Ferrum said:
Thanks for the report. This seems more effective than using pure/white salvinorin + HPBCD, and simpler. The other plant stuff that was extracted may have helped too, IDK.
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Salvinorin Cyclodextrin Complexation for Sublingual Administration
- Thread starter InMotion
- Start date
Thanks for the report. This seems more effective than using pure/white salvinorin + HPBCD, and simpler. The other plant stuff that was extracted may have helped too, IDK.
Ferrum
Esteemed member
I think so too. I think it's kind of like how some folks say that the full spectrum extracts from San Pedro cactus and others that instead of further cleaning for a more pure isolation that a lot of the additional compounds make the experience more complex naturally. and some even say stronger .
There are other salvinorins I know in the leaf but im unsure their effects alone . maybe they build a richer effect together?
I'm happy the process worked and is simple bc salvia is one of my favorites through quids . I hate smoking it. It's too much chaos and too short. But when ate it's not as deep normally but you can comprehend it better if you can at all haha and it's effects as far as its antidepressant qualities go are drawn out too as many know as well.
I really look forward to making more and playing with the ratios and making a quantified extraction for measurement sake too. Thank you so much really ! I hope others also use this . perhaps a wiki tek of your method could be added here to the salvia section ?
There are other salvinorins I know in the leaf but im unsure their effects alone . maybe they build a richer effect together?
I'm happy the process worked and is simple bc salvia is one of my favorites through quids . I hate smoking it. It's too much chaos and too short. But when ate it's not as deep normally but you can comprehend it better if you can at all haha and it's effects as far as its antidepressant qualities go are drawn out too as many know as well.
I really look forward to making more and playing with the ratios and making a quantified extraction for measurement sake too. Thank you so much really ! I hope others also use this . perhaps a wiki tek of your method could be added here to the salvia section ?
So I was thinking about making a Salvia Nosespray the first time I had some, but then tossed it as my stuff still had some grey impurity. My only experience with smoked Salvia in Holland was way too harsh to give it another BIG go :shock: . Therefore I thought I would toss this molecule completely.
But now I might tackle it again as I may pre-weigh the Salvinorin much better with some crystals.
So Loveall you found that you should stirr the Salvinorin in excess Ethanol while evaporating, to ensure close contact with HPBCD and then re-dissolve in any suitable liquid?
My plan would be as following:
10 mg Salvinorin A
3x EQ of HPBCD
in 0,5 ml Ethanol
stirred for 2 h and then evaporated overnight.
This is dissolved in 0,5 ml water and put into a Nosespray.
I guess a super easy proof of Complexation is even if everything dissolves later in water or not :?
As I know that 1 push Nosespray = 0,... mg of Salvinorin A (in theory), I could sit there and start ramping up that Nosespray to record whenever I get some effects.
So I guess 10 mg totaly would be enough to at least get a threshold effect IF all the Salvinorin was complexed?
If absolutely nothing happens after incorporating that 10 mg I guess it is more likely that the complexation did not work (or did not enhance bioavailability) than the dose was too small?
But now I might tackle it again as I may pre-weigh the Salvinorin much better with some crystals.
So Loveall you found that you should stirr the Salvinorin in excess Ethanol while evaporating, to ensure close contact with HPBCD and then re-dissolve in any suitable liquid?
My plan would be as following:
10 mg Salvinorin A
3x EQ of HPBCD
in 0,5 ml Ethanol
stirred for 2 h and then evaporated overnight.
This is dissolved in 0,5 ml water and put into a Nosespray.
I guess a super easy proof of Complexation is even if everything dissolves later in water or not :?
As I know that 1 push Nosespray = 0,... mg of Salvinorin A (in theory), I could sit there and start ramping up that Nosespray to record whenever I get some effects.
So I guess 10 mg totaly would be enough to at least get a threshold effect IF all the Salvinorin was complexed?
If absolutely nothing happens after incorporating that 10 mg I guess it is more likely that the complexation did not work (or did not enhance bioavailability) than the dose was too small?
Some valuable information of a new member in the new member section. Long-time reader with a full protocol of how to efficiently complex DMT and probably just applicable to Salvinorin!
