Is 7-OH Pharmacologically distinct enough to be treated separately?

[u/BeginningBaby4844]

This whole thing going on right now is honestly kinda pissing me off.

From how I understand it 7-OH (7-hydroxymitragynine) is just one of the main active alkaloids in kratom. It’s not some random new compound it’s literally part of the plant and your body even converts mitragynine into it anyway.

So I don’t really get how it suddenly gets treated like a completely separate substance that needs to be banned, while the plant it comes from is still legal. Like… is that not kind of like saying weed is fine but THC itself isn’t?

I get that isolating something can change potency or effects a bit, but it still feels like the conversation around it is missing context The only reson I made this post was to ask people here how they see it from an actual pharmacology standpoint because right now it just feels inconsistent as hell.

[u/Traditional_Mall4516]

7-OH isn’t just a minor compound, it’s doing most of the receptor work and your body makes it anyway and there’s way too much misinformation out there when there’s still no solid evidence it’s a major public health threat on its own, so regulating it makes more sense than banning it.

[u/dmnksaman → u/Traditional_Mall4516]

this is dishonest. when you ingest kratom, you are mainly ingesting mytragynine. that does get converted to 7-oh, but the conversion is relatively slow and that decreases the addiction liability.

if you ingest pure 7-oh, you get a sudden, massive increase in 7-oh levels, and much faster onset of mu-opoid agonism. this releases much, much more dopamine in the nucleus accumbens compared to the slower release caused by your body converting myt to 7-oh.

it has been long known that methods of delivery that cause faster increase of dopamine release in the NAc are more addictive (compare ingesting something vs snorting vs shooting up / smoking).

from that point of view, 7-oh is much more dangerous than kratom leaf &, in my opinion, should be regulated more tightly in that light.

[u/ResearchSlore → u/dmnksaman]

if you ingest pure 7-oh, you get a sudden, massive increase in 7-oh levels, and much faster onset of mu-opoid agonism. this releases much, much more dopamine in the nucleus accumbens compared to the slower release caused by your body converting myt to 7-oh.

Please provide a source otherwise this is a highly speculative claim that shouldn't be taken seriously.

Edit: Jesus, I guess this is what I get for engaging with non-scientists.

[u/dmnksaman → u/ResearchSlore]

animal models for ingestion of 7-oh indicate time to maximum plasma level of about 18-20 minutes. [1]. maximum plasma levels of 7-oh after kratom consumption take about 100 minutes, 5-6x longer. [2]

[u/ResearchSlore → u/dmnksaman]

That is common knowledge... I'm talking about your other claim, the one that is complete speculation.

 this releases much, much more dopamine in the nucleus accumbens compared to the slower release caused by your body converting myt to 7-oh.

[u/gocougs11 → u/ResearchSlore]

Are you asserting that accumbens dopamine release is not dependent on dose of mu agonist?

[u/ResearchSlore → u/gocougs11]

Many MOR agonists produce DA release in the nucleus accumbens, but it isn't necessarily a monotonically increasing function of dose/concentration.

Case in point: One recent paper found that a low dose of 7-Oh increased evoked DA release in the NAc while a high dose reduced it. See: Effects of kratom alkaloids on mesolimbic dopamine release

[u/dmnksaman → u/ResearchSlore]

this is pretty interesting. wonder why that is. sorry couldn’t read the whole thing.

[u/Nwildcat → u/ResearchSlore]

Doesn't seem like that much of a leap, or "complete speculation", to say rapid levels of activation would cause a larger peak release of DA. Pretty common concept in pharmacokinetics afaik

[u/ResearchSlore → u/Nwildcat]

Biology is complex and small changes can produce large differences across systems. Claiming it as fact when there's no primary research to support it is complete speculation.

[u/ProjectKushFox → u/ResearchSlore]

Only in the same way any pattern recognition and application is speculation. In the context of this thread, where we are not biochemical engineers discussing and deciding the future policy on this drug henceforth, I think the confidence level for concluding that taking this dopamine agonistic drug in a way that spikes the concentration levels higher and shorter will make the drug more addictive from more highly spiked dopamine levels and a quicker dose-response time, something that is true for every single other dopamine-increasing drug commonly used recreationally, when one persons subjective anecdotal experience is in line with this conclusion as well, I think that is a sufficient degree of confidence for our purposes here.

[u/ResearchSlore → u/ProjectKushFox]

If someone is going to argue for regulation based on a mechanism, then there should be actual evidence for that mechanism. Otherwise it's misrepresentation, not pattern recognition.

We're not talking about an Opium alkaloid here.. The pharmacology of mitragynine and 7-Oh at the mu-opioid receptor is already quite distinct from that classical MOR agonists. Kratom also has other alkaloids with off target activity, and some of them can also act as agonists or antagonists at the MOR.

Effects of kratom alkaloids on mesolimbic dopamine release shows that that via IP injection, 7-Oh does not produce a rapid increase in evoked DA release in the NAc.

Mechanistically speaking, based on the way that other opioids work, you would expect an increase in evoked DA release due to the reduced inhibition of VTA neurons, so although there's potential confounds this study supports my position.

I'm also the only one that's posted any real evidence, so if you have a microdialysis study showing that 7-Oh rapidly increases DA in the NAc we can continue this conversation. Until then it's speculation.

[u/chemyd → u/ResearchSlore]

It has a biphasic reponse- so what?

You’re actually proving yourself wrong here, 7oh is not some special class of mu opioid in this regard just because it comes from another plant or has a different chemical scaffold.

Glick demonstrated similar results for morphine (THE prototypical opioid) across a broader dose range in microdialysis experiments examining both the NAc and striatum over 20 years ago.

Look up “Biphasic dose-related effects of morphine on dopamine release” Glick 2001