Have you heard influencers or other media fearmonger-ers say that 7-OH is "13 times more powerful than morphine"? Here's the context: it is 13x more potent at inhibiting the contractions of guinea pig intestines compared to morphine

[u/MildlySuspiciousBlob]

https://www.fda.gov/media/187899/download?attachment

From 7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat (page 15):

Similarly, Matsumoto and colleagues concluded that 7-OH was “found to have an opioid agonist property on µ- and/or κ-opioid receptors” based on its ability to inhibit contraction of isolated guinea pig ileum. In this assay, 7-OH displayed approximately 13-fold greater potency than morphine and 46-fold greater potency than mitragynine. The inhibition was reversed by naloxone, suggesting the effects are mediated via mu opioid receptors (Matsumoto et al., 2004). Other functional assays produced results that are aligned with Matsumoto and colleagues. For example, using a cAMP mobilization assay as a measure of functional effects, 7-OH acted as a full agonist with an EC50 of 7.6 nM, and was more potent than mitragynine (EC50 307.5 nM) (Obeng et al., 2020). Likewise, when evaluating the agonist activity of 7-OH in an electrically stimulated guinea pig ileum, 7-OH acted as a full agonist and was more potent than morphine (Takayama et al., 2002). Finally, using a [35S] GTPγS functional assay, 7-OH produced an Emax of 77% with an EC50 of 53.4 nM, further demonstrating its agonist effects (Varadi et al., 2016).

[u/RecklessPope]

I’m a scientist studying this topic, feel free to ask away. In my hands 7-OH is nearly equipotent to morphine in GTPyS, with a similar binding affinity. Guinea pig ileum contractions are a very old school way of measuring ligand activity (thing 1960s, 1970s)

[u/Sufficient_Meet6836 → u/RecklessPope]

In my hands 7-OH is nearly equipotent to morphine in GTPyS, with a similar binding affinity.

Sorry, just for clarification, are you saying these are results from tests you've done, or are you citing the literature?

[u/RecklessPope → u/Sufficient_Meet6836]

Tests I’ve done

[u/Sufficient_Meet6836 → u/RecklessPope]

That's super cool! Thanks for clarifying and the work that you do

[u/RecklessPope → u/Sufficient_Meet6836]

Anytime dawg, ask away if you have any questions about anything. I’ve spent years studying this stuff so it’s nice to explain it to others 🙌

[u/G1nnnn → u/RecklessPope]

Are you doing lab work at a company or university/institute? I'd love to work in honestly any analgesic-related pharma research doesnt even have to be opioids or smth like that, but outside of some MAGL-Inhibitor related research during my masters i never had a good opportunity...

So basically just wondering how you got the job if it is one and if you have any recommendations regarding getting into such positions. Im currently considering a PhD for example, not sure if i really wanna go through it though considering how i've heard that its often not needed for such positions

[u/RecklessPope → u/G1nnnn]

Almost done w PhD at university! Depends what country you’re in, but 99% of scientist positions require a PhD if you want to be promoted within your company. Obviously there are exceptions. If you’re young I’d recommend a PhD

[u/G1nnnn → u/RecklessPope]

Interesting, i hear vastly differing opinions on the PhD stuff, some say its only necessary for immediately getting into higher up positions and that mostly experience matters, some say a PhD is required either way... may i ask what country you are studying in?

[u/RecklessPope → u/G1nnnn]

I’m in the US - for basic bench positions you definitely don’t need a PhD! And if you’re there for a long time you will gain enough skills for promotion (possibly) to higher level positions

[u/G1nnnn → u/RecklessPope]

Ok cool, thx for the opionion/tip!

[u/MildlySuspiciousBlob → u/RecklessPope]

I don’t think there’s anything wrong with this assay; there’s a time and place for all of them. But for weeks I’ve seen media and influencers introduce 7-OH as an “opioid 13 times more potent than morphine.” That’s a misleading way to describe its potency in terms of addiction and overdose potential.

[u/RecklessPope → u/MildlySuspiciousBlob]

I completely agree, but I completely agree because it’s an old school assay. There is very little time and place for it nowadays. We used that assay back then because we didn’t have cell lines over expressing the mu opioid receptor. Guinea pig ileum expresses a whole host of other proteins 7-OH likely binds to, hence the 13x more potent stat.

Bio activity-wise, It’s nearly equivalent to morphine, not 13x. So yes

[u/MildlySuspiciousBlob → u/RecklessPope]

There might be interest in 7-OH’s effect on Guinea pig intestinal motility because constipation is a side effect of other commonly used opioids, and someone wants to develop an opioid with an improved side effect profile. Even today, the Guinea pig ileum assay might be more useful for studying opioid-induced constipation than binding affinity, etc.

[u/RecklessPope → u/MildlySuspiciousBlob]

Hey king - I love your enthusiasm but you’re trying to fight a losing battle. Please see attached paper, figure 2 - nowadays, we use a little more robust assays.

Do you know why we USED guinea pig ileum? Because it expresses a whole lot of opioid receptors. What do ALL opioids do? Cause constipation. Because there’s a whole lot of opioid receptors in the gut. All opioids will cause constipation, you can’t design an opioid that will not cause constipation unless you use positive allosteric modulators etc

https://www.biorxiv.org/content/10.1101/2025.10.16.682975v1.full.pdf+html

[u/ResearchSlore → u/RecklessPope]

What do ALL opioids do? Cause constipation. Because there’s a whole lot of opioid receptors in the gut. All opioids will cause constipation, you can’t design an opioid that will not cause constipation unless you use positive allosteric modulators etc

This is quite misleading because the relative potency for antinociceptive effects and constipating effects can dramatically differ from one MOR agonist to another.

