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Journal: 50 Sublingual HPBCD DMT Ayahuasca journeys over a years time Options
 
Mitakuye Oyasin
#1 Posted : 5/3/2021 1:56:23 AM

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That is fascinating. I had never heard of HPBCD before now. The molecular arrangement and the fact that is forms a cone that substances can be 'hidden' in is really interesting. I wonder if this could be beneficial to other psychoactive substances than DMT. Thanks for sharing.
Let us declare nature to be legitimate. All plants should be declared legal, and all animals for that matter. The notion of illegal plants and animals is obnoxious and ridiculous.
β€” Terence McKenna


All my posts are hypothetical and for educational/entertainment purposes, and are not an endorsement of said activities. SWIM (a fictional character based on other people) either obtained a license for said activity, did said activity where it is legal to do so, or as in most cases the activity is completely fictional.
 

STS is a community for people interested in growing, preserving and researching botanical species, particularly those with remarkable therapeutic and/or psychoactive properties.
 
Loveall
#2 Posted : 5/3/2021 1:45:08 PM

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Hi, thanks for the research and tests.

I have limited time to answer, so please excuse the lack of links and mistakes/commissions - I'm going off memory alone.

1) I believe someone by the name of Inmotion had a DMT/HPBCD complexation thread. Someone tested it and in their experience the resulting powder was too bulky/not practical.
2) Why use a 1 to 1 molar ratio? As I understand it % complex and permeability increases with HPBCD as the complex is in equilibrium with the separate molecules. As HPBCD is increased, permeability reaches an optimal point since at some time excess empty HPBCD starts getting in the way (the salvinorin complexation thread discusses this and has some data and examples from the literature for some molecules).
3) We had some success making salvinorin/HPBCD buccaly/orally active here at the nexus, but reproducing it was spotty. Zebbie had success and strong effects buccaly using the green gunk from wa acetone salvia extraction (made powdery with some form of starch).

I wonder what would happen if spent salvia (from chilled acetone leftovers) was extracted with room temp acetone to get the green gunk and make the starchy powder that worked for Zebbie. Them mix that with DMT and test for buccal activity.

Also, as you may already know, FB harmalas are buccaly active on their own at 20mg in my experience (there are threads on that too).

Cheers and thanks again.
πŸ’šπŸŒ΅πŸ’š Mescaline CIELO TEK πŸ’šπŸŒ΅πŸ’š
πŸ’šπŸƒπŸ’š Salvinorin Chilled Acetone with IPA and Naphtha re-X TEKπŸ’šπŸƒπŸ’š
 
Loveall
#3 Posted : 5/5/2021 1:32:40 PM

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Do you have any references to backup the statement that most studies use a 1:1 drug/cyclodextrin ratio?

What I have come across is that usually it is not 1:1 (see example table below).

Attaching a paper that systematically goes over what affects the ratio/preparation (complexation efficiency).

Also, both FB and salt drug forms complex with HPBCD as I understand it.

Setting all that aside, I think you have a promising experimental claim. I'll try to replicate it at some point. If it works I would test higher HPBCD ratio also, let the experimental results see if there is a modulation/improvement.
πŸ’šπŸŒ΅πŸ’š Mescaline CIELO TEK πŸ’šπŸŒ΅πŸ’š
πŸ’šπŸƒπŸ’š Salvinorin Chilled Acetone with IPA and Naphtha re-X TEKπŸ’šπŸƒπŸ’š
 
Jagube
#4 Posted : 5/5/2021 6:34:14 PM

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downwardsfromzero wrote:
This combined with the HPBCD complexation results (which we really ought to replicate and confirm) makes me wonder whether there are saccharides in leaf brews which perform a similar effect to HPBCD. There is still so much scope for really interesting research here - thanks for posting.

