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PSiLO187
newbie
Registered: 06/12/00
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Re: Resistant to Salvia?!? [Re: Azmodeus]
#1190394 - 01/04/03 01:30 PM (21 years, 28 days ago) |
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Given this probably has nothing to do with cross tolerance. Maybe this is where people's assumptions originated.
Here is the scientific abstract:
Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.
Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB.
National Institute of Mental Health Psychoactive Drug Screening Program and Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH 44106, USA. roth@biocserver.cwru.edu
Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as legal hallucinogens. We discovered that Salvinorin A potently and selectively inhibited (3)H-bremazocine binding to cloned kappa opioid receptors. Salvinorin A had no significant activity against a battery of 50 receptors, transporters, and ion channels and showed a distinctive profile compared with the prototypic hallucinogen lysergic acid diethylamide. Functional studies demonstrated that Salvinorin A is a potent kappa opioid agonist at cloned kappa opioid receptors expressed in human embryonic kidney-293 cells and at native kappa opioid receptors expressed in guinea pig brain. Importantly, Salvinorin A had no actions at the 5-HT(2A) serotonin receptor, the principal molecular target responsible for the actions of classical hallucinogens. Salvinorin A thus represents, to our knowledge, the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist. Because Salvinorin A is a psychotomimetic selective for kappa opioid receptors, kappa opioid-selective antagonists may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders). Additionally, these results suggest that kappa opioid receptors play a prominent role in the modulation of human perception.
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Macey Howard
Formally MOE HOWARD


Registered: 07/02/99
Posts: 14,165
Loc: Georgia
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Post deleted by Moe Howard [Re: Azmodeus]
#1200537 - 01/08/03 10:33 AM (21 years, 24 days ago) |
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-------------------- Hugs and Kisses!
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Azmodeus
Seeker

Registered: 11/27/02
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My appologies Neuro, thank you for your contribution. 
Moe, whats up with that?! What were you thinking lying on the floor that would give you a craving for ice cream....
-------------------- "Know your Body - Know your Mind - Know your Substance - Know your Source. Lest we forget. "
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reite
journeyman
Registered: 06/26/02
Posts: 61
Last seen: 16 years, 8 months
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Re: Resistant to Salvia?!? [Re: neuro]
#1207597 - 01/10/03 04:07 PM (21 years, 22 days ago) |
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Well, there has been a little confusion since I posted about cross tolerance. Let's see if I can clear things up a bit. First up. Good post by Psilo of the Kenner Rice article, that article basically says that Salvinorin-A is a kappa opioid selective agonist (and doesn't seem to hit any other receptors in the bank they tested, but they left out the CB receptors, interesting). What does this mean, Salvinorin-A acts through the kappa opioid receptor, i.e. it's a kappa agonist.
Now my original post, a little short and unclear in retrospect, said. "Tolerance will develop to this drug, and it will probably be cross tolerant with any of the other opioids?"
Let's examine why I said this. If you accept as proof scientific studies as the only thing that will satisfy you, then, I can show you nothing that says that Salvinorin-A has been tested for the development of tolerance. However kappa receptor agonists have been shown to produce tolerance in both human and animal models. If you want to look for these studies look for the drug pentazocine. Since Salvinorin-A acts through kappa receptors, tolerance will develop to this drug.
Now cross tolerance. Neuro said "I'll tell you, cross tolerance with opiates is untrue." I said that Salvinorin-A will probably be cross tolerant; if I were to rewrite what I said I would include my unspoken message which is "to the extent that the opioid in question has kappa agonist activity." If an opioid stimulates the kappa receptor it will be cross tolerant with Salvinorin-A, just as if an opioid stimulates the mu receptor (the effects people are most familiar with) it will be cross tolerant with morphine (like heroin). So pentazocine (kappa agonist) will be cross tolerant with Salvinorin-A.
Now to the sticking point I said "any of the other opioids" which implies that Salvinorin-A is an opioid, yes? Yes.
Neuro said "Opiate cross tolerance is not real, whoever said that doesn't know what they're talking about. Salvinorin A is not even anywhere close to being an opiate, there is no cross tolerance."
Well he is right and he is wrong. I do know what I am talking about. He is right when he says that Salvinorin-A is and never will be an "OPIATE", why? Definitions. When I use the words opiate and opioid I use them VERY specifically, though it may seem like I am tossing them about, it is because I use them so frequently that their definitions are part of my every day working vocabulary. An OPIATE is any active alkaloid from the plant papavir somniferum. So let's take a quick quiz. Select the opiates from the following list. Morphine Thebaine Codeine Heroin Fentanyl The first three are opiates and the last two are NOT, why, because they don't come from the poppy plant. Therefore Neuro was right when he said that Salvinorin-A is not close to being an OPIATE because it dosen't come from the poppy, it comes from Salvia and is therefore not an OPIATE. The last two on the list are OPIOIDS, (heroin is modified morphine, and fentanyl is an analog without a constraining ring). OPIOIDS are defined as any molecule which acts through the opioid receptors (basically considered mu, delta, and kappa at present, though there is debate weather sigma and epsilon are opioid receptors and that is an whole other discussion). The suffix -oid means like, which is where the word opioid came from "opi" and "oid" meaning "opium like". Now as more and more compounds were discovered/synthesized and the receptors cloned and expressed the term came to include synthetic derivatives like heroin (which ironically was originally touted as a cure for morphine addiction, gotta love those marketing gurus), antagonists, peptides including the endorphins (mu agonists), enkephalins (delta agonists), and dynophin (kappa agonist), the peptide derivatives, and delta and kappa non peptide molecules. Therefore Salvinorin-A is not just possibly an opioid, it is an OPIOID.
I hope this helps, I will check back if you have any questions.
reite
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Ripple
Ripple



