Quoi de neuf ?

Bienvenue sur Psychonaut.fr !

En vous enregistrant, vous pourrez discuter de psychotropes, écrire vos meilleurs trip-reports et mieux connaitre la communauté

Je m'inscris!

Salvia and Opioid Kappa Receptors

Scarecrow

Matrice périnatale
Inscrit
12 Nov 2008
Messages
16
So apparently Salvinorin A is a Kappa receptor agonist, the same receptor that produces unquantifiable feelings of negative discomfort in research volunteers. Is it just me, or does that completely make sense? I have had some fantastic experiences with it, but there is no doubt in my mind that salvia is a highly uncomfortable trip to enter into.

Does anyone know about potential studies discussing how long the Salvinorin remains attached to Kappa receptors?

Such interesting stuff!
 

Caduceus Mercurius

Holofractale de l'hypervérité
Inscrit
14 Juil 2007
Messages
9 628
From salvia.net: "While salvinorin does activate opioid receptors in the brain, it's important to draw a distinction between the mu-opioid receptor (activated by narcotics like heroin) and the kappa(1)-opioid receptor (activated by salvinorin A). Drugs that work on the mu-opioid receptor cause sedation, pain-relief, and euphoria, but drugs that work on the kappa(1)-opioid receptor generally cause hallucinogenic, but often unpleasant (or even dysphoric) effects. This explains why many people describe the Salvia experience as being unpleasant compared to the effects of the tryptamine psychedelics (such as psilocybine, DMT and LSD), which activate other receptors in the brain."
 

st.bot.32

Holofractale de l'hypervérité
Inscrit
5 Oct 2007
Messages
3 886
that explains it. the actual high, the feeling of being ON salvia i find to be a somewhat unpleasant sensation. not euphoric like lsd or cannabis.

although the quid method was a lot more enjoyable, when it actually worked..
 

Synith

Sale drogué·e
Inscrit
9 Nov 2008
Messages
790
st.bot.32 a dit:
that explains it. the actual high, the feeling of being ON salvia i find to be a somewhat unpleasant sensation. not euphoric like lsd or cannabis.

although the quid method was a lot more enjoyable, when it actually worked..

Hm. I do feel a general sense of euphoria while/during the Salvia trip. Once you're back to normal, a light sense of 'good feeling' lingers for a few days. I have noticed, however that I become irritable the day I meditated. Some one will ask me a question twice and I'll bark back at them. It's a negative feeling. It stops me and I go, 'Whoa. Where did that come from?'
Quite odd.
 

Scarecrow

Matrice périnatale
Inscrit
12 Nov 2008
Messages
16
Synith a dit:
Hm. I do feel a general sense of euphoria while/during the Salvia trip.
Me too, though I generally feel like the sensation of actually going INTO a trip is unpleasant. That's why I wonder how long Salvanorin A actually remains attached to the receptors - maybe it's variable from person to person, explaining why some people enjoy the feeling and some find it distinctly unpleasant all of the way through.
 

significationof?!?

Elfe Mécanique
Inscrit
9 Déc 2008
Messages
348
Are there any other (known?) substances that affects kappa-opioid receptors? Do they show any spiritual potential like salvia does?
 

fluoroantimonic

Neurotransmetteur
Inscrit
28 Déc 2008
Messages
26
Better yet, there are analogues of salv-A that are much more potent and long lasting. They are also orally active, so they could be pilled.

They have not been studied long, so as far as I know no human has tried them (and documented it). It is certainly possible that they could cause a very unpleasant experience, it might be hard to predict. Some last many hours! They are very selective to the kappa-opioid receptors just like salv-A is, so I would guess the effects would be similar.

For example, methoxymethyl salvinorin-B is ~7 times more potent in animal tests compared to salv-A, and lasts much longer.

Interestingly analogues of salv-A would actually not be that hard to synthesize from salv-A itself. Only a couple steps, and the reagents are not extremely hard to come by. I'd love to try it some day.
 
G

Guest

Invité
fluoroantimonic a dit:
Interestingly analogues of salv-A would actually not be that hard to synthesize from salv-A itself. Only a couple steps, and the reagents are not extremely hard to come by.

I'd love to hear more about this. Do you have any links to pages detailing such any synthesis? Or do you know of a book that would cover such a process?

I'd gather that you'd need to extract the Salvanorin from the leaf matter, also, but I think I've read about that before... I'll look it up when I'm next online, but if you have a link to an extraction procedure that works, please do post. :)

Even if it means a few hours of a terribly unpleasant trip, I'm willing to go down that route for the sake of Psychonautics.
 

fluoroantimonic

Neurotransmetteur
Inscrit
28 Déc 2008
Messages
26
:D Glad somebody likes the idea.

I read several papers that detailed the synthesis, but I don't have them, I'll have to find them again. If I remember correctly the first step is to hydrolyze off the acetate group of the salv-A to produce salvinorin-B. Not a hard step. The second step is to react it with methoxymethyl chloride (also known as chloromethyl methyl ether) which is not OTC but can be synthesized with a bit of effort (via dimethoxymethane and benzoyl chloride which can both be synthed from OTC materials IIRC). The yields on both steps are pretty good too.

The isolation of salv-A from leaves is pretty simple. Pretty much consists of extracting with cold acetone, boiling off the acetone, washing the residue with toluene/naptha, recrystalizing from methanol and if you want, dissolving it and running it through a column of activated carbon. That should give a pure product and is basically the method used by university researchers. Yield is around 1g per pound of dry leaf. If it's 7 times the potency of salv-A, 1g would go a long way!

I too would love to try this stuff at least once, even if it was not a fun trip.

