So I have been wondering if anyone has had any good results using other plants to potentiate the oral use salvia. From what I have read it seems MAOIs work on different systems, but a class of compounds called carboxylesterase inhibitors could yield an oraly active tea. Interestingly enough another species, salvia verbenaca, is said to contain some content of the carboxylesterases inhibitors. The most promising plant was said to be Cleome Arabica.

I wonder if brewing these two plants together would yield an Ayahuasca style brew, with the active compound and the enzyme inhibitor to make sure it reaches the brain?

If something like this works, could it be added to an Ayahuasca brew for a very profound experience?

Oh ya, here is my reference:

http://px7gv7gt2n.schola...e=719&issn=1475-6366

I'm afraid your reference requires a login.

In any case, I suppose you have already had a look at the cyclodextrin salvia complexation thread and the very relevant thread linked by Infundibulum.

What I can add in this sense is that I tried a strong Arenaria tea followed by ingestion of 500mg + 500mg 40 minutes later of dry salvia leaf, without significant effects (mild buzz, most likely placebo). Arenaria serpyllifolia was one of the species brought up in the paper Infundibulum shared regarding carboxylesterase inhibitors in certain mammals, and the Arenaria I found and tried was most likely Arenaria Montana. I'm guessing because it's the most frequently mentioned in my local herbal lore.

I still want to obtain A. serpyllifolia and repeat the assay.

But that would be an experience by itself, besides ayahuasca.

Really? I'll see if I can find a different link.

I have been trying to find more info on Arenaria serpyllifolia, but there is not much.

Ill try attaching it

Can we post links to herb vendor sites as long as they do not sell anything illicit?

In our effort to push our members toward personal sustainability and responsibility in their use of these substances, only vendors of live plants and viable seeds are allowed to be posted here now.

We are all proficient in the use of search engines these days, I'm quite sure we can seek out anything else we might need with a little of that old google-fu.

Ok, just making sure, found a good site that has some the the plants mentioned in the report. But I'm sure it would not be hard to find

I hope someone tries this and reports back. Good preliminary work Vodsel.

My only curiosity is in Infund's thread there is also mention of lactonase enzymes splitting open the lactone ring moeity. Blocking those sounds like a whole different story.

Yes, at first I'm trying to focus on carboxylesterase inhibitors. There's quite a few plant candidates to try. Besides the mentioned ones, I was reading about Euphorbia Hirta (CEi properties tested here) which happens to be a known plant used in the Philippines for treating dengue, and attributed to have several other therapeutic properties. One of the local names is tawa-tawa, and herbal extract can be found online.

Also, have you checked the paper posted by Lumos, InMotion? I'm saying because P. Harmala (mistyped Pyganum in the text) appears in the list with significant CE inhibition in pigs, using polyphenol extract.

I'm assuming a phenolic extract is performed with MeOH, is this correct? Would that pull alks and flavonoids from ground rue?

I was surprised to see that P. Harmala was in the list of plants that contain CEI's. I have not been able to locate a source of Cleome Arabica, but Agropyrum repens is another good candidate and is easily obtainable.

I plan on doing some tests using as many of the listed plants as I can get.

So, here is my list of easily obtainable plant CEI candidates:

Agropyrum repens
Peganum harmala
Euphorbia Hirta
Levisticum officinale
Malva silvestris

I plan on testing all of these and any others I can find, but these ones for sure.

Now my next question, there are quite a few different strains of S. divinorum strains out there. Are some more potent than others? And, what are their differences, if any?

These seem to be the main ones out there.

'Blosser Strain'
'Cerro Quemado'
'Hoffman & Watson'
'La Fuezra'
'Luna'
'Paradox'

It sounds like Luna is an interesting strain, it has a unique look, and I heard it's more potent; is there any fact to that?

Last time anyone published a study comparing different strains was over a decade ago... but as I recall, variation between different individual plants of the same strain was more significant than variation between different strains.


Regarding this whole issue of carboxylesterase inhibitors... might'nt you be putting the cart before the horse a bit? Carboxylesterase has been identified as an enzyme that rapidly degrades salvinorin A in the blood. So halting that metabolism will only potentiate a drug that is actually making it to the blood in appreciable quantities... and it's not clear that happens with oral S. divinorum.

I'm not saying you shouldn't try this... actually, I think that such an experiment would be very worthwhile. It's possible that carboxylesterases are also metabolizing salvinorin A in the intestine and in the liver, in which case carboxylesterase inhibitors could very be helpful. If it works, that's some very good information (and if it doesn't, that's useful information too). But I'd caution not to get your hopes too high due to the number of other factors involved.

The biggest factor is getting salvinorin A into your bloodstream from your gut. Medicines which are poorly soluble in biological fluids typically don't work well orally, and require special preparation. That's the part of the purpose behind the thread about complexing salvinorin A with cyclodextrins. But even if you generate a preparation with a better solubility profile, there's still the question of how readily it can permeate the membranes of the stomach/pylorus/duodenum/wherever... For salvinorin A, the question of permeability hasn't been studied yet (to my knowledge).

It's also worth considering the other metabolic processes (besides carboxylesterases) that degrade salvinorin A:

• Lactonases: The same group that found carboxylesterases to be responsible for the rapid metabolism of salvinorin A in the blood also noted a lactone ring-opened metabolite. It appeared to be the primary metabolite of salvinorin B, so perhaps salvinorin A's acetate ester blocks this lactonase from causing trouble. Or maybe the esterases are just de-acetylating the ring-opened metabolites of salvinorin A so they look like metabolites of salvinorin B.
  
• CYP-450 enzymes: There's some evidence that CYP2D6, CYP1A1, CYP2C18, and CYP2E1 are all able to metabolize salvinorin A to some extent. A different study found that liver microsomes metabolize salvionrin A rapidly, and that this metabolism decreases in the absence of NADPH (a CYP-450 cofactor), supporting the notion that CYP-450 likely plays a role, especially in first-pass metabolism.
  
• Glucuronidation: UGT2B7 (UDP-Glucuronosyltransferase-2B7) also appears to metabolize salvinorin A.

Shouldn't those same enzymes cause a problem while quiding? Since the salvinorin a goes directly into the blood stream from the mouth. Maybe that's the reason it only works for about an hour? There are probably some other enzymes in the brain that break it down too.

I'm not too worried about it working or not, I just like to do experiments

That's essentially my point. Quidding works in spite of these enzymes... which makes me think the issue with oral use is not related to metabolism after salvinorin A has entered the bloodstream. I think it's an issue with getting it into the bloodstream in the first place -- either from poor bioavailability due to solubility/permeability issues, or from significant first-pass metabolism.

Carboxylesterase inhibitors seem like they have greater potential to augment the effects of quidding, smoking, etc., than of oral ingestion. But even with those more effective routes, metabolism still might not be the most significant factor. Researchers have shown that salvinorin A gets cleared rapidly from the brain due to issues other than rapid metabolism (they showed this by comparing salvinorin A with a salvinorin analogue that is metabolized more slowly).

Would there be a reason that salvinorin a would have a hard time entering the blood stream? It seems like it is fairly lipid soluble. Like LSA has no problem entering the bloodstream after eating some HBWS.

One interesting thing that I read reminds me of a post about quidding, someone said that eating chili peppers increases the absorption rate. On Wikipedia there is a statement about intestinal mobility "A pharmacologically important aspect of the contraction-reducing properties of ingested salvinorin A on gut tissue is that it is only pharmacologically active on inflamed and not normal tissue, thus reducing possible side-effects. Could slight inflammation in the mouth have anything to do with this?