Rimonabant, salvinorin A and the cannabinoid receptors

This is the place to discuss Salvia divinorum, splendins, and the other psychoactive salvias.
bombazil
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Re: Rimonabant, salvinorin A and the cannabinoid receptors -

Post by bombazil » Thu Jul 07, 2011 12:45 pm

Chaotechnic wrote:I'm hoping to eventually make a career somewhere in the field of pharmacology, but there's not many options in my area, and I probably need to go back to school at any rate. At the moment I'm just an average worker bee who likes to research psychoactive plants in his free time.
But you have at least a first degree in biology/pharmacology right? Speaking from experience, as a hopefully not-too-stupid person, getting one's head even halfway around this kind of material is veeeery tricky. Even when one does, it's very difficult to do more than take papers individually at face value. You're making inferences from a whole body of knowledge. Whatever you're doing right now, as far as I can tell you're a scientist. :)

I wonder whether your reading on salvia/norins could be form the basis for a review paper? (& whether getting one published might help you get where you want to go?)

Anyway, it my original suggestion was based on the misconception that salvia itself contains cannabinoid agonists. But your comment on possible independent influences on calcium ion flux from rimonabant suggests that we wouldn't necessarily learn anything about the involvement of cannabinoid receptors in the overall salvia experience by trying salvia+rimonabant. :|

What's the significance of calcium ion flux? I was able to find out that it's affected by cannabinoid receptors. But I don't have a big picture to fit that into... :lol:

(BTW, if you have any thoughts about salvia's immunosuppressant properties they'd be much appreciated.)

Chaotechnic
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Re: Rimonabant, salvinorin A and the cannabinoid receptors -

Post by Chaotechnic » Fri Jul 08, 2011 4:01 am

Anyway, it my original suggestion was based on the misconception that salvia itself contains cannabinoid agonists. But your comment on possible independent influences on calcium ion flux from rimonabant suggests that we wouldn't necessarily learn anything about the involvement of cannabinoid receptors in the overall salvia experience by trying salvia+rimonabant. :|
I think it's likely that salvinorin A has an effect on the endocannabinoid system (through some signal-transduction pathway initiated by it's action at the KOR). Rimonabant probably exerts its influence on the effects of salvinorin A because it blocks the effects that salvinorin exerts (indirectly) on the cannabinoid receptors. I was just pointing out that alternate mechanisms of rimonabant interacting with the KOR signal transduction pathway haven't been ruled out.
What's the significance of calcium ion flux? I was able to find out that it's affected by cannabinoid receptors. But I don't have a big picture to fit that into... :lol:
Alas, I don't have much background in neurochemistry, so all I really know is that the calcium ion flux affects synaptic transmission, and consequently affects behavior. I'll need to do more reading to go any deeper than that.
(BTW, if you have any thoughts about salvia's immunosuppressant properties they'd be much appreciated.)
That's one of about four papers that have come out since I put together my rough notes on S. divinorum. I'll have to track down a full copy of the paper to see what I can get out of it; I'm hesitant to comment based on the abstract alone.

bombazil wrote:But you have at least a first degree in biology/pharmacology right? Speaking from experience, as a hopefully not-too-stupid person, getting one's head even halfway around this kind of material is veeeery tricky. Even when one does, it's very difficult to do more than take papers individually at face value. You're making inferences from a whole body of knowledge. Whatever you're doing right now, as far as I can tell you're a scientist. :)
I appreciate that :). I think of myself as more of a well-informed amateur, but on the other hand my favorite author on psychoactive plants (Jonathan Ott) has only a bachelor's degree.

My bachelor's degree is in biochemistry. I think this sort of background is mostly helpful in terms of having confidence that one can understand scientific literature, rather than actually providing much specific background on these topics. None of the courses dealt with the endocannabinoid or kappa-opioid systems in anything but the most cursory terms, but there were discussion groups where the focus was basically "read this paper and figure out the main points and implications that it presents." That's basically what I've done; taken notes on the key points of all the papers related to S. divinorum that I can find, and now I'm working on organizing that information into a digestible structure.
I wonder whether your reading on salvia/norins could be form the basis for a review paper? (& whether getting one published might help you get where you want to go?)
I've been wondering the same thing myself. While there are a couple of decent reviews on the synthetic chemistry behind the development of salvinorin analogues, and of the structure-activity relationships seen in the analogues, there are no review papers (yet) on the pharmacology of salvinorin A. I have organized my notes on the pharmacology into an outline from which such a paper could be written, so perhaps it's worth submitting to some journals once I get a final draft finished. Most journals seem to only publish from authors affiliated with research institutions, but still, it's probably worth a try.

I also have written a review on what we know of the Nahua plant pipiltzintzintli that I'm not sure what to do with. Whether it may be S. divinorum has been the subject of a fair amount of debate (personally I think the evidence weighs heavily against this possibility). I'm not sure whether a periodical like the Journal of Psychoactive Drugs might find it interesting enough to warrant publication. I'm hoping to put all this work into a short-but-dense (perhaps 180 page) reference book on S. divinorum, its history, chemistry, and pharmacology sometime within the next year or so, but it might be better to try have some of the work published in scholarly journals as I write it. I'm new to the world of publishing (aside from one rather lengthy paper published in the Entheogen Review) so I'm still trying to figure out protocol on things like that.
Last edited by Chaotechnic on Fri Jul 08, 2011 4:12 am, edited 1 time in total.