I've seen anecdotal reports of quidded D. cabrerana leaf being active.
 
murklan
#5 Posted : 5/12/2021 7:47:59 AM

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Thanks for the posts and findings ava69, really interesting. I find it hard to get hold of HPBCD (I'm in europe) but if I can I will experiment with it for sure.
 
Brennendes Wasser
#6 Posted : 5/12/2021 5:28:27 PM

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Interestingly I found out that a colleague at work also has HPBCD and ACD. I thought of trying the Salvia-complexation-thing.

But I did not find any real procedure for this on the nexus. I thought I will need to make sure that both ingredients will be soluble in the same solvent, for maximized contact. This can only be achieved for pure mixtures in DMSO and this is not a solvent to be removed again.

But I figured out some mixtures of Acetone to use for Salvinorin AND HPBCD.

Dissolve Salvinorin in minimal amount of Acetone, add 4x volume of water afterwards. 20 % Acetone in Water still keeps Salvinorin dissolved. Then you can dissolve any HPBCD.

ACD has a much worse solubility (HPBCD seems to be just made for improved solubility in general) and will not do the trick. Then you could stirr and cause complexation.




Now while you have DMT and not Salvinorin this is not directly comparable, but I am still quite wondering why only plain water can be used. I mean yes the dissolved HPBCD may take up the DMT. But if the DMT will NEVER get dissolved in the first place, then there is no contact between guest and host. So I really wonder if this would really do the trick, if you just have a suspension of DMT?

Normally I would assume this leads to a HPBCD-solution with suspended DMT Confused

Maybe I should try with Salvia and my solvent mix and then try pure water ...
Check the

BIG Analysis on DMT !

Lots of interesting and possibly new stuff unraveled ;o
 
Loveall
#7 Posted : 5/14/2021 1:50:25 PM

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Brennendes Wasser wrote:
Interestingly I found out that a colleague at work also has HPBCD and ACD. I thought of trying the Salvia-complexation-thing.

But I did not find any real procedure for this on the nexus. I thought I will need to make sure that both ingredients will be soluble in the same solvent, for maximized contact. This can only be achieved for pure mixtures in DMSO and this is not a solvent to be removed again.

But I figured out some mixtures of Acetone to use for Salvinorin AND HPBCD.

Dissolve Salvinorin in minimal amount of Acetone, add 4x volume of water afterwards. 20 % Acetone in Water still keeps Salvinorin dissolved. Then you can dissolve any HPBCD.

ACD has a much worse solubility (HPBCD seems to be just made for improved solubility in general) and will not do the trick. Then you could stirr and cause complexation.




Now while you have DMT and not Salvinorin this is not directly comparable, but I am still quite wondering why only plain water can be used. I mean yes the dissolved HPBCD may take up the DMT. But if the DMT will NEVER get dissolved in the first place, then there is no contact between guest and host. So I really wonder if this would really do the trick, if you just have a suspension of DMT?

Normally I would assume this leads to a HPBCD-solution with suspended DMT Confused

Maybe I should try with Salvia and my solvent mix and then try pure water ...


See attached for a thesis that looked at salvinorin A solubility in water in the presence of an BCD (they used captisol which is similar to HPBCD and has the same inner ring). Solubility increased linearly with the BCD.

I believe there is a finite solubility of DMT FB in water and HPBCD would increases it several fold and linearly with HPBCD concentration.

In the salvinorin complexation thread aqueous ethanol dissolved both salvinorin and HPBCD for complexation - just FYI in case you hadn't seen that already.
πŸ’šπŸŒ΅πŸ’š Mescaline CIELO TEK πŸ’šπŸŒ΅πŸ’š
πŸ’šπŸƒπŸ’š Salvinorin Chilled Acetone with IPA and Naphtha re-X TEKπŸ’šπŸƒπŸ’š
 
Loveall
#8 Posted : 5/14/2021 2:15:19 PM

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Note that (as I understand things) linear drug solubility increase with HPBCD concentration is a sign of complexation. The slope when moles are used represents the complexation efficiency (can be > 1 if two molecules fit in one HPBCD site). There are papers with explicit formulas.

