Just to bring the uninitiated up to speed on some of the concepts.

As it is known cyclodextrin(a,b,y,etc) complexation of molecules can improve bioavialability of some drug molecules via buccal(sublingual) administration. This is the case for certain nitrogen containing compounds such a 25i-NBOMe. A similar methodology has some-what recently been applied to cannabidiol a terpenoid(see attached paper for details).

Normally terpenes and many drug molecules have a hard time crossing into the blood stream by sublingual means. This can be aided by 'enclosing' these molecules in cyclodextrins. Cyclodextrins, or CD's for brevity, are essentially cylindrical sugar polymers. When a molecule is complexed with them the molecule fits inside of them like a ring to a finger.


The CD is the cylindrical shaped molecule.Note this image is not a completely accurate depiction of the goal but it is demonstrative
(Image taken from wikipedia)

The issue with extracted Salvinorin(s) is that they aren't really active sublingually. From personal experimentation I obtained a come-up of a salvia experience lasting maybe 20 seconds, as did a friend of mine. Nothing more, and on most other trials less. This is well known.(Reference: https://www.maps.org/sys...llinfo&type=citation)

In theory the salvinorins could be easily complexed with B-CD or Y-CD by the same means mentioned in the cannabidiol paper that is attached. Precipitation from ethanol and water. The salvinorin could then be laid on blotting paper or impregnated easily into lamels for controlled dosages. The choice of the CD to use is a bit daunting due to the size of the molecule(salvinorin A), Y-CD may be the best option, though maybe B-CD would also work. It would be nice to know some of the relative dimensions in Angstroms of the molecule to get a feel.

In my opinion this is a very viable concept for adequate sublingual administration. As much as I would love to pave the way I have no access to salvia bio-mass as it was out-lawed where I live. However, for any other savvy experimenters I feel this could be of interest.

Cyclodextrins can be bought without hassle to my knowledge. They are commonly made through enzymatic means using a starch source(paper attached). The commercial availability of the CGTase enzymes is unknown to me. B-CD being the easiest to isolate because of it's miniscule water solubility. The product fabreeze also contains a hydroxpropyl-cyclodextrin which is another idea to work with, though I do not know of it's toxicity.

I recall looking into this for 25I-NBOMe because doing this would make dosing sublingually/buccally significantly easier. As far as I remember, it isn't a simple matter of mixing chemical A with chemical B to produce this complexed chemical AB. But if one has the necessary lab tools to do so and desires to, then by all means do it in the name of science for us! But I don't think any average user would have the necessary tools lying around their house to do this. Then again, we aren't average users.

I'd love to be able to complex my own blotters!!

I have some salvia plants and leaves and have been trying to come up with some way to ingest them sublingually.



What might this look like to the kitchen chemist?

Actually, this is not the case. At least in the case of 25i, it is simply a matter of putting the chemical to be complexed and the complexing agent in solution together and mixing. AFAIK the most involved tools one would need for this are a reasonably accurate scale and a magnetic stirrer.

I will be looking into this further in the coming weeks to see if there are any more complications to the issue that I am not aware of, as well as to get some theoretical mass ratios for complexation. I do have hydroxypropylbetacyclodextrin available to me; however, I will have to do some extraction/purification work in order to have salvinorin A suitable for experimentation.

Perhaps this will result in a notable improvement of the already-impressive activity of sublingual tincture.

As long as the hydrophobic pocket of the cyclodextrin fits the molecule, that's correct.

For what it's worth, you can reach 0.5 mg/mL salvinorin A in an aqueous solution of 0.25 M Captisol (a polyanionic variably substituted sulfobutyl ether of β-CD). From the source [lovell2011]:



Sonication for 72 hours is probably overkill. As long as the salvinorin A is very finely ground, letting it stir for a day or two ought to do the trick. And the centrifugation and syringe filters were only used to remove the excess salvinorin A. If you only add an amount you know will dissolve (like 0.5 mg/mL in 0.25 M Captisol), they shouldn't be necessary -- unless you're planning to inject the solution, in which case you should always take extra precautions including the use of micron filters.



BibTeX

I have experience with complexed nbome tabs and my own layed nbome hcl uncomplexed tabs. There is no difference. It is also much cheaper and easier to just convert the freebase to HCL, so I'd just go with that.