DISCLAIMER:
It seems the person in that link above is an Alias of 69ron, who has also spread some misinformation / hype on substances to be involved in their monetarization meanwhile in online shops.
Therefore all this information might not be wrong, but needs some verification first :?:
Regarding that mixture I spoke above:
Now I evaporated an ethanol-water mixture of 10 mg Salvinorin A in 150 mg HPBCD. I just added so less water that the HPBCD just did not dissolve 100 %.
So the ethanol itself might already be a weaker solvent, as at least methanol has 1,8 mg / 1 ml at room temperature. So adding water I was afraid that the Salvinorin might precipitate while evaporation of EtOH. It will form an azeotrop with water, but probably at a way too low ratio. So after evaporating I also saw some non-homogeneous stuff on the bottom of my glass, so maybe the salvinorin precipitated kind of fast and the HPBCD just stayed dissolved until the very end and therefore no host-guest-interaction? Picture is attached.
Maybe it could be also done in DMSO which might dissolve the HPBCD but it will not evaporate ... :/
I will check if everything dissolves in water, but if something remains the complexation might not have worked (completely).
Anyways there are many working suggestions of Secrets of Summer in that link above so that should be also tried.
DISCLAIMER:
It seems the person in that link above is an Alias of 69ron, who has also spread some misinformation / hype on substances to be involved in their monetarization meanwhile in online shops.
Therefore all this information might not be wrong, but needs some verification first :?:
Regarding that mixture I spoke above:
Now I evaporated an ethanol-water mixture of 10 mg Salvinorin A in 150 mg HPBCD. I just added so less water that the HPBCD just did not dissolve 100 %.
So the ethanol itself might already be a weaker solvent, as at least methanol has 1,8 mg / 1 ml at room temperature. So adding water I was afraid that the Salvinorin might precipitate while evaporation of EtOH. It will form an azeotrop with water, but probably at a way too low ratio. So after evaporating I also saw some non-homogeneous stuff on the bottom of my glass, so maybe the salvinorin precipitated kind of fast and the HPBCD just stayed dissolved until the very end and therefore no host-guest-interaction? Picture is attached.
Maybe it could be also done in DMSO which might dissolve the HPBCD but it will not evaporate ... :/
I will check if everything dissolves in water, but if something remains the complexation might not have worked (completely).
Anyways there are many working suggestions of Secrets of Summer in that link above so that should be also tried.
Attachments
So here are some results of a Salvinorin Spray test:
10 mg Salvinorin A
90 mg HPBCD (1:3 as I think it wont hurt)
added 5 droplets of water, put in small vial and then in hot water bath ...
I think instead of letting hot water cool and stirring / mixing I just rather let it sit there and boil, as I think thermal energy might do better at bringing both in close proximity while just waiting for like 5 min or 10.
Sadly afterwards still seeing really sharp Needles = Salvia. So maybe some was complexed, but more likely not all or nothing.
When I did it with MeO-DMT I heated it also to a boil. The MeO-DMT welted and then still just was a brown topping flowing on top of the HPBCD solution. But then mixing it somehow made it become quite homogeneous.
I think if I throw crystals of ANY kind on top of a HPBCD solution it sounds not realistic to me that Alkaloids will get absorbed. Reason is that I would think any kind of 1-phase process is much more likely to lead to complexation than running this in a heterogeneous way. When I melted those MeO-DMT it could be mixed at least to a high degree via strong stirring, like you would shake a separation funnel upon A/B extraction. This immensely increased phase contact makes extraction from X to Y possible and I guess it is very likely to promote also Host Guest Interaction. I just think it makes more sense that the Guest has to hit the Host as a solitary dissociated molecule, meaning free of any crystal lattice. So when throwing in some truly crystalline material and never breaking up that solid state how would your guest ever reach the host?
Now have not read anything about HPBCD in research or patents and maybe indeed there are many examples of how to just throw the crystalline compound on top of dissolved HPBCD and it still will get absorbed. But I'm sure for MeO-DMT the key was the mixing of the molten = liquid Alkaloid with the HPBCD in solution. Otherwise no homogenisation possible?
Now Salvinorin can't get molten until > 220 °C, I still have pretty long shards of crystals in my mini-glass when I look inside after 10 min @ 80 °C ...
