How All Kratom Works: A Revised Theory of One Alkaloid

[7ohm]

Theory:
All effects from Kratom come from varying the level of one alkaloid: Mitragynine. So, you should be able to get every effect from every strain simply by adjusting your dosage. Every strain is essentially just a different level of mit.

How do We Know That?
Some researchers did a study of a handful of "strains" from various vendors and tested them. They found that there was no significant difference in the level of 7ohm across strains. Believing that there was inaccurate sampling because "strains" are actually just blends, I did my own study looking at various strains and drying methods from several vendors.

Here's what I found:
No significant difference in levels of 7ohm across all drying methods and strains. There was the random strain with higher levels of 7ohm. McCurdy et al. thought that it was adulteration. however, I think that it's safe to say that it's not a legitimate concern in our industry. The only notable difference was in the level of Mitragynine. The other alkaloids don't really have Psychoactive effects, and they are found in such small amounts for it to conceivably make a difference. There have been limited studies on the other alkaloids with the exception of the anti-inflammatory Mitraphylline, which is also found in cats claw and has shown much promise in treating cancerous tumors much like CBD. leaf actually also contains a flavenoid called epicatechin found in tea, which is also effective against cancer. Reds, which are all essentially bentuangie (dried in plastic bags in the sun), simply have low levels presumably from the oxidizing effects of the sun. I found that pure bents had levels as low as .3%. Indoor dried leaf was as high as 2.3%. this would explain why a lot of reds are perceived as "weak". They really are and they don't have this corresponding increase in 7ohm. In fact, you are simply getting an "inferior' product which has less alkaloids.

Here's what we used to think:
1)The sun caused photooxidation to occur inside the plant leaf converting the Mitragynine into 7ohm through the reaction of phytochemicals and sunlight.
Why did we think that?
the chemical compound 7ohm is reddish in color. oxidation turns leaf red/brown. reds have a different effect (allegedly more opioid).
A study showed that the conversion took place easily inside of a petri dish just by exposing the solution to sunlight.

2)Kratom is similar to other medicinal plant chems, like cannabinoids, which have psychoactive effects that contribute to the entourage effect from synergy of multiple compounds.
Why did we think that?
Because there seems to be so many different effects from kratom, a logical explanation would be that it's not unlike Cannabis.

Here's what we recently discovered through research (Mainly CNS receptor panel from McCurdy et al):
It validated what we had suspected all along, but this one study measured (quantified) the affinities to which Mitragynine binds to various receptors in a rats brain and either agonizes or inhibits.

Mitragynine seems to be single handedly responsible for all of the other psychoactive effects of Kratom minus the opioid effect:
1) stimulation through adenosine receptore antagonism like caffeine. adenosine causes and regulates sleep. without it, you get anti-sleep aka caffeine buzz. It' s noteworthy that you can only inhibit this receptor so much, ie there's a ceiling on effects just like coffee. You can only have zero adenosine production as the max inhibition. You can't have negative chemicals in the brain.
2) mood
it is serotonergic, ie it causes your brain to release more serotonin. It is an agonist at this receptor.
3) motivation/elation
dopaminergic,
4) adrenergic
the a2 receptor agonism is how clonidine works to prevent opiate w/d. unfortunately, it is also a known contributor to erectile dysfunction. interesting to note yohimbine, the chemical cousin of mitragynine (structural similarity), is an antagonist. this is presumably why it is so helpful with opioid withdrawal (aside from the obvious mu opioid agonism).

Very important new finding:
Mitragynine at high concentrations blocks uptatke and effects of all opioids including heroin and morphine. Rats with high concentrations of mit, showed no mor effects at all. The hot plate test, the tail flick test, preference to the site of admin (they don't come back for more) all tested at baseline, ie it was the same as when sober.
Mitragynine is also a cyp3a4 inhibitor. So, there appears to be a scientific explanation for 2 clear cut effects of Kratom that trade off depending on dosage:
mitragynine
7ohm

All strains (varied level of MG) fall somewhere in the middle. Reds have little blocking and reported Wobbles presumably because of it's lower levels. there appears to be this precarious balance between max opioid effect and opioid blocking.

If you take too much, you are not going to feel the effects of 7ohm. Instead, you will feel wobbles, stim, mood, etc. This can phenomenon can be seen in extract, as well as certain "strains'" (presumably indoor dried, which minimized oxidation of Mitragynine causing higher concentrations).

What this means: Dosing is Key

There's a sweet spot for every strain. Taking the same dose for every strain and for every effect is a mistake. Strains do not have any specific properties that would vary effects except the concentration of Mitragynine. For more stim, take more. There is a threshold of Mitragynine, where it stops the conversion of 7ohm, and even stops all opioid effects. Lower levels/concentrations (like with reds) seem to allow for more opioid effect all the way up until this threshold is reached. Smaller doses allow for less opioid blocking and more production of said enzyme.

Here's what I think now:
Wobbles are caused by Mitragynine

why?
there are no opioid effects when you have the wobbles.
there is a study that calls Mitragynine the great Neuromuscular blockade. they took a leg off of a rats cadaver and hooked up an electrode to the nerve to make the leg twitch. When they gave the leg enough Mitragynine they were able to get it to stop twitching. the idea is that it slows/stops nerve communication to a level where the muscles in your eyes and other parts of your body stop responding. it physically blocks nerve communications. EDIT: I should mention this is why it's assumed to be so helpful with fibromyalgia. There's 2 components, analgesia and complete relaxation of the nerves and therefore muscles. Think about what happens to your eyes. One could describe it as unresponsive, or relaxed. Some of the muscle relaxing properties are probably from this phenomenon on a lesser level. It seems to affect motor skills as well. Even your upper body, and your arms get like paralyzed to some degree. It feels like you can't use your hands very well. I would say it's best not to drive on it. I've wrecked my car a couple of times. tangent.

All of the effects seem to be a result of the one alkaloid Mitragynine, which in turn converts to 7ohm from oxidization inside of our bodies specifically from the cytochrome enzyme cyp3a4. So, it's not the leaf that makes a difference, it's us and how much we take. To make things more complicated, the liver has the most of this enzyme and is also responsible for metabolizing drugs from our system. So, as mitragynine is cleared out of our bloodstream, some of it (estimated 6% by recent study) is being converted to 7ohm and being put back into our bloodstream. Then, as this enzyme is used up for the conversion, or inhibited by Mitragynine, it slows the rate at which drugs are removed from the body. This means that drugs will stay inside your system for a longer time, and possibly build. Most opiate potentiators, like grapefruit juice are cyp3a4 inhibitors. St John's wort is an example of an inducer. It makes sense to me that if you want more opioid effect that you would want more of that enxzyme. EDIT: it would also explain why wobbles last for so long sometimes. I feel like i've had it 2 days in a row. Each time seems easier to get. I feel like I"m wDing and take just a little bit hoping for just a hair of relief from the jitters, and boom. here it is again. your friend the wobbles. tangent

There seem to be a lot of different effects from Kratom. So, naturally it's believable that there are different types, or "strains". It's not like the Cannabis Industry where there has been extensive and complex breeding practices which effect the complex chemical profiles and vary by genetic varietal: phenotypes. We know that Indonesians are not growing different strains of the leaf. It's not that they don't exist, but moot since they are not differentiating it. Even if there were different strains, the only compound that seems to matter is the one.

7ohm is the opioid alkaloid and it's created by our bodies (converted through oxidation from cyp enzymes). Researchers have scored it on par with Morphine in it's Mu Opioid value (some as strong as 14 times the value).

What's the significance of Mu Opioid recpetor?
We don't know. We do know that it's the same receptor that opiates like morphine and heroin hit and seems to be responsible for the perception of sedation, analgesia, and euphoria.

BOTTOM LINE: All effects from Kratom are dependent on the dose of this one alkaloid. If you're not feeling the opioid effects, you could be taking too much and blocking it. At this point, it should be obvious (eye problems, stim, no opioid effect). Then, because you don't feel it, you chalk it up to tolerance and take even more. Leaf is complicated, but in more ways than can be explained by the strain/vein color paradigm. Asians don't have problems wtih addiction becasuse a) mitragynine is not addicting (rats don't come back for more) b) they take larger doses than we do. In fact, the main reason they use it is for it's stimulating properties. Chris McCurdy, the leading expert, surmised that addiction was due to "inferior" product, or leaf that has lower concentrations of Mitragynine. It is interesting to note that the Thai/malaysians do not have bentuangie (red). Americans, on the other hand are experiencing w/d, addiction, etc...The main reason we take it is for the Opioid effect according to the largest survey in history. So, it may be the case that you need to take less for more opioid effect and more for stim. This indicates that there is probably a sweet spot for every strain and what that it depends on what the concentration of Mitragynine is in the leaf, eg you can take a lot of a red before wobbles. to get more effect, take more up until you start getting the effect blocked, at which point it will be more stim (mitragnine effect). At a particular set dose, you can categorize "strains" as being fast or slow. or, you can just adjust your dosage. Theoretically, it should all have the same effect.

