7-OH potency in humans relative to morphine?

[TheLightBringer]

Posting this here since I got no response in another thread

from using google it seems as if 7-OH is around 13x more potent than morphine. Seems a bit too high for what people are describing no?
I cant see how it would be 13x stronger when non tolerant users report taking 25mg their first time which would be equivalent to 325mg oral morphine and being fine

Theyre probably quoting this study which stated 7-oh is 13 fold more potent than morphine and 46 fold more potent than mitragynine

Evaluation of the rewarding effects of mitragynine and 7-hydroxymitragynine in an intracranial self-stimulation procedure in male and female rats - PMC

Kratom (Mitragyna speciosa Korth.) has been used in Southeast Asia for hundreds of years to increase energy, for relaxation, and to diminish opioid withdrawal. Kratom use has recently spread to Western countries. Kratom could potentially be used for ...

pmc.ncbi.nlm.nih.gov

However this was done in guinea pigs and with intracranial administration which will not necessarily translate to the same potency in humans


From this study:

7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects - PMC

Mitragyna speciosa, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction. Recently, growing use of the plant in the United ...

pmc.ncbi.nlm.nih.gov

It is stated: ”mitragynine and 7-OH are partial agonists of the human μ-opioid receptor (hMOR) in vitro, with 7-OH (EC50 = 34.5 nM; Emax = 47%) being ∼10-fold more potent than mitragynine”


The EC50 of morphine is between 50 - 100nm according to google
Correct me if Im wrong, I might be unintentionally cherry picking studies but this should in practice mean 0.014093mg 7-OH should activate the μ opioid receptor as much as around 0.014267 - 0.028534mg Morphine? So its really only around 1 - 2x the potency of morphine at the receptor??

Anyone with more knowledge on pharmacology that could come with any insights?

Also curious about subjective experiences since they might tell a bit more ab the relative potency at recreational dosages.
What potency do YOU feel 7-OH has compared to morphine?

 

[Dr. Morphine]

Posting this here since I got no response in another thread

from using google it seems as if 7-OH is around 13x more potent than morphine. Seems a bit too high for what people are describing no?
I cant see how it would be 13x stronger when non tolerant users report taking 25mg their first time which would be equivalent to 325mg oral morphine and being fine

Theyre probably quoting this study which stated 7-oh is 13 fold more potent than morphine and 46 fold more potent than mitragynine

Evaluation of the rewarding effects of mitragynine and 7-hydroxymitragynine in an intracranial self-stimulation procedure in male and female rats - PMC

Kratom (Mitragyna speciosa Korth.) has been used in Southeast Asia for hundreds of years to increase energy, for relaxation, and to diminish opioid withdrawal. Kratom use has recently spread to Western countries. Kratom could potentially be used for ...

pmc.ncbi.nlm.nih.gov

However this was done in guinea pigs and with intracranial administration which will not necessarily translate to the same potency in humans


From this study:

7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects - PMC

Mitragyna speciosa, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction. Recently, growing use of the plant in the United ...

pmc.ncbi.nlm.nih.gov

It is stated: ”mitragynine and 7-OH are partial agonists of the human μ-opioid receptor (hMOR) in vitro, with 7-OH (EC50 = 34.5 nM; Emax = 47%) being ∼10-fold more potent than mitragynine”


The EC50 of morphine is between 50 - 100nm according to google
Correct me if Im wrong, I might be unintentionally cherry picking studies but this should in practice mean 0.014093mg 7-OH should activate the μ opioid receptor as much as around 0.014267 - 0.028534mg Morphine? So its really only around 1 - 2x the potency of morphine at the receptor??

Anyone with more knowledge on pharmacology that could come with any insights?

Also curious about subjective experiences since they might tell a bit more ab the relative potency at recreational dosages.
What potency do YOU feel 7-OH has compared to morphine?

Yet I've not yet come across anyone who would rather have 1 tablet if 7-OH instead of 1 tablet Morphine Sulfate if given the choice. Gee I wonder why.

 

[TheLightBringer]

Yet I've not yet come across anyone who would rather have 1 tablet if 7-OH instead of 1 tablet Morphine Sulfate if given the choice. Gee I wonder why.

Not sure what you mean, I assume we think the same thing though. That even while 7-OH is more potent that morphine its partial agonist properties and short duration of action make for a less euphoric and shorter acting high.