Now dropping droplets of Aceton on top, but even that low water content is enough to keep Salvinorin from dissolving. Only thing happening is always shortly precipitating some HPBCD with every drop and then dissolving again.
Therefore will try tomorrow the same, but use DMSO - absolute minimal amount. If BOTH are dissolved, maybe stirr for 5 h at low heat to make sure that Host-Guest complex is even more likely to form. Afterwards throw into required amount of Water to make it 200 µg / 1x Spray. If any precipitation arises by that time, either complexation did not work or is reversed upon water addition.
If indeed drug + HPBCD must be in the same phase for complexing I would rather go the same way with all Alkaloids: Put both compounds on spoon with minimal water added to just dissolve all the HPBCD. Then start heating it until the Alkaloid melts and mix with a Toothpick (the smaller the better as the Alkaloid might be sticky). Excess HPBCD might speed up that step.
Could try to spray that stuff now up my nose, but feel like this might be a waste of 10 mg.
10 mg Salvinorin A
90 mg HPBCD (1:3 as I think it wont hurt)
added 5 droplets of water, put in small vial and then in hot water bath ...
I think instead of letting hot water cool and stirring / mixing I just rather let it sit there and boil, as I think thermal energy might do better at bringing both in close proximity while just waiting for like 5 min or 10.
Sadly afterwards still seeing really sharp Needles = Salvia. So maybe some was complexed, but more likely not all or nothing.
When I did it with MeO-DMT I heated it also to a boil. The MeO-DMT welted and then still just was a brown topping flowing on top of the HPBCD solution. But then mixing it somehow made it become quite homogeneous.
I think if I throw crystals of ANY kind on top of a HPBCD solution it sounds not realistic to me that Alkaloids will get absorbed. Reason is that I would think any kind of 1-phase process is much more likely to lead to complexation than running this in a heterogeneous way. When I melted those MeO-DMT it could be mixed at least to a high degree via strong stirring, like you would shake a separation funnel upon A/B extraction. This immensely increased phase contact makes extraction from X to Y possible and I guess it is very likely to promote also Host Guest Interaction. I just think it makes more sense that the Guest has to hit the Host as a solitary dissociated molecule, meaning free of any crystal lattice. So when throwing in some truly crystalline material and never breaking up that solid state how would your guest ever reach the host?
Now have not read anything about HPBCD in research or patents and maybe indeed there are many examples of how to just throw the crystalline compound on top of dissolved HPBCD and it still will get absorbed. But I'm sure for MeO-DMT the key was the mixing of the molten = liquid Alkaloid with the HPBCD in solution. Otherwise no homogenisation possible?
Now Salvinorin can't get molten until > 220 °C, I still have pretty long shards of crystals in my mini-glass when I look inside after 10 min @ 80 °C ...
Now dropping droplets of Aceton on top, but even that low water content is enough to keep Salvinorin from dissolving. Only thing happening is always shortly precipitating some HPBCD with every drop and then dissolving again.
Therefore will try tomorrow the same, but use DMSO - absolute minimal amount. If BOTH are dissolved, maybe stirr for 5 h at low heat to make sure that Host-Guest complex is even more likely to form. Afterwards throw into required amount of Water to make it 200 µg / 1x Spray. If any precipitation arises by that time, either complexation did not work or is reversed upon water addition.
If indeed drug + HPBCD must be in the same phase for complexing I would rather go the same way with all Alkaloids: Put both compounds on spoon with minimal water added to just dissolve all the HPBCD. Then start heating it until the Alkaloid melts and mix with a Toothpick (the smaller the better as the Alkaloid might be sticky). Excess HPBCD might speed up that step.
Could try to spray that stuff now up my nose, but feel like this might be a waste of 10 mg.
I think something about this last post was wrong, but maybe I understood it better now.
Maybe it sounds reasonable that if both molecules are dissolved in the same phase, they can have contact to each other and possibly interact as Host-Guest. But as Loveall said it would be then mandatory to evaporate it. If I just dissolve both in DMSO, and then add water, then there will have been no complexation while stirring in DMSO even for years, because Salvinorin will always prefere staying just in solution (of DMSO) instead.
