That's all beyond my knowledge but makes sense.

In my particular trials above, I just used the straight up extract (which was probably 2:1 chlorophyll/leaf:salvinorin) and not a re-fortified leaf. So maybe that's why it worked. I haven't actually tried quidding any of my enhanced leaf...perhaps that experiment would fail.

I have read through this entire thread half a dozen times, because it is so interesting, and corresponds well with what I am trying to achieve.

Your straight up extract intrigues me. It is chemically active, but does not disperse well in saliva. It appears to be sticky, because it became embedded in your molars.

Perhaps it can be deposited onto an inert, non-porous substrate, like unscented talcum powder. Maybe corn starch is suitable. Under an electron microscope, corn starch granules appear smooth and round, without cracks or fissures. Cellulose fibres would probably work as well, because they are not porous. You need to avoid things like dried leaf, which behaves like a sponge. It is important to get the salvinorin to reside on the outside of the substrate, not the inside.



I would like to repeat your extraction, and try depositing onto various substrates. I think the choice of solvent is important. Did you use 75% ethanol or 99% ethanol as a solvent? 99% ethanol may be an excellent solvent for salvinorin A, but a poor solvent for the gums and saponins you need. The 75% ethanol is a worse solvent for salvinorin A, but may be better for the other components.

I could also try a sequential extraction, e.g. acetone, followed by something that would dissolve the more water-soluble components in salvia leaf. I would combine the extracts, and deposit that onto my non-porous substrate.

Just to clarify, I only used the 75% Everclear during the complexation process...not during the salvinorin extraction process.

I used cold-to-luke warm acetone for the pulls (started at 20F), then naphtha several times to clean. I did not use additional cleaning steps with IPA to get a pure extract...I just left it at that somewhat crude phase which I eventually bioassayed.

For the extraction process, I basically followed the first half of Gibran's method from his pinned thread here.

I'm guessing you've extracted salvinorin previously, but if not, you can avoid the black tar mess I created on my most recent extraction if you use colder acetone and/or shorter pulls. It will save you a few days of extra cleaning that I had to go through. When I did my last one, I realized AFTER that I could have set my freezer much colder .

Obviously, I'm interested in what you come up with!

Black tar mess is good! It contains the magic molecules needed to make the extract orally active. You just need to spread it over a bigger surface area. So I will be buying some acetone this weekend, and do a warm extraction.

Maybe I'm misunderstanding...is your plan is to leave it as a black tar, without cleaning it and getting it into a (seemingly more usable) powder form? Then disperse the tar over various substrates?

Yes, exactly! This is the low tech alternative to cyclodextrin complexation.

Thomas Munro wrote a PhD thesis entitled "The chemistry of Salvia Divinorum" links here and here.

On page 49 he says that amorphous solids (as in crude extracts) have better solubility than crystalline material. In the text, 1a refers to salvinorin A

On page 50 he says, "Many instances have been reported of enhanced absorption of active compounds from a crude extract relative to the pure compound. For instance, some terpenoids are known to act as permeation enhancers, increasing trans-dermal absorption of co-administered drugs up to 90x". I think both you and Loveall have found the same thing.

Are you familiar with the expression "throw the baby out with the bath water"? There are substances naturally present in the leaf that disperse and transports the salvinorin A across the mucous membrane. These substances are removed and discarded during purification. Purification is good if you want to smoke salvia, but bad if you want to absorb it sublingually.

I did not mean to derail the cyclodextrin thread. But it seemed to have reached an impasse. My reason for posting was to stimulate creative thinking in this area.

Thanks Zebbie, that is interesting

I want to do more work on cyclodextrin complexation, which seems reversible if heated. Want to thank all of you for being paitient.

It looks like complexed salvia does work, but it needs to be evaporated at low temperatures to achieve good complexation. It is a simple procedure, mix the extract with everclear and cyclodextrin powder and evap at room temp over a fan.

There a lot of questions such as how much has completed? Should the mix/dry process be repeated a few times to complex completely? Do we need a certain salvinorin/| High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | ratio to maximize complexation? Does salvinorin need to be pure to complex properly without other stuff getting in the way?

I found good results: complexed salvinorin was active when drinking it. I think that was marvelous. physics envy had some promising results, but at the end of the day the crude uncompled extract and the complexed extract seemed similar in activity (for me the uncomplexed extract was not active). This may be due to different sensitivity and/or different amount of terpentines on our extracts.

I've promised physics envy a follup-up and that is coming. Salvia plants are happy growing outside. I also got thymeleaf sandwort to test too, see if we can make an effective complexed salviauasca.

