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Matrine

Unfortunately still puts Matrine out of financially attainable recreational range.

It's unfortunate that most other kappa-agonists are tied into µ also. I swore off opiates a few years ago. That's the one class of drugs I feel like were more powerful than I could ever be. And I don't know if I'd want to toe the line with physical opiate addiction again just to get at the kappa-opioid headspace.

Obviously Salvia's existence means it is possible to separate the action of the two, but how might one continue to do so? Like how would one go about creating the "new generation" of dissociatives?" in terms of chemical structure. Like is building off Salvanorin the easiest most obvious thing to do? Or are the ways to predict (in any capacity) receptor activity of a given chemical?
 
Don't think mu agonism has to be bad per se, it depends on the overall profile of the drug. MXE has moderate affinity through one of it's metabolites, strong enough to feel it, and afaik nobody got ever opioid withdrawal from it, most, including me, get away with nothing. Depends on how kappa works.
 
I meant more that of the drugs I could find that notably act on Kappa are predominately opiates like pentazocine mentioned above, which is opiate enough for me to not want to touch it. MXE though, is definitely gods gift to the Earth.
 
ok, so this thread has gone away now, BUT matrine is coming back on some vendors online just recently as i have noticed, so it is of extreme importance i get as much more new information about this shit before i go all out for it. solely based on its opiate activity, of course! it has similar profile to tianeptine, which im trying to quit. so this thing might be of importance for me, very much so actually. AND hopefully i get some updates and recommendations as to what to do with it at this point.... thanks!!!
 
ok i figured nobody gives a shit on this forum, as it is usually pretty dead anyway. BUT i still have to ask this in high hopes i can get some information; whats the accepted typical dose of matrine without overdosing and experiencing negative effects??
 
most modern studies.... what studies?? on rats?? i dont care about that crap. this stuff is LEGAL, so why are there no human subjects testing it by now?? WHERE ARE THE DAMN HUMAN EXPERIENCES??
 
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allone said:
so when you tried it, did you feel anything worth to report or not? this article you linked me to, is way too subtle. it doesnt directly really report anything at all worth of notice.
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If you're looking for anyone saying they've outright tripped balls on it, that data does not exist, no one has reported such a thing yet, though exploration of this drug has only begun recently. The information included in the article is the only information I was able to find on this drug. You're free to do your own research but when I took a deep dive into studying this compound (in late July), this was all I could obtain. Perhaps more reports have been posted since then. I have not personally tried this substance or encountered it yet.
 
A very important (I would say the most famous..) nootropic vendor in USA has released matrine, in both capsule and powder form.
I trust that guy so I probaby will get some asap,
nowadays I'm running low on money so I need to wait between purchases, but this substance seems pretty interesting to get (I love subtle substances with strange effects).
 
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Like Sekio alluded to, that wikipedia write up on matrine paints an inaccurate picture. I remember looking into it a few years back, matrine does not bind to opioid receptors. In that sense, it isn't an opioid. Any activity it might have in that regard would be downstream, like cannabis (which also modulates the MOR and KOR). Aspects of THC's effects can be blocked by MOR and KOR antagonists, but this doesn't make THC an opioid. Matrine is more of a calcium channel blocker than anything else from what I recall.

***as far as odd plant opioid alkaloids, what i do have and am meaning to try, is some psychotria colorata which I imported from Ghana, but got a bit spooked about the eseroline-like structure of some of the alkaloids, so never ended up taking it. G_chem, you like eating toxic honey, you want some psychotria colorata 🤣
 
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I have some matrine, I got it some time ago when I was looking to come off of kratom, hoping the supposed mu agonism would help. What I got was a vague feeling that definitely did not ease my withdrawals. Also worth noting, I started to try to do sublingual, and it gave me chemical burns on my tongue.
 
Just to be sure had to look it up, and here is the brass tax:

Radioligand binding assay demonstrated that (+)-matrine had no affinity for mu-, kappa- or delta-opioid receptors in a wide concentration range (1 x 10(-11)-1 x 10(-3) M). The results suggest that (+)-matrine exerts its antinociceptive effect through multiple mechanism(s) such as increasing cholinergic activation in the CNS rather than acting on opioid receptors directly.

Yin, Lin-Lin & Zhu, Xing-Zu. (2005). The involvement of central cholinergic system in (+)-matrine-induced antinociception in mice. Pharmacology, biochemistry, and behavior. 80. 419-25. 10.1016/j.pbb.2004.12.008.