For 7-hydroxymitragynine, therapeutic doses almost never produce constipation in my experience, whereas the constipation from therapeutic doses of 'partial agonist' buphrenorphine can be horrific.

7-hydroxymintragynine dose-dependently and significantly inhibited gastrointestinal transit in mice. The ED50value of 7-hydroxymitragynine on gastrointestinal transit was larger than its antinociceptive ED50 value. On the other hand, morphine significantly inhibits gastrointestinal transit at a much smaller dose than its antinociceptive dose. [ref]

Edit: Downvoting me because you don't actually understand the pharmacology is priceless.

[u/RecklessPope → u/ResearchSlore]

True, but bup also is 200x more potent than 7-OH in vitro. I understand it’s misleading, but I’m trying to illustrate how narrow the therapeutic window is with these ligands - even 7OH. It is a generalization to convey a point to a lay audience (this sub)

[u/MildlySuspiciousBlob → u/RecklessPope]

Thanks for the friendly reply. Not sure where I came off as “enthusiastic” though

[u/RecklessPope → u/MildlySuspiciousBlob]

And your last sentence is completely wrong. Stop postulating and trying to talk about things you don’t know

[u/RecklessPope → u/[deleted]]

Hi there - I’m well aware potency isn’t affinity. That’s what I meant in my message, it has a potency similar to morphine, as well as an affinity similar to morphine. Equipotent means it has a similar functional (potency) profile to morphine. Equipotent = equal potency.

I’m assuming you mean intrinsic efficacy by instinct efficacy. In simple terms, the intrinsic efficacy of a ligand describes an agonist’s potency/affinity in a given system.

Biased agonism refers to its activity in arrestin vs. G protein pathways. These mitragynine ligands have very little arrestin recruitment relative to G protein recruitment. These functional values are in essence its potency in these given ways of measuring agonist activity.

[u/Mouse_Manipulator → u/[deleted]]

Did you just try to teach a scientist something about their area of study? l m a o

[u/Majestic_True_Lilly]

Wait til these halfwits learn about loperamide...

[u/dylanneedsalife → u/Majestic_True_Lilly]

Shhhhh, that's our lil secret lol

[u/Majestic_True_Lilly → u/dylanneedsalife]

"Theres a opioid 1000x stronger than fentanyl in your local grocery store! Learn how to keep your children safe and more at 11 oclock, here on your trusted news source."

Then the segment is 10 seconds of a professional stating its an opioid thats 1000x better at inhibiting intestinal mobility than fent, followed by 10 minutes of ignorant idiots hysterically misconstruing what that means, then extrapolating more incorrect shit to be mad at (ancient aliens style), capped with a 5 second clip of the professional from the first clip stating it doesnt cross the BBB and so cant get you high or kill you. Then everyone confuses the incorrect shit said by the idiots as being from the actual expert, and a brand new hysteria is born, merch and subs are sold, and big pharma gets to release a patented new derivative that doesnt work as well after cheap generic lope is banned.

Same typa shit happens every day

[u/Kalki_X → u/Majestic_True_Lilly]

I wonder if the "polypharmacy" of regular kitchen spices & incense resin will ever get a news segment.

[u/fgohr → u/Majestic_True_Lilly]

Hahahahahhq

[u/pickledeggmanwalrus]

I feel like anyone who has ever taken 7oh and morphine is aware that those marketing claims don’t mean what the maker tries to portray.

I was using it for sciatic nerve pain. It was the most effective thing I have used to try to relieve the pain. Worked better than steroids, muscle relaxers, NDAIDs and even strong THC extracts. THC extracts would help me ignore the pain but 7OH would actually make it go away for a few hours.

I only used daily for about 6 months and at the highest was taking 200mg+ per day but when the ban was announced i tapered myself down to 60mg per day for a week or so and then quit. The withdrawal symptoms were rough but not as bad as I was expecting after reading all the horror stories online. Honestly think reading online and preparing for the withdrawals caused some unneeded anxiety and may have even worsened symptoms because I was “expecting” the side effects to be severe. Withdrawal began about 8 hours after my last dose and lasted about 36 hours total. The worst of it being hours 12-24. After the 24 hour mark it began to ease up a lot. I did use copious amounts of D9THC/thca(500mg+ vaped), HHC (1000mg+ vaped), and took a small dose(5mg) of THCp during the withdrawal window and that probably helped some of the negative side effects.

I think they should bring it back but this time let it be schedule 3 and let doctors prescribe it for acute pain like they used to be able to do with opiate based opioids. I feel it’s safe to do so since it doesn’t have the respiratory depression risks that other opiate opioids carry

[u/evincarofautumn → u/pickledeggmanwalrus]

Yeah, 7-OH-mitragynine was really the only thing I found to work for sciatic nerve pain as well. And likewise I don’t use it anymore. It helped me quit drinking, which removed a lot of the inflammation that had been exacerbating my chronic pain to begin with. Tapering off did take a while but it was fine.

Personally I think it should just be legal with an age limit, but failing that, I absolutely agree that hydroxymitragynine should be available by prescription. It’s essentially the best alternative to opiate pain meds and “replacement therapy” meds that we have right now.

[u/Sert1991]

People also confuse potency with the strength a drug exhibits on receptors.
For example buprenorphine is said to be over 100 times more potent than morphine, because it requires micrograms to work.

But try to saturate 90% of your receptors with buprenorphine and then do it with morphine, tell me if buprenorphine is over 100 times stronger than morphine.
Oh wait, you can't tell me cause you're dead.

Maybe this is a similar confusion?

[u/Former_Quality_9867 → u/Sert1991]

Yh people don’t understand intrinsic efficacy or affinity and how the two work together. People just associate potency with strength

[u/SiNoSe_Aprendere]

This explains why the constipation was so bad even at moderate doses of 7OH... I really wish I saw this sooner.