If anyone wants to try complexing something at home and does not have a magnetic stirrer, just google 'how to make a magnetic stirrer, it's super easy.

How do you know that you actually complexed the two molecules? what evidence cues you to that?


I'd like to see more evidence of that, because for the moment I am not convinced that complexing can be as simple as A-B-C.

Give us hard data (or at least some decent indications). For the moment your claims stand unsubstantiated.

Where did I say I complexed anything ? I have layed my own HCL tabs and I have tried | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | complexed tabs from a reputable source.

I've seen you misinterpret many things people have said lately and then had a go at them.

Also regarding the complexing, try other forums, there are many reports of freebase NBOMes being ineffective until the person complexed them, which infact is just a simple case of mix the correct amounts together in solution. It's very easy and many have done it.

As for how easy this might work with salvinorin I cannot say.

Thanks for the heads up InMotion, I was wondering about this recently, re: low sublingual activity of salvinorin vs. high sublingual activity of leaf quids. The tincture commercialized by Siebert is reportedly active (and is allegedly made from leaf following a different process than plain ethanol extraction) so, unless Siebert's tincture has additives, I wondered which other chemical in the leaf is responsible for the activation/solubility enhancing of salvinorin.

The barely hydrolyzable A and B cyclodextrins occur in nature, but they require the CTGase enzyme common in some types of bacteria to be produced, so either (and I'm just thinking out loud here, allow me to speculate)

1) There might a chemical in the leaf that complexes with salvinorin, improving its sublingual absorption, but it's not a cyclodextrin
2) Bacteria with CTGase might be present in the plant, so the more effective BCD would be present in the leaves and complex with salvinorin when dissolved in saliva
3) Bacteria with CTGase can be present in the mouth, producing cyclodextrin out of the leaf starches when quidding

In either case, other diterpenes with low water solubility are indeed effectively complexated with | High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) | or methylated BCD. One effective way, for instance, might be recrystallizing the diterpene and adding it to a high concentration solution (66%) of random methylated BCD, well agitated at ambient temp. This reportedly has increased the availability in solution of certain diterpenes x5000 (source).

I'm actually more curious about the possibility of activating swallowed leaf or tea in a reliable way, by inhibiting carboxylesterase. Benzil might be a safe inhibitor (source).

Good point, my apologies.

This is a good place to start from if you're looking for enzymes to inhibit and orally activate salvinorin

https://www.dmt-nexus.me....aspx?g=posts&t=4823

both carboxylesterases and lactonase inhibitors might be useful

Thank you, I found a ton of useful information starting there. Arenaria serpyllifolia can certainly be found in my area, and it's been used safely for detoxifying and losing weight. Thapsia garganica and Rhamnus alaternus are purgatives in local herb lore, the second (aladierna in spanish) being quite common. Nice lead to follow.

Nothing new on this ?

I had posted a High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) |)" title="https://www.anoniem.org?http://www.bluelight.ru/vb/threads/599533-Salvinorin-A-and-hydroxypropyl-cyclodextrine-(| High Pobability of Braindamage by Creepy non tested Drugs (forced by scammer 69ron) |)">thread about this on bluelight that is now archived.

Salvinorin blotters would be great indeed, IME it is not easy to get a strong experience with the quid method.

But maybe a complexed tincture would be easier to make and sufficiently effective ?

Do someone knows if beta-Cyclodextrin would be suitable to do this (if not why) and in what proportion it should be used ? Maybe we can use it in excess without trouble ? Or, as suggested in the bluelight thread maybe a common sufractant would be enough (soy lecithin ?)

Now that I have the time, I plan to try this anyway but because I really don't know what quantities of beta-Cyclodextrin is needed, any advice would be appreciated !

Wow maybe I should read blue-light more often. Great minds think a like only your was a year ahead of mine, so that may say something, hehehe.

Anyways, I would try working with the same proportions for cannabidiol and use a similar method. The centrifugation can likely be omitted. The article claims a 1:2(CBD to CD) molar ratio. I have no means to measure the molecules in angstroms but that is the key as to which cyclodextrin to use. I'm sure a C.D. could be extracted from say fabreeze but I wouldn't go that route.

Wish I could actually kick-start this beyond theory but access to the plant material is not in my favor and hasn't been for several years now... Hoping to see someone try this out!