Also, there are glaucoma drugs delivered with | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | as eye drops. Not telling anyone to try this but that would be a new ROI complexation may open up one day.

Well - I'm curious as to how easy it will be to disperse the black tar, and then what it's like to use it. In my experience, it was just a sticky clump which was a PITA to break down...at least with my low-tech home-lab equipment (I have only very rudimentary kitchen/lab equipment and skills...part of the reason this thread has been on pause.)

Loveall has some ideas on increasing the comlpexation efficiency (using more | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) |, dissolving and drying several times, drying with a fan, etc.) that he is planning on trying after growing some more leaf this summer.

Also, he will be able to test via TLC, so we will then have a better idea of how much is actually being complexed. We had planned on having me test his batch next round, so perhaps that will happen this fall.





I haven't re-read this thread in a while, and I probably mentioned this, but in my complexation bioassays it always felt like something was missing (although I realize that doesn't really make sense). But it was very hard for me to get all the way to that point that I shoot for when using my complexed material. It gets me most of the way, but not quite all the way. And I tried using much more material a few times which as I recall only resulted in longer trips, not deeper ones. This was another reason I paused working on this - to wait for a potentially stronger batch from Loveall.

Far out! I love crazy ideas!

I managed to buy a small bottle of acetone this afternoon. So I am about to re-create physics envy's black tar mess.

Ready, Zebbie, go!

Attaching a new 2018 paper that used | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | to improve a the bioavailability of a drug.

The paper uses TLC to check complexation. Also measures a spectra, which we may be close to doing with home Raman. It then uses NMR to propose how the complexed drug looks (and some nexians have shown NMR results for DMT).

To form the drug complex they mix it and evaporate it (they do it in acetonitrile under alkaline conditions before going back to ph7). Anyone know why they used alkali conditions? Do they simply need the drug to be lipophilic so it slides into the cyclodextrin cavity? Makes me want to add ammonia to the everclear/salvinorin mix as a test.

It's a very nice paper for anyone interested in the subject.

I think the reason for using alkali is to maintain stability. Toltrazuril has a triazone trione moiety in its structure. Many years ago I made triazone urea fertilizers. These were stable under alkaline conditions but hydrolyzed under acid conditions.

I believe adding ammonia will be detrimental to your process. The ester and lactone bonds in Salvinorin A will be targeted by ammonia.

Esters hydrolyze in water. Ester + water ⇌ carboxylic acid + alcohol. Any alkali will react with the carboxylic acid to form the salt. This effectively removes one of the products, and shifts the reaction towards the right (Le Chatelier's principle).

I think salvinorin A is stable while it is inside trichomes, or deep within a leaf as an extract, or as salvinorin A crystals. But once it is in molecular form, it is easily degraded by light (tinctures, for example) or maybe oxygen and substances like alkalis and esterase enzymes in solution or thin films.

How stable is your complexed salvinorin, Loveall? Have you done any stability tests?

It seemed pretty stable over a couple of weeks. I have a tiny bit of 1 year old complexed salvinorin in the pantry I need to test again by drinking. Since | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | can stabilize some drugs for long term storage maybe it protects salvinorin too.

The one thing that made it innactive was redisolving it in hot water. One possibility considered was that the heat kicked out the salivnorin from the complexed structure. That is why physicsenvy was saying that we are going to try again, this time evaporatating the alcohol/water/| High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) |/salvinorin dispersion at room temp with a fan.

Regarding the pH during complexation, I think we will want to target/test a pH where the molecule is neutral. Being neutral may help it get into the | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | lipophilic ring center. Will run the chemichalize demo to see what that pH is in water (I can't find a pka for salvinorin A). Will need to be careful since as you say some functional goups can break down at certain pH though. Not sure how it will work though since as we evaporate the pH can change. Hopefully simple neutral distilled water works.

Thanks for the response, Loveall. It is quite possible that the instability I observe in my experiments is not due to any degradation of salvinorin A, but due to degradation of the "carriers" present in the crude extract. If the carriers get destroyed, then they are unable to transport salvinorin into the mucous membrane.

The article you attached is very interesting! I hope you and physics envy succeed in your quest.

There is no pKa for salvinorin A, because it does not have any ionizable acidic or basic groups, see attached image. But your refined salvinorin extract may still contain impurities that affect the pH of the alcohol/water mixture.

If you want to conduct your complexation at a neutral pH, you could buffer the alcohol/water mixture with a pH 7.00 buffer. These are sodium or potassium phosphate buffers made up for calibrating pH meters. The commercial buffers probably contain a biocide, so you would have to prepare your own from scratch.

Thanks, that saves me from running the chemicalize(Marvin) program.