The 2 faces of Kratom: Mitragynine and 7ohm. These appear to be the main 2 that synergize. Stimulant and Opioid.

EDIT: make no mistake about it, kratom has addiction potential despite having this limiting factor. In fact, it happens quite a bit, although it def makes it harder to abuse, I think. There's this miraculous, natural regulating effect of Mitragynine that prevents overdose on 7ohm. What a combo, right? I hear a lot of people claim that they stopped using because it stopped having opioid effect on them. According to science, tolerance shouldn't build like it does with opiates.

Let me clarify:
I think it has something to do with the concentration of the dose. one phenomenon that I can't explain is why I can't get 7ohm effects from 45% extract. Others claim no effect. Taking higher concentrations like extract might actually lower your tolerance to 7ohm. Mitragynine's fast absorbtion rate might be a factor. It's possible that you may have to slow it down to allow for conversion to 7ohm.

The latest survey of Americans from Johns hopkins found kratom addiction happens to 1 in 5 users. 20% is no joke. Keep in mind that this is self reported and denial happens to be a symptom of addiction making the results slightly skewed. At some point I think that it's possible get to a habit of use despite harmful consequences. i know a lot of people that would argue that there are no harmful consequences, ie no side effects, so no such thing as addiction. Or, addiction to the level of say a cup of coffee. But, it's apparent now, that the prevalence of addiction here is twice as high as it was in thailand. There are cases of severe, opiate like withdrawal in the US, where it occurs relatively infrequently.

If you want to quit, and it causes you stress. Then, one could argue that is addiction, since that is a negative consequence. If you don't want to quit because it doesn't cause you harm, then you're cool. That's healthy use. It doesn't matter why you use it. It's your right. Just because it's natural doesn't mean it's not harmful, though. Opium is natural, so is tobacco. You should treat it like any drug when deciding to use it. the fda approves drugs all the time that kill people because it expects that you and/or your doctor are weighing the costs and benefits. if it makes sense do it. but, make an informed decision. weigh the potential costs and benefits, do some due diligence. it's your health for christ sake. Don't listen to some rando's opinion.

Kratom is a drug, just like Alcohol, Cannabis, Tobacco, Coffee. It does have abuse and addiction potential. Anything when abused can be harmful, natural or not. Saying that it's not addicting or not harmful is irresponsible. Let's be realistic about the potential risks and incorporate that in our decision making process. Ignoring the dangers could result in addiction. There is an entire subreddit of people who are pissed cuz they say Kratom ruined their lives r/quittingkratom. It's probably something you at least want to be aware of. There is withdrawal syndrome and the severity depends on how much you use. Some have reported it to be as bad as opiates while some have reported none at all. There has been one death in the US where Kratom was the only substance found and was deemed to be the cause of death. The history of abuse in the US has been unremarkable. It is interesting to note that treatment centers are now offering services for Kratom addiction.

[DylanJames]

Wow, thank you! Very interesting and useful information.

This would mean that leaf right off the tree or boiled into a tea would be much more stimulating than we in this part of the world are used to, right? This also explains why we want that sweet spot when it comes Kratom. Would this also mean that if you took Kratom with an opiate that you would be blocking its effects at some point? I know I must have done this years ago when I first started Kratom, but I don't remember anything specific.

I want to make sure I am comprehending the data and drawing correct conclusions.

[fusedflora]

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/

[BallzDeep9]

[
Here's what we used to think:
1)The sun caused photooxidation to occur inside the plant leaf converting the Mitragynine into 7ohm through the reaction of polyphenols and sunlight.
Why did we think that?

Here's what we recently discovered through research ...

Man... Hall Of Fame post here. I'm re-reading this, you give SO much good Info... I just wanted to say, Great Stuff! I mean this post. Reviews of your kratom are also great. You are obviously into the science, state Of the Art! Thanks for taking your time, to write this out... Yes, we have new discoveries and, finding more answers all the time.

[Daniel]

Theory:
All effects from Kratom come from varying the level of one alkaloid: Mitragynine. So, you should be able to get every effect from every strain simply by adjusting your dosage.

How do We Know That?
Some researchers did a study of a handful of "strains" from various vendors and tested them. They found that there was no significant difference in the level of 7ohm across strains. Believing that there was inaccurate sampling because "strains" are actually just blends, I did my own study looking at various strains and drying methods from several vendors.

Here's what I found:
No significant difference in levels of 7ohm across all drying methods and strains. There was the random strain with higher levels of 7ohm. McCurdy et al. thought that it was adulteration. however, I think that it's safe to say that it's not a legitimate concern in our industry. The only notable difference was in the level of Mitragynine. The other alkaloids don't really have Psychoactive effects, and they are found in such small amounts for it to conceivably make a difference. There have been limited studies on the other alkaloids with the exception of the anti-inflammatory Mitraphylline, which is also found in cats claw and has shown much promise in treating cancerous tumors much like CBD. leaf actually also contains a flavenoid called epicatechin found in tea, which is also effective against cancer. Reds, which are all essentially bentuangie (dried in plastic bags in the sun), simply have low levels presumably from the oxidizing effects of the sun. I found that pure bents had levels as low as .3%. Indoor dried leaf was as high as 2.3%. this would explain why a lot of reds are perceived as "weak". They really are and they don't have this corresponding increase in 7ohm. In fact, you are simply getting an "inferior' product which has less alkaloids.

Here's what we used to think:
1)The sun caused photooxidation to occur inside the plant leaf converting the Mitragynine into 7ohm through the reaction of polyphenols and sunlight.
Why did we think that?
the chemical 7ohm is reddish in color. oxidation turns leaf red/brown. reds have a different effect (allegedly more opioid).
A study showed that the conversion took place easily inside of a petri dish just by exposing the solution to sunlight.

2)Other medicinal plant chems, like cannabinoids, have psychoactive effects which contribute to this synergy of effects.
Why did we think that?
Because there seem to be so many different effects from kratom, the logical explanation would be that it's not unlike Cannabis.

Here's what we recently discovered through research (Mainly CNS receptor panel from McCurdy et al):
It validated what we had suspected all along, but this one study measured (quantified) the affinities to which Mitragynine binds to various receptors in a rats brain.

Mitragynine is responsible for all of the other psychoactive effects of Kratom minus the opioid effect:
1) stimulation through adenosine receptore antagonism like caffeine. adenosine causes and regulates sleep. without it, you get anti-sleep aka caffeine buzz. It' s noteworthy that you can only inhibit this recptor so much, ie there's a ceiling on effects just like coffee. You can only have zero adenosine production as the max inhibition. You can't have negative adenosine in the brain.
2) mood
it is sertonergic, ie it causes your brain to release more serotonin. It is an agonist at this receptor.
3) motivation/elation
dopaminergic,
4) adrenergic
the a2 receptor agonism is how clonidine works to prevent opiate w/d. unfortunately, it is also a known contributor to erectile dysfunction. interesting to note yohimbine, the chemical cousin of mitragynine (structural similarity), is an antagonist. this is presumably why it is so helpful with opioid withdrawal (aside from the obvious mu opioid agonism).

Very important new finding:
Mitragynine at high concentrations blocks uptatke and effects of all opioids including heroin and morphine.
Mitragynine is also a cyp3a4 inhibitor. So, there appears to be a scientific explanation for 2 clear cut effects of Kratom that trade off depending on dosage:
mitragynine
7ohm

All strains (varied level of MG) fall somewhere in the middle. Reds have little blocking and reported Wobbles presumably because of it's lower levels. there appears to be this precarious balance between opioid effect and opioid blocking.

If you take too much, you are not going to feel the effects of 7ohm. Instead, you will feel wobbles, stim, mood, etc. This can phenonmeon can be seen in extract, as well as certain "strains'" (presumably indoor dried, which minimized oxidation of Mitragynine causing higher concentrations).

What this means: Dosing is Key

There's a sweet spot for every strain. Taking the same dose for every strain and for every effect is a mistake. Strains do not have any specific properties that would vary effects except the concentration of Mitragynine. For more stim, take more. There is a threshold of Mitragynine, where it stops the conversion of 7ohm, and even stops all opioid effects. Lower levels/concentrations (like with reds) seem to allow for more opioid effect all the way up until this threshold is reached. Smaller doses allow for less opioid blocking and more production of said enzyme.

Here's what I think now:
Wobbles are caused by Mitragynine

why?
there are no opioid effects when you have the wobbles.
there is a study that calls Mitragynine the great Neuromuscular blockade. they took a leg off a rats cadaver and hooked up an electrode to the phrenic nerve to make the leg twitch. When they gave the leg enough Mitragynine they were able to get it to stop twitching. the idea is that it slows/stops nerve communication to a level where the muscles in your eyes and other parts of your body stop responding.

