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TOPIC: Kratom less is more theory(ceiling effect)

Kratom less is more theory(ceiling effect) 6 months 1 week ago #24342

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Hello all I have been looking at kratom's indoles and oxindoles within kratom and have realized that there is a sweet spot with kratom dosage. Of course this depends on a Persons tolerance, chemical makeup of ones body, Strain, location the kratom is grown and alkaloidal profiles of the specific leaf color and strain.

The main indoles of kratom are Mitragynine, speciogynine and 7-hydroxymitragynine(7-OH-MG). There is a certain point where an antagonist to the mu and primarily delta sites counteracts mitragynine's occupation of receptor sites.
antagonist to mu and delta would counteract the main indoles within kratom possibly causing negative side effects but only when taking to much. It would also block most of the mu and delta agonists like mitragynine from attaching to receptor sites. In other words taking to much kratom builds up to much corynantheidine and thus creates a ceiling effect where the main alkoloids within kratom are counteracted causing effects to possibly half or subside if enough is taken.

corynantheidine compared to all other alkoloids within kratom is less than 1% of all alkoloids. needless to say it does not have a large presence within kratom doses.

some believe corynantheidine the antagonist to delta and mu regions has a weak grip on those receptor sites, especially to the a1-agrenergic regions. It is my belief that it would not matter because mitragynine and other main alkoloids have a very low affinity to mu, delta and kappa regions.
It is also my belief that if we could remove corynantheidine from kratom it could be possible to eliminate the ceiling effects associated with kratom.

Pseudoindoxyls like corynantheidine primarily partial agonism to mu with strong antagonism to delta regions.

Ive also herd theroys of one gaining a dependency to corynantheidine only then later having a tolerance to it later on removing the ceiling effect. I believe removing corynantheidine from kratom would be more beneficial than gaining a tolerance to.

Science that supports my theroy:

pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00748

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 report the pharmacology and SAR studies both in vitro and in vivo of mitragynine pseudoindoxyl (3), an oxidative rearrangement product of the corynanthe alkaloid mitragynine. 3 and its corresponding corynantheidine analogs show promise as potent analgesics with a mechanism of action that includes mu opioid receptor agonism/delta opioid receptor antagonism. In vitro, 3 and its analogs were potent agonists in [35S]GTPγS assays at the mu opioid receptor but failed to recruit β-arrestin-2, which is associated with opioid side effects. Additionally, 3 developed analgesic tolerance more slowly than morphine, showed limited physical dependence, respiratory depression, constipation, and displayed no reward or aversion in CPP/CPA assays, suggesting that analogs might represent a promising new generation of novel pain relievers.


possible ways to extract corynantheidine:
alcohol has a large hydroxyl chain which pulls many alkoloids. most extractions are water, acidic acid and ethenol based with some being done with chloro.

what is everyones take on this, does anyone know what could possibly isolate corynantheidine(mu-delta antagonist) and fully remove it from kratom leaf, extracts, tincures and full spectrum extracts?

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"Kratom is a safe and does not cause respitory depression. Kratom is a mildly addicting substance, comparable to Caffeine, it is my belief that Kratom does NOT fit within the CSA scheduled list I-V."
- DR. Henningfeild (kratom expert) Organic Chemist and scientist.
Last edit: by Chemist4hire.

Kratom less is more theory(ceiling effect) 6 months 1 week ago #24346

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I think you might as well be speaking another language I have no idea what half those terms even mean. Great question for a more scientific audience forum IMO.
Is there a sweet spot for dosage dependent on certain factors? Yeah. That's pretty obvious. I'm not sure what's being asked beyond that.
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Kratom less is more theory(ceiling effect) 6 months 1 week ago #24353

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The less is more theory has always been a mystery to me.

Less of something does not produce more of the effects you want. Conversely MORE of something can get you into trouble with toxicity. Hence our reference to the individual "sweet spot".

The ONLY way less can be more beneficial is IF the alkaloids that you need are in lesser quantity than the main ones (mitragynine and 7-hydroxymitragynine). Taking less MAY give these alkaloids a chance to shine without being overpowered by the main ones.

Great question for a more scientific audience forum IMO.


Well the original post from chemist4hire reads more like a crude cut and paste from a translation. I am now suspect of the veracity and intent of all his/her posts.

Moderator needs to take note.
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Last edit: by bomalley.

Kratom less is more theory(ceiling effect) 6 months 1 week ago #24362

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I actually like the fact that you can’t over do it on dosing. What I mean is, if you take too much you won’t feel good, there for there is like a built in safety mechanism that tells you not to take that much. If you over do you will get dizzy or maybe want to vomit, so it’s kind of a good thing. That way people won’t feel the need to take more and more and more higher doses because you can’t, because you won’t feel good. So trying to eliminate one certain thing, so you can take higher doses, I don’t think is such a great idea from my stand point. Kratom is actually perfect the way it is. I don’t even like taking extracts personally, I just like plain old Kratom the way it is, it’s a wonderful tree, and needs no improving.
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Kratom less is more theory(ceiling effect) 6 months 1 week ago #24364

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, I just like plain old Kratom the way it is, it’s a wonderful tree, and needs no improving.


