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  • Trip Reports Moderator: Xorkoth

Major, major, MAJOR kratom potentiator

CmonYouShouldKnowBetter said:
pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Consequences of Cytochrome P450 3A Inhibition on Mitragynine Metabolism in Rats - PubMed

Mitragynine, an opioidergic alkaloid present in <i>Mitragyna speciosa</i> (kratom), is metabolized by cytochrome P450 3A (CYP3A) to 7-hydroxymitragynine, a more potent opioid receptor agonist. The extent to which conversion to 7-hydroxymitragynine mediates the in vivo effects of mitragynine is...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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but wouldn't inhibition stop the CYP from converting the mitragynine to the more powerful 7-OH thus rendering it weaker.
 
somnilicious said:
but wouldn't inhibition stop the CYP from converting the mitragynine to the more powerful 7-OH thus rendering it weaker.
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I think 7ohm and mitragynine feel pretty different, some people prefer the mitra feeling and some others prefer the (generally red strain´s) 7-ohm feeling...
so I guess the "potency" is subjective also because of that, and of course there's more alkaloids and stuff that can affect the profile of effects.
I notice the difference between vendors, some subtile but clearly non-placebo differences.
 
I think "reds" containing more 7-ohm is mostly a myth. I heard something like, sun drying it so it gets all brown increases the 7-ohm by a slight amount but still not enough to really notice but I'm not sure. I never saw anything for sure about this. Maybe there is a proper sun drying method because a lot of vendors do it for so long it just renders the kratom very weak, which was the case with a vendor I previously used.

I tried a few of their reds and they were all impossible to get any effect from. But when I was new I had some like Bentuangie that definitely felt distinct and different. Weaker in a way but just, different. Like I could go into this half sleep lucid state on that one easily. So maybe there is truth to the sun drying, and that vendor had actually done it properly without turning it dirt brown. The vein color itself is irrelevant since the same plant can have different colored stems. At the end of the day there's just good or bad kratom, it's not as diverse as cannabis or even kava.
 
CmonYouShouldKnowBetter said:
NIgella Sativa is a calcium channel blocker. It doesnt "tickle" the MOR. https://www.mdpi.com/2218-273X/12/1/20

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I read that it did awhile back but I don't remember where. I just say tickle because in my mind that's how it worked, I can't see why it wouldn't potentiate to the extreme extent it does or help with opioid withdrawal so much if it didn't have some affinity to the MOR.

According to this source: "It has been proved in many in vitro studies that calcium channels/blockers modulate the opioid receptors or release of endogenous opiopeptins in one or other way."

I'm not entirely sure how to interpret that but it sounds like it at least has some involvement in the MOR. It's particularly popular for people coming off kratom, it helps with opioid withdrawal in general but it seems to help with kratom withdrawal the most.
 
BourbonMac said:
I read that it did awhile back but I don't remember where. I just say tickle because in my mind that's how it worked, I can't see why it wouldn't potentiate to the extreme extent it does or help with opioid withdrawal so much if it didn't have some affinity to the MOR.

According to this source: "It has been proved in many in vitro studies that calcium channels/blockers modulate the opioid receptors or release of endogenous opiopeptins in one or other way."

I'm not entirely sure how to interpret that but it sounds like it at least has some involvement in the MOR. It's particularly popular for people coming off kratom, it helps with opioid withdrawal in general but it seems to help with kratom withdrawal the most.
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Because it is a calcium channel blocker :) Let me just link this again https://onlinelibrary.wiley.com/doi/full/10.1002/jppr.1769
 
BourbonMac said:
I think "reds" containing more 7-ohm is mostly a myth. I heard something like, sun drying it so it gets all brown increases the 7-ohm by a slight amount but still not enough to really notice but I'm not sure. I never saw anything for sure about this. Maybe there is a proper sun drying method because a lot of vendors do it for so long it just renders the kratom very weak, which was the case with a vendor I previously used.

I tried a few of their reds and they were all impossible to get any effect from. But when I was new I had some like Bentuangie that definitely felt distinct and different. Weaker in a way but just, different. Like I could go into this half sleep lucid state on that one easily. So maybe there is truth to the sun drying, and that vendor had actually done it properly without turning it dirt brown. The vein color itself is irrelevant since the same plant can have different colored stems. At the end of the day there's just good or bad kratom, it's not as diverse as cannabis or even kava.
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Reds are fermented. They are tied up wet into plastic bags air tight and left to rot in the sun for 3 days. However, when you compare alkaloid profile C of A's of the 3 main colors. the 7oh really doesnt differ, you are spot on there
 
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somnilicious said:
but wouldn't inhibition stop the CYP from converting the mitragynine to the more powerful 7-OH thus rendering it weaker.
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from the study you replied to "Our results in rats demonstrate that cytochrome P450 3A (CYP3A) inhibition can increase the systematic exposure of both mitragynine and 7-hydroxymitragynine and their potency to produce MOR-mediated behavioral effects."
 