All of the effects seem to be a result of the one alkaloid Mitragynine, which in turn converts to 7ohm from oxidization inside of our bodies specifically from the cytochrome enzyme cyp3a4. So, it's not the leaf that makes a difference, it's us and how much we take. To make things more complicated, the liver has the most of this enzyme and is also responsible for metabolizing drugs from our system. So, as mitragynine is cleared out of our bloodstream, some of it (estimated 6% by recent study) is being converted to 7ohm and being put back into our bloodstream. Then, as this enzyme is used up for the conversion, or inhibited by Mitragynine, it slows the rate at which drugs are removed from the body. This means that drugs will stay inside your system for a longer time, and possibly build. Most opiate potentiators, like grapefruit juice are cyp3a4 inhibitors. St John's wort is an example of an inducer. It makes sense to me that if you want more opioid effect that you would want more of that enxzyme.

There seem to be a lot of different effects from Kratom. So, naturally it's believe that there are different types, or "strains". It's not unlike the Cannabis Industry where there has been extensive and complex breeding practices and the complex chemical profiles vary by genetic varietal: phenotypes. We know that Indonesians are not growing different strains of the leaf. Well, it's not that they don't exist, but moot since they are not differentiating it. Even if there were different strains, the only chemical that seems to matter is the one.

7ohm is the opioid alkaloid and it's created by our bodies. Researchers have scored it on par with Morphine in it's Mu Opioid value (some as strong as 14 times the value). What's the significance of Mu Opioid recpetor? We don't know. We do know that it's the same receptor that opiates like morphine and heroin hit and seems to be responsible for the perception of sedation, analgesia, and euphoria.

BOTTOM LINE: All effects from Kratom are dependent on the dose of this one alkaloid. If you're not feeling the opioid effects, you could be taking too much and blocking it. At this point, it should be obvious (eye problems, stim, no opioid effect). Then, because you don't feel it, you chalk it up to tolerance and take even more. Leaf is complicated, but in more ways than can be explained by the strain/vein color paradigm. Asians don't have problems wtih addiction becasuse a) mitragynine is not addicting (rats don't come back for more) b) they take larger doses than we do. In fact, the main reason they use it is for it's stimulating properties. Chris McCurdy, the leading expert, surmised that addiction/tolerance/dependence/opioid effect, was due to what's considered "inferior" product, or leaf that has lower concentrations of Mitragynine. It is interesting to note that the Thai/malaysians do not have bentuangie (red). Americans, on the other hand are experiencing w/d, addiction, etc...The main reason we take it is for the Opioid effect according to the largest survey in history. So, it may be the case that you need to take less for more opioid effect and more for stim. This indicates that there is probably a sweet spot for every strain and what that it depends on what the concentration of Mitragynine is in the leaf, eg you can take a lot of a red before wobbles. to get more effect, take more up until you start getting the effect blocked, at which point it will be more stim (mitragnine effect). At a particular set dose, you can categorize "strains" as being fast or slow. or, you can just adjust your dosage. Theoretically, it should all have the same effect.

Thanks for posting this. Great stuff, although I'm a little confused. You write "Mitragynine is responsible for all of the other psychoactive effects of Kratom minus the opioid effect" (emphasis mine). So, what you're saying is that Mitragynine is not an opioid receptor agonist, instead it is broken down in the body into 7-OHM which is an opioid agonist on the mu-delta sites? For what it's worth, at least ten years ago I tried Mitragynine extract and 7-OHM extract. (These were far different extracts than the ones offered today and I have yet to see them again) and I noticed the Mitragynine extract was as powerful as a Oxycodone in it's analgesic effects, euphoric effects and stimulation. In fact, the mood/euphoria from the Mitragynine extract was off the charts. (I was prescribed some Oxycodone after surgery and was able to compare.) The 7-OHM wasn't nearly as potent in its analgesic effects, stimulation, and mood/euphoric effects. It was still effective, but far more subtle.

I do have a question for you, what is the highest % of 7-OHM that you've seen in a batch?

[pray4peace4]

I've considered in the past that the CYP3A4 enzyme may well be the key, or at least is part of the key to figuring this out. Tylenol is detoxified in the liver by a chemical called glutathione. If a person takes too much Tylenol, there isn't enough glutathione to detoxify it all & then the liver is damaged by the excessive buildup of toxins. So it's possible that daily kratom use could use up all the enzyme used to convert it to 7ohm, so the pleasurable effects cease. That would account for why taking a break causes a return of effects. I've also noticed that reducing my dose size or frequency also causes an increase in effects if I have a decrease in effects. Very interesting stuff.

[RubberToes]

Good Stuff!!!

[WickedMadScientist]

I've considered in the past that the CYP3A4 enzyme may well be the key, or at least is part of the key to figuring this out. Tylenol is detoxified in the liver by a chemical called glutathione. If a person takes too much Tylenol, there isn't enough glutathione to detoxify it all & then the liver is damaged by the excessive buildup of toxins. So it's possible that daily kratom use could use up all the enzyme used to convert it to 7ohm, so the pleasurable effects cease. That would account for why taking a break causes a return of effects. I've also noticed that reducing my dose size or frequency also causes an increase in effects if I have a decrease in effects. Very interesting stuff.

This is definitely a variable. This little guy is a game changer for healing your liver and providing homeostasis with your neurotransmitters, clearing your lungs, breaking up biofilms, and has countless other benefits, even to which you spoke on involving Glutathione. Many people that have a past with bad diet, drugs and alchohol, have low glutathione and it helps to restore it. It really changed my life, and is something I started before my Kratom journey and it assisted with leading me to Kratom when I was searching for things to restore health and natural alternatives for pain management. In fact I only have one left and have to order more! I swear that it acts like a tolerance break would, so what you are theorizing must have an effect with resetting that liver enzyme. It also really helps for when you do take a break to lessen the WDs. I’m sure you are aware, but for those that aren’t:

N-Acetyl Cystine - https://selfhacked.com/blog/nac-top-43- ... teine-nac/

Take it with a liposomal Vit c, or orange juice. It’s friggin amazing, specially for those that have done a lot of percoset/hydros and/or Advil/acetaminophen. NAC is actually an amino acid that’s pumped into peoples bloodstreams in the ER when they have an overdose as well. I have good results with the Jarrows Formula brand. It seems to work better if you do the NAC at bedtime, or two hours after you take Kratom. There are others personal experience that taking it close to Kratom can dull the effects. Make sure you don’t take it with food, so wait two hours after food at minimum.

[7ohm]

Wow, thank you! Very interesting and useful information.

This would mean that leaf right off the tree or boiled into a tea would be much more stimulating than we in this part of the world are used to, right? This also explains why we want that sweet spot when it comes Kratom. Would this also mean that if you took Kratom with an opiate that you would be blocking its effects at some point? I know I must have done this years ago when I first started Kratom, but I don't remember anything specific.

I want to make sure I am comprehending the data and drawing correct conclusions.

That is correct. A high dose, like extract or shade dried leaf, might block oxy as well. It stands to reason since it blocked morphine. It feels like it blocks 7ohm for sure. People have complained that they didn't feel their other pain meds while on kratom. My guess is that they're taking too high a concentration of kratom then taking another opiate.

[7ohm]

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/

There's something more to it for sure. Something needs to explain why there's no 7ohm effect with extract. it's missing something. or, something.

[7ohm]

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/

Interesting the wobbles phenomenon. I wonder if it's the naloxone doing similar thing as mit.

I couldn't even find much on indoxyl. What is it, another metabolite?

i think cyp enzymes play a huge role. there's a lot of complicated, paradoxical effects going on. its found in the stomach, and intestines too. There's someting in plain leaf that's not in extract that allows for more opioid effect. Or, thats how it seems anyway.

[7ohm]

[
Here's what we used to think:
1)The sun caused photooxidation to occur inside the plant leaf converting the Mitragynine into 7ohm through the reaction of polyphenols and sunlight.
Why did we think that?

Here's what we recently discovered through research ...

Man... Hall Of Fame post here. I'm re-reading this, you give SO much good Info... I just wanted to say, Great Stuff! I mean this post. Reviews of your kratom are also great. You are obviously into the science, state Of the Art! Thanks for taking your time, to write this out... Yes, we have new discoveries and, finding more answers all the time.

thanks for the positive feedback.

[7ohm]

Thanks for posting this. Great stuff, although I'm a little confused. You write "Mitragynine is responsible for all of the other psychoactive effects of Kratom minus the opioid effect" (emphasis mine). So, what you're saying is that Mitragynine is not an opioid receptor agonist, instead it is broken down in the body into 7-OHM which is an opioid agonist on the mu-delta sites? For what it's worth, at least ten years ago I tried Mitragynine extract and 7-OHM extract. (These were far different extracts than the ones offered today and I have yet to see them again) and I noticed the Mitragynine extract was as powerful as a Oxycodone in it's analgesic effects, euphoric effects and stimulation. In fact, the mood/euphoria from the Mitragynine extract was off the charts. (I was prescribed some Oxycodone after surgery and was able to compare.) The 7-OHM wasn't nearly as potent in its analgesic effects, stimulation, and mood/euphoric effects. It was still effective, but far more subtle.