The old school method of, "naloxone reverses the antinociceptive effect of substance X when we burn the mouse's tail on a hotplate, thus it must be a MOR agonist" resulted in a number of questionable findings over the years. The language in the Wikipedia entry on matrine should definitely be changed (though the vendors of matrine would probably change it back 🤯).
 
negrogesic said:
Like Sekio alluded to, that wikipedia write up on matrine paints an inaccurate picture. I remember looking into it a few years back, matrine does not bind to opioid receptors. In that sense, it isn't an opioid. Any activity it might have in that regard would be downstream, like cannabis (which also modulates the MOR and KOR). Aspects of THC's effects can be blocked by MOR and KOR antagonists, but this doesn't make THC an opioid. Matrine is more of a calcium channel blocker than anything else from what I recall.

***as far as odd plant opioid alkaloids, what i do have and am meaning to try, is some psychotria colorata which I imported from Ghana, but got a bit spooked about the eseroline-like structure of some of the alkaloids, so never ended up taking it. G_chem, you like eating toxic honey, you want some psychotria colorata 🤣
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For what it's worth eseroline doesn't seem to be more toxic than physostigmine, so as long as you keep some atropine on hand to take the edge off the anticholonergic toxidrome, you should be safe wrt pervasive neurotoxicity. Not that that approach isn't a bit of a high wire act...
 
Skorpio said:
For what it's worth eseroline doesn't seem to be more toxic than physostigmine, so as long as you keep some atropine on hand to take the edge off the anticholonergic toxidrome, you should be safe wrt pervasive neurotoxicity. Not that that approach isn't a bit of a high wire act...
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Yes, plus I don't know if the main psychotria colorata alkaloids (hodgkinsine and psychotridine) are as toxic eseroline, but based on their structutes, they sure look like they might be prodrugs to eseroline or an eseroline-like compound. I can't imagine hodgkinsine could actually dock at the MOR in its bulky unmetabolized state without first becoming a prodrug for something else (like an eseroline-like compound). But yes, the toxicity can be managed. Plus what's a little more neuronal cell death, I'm sure I've taken more toxic compounds anyhow.

I went through a fair amount of trouble obtaining the p. colorata, I was able to get a significant amount of large, beautiful, fresh leaves express shipped straight from Ghana. I dehydrated and froze some whole, others I dehydrated and made a powder, and I also made a tincture. Yet I never consumed any of it:



I should try some, don't have atropine, have some scopolamine though. Perhaps a few benadryl might suffice. Again, psychotria colorata isn't known to be toxic, but then again, there is almost no information on it.
 
negrogesic said:
Just to be sure had to look it up, and here is the brass tax:

Radioligand binding assay demonstrated that (+)-matrine had no affinity for mu-, kappa- or delta-opioid receptors in a wide concentration range (1 x 10(-11)-1 x 10(-3) M). The results suggest that (+)-matrine exerts its antinociceptive effect through multiple mechanism(s) such as increasing cholinergic activation in the CNS rather than acting on opioid receptors directly.

Yin, Lin-Lin & Zhu, Xing-Zu. (2005). The involvement of central cholinergic system in (+)-matrine-induced antinociception in mice. Pharmacology, biochemistry, and behavior. 80. 419-25. 10.1016/j.pbb.2004.12.008.


The old school method of, "naloxone reverses the antinociceptive effect of substance X when we burn the mouse's tail on a hotplate, thus it must be a MOR agonist" resulted in a number of questionable findings over the years. The language in the Wikipedia entry on matrine should definitely be changed (though the vendors of matrine would probably change it back 🤯).
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Naloxone reverses the analgesia from the placebo effect for what it's worth.
negrogesic said:
I should try some, don't have atropine, have some scopolamine though. Perhaps a few benadryl might suffice. Again, psychotria colorata isn't known to be toxic, but then again, there is almost no information on it.
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Scopolomine is going to be a way better antidote than benadryl. Very close to atropine in selectivity. Benadryl will throw in SERT blockade and some sodium channel blockade that may or may not play nice.

If you were to take the plunge (and frankly I don't want to say "go for it, " as I don't know enough about the plant to make that call), definately look into physostigmine protocols to see what to watch out for. Of course there are always the unknown unknowns.
 
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