EDIT:
OK I found it:

Synthesis of Salvinorin-B:
"To a cold (0° C.) solution of salvinorin-A (153.0 mg, 0.35 mmol) in MeOH (3 mL) and CH2Cl2 (3 mL) was added K2CO3 (98 mg, 0.71 mmol) and the mixture was stirred at 0° C. (20 minutes). Water (5 mL) and CH2Cl2 (5 mL) were added to the reaction mixture. The organic layer was concentrated in vacuo and then purified by column chromatography (SiO2 ; 4:1, CH2Cl2 :EtOAc) to obtain 66 mg (48%) of pure Salv-B as a white solid.

Synthesis of 2-methoxymethyl-salvinorin-B:
"10 mg of Salvinorin-B was dissolved in 5 mL of anhydrous CH2Cl2 to which was added a catalytic amount of dimethylaminopyridine (1 mg), N,N-Diisopropylethylamine (2 eq) and methoxymethyl chloride (2 eq) at room temperature and the reaction was stirred for 48 hours. After completion of the reaction, water was added (10 mL) to the reaction mixture followed by extraction with EtOAc (2×10 mL). The organic layer was dried (Na 2 SO 4 ) and concentrated to afford a crude mixture. The crude mixture was further purified by column chromatography (1:2, EtOAc:Hexane) to give the pure compound"

I had forgot about needing the catalytic dimethylaminopyridine and N,N-Diisopropylethylamine. That does make things a little harder.. Still these compounds are certainly not insurmountable, and an alternative route may be possible.
 

Synith

Sale drogué·e
Inscrit
9 Nov 2008
Messages
790
'Better yet, there are analogues of salv-A that are much more potent and long lasting. They are also orally active, so they could be pilled.'

Where'd you find this information?

Salvinorins B, D and E are considered inactive. Salvinorins C and F are unknown to have effect; while some point that Salvinorin C might be more potient than A.

It should be said that Salvinorin A is to be the only active naturally occurring Salvinorin. It seems pointless to make extraction after extraction of Salvinorin to get a more powerful effect. Salv. A will do quite a job on its own.

However, if chemists were to add a Nitrogen atom to Salvinorins A-F, the effects might be more powerful and quite different. Perhaps even dangerous. Who knows. This should be tested, methinks.

:)
 

fluoroantimonic

Neurotransmetteur
Inscrit
28 Déc 2008
Messages
26
:p You misunderstand. I was talking about synthetic analogues. Mainly at the 2 carbon, replacing the acetate group with other things. They have tried many different analogues, most are less potent than Salv-A, but a few are quite a bit more so. One such example is methoxymethyl salvinorin. And yes they have tried adding various nitrogen containing groups to it, but so far only a couple have a potency near that of Salv-A.

If I understand correctly, the C-2 substituted salvinorins are orally active because they do not contain the acetate group that is quickly hydrolyzed off in the body to produce the inactive Salv-B. Other groups such as methoxymethyl are much harder to hydrolyze, thus making the molecule survive the digestive tract, and last much longer in the body in general.
 

Synith

Sale drogué·e
Inscrit
9 Nov 2008
Messages
790
'You misunderstand. I was talking about synthetic analogues. Mainly at the 2 carbon, replacing the acetate group with other things. They have tried many different analogues, most are less potent than Salv-A, but a few are quite a bit more so.'

Where did you get this information?


One such example is methoxymethyl salvinorin. And yes they have tried adding various nitrogen containing groups to it, but so far only a couple have a potency near that of Salv-A.

Again, Salvinorin B (methoxymethyl) is inactive.


'...thus making the molecule survive the digestive tract, and last much longer in the body in general.'

Salvinorin B may be able to survive in the stomach; etc, but how many reports are there that Salvinorin B is as strong as A?
 

fluoroantimonic

Neurotransmetteur
Inscrit
28 Déc 2008
Messages
26
Dude... you're still misunderstanding me... did you try googleing "methoxymethyl salvinorin"? You will see many references just on the first google page... Do you even know what the structures look like? If you did, you would understand what I'm saying..

See this picture:
http://en.wikipedia.org/wiki/File:Salvinorins_AB.png

With Salv-A R1 is an acetate (OCOCH3). With Salv-B R1 is an OH. With Methoxymethyl-Salv-B, R1 is a methoxymethyl group (OCH2OCH3)! Its simple as that! And yes, MOM-Salv-B is very much active! I never said Salv-B is active.

When in the body, whether in the stomach or anywhere else, there are enzymes that quickly remove the acetate group from Salv-A to produce Salv-B which is inactive... On the other hand, these enzymes are not built to deal with the methoxymethyl group, so MOM-Salv-B lasts far longer in the blood stream, and may have the ability to pass through the stomach and absorb into the intestines. Even if it can't survive the stomach, it would still be very easy to absorb sublingually because the dose size is so small (maybe 50-200 mcg)

Do you get it now?

PS. This stuff could be very dangerous.. in test animals it causes immediate immobility, antinociception, and hypothermia, for a few hours (although at doses much higher than those likely encountered by humans). This is in contrast to Salv-A which does not cause any of that even at 10mg/kg(!) Still, I would be willing to try it at very low initial doses..
 

fluoroantimonic

Neurotransmetteur
Inscrit
28 Déc 2008
Messages
26
Hah. Somebody beat us to it. Very interesting information.

I'm surprised the stuff lasts such a short time.. In animal trials they were shown to last many times longer than Salv-A. Maybe it has to do with the route of administration?

Can't wait to see if/when they test some other analogues..

I guess the stuff isn't as exiting as I thought it might be. The possibility of converting extracted Salv-A to an alogue like EOM-Salv-B to multiply the number of possible doses seems uneconomical since the reagents are fairly expensive, the workups are a bitch, and the yield are not great..
 
Haut