Even though maybe for some drugs it might work by just mixing the solids by hand in a little water, I think this whole process mostly works as follows:
The drug has to enter the HPBCD as a solitary molecule, meaning fully dissociated from any previous solid state. That could be achieved by dissolving it, but without removing the solvent, it would still just stay separate from the HPBCD. But from this successfull experiment with 5-MeO-DMT I guess this is the way what happened:
5-MeO-DMT cannot dissolve in water where we already have all the HPBCD. But it can be molten, thus dissociating from each other. Now both need to be fixed as much as possible. While this is essentially still a 2-phase-system it maximizes contact area between both phases. This allowed the (now solitary) 5-MeO-DMT molecules get in any possible contact with HPBCD and therefore be absorbed. Therefore I also think the HPBCD concentration should be as high as possible to accelerate this step. After cooling down the 5-MeO-DMT did not precipitate as an oil on top. The whole thing stayed homogeneous. As it normally must precipitate (and form a brown layer on top) I am quite sure that the complexation worked indeed and probably also happened like described above.
That means liquifying a drug due to melting and then mixing it with a high-concentration HPBCD solution in water might do the job.
Now that can't be done for Harmalas / THH and also Salvinorin.
So I was testing a different method. If Something precipitates, it will quickly form crystallization nuclei from previously solitary molecules, which grow and grow to large crystals. If I let Salvinorin precipitate in a high-concentration HPBCD solution, maybe it will be absorbed faster by complexation than it can form crystals.
Trial 1: Precipitation from DMSO
10 mg Salvinorin
90 mg HPBCD
500 µl DMSO
stirred at 600 RPM.
Now I added water in droplets until it became opaque, indicating Salvinorin Precipitation. At this point I hoped that when stirring so fast the molecules will rather be complexed to the excess HPBCD. The precipitation started at addition of 250 µl water.
After ages of stirring it sadly stayed opaque ... indicating that some or all Salvinorin just precipitated, maybe crystal formation was still faster than complexation?
Trial 2: Fast Precipitation in H2O
Here I wanted to use even less Salvinorin to make likelyhood of Complexation even higher. Also make a super fast precipitation instantly in water, to have the most and therefore smallest crystallization nuclei formed, which might also slow down crystallization.
5 mg Salvinorin
in 100 µl Aceton
200 mg HPBCD
in 600 µl H2O
stirred at 600 RPM.
Now threw the Salvinorin/Aceton into the HPBCD/Water. Obviously instantly got some white clouds, but these stayed and did not vanish. So I guess same happened like with #1.
If I would be super lucky, still SOME Salvinorin got complexed. Or that precipitate was HPBCD instead - but very unlikely ...
Therefore crystal formation might be always faster than complexation so this is possibly not a viable route. Anyways you need > 220 °C to melt salvinorin, so I have no idea how to create solitary molecules of Salvinorin A inside of a HPBCD (water) solution. Picture attached shows both trials. No crystal formation and just an opaque solvent would be more likely to precipitated HPBCD. But I'm more convinced this is still Salvinorin, smashed so hard while precipitation that it formed µm-crystals which float around.
Might try out that stuff which I made for bioactivity later, but not having high hopes :x
Anyways it could be easily tried by heating a HPBCD solution to 70 °C without stirring.
Drop your DMT on top. It will melt and form an orange oily layer.
Turn on stirring as fast as possible for ~ 5 min. The HPBCD should have a high concentration and be used in excess to boost this process.
Stop stirring and verify if you will get an oily layer on top again or not. If not it was successfully complexed, which shows that the Alkaloid must be molten to enter the HPBCD if water is used. The water could be evaporated down later to a desired volume. If you dont see a new brown layer forming, complexation remains. 69ron said the water cant be removed completely, it would stay a sticky mess. But I heated it off with a flame and it indeed went solid - but it's super hard and harsh to be removed from the surface / broken apart then, like candy sticks.
I think the problem with stirring both in the same solvent instead and evaporating it could be that if both substances dont precipitate somehow at the same speed, you risk only precipitating 1 too early and it will form crystals instead of entering the host. Then again this other route above is restricted to drugs having a melting point < 100 °C, which are luckily still many.
