Kratom chemistry & pharmacology minithread

[Jabberwocky]

I wanted to start a thread focused on kratom's alkaloids, their pharmacology and methods to isolate/extract them. Kratom science.

If this belongs in OD let's move it, but I wanted to get technical here

 

[Jabberwocky]

gonna take some more kratom and give it a watch.

What do you think I'm doing :D

they get to the juicy technical stuff a little less than half way in

 

[Jabberwocky]

They seem to be talking about genetic variances in how kratom is metabolized, some people a lot slower than others, which would explain the variances in effects and withdrawal timelines

(I'm kinda half watching while getting ready for work)


"psuedoindoxyl-mytragynine" which is metabolized in the blood and not in the liver *?

 

[bingey]

The main difference between mitragynine and 7-hydroxymitragynine is potency. Research indicates that the pain-relieving potency of 7-HMG is 46 times higher than mitragynine and 13 times higher than morphine

While the alkaloid content of kratom can vary, mitragynine is far more prevalent in natural kratom in comparison to 7-HMG. Scientists analyzing an alkaloid extract from Thailand kratom leaves found that mitragynine made up 66% of the total alkaloids while 7-HMG accounted for only 2%. However, the 7-HMG alkaloid content was believed to be much more potent, even in such a lower concentration

 

[Jabberwocky]

The main difference between mitragynine and 7-hydroxymitragynine is potency. Research indicates that the pain-relieving potency of 7-HMG is 46 times higher than mitragynine and 13 times higher than morphine

While the alkaloid content of kratom can vary, mitragynine is far more prevalent in natural kratom in comparison to 7-HMG. Scientists analyzing an alkaloid extract from Thailand kratom leaves found that mitragynine made up 66% of the total alkaloids while 7-HMG accounted for only 2%. However, the 7-HMG alkaloid content was believed to be much more potent, even in such a lower concentration

Yeah, it's the other alkaloids and metabolites and the variances in how people metabolize them - the more mysterious side to kratom I'm researching

in this video they are saying that the full picture of kratom cannot be explained simply be researching mitragynine

 

[izo]

the adrenoceptor agonism is a bit icky, not good if i take more than five grams. i read in blacklight that a kratom a/b extraction was way more euphoric than the crushed leaves, dont know what to make out of it.

 

[JackARoe]

It is funny I do not get adrenic effects from kratom. And to me I think the stimulating part is just the normal stimualtion some of us get from any opiate. Poppy tea makes me superman as well as Mr. Nod.

I think the 7-hydroxymitragynine and mitragynine can really latch on to the receptors and prevent lighter opiates from working. But in a tolerance way, not antagonist like bupe. And in a lighter way that we do not understand yet.

I could never reconcile 7-hydroxymitragynine being 46 times higher tha morphine. Poppy tea will crush kratom for me, steam roll right over it. So if 7-hydroxymitragynine is 46 times stronger then it either must be in very small amounts. But that would mean someone would have already made a pure 7-hydroxymitragynine that technically should knock you out but that has not happened.

Good thread. I think we will learn more from personal experience than science right now.

 

[izo]

ive heard that the indole N of mytragynine makes a center like fentanyl s proprionyl anilide and that might be how it acts at the receptor, idk.

 

[Jabberwocky]

the adrenoceptor agonism is a bit icky, not good if i take more than five grams. i read in blacklight that a kratom a/b extraction was way more euphoric than the crushed leaves, dont know what to make out of it.

My understanding is there is no such thing as a simple a/b extraction Tek for kratom? I'm not that sure though

 

[izo]

it should work on the active principles..

 

[Jabberwocky]

it should work on the active principles..

I found this video to be good. I said it wasn't simple, not that it was impossible

 

[plumbus-nine]

Just learned that mitragynine indeed seems to be a D2 antagonist, among others. Unfortunately, cause I hoped to some day extract a more pure kratom. Interestingly it only feels like an antipsychotic in the presence of another dopaminergic, like memantine which is a D2 agonist, but when used as the sole drug, kratom doesn't share that nasty signature. Still, it feels somewhat 'locked-down' to me in terms of euphoria, but too I happen to be very sensitive to this sort of stuff.

@JackARoe: All these strains differ so widely that anything's possible. I've had a red vein strain which put me straight to nod when my tolerance was much higher than now, and from just one spoon of material. Was a sample pack, so quickly used up and re-ordered but got bunk stuff. This now is more like a cleaner coffee - usable on its own but barely touches withdrawal symptoms. The shit they sell in NL smartshops just eats a hole in your wallet but was next to inactive. We deal with more than 30 active alkaloids (though many of them probably in low to very low concentration)..

 

[bingey]

Just learned that mitragynine indeed seems to be a D2 antagonist, among others. Unfortunately, cause I hoped to some day extract a more pure kratom. Interestingly it only feels like an antipsychotic in the presence of another dopaminergic, like memantine which is a D2 agonist, but when used as the sole drug, kratom doesn't share that nasty signature. Still, it feels somewhat 'locked-down' to me in terms of euphoria, but too I happen to be very sensitive to this sort of stuff.