Jupe
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Re: Rimonabant, salvinorin A and the cannabinoid receptors -

Post by Jupe » Sun Jul 10, 2011 1:44 pm

great discussion Peoples!!! Most goes right over my head. I tend to highgrade a bit when looking for nuggets.
I'm better at composting the gardens, my Env/ St. degree is 30 yrs old tooImage
Last edited by Jupe on Sun Jul 10, 2011 1:50 pm, edited 1 time in total.
Reason: add an edit

bombazil
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Re: Rimonabant, salvinorin A and the cannabinoid receptors -

Post by bombazil » Mon Jul 11, 2011 3:20 am

Chaotechnic wrote:I think it's likely that salvinorin A has an effect on the endocannabinoid system (through some signal-transduction pathway initiated by it's action at the KOR). Rimonabant probably exerts its influence on the effects of salvinorin A because it blocks the effects that salvinorin exerts (indirectly) on the cannabinoid receptors.
So perhaps there is something to be learned by trying salvia + rimonabant? (Just not something about the role direct effects of salvia on the cannabinoid receptor plays in the subjective experience...)
Chaotechnic wrote:That's one of about four papers that have come out since I put together my rough notes on S. divinorum. I'll have to track down a full copy of the paper to see what I can get out of it; I'm hesitant to comment based on the abstract alone.
Well, if you can get hold of it and have a look, it'd be great. Some people are using salvia frequently and long-term enough that it could be a health issue.
Chaotechnic wrote: There are no review papers (yet) on the pharmacology of salvinorin A. I have organized my notes on the pharmacology into an outline from which such a paper could be written, so perhaps it's worth submitting to some journals once I get a final draft finished. Most journals seem to only publish from authors affiliated with research institutions, but still, it's probably worth a try.
Well, FWIW I know someone who's published numerous papers on the Napoleonic wars, who doesn't have a history degree.
Chaotechnic wrote:I also have written a review on what we know of the Nahua plant pipiltzintzintli that I'm not sure what to do with. Whether it may be S. divinorum has been the subject of a fair amount of debate (personally I think the evidence weighs heavily against this possibility). I'm not sure whether a periodical like the Journal of Psychoactive Drugs might find it interesting enough to warrant publication.
There must be quite a few places that might publish something like that. The MAPS journal springs to mind. "Time and Mind" published the Shannon article about Moses...
Chaotechnic wrote:I'm hoping to put all this work into a short-but-dense (perhaps 180 page) reference book on S. divinorum, its history, chemistry, and pharmacology sometime within the next year or so, but it might be better to try have some of the work published in scholarly journals as I write it. I'm new to the world of publishing (aside from one rather lengthy paper published in the Entheogen Review) so I'm still trying to figure out protocol on things like that.
Feel free to use us as a test audience. :D Good luck!

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salvialover24
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Re: Rimonabant, salvinorin A and the cannabinoid receptors -

Post by salvialover24 » Tue Jul 12, 2011 5:05 pm

jupe wrote:great discussion Peoples!!! Most goes right over my head. I tend to highgrade a bit when looking for nuggets.
I'm better at composting the gardens, my Env/ St. degree is 30 yrs old tooImage
I agree. Very interesting conversation. Also, what a crazily beautiful picture here. Is it a composition by you, jupe? You do make beautiful picture of the salvia plant.

Chaotechnic
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Re: Rimonabant, salvinorin A and the cannabinoid receptors -

Post by Chaotechnic » Wed Jul 13, 2011 4:12 am

bombazil wrote:So perhaps there is something to be learned by trying salvia + rimonabant? (Just not something about the role direct effects of salvia on the cannabinoid receptor plays in the subjective experience...)
Absolutely. I would be very interested to learn if someone has tried taking S. divinorum while their CB1 receptors are antagonized. While there certainly seems to be some interplay between the kappa opioid receptors and the endocannabinoid system, it's unclear how this relates to the subjective psychoactive effects of the plant. Taking rimonabant prior to consuming S. divinorum would certainly help shed light on the degree of influence that endocannabinoid interaction has on the subjective visionary experience.

bombazil
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Re: Rimonabant, salvinorin A and the cannabinoid receptors -

Post by bombazil » Wed Jul 13, 2011 6:37 am

Chaotechnic wrote:Absolutely. I would be very interested to learn if someone has tried taking S. divinorum while their CB1 receptors are antagonized. While there certainly seems to be some interplay between the kappa opioid receptors and the endocannabinoid system, it's unclear how this relates to the subjective psychoactive effects of the plant. Taking rimonabant prior to consuming S. divinorum would certainly help shed light on the degree of influence that endocannabinoid interaction has on the subjective visionary experience.
If someone can get hold of rimonabant, perhaps they could distribute it so we can get a range of reports?

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