Kratom Kratoms serotonin release values

[Innerpeace]

Last night I dosed five grams green malay, pre-workout, afterwards , a few hours little feeling really good, watched a six main brain chemical cal video and how drugs manipulate these chemicals, and I came across opioid s increase serotonin levels

Me feeling " happier" than normal I did some research and found kratom does in fact increase serotonin levels

I've searched and not came across any studies in how much serotonin is released with kratom. I've even searched prescription opiods like hydrocodone, say 10 mgs to compare sert values as I thought a five gram kratom dose may be equivalent and nothing.

Kratom releases dopamine like opioids as well, which I didn't know either , although not that interested as dopamine replenishes itself fast, generally, and I use hydrafinil
And l Dopa, velvet bean extract, some days and haven't mixed them

Does anyone have any information on kratom and how much serotonin is released with say a five gram dose?

 

[negrogesic]

Well its a sort of yohimbine like indole alkaloid and would be expected to have similar weak agonist and even antagonist action on a variety of serotonin receptors. Would not be expected to be a significant releasing agent of serotonin. May have some weak MAOI effects. I believe it also has some weak dopamine (D2) antagonist properties which perhaps might have a role in the kratom dysphoria that sometimes occurs.

 

[Innerpeace]

I've recently seen some people say coming off of kratom is like coming off of ssris , which could be possible if dose is high every day

I could be wrong but from what I know now, at those that use 3- 8 grams a few times a week max, it seems like it wouldn't be an issue

 

[Xorkoth]

I don't think kratom releases serotonin nor inhibits it reuptake. it may be a serotonin agonist though, I wouldn't be surprised since mitragynine is a heavily modified tryptamine. But serotonin agonism doesn't case withdrawals. However kratom is a delta and mu opioid agonist which obviously causes withdrawals, and also is a stimulant which produces its own sort of withdrawals.

However I could be wrong, I don't think it's fully known all of the ways in which kratom affects receptor sites.

In any case, I have withdrawn from kratom many times and it is pretty much like any other opioid, except worse restlessness and less sickness/flu-like stuff.

From wiki:

Mitragynine acts on a variety of receptors in the CNS, most notably the mu, delta, and kappa opioid receptors.[21] The nature of mitragynines' interaction with opioid receptors has yet to be fully classified with some reports suggesting partial agonist activity at the mu opioid receptor[4][21] and others suggesting full agonist activity.[3] Additionally, mitragynine is known to interact with delta and kappa opioid receptors as well, but these interactions remain ambiguous with some reports indicated mitragynine as a delta and kappa competitive antagonist[21] and others as a full agonist of these receptors.[3] In either case, mitragynine is reported to have lower affinity to delta and kappa receptors compared to mu receptors.[2] Mitragynine is also known to interact with dopamine D2, adenosine, serotonin, and alpha-2 adrenergic receptors, though the significance of these interactions is not fully understood.[21][3] Additionally, several reports of mitragynine pharmacology indicate potential biased agonism activity favoring G protein signaling pathways independent of beta - arrestin recruitment,[21][6][4] a primary component in opioid induced respiratory depression.[21]

 

[Neuroborean]

Don't know about levels, but I can tell you that the first time I withdraw from it I got crippling depression, and it was quite fucked up for a week more or less.
Then the last times I withdraw from it (for t-breaks) I've used BSO which is a serotonin/dopamine modulator, and sometimes 5-htp or l-tryptophan that has helped a lot to stabilize my mood. Normally l-tryptophan or 5-htp don't do anything for me.
For that reason, I'm pretty sure that there's some serotonin involvement with kratom, I also get some spaciness sometimes with high doses and some strains, some spaciness that is very clearly (subjectively) not dopamine, noradrenaline or, I guess, opioid related. That gives some space to think that the sero hypothesis is not far fetched in any way

 

[Snafu in the Void]

Kratom certainly has an effect on increasing serotonin, although I believe it does it in an indirect way. It does not inhibit reuptake, but does ultimately increase the amount of serotonin flowing around in your brain even if there is no immediate increased action of that serotonin. Kratom is indicated in many documented cases of serotonin syndrome, although I believe it does this in a similar way to certain antipsychotics like risperidone. The combination of a drug which directly increases serotonin + a drug that blocks the action of serotonin (antagonist) often leads to serotonin syndrome.