As long as there is enough water to dissolve the HPBCD and room for the complex (linear regime), the total amount of complexed drug is a function of the HPBCD and drug ratio, independent of the water volume. Adding more water does nothing other than increase the volume, not the complexation %.

So in practice, choose a drug/HPBCD molar ratio (1 is a good start). Slowly add water till it all dissolves. If drug won't dissolve well try a higher molar ratio. Something along those lines makes sense to me.

ava69, have you tried harmala FB/DMT FB/HPBCD/water paste sublingually. Maybe it would be interesting to try to make an Pharmahuasca/HPBCD paste.
πŸ’šπŸŒ΅πŸ’š Mescaline CIELO TEK πŸ’šπŸŒ΅πŸ’š
πŸ’šπŸƒπŸ’š Salvinorin Chilled Acetone with IPA and Naphtha re-X TEKπŸ’šπŸƒπŸ’š
 
Loveall
#9 Posted : 5/14/2021 2:49:59 PM

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Sublingual harmala FB is pretty strong (but shorter lasting). I would start with a lot less harmalas for sublingual route, maybe, 10mg of harmala FB (harmine/THH mix), 20mg DMT, 200mg HPBCD.

I'm thinking of trying this with the dense paste/knead method.
πŸ’šπŸŒ΅πŸ’š Mescaline CIELO TEK πŸ’šπŸŒ΅πŸ’š
πŸ’šπŸƒπŸ’š Salvinorin Chilled Acetone with IPA and Naphtha re-X TEKπŸ’šπŸƒπŸ’š
 
Loveall
#10 Posted : 5/15/2021 1:33:19 PM

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Brennendes Wasser wrote:
Interestingly I found out that a colleague at work also has HPBCD and ACD. I thought of trying the Salvia-complexation-thing.

But I did not find any real procedure for this on the nexus. I thought I will need to make sure that both ingredients will be soluble in the same solvent, for maximized contact. This can only be achieved for pure mixtures in DMSO and this is not a solvent to be removed again.

But I figured out some mixtures of Acetone to use for Salvinorin AND HPBCD.

Dissolve Salvinorin in minimal amount of Acetone, add 4x volume of water afterwards. 20 % Acetone in Water still keeps Salvinorin dissolved. Then you can dissolve any HPBCD.

ACD has a much worse solubility (HPBCD seems to be just made for improved solubility in general) and will not do the trick. Then you could stirr and cause complexation.




Now while you have DMT and not Salvinorin this is not directly comparable, but I am still quite wondering why only plain water can be used. I mean yes the dissolved HPBCD may take up the DMT. But if the DMT will NEVER get dissolved in the first place, then there is no contact between guest and host. So I really wonder if this would really do the trick, if you just have a suspension of DMT?

Normally I would assume this leads to a HPBCD-solution with suspended DMT Confused

Maybe I should try with Salvia and my solvent mix and then try pure water ...


In one salvinorin complexation thread we used aqueous ethanol (75.5% everclear) and that dissolved everything. Got some good results, but ran into issues with repeats. Maybe heat/light were causing issues in the process.

I think there is merit to using only water. Why? Because how the low solubility drug dissolves in water when HPBCD is present informs us of the complexation.

Looking at the details behind this statement. Let's call,

[So], drug solubility in pure water (can be low)
[Ht], total HPBCD concentration

For a 1 to 1 drug (S) and HPBCD (H) complex (SH),

S + H <-> SH

The total amount of cyclodextrin concentration is [Ht] = [H] + [SH]

The complexation is in dynamic equilibrium:

Kc = [SH]/([S][H])

Combining the last two equitons we can get [SH]:

Kc = [SH]/([S]([Ht]-[SH])) ==> [SH] = Kc[Ht][S]/(1+Kc[S])

The total drug solubility is:

e = [S] + [SH] = [S] + Kc[S]/(1+Kc[S]) * [Ht]

When [Ht] = 0, e = [S], which can be interpreted as the plain water solubility ([So]). As long as there is enough starting drug trying to be dissolved, [S] = [So].

e = [So] + Kc[So]/(1+Kc[So]) * [Ht]


Which is a very nice linear equation and explains the plot in the previous post for salvinorin and captisol.