Im just trying to find out its relative potency to morphine, which seems to be 2x on paper if Im not misinterpreting the study

 

[chippermonk]

I can't really judge the comparison very well, but I will say that my handful of experiences with morphine were that it always left me sleepy, numb, and bored. No euphoria. Whereas I recently got some 5 mg 7OH pills, and split one in half for my first try ( I have low tolerance to opioids, though I take either kratom or hydrocodone in low doses on average once or twice a week) My first time with the 7OH, it was a district opioid feeling but kind of so-so. But yesterday I took the other half and it was actually a very nice feeling, euphoric and energizing. More enjoyable than morphine ever was.
But everyone's experience can be different. Isn't that how it often is with drugs? And I will also say that kratom at it's best is very appealing to me, but sometimes it is just a lousy dud, and I'm not even sure why there is such variance. In general, over the last couple months kraton powder has become really crappy for me, though I have not responded by upping my dose. Maybe a higher dose would bring back the fun but I don't want to go there. As for the 7 OH, I don't plan to move on to higher doses with it either. Either it works at low dose , taken once in awhile, or I take a really long tolerance break.
.

 

[DeathIndustrial88]

My response isn't gonna be worth much, but I've always found kratom to be a horrible "opioid" substitute.
I've never once felt what I would describe as genuine opioid euphoria from kratom. I'm more likely to catch a worthwhile euphoria from buprenorphine & bupe has a terrible lack of euphoria in most cases. So I've always questioned why people describe kratom like it's basically a "legal heroin/hydrocodone/tramadol." I hear it described as "like tramadol" so often too, yet I was addicted to tramadol for 11 years & kratom can't even come anywhere close to the level of greatness that a pure tramadol experience gives. People seem addicted to kratom & maybe I'm just a non-responder, but I find it interesting.

The closest thing I get from kratom would be some sedation/feeling like I need to take a nap. But it's not enjoyable at all, it just feels like I'm tired. Not "energizing" in any sense. Tramadol & heroin use to make me get up & clean or exercise because it stimulated me, while simultaneously making me nod/sedated.

So these studies saying it's more potent than morphine are pretty confusing to me too. But my guess is that because it's a partial agonist, it can still be more potent than morphine, while giving awful effects / crappy buzz. Similar to buprenorphine. Bupe is like 30-50x more potent than morphine, more potent than heroin even, yet I don't know many people who would prefer a buprenorphines "high" or pain relief versus heroin or a full agonist.

Kratom seems like an expensive habit too. Unless you're buying plant powder in bulk. And even then, chugging all that plant residue every day can't be great for your stomach. And with how often I'd need to dose it, I think I would be puking & gagging before I could even get my dose down. Not worth it.

I honestly couldn't compare it to morphine because it just does not give genuine, subjective "opiate" effects for me. I once used a bunch of kratom to get through a week of buprenorphine withdrawals & that week was still awful, no sleep, complete restlessness, yet lethargic. It did not even help bupe withdrawal, so I can't understand how people are so addicted to this stuff.

 

[Smyth2]

I threw my kratom in the garbage. It came from Sweden and the labels had indigo hair dye on it which i think was to pass customs but it was very dubious stuff and made me vomit and not experience any sort of high.

My friend in USA says his stuff he buys from his local supplier does work so all I can say is that depending on the source you can pick up some really garbage stuff that is not worth taking.

 

[TheLightBringer]

My response isn't gonna be worth much, but I've always found kratom to be a horrible "opioid" substitute.
I've never once felt what I would describe as genuine opioid euphoria from kratom. I'm more likely to catch a worthwhile euphoria from buprenorphine & bupe has a terrible lack of euphoria in most cases. So I've always questioned why people describe kratom like it's basically a "legal heroin/hydrocodone/tramadol." I hear it described as "like tramadol" so often too, yet I was addicted to tramadol for 11 years & kratom can't even come anywhere close to the level of greatness that a pure tramadol experience gives. People seem addicted to kratom & maybe I'm just a non-responder, but I find it interesting.

The closest thing I get from kratom would be some sedation/feeling like I need to take a nap. But it's not enjoyable at all, it just feels like I'm tired. Not "energizing" in any sense. Tramadol & heroin use to make me get up & clean or exercise because it stimulated me, while simultaneously making me nod/sedated.

So these studies saying it's more potent than morphine are pretty confusing to me too. But my guess is that because it's a partial agonist, it can still be more potent than morphine, while giving awful effects / crappy buzz. Similar to buprenorphine. Bupe is like 30-50x more potent than morphine, more potent than heroin even, yet I don't know many people who would prefer a buprenorphines "high" or pain relief versus heroin or a full agonist.