I do have a question for you, what is the highest % of 7-OHM that you've seen in a batch?

Out of everything that I looked at, the highest was .05%. Nobody thought it was magical at all.

the opioid effect from teh mit extract wwas probbloy from your body converting it. i think the stim properties are much more noticeable when the 7ohm effects are blocked. like pre wobbles, when your eyes start getting tight. My guess is that it probably wasnt 7ohm isolate. I think it would blow your socks off. the process of isolating it would be pretty entailed and expensive.

mit, might be a partial agonist. i can't remember. i think it does have a relatively low mor score. you are right, prob. sounds right. they used to think that mit was teh opioid alkaloid. but, evidence suggestst that its 7ohm.

it starts oxidizing in your stomach and then intestines all the way to your liver, which has the most. what seems to be more important than 7ohm is mit. in extract for examrple, theres plenty of 7ohm. but there's also a lot of mit. you got to squash that mit down

[Bubba5150]

I assume everybody's individual sweet spot would have to be obtained through trial and error, basically a controlled scientific study with one's self that repeats every time we purchase a new strain from a new vendor (or even a new strain from the same vendor). Perhaps McCurdy or somebody else will someday find out that magical equation of total mitragynine needed to obtain a specific effect. Then when we buy from those vendors that post the total amount of mit in their product, it would take out all the guess work and we would know exactly how much to take, even the first time we use that strain. I mean if we are substituting or even replacing other medications with Kratom why not be as specific with dosage right? It's times like these I wish I was gifted enough to figure this out on my own and pass that info on.

Great post nonetheless, I really appreciate learning more about the science of this!

[Grimble_Gromble]

Wow, thank you! Very interesting and useful information.

This would mean that leaf right off the tree or boiled into a tea would be much more stimulating than we in this part of the world are used to, right? This also explains why we want that sweet spot when it comes Kratom. Would this also mean that if you took Kratom with an opiate that you would be blocking its effects at some point? I know I must have done this years ago when I first started Kratom, but I don't remember anything specific.

I want to make sure I am comprehending the data and drawing correct conclusions.

In my experience (as many others will often attest) opiate effects are diminished, if not totally voided, when kratom is in your system. I've found that even with a day or two of space in-between, kratom still dulls the opiates. The positive of that is I've turned down opiates multiple times because I had kratom in my system and knew it would be a waste. Personally I think kratom works better anyway so I think it's a win win.

[pray4peace4]

Somebody in this string commented on fresh leaves as compared to powder. I've tried fresh leaves, & by fresh I mean leaf right off the tree. They're all stimulant action - not like powder at all.

I've pondered this whole "how does someone get the best out of kratom" topic a lot. There's a lot of variables to sort out. My first 2 years I only used 1 strain from Herbal RVA, his PMD, & I always got exactly the same effects & got them powerfully. I never had to increase my dose, never increased the frequency. It was fantastic! But reading all the reviews on Reddit, I wanted to branch out & try something else, so I bought some different strains. After that first dose of Gaia Red Bali, my PMD never worked again. To this day Jonathan's PMD does absolutely nothing, and that's crummy because I bought 6 kilos of it.

But what caused that loss of effects? Was it just coincidence it happened right after I took a different strain & I simply suffered from overtaxing my receptors at that exact moment? Maybe it was something else where a sun dried strain cancels out the green. I noticed I was developing bad indigestion at the same time, so maybe something involved with that changed my digestive enzymes so the kratom wasn't being processed correctly. Does diet alter how kratom is processed? I'm doing some self-experimentation right now to see if any category of food can increase the effects. Plus I'm on quite a few pills now that I'm an 'ol fart that I wasn't on 5 years ago & they might be reducing the effects for me.

Now yah know, if kratom in the USA made big bucks for the pharmaceutical companies, you can believe kratom would be researched inside out & we'd have answers for this big unknown. Of course the price would skyrocket & there'd be many hoops to jump through like getting a prescription. We need more research on kratom.

[7ohm]

Somebody in this string commented on fresh leaves as compared to powder. I've tried fresh leaves, & by fresh I mean leaf right off the tree. They're all stimulant action - not like powder at all.

I've pondered this whole "how does someone get the best out of kratom" topic a lot. There's a lot of variables to sort out. My first 2 years I only used 1 strain from Herbal RVA, his PMD, & I always got exactly the same effects & got them powerfully. I never had to increase my dose, never increased the frequency. It was fantastic! But reading all the reviews on Reddit, I wanted to branch out & try something else, so I bought some different strains. After that first dose of Gaia Red Bali, my PMD never worked again. To this day Jonathan's PMD does absolutely nothing, and that's crummy because I bought 6 kilos of it.

But what caused that loss of effects? Was it just coincidence it happened right after I took a different strain & I simply suffered from overtaxing my receptors at that exact moment? Maybe it was something else where a sun dried strain cancels out the green. I noticed I was developing bad indigestion at the same time, so maybe something involved with that changed my digestive enzymes so the kratom wasn't being processed correctly. Does diet alter how kratom is processed? I'm doing some self-experimentation right now to see if any category of food can increase the effects. Plus I'm on quite a few pills now that I'm an 'ol fart that I wasn't on 5 years ago & they might be reducing the effects for me.

Now yah know, if kratom in the USA made big bucks for the pharmaceutical companies, you can believe kratom would be researched inside out & we'd have answers for this big unknown. Of course the price would skyrocket & there'd be many hoops to jump through like getting a prescription. We need more research on kratom.

Metabolism seems to play a role. There are enzymes involved, so diet also.

That is a weird phenomenon that seems to happen quite a bit. If i had to guess, i would say that it might have a mit level that's too high. the red is most likely a lower level. It might be the case that your body specifically prefers that level of mit for optimal conversion. I feel like it's not necessarily the total amount of mit in your system, but it seems like it's more dependent on the concentration that you take at one time. There's def a threshold, and it prob is different for people. I took a poll of vendors who test a lot, and the "best" leaf ranged from .8 to 1.9. So, it's sitll a bit of. mystery despite what weve just learned.

What people never think of when there is no effect is take less. There is clearly an effect happening, it's just not noticed because we're all looking for something else. But, wobbles are not something that can be placebo. The synergy of 7ohm and mit appear to be where the magic lies.

[7ohm]

Wow, thank you! Very interesting and useful information.

This would mean that leaf right off the tree or boiled into a tea would be much more stimulating than we in this part of the world are used to, right? This also explains why we want that sweet spot when it comes Kratom. Would this also mean that if you took Kratom with an opiate that you would be blocking its effects at some point? I know I must have done this years ago when I first started Kratom, but I don't remember anything specific.

I want to make sure I am comprehending the data and drawing correct conclusions.

In my experience (as many others will often attest) opiate effects are diminished, if not totally voided, when kratom is in your system. I've found that even with a day or two of space in-between, kratom still dulls the opiates. The positive of that is I've turned down opiates multiple times because I had kratom in my system and knew it would be a waste. Personally I think kratom works better anyway so I think it's a win win.

Hopefully we'll be better able to utilize this plant if we learn more about it. Thanks for pointing that out. Observations like that lend support to our theory. Even one instance where it doesn't occur can disprove our theory. It's observations like this that spur studies.

How they have measured MOR scores in rats?
tail flick test. light beem shined on tale. time before they flick measured.
hot plate test. heat it up at a constant rate and measure time for reaction.

2 studies scored it above morphine. 1 an 1/8th of the strength.

[starshine]

very interesting. thank you for sharing.

I was thinking you should edit this part. we know that not all reds are bents. this could be misleading to a new person.

Reds, which are all essentially bentuangie (dried in plastic bags in the sun)

I appreciate the vendors who take the time to share studies and their own personal knowledge. thanks again!

[7ohm]

I assume everybody's individual sweet spot would have to be obtained through trial and error, basically a controlled scientific study with one's self that repeats every time we purchase a new strain from a new vendor (or even a new strain from the same vendor). Perhaps McCurdy or somebody else will someday find out that magical equation of total mitragynine needed to obtain a specific effect. Then when we buy from those vendors that post the total amount of mit in their product, it would take out all the guess work and we would know exactly how much to take, even the first time we use that strain. I mean if we are substituting or even replacing other medications with Kratom why not be as specific with dosage right? It's times like these I wish I was gifted enough to figure this out on my own and pass that info on.

Great post nonetheless, I really appreciate learning more about the science of this!

I think it's going to vary by individual. The sweet spot will change for every Mit % and dosage. I have a bali, that people are finding to have a stronger 7ohm effect. I had a customer return that same exact strain saying he got no 7ohm effect and wobbles.