Since salvinorin is non ionazible I won't mess around with the pH, salvinorin should simply be in a lipophilic state. If on the other hand I one day try to complex DMT I'd try in a basic solution for starters, psilocybin at it's isoelectric point (pH~4 if I recall correctly), etc.

If you are interested is easy to get | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | for complexation tests. It can be seen as a fiber supplement I think. The most interesting part about complexation is that it seemed active orally (drinking it). However, we need to repeat and standardize the process. | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | boost to drug bioavailability opens interesting ROI possibilites like nebulizers and eyedroppers.

Edit: this particular passage in the previous attachment sounds interesting:

I have no information to add to this thread but I do have a ton of thanks and respect to give. Every post was fascinating and inspiring to read. Thank you to everyone who contributed. Our community is amazing. I never experienced salvia and don't plan to any time soon, but I will be rereading this thread multiple times to gain knowledge about the process. Your hard work is highly appreciated.

Every member who hasn't read this, get your butt in here!

I do have one question. How could we tell if we successfully complexed the molecules without technology? Do we have to rely on our senses? Say, if the original molecule is bitter, like salvia, when it's complexed will it no longer be bitter?

I don't know if anyone have any success with Salvia divinorum extracts complexion but this would be great as this plant is quite productive in its terpenic production. We just have to get different ways of absorbtion. Smoking it is easy but lame ... so far I use it varpirized high temp, but I tend to prefer the effect of sublingual but those are often too mild..

Maybe complexed Salvinorin A dissolves differently in water. That may be a way to check, not sure (uncompleted Salvinorin A with simple | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | added may also increase water solubility).

Another option is to destroy | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | in a strong acid. Salvinorin A may precipitate from a water solution. Downside is that the precipitate may be something else if the acid is too strong and destroys everything or if there is no window where Salvinorin A survives while | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | is destroyed.

This is all theoretical, but could make for some fun experiments. Maybe there other better ideas.

Edit: it is possible that | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | (and complexed | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) |+Salvinorin A) gets trapped by a water purification ion exchange resin, while Salvinorin A does not. That may open an interesting line of experiments.

Below is a table from a review on buccal drug delivery enhancers (from 2011).

Some interesting options that are over the counter

Cyclodextrines: Tested here with mixed results, at the moment does not seem completely robust.
Chitosan
Citric acid
L-lysine
Oleic acid

Several others are easy to get a hold of. Maybe we need to more than one compounds with different mechanism of action. Testing would be simple. Maybe quids could also be enhanced.

Cheers.

I really hate to bring this post back to life but I just complexed some and I felt I needed to post my results .

First I used 15 grams dried leaf and put it in acetone (100ml) per 5gr amounts on magnetic stir for a few days . overkill really but I had other tasks that were priority .

I then put the combined 100mls ...300ml total more or less into a sep funnel and let it settle and after a couple days drained off some minor debris . oh prior to that step is I had filtered the acetone extractions as well using common coffee filters .

I evaporated the acetone and added 91 percent isopropyl and added 2 to 2.5 tsp | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | powder turned stir on and set the temp on the hot plate to 170F.

All of this boiled off till I had roughly 50ml of dark green solution .

I placed it in a plexiglass baking dish for a decent cake size and put it on an electric stove on the lowest setting and finished evaporating . after 2 days I scraped off a partly crystal dark green like powder 3 tsp approx. I haven't weighed it yet .

I wasn't planning on trying it but some was on my fingers . I'd say it was a 2x match head sized amount and I really didn't think anything would happen. Within 2 minutes i had to lay down . familiar quid amounts way way more than that amount taken in the many gram area of rehydrated leaf effects were felt. I was at the point of minor water like wave overlays oev only . it was a little difficult to see clear and some warping was beginning . the body load was heavy as well so I really wasn't sure how deep this was going to go. I kinda started hoping it didnt get stronger bc i wasn't prepared for that and was alone in case of anything .

It didn't . it slowly faded over an hour and the last hour i felt fantastic .a rainy day had turned sunny. All the fall tree colours and blue sky was absolutely perfect to witness . I would certainly say this is my preference roa for salvia .

Normally I rehydrate many grams of leaves in small amount of red wine and hold for 15 min. In my mouth but this onset was within 2 to 3 minutes . fast !

I think the stir over 2 days complexed the two better at room temp then at near boiling temps for a couple hours also for isopropyl alcohol possibly . thank you loveall and everyone who contributed to find this roa. Deeply thank you ! I've been feeling great all evening and look forward to exploring with small increases to find what I believe my actual dose is . there couldn't be more than 50mg salvinorin a total but whoa man that was maximal efficiency !