Essentially, as Ht is added, more drug goes into solution at a certain rate. That rate is the slope of the equation above and we can see the explicit forms depends on the drug solubility in plain water and the complexation equilibrium constant. For large Kc[So] (good complexation and decent water solubility), the slope tends to ~1. So a 1 to 1 molar ratio make perfect sense. Otherwise, more HPBCD will be needed to dissolve all the drug and in practice the ideal molar ratio is 1+1/(Kc[So]) > 1.

Anyway, start with a high [Ht] solution. Then add drug, it will go into solution as So and also as it complexes (which should be most of it for poorly soluble FB). Eventually, it will stop going into solution once e is reached.

Attaching a file that also explains this as I understand it.
πŸ’šπŸŒ΅πŸ’š Mescaline CIELO TEK πŸ’šπŸŒ΅πŸ’š
πŸ’šπŸƒπŸ’š Salvinorin Chilled Acetone with IPA and Naphtha re-X TEKπŸ’šπŸƒπŸ’š
 
Loveall
#11 Posted : 5/16/2021 5:00:29 PM

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A few more thoughts on HPBCD for optimal buccal delivery. We don't want excess HPBCD since it will get in the way and "hold on" to the drug. On the other hand, we want enough HPBCD to dissolve the drug so it can diffuse into the body.

So there is an optimal molar ratio. 1:1 is a great starting point, but there may be a higher or lower ratio that is better if the complexation slope is larger than 1 or if So is large.

The attached paper has a great explanation, and some data for hydrocortisone (see image). Absorption of a 1.6% hydrocortisone peaks at 8% cyclodextrin (which is the point when all the drug dissolves), that is a 1:1.25 Drug:HPBCD ratio.

So in experiments, 1:1 molar is a great starting point, but tests at slightly higher HPBCD would be interesting. We could see effects getting stronger and then decreasing as HPBCD is increased.

This may be important in the salvinorin work also. From the solubility curve in the previous post, saturation for salvinorin happens at ~ 1:200 drug:HPBCD molar ratio, which is much higher than anything we tested on the salvinorin complexation thread.

In principle, one can start with undissolved drug and water. Then add 1:1 HPBCD, does all the drug dissolve? If yes, it's likely we are close to optimal already, perhaps less HPBCD could improve things. If no, add HPBCD slowly and stop when all the drug is dissolved. The HPBCD/Drug ratio saturation point should be optimal for buccal administration.

Finally, in practice as the drug is absorbed the remaining drug:HPBCD ratio decreases, pushing the system towards the unsaturated direction. Maybe starting at a lower HPBCD delivers the maximum amount of drug since both sides of the diffusion peak are utilized (going from the saturated to unsaturated region as drug is absorbed.
πŸ’šπŸŒ΅πŸ’š Mescaline CIELO TEK πŸ’šπŸŒ΅πŸ’š
πŸ’šπŸƒπŸ’š Salvinorin Chilled Acetone with IPA and Naphtha re-X TEKπŸ’šπŸƒπŸ’š
 
fog
#12 Posted : 5/17/2021 11:03:11 AM
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Really interesting findings! Do you know if the complex would be stable in solution? If one were to make a tincture for example?
 
fog
#13 Posted : 5/19/2021 8:27:26 AM
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ava69 wrote:
it stings a little, but the results are worth it


Have you ever tried any dmt salts sublingually? How does the sting compare? In my experience the burn from salts is too much to handle.
 
downwardsfromzero
#14 Posted : 5/19/2021 10:15:36 PM

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Over on the salvia thread:
Loveall's posts seemed worhtwhile to link.