Maybe it sounds reasonable that if both molecules are dissolved in the same phase, they can have contact to each other and possibly interact as Host-Guest. But as Loveall said it would be then mandatory to evaporate it. If I just dissolve both in DMSO, and then add water, then there will have been no complexation while stirring in DMSO even for years, because Salvinorin will always prefere staying just in solution (of DMSO) instead.
Even though maybe for some drugs it might work by just mixing the solids by hand in a little water, I think this whole process mostly works as follows:
The drug has to enter the HPBCD as a solitary molecule, meaning fully dissociated from any previous solid state. That could be achieved by dissolving it, but without removing the solvent, it would still just stay separate from the HPBCD. But from this successfull experiment with 5-MeO-DMT I guess this is the way what happened:
5-MeO-DMT cannot dissolve in water where we already have all the HPBCD. But it can be molten, thus dissociating from each other. Now both need to be fixed as much as possible. While this is essentially still a 2-phase-system it maximizes contact area between both phases. This allowed the (now solitary) 5-MeO-DMT molecules get in any possible contact with HPBCD and therefore be absorbed. Therefore I also think the HPBCD concentration should be as high as possible to accelerate this step. After cooling down the 5-MeO-DMT did not precipitate as an oil on top. The whole thing stayed homogeneous. As it normally must precipitate (and form a brown layer on top) I am quite sure that the complexation worked indeed and probably also happened like described above.
That means liquifying a drug due to melting and then mixing it with a high-concentration HPBCD solution in water might do the job.
Now that can't be done for Harmalas / THH and also Salvinorin.
So I was testing a different method. If Something precipitates, it will quickly form crystallization nuclei from previously solitary molecules, which grow and grow to large crystals. If I let Salvinorin precipitate in a high-concentration HPBCD solution, maybe it will be absorbed faster by complexation than it can form crystals.
Trial 1: Precipitation from DMSO
10 mg Salvinorin
90 mg HPBCD
500 µl DMSO
stirred at 600 RPM.
Now I added water in droplets until it became opaque, indicating Salvinorin Precipitation. At this point I hoped that when stirring so fast the molecules will rather be complexed to the excess HPBCD. The precipitation started at addition of 250 µl water.
After ages of stirring it sadly stayed opaque ... indicating that some or all Salvinorin just precipitated, maybe crystal formation was still faster than complexation?
Trial 2: Fast Precipitation in H2O
Here I wanted to use even less Salvinorin to make likelyhood of Complexation even higher. Also make a super fast precipitation instantly in water, to have the most and therefore smallest crystallization nuclei formed, which might also slow down crystallization.
5 mg Salvinorin
in 100 µl Aceton
200 mg HPBCD
in 600 µl H2O
stirred at 600 RPM.
Now threw the Salvinorin/Aceton into the HPBCD/Water. Obviously instantly got some white clouds, but these stayed and did not vanish. So I guess same happened like with #1.
If I would be super lucky, still SOME Salvinorin got complexed. Or that precipitate was HPBCD instead - but very unlikely ...
Therefore crystal formation might be always faster than complexation so this is possibly not a viable route. Anyways you need > 220 °C to melt salvinorin, so I have no idea how to create solitary molecules of Salvinorin A inside of a HPBCD (water) solution. Picture attached shows both trials. No crystal formation and just an opaque solvent would be more likely to precipitated HPBCD. But I'm more convinced this is still Salvinorin, smashed so hard while precipitation that it formed µm-crystals which float around.
Might try out that stuff which I made for bioactivity later, but not having high hopes :x
Anyways it could be easily tried by heating a HPBCD solution to 70 °C without stirring.
Drop your DMT on top. It will melt and form an orange oily layer.
Turn on stirring as fast as possible for ~ 5 min. The HPBCD should have a high concentration and be used in excess to boost this process.
Stop stirring and verify if you will get an oily layer on top again or not. If not it was successfully complexed, which shows that the Alkaloid must be molten to enter the HPBCD if water is used. The water could be evaporated down later to a desired volume. If you dont see a new brown layer forming, complexation remains. 69ron said the water cant be removed completely, it would stay a sticky mess. But I heated it off with a flame and it indeed went solid - but it's super hard and harsh to be removed from the surface / broken apart then, like candy sticks.
I think the problem with stirring both in the same solvent instead and evaporating it could be that if both substances dont precipitate somehow at the same speed, you risk only precipitating 1 too early and it will form crystals instead of entering the host. Then again this other route above is restricted to drugs having a melting point < 100 °C, which are luckily still many.