1.6% seems to come up a lot when talking about good leaf. at 10 grams of it would be 160 miligrams of mit, which is a shit ton. I would be inclined to take half or less. 3-9% was the estimate by mccurdy et al. If we just take another average of 5%, then we're talking about 8 milligrams of 7ohm at 5 grams of leaf. That dose with morphine would be unsustainable. Some people report no tolerance and have been taking the same amount for years. I think more needs to be researched about the w/d, rebound and tolerance.

shots have roughly 200 miligrams, and 45% extract has 450 miligrams in a gram. If we assume 80 mgs of mit from above, to be a good dose, these are way too high. This would explain why there's no 7ohm effect from extract. I can't get 7ohm effect no matter how little i take. It's weird.

[7ohm]

very interesting. thank you for sharing.

I was thinking you should edit this part. we know that not all reds are bents. this could be misleading to a new person.

Reds, which are all essentially bentuangie (dried in plastic bags in the sun)

I appreciate the vendors who take the time to share studies and their own personal knowledge. thanks again!

I honestly don't know of anyone making reds without shoving it in a bag. It creates this weird red color. leaf dried in the open sun comes out brown. It seems that indonesians are more enamored by the color than effects, for obvious reasons. I do know of a processor allegedly drying it in ovens now. I think there's something inherently flawed about bentuangie. Mold exists in like at least 50% of batches.

There was a study that dried leaf in diff ways. Fresh leaf had the most, shade dried, sun dried and oven dried, in that order. In plastic bags was not one of them. I don't even know where it came from. The fermentaton process is not even possible here. I imagine they were treating it like tea and seeing if they could ferment it. there might be somehting about the heat from the oven that helps oxidation to 7ohm.

[oftheshire]

So does everyone get such opposite burns from each other when it comes to specific strains because of that?
I.e someone who takes ten gram doses uses a strain with a high percentage and says they don’t get any effects while someone who takes 4 gram doses says they get great affects from that same strain.
But when the person who takes larger doses uses a strain with a smaller percentage, they get great effects
While the person who takes smaller doses, when taking that smaller percentage strain, will not get good effects ?

[7ohm]

So does everyone get such opposite burns from each other when it comes to specific strains because of that?
I.e someone who takes ten gram doses uses a strain with a high percentage and says they don’t get any effects while someone who takes 4 gram doses says they get great affects from that same strain.
But when the person who takes larger doses uses a strain with a smaller percentage, they get great effects
While the person who takes smaller doses, when taking that smaller percentage strain, will not get good effects ?

That's my guess. High mit strains are very dose dependent, eg if we have leaf that's a 2.1 ( that would for sure block 7ohm for me) and we normally take 2 grams, compared to someone who takes 4 grams or more ( my dose). I would imagine it's going to be opioid for one but not the other. At 5-6 grams i would guess certain wobbles.

People report such varying effects, you can't really explain it otherwise. You swear that it's tolerance, or personal body chemistry, and then you take more. But, if you think about it, you'd have to be taking enormous amounts at extremely close intervals to build tolerance to 7ohm to a point where there's zero effect like people report. Just becasue it acts like an opiate doesn't mean it has the same side effects like tolerance. Think about how someone is able to take 180 mgs of morphine. That could never happen with Kratom. some people call it a shortcoming, some say that's what's so miraculous about it. It has a governor on mor activiy, and it's g protein. DISLAIMER; that doesn't mean it's not addicting. people can get addicted to picking their nose. sex. masturbating. coffee. just be well informed when making the decision. I can't emphasize this enough. It is addicting to 20% of users according to this survey. Something you should def be aware of if you're that kind of person. I would set a specific schedule of dosing and keep track of exactly how much you're consuming. It isn't completely abuse proof. I'm sure there are a lot of would be abusers who were turned away from kratom because they used it improperly. I'm super paranoid about getting accused of teaching people how to get more opioid effect. I'm advocating that you take less, actually. But, is that good or bad?

People say they get no effect from extract. But, it's not that it's no effect, it's no 7ohm effect, and that's what we're expecting so we don't notice the others. The entourage effect is probably mostly from mit and 7ohm. The other alkaloids probably contribute to opioid effect somewhat too, i'm sure.. They may actually affect the enzyme production and/or metabolism which looks like it could affect your burn. There are a lot of physiological effects from the other alkaloids. There's immunoboost, lowers choleterol, lowers blood pressure, anti viral, anti fungal, etc...

When strains are perceived as jittery, or too fast, it could be that you are withdrawing from 7ohm slightly. It's not necessarily full blown opioid withdrawal because the mit induces the adrenergic receptor, but it could be something. If coffee makes you jittery, then kratom also will. Large amounts of it would be just like strong coffee. meds like clonidine help physical symptoms, but I don't think they eliminate them completely.

What's hard to distinguish is the mit effects except at high doses. The 7ohm are obvious to me. But there's never 7ohm without mit, where high doses will be predominantly mit et al without 7ohm. When we feel w/d it's prob from the 7ohm for obvious reasons. Even though w/d, tol, side effects do exist, compared to beta arrestin signalling like opiates, gprotein receptor signalling is a walk in the park. It's interesting to note that other receptors that recruit beta arrestin experience the same crazy side effects and tolerance like benzos and the gaba receptor.

Wobbles seem to be a phenemenon experienced by almost everyone providing more evidence to the theory that g protein signalling does not build tolerance. Mit also uses g protein signalling. while there is rebound with the neurotransmitters like serotonin and dopamine, it doesn't appear to be that significant. Depression, mood swings and lack of motivation have been reported during w/d, but later dissipate.

for those that don't know: an opiate is derived specifically from the opium plant, while an opioid (broad def) is anything that is active on one of the many opioid receptors in the brain and body. All opiates are opioids but not all opioids are opiates.

There are several types of proteins used to signal (instructions) receptors in your brain. The 2 of interest are beta arrestin and g protein. beta arrestin is the cause of the crazy opioid epidemic we're experiencing. someone overdoses every 10 minutes in the US. Since covid it most likely has increased significantly. beta arrestin is the reason why there's so many side effects like tolerance, w/d, respirtory depression. What if they knew about kratom? Then wouldn't it be a good thing that it's addictive? The best cure for addiction inarguably is addiction. Suboxone/methadone is the gold standard in treatment right now. Nothing else is working. 70k deaths a year in the US. That's like the vietnam war every year.

Interestingly, the kappa is associated with ltos of dopamine and serotoninn activity, along with psychedelic experiences like with ketamine, which has been shown to make new neural connections in the brain. it has been a breakthrough for treatment resistant depression. Ketamine is an amazing drug, in fact (im not promoting it, kinda). Terrible on your bladder though with a fair amount of addiction and abuse potential. Ketamine uses g protein signalling, which would explain it's amazing safety profile. It's the number one used opioid in the world for this reason. You don't need to be intubated during surgery as it doesn't cause respiratory depression. It's used a lot in veterninary medicince, eldelry, children. It is elemental in rural medicine in developing countries and probably the most ubiquitos med next to penicillin. It is supposedly notoriously hard to synthesize, and the recipe is a closely guarded secret,

Damn, i need to chill on these tangents. i swear im getting carpo tunnel.

[oftheshire]

Dang these are all really interesting points. Definitely gonna have to start a thread at some point where people can write about a strain, its percentage, the individuals normal dose size, etc. Then people who have also taken the same batch of whatever strain can write their experience and dose size. Then we can see if strains effects commonly follow the amount/percentage combo theory

[MagPie]

Great idea! I'm still having some trouble...this would really help.

[IjustFeltLikeRunnin’]

Great idea! I'm still having some trouble...this would really help.

I agree!

All this new information makes me want to reevaluate visiting “faster strains” again. My initial response to them was to experience nothing but awful headaches. But now I’m thinking that, dose dependent, I may be missing out on some real gems.

It’s also kinda nerve wracking as well trying out new stuff. With the constant fear of just experiencing a bad burn and giving up on it right off the bat. But according to this information, the trick is just finding the sweet spot on each and every strain. If somebody has already done that, and we have an idea based on size and dose, we (in theory) would just have to tweak for our own size.

I liked the idea I read in another thread, of somebody saying to write the dose on the bag that gave you the desired effects. Or keep a journal of doses, blends, etc. We always think that we’re going to remember, but by the time we’ve finished our rotation and come back to it, it’s like we’re starting from scratch.

All in all, it still boils down to every person’s own reasons for using Kratom, as well as each individual’s expectations of the “feelings” they want from it.

But still....it’s a start.

[fusedflora]

There's something more to it for sure. Something needs to explain why there's no 7ohm effect with extract. it's missing something. or, something.

I agree, I think there's so much missing. I want to say thanks for sharing this, it's nice to see others trying to study and have great discussions about it, you've identified a lot of things I need to look further into.

Interesting the wobbles phenomenon. I wonder if it's the naloxone doing similar thing as mit.