The interior cavity of β-cyclodextrins is 15.3 Å (according to this NIH webpage).

We can find information on the geometry of salvinorin A from chemicalize.org. As I understand it, we're mainly concerned with the diameter of the minimal projection area, since that's what we want to stick into the cyclodextrin cavity. In this case, the minimal projection area is 67.07 Å^2, which translates to a diameter of 9.241 Å.

The dissertation mentioned above used Captisol, which is a modified β-cyclodextrin. If you want to use that dissertation as a starting point, the molar ratio of salvinorin A to cyclodextrin can be easily calculated from the figures given above. 0.5 mg/ml = 0.5 g/L. For salvinorin A, 1 mol = 432.4636 g. So 0.5(g/L)/432.4636(g/mol) = 0.001156 mol/L = 0.001156 M. Let's round that to 0.001 M for simplicity.

Now, I just noticed an anomaly in Lovell's dissertation. In the text, she talks about solutions of Captisol ranging from 0.5 M to 2.5 M, but in her data table she gives the concentrations as ranging from 0.05 M to 0.25 M. If the figures from the data table are correct, than the molar ratio of salvinorin A to cyclodextrin is 1:250. If the figures from her text are correct, the ratio is 1:2500.

Either way, that's a whole lot more than the 1:2 ratio given for CDB. But then, CBD is a smaller molecule. Its minimal projection area has a diameter of 8.087 Å... but that's a deceptive number, since CBD probably only needs to stick in up to its benzene ring, the other substituent ring can probably dangle outside.

Perhaps the larger cavity of gamma-cyclodextrin would be more effective for salvinorin A? Hopefully someone a bit more versed in the mechanics of intermolecular interactions can chime in.

You must be misinterperating the paper, or maybe I am misinterperating what you have said. This is a ridiculously massive excess. I mean in order to complex 0.1g of salvinorin{0.1g / 432.46g/mol = 2.312e-4mol} one would need 65 grams of b-cyclodextrin(1mol:250mol){2.312e-4mol * 1135g/mol * 250 = 65.60g}... Or 656g if(1mol:2500mol){2.312e-4mol * 1135g/mol * 2500 = 656.03g}. Does not even sound right. Salvinorin A is not THAT big of a molecule compared to Cannabidiol. Please upload this article/dissertation.

edit - just because someone uses a 0.5M solution does not mean they used 0.5mol of reagent...

I don't own the copyright to the paper, but I believe that attaching the relevant 4-page excerpt for discussion in this context constitutes fair use.

Unless you read it differently than I do, it seems to indicate that the equilibrium significantly favors dissociation of the Captisol-salvinorin A complex.

Now, I understand the study a lot better. Thank you for uploading that. You were definitely right in that the equilibrium is far towards the reactants verses complexed Salvinorin A.

What Lovell did was added excess 'Salvinorin A' to different molarities of "Captisol" then measured the absorbance of the solutions. Which is great. 0.5mg or 500mcg of salvinorin per mililiter is totally acceptable for oral administration. Sadly that means about 5.4 of capitisol must be used per mL of liquid, making such a solution pretty expensive.

Here's something a bit confusing though. I looked into the solubility of capitsol(http://www.captisol.com/faq/how-to-solubilize-a-drug-with-captisol/); the solubility is listed as >1.500g/mL or >1500mg/mL or . So how does someone make a 2.5M solution in 'sterile water'? F.M. of Captisol TM = 2163 g/mol, meaning 2.5M soln has 5407.5g per liter or 5.408g/mL. Under these conditions the solution would likely become a gel, like some of the other cyclodextrins at high concentration. Thus making the actual solubility impossible to calculate and a 2.5M solution reasonable.

It is a bit peculiar though that they use a solvent(water) Salvinorin A is poorly soluble in. Suppose they relied on the ultrasound and the 72 hours to reach the equilibrium. I see why they wouldn't use ethanol and water mixture like the CBD paper, because they wanted no amount of ethanol due to it's opiod activity for biological studies. Although using a different solvent could have a very different result. Solvent effects seem like they would be critical for this, in-fact that's essentially what this intermolecular 'interaction' is. At least that's the way I see it, I'll have to think about this a bit more...

This is really interesting, has anyone trying something about this?