Loveall wrote:
Are we sure the starch is not helping with sublingual administration?

Reading this review paper they mention that salvinorin is lyophilic. I think starch makes a lyophilic colloidal solution.

So maybe the starch helps salvinorin go unit solution and diffuse into the body sublingually? As I understand this thread all strong positive results had starch as part of the formulation. Of course, it could still be an inert carrier as had been assumed, but do we have the dedicated experiment to be sure?

Maybe I'll test pure crystalline salvinorin + starch sublingually, see what happens.
I shall try a sublingual DMT/starch blend sometime soon. Cornstarch is more OTC than HPBCD.




β€œThere is a way of manipulating matter and energy so as to produce what modern scientists call 'a field of force'. The field acts on the observer and puts him in a privileged position vis-à-vis the universe. From this position he has access to the realities which are ordinarily hidden from us by time and space, matter and energy. This is what we call the Great Work."
― Jacques Bergier, quoting Fulcanelli
 
downwardsfromzero
#15 Posted : 5/24/2021 8:46:07 PM

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I tried the cornstarch variation this morning. Naturally - me being me - the approach was a little vague and wonky as I neglected to write down the concentration of my alkaloid tincture. Nonetheless, knowing that 3 drops of it orally administered after 3g of rue were like a threshold psilocybin dose, it seemed straightforward enough reasoning to use twice that amount. I had held off eating breakfast, having only had a glass of water, and the house was quiet.

400mg of cornstarch were weighed on a small dish, after which the 6 drops of tincture were added. These weighed a total of 160mg and the amount of cornstarch was ample to absorb all the liquid with dry cornstarch to spare. The dry starch was mixed into the now waxy material where the tincture was added. In retrospect, it may have been worth testing this crumbly powder without addition of water but at the time I didn't fancy the extra alcohol burn it may have caused.

Freshly boiled tap water was poured into a cup and a Pasteur pipette was used to transfer 10 drops of very hot water into the cornstarch mixture. This was then mixed thoroughly and by chance took on the perfect thixotropic consistency, where it will pour like a viscous liquid but if poked or scraped it transforms into a solid until the shearing force is removed - something for which cornstarch is famed. I took this to be a good sign and scraped the goo from the small dish using a teaspoon and placed it under my tongue. Remnants in the dish and teaspoon were scooped of with a finger and also transferred, as best they could be, under my tongue.

After a few minutes, a light tryptaminic energy thrilled through my body as I became mesmerised by the wind-tossed leaves of the trees and bushes outside. With the sunshine out there it was a joyful scene and I relished the sun's warmth upon my body. My mind was transported to a lightly meditative state and overall the moment felt perfect.

I quickly tidied the kitchen and prepared myself a cup of very fine matcha with the remaining hot water, which was now at just the right temperature. The noticeably altered state deepened from the initial ±/+ to a clear + (Shulgin); it was 20 minutes since the paste had entered my mouth. I went and stretched out on the sofa, lightly shading my eyes with my hood. There was little in the way of CEVs - if anything it was clearer and calmer than my usual level of mind fizz.

The body buzz continued and it seemed like the molecule was seeking out areas of tension in my body. As I stretched out to relax, my lower spine - a long time problem area for me - gave a very satisfying crunch and the great majority of the pain that has been bothering me there of late simply melted away into nothing.

After a time of lying there on the sofa feeling these gentle effects - both physically healing and mentally positive, like a cleaning out of the cobwebs - the voices of some passersby stirred me from my reverie. My family had gone out to a park nearby and now it was time to drink the rest of the matcha, eat a light breakfast and meet up with them. In the park I was greeted with hugs beneath a magnificent beech tree.

Low doses can be special too!


