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OnlineTiberjuggaligger
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Registered: 08/19/17
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Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason
    #24622006 - 09/11/17 10:11 PM (10 days, 2 hours ago)

http://gizmodo.com/scientists-want-to-synthesize-salvia-s-hallucinogenic-m-1803131655/amp



You’re probably familiar with Salvia divinorum, the hallucinogenic plant used for religious purposes in some indigenous cultures, and for watching celebrities giggle in some decaying cultures. But when you were sitting in a frozen Massachusetts cul-de-sac one late night in 2009 bouncing as if you were riding a motorcycle while your friends laughed at your babbling, you probably didn’t think about the scientists interested in the drug’s therapeutic properties. I certainly didn’t.

A team of scientists are now reporting that they’ve found an easier way create a slightly-altered version of the chemical responsible for salvia’s hallucinogenic effects, Salvinorin A. They’re not doing it so that you can continue having wild trips with your high school friends, though. Instead, these researchers are looking for a painkiller with opiate-like effects, but with a lower potential to abuse. They think their new method will take advantage of the chemical’s potential as an analgesic without the trip.

“Drug overdose has become the leading cause of death for Americans under 50, driven largely by abuse of opioids,” the authors report in their paper published recently on the new preprint server, ChemRxiv. “To counter this epidemic, replacement of abused opioids with alternate pain therapeutics has emerged as an increasingly sensible goal.”

The authors write that Salvinorin A is unstable, making it difficult to alter. Others have been able to produce the chemical in the lab and change its structure somewhat, but some complexities have limited the options available to alter the molecule and change the effects it might have on the nervous system.

This time around, the team of scientists from the Scripps Research Institutes in California and Florida, and others at the University of Southern California hypothesized that slightly altering the molecule during synthesis should make something with a more stable backbone for easier customization, that retains some of its opiate-like effects. They didn’t really know if their molecule would actually work, though. “Careful attention to modeling gave a measure of confidence to the venture, although to some extent, it was still a leap of faith,” Jonathan Scheerer, an organic chemist at William & Mary college who not involved in the study told Chemical and Engineering News.

The final molecule, called 20-nor-Salvinorin A, differs just slightly from Salvinorin A. One single piece of the large molecule, a dangling carbon atom with three hydrogen atoms attached, is replaced by a hydrogen atom. The process starts with two commercially available chemicals, one called “Hagemann’s ester,” and the other a chemical reaction starter they made from this mouthful of a chemical. Ten shape-altering steps left them with their 20-nor-Salvinorin A.

The researchers then had to put their molecule to the test. They made enough to use it on some lab mice, and it seemed to be about as effective as Salivnorin A in getting rid of an induced itching sensation. Plus, it only bonded to the opioid receptors they were trying to target. It worked—though they didn’t test whether the mice were also tripping.

“We have simultaneously stabilized the salvinorin scaffold and simplified its synthesis, while maintaining target engagement,” the authors wrote. Nice!

There’s still plenty of work to do; something that works in mice might not work in humans, for example, and this was just a proof-of-concept synthesis. Nor has this paper been peer reviewed, so it’s worth taking the conclusions with a grain of salt. But the researchers have put forth a few goals for their new chemical, like changing how long it sticks around in the blood, and the proportion of the drug the body actually uses, according to the paper. The authors write: “Success in these goals should deliver multiple candidates for next generation analgesics.”


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McCoy: Jim, what are you doing?
Kirk: I'm asking a question.
"God": Who is this creature?
Kirk: Who am I? Don't you know? Aren't you God?
Sybok: He has his doubts.
"God": You doubt me?
Kirk: I seek proof.
McCoy: Jim! You don't ask the Almighty for his ID


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InvisibleMush 4 Brains
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Re: Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason [Re: Tiberjuggaligger]
    #24622047 - 09/11/17 10:21 PM (10 days, 2 hours ago)

I remember hearing about salvia having effects on the kappa opiate receptors. Kappa opiate receptor agonists have been shown to cause dysphoria. Really spooky stuff I think.


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Invisibletyrannicalrex
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Re: Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason [Re: Mush 4 Brains]
    #24622220 - 09/11/17 11:24 PM (10 days, 1 hour ago)

hmmm, seems like the ketamine process for pain. I don't know the details about ket though. They're using IV drips of ket over a 5 hour period for pain.


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Offlinedurian_2008
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Re: Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason [Re: tyrannicalrex]
    #24622251 - 09/11/17 11:32 PM (10 days, 1 hour ago)

Small amounts, daily, lifted my mood.

I felt that synthetic cannabinoids led to scary news stories, so would have questions about a potent hallucinogen.


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InvisibleCelestial Traveler
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Re: Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason [Re: Tiberjuggaligger]
    #24622479 - 09/12/17 01:13 AM (9 days, 23 hours ago)

I don't like how drug-related articles like these talk down to their audience, as if everyone reading them is a retarded stoner...it's not even because it's offensive, but because it's really old and assumes that a stereotype is reality, which is ignorant.


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OfflineKonyap
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Re: Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason [Re: Celestial Traveler]
    #24622597 - 09/12/17 03:18 AM (9 days, 21 hours ago)

"I got so spun out the voices stopped."


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Offlinedurian_2008
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Re: Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason [Re: Konyap]
    #24623251 - 09/12/17 01:02 PM (9 days, 11 hours ago)

Quote:

Konyap said:
"I got so spun out the voices stopped."



With pic of a circumscribing radius, of the variety, used to create tessellations.


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Offlinetacodude
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Re: Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason [Re: durian_2008]
    #24623699 - 09/12/17 04:31 PM (9 days, 8 hours ago)

http://cen.acs.org/articles/95/i10/opioid-minus-major-side-effects.html?type=paidArticleContent

They need to release this compound ASAP... If it is really what they say it is it could end the "epidemic" and then allow people pain relief as well as bring the heat down so we can start growing opium to smoke after eating shrooms.


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Offlinedurian_2008
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Re: Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason [Re: tacodude]
    #24626651 - 09/13/17 05:31 PM (8 days, 7 hours ago)

Is an agonist comparable to a re-uptake inhibitor?

For instance, an SSRI is supposed to result in higher levels of serotonin?

Does an opiod agonist result in higher levels of opiates?

(I am just asking, not saying it is so.)


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Offlinebreeg89
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Re: Scientists want to synthesize Salvia Divinorum's hallucinogenic molecule for a surprising reason [Re: durian_2008] * 2
    #24627124 - 09/13/17 08:20 PM (8 days, 4 hours ago)

^ They can be comparable in the end result that is produced (i.e., an SSRI increases serotonin, which can produce similar biological response to a serotonin agonist binding to serotonin receptors). But the mechanism of an agonist and a reuptake inhibitor is different.

An agonist binds to a receptor (e.g., a G-protein coupled receptor) and activates the biochemical function of that receptor. Activation of G-protein coupled receptors involves complex signaling cascades, often resulting in changes in calcium ion and/or cyclic AMP concentrations.

Here's another link for those interested in opioid modulators with reduced abuse potential: http://blogs.sciencemag.org/pipeline/archives/2017/03/13/hope-for-nonaddictive-opioid-painkillers


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