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Salvinorin Cyclodextrin Complexation for Sublingual Administration

Migrated topic.
Tonight I tested my water-washed material. Based on my minimum estimates for the amount of plant matter in my initial crude extract from the leaves, I calculated that roughly 20mg of this cleaned amount would be similar to using 30mg of my non-washed mixture.

I used 23mg (cleaned) tonight, and found it to be only about 75% as strong as the 30mg (pre-cleaned) trip.

I'll outline my cleaning process:

Started with 100mg of complexed mixture. I added water, mixed, let settle for several hours, then
recovered the liquid and placed in a drying dish with a fan on it. After more than a day without full evaporation, I placed the dish in the oven at 350F for roughly 10 minutes to finish the drying process. This left the 47mg shown in the previous picture.

I decided to do a second wash as I could still see some green material. After the settling, I recovered as much water as I could without collecting any particulates, and dried in the over at 245F for 20-30 minutes. I scraped up what I could which resulted in 31mg of whiter product than before, and stored.

Tonight, when I weighed all of the product to make sure it was the same, I found the amount to be only 23mg. I do have an inexpensive mg scale which says is +/-3mg, but that decrease was more than I would expect.

In any case, I decided I might as well try it all, and assumed I'd have a little stronger trip than my last test. But it turned out to be noticeably less.
 
I wonder if the heat from the oven was a factor (along with the extra oven cycle). I'll be testing my cleaned up solution soon and I only used a low temperature setting (175F, and with an IR gun I checked the solution and it remained at 120F while drying and my oven seems to run cold when I bake, I think it is about 20F low).

The steroid guys do caution against too much heat -above 100F in solution (link). On the other hand, this patent finds good results up to 140F on complexed drug stability that otherwise degrades.

Maybe with enough heat, the complexed molecule can jump out of the HPBCD (and the temperature may depend on the drug)? Also, HPBCD is simply a carbohydrate, at some point it will burn (oxidize) and break down.

We are in a position to experimentally check this. I can test the current powder I have, then send some samples through a couple other oven hot cycles and see of potency degrades. Also can put it on a hot-plate and check for changes in the powder appearance while monitoring the temperature.
 
Last night I performed another experiment on my complexation to-do list.

In a previous post, I reported my success at using a 30mg dose of the initial (non water-washed) complexed product.

Last night I tested my remaining 105mg of the same non water-washed product.

Although it didn't feel like 3x as strong, it was stronger and a bit longer than before. And to be fair, if I quid 3x my normal dose of 0.8g, that doesn't feel 3x as strong either. With quids, I've found that there seems to be a middle range where adding more doesn't create a stronger trip, but allows for a longer experience. This 3x test seemed similar. At some point I'll try a much stronger test as well.

But the main thing I noticed this time was how it came on. It took much longer. After 20 minutes, nothing was really happening...and with a quid it is always on by 8-12 minutes.

So I started swishing the juice around in my mouth, especially between my cheek and gum where I place quids, and the effects then started to come on as hoped.

So I'm now wondering whether for me personally, I can absorb through my gums/cheek area much easier than under my tongue? Or if there is some additional technique that would help, such as keeping my tongue raised up to prevent excessive saliva production, as I think Loveall mentioned doing in one of his tests.

And if so, I wonder if that is part of the reason my water-washed test was rather unsuccessful?

I did one other thing I should note for the record. Previously while quidding, I've noticed that the repetitiveness and sound of the act of constantly chewing seems to help entrance myself into the salvia space. So when I started swishing the juice around last night, I also started chewing to add that sound/motion to see if it would assist. I don't know if that chewing might have actually broken down the molecules and the waxy coating that I believe surrounds salvinorin or not.

I started a new salvinorin extraction last week from 2oz of leaves. I used long pulls which resulted in a black tar mess initially, and performed roughly 10 naphtha washes over 5 days before drying it out to end up with a nice light-green powdery residue. I plan to complex most of it for further testing as I'm currently out of my previous small test batches. I also plan to try do a 'control' experiment using a bit of the powder orally by itself without complexing.

I'll report back with further tests...
 
Last night I tried an experiment to see if I could chew crude extract by itself (pre-complexation) with positive results.