@JackARoe: All these strains differ so widely that anything's possible. I've had a red vein strain which put me straight to nod when my tolerance was much higher than now, and from just one spoon of material. Was a sample pack, so quickly used up and re-ordered but got bunk stuff. This now is more like a cleaner coffee - usable on its own but barely touches withdrawal symptoms. The shit they sell in NL smartshops just eats a hole in your wallet but was next to inactive. We deal with more than 30 active alkaloids (though many of them probably in low to very low concentration)..

Yah I get dysphoric from kratom I think it has something to do with being on aripiprazole.

And I can vouch for the Dutch smartshop thing, overpriced and basically bunk

 

[plumbus-nine]

Yah I get dysphoric from kratom I think it has something to do with being on aripiprazole.

Must have pretty strong affinity then, the mitragynine at D2, no?

Indeed I find at least this current strain here (Green Maeng Da, they sent me wrong, ordered red) to be dysphoric to the point of not using it for withdrawal.. it's got a stronger antidopaminergic signature than 10mg olanzapine! They could straight prescribe kratom to psychotics.

Needa acquire a decent dopamine agonist to combine. I know people say dopamine agonists aren't euphoric but they for sure work to some degree, it's just nothing like amphetamine at all.
Or try this extraction technique linked above but when mitragynine itself is to blame it won't have much success.

 

[sekio]

there was actually a recent study showing that mitragynine is probably a prodrug for 7-OH-mitragynine which is the actual active mediator of opioid effects. conversion is via the CYP3A4 enzyme. they gave mitragynine to mice and detected 7-OH in the brain and blood after.

the study actually shows that the brain mitragynine concentration does not correlate to analgesic activity, instead it is entirely the 7-OH that produces the opioid activity. giving an equianalgesic dose of mitragynine vs 7-OH turns out that the brain 7-OH concentrations are the same...

In the present report, we provide evidence that hepatic formation of 7-OH as a metabolite is important in mediating the analgesic activity (and presumably other MOR-mediated effects) of mitragynine, the major active alkaloid of the kratom plant. The analgesic effects of mitragynine and 7-OH each depended on activation of MORs. Further, the analgesia induced by mitragynine appears to depend largely on formation of 7-OH as a metabolite and not on the parent compound.

All these strains differ so widely that anything's possible

when I was back in the lab I looked at several different strains of kratom (even stems/twigs vs leaf) and to my surprise they all had very similar alkaloid profiles. there were some differences but in general there was mostly mitragynine (50-70% if I remember right) and maybe two or three others in significant amounts.

given that I have had people insist that two batches of a certain drug have different effect profiles, and then testing them and finding they are both the same compound and both quite pure... never discount the expectation effects. (similar with cannabis... people insist that there are differences between strains but GC could very well say they're all mostly THC...)

My understanding is there is no such thing as a simple a/b extraction Tek for kratom? I'm not that sure though

the malaysians figured one out. It's not even an acid/base extraction. Basically they first defat the leaves with petroleum ether (i.e. hexane/heptane) then extract with chloroform using a soxhlet extractor. that provides 70% pure mitragynine (they say about 7g crude product from 300g dry leaf) which is further purified by flash chromatography to 92-98% (with a decrease in yield to 0.8g).

I think because mitragynine is an ester it would not like the pH extremes in an acid/base extraction...

 

[negrogesic]

This is an interesting article that goes into the SAR of mitragynine and various analogs and most interestingly (to me) delves into the chemistry behind the MOR/KOR/DOR selectivity of the compounds.

Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2 - PMC

Natural products found in Mitragyna speciosa, commonly known as kratom, represent diverse scaffolds (indole, indolenine, and spiro pseudoindoxyl) with opioid activity, providing opportunities to better understand opioid pharmacology. Herein, we ...

www.ncbi.nlm.nih.gov

It does seem to appear that mitragynine is active in its own right, being over 10x more selective for the MOR over KOR (compared to 7-hydroxymitragynine). Of course being a much more potent opioid, mitragynine's metabolism to 7-hydroxymitragynine has profound implications.

 

[negrogesic]

Here are those analogs and their associated affinity/selectivity:

 

[AutoTripper]

Now, just on my 30 day experience with Kratom 2 years ago, resulting in addiction a sped WD for over 4 days due to a forced, health and allergy related reason.

But, I have been dependant on raw crushed organic garlic with maximum Allison formation, crushed and sat for 10 minutes.

Decades ago, I noticed how if I took ketamine after dinner with red garlic, the tiniest lines could K hole me.

I swear, with any form of cannabis too, proper active, I.e. allicin high, is honestly the most powerful food based very broad range Psychoactive substance potentiator I have ever experienced.

Taken alongside cracked them for example and also my afternoon cannabis sessions but then I would notice virtually a Doubling of the effect of the Kratom. and cannabis with the garlic.

 

[izo]

i was on kratom and o-dmt and a little bit of poppy tea for about 3 month daily once, stopped cold, no withdrawal at all.

 

[sekio]

But, I have been dependant on raw crushed organic garlic

what are garlic withdrawals like?