BourbonMac said:
No need to be snarky. I'm aware it's a calcium channel blocker, but my point still stands that it does have some involvement with the mu-opioid receptor at least as far as I can tell. If you wanted to correct me you could've done so in a more congenial way.
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LOL Im trying to show you that blocked calcium (ligand or voltage-gated) channels can modulate opioid receptors.
I simply linked a study to demonstrate this MOA. You missed it the first time (judging by your comment) so I linked it again and even added a smiley-face emoji so that your feelings didnt get hurt.
I'm literally trying to help YOU, bro. My apologies for not giving you a rimjob with it

pubmed.ncbi.nlm.nih.gov

Spinal L-type calcium channel blockade abolishes opioid-induced sensory hypersensitivity and antinociceptive tolerance - PubMed

Recent studies have suggested that prolonged exposure to morphine results in the development of paradoxical, abnormal enhanced pain. It has also been suggested that this enhanced pain state may be interpreted as antinociceptive tolerance. Although the precise mechanisms that drive opioid-induced...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov

Effects of prototypic calcium channel blockers in methadone-maintained humans responding under a naloxone discrimination procedure - PubMed

Accumulating evidence suggests that L-type calcium channel blockers (CCBs) attenuate the expression of opioid withdrawal and the dihydropyridine L-type CCB isradipine has been shown to block the behavioral effects of naloxone in opioid-maintained humans. This study determined whether two...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov

Opioid Receptor Regulation of Neuronal Voltage-Gated Calcium Channels - PubMed

Neuronal voltage-gated calcium channels play a pivotal role in the conversion of electrical signals into calcium entry into nerve endings that is required for the release of neurotransmitters. They are under the control of a number of cellular signaling pathways that serve to fine tune synaptic...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
 
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Bioperine is brand-name. It's a concentrated extract of a constituent of Black Pepper called Piperine. Bioperine is a trademarked version of this Piperine that is stated to be "more-effective" yada yada yada than regular Piperine. The Piperine content of Black Pepper is generally 10mg/gram. You can do the same thing by getting some empty capsules and filling them with Black Pepper from your spice rack. Two large "00" capsules is going to hold at least a couple of grams of ground pepper.

I've read that Piperine delays gastric-emptying and that this is likely the mechanism of action in its tendency to potentiate a variety of different substances. This seemingly-universal effect is well-explained by this theory, in that it's clearly not an enzymatic deal as is common with many other substances.

I've taken Piperine with Methadone before and I'd be confident in saying it made the Methadone as much as 20% stronger when used over the course of a few days consistently. This isn't too far from what one might expect using other "potentiators" that are more well-known.

There are definitely a lot of potentiators out there, but I've yet to find a "holy grail" that really ends up making some kind of difference in my life or my usage if I take it. It's like, 3-4 days later once my tolerance catches up, now I'm taking 5 grams of black pepper every morning, along with my huge dose of Cimetidine (Tagamet), oh shit, I ran out of fresh grapefruits, wait, I better call my girlfriend to make sure she gets some Black Seed Oil or I'll be too sick to work!" It just puts you in a similar place with an unfamiliar need to fill in order to keep yourself going at a constant.

I'm not saying it's a stupid pursuit. I love talking about potentiators and such, even when I'm no longer in that game in that way. It's all really fascinating stuff. I just mean that, in the end, more of the drug is not the ticket to freedom that we make it out to be.
 
I'd like to think with kratom it's not particularly harmful, I mean if I don't take it then it still gets me nice, I just notice it lasts significantly longer with the turmeric/black pepper. It's becoming a bit undesirable actually. If it actually does delay gastric emptying, the black pepper that is, I wonder if it's why I'm not so regular lately? Kratom itself never caused issues with that, not even Oxy (only ever took it after surgeries). Kratom's the only opioid I use recreationally.

BergenRichNYC said:
Still not sure about kratom yet.
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In what way, like not sure about trying it? Unless you lived with chronic pain or something I probably wouldn't touch it. I love the stuff but I will admit it's addicting, although I think weed is 100x more addicting, hell I think DMT is addicting lol, but that's not usual. It just alleviates so much mental anguish. I'd flush all my kratom in 5 seconds if it meant I could never get high again.
 
Doesn't seem addicting to me. Just not experiencing any effects., but then again I still haven't been addicted to crack either, been 3 weeks since a blast.
 
How much are you taking? There's a lot of bunk stuff out there too. If it looks brown and all it's as good as garbage. This is what most "red vein strains" are, overly sun dried kratom. Good kratom dosed well will give you a VERY nice opioid high, but unlike other opioids eating tends to kill the effects and taking it on a full stomach won't yield much, but it still works for some people.

Half the time eating will boost the high, and on this turmeric/ginger combo eating doesn't kill the high whatsoever, it always used to most of the time reduce the effects some if not all but with these potentiators that isn't the case. Most stuff like Oxy will often be potentiated by food pretty much every time, with kratom it's a gamble.

Sounds like you haven't done enough crack then... I'd probably not delve any further into that. We've heard too many stories of "oh I use H and I'm not addicted" and then they either wind up in rehab 2 months later or dead. Just be careful.
 
Yeah I used to take my Kratom with turmeric and black pepper. Was supposed to potentiate it. But I eventually dropped them. It didn't seem to make a huge difference.
 
BourbonMac said:
How much are you taking? There's a lot of bunk stuff out there too. If it looks brown and all it's as good as garbage. This is what most "red vein strains" are, overly sun dried kratom. Good kratom dosed well will give you a VERY nice opioid high, but unlike other opioids eating tends to kill the effects and taking it on a full stomach won't yield much, but it still works for some people.
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Yeah here's the problem with Kratom, take it on empty stomach and you'll get this great high that gives you the munchies. Then all you can think about is eating, but as soon as you do your high goes away. The only kind of workaround is to fill your stomach with coffee.
 
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