I couldn't even find much on indoxyl. What is it, another metabolite?

i think cyp enzymes play a huge role. there's a lot of complicated, paradoxical effects going on. its found in the stomach, and intestines too. There's someting in plain leaf that's not in extract that allows for more opioid effect. Or, thats how it seems anyway.

yes, indoxyl is a metabolite. There's very few articles and data about it, but they're around if you look. Those two I posted are pretty good, when I get some time, I'll post a lot of the others so you can check it out.

The other thing, is that interests me is that opioid receptors are not only in the brain, but in the gut as well.
https://pubmed.ncbi.nlm.nih.gov/26702845/

Short, perhaps the amounts of alks absorbed in the gastrointestinal tract are just as important to or more so than the liver. There's little study in this as well. So maybe the oxidation allows for it to broken down before hitting the intestines, leaving the non-oxidized to be broken down some in stomach and into liver and some into the intestines to activate those receptors. This could be the case, perhaps explaining why we typically don't feel the warming sensations with reds that we do with greens. Perhaps this further explains why caps feel different even with the same strain, allowing for processing further down than just the stomach. There's so many gaps in knowledge at this point... I fell like when I find something out, there's like 2-3 other branches now of understanding another function on krater's effects.

Again, I really appreciate the time you put into this and the responses.

[starshine]

There's so many gaps in knowledge at this point... I fell like when I find something out, there's like 2-3 other branches now of understanding another function on krater's effects.

Again, I really appreciate the time you put into this...

oh my gosh. agreed. I've been obsessed with the science recently and it's definitely going down the rabbit hole lol. I really appreciate both of you. I've learned so much from your generous contributions and taking precious time to share. thank you thank you.

I've been thinking about starting a mewe group to share and discuss the science of kratom. I'm only a couple of years in, but probably 10 years of researching and learning crammed in there lol. I'm no expert whatsoever. not even close. I don't hold a candle to you guys. but if we had a space to combine our discoveries and talk about them, I think that would be beyond amazing. if you and Steve, and other science enthusiasts, could drop in now and then to share discoveries, I think a dedicated platform like that has the potential to be priceless. at least to me

[MagPie]

Thanks for all this info!! I keep rereading it...lol. I'd rather come here daily and hope for new info than anywhere else.

[7ohm]

There's so many gaps in knowledge at this point... I fell like when I find something out, there's like 2-3 other branches now of understanding another function on krater's effects.

Again, I really appreciate the time you put into this...

oh my gosh. agreed. I've been obsessed with the science recently and it's definitely going down the rabbit hole lol. I really appreciate both of you. I've learned so much from your generous contributions and taking precious time to share. thank you thank you.

I've been thinking about starting a mewe group to share and discuss the science of kratom. I'm only a couple of years in, but probably 10 years of researching and learning crammed in there lol. I'm no expert whatsoever. not even close. I don't hold a candle to you guys. but if we had a space to combine our discoveries and talk about them, I think that would be beyond amazing. if you and Steve, and other science enthusiasts, could drop in now and then to share discoveries, I think a dedicated platform like that has the potential to be priceless. at least to me

I"ve actually started one on reddit, but again samer story. Pelple want to tak about the voodoo magic of strains.

[oftheshire]

“This could be the case, perhaps explaining why we typically don't feel the warming sensations with reds that we do with greens. Perhaps this further explains why caps feel different even with the same strain, allowing for processing further down than just the stomach. There's so many gaps in knowledge at this point... I fell like when I find something out, there's like 2-3 other branches now of understanding another function on krater's effects.”

I’m really interested in this and the point on capsules. I used to mix different strains in different types of capsules and take them all at once. My theory was that since they were diff types of capsules, they would break down at slightly different times. I preferred this method for a while because it seemed to make for a longer, cleaner burn. The usual chug seemed to be a bit stronger but shorter.

[7ohm]

There's so many gaps in knowledge at this point... I fell like when I find something out, there's like 2-3 other branches now of understanding another function on krater's effects.

Again, I really appreciate the time you put into this...

oh my gosh. agreed. I've been obsessed with the science recently and it's definitely going down the rabbit hole lol. I really appreciate both of you. I've learned so much from your generous contributions and taking precious time to share. thank you thank you.

I've been thinking about starting a mewe group to share and discuss the science of kratom. I'm only a couple of years in, but probably 10 years of researching and learning crammed in there lol. I'm no expert whatsoever. not even close. I don't hold a candle to you guys. but if we had a space to combine our discoveries and talk about them, I think that would be beyond amazing. if you and Steve, and other science enthusiasts, could drop in now and then to share discoveries, I think a dedicated platform like that has the potential to be priceless. at least to me

that's awesome. great minds think alike. I"ve actually started one on reddit, but again same story. people want to talk about the voodoo magic of strains. My MO is to educate. so people can better understand how to use it and get better results, less adverse reactions, mainly death. to be evern more ambitious i would like to start a treatment facility using kratom, kava, and kanna in different formulations of course. It's a big undertaking and i won't have a lot of money at first as i have to invest everything back into infrastructure. i would also like to hold evernts where we have fun, listen to music, listen to speakers of success stories, and of coarse give free kratom. If you're interested in admining, contributing, moderating, helping me spearhead this im all for it. It would be a combo of business operations and growth strategy or admining that group we shoudl talk. Same wioth anyone who has that kind of motivations. i ahve now shortage of ideas (hallucinations, whatver you want to call them) I also have 2 great admins that would be very helpful and are team players.

If anhyone is interested in collaborating (not necessarily in seatlle, hit me up with some ideas on how you can help,

[7ohm]

There's so many gaps in knowledge at this point... I fell like when I find something out, there's like 2-3 other branches now of understanding another function on krater's effects.

Again, I really appreciate the time you put into this...

oh my gosh. agreed. I've been obsessed with the science recently and it's definitely going down the rabbit hole lol. I really appreciate both of you. I've learned so much from your generous contributions and taking precious time to share. thank you thank you.

I've been thinking about starting a mewe group to share and discuss the science of kratom. I'm only a couple of years in, but probably 10 years of researching and learning crammed in there lol. I'm no expert whatsoever. not even close. I don't hold a candle to you guys. but if we had a space to combine our discoveries and talk about them, I think that would be beyond amazing. if you and Steve, and other science enthusiasts, could drop in now and then to share discoveries, I think a dedicated platform like that has the potential to be priceless. at least to me

that's awesome. great minds think alike.

[7ohm]

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.

gundaman is the one who conducted the survey, the largest one of it's kind.

the others were done a while ago in thailand and malaysia where they take it the same way.

They boil it quick, like seconds, then take the leaf out and use the water/tea that they keep with them all day and drink. I can't help but to wonder if maybe more boiing could yield more oxidation.

[7ohm]

There's so many gaps in knowledge at this point... I fell like when I find something out, there's like 2-3 other branches now of understanding another function on krater's effects.

Again, I really appreciate the time you put into this...

oh my gosh. agreed. I've been obsessed with the science recently and it's definitely going down the rabbit hole lol. I really appreciate both of you. I've learned so much from your generous contributions and taking precious time to share. thank you thank you.

I've been thinking about starting a mewe group to share and discuss the science of kratom. I'm only a couple of years in, but probably 10 years of researching and learning crammed in there lol. I'm no expert whatsoever. not even close. I don't hold a candle to you guys. but if we had a space to combine our discoveries and talk about them, I think that would be beyond amazing. if you and Steve, and other science enthusiasts, could drop in now and then to share discoveries, I think a dedicated platform like that has the potential to be priceless. at least to me

That would be awesome to have somewhere to discuss the science. Not easy finding that audience though.

[BallzDeep9]

That would be awesome to have somewhere to discuss the science. Not easy finding that audience though .... great minds think alike. I"ve actually started one on Reddit, but again same story. people want to talk about the voodoo magic of strains. My MO is to educate. so people can better understand how to use it and get better results, less adverse reactions, mainly death. to be even more ambitious i would like to start a treatment facility using kratom, kava, and kanna in different formulations of course.

Right now, this place right here! MM - is the best platform currently available. . Chat rooms are not a place for serious discussion, where you could Save or Search on things... sadly, we had some great folks on MeWe back in 2018. Some really good, vendors and suppliers. Harry from KOG, several Indo guys, even a USA expat living in Aceh Sumatra... All aspects of the business were discussed... then poof. All gone! You can't archive Search on MeWe, its like FB groups. can't have Topics like MM. All one rolling Chat...

the Group got invaded by casual folks and noobs, posting jokes and gif's and going off topic. Finally most left, Mewe broke up into little Vendor chat rooms. . Reddit is good because its got Topics, and Archive Search function. But you'd have the same problem with casuals and trolls, like everywhere else online... Reddit does have Private groups? But like Steve says, too much talk about "strains" and poop.