Registered: 05/16/02
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Re: Resistant to Salvia?!? [Re: reite]
#1207826 - 01/10/03 05:53 PM (21 years, 22 days ago) |
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Great post, I thought that heroin would have been considered an opiate.
-------------------- The bus came by and I got on that's when it all began!
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neuro
Phytophiliac


Registered: 08/10/99
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Re: Resistant to Salvia?!? [Re: reite]
#1208774 - 01/11/03 07:11 AM (21 years, 21 days ago) |
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Thanks for the clearing up.
one thing though: not all drugs that act on specific receptors have shown cross tolerances.. I have some articles laying around my room somewhere that i could post, i gotta find them and probably would have to type them, but i know i have them.. give me some time plus some free time to get them up. These were handed out during neuropharmacology one day at school, i may have shoved them in one of my med books. But it basically shows that just because an chemical acts on a "shared" receptor does not mean that it will produce tolerance to other drugs that are unrelated chemically to it. At the present time, through experience and journal articles written about Salvinorin-A i don't believe it will produce cross tolerance, until further is written about it to persuade me, that's my position.
You have to admit that current studies regarding receptor binding and action are still very far in the gray.
Can you provide further articles that may demonstrate further binding to kappa receptors producing cross tolerances?
As for your use of words. By definition i don't accept that Salvinorin-A is an opioid because, to be an opioid it would have to satisfy three things: First, it would have to have similar chemistry, Salvinorin-A and an drug considered an opiate or opioid are far from similar in molecule shape and constituents. Drugs that are marked into classes are called so because they have similar chemistry and second, similar pharmokinetics. Salvinorin-A does not meet the criteria for Shape and Constituents, and much is not known about pharmokinetics except for kappa receptor action (which i have to find that article for). Third, it does not produce the same effects as an opiate or chemically classed opioid. Like i said before, touching or binding to one receptor does not neccessarily mean that it will produce the same effects if other bindings, as well as chemical shape and properties, are occuring at the same time. If you were to find a list of what are traditionally considered opioids, you will see that Salvinorin-A is far different in all respects.
Again, this isn't currently sientifically proven fact, but through my knowledge of medicine, pharmacology, and experience, i don't find, at the present time, Salvinorin A to meet the criteria to be an opioid, nor produce cross tolerance based on one receptor action. Currently there are no articles to my knowledge that will go so far as to define Salvinorin-A as an opioid based on this single finding. If anyone does this will require elimination of the term opioids, since Salvinorin-A doesn't fit the three criteria i listed above. And if listed, this will be a rewriting of the definition.
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reite
journeyman
Registered: 06/26/02
Posts: 61
Last seen: 16 years, 8 months
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Re: Resistant to Salvia?!? [Re: neuro]
#1227643 - 01/17/03 07:17 PM (21 years, 15 days ago) |
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"At the present time, through experience and journal articles written about Salvinorin-A i don't believe it will produce cross tolerance, until further is written about it to persuade me, that's my position."
That is fine, it is my position it does. Time will tell.
"You have to admit that current studies regarding receptor binding and action are still very far in the gray." The one BINDING study published was pretty clear, though it was only one study.
"Can you provide further articles that may demonstrate further binding to kappa receptors producing cross tolerances?" I said previously there are no such studies with the Salvinorins.