Kratom seems like an expensive habit too. Unless you're buying plant powder in bulk. And even then, chugging all that plant residue every day can't be great for your stomach. And with how often I'd need to dose it, I think I would be puking & gagging before I could even get my dose down. Not worth it.

I honestly couldn't compare it to morphine because it just does not give genuine, subjective "opiate" effects for me. I once used a bunch of kratom to get through a week of buprenorphine withdrawals & that week was still awful, no sleep, complete restlessness, yet lethargic. It did not even help bupe withdrawal, so I can't understand how people are so addicted to this stuff.

Oh absolutely agree, basically all partial agonists seem to lack that typical blissfull euphoria. They will definetly still produce ”euphoria” in people with low to moderate tolerance but give that same person morphine or oxycodone and it will blow it out of the water.

Altough I have to kind of agree with the comparison between kratom and tramadol, kratom feels like a mild tramadol type feeling if you dont have tolerance to opiates. From memory id say somewhere between 30 - 50mg tramadol per gram of kratom, so 10gs felt like maybe 300 - 500mg ish tramadol to me

I am unaware of any full agonist mitragynoids but I bet they might show some promise euphoria wise, regular kratom and 7-OH I would still put ahead of bupe and fent in terms of euphoria at equivalent dosages

 

[DeathIndustrial88]

Oh absolutely agree, basically all partial agonists seem to lack that typical blissfull euphoria. They will definetly still produce ”euphoria” in people with low to moderate tolerance but give that same person morphine or oxycodone and it will blow it out of the water.

Altough I have to kind of agree with the comparison between kratom and tramadol, kratom feels like a mild tramadol type feeling if you dont have tolerance to opiates. From memory id say somewhere between 30 - 50mg tramadol per gram of kratom, so 10gs felt like maybe 300 - 500mg ish tramadol to me

I am unaware of any full agonist mitragynoids but I bet they might show some promise euphoria wise, regular kratom and 7-OH I would still put ahead of bupe and fent in terms of euphoria at equivalent dosages

Yeah I guess this just goes to show that everyone's biochemistry is different & we all experience drugs in different ways.
With no tolerance, 300-400mg of tramadol always produced a great stimulating, contented euphoria & even in a nod in me similar to heroin. Some days the SNRI effects would be a little too strong & make me a bit sick/dysphoric, but only once in awhile.
Of course you can't really re-dose 400mg of tramadol in a day without risking seizures, but it lasted a good chunk of the day at least. Some times I'd still wake up the next day itching & feeling the effects from it.

I've never had a kratom experience similar to tramadol. Actually I take that back. In 2011ish, I ordered some kratom online & it definitely felt like a cross between tramadol & hydrocodone.
But all of the kratom since then that I've tried has never reproduced this effect. I did read that around 2009-2012, a lot of vendors were spiking their kratom with the metabolite of tramadol, O-desmethyltramadol, which was an unscheduled full agonist in the US at the time. I believe this is what happened to the "kratom" I got that one time in 2011 & why I've never felt it again since.



I'd personally still say bupe is more "euphoric", with no tolerance... And can even produce a little bit of an energizing stimulation similar to tramadol, more so than kratom. But that's just my experience. I wish kratom was worthwhile for me, since it's one of the only "legal" opioid-like products in the US, aside from crappy loperamide.

 

[Deleted member 576750]

"The binding affinity of mitragynine at MOR [Ki value = 709 (451–1130) nM] was at least 89-fold higher than those of fentanyl [Ki value = 7.96 (6.19–10.3) nM], morphine [Ki value = 4.19 (2.03–11.1) nM], and naltrexone [Ki value = 1.84 (1.14–3.03) nM]"

something is strange here, i suspect they meant lower because a lower Ki value means that a higher concentration was needed to displace DAMGO which means a lower affinity than one that had a lower concentration effectively displace the DAMGO

even in their behavioral assays 7oh and mitragynine were far less effective at eliciting lever presses than morphine

Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for μ-Opioid Receptor and Opioid-Like Behavioral Effects in Rats - PMC

Relationships between µ-opioid receptor (MOR) efficacy and effects of mitragynine and 7-hydroxymitragynine are not fully established. We assessed in vitro binding affinity and efficacy and discriminative stimulus effects together with ...

pmc.ncbi.nlm.nih.gov

how this translates to humans isnt straight forward but should give a reasonable estimation