Science is always interesting. I'm a consumer of research, not a scientist lol.. My background is Marketing. Right now imo there's a real need for new thinking, new strategies... Where is kratom going in 2021 ?? I had a kind of flash revelation last week, then got into another "opioid" debate... There is a crossover of science and marketing. So, on ONE hand... the AKA says: Kratom is NOT a drug. It's a dietary supplement. Right? That's what they say, but... All of the AKA vendors, are "selling drugs" in gas stations. It's all these OPMS "shots" and Legal High crapola. That's the history going back to "bath salts", some of the same people and Drug Labs go back a decade.

Now, the opioid label on kratom hasn't gone away, thanks to Trump's guy Scott Gottlieb FDA... even though the science says otherwise! . And I was waiting for Dr. McCurdy to speak out more clearly on the chemistry, and what the past 5 Years of research has shown us on kratom's safety profile? So I guess we assume there's some politics (of course) and the usual Big Pharma money at work... it's gotten to the point where Wikipedia only quotes FDA and Gottlieb, and the NEW revised, Merriam Webster dictionary has now changed their definition of "opioid" to include natural compounds. QUOTE

Note: The word opioid was originally used only for morphine-like substances not derived from opium, but it has now become widely accepted as a broader term encompassing any substance—natural or synthetic, opium-derived or not—that binds to opiate cell receptors and induces sedation, analgesia, and euphoria. https://www.merriam-webster.com/dictionary/opioid

[starshine]

That would be awesome to have somewhere to discuss the science. Not easy finding that audience though .... great minds think alike. I"ve actually started one on Reddit, but again same story. people want to talk about the voodoo magic of strains. My MO is to educate. so people can better understand how to use it and get better results, less adverse reactions, mainly death. to be even more ambitious i would like to start a treatment facility using kratom, kava, and kanna in different formulations of course.

yea... the audience likely isn't as big as it should be. too many people only care about instant gratification and not the how or why. b u t for those of us who are fascinated by the science, even a small group of us would undoubtedly benefit from the discussion. there would surely be an even larger population of lurkers who would also benefit.

for me, the fact that kratom provides quality of life in place of pharma meds, that offered only terrible side effects and little efficacy, is a big part of the reason it's important to me to learn all I can about this amazing, lifesaving, plant. it is the only medicine I take. for me, kratom greatly reduces what is otherwise excruciating, 24/7, full-body pain, (even blessed moments of zero pain), debilitating fatigue is eliminated, crushing anxiety is now a distant memory, and there is light where there once was soul-devouring darkness. and all of this from one, beautiful, plant? yes. I also like learning because it provides me with better knowledge to be able to, accurately, educate and help others. I was already 3 1/2 years sober when I discovered kratom. oh how helpful that would have been! but the potential for kratom to obliterate the opiate epidemic (and other addictions) is glaringly obvious. at least to me.

Right now, this place right here! MM - is the best platform currently available. . Chat rooms are not a place for serious discussion, where you could Save or Search on things... sadly, we had some great folks on MeWe back in 2018. Some really good, vendors and suppliers. Harry from KOG, several Indo guys, even a USA expat living in Aceh Sumatra... All aspects of the business were discussed... then poof. All gone! You can't archive Search on MeWe, its like FB groups. can't have Topics like MM. All one rolling Chat...

good point. I'm relatively new to mewe since migrating over there to connect with the best vendors but, you're right, there is no search function. which is a necessity. I also think you're right about double m possibly being the best platform. I wonder if there would be enough interest to allow for it's own forum link? the good stuff tends to get lost/buried by new posts. a dedicated space for it would be awesome.

[Fallguy]

So is chocolate now an opioid?

[GrannyJ62]

Theory:
All effects from Kratom come from varying the level of one alkaloid: Mitragynine. So, you should be able to get every effect from every strain simply by adjusting your dosage. Every strain is essentially just a different level of mit.

How do We Know That?
Some researchers did a study of a handful of "strains" from various vendors and tested them. They found that there was no significant difference in the level of 7ohm across strains. Believing that there was inaccurate sampling because "strains" are actually just blends, I did my own study looking at various strains and drying methods from several vendors.

Here's what I found:
No significant difference in levels of 7ohm across all drying methods and strains. There was the random strain with higher levels of 7ohm. McCurdy et al. thought that it was adulteration. however, I think that it's safe to say that it's not a legitimate concern in our industry. The only notable difference was in the level of Mitragynine. The other alkaloids don't really have Psychoactive effects, and they are found in such small amounts for it to conceivably make a difference. There have been limited studies on the other alkaloids with the exception of the anti-inflammatory Mitraphylline, which is also found in cats claw and has shown much promise in treating cancerous tumors much like CBD. leaf actually also contains a flavenoid called epicatechin found in tea, which is also effective against cancer. Reds, which are all essentially bentuangie (dried in plastic bags in the sun), simply have low levels presumably from the oxidizing effects of the sun. I found that pure bents had levels as low as .3%. Indoor dried leaf was as high as 2.3%. this would explain why a lot of reds are perceived as "weak". They really are and they don't have this corresponding increase in 7ohm. In fact, you are simply getting an "inferior' product which has less alkaloids.

Here's what we used to think:
1)The sun caused photooxidation to occur inside the plant leaf converting the Mitragynine into 7ohm through the reaction of phytochemicals and sunlight.
Why did we think that?
the chemical compound 7ohm is reddish in color. oxidation turns leaf red/brown. reds have a different effect (allegedly more opioid).
A study showed that the conversion took place easily inside of a petri dish just by exposing the solution to sunlight.

2)Kratom is similar to other medicinal plant chems, like cannabinoids, which have psychoactive effects that contribute to the entourage effect from synergy of multiple compounds.
Why did we think that?
Because there seems to be so many different effects from kratom, a logical explanation would be that it's not unlike Cannabis.

Here's what we recently discovered through research (Mainly CNS receptor panel from McCurdy et al):
It validated what we had suspected all along, but this one study measured (quantified) the affinities to which Mitragynine binds to various receptors in a rats brain and either agonizes or inhibits.

Mitragynine seems to be single handedly responsible for all of the other psychoactive effects of Kratom minus the opioid effect:
1) stimulation through adenosine receptore antagonism like caffeine. adenosine causes and regulates sleep. without it, you get anti-sleep aka caffeine buzz. It' s noteworthy that you can only inhibit this receptor so much, ie there's a ceiling on effects just like coffee. You can only have zero adenosine production as the max inhibition. You can't have negative chemicals in the brain.
2) mood
it is serotonergic, ie it causes your brain to release more serotonin. It is an agonist at this receptor.
3) motivation/elation
dopaminergic,
4) adrenergic
the a2 receptor agonism is how clonidine works to prevent opiate w/d. unfortunately, it is also a known contributor to erectile dysfunction. interesting to note yohimbine, the chemical cousin of mitragynine (structural similarity), is an antagonist. this is presumably why it is so helpful with opioid withdrawal (aside from the obvious mu opioid agonism).

Very important new finding:
Mitragynine at high concentrations blocks uptatke and effects of all opioids including heroin and morphine. Rats with high concentrations of mit, showed no mor effects at all. The hot plate test, the tail flick test, preference to the site of admin (they don't come back for more) all tested at baseline, ie it was the same as when sober.
Mitragynine is also a cyp3a4 inhibitor. So, there appears to be a scientific explanation for 2 clear cut effects of Kratom that trade off depending on dosage:
mitragynine
7ohm

All strains (varied level of MG) fall somewhere in the middle. Reds have little blocking and reported Wobbles presumably because of it's lower levels. there appears to be this precarious balance between max opioid effect and opioid blocking.

If you take too much, you are not going to feel the effects of 7ohm. Instead, you will feel wobbles, stim, mood, etc. This can phenomenon can be seen in extract, as well as certain "strains'" (presumably indoor dried, which minimized oxidation of Mitragynine causing higher concentrations).

What this means: Dosing is Key

There's a sweet spot for every strain. Taking the same dose for every strain and for every effect is a mistake. Strains do not have any specific properties that would vary effects except the concentration of Mitragynine. For more stim, take more. There is a threshold of Mitragynine, where it stops the conversion of 7ohm, and even stops all opioid effects. Lower levels/concentrations (like with reds) seem to allow for more opioid effect all the way up until this threshold is reached. Smaller doses allow for less opioid blocking and more production of said enzyme.

Here's what I think now:
Wobbles are caused by Mitragynine

why?
there are no opioid effects when you have the wobbles.
there is a study that calls Mitragynine the great Neuromuscular blockade. they took a leg off of a rats cadaver and hooked up an electrode to the nerve to make the leg twitch. When they gave the leg enough Mitragynine they were able to get it to stop twitching. the idea is that it slows/stops nerve communication to a level where the muscles in your eyes and other parts of your body stop responding. it physically blocks nerve communications. EDIT: I should mention this is why it's assumed to be so helpful with fibromyalgia. There's 2 components, analgesia and complete relaxation of the nerves and therefore muscles. Think about what happens to your eyes. One could describe it as unresponsive, or relaxed. Some of the muscle relaxing properties are probably from this phenomenon on a lesser level. It seems to affect motor skills as well. Even your upper body, and your arms get like paralyzed to some degree. It feels like you can't use your hands very well. I would say it's best not to drive on it. I've wrecked my car a couple of times. tangent.

