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Salvinorin Cyclodextrin Complexation for Sublingual Administration Options
 
physics envy
#41 Posted : 12/20/2017 5:40:25 PM

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Thank you for the additional information - that will be helpful :-)
Salvia quid enthusiast
 

Good quality Syrian rue (Peganum harmala) for an incredible price!
 
Loveall
#42 Posted : 12/23/2017 12:59:30 PM

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I have good news. Last night I drank 25mg of complexed salvia (3.6mg of salvinorin estimated) dissolved in water (about 1/4 of a cup). It did not completely dissolve and I saw bits of undissolved material, I wonder if that is plant material that could be removed by filtering the water solution (HPBCD is very soluble in water and I'm guessing complexed HPBCD is soluble too).

Anyway, I drank the water with dissolved HPBCD/Salvinorin/PlantStuff. It had a faint bitter taste, not unpleasant or overpowering. I was thinking it probably would not work (HCl in the stomach). But I was also hoping that HPBCD could protect the salvinorin and help it into the body while in the digestive track.

It worked. I felt the effects. They were milder than the sublingual effects from the last test, but they lasted longer. There was a nice plateau where stories were being told in a mild dream-like state. The plateau lasted quite a bit which was surprising, and to be honest got me a little worried since it was lasting longer than any other salvia trip and I had never really plateaued for a significant amount of time (more than 10 minutes) with other salvia administration methods. Everything was fine though and eventually the effects started to fade (as they always do).

It would be interesting do drink a larger dose at some point. For now the complexed salvia sits quietly in the pantry, waiting for an opportunity to tell its stories.
“... (a) psychedelic substance occasionally causes psychotic behaviour in people who have not taken it.”
Excerpt from a McKenna talk transcript / audio.
 
physics envy
#43 Posted : 12/24/2017 1:39:54 AM

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I'm giving the process a go now, but I may need to redo it. The HPBCD arrived earlier than expected, and I did not have any crude extract ready to go. I decided to initially try extracting from one gram of a recent 15x enhanced leaf I made because I'm low on plain leaf. I recovered less crude extract than expected (only 70mg)...so I'm not sure how well it worked. Maybe I recovered a full 48mg of salvinorin with only a little chlorophyll, but I'm not holding my breath. I also noticed quite a lot of tiny particulates in the Everclear that never fully dissolved.

Simultaneously, I have a new small batch of crude extract in the process of letting the sediment settle for a better test soon. Only had about 20 grams of leaves to use, but should be enough for a second complexation attempt.

I ended up trying to use a crockpot water bath to heat/reduce the everclear mixture outside. I left the lid off, and it's taking a long time to reduce as the water is only reaching about 140F without a lid on. I also had a choice between a large round bowl or a smaller square bowl that's easier to scrape, and chose the small one. I should have instead started with the larger one then poured the contents into the smaller one near the end. After much of the everclear evaporated, I put the lid on and the water temp went up pretty quickly. It's almost done now...will see what happens when it finishes. With any luck I'll give it a shot tonight, but because this trial is using an extract from enhanced leaf, it's hard to say how much salvinorin is in there. By Tuesday I should have a chance to test a second attempt...but perhaps this one will work. Fingers crossed...
Salvia quid enthusiast
 
Loveall
#44 Posted : 12/24/2017 2:41:07 AM

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A fan should speed up evaporation (did you try that already?). Did you see the solution become milky at any time while drying?

How much 75% everclear did you use? The HPBCD dissolved very easily, right? What is floating in the ever clear sould not be undissolved salvinorin. I looked it up and salvinorin dissolves in pure ethanol at 1.3mg/ml, so using 2ml of 75% ethanol for every estimated mg of salvinorin should work. Did you filter out the solids or leave them there (I filtered them out but leaving them in should not cause any issues I think).

Looking forward to your results!
“... (a) psychedelic substance occasionally causes psychotic behaviour in people who have not taken it.”
Excerpt from a McKenna talk transcript / audio.
 
physics envy
#45 Posted : 12/24/2017 5:39:43 AM

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Hi Loveall,

I probably shouldn't have mucked up this thread with a bunch of mid-process posts, but maybe we can clean it up later...

I didn't think to put a fan on it today. Maybe starting by putting the everclear mixture in a wide glass pan and putting a fan on it to start the reduction would be better than trying in the crock pot immediately.

I had to leave for a while, so I pulled the glass out of the crock pot until I returned. I've now put it back in, and it currently looks like this:



I started with 70mg crude extract of which the maximum amount of Salvinorin would be roughly 48mg (but may be quite less). So I used 100ml of everclear and 250mg of HPBCD. Yes, the HPBCD did dissolve very quickly. I did try to filter out the particulates with two fine mesh screen from my coffee press, but most solids made it through. You can see how green the remaining mixture is from them.