"As for your use of words. By definition i don't accept that Salvinorin-A is an opioid because, to be an opioid it would have to satisfy three things: First, it would have to have similar chemistry, Salvinorin-A and an drug considered an opiate or opioid are far from similar in molecule shape and constituents. Drugs that are marked into classes are called so because they have similar chemistry and second, similar pharmokinetics. Salvinorin-A does not meet the criteria for Shape and Constituents, and much is not known about pharmokinetics except for kappa receptor action (which i have to find that article for). Third, it does not produce the same effects as an opiate or chemically classed opioid. Like i said before, touching or binding to one receptor does not neccessarily mean that it will produce the same effects if other bindings, as well as chemical shape and properties, are occuring at the same time. If you were to find a list of what are traditionally considered opioids, you will see that Salvinorin-A is far different in all respects."
Pardon my bluntness. Where do you get that definition of an opioid? "have to have similar chemistry" - that's vague "similar in shape and constituents" - again vague. How similar is similar? Who decides that? How do you draw the line, and why do you draw it there? Why do they have to be similar? They don't. In the opioid family fentanyl looks nothing like morphine, neither does methadone, LAAM, or tramadol. What about the opioid peptides, they certainly look nothing like the opiates or opioids. For that matter (+)morphine looks nothing like morphine, and everything like morphine (for non-chemists pretend for a moment your left hand is morphine, place it on the table palm down, now pretend your right hand is (+)morphine, now place it on top your left hand, palm down. The thumbs are opposite each other so your hands are different, but very similar looking mirror images, this is the way morphine, actually (-)morphine, and its enantiomer (+)morphine look. Five bonus points to the person who can tell me the only pharmacological property they have in common). The truth is that compounds don't have to look the same to be opioids. But don't take my word on it, go look it up for your self.
"similar pharmokinetics" Do antagonists have similar pharmokinetics? Do partial agonists? Do full agonists? Ten bonus points to the person who can tell me what the name of the full agonist for mu is. Do dual agonists? Do delta and kappa agonists? Yes and no. The full explanation of this is about an hour lecture, if you are curious get a book on pharmacology.
"Third, it does not produce the same effects as an opiate or chemically classed opioid." Now you are making a tautology.
If you want me to quote, lets look at Casy and Parfitt (from their book Opioid Analgesics)
"The aim of this chapter is to bring together data on opioid ligands [you can basically take ligand to mean molecule] that (1) antagonize the actions of morphine and its surrogates, (2) possess both agonist and antagonist properties, and (3) possess the unique pharmacological profile of the so-called kappa agonists [the reason they say "so-called" is because most all opioids bind to all three receptors, kappa agonists bind tighter to kappa than mu or delta and are selective for kappa, Salvinorin A seems to exhibit virtually no binding to mu or delta which makes it exciting. Also of note there are now delta selective agonists which have come out since the writing of the book]. The majority of these compounds fall within the morphine [have the 4-5 epoxide bridge or d ring], morphinan [lack the d ring], and benzomorphinan [lack the d and c rings, of note this is where some of the kappa selective agonists fall] groups of opioid ligands (Chapters 2, 3, and 4)."
"If anyone does this will require elimination of the term opioids, since Salvinorin-A doesn't fit the three criteria i listed above. And if listed, this will be a rewriting of the definition."
This is where you can find the flaw in your Belief System, the term opioid does not mean the same thing that you think it does, and the definition has already been rewritten. You mentioned you are/were in school (if pharmacy) ask your med chem professor "what is the definition of an opioid, and how does it differ from an opiate". If you are in med school well, go over to the pharmacy school and find the med chem professor and ask him (med students get only a tiny amount of pharmacology, 1 semester at my nearest med school). I empathize with you, when what you previously believe is challenged and shown to be wrong it is scary, you want to defend your old beliefs, scarier still is accepting the new belief. Again, don't just trust me, go out and find things that prove or disprove what I have said.
r.
-------------------- Imagine, your having a great day...
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joeshitragpicker
Home Sweet Home