(L)(L)(L) Yes! I second that. (L)(L)(L)
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Kratom less is more theory(ceiling effect) 6 months 1 week ago #24376

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cybin_spores wrote: I actually like the fact that you can’t over do it on dosing. What I mean is, if you take too much you won’t feel good, there for there is like a built in safety mechanism that tells you not to take that much. If you over do you will get dizzy or maybe want to vomit, so it’s kind of a good thing. That way people won’t feel the need to take more and more and more higher doses because you can’t, because you won’t feel good. So trying to eliminate one certain thing, so you can take higher doses, I don’t think is such a great idea from my stand point. Kratom is actually perfect the way it is. I don’t even like taking extracts personally, I just like plain old Kratom the way it is, it’s a wonderful tree, and needs no improving.


Not so sure cybin_spores

As tolerance increases the ceiling level for "overdose" goes up.

When I was uneducated and naive about Kratom use over 2Gms used to put my head in the toilet bowl.
I have NO problem now with 5 gms. I try to keep my dose under 4.5 Gms to manage tolerance.

So the dose "ceiling" is in fact a moveable one. BUT the main thing is even if you overdo it, you cannot overdose. That is, there is no respiratory depression or other dangerous effects from taking more than your own body can handle.

I do everything that promotes tolerance ie I take it regularly and almost every 4 hours during the day to manage pain. I have been taking it for just about one year.

I wish I knew better when I started ... BUT I didn't...But I do now!

Hence my passion for responsible Kratom use.
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Last edit: by bomalley.

Kratom less is more theory(ceiling effect) 6 months 1 week ago #24383

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What I meant was, Kratom teaches you not to mis-use it, pretty quickly. I’ve been using it for about 7-8 years or so, and it has taught me to keep my doses low. When I said over-do-it, I was meaning doses like 8grams, 10grams, 12grams, 14grams. Because even when you build up a tolerance like I have, if you try an take a large dose upwards of 12-14grams, it’s not going to help you out anymore. When I started using it after opioids, I WAS taking huge doses, and I tried upping my dose every so often, one point I was trying to take like 16-18 grams, trying to get better effects, and I learned quickly that, THAT does not help whatsoever.
Or maybe that’s just my experience, I guess I can’t speak for everybody. I’ve just learned from using it this long, that there isn’t a real benefit from taking enormous doses of powder. I dose every 4-6 hours, usually 2-3 grams at a time, and it does wonders for me. As long as you have a quality batch, there’s no good reason to take enormous doses.
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Kratom less is more theory(ceiling effect) 6 months 1 week ago #24385

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Moderator has taken note.

That said, I think that what you’re asking is how to undo the leaf into parts for pharmaceutical application. It would be handy for pharmaceutical reinventing the wheel. Removing the ceiling affect would definitely ruin the leaf. But for pharmaceutical use, removing the ceiling affect COULD BE very handy for getting a future drug that could be abused on the market.
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Laurie

Kratom less is more theory(ceiling effect) 6 months 1 week ago #24394

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Chemist4Hire,

Most of us are not scientists, but we're always eager to learn.

Please share how this can be applied, and how we may benefit from this.

Maybe you could send this question to www.americankratom.org/science

Thanks for sharing your thoughts! :-)
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Last edit: by Donut. Reason: salutation

Kratom less is more theory(ceiling effect) 6 months 1 week ago #24398

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Donut wrote: Chemist4Hire,

Most of us are not scientists, but we're always eager to learn.

Please share how this can be applied, and how we may benefit from this.

Maybe you could send this question to www.americankratom.org/science

Thanks for sharing your thoughts! :-)


i have sent several articles to the AKA, DEA and local representatives.

I am not sure how to isolate corynantheidine within mitragyna speciosa. I am however trying to figure it out. it would have many benifits including alowwing for larger dosage with those of high tolerance to opioids like me and my brother. I have cut my dose from 50g 4 times per day to 11g 4 times per day. It is very hard for those of us with large opioid dependency to function off of kratom when we have larger than normal tolerance to opioids. Mitragynine has one of the lowest afiinitys for mu opioid receptors.

if anyone needs me to explain things in a different way i understand. Even for chemists like myself there is many topics even within my feild of study that i do not comprehend. I have to constantly branch out to others for guidance and more information reguarding substances especially when it's a plant like kratom that is not FDA approved with no accepted treatment potential by the FDA. so naturally not many are funded or conducted.

My best guess to isolate it would revolve around using acid base extraction, water base extraction or cloroform because all the alkoloids seem to like them the best. but the trick is to isolate a single oxindole, that is going to require equipment that is far more expensive than i have access too. i think it might be best discovered with industrial solvents that survive at temps above 300 degrees F with no reactions.
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#IAmKratom #KeepKratomLegal
"Kratom is a safe and does not cause respitory depression. Kratom is a mildly addicting substance, comparable to Caffeine, it is my belief that Kratom does NOT fit within the CSA scheduled list I-V."
- DR. Henningfeild (kratom expert) Organic Chemist and scientist.
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