If it doesn't work, I imagine it is just from starting with a bad batch of crude extract. Will let you know how it finishes up...
Salvia quid enthusiast
 
Loveall
#46 Posted : 12/24/2017 10:20:40 AM

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That looks milky, right? It was clear before? Similar thing happened to me. Particles should not matter they should be passive observers.

Looking forward to moar updates.
“... (a) psychedelic substance occasionally causes psychotic behaviour in people who have not taken it.”
Excerpt from a McKenna talk transcript / audio.
 
physics envy
#47 Posted : 12/27/2017 10:25:15 AM

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SUCCESS!! Big grin Thumbs up

I just tested 30mg of the final product sublingually (approx 3.4mg Salvinorin max), and it produced a trip very similar in strength to my normal light-dose quids of 0.75-1g dried leaf. Compared to the quids, it took slightly longer to notice effects (12-15 minutes), was the same length (a bit over an hour), and was the same bitterness (which I kind of like).

Thank you to everyone who contributed to this tek, and especially Loveall for providing the step-by-step details!

Some notes:

My first try did not succeed (I believe due to a bad starting extract), but a second round with a small batch of 120mg of fresh crude extract did. Assuming 3mg/g from 10g of leaf, this extract should have had a maximum of 30mg Salvinorin, and 90mg of other stuff...

This time, in addition to using a proper extract, I also spent a good amount of time trying to dissolve the clumps of crude extract in everclear before adding the HPBCD. I did not do this during my first test, and there had been a lot of particulates floating around. I wasn't sure if I needed to try to separate the salvinorin from these clumps or not, but I heated the everclear to about 150F in my crockpot and stirred well. It seemed like this reduced the number of particulates in the mix before adding the HPBCD.

(I had wanted to remove some chlorophyll via naphtha washes, but my state doesn't allow its sale, and I didn't know what I could substitute. I tried Gamblin Gamsol's odorless mineral spirits, which was previously used for spice pulls from MHRB, but it didn't appear to work here. Does anyone have a naphtha substitute to suggest for this? I'm testing some Ronsonal lighter fluid now as I'd read that was a potential substitute for spice pulls.)


Loveall wrote:
I have good news. Last night I drank 25mg of complexed salvia (3.6mg of salvinorin estimated) dissolved in water (about 1/4 of a cup).


That's great to hear, too! How long did it take for the effects to begin when you drank the mixture? And did you swish it around at all, or just drink it straight down?
Salvia quid enthusiast
 
Loveall
#48 Posted : 12/27/2017 3:42:14 PM

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Great job physics envy! I'm so thankful and happy that it worked for you.

Now that you have what is likely complexed salvia you could try a water cleanup I think. Dissolve in water, the complexed HPBCD should still be very soluble in water and chlorophyll will not I think. Filter the water and dry again, you should get a cleaner product and very little water should be needed. Also, one could use anhydrous acetone and keep the undissolved HPBCD (big assumption here being that complexed HPBCD does not dissolve in acetone like HPBCD, an assumption that could be wrong). I still need to test these cleanup strategies and plan to do so one day, but would be great to hear of any results from others.

Also, another thing we can try is to start with the water solution from the last paragraph and add dilute HCl. HCl may attack the HPBCD and we should see salvinorin precipitating out. Mindlusion said this may work in the chat, so definitely worth a try at some point.

Regarding bitterness, have you tried HPBCD by itself? In my complexed extract the bitterness seems to be the same between the two and it subsides quickly. With cleanish HPBCD complexed extract the flavor should be the same as with pure HPBCD I think. To me it is slightly bitter but not unpleasant, where my plants are too bitter and unpleasant (which could be a function of the salvia clone too).

It would be very interesting to see how the complexed extract affects those who don't feel much effects when quidding. Do they feel more with the HPBCD complexed extract? If yes, that would indicate that the reason quidding is not effective for them is because of they have a different quidding absorption rate (different saliva/gum tissue/mouth ph) and not because of a different sensitivity to salvinorin once it is in the blood.

When I drank the dissolved complex I did it in quick gulps. I did not swish and tried to minimize the time in the mouth since I was trying to test absorption in the gastrointestinal track. Effects where more subtle and dreamy but lasted longer. Not sure when the effects started as they built up slowly, but I would say that after 30 minutes I was surely in a different head space.

There is a lot of work to be done. Need more folks to repeat these results as salvia can be tricky. I'm getting a neighbor to volunteer as a test subject soon. Then there is the thymeleaved sandwort tea which infundibulum pointed to that could be combined with this.

