metabolized first, then the already available 7ohm and/or mitragynine pseudoindoxyl would create most the initial elation, allowing for aging (breaking away from receptors for the higher affinity) and a slower decline. I suspect this is the case, as a lot of folks talk about "legs" of a burn and would explain the wobbles better to me, as the 7ohm and mitragynine pseudoindoxyl hit, you feel great, and as the mitragynine finally makes contact your brain is perhaps overwhelmed as the offensive players tag in with the defensive (I'd agree that the mitragynine likely causes wobbles). Anecdotally, abusers that transition from opioids to suboxone or suboxone to kratom often describe a similar feeling to wobbles.

So while I agree with portions of this theory, I think a larger portion will be revealed with more research into liver processing kratom and the effects and role of mitragynine pseudoindoxyl.

Most the liver stuff I hit on here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425236/

I'm not sure if you are quoting the same study I just found:
https://pubs.acs.org/doi/pdf/10.1021/acsptsci.0c00075

but if you read through the abstract, McCurdy was part of this research, finding that 7-hydroxymitragynine is converted by human plasma into mitragynine pseudoindoxyl, which is far more of a mu receptor agonist than mitragynine or 7-ohm. So the liver converts mitragynine to 7-ohm & the plasma converts the 7-ohm to mitragynine pseudoindoxyl. Humans are the only mammals that this process occurs in. It wouldn't surprise me that this process would vary between individuals & vary according to dose, especially since kratom lingers in the bloodstream, there could be a limit of how much the plasma can convert before it exhausts whatever chemicals it uses for the conversion.

[Markw760]

Man I love MM. Y'all definitely delve deeper than any other platforms with seemingly far greater knowledge than I've seen anywhere else. School is in session..Greatly appreciated.

[GrannyJ62]

Just one more bump

[GrannyJ62]

There's just so much good information in this thread I had to come and read it again.
Thank you 7OHM for starting it here in a place I can come back and re read retention has never been one of my strong points.

[Arob1000]

Did you guys read this article?

https://www.nature.com/articles/s41598-020-76119-w

Interesting unbiased metabolomics analysis of kratom, the main difference they found was speciofoline which seemed higher in whites/might lead to a lot of the stim effects. I asked the researcher for the processed data to look into more detail and to see if any trends were missed but was ignored unfortunately. I could go through the raw data if I wanted but don't have the time right now.

An unbiased analysis is key for understanding this sort of complex dataset with so many alkaloid measurements. It was cool to see this well thought out study in the literature. Pretty sure all of their samples were bulk kratom but still an interesting study.

[Lokey]

So is chocolate now an opioid?

I don't know but lately I've been eating a lot of Tony chocolonely sea salt and caramel. Maybe it's the kratom. And I still have a hard time believing anyone died from kratom despite that one test there's something they're missing in my opinion either an unknown medical condition or an unknown substance that wasn't tested for. The rest of this information is going to take a while to absorb and understand if I ever actually can do it. Very interesting for sure.

[Sanbutsushin]

So is chocolate now an opioid?

I don't know but lately I've been eating a lot of Tony chocolonely sea salt and caramel. Maybe it's the kratom. And I still have a hard time believing anyone died from kratom despite that one test there's something they're missing in my opinion either an unknown medical condition or an unknown substance that wasn't tested for. The rest of this information is going to take a while to absorb and understand if I ever actually can do it. Very interesting for sure.

Could be that a medication interaction happened, too. A lot of supplements - dare I say most of them - aren't tested or studied in relation to meds, so who knows! Yet another area where we could do with more information.

(and... now I'm craving salted caramel...)

[Lokey]

So is chocolate now an opioid?

I don't know but lately I've been eating a lot of Tony chocolonely sea salt and caramel. Maybe it's the kratom. And I still have a hard time believing anyone died from kratom despite that one test there's something they're missing in my opinion either an unknown medical condition or an unknown substance that wasn't tested for. The rest of this information is going to take a while to absorb and understand if I ever actually can do it. Very interesting for sure.

Could be that a medication interaction happened, too. A lot of supplements - dare I say most of them - aren't tested or studied in relation to meds, so who knows! Yet another area where we could do with more information.

(and... now I'm craving salted caramel...)

It's so good, more like bits of toffee with big chunks of sea salt in fair-trade Belgium chocolate. I don't take a lot of supplements but I do take a couple meds besides kratom but I do think it gave me a sweet tooth.

[K-fox]

I do feel it is dose dependent for me for sure but I also feel that some of the other alkaloids help with some effects some how just not that noticeable

Same here. I also think that mitragynine produces some opioid effects on it’s own as well.

[K-fox]

I don’t know about framing reds as an inferior product because they contain less alkaloids. That’s like saying food that has less spices has inferior taste. It’s all about quality and the subjective experience. As the saying goes...the whole is greater than the sum of its parts.