Registered: 10/16/02
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Re: Resistant to Salvia?!? [Re: Ripple]
#1227940 - 01/18/03 12:18 AM (21 years, 15 days ago) |
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How can you expect anyone to pack 3 bowls of 10x in a bongh if 1 g of it runs for about $50?
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neuro
Phytophiliac


Registered: 08/10/99
Posts: 6,633
Loc: Rigel 7
Last seen: 2 months, 15 days
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Re: Resistant to Salvia?!? [Re: reite]
#1228994 - 01/18/03 12:02 PM (21 years, 14 days ago) |
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I'm not going to jump into this but, i simply don't believe the Salvinorin-A is the bombshell to the opioid/ opiate. And i do understand the difference between opiate and opioid. But trans/cis isomers of morphine although not chemically exact is still the same make up of morphine, like one would recognize the idea that a rabbit and a rabbit held upside down are still both rabbits -- that's also like saying L-sucrose and D-Sucrose are still not sugars, sure Levatory sugar is regular table sugar and Dexatory sugar can't be digested hence can't add fat and sugar to the blood, but it still looks like sugar chemically and physically. and acts the same.. Besides even Parfitt and Casey are about ready to announce that Salvinorin-A is fully an opioid, notice they say "so-called"...Shape and Constituents, as i meant was you'll find an amine in all the base parts of the rings in predictable places or a methyl group or a ketone. Of Course the side chains will be different, but they'll have what seems to be "common ancestry" ..if you compare salvinorin-a to any of them, it's so far different and shows no common ancestry. all i'm saying is, i want more evidence on Salvia's actions to declare it an opioid. till now i'm fine with kappa agonostic diterpene.
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cybrbeast
Up, then down, then...



Registered: 01/06/03
Posts: 4,777
Loc: event horizon
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I don't understand why some people or groups don't get any effects and some do. But I think it has to be the smoking technique.
This has worked for me and three of my friends Dark room, one candle or small light. Low volume background music. 1/16th of a gram of STANDARDIZED 10X in a water bong. Hold a butane lighter directly above it. Take it in one very deep hit. Hold the smoke for a long time. 30+ seconds. We were usually trippin before we could put the bong down. It's important for the people in the room not to talk or make many sounds or movements, when the someone is tripping unless asked to do so. Tripping should last 5-10 minutes
What also worked is a Salvia joint. Roll a big joint with only weed and 0,5g of 10X in it. No tabacco because that burns at a low temperature. Smoke it, breathe deep and long. Such a joint was enough to make four of us have a trip of 1 or 2 hours. But it wasn't as intense as a pure Salvia trip.
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futuretribe.space
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santashroom
"PsilocybinSyrup"

Registered: 09/26/03
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Re: Resistant to Salvia?!? [Re: cybrbeast]
#2037365 - 10/23/03 06:30 PM (20 years, 3 months ago) |
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Tobacco burns at a higher temperature than weed. That's why people roll hash into tobacco joints.
I just roll a phat cone of salvia leaf and a little tobacco and then I'm off! It's a three paper cone and took about three tries before I started to trip but the third time all i remember is smoking the cone out side and then waking up in my bed fully clothed saying wtf! I had no idea what happened. Each time i try it i seem to go a little futhur. In a little bit i'll time for the fourth time and i'll report back in a couple of hours!
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SkorpivoMusterion
Livin in theTwilight Zone...


Registered: 01/30/03
Posts: 9,954
Loc: You can't spell fungus wi...
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Re: Resistant to Salvia?!? [Re: santashroom]
#2041001 - 10/24/03 09:08 PM (20 years, 3 months ago) |
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Would a good nice expensive Vaporizer work with Salvia? Volcano - Medical grade vaporizer from Germany tested by California NORML and MAPS, found to eliminate over 100 chemicals, delivering 95% pure cannabinoids in vapor. Unique collection system avoids wastage by collecting vapor in a balloon. Very high quality. Very expensive. But, it IS Medical Grade
-------------------- Coffee should be black as hell, strong as death, and sweet as love.
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SkorpivoMusterion
Livin in theTwilight Zone...


Registered: 01/30/03
Posts: 9,954
Loc: You can't spell fungus wi...
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and isnt there some kind of like Salvia Oil extract I can get somewhere?
-------------------- Coffee should be black as hell, strong as death, and sweet as love.
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