I recently completed an extraction from 2oz of leaf. (I used long pulls, which resulted in black tar, but after about 10 naphtha washes, I dried it and it turned into a green powder as hoped). I ended with 525mg, so assuming 3mg salvinorin/gram of leaf, that works out to a nice 1:2 ratio of 175mg salvinorin to 350mg plant material.

I only have a cheap milligram scale, so measuring small amounts is tricky, but I started with ~9mg which should have about 3mg of salvinorin, or about the same as a 1g leaf quid.

The 9mg worked, but after 30 minutes it only felt equal to about 0.5g quid of leaf. I was barely getting threshold results. I checked and found quite a bit of green material in my molars, so it was obvious that I wasn't able to grind all of it.

I decided to add another ~10mg. I let it sit under my tongue for a few minutes to make sure it wouldn't dissolve (it didn't), then started grinding away. This increased the strength of the trip quite a bit.

It lasted a couple hours, and felt equal to about a 1.5g leaf quid, which is a nice light-to-medium dose for me.

Although the general consensus seems to be that quidding extracts doesn't work...at least not well...I had read RedGreenVines's posts on the Shroomery about his salvinorin-infused rolling papers working when chewed, so I thought this *should* work if I could just chew the powder properly. And it certainly did :)

However, I've realized that in all of my complexation trials, at some point I chewed while swishing the dissolved mixture as it's a habit from regular quidding. I'm not sure if that should render my previous results null or not. Either way, I'll attempt to complex this latest extract soon and will re-test making sure *not* to chew when specifically testing for sublingual activity.
 
Yes, I think that the replication is null now since you feel the effects with raw extract. I can only get effects when complexed, but now the sample for evidence of complexation is down to n=1.

Another test you can try is to drink it, if you decide that is safe (plenty of info out there and some attached to older posts). You may not get effects with the extract, but you should feel effects with the complexed salvinorin if you get the same results I did.

I'm doing other tests, including nebulizing. Will report back.
 
I just finished up a new complexation batch last night and will hopefully be able to test it later this week. This time I'll be sure to just let it dissolve, then swish but not chew. I definitely chewed the extract to get it to work...

I'll add drinking the product to my list of tests as well, but I fear it may take longer to find time to perform that test.
 
TL;DR - Tested newly complexed batch...made sure not to chew...success. Takes me 4x salvinorin via complexation than via leaf quid for equal results. Having difficulty detaching from body with complexed material so far.

============================

Last night I tested my newly complexed batch with success.

This time, I made sure to leave the product under my tongue and did not chew the dissolved liquid at all.

Notes: When complexing I used a round bowl in a crock pot for the heating/reduction. When complete, I separated the product scraped from the bottom of the bowl from the product scraped from the sides, which had much more green material. The 'greener' material was immediately ran through a single water wash, then dried at room temp with a fan over two days until completely dry.

This once-washed product was lighter in color than the non-washed product, but wasn't completely clean yet.

In last night's test, I started with ~25mg of the once-washed product, which I calculate should have approx 3.5mg salvinorin.

As in my previous 'washed' tests, the results were much less in strength than expected for that dose of salvinorin compared to leaf quids. The effects started to come on around 20 minutes in with light physical effects and no visual component. It compared to 1-1.5mg salvinorin from a leaf quid experience for me.

After 40 minutes, the effects had not strengthened, so I swallowed the juice and added ~25mg of the non-washed complexed product, which I calculate to have ~ 3mg salvinorin. The experience soon strengthened slightly to the point that I was able to coax some light visuals of a location from my childhood. The combo was a bit stronger than the first round alone, but still only equal to about 1.5-1.75mg salvinorin from a quid.

The effects from last night were very similar to my previous tests where I had also 'chewed' the liquid eventually, so I don't think the chewing in previous tests affected absorption.

I am noticing that for me personally, it is consistently taking about 4 times as much salvinorin via complexed product to reach the same trip levels as using leaf quids. So I don't know if this means that this absorption method is less efficient for me, or if not all of the salvinorin is being complexed, but the difference in required amounts is becoming very obvious.