Attachments
So I played around a little more with Tryptamines and contrary to what I first believed these Tryptamines indeed get complexed in just HPBCD + water even without melting, AKA being just stirred as Freebase Crystals. Therefore I had some hope that would work with Salvinorin too if I would just wait long enough.
50 mg HPBCD
600 µl water
+
12 mg Salvinorin A (2 HPBCD : 1 Salvinorin)
Salvinorin is just suspended inside and stirred for 5 h, but nothing happened ... I added some more concentrated HPBCD-water-solution to make it ~ 8:1 and stirred over night, but no success.
That Salvinorin was re-xed 2x, still a little grey. It is already 3 years old, but I guess that would not matter. So whatever was happening to DMT / Bufotenin without heating, it did not work for Salvinorin. Maybe it is too big for beta-CD? Maybe some literature will tell which size of CD is suited up to which molecular mass. Salvinorin with M = 400+ u is just so big ...
Cavity seems to be ~ 20 % bigger in diameter, which exactly means a 200 % cavity volume if spherical shape is assumed for that cavity. Maybe there is a list of maximum possible molecular mass per glucose unit?
Maybe would still try that Spray for now and creating a 500 µg / Spray solution to see if there is any effect ... but would need to of course also compare to same situation without HPBCD. Still I believe if that stuff is not clear - but opaque - it will not be complexed anyways ...
50 mg HPBCD
600 µl water
+
12 mg Salvinorin A (2 HPBCD : 1 Salvinorin)
Salvinorin is just suspended inside and stirred for 5 h, but nothing happened ... I added some more concentrated HPBCD-water-solution to make it ~ 8:1 and stirred over night, but no success.
That Salvinorin was re-xed 2x, still a little grey. It is already 3 years old, but I guess that would not matter. So whatever was happening to DMT / Bufotenin without heating, it did not work for Salvinorin. Maybe it is too big for beta-CD? Maybe some literature will tell which size of CD is suited up to which molecular mass. Salvinorin with M = 400+ u is just so big ...
Cavity seems to be ~ 20 % bigger in diameter, which exactly means a 200 % cavity volume if spherical shape is assumed for that cavity. Maybe there is a list of maximum possible molecular mass per glucose unit?
Maybe would still try that Spray for now and creating a 500 µg / Spray solution to see if there is any effect ... but would need to of course also compare to same situation without HPBCD. Still I believe if that stuff is not clear - but opaque - it will not be complexed anyways ...
That whole 12 mg were sprayed up the Nose - no effect :thumb_dow
12 mg Salvinorin "complexed"
1,75 ml water
= 24 sprays
= 500 µm per spray
It took 32 min to slowly spray that full thing (just in case) and until the end no effect felt. Maybe a little body high? Can't really say because not being sober completely anyways. But definetly nothing that made those 12 mg truly being any experience. So it was by 99 % safety anyways not complexed so probably this is just a direct sign again how pure (AKA not complexed) Salvinorin has nearly no bioavailability. Should try with Gamma-CD then ... :?
To calculate pore size in last comment I used just mathematics for round objects, but it seems Cyclodextrin is rather hour-glass shaped .
Would still be big enough I guess if M = 430 u would be too small for beta-CD - IF size is the problem here.
12 mg Salvinorin "complexed"
1,75 ml water
= 24 sprays
= 500 µm per spray
It took 32 min to slowly spray that full thing (just in case) and until the end no effect felt. Maybe a little body high? Can't really say because not being sober completely anyways. But definetly nothing that made those 12 mg truly being any experience. So it was by 99 % safety anyways not complexed so probably this is just a direct sign again how pure (AKA not complexed) Salvinorin has nearly no bioavailability. Should try with Gamma-CD then ... :?
To calculate pore size in last comment I used just mathematics for round objects, but it seems Cyclodextrin is rather hour-glass shaped .
Would still be big enough I guess if M = 430 u would be too small for beta-CD - IF size is the problem here.
lobo
Rising Star
Anyone try it?? or confirmation on this?
Im very interesting in a effective oral ROA for salvia...
I would make a try and then will post the result...