Further notes on dosing and technique:
I didn't manage to spit out anything after 15 minutes because I produce saliva rather readily and compulsively swallowed some of it. This was quite irritating for my throat and produced a minor coughing fit at about the 15 minute mark. A short while later, some of the swallowed material must have hit some 5HT-3 receptors in my stomach as there was a brief wave of nausea. Fortunately this was cleared up with a few sips of matcha.

The choice to try this experiment without any pre-dose of THH or harm~ine was in order to eliminate possibility of confounding effects. Thus I can confirm that DMT freebase absorbed on cornstarch does show some activity through sublingual absorption. Further tests are required in order to quantify the effective dosage for this ROA variation, but it definitely works. If any of you who have tried the sublingual HPBCD complex are willing to try a comparison using cornstarch that would be very helpful.




β€œThere is a way of manipulating matter and energy so as to produce what modern scientists call 'a field of force'. The field acts on the observer and puts him in a privileged position vis-à-vis the universe. From this position he has access to the realities which are ordinarily hidden from us by time and space, matter and energy. This is what we call the Great Work."
― Jacques Bergier, quoting Fulcanelli
 
shroombee
#16 Posted : 5/24/2021 8:57:07 PM

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downwardsfromzero wrote:
I can confirm that DMT freebase absorbed on cornstarch does show some activity through sublingual absorption. Further tests are required in order to quantify the effective dosage for this ROA variation, but it definitely works. If any of you who have tried the sublingual HPBCD complex are willing to try a comparison using cornstarch that would be very helpful.

Nice! I assume your tincture is using ethanol? Do you have a rough idea of the concentration? I will give the cornstarch a try within a week and report back.

Here is my experience report for THH and sublingual DMT complexed with HPBCD:

https://www.dmt-nexus.me...mp;m=1106140#post1106140
 
downwardsfromzero
#17 Posted : 5/24/2021 9:32:30 PM

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shroombee wrote:
I assume your tincture is using ethanol? Do you have a rough idea of the concentration?
The ethanol used was 90% ABV, and the solution itself I estimate to be around 30% W/W, based on vague recollections and inferences.

Thanks for volunteering, I look forward to hearing of your results.




β€œThere is a way of manipulating matter and energy so as to produce what modern scientists call 'a field of force'. The field acts on the observer and puts him in a privileged position vis-à-vis the universe. From this position he has access to the realities which are ordinarily hidden from us by time and space, matter and energy. This is what we call the Great Work."
― Jacques Bergier, quoting Fulcanelli
 
Violet Quark
#18 Posted : 5/27/2021 9:46:06 AM

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Hi All
I have read this entire thread 3 times.
It looks totally amazing but HPBCD seems impossible to source in my country.
Is this the same stuff?
beta cyclodextrin Ξ²-cyclodextrin CAS NO 7585-39-9
If not, Are there any alternatives?
VQ
 
Loveall
#19 Posted : 5/27/2021 12:07:26 PM

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Violet Quark wrote:
Hi All
I have read this entire thread 3 times.
It looks totally amazing but HPBCD seems impossible to source in my country.
Is this the same stuff?
beta cyclodextrin Ξ²-cyclodextrin CAS NO 7585-39-9
If not, Are there any alternatives?

I think that cyclodextrin is missing outer ring hydroxypropyl groups to make it more water soluble. What was used here is (2-Hydroxypropyl)-Ξ²-cyclodextrin powder; CAS Number: 128446-35-5 I believe.

How about trying cornstarch like DWZ did above? I think chitosan may also be worth an experiment also.
πŸ’šπŸŒ΅πŸ’š Mescaline CIELO TEK πŸ’šπŸŒ΅πŸ’š
πŸ’šπŸƒπŸ’š Salvinorin Chilled Acetone with IPA and Naphtha re-X TEKπŸ’šπŸƒπŸ’š
 
Violet Quark
#20 Posted : 5/27/2021 7:27:54 PM

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Thanks for the update ava.
I am totally going to give this a go.
Maybe with cornstarch as suggested until I can get some proper supplies.
I will report my findings in due course.
VQ
 
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