I've also noticed that the main experience that I shoot for with quids, bodily detachment, has been difficult for me to achieve via the complexed trials (possibly due to not using enough yet). When quidding, if I use 750mg+ leaf (~2.2mg Salvinorin), once the effects begin, I soon reach a point of 'detaching' from my body. It is very consistent. If I use 0.5g leaf, I don't reach it, but if I use 0.75g, I do. Every time. So 0.75g+ is my standard quid amount. That detachment has thus far been difficult to obtain, so I will be testing larger complexed amounts to see if I can begin consistently achieving it.

In my initial complexation trials, I believe I was equating my experiences to higher levels of quid experiences than I should have. Last week I did a 900mg leaf quid to remind myself of quid strengths, and to have those trip elements fresh in my mind. I was reminded that those 750+mg quids are quite a bit stronger than I had recalled. I've since developed a personal 'trip level' scale to be able to compare experiences going forward. I'll detail it further below.

I hesitate to add this next note without further testing to verify, but will make it here just in case. So far, it has felt like the non-washed complexed product has been stronger than the washed product when equal calculated salvinorin amounts are used. This doesn't make sense unless the washing is breaking down some of the complexed molecules, or unless the chlorophyll somehow aids in absorption. Now that I have specific items to check off during future experiences, and more product to test with, I'll verify if this continues to be the case or not.

My general trip levels/effects:

1 - light physical: While rolling my head around I can start to feel the salvia gravity/current. Diuretic effects noticed later in trip.

2 - heavy physical: Starting bodily movement with head/arms/hands continues on its own easily without trying. The energy may compel me to sit up straight, move, etc.

3 - light visuals: With eyes closed and covered, visual scenes will come and go but not necessarily constant. Can dance/flow with the current and with eyes closed may be able to visualize the rolling/flowing current. (I have videos but not sure if I should post due to privacy concerns...)

4 - BODILY DETACHMENT; heavy visuals: With eyes closed (and sometimes open), obvious perspective shift from eyeballs/front of face to behind face/center of head and farther away. If I'm working/talking with someone, I'll state 'Ok...I'm out...let's begin'.

5 - body sleeps: Body falls asleep, sleep breathing patterns begin

6 - ???: Unknown higher dose effects

With quids, level 1 begins around 1.25-1.5mg Salvinorin, and I reach level 4 around 2-2.25mg. It ramps up quickly. But it takes 4-4.5mg to reach level 5. There is an obviously plateau at that 2-2.25mg level where detachment occurs.
 
Very interested Physics Envy.

I have done one test with the complexed and water washed material from post #60:

I made a nebulizable solution by dissolving 30mg of it in 20ml of water that had been boiled and still hot (140F) and added 180mg of pickling salt so it would be at 0.9% NaCl (isotonic).

After it reached room temperature, I nebulized a few ml into the lungs with no effect. I drank the reminder with no effect either.

So there must have been some loss of activity during the prep steps because the raw extracted complex (before water washing) was very active both sublingually and orally. Issue could be from adding the complex to hot water, adding the salt, or from the water wash (to add to what you mentioned, complexed salvinorin may not being easily soluble in water - we are assuming it is, but maybe it is not since the large salvinorin molecule may still repel water somewhat, that should be testable by trying the green gunk that is left behind during a water wash). Issue could even be from adding salt (who knows). I got too ambitious and shot for the moon only to get nowhere.

I can retrace my steps try to see where the loss of activity occurred.

The unwashed complexed product has been nice and strong so far. I think gentle heat while drying may be important (the paper mentioned in post #36 recommended 45C(113F) to dry/complex the ethanol/drug/water/HPBCD solution - too hot and the molecules may be vibrating too much to allow complexation - but that is just speculation on my part).

If not wanting to nebulize, cleaning with water may be unnecessary for now until we understand the first complexed product better. In my case where I'm not as sensitive to quidding as you are, the unwashed complex seems at least matched and maybe more powerful than quidding so far.
 
"I think gentle heat while drying may be important (the paper mentioned in post #36 recommended 45C(113F) to dry/complex the ethanol/drug/water/HPBCD solution - too hot and the molecules may be vibrating too much to allow complexation - but that is just speculation on my part)"

Oh - I didn't realize the temp may need to be that low. I kept a thermometer in my water bath to monitor during drying, and the temp was between 150-180F. This may explain the much higher calculated salvinorin doses I've needed than when quidding. Maybe there is a lot of excess crude extract in the mix? Since I've required 4x the quidding amounts, maybe only 1/4 of the extract is being complexed due to the heat (or other issues...). This excess should fall out during the water wash stage, yes?