All of the effects seem to be a result of the one alkaloid Mitragynine, which in turn converts to 7ohm from oxidization inside of our bodies specifically from the cytochrome enzyme cyp3a4. So, it's not the leaf that makes a difference, it's us and how much we take. To make things more complicated, the liver has the most of this enzyme and is also responsible for metabolizing drugs from our system. So, as mitragynine is cleared out of our bloodstream, some of it (estimated 6% by recent study) is being converted to 7ohm and being put back into our bloodstream. Then, as this enzyme is used up for the conversion, or inhibited by Mitragynine, it slows the rate at which drugs are removed from the body. This means that drugs will stay inside your system for a longer time, and possibly build. Most opiate potentiators, like grapefruit juice are cyp3a4 inhibitors. St John's wort is an example of an inducer. It makes sense to me that if you want more opioid effect that you would want more of that enxzyme. EDIT: it would also explain why wobbles last for so long sometimes. I feel like i've had it 2 days in a row. Each time seems easier to get. I feel like I"m wDing and take just a little bit hoping for just a hair of relief from the jitters, and boom. here it is again. your friend the wobbles. tangent

There seem to be a lot of different effects from Kratom. So, naturally it's believable that there are different types, or "strains". It's not like the Cannabis Industry where there has been extensive and complex breeding practices which effect the complex chemical profiles and vary by genetic varietal: phenotypes. We know that Indonesians are not growing different strains of the leaf. It's not that they don't exist, but moot since they are not differentiating it. Even if there were different strains, the only compound that seems to matter is the one.

7ohm is the opioid alkaloid and it's created by our bodies (converted through oxidation from cyp enzymes). Researchers have scored it on par with Morphine in it's Mu Opioid value (some as strong as 14 times the value).

What's the significance of Mu Opioid recpetor?
We don't know. We do know that it's the same receptor that opiates like morphine and heroin hit and seems to be responsible for the perception of sedation, analgesia, and euphoria.

BOTTOM LINE: All effects from Kratom are dependent on the dose of this one alkaloid. If you're not feeling the opioid effects, you could be taking too much and blocking it. At this point, it should be obvious (eye problems, stim, no opioid effect). Then, because you don't feel it, you chalk it up to tolerance and take even more. Leaf is complicated, but in more ways than can be explained by the strain/vein color paradigm. Asians don't have problems wtih addiction becasuse a) mitragynine is not addicting (rats don't come back for more) b) they take larger doses than we do. In fact, the main reason they use it is for it's stimulating properties. Chris McCurdy, the leading expert, surmised that addiction was due to "inferior" product, or leaf that has lower concentrations of Mitragynine. It is interesting to note that the Thai/malaysians do not have bentuangie (red). Americans, on the other hand are experiencing w/d, addiction, etc...The main reason we take it is for the Opioid effect according to the largest survey in history. So, it may be the case that you need to take less for more opioid effect and more for stim. This indicates that there is probably a sweet spot for every strain and what that it depends on what the concentration of Mitragynine is in the leaf, eg you can take a lot of a red before wobbles. to get more effect, take more up until you start getting the effect blocked, at which point it will be more stim (mitragnine effect). At a particular set dose, you can categorize "strains" as being fast or slow. or, you can just adjust your dosage. Theoretically, it should all have the same effect.

The 2 faces of Kratom: Mitragynine and 7ohm. These appear to be the main 2 that synergize. Stimulant and Opioid.

EDIT: make no mistake about it, kratom has addiction potential despite having this limiting factor. In fact, it happens quite a bit, although it def makes it harder to abuse, I think. There's this miraculous, natural regulating effect of Mitragynine that prevents overdose on 7ohm. What a combo, right? I hear a lot of people claim that they stopped using because it stopped having opioid effect on them. According to science, tolerance shouldn't build like it does with opiates.

Let me clarify:
I think it has something to do with the concentration of the dose. one phenomenon that I can't explain is why I can't get 7ohm effects from 45% extract. Others claim no effect. Taking higher concentrations like extract might actually lower your tolerance to 7ohm. Mitragynine's fast absorbtion rate might be a factor. It's possible that you may have to slow it down to allow for conversion to 7ohm.

The latest survey of Americans from Johns hopkins found kratom addiction happens to 1 in 5 users. 20% is no joke. Keep in mind that this is self reported and denial happens to be a symptom of addiction making the results slightly skewed. At some point I think that it's possible get to a habit of use despite harmful consequences. i know a lot of people that would argue that there are no harmful consequences, ie no side effects, so no such thing as addiction. Or, addiction to the level of say a cup of coffee. But, it's apparent now, that the prevalence of addiction here is twice as high as it was in thailand. There are cases of severe, opiate like withdrawal in the US, where it occurs relatively infrequently.

If you want to quit, and it causes you stress. Then, one could argue that is addiction, since that is a negative consequence. If you don't want to quit because it doesn't cause you harm, then you're cool. That's healthy use. It doesn't matter why you use it. It's your right. Just because it's natural doesn't mean it's not harmful, though. Opium is natural, so is tobacco. You should treat it like any drug when deciding to use it. the fda approves drugs all the time that kill people because it expects that you and/or your doctor are weighing the costs and benefits. if it makes sense do it. but, make an informed decision. weigh the potential costs and benefits, do some due diligence. it's your health for christ sake. Don't listen to some rando's opinion.

Kratom is a drug, just like Alcohol, Cannabis, Tobacco, Coffee. It does have abuse and addiction potential. Anything when abused can be harmful, natural or not. Saying that it's not addicting or not harmful is irresponsible. Let's be realistic about the potential risks and incorporate that in our decision making process. Ignoring the dangers could result in addiction. There is an entire subreddit of people who are pissed cuz they say Kratom ruined their lives r/quittingkratom. It's probably something you at least want to be aware of. There is withdrawal syndrome and the severity depends on how much you use. Some have reported it to be as bad as opiates while some have reported none at all. There has been one death in the US where Kratom was the only substance found and was deemed to be the cause of death. The history of abuse in the US has been unremarkable. It is interesting to note that treatment centers are now offering services for Kratom addiction.

Thank you for all this information legendary thread.Boom there it is.

[GrannyJ62]

That would be awesome to have somewhere to discuss the science. Not easy finding that audience though .... great minds think alike. I"ve actually started one on Reddit, but again same story. people want to talk about the voodoo magic of strains. My MO is to educate. so people can better understand how to use it and get better results, less adverse reactions, mainly death. to be even more ambitious i would like to start a treatment facility using kratom, kava, and kanna in different formulations of course.

Right now, this place right here! MM - is the best platform currently available. . Chat rooms are not a place for serious discussion, where you could Save or Search on things... sadly, we had some great folks on MeWe back in 2018. Some really good, vendors and suppliers. Harry from KOG, several Indo guys, even a USA expat living in Aceh Sumatra... All aspects of the business were discussed... then poof. All gone! You can't archive Search on MeWe, its like FB groups. can't have Topics like MM. All one rolling Chat...

the Group got invaded by casual folks and noobs, posting jokes and gif's and going off topic. Finally most left, Mewe broke up into little Vendor chat rooms. . Reddit is good because its got Topics, and Archive Search function. But you'd have the same problem with casuals and trolls, like everywhere else online... Reddit does have Private groups? But like Steve says, too much talk about "strains" and poop.

Science is always interesting. I'm a consumer of research, not a scientist lol.. My background is Marketing. Right now imo there's a real need for new thinking, new strategies... Where is kratom going in 2021 ?? I had a kind of flash revelation last week, then got into another "opioid" debate... There is a crossover of science and marketing. So, on ONE hand... the AKA says: Kratom is NOT a drug. It's a dietary supplement. Right? That's what they say, but... All of the AKA vendors, are "selling drugs" in gas stations. It's all these OPMS "shots" and Legal High crapola. That's the history going back to "bath salts", some of the same people and Drug Labs go back a decade.

Now, the opioid label on kratom hasn't gone away, thanks to Trump's guy Scott Gottlieb FDA... even though the science says otherwise! . And I was waiting for Dr. McCurdy to speak out more clearly on the chemistry, and what the past 5 Years of research has shown us on kratom's safety profile? So I guess we assume there's some politics (of course) and the usual Big Pharma money at work... it's gotten to the point where Wikipedia only quotes FDA and Gottlieb, and the NEW revised, Merriam Webster dictionary has now changed their definition of "opioid" to include natural compounds. QUOTE

Note: The word opioid was originally used only for morphine-like substances not derived from opium, but it has now become widely accepted as a broader term encompassing any substance—natural or synthetic, opium-derived or not—that binds to opiate cell receptors and induces sedation, analgesia, and euphoria. https://www.merriam-webster.com/dictionary/opioid

YES I LOVE MM