Exciting stuff Pleased
“... (a) psychedelic substance occasionally causes psychotic behaviour in people who have not taken it.”
Excerpt from a McKenna talk transcript / audio.
 
physics envy
#49 Posted : 12/29/2017 6:45:44 PM

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I've not tried the HPBCD by itself yet, but I'm not concerned with the bitterness.

I'm pretty low on leaves and my recent test produced a small batch, so I may need to wait to test some of the purification methods you suggest.

I mentioned this experiment on the Shroomery and someone who had been interested in complexing salvia to put on blotters in the past responded with interest. Do you think this would be viable, and if so, do you have any suggestions on how to transfer this end product onto them?

My main interest in this project is finding a way help others try salvia orally as I think this is a very worthwhile method of use. But getting friends to try a quid...and then getting it to actually work for them, is difficult. This powder should make that process much simpler, but using blotters could be an even easier way to transport and use if viable.

Salvia quid enthusiast
 
SpiritualBeggar
#50 Posted : 12/29/2017 8:02:47 PM
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say the dosage is 30mg complexed salvanorin, i cannot imagine how big the blotter will be? 1sq inch?
however i love the blotter idea.
 
physics envy
#51 Posted : 12/29/2017 8:09:29 PM

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Quote:
say the dosage is 30mg complexed salvanorin, i cannot imagine how big the blotter will be? 1sq inch?
however i love the blotter idea.


Haha - yes, I was thinking the same thing. But perhaps with the additional purification steps this amount could be reduced significantly. Also, people talk about doing 10-strips or whatever of LSD, so it must not be that difficult to stack several at a time if you need/want a large dose. And it would be so much easier to give people blotters to try rather than vials of powder.
Salvia quid enthusiast
 
SpiritualBeggar
#52 Posted : 12/29/2017 8:19:57 PM
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physics envy wrote:
Quote:
say the dosage is 30mg complexed salvanorin, i cannot imagine how big the blotter will be? 1sq inch?
however i love the blotter idea.


Haha - yes, I was thinking the same thing. But perhaps with the additional purification steps this amount could be reduced significantly. Also, people talk about doing 10-strips or whatever of LSD, so it must not be that difficult to stack several at a time if you need/want a large dose. And it would be so much easier to give people blotters to try rather than vials of powder.



i guess it will be easier than to putting a mouthful of leaves Very happy
but a consistent and precise dosaging will be a breakthrough roa for salvanorin.
 
Loveall
#53 Posted : 12/30/2017 1:39:27 PM

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According to this up to 5mg can fit on a piece of blotter paper. One would need to test and confirm to be sure.

Theoretically, complexed HPBCD could get up to 25% salvinorin by weight (based on molar mass ratio). We are at about half of that currently. Anyway, if all works at peak efficiency you could get 3mg of salvinorin complexed and in to ~2.5 blotters.

I see that the person in the shroomery has some good questions and wants to see solid evidence which is great. We need critical peer review of this work to make sure it is valid and/or improve it.

Some of the answers to his questions are in the Nexus:

1) We only have indirect evidence of complexation based on bioassay results. When HPBCD and extract are administered together sublingually nothing happens. When taken after a 75% ethanol dissolve and dry steps, the mix becomes active. Based on these observations we are assuming that HPBCD and salvinorin are complexed.
2) The complexation technique we are using is essentially #4 from this paper. It is claimed that thorough dissolving and drying in a miscible water alcohol solution is an effective complexation technique and requires no sonication.
3) To get more evidence of complexation, solubility and HCl hydrolyzation of HPBCD tests have been suggested.
4) More bioassays are needed to see if our current signal holds. We are only at two individuals Wink

I'm interested in the oral activity right now from simply swallowing the (presumably) complexed salvinorin powder. A simple small pill may be a good way to administer complexed salvinorin. Dose could be controlled well and the come on was gentle and pleasant.

“... (a) psychedelic substance occasionally causes psychotic behaviour in people who have not taken it.”
Excerpt from a McKenna talk transcript / audio.
 
Loveall
#54 Posted : 1/2/2018 5:45:42 AM

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Physics envy, I see that HPBCD safety has been brought up in the shroomery forum.

HPBCD is considered safe (along with several other CDs), this has been touched on before, and for a clear and concise summary please see the attached document. In the text you will see that for medications, the daily dose of HPBCD can be up to 8000mg/day. In the document it also says that if you swallow HPBCD most goes straight through you and ends up in your poop. Even if it does not end up in your poop, direct injection toxicology studies have been done with no major issues using large doses of the order of grams (see second document). Note that the document also discusses the safety of nose and eye drops too (not recommending this, oral seems to work great, just pointing out that the info is there).