"to add to what you mentioned, complexed salvinorin may not being easily soluble in water - we are assuming it is, but maybe it is not since the large salvinorin molecule may still repel water somewhat, that should be testable by trying the green gunk that is left behind during a water wash"

I do have the gunk left behind from the small water wash mentioned above. So perhaps that gunk also contains both excess extract AND some amount of complexed salvinorin. Based on my trials, I think the gunk would contain only a minimal amount of complexed product, but may contain quite a lot of excess extract.

I'll try chewing/grinding the gunk and see if the results are anywhere near my results from chewing the extract by itself recently. I'm not sure if I have enough for a good test yet...I may need to do a bigger wash to collect more 'gunk'. I don't know anything about smoking HPBCD, so I'm reluctant to try that ROA for testing...
 
Last night I tested the water-washed residue/gunk from the complexed product, which should not be active if 100% of the extracted salvinorin was complexed, and if the complexed savlinorin is 100% soluble in the water wash.

I used 24mg of 'gunk', and the experience was lightly active at an estimated amount equal to 1-1.5mg Salvinorin from a leaf quid.

However, the gunk was very gummy and hard to grind/chew. Lots of pieces remained in between my teeth and stuck in my molars. I'm not sure how much of the salvinorin remained in the un-ground gunk, but I need to do another test after de-gumming (and most likely infusing on some neutral leaf) for easier chewing.

If I did indeed get all of the salvinorin out of that test amount (1.5mg Salvinorin, 22.5mg plant matter), then that would indicate a successful complexation rate of 83%.

And if the Salvinorin in that 24mg test was actually doubled, my successful complexation rate drops to 70%.

Comparing my complexed product tests against leaf quids thus far, I was guessing that the complexation rate may only be 25%. Based on that, I expected the 24mg test to have 6.5mg Salvinorin.

While it's very hard to guess at how much material was left unchewed, I think it was a little under half. So I expect a more accurate re-test to indicate closer to 2-3mg Salvinorin than 6mg.

Of course, small changes in the amounts make large changes in the calculated complexation rate...and I'm using an inexpensive scale which is +/- 3mg.

But at this point, I can say that the water-washed residue either contains un-complexed salvinorin, or a noticeable amount of complexed salvinorin was not dissolved into the water mix.
 
Thanks physics envy. Seems like the water wash is complicating things. I may try the opposite approach: anhydrous acetone wash where HPBCD is NOT dissolved (this time the hope would be that complexed salvinorin does not go into solution and only the gunk is picked up).

Also, this discussion may be relevant to our work here.

As for nebulizing, it is not really smoking, it is making small water droplets (5um) and breathing that in. There is research coming out now where dry HPBCD is being consider for pulmonary drug delivery (example).
 
"As for nebulizing, it is not really smoking, it is making small water droplets (5um) and breathing that in."

Sorry - my previous comment about not wanting to smoke the product wasn't referring to your nebulizing idea. I was just thinking that smoking the 'gunk' would be a quick way to test if it had any active salvinorin or not...but since I don't know if smoking the HPBCD is safe or not, I probably should skip that ROA for now.

I think the water wash is a good idea to determine whether or not there is any un-complexed savlinorin in the product, and possibly how much. Plus, since my friends all seem to need large quantities of leaf for quids, any reduction in the amount of complexed product would be nice for their sake.
 
My bad, gotcha :thumb_up:

If cleanup is really desired, perhaps the acetone route is better based on our current results.

Worst case would be that complexed salvinorin partially dissolves in both water and acetone. In that case we have no new good cleanup options.

1) salvinorin: very soluble in acetone and virtually insoluble in water (~25mg/L)
2) HPBCD: insoluble in anhydrous acetone and very soluble in water
3) Complexed salvinorin: ????????
 
I just read through a couple of the linked pages at Bluelight, and now have a question. Do you foresee any storage issues with the complexed product, or do you think it might break down over time?

