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mechanism of action for kratom

Pickledlemons

Pickledlemons

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Oct 4, 2017
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Does anybody have any information about what causes the stimulant properties of kratom? I have heard mitragynine/7-hydroxy-mitragynine have an effect on delta opioid receptors at lower doses. But targets mu-opiate receptors at higher doses. Can anybody confirm or deny this? If that was the case, it doesn't make sense to me why some strains are more stimulating than others. But obviously either way, some of the other dozens of alkaloids in the plant must play a part. Just curious how this interesting plant does what it does. With both stimulating and depressant effects.

Thanks.
 
I was under the impression the stimulating effects came from alkaloids binding to alpha2 adrenoreceptors, similar to the activity of yohimbine. Mitragynine is quite closely related, structurally.
 
I'm sure that has some additive affect. But honestly I think most of the stimulation reported by kratom users can be more attributed to its opioid action, much the way moderate doses of hydro/oxycodone give people lots of energy. Most the people who use kratom have little opioid tolerance so they still get strong effects and its hard to take a large enough dose to start "nodding", and they classify the energy obtained from kratom as being stimulating, and this is reinforced by the fact that its very hard to cross the threshold into sedation(unlike with regular opiates, where higher doses become sedating). I don't think anyone would compare kratom to classical stimulants like methylphenidate or amphetamine, at any dose of either. And it doesn't cause anxiety, at any dose or after prolonged usage.
 
Look at how structurally similar yohimbine and mitragynine are:
17qbGbT.png


I actually suspect that the adrenergic affinity of the kratom alkaloids is the reason for the stimulation as well as the different experience at high dose levels. If kratom were a straight up opioid I'd bet you'd be seeing more somnolence/soporific effects at even moderate dose levels - hydrocodone and oxycodone do have a stimulating effect in some people, but it's not as notable as the effect that kratom produces.

Ceratinly it seems to me there must be some other factor counteracting the sedation of mu-opioid receptor binding.

Also, some people do get anxious on kratom, especially those who are suspicious of liver/kidney/other physical toxicity.
 
there are several types of kratom with difference effects. not sure whats the difference in chemistry that makes them so different. for example mang da is super stimulative for me, but borneo or bali cant recall made me sedated without stimulation. so thats something to consider when you buy kratom for what you aim with it, stimulation or sedation
 
Thanks for the info seiko that is very interesting.

And kratom did give me anxiety, after using daily for over a month.
 
pickledlemons which type of kratom were you using? there are several as i mentioned and i have experienced different results from each. now days i avoid it because of severe dangerous interactions with alcohol and pills but back then, that stuff was different and felt differently each type
 
asecin said:
pickledlemons which type of kratom were you using? there are several as i mentioned and i have experienced different results from each. now days i avoid it because of severe dangerous interactions with alcohol and pills but back then, that stuff was different and felt differently each type
Click to expand...

I've used red bali, gold bali, green malay, maeng da and uh... white kalimantan maybe? I cant remember. I ended up mixing all 5 or 6 strains I had together.
 
I get that, and I'm sure the high would be subjectively different without those affects. But I have taken my fair share of kratom and have also tried yohimbine. Yohimbine was an absolutely awful fucking experience, kratom is pleasant, and easy enough to go to sleep on. And at no dosage did I get the jitteriness, paranoia, head ache, palm seating, etc associated with yohimbine and could sleep just fine even at extremely high doses...but people do say the stimulation occurs more at low doses and the opioid effects become more apparent at higher doses, so maybe its opioid action just quickly cancels out its a2a action. But I would be willing to bet if mitragynine had a novel structure and no binding studies had been done to show a2a action then no one would be calling it a stimulant, maybe it would be described as a "more activating" low potency opioid, but IME its stimulant action is exaggerated due to its association with yohimbine. I just chalked its "ceiling" effect up to its unique action on the opioid system such as its delta affinity, partial agonism, and possibly functional selectivity(or whatever is analogous to such an attribute in opioid agonists) not to say it has no a2a action, just in my personal experience the stimulation and energy provided by kratom is more reminiscent of how I used to feel on lower doses of vicadon rather than something like yohimbine or even caffeine.
 
yeah ive done yohimbine and kratom and i cannot connect them at all. im so surprised they have similar chemicals...
 
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