That being said, if there is any credible info out there indication HPBCD is not safe we should know ASAP. No specific issues have been raised at the shroomery, so far seems like suspicious caution, which is good to have initially, but I think there is sufficient information and experience with HPBCD in the field to answer/settle such concerns.
“... (a) psychedelic substance occasionally causes psychotic behaviour in people who have not taken it.”
Excerpt from a McKenna talk transcript / audio.
 
physics envy
#55 Posted : 1/2/2018 6:56:20 PM

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Thank you very much for the HPBCD documents, and thanks for jumping in the thread at the Shroomery with this information also. RedGreenVines is quite astute and has been posting there on Salvia since 2004 or earlier I believe. He has recently re-posted a very thorough document regrading extracting salvinorin and placing it onto rolling papers that he made several years ago which is pretty interesting.

But you may be right - he may simply be being cautious regarding HPBCD usage.

Regarding refining methods you listed above, I took 100mg of the active complexed product and mixed it with a few ml of water. After letting it settle and decanting, I was left with about 33mg of residue. However, I have not bio-assayed it yet to check its activity/strength. I'll report back once I've had a chance to do so...
Salvia quid enthusiast
 
Loveall
#56 Posted : 1/2/2018 7:35:04 PM

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Thanks for doing the experiment. Did you dry the water to get the 33mg? That is where the HPBCD may have moved to. Or is the 33mg of residue the dried material left behind during decanting?
“... (a) psychedelic substance occasionally causes psychotic behaviour in people who have not taken it.”
Excerpt from a McKenna talk transcript / audio.
 
physics envy
#57 Posted : 1/3/2018 12:05:39 AM

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Whoops...I just re-read your post and see I misunderstood.

So after adding a few ml of water to the 100mg, I siphoned off the water and put it in a jar. There was 33mg of remaining residue. I have not dried what is in the jar yet, and I now see that is where the complexed salvinorin should be. I don't have any HCl, so I'll go ahead and set out the water to dry and see what remains, then test at some point soon.

Salvia quid enthusiast
 
Loveall
#58 Posted : 1/3/2018 1:22:02 AM

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Whew, had a worry that the water had been discarded. You can wash the residue with water one or two more times wih water and add that to the jar you already have to make sure you pick up all the HPBCD. Good call on keeping everything while doing experiments. Thumbs up

Note that we are guessing that if the HPBCD complexed, it still soluble in water which is a reasonable expectation since it contains the hydrophilic parts on the outside of the ring. However, this is all experimental and we won't know until we try.
“... (a) psychedelic substance occasionally causes psychotic behaviour in people who have not taken it.”
Excerpt from a McKenna talk transcript / audio.
 
physics envy
#59 Posted : 1/5/2018 6:55:02 PM

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The active 'complexed' product, created from a very crude salvinorin extract with at least 3x plant matter-to-salvinorin, looked like this:




I washed 100mg of the product above with warm water, resulting in 47mg of much whiter product:




I'll report back after having a chance to bio-assay...
Salvia quid enthusiast
 
Loveall
#60 Posted : 1/6/2018 4:54:57 PM

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Physics envy, following in your footsteps I cleaned up 208mg of complexed salvinorin using water (from same material above, expect 30mg of plant material, 30mg of salvinorin, 148mg of HPBCD - of this about 90mg of HPBCD is complexed and 58mg is excess in theory).

Starting material:




Procedure was:

1) Add powder to centrifuge tube

2) Dissolve in water. Plant material clumps formed:

3) Centrifuge. Result after 20minutes at 4000rpm:

4) Collect liquid. It was crystal clear at this time, good sign:

5) Low temp oven dry and collect residue. I got 145mg of an off white crystaline powder:


6) Wash the centrifuge tube with fresh water and repeat 2-5, about 6mg was collected. A second wash may not be needed but did give 4% more.

7) Final yield was 151mg. I think this verifies the clean-up procedure that you have pioneered.

I collected the plant material with ethanol and dried. Got about 10mg (expecting about 30mg, but it was not very powdery and was clumping up a bit and not as easy to collect).

I have some losses from not scraping enough (eg, I could not pick this up and gave up):


Will bioassay the cleaned up complexated salvinorin and report back. I think I'll dissolve 60mg in a nice herbal tea and drink it, it should contain 10mg of salvinorin and some of that would be slowly absorbed into the blood thanks to HPBCD. Interestingly we could also dissolve in saline water and attempt to nebulize this cleaned up complexed powder one day.
“... (a) psychedelic substance occasionally causes psychotic behaviour in people who have not taken it.”
Excerpt from a McKenna talk transcript / audio.
 
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