"Worst case would be that complexed salvinorin partially dissolves in both water and acetone. In that case we have no new good cleanup options."

Right. Which would mean starting with pure salvinorin extract would be best if the amount of powder becomes an issue.
 
physics envy said:
I just read through a couple of the linked pages at Bluelight, and now have a question. Do you foresee any storage issues with the complexed product, or do you think it might break down over time?
Click to expand...

I don't know, but based on it being used to stabilize other drugs, I would hope that it has very good shelf-life. I guess we'll need to test it to know.
 
An additional note on water washes:

I just collected the product after 3 days of drying using only a fan, no additional heat.

I started with 350mg of complexed product. I didn't measure the amount of water, but it was 5ml or less.

I ended with 65mg of gunk and 245mg washed residue for a 40mg loss.

I may have left a few milligrams of gunk and washed residue on the evap dishes, but I certainly did not leave 40mg...
 
Guys, it is a very interesting reading! I will hopefully join with my tests as well.

Is there a difference between what is sold as "beta-cyclodextrin", HPBC and HPBCD ?

I would get some beta-cyclodextrin (e.g. this) but I am not sure if it's the right one or should I really have to search specifically for "(2-hydroxypropyl)-beta-cyclodetrin" ?
 
Hey Blue.magic,

Great to hear you jumping in and giving this a try!

Loveall can probably answer your question better than I can, but here is the stuff I purchased: HPBCD

Note that it seems low-temp drying may be necessary for better complexation rates. I dried my last batch in a water bath between 150-180F and my tests indicate a low rate of complexation.

I'm curious how much experience you have with regular quids?
 
Physics envy is correct, get HPBCD. It is the same as "(2-hydroxypropyl)-beta-cyclodetrin". Also, like physics envy said the drying temperature may matter a lot. For now we are trying to stick as close as possible to the following general complexing method (full paper attached in post #23):


Patil J.S.* said:
4. Solution/solvent evaporation method
This method involves dissolving of the drug and CDs
separately in to two mutually miscible solvents, mixing of
both solutions to get molecular dispersion of drug and
complexing agents and finally evaporating the solvent
under vacuum to obtain solid powdered inclusion
compound. Generally, the aqueous solution of CDs is
simply added to the alcoholic solution of drugs. The
resulting mixture is stirred for 24 hours and evaporated
under vaccum at 45 ºc. The dried mass was pulverized and
passed through a 60-mess sieve. This method is quite
simple and economic both on laboratory and large scale
production and is considered alternative to the spray
drying technique.
Click to expand...

We don't dry under vacuum though and mix everything in everclear (instead of starting with two separate water and alcohol solutions). Since you like to experiment would be interesting to see if you test other complexation methods.

Good luck!
 
physics envy said:
Although the general consensus seems to be that quidding extracts doesn't work...at least not well...
Click to expand...

Have you ever wondered why extract has a patchy record when quidded? Extracts are made by infusing dried leaf with a solution containing salvinorin A. The solution fills the empty cells that once contained sap. When the solvent evaporates, the salvinorin A is deposited on the INSIDE of the cells. Not a problem when you smoke the leaf, but a big problem for quidding. Salvinorin particles have to be in direct contact with the mucous membrane to be absorbed.

Why then do some people report success with quidding extract? This probably is related to how the extract was made.

I believe that whole salvia leaf contains substances like saponins and water soluble gums that form stable suspensions of finely divided salvinorin A. This is far easier to absorb than pure salvinorin A.

If the person making the extract purifies the salvinorin solution to remove chrorophyll, gums, resins and tarry compounds, he would end up with a fortified leaf that would produce a poor quidding experience. This is because he has also removed the substances that help transport salvinorin A across the mucous membrane.

On the other hand, if someone is lazy and does not purify the salvinorin solution, they would have a better fortified leaf for quidding.

Another factor is the concentration and therefore the viscosity of the solution applied to the dried leaf. If most of the solvent is allowed to evaporate before the solution is applied to the dried leaf, the solution would have a higher viscosity, and therefore less likely to penetrate into the leaf. If the dried leaf is infused multiple times with a dilute solution, it would even wash off the salvinorin on the outside of the leaf, and deposit it on the inside.
 
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