Interestingly antipsychotics like risperidone, which are very potent serotonin antagonists, are paradoxically indicated in both causing and curing serotonin syndrome. Science doesn't really know why.

Personally I developed serotonin syndrome from a combination of things while I was also on kratom. I cut out all other substances other than kratom because I was highly dependent on it. All I was using was kratom in very low doses and it kept getting worse, and worse, and worse. It got to the point where just 500mg of kratom powder would throw me into extreme agitation and other SS symptoms for 8 hours. Resulted in 2 trips to the emergency room. I really can't explain what was going on there, only that if you have a very unbalanced serotonin system kratom makes it a lot worse.

After I recovered, I still use kratom and do not experience that reaction anymore.

 

[Neuroborean]

but does ultimately increase the amount of serotonin flowing around in your brain even if there is no immediate increased action of that serotonin.

What would you say it's the ultimate reason?
I think, (but I'm no expert here) that it's likely that it may increase serotonin levels in certain receptors as a reactive response of being an antagonist on other 5-HT receptors:

"While mitragynine has affinity to dopamine receptors assisting in the alleviation of positive symptoms (auditory, visual, and tactile hallucinations, delusions), it is suggested that mitragynine would also have the ability to reduce negative symptoms (alogia, avolition) through antagonism at serotonin 5-HT2A and 5-HT2C receptors."

Focus: Plant-based Medicine and Pharmacology: The Potential for Kratom as an Antidepressant and Antipsychotic

Mitragyna speciosa, otherwise known as kratom, is a plant in the coffee family (Rubiaceae) native to Southeast Asia and Thailand whose leaves have been shown to cause opioid-like and stimulant responses upon ingestion. The major pharmacologically active ...

www.ncbi.nlm.nih.gov

 

[Snafu in the Void]

What would you say it's the ultimate reason?

100% ashwagandha extract

I had used every drug related into this episode for many years, in combination, with no major ill effect. Ashwagandha was the new factor and at a certain point it became the obvious ultimate cause.

I started using ashwagandha, and after a few months and irresponsible increases in dosage, it triggered a series of neurological changes which eventually became quite extreme and led to me to be hypersensitive to any serotonergic drug at any level.

 

[Neuroborean]

Also, this is the most typical receptor used in anti-psychotics: 5-HT1A
This interesting paper was released not so long ago:

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2021.35.S1.04764

The thing is that it's very typical from long-term kratom users (me included) that some of them end up anhedonic and zombie-ish which is also an usual subjective "side effect" of anti-psychotics...

 

[Neuroborean]

100% ashwagandha extract

I had used every drug related into this episode for many years, in combination, with no major ill effect. Ashwagandha was the new factor and at a certain point it became the obvious ultimate cause.

I started using ashwagandha, and after a few months and irresponsible increases in dosage, it triggered a series of neurological changes which eventually became quite extreme and led to me to be hypersensitive to any serotonergic drug at any level.

nah, but I didn't mean your SS, I meant the fact that serotonin increases in certain parts of the brain, that's why I selected that specific part of your post.

 

[Neuroborean]

100% ashwagandha extract

I had used every drug related into this episode for many years, in combination, with no major ill effect. Ashwagandha was the new factor and at a certain point it became the obvious ultimate cause.

I started using ashwagandha, and after a few months and irresponsible increases in dosage, it triggered a series of neurological changes which eventually became quite extreme and led to me to be hypersensitive to any serotonergic drug at any level.

I have a friend who have that same problem with serotonin drugs, I think people with ADHD tend to have higher than normal sero levels instead of having balanced dopamine/sero levels.
His case is quite extreme since he cannot take almost anything that even slightly raises serotonin, and on the other hand he has horrible RLS which are normally due to low dopamine...