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No MAOI: Complexing DMT freebase for sublingual administration

Migrated topic.
What do you mean by bioactivity exactly?

Oh well it was late at night, I wanted to write Bioactivity :? 😁

Ok. So cyclodextrin simply aids initial absorption and possibly lowers the threshold for +1 experience. Not revolutionary or worth the effort.

Not sure, but this is what I most likely would expect. It aids absorption / passage of the drug, but it will ultimately not inhibit the quick degradation of DMT by enzymes. Maybe you would need a little less for an effect without MAOI, but it will still be a very high dosage - but again, this is just speculation. So far I think all thoughts about Cyclodextrin-usage were just hypothetical.

200mg of liquid acacia alkaloids on an empty stomach in a gel cap, 45 minute peak 15 minutes after consumption followed by 1 hour offset and long afterglow. If maoi were involved it may well have been a 6 hour, way too intense, trip.

Well regarding oral DMT + MAOI I once ate 200 mg with 200 mg MAOI and it was intense, but I would describe it more like 15 - 20 mg smoked, so I was not able to cut garlic anymore as meal preparation, but hanging out with dudes was still possible 😁 Also I never encountered it to last 6 h, even though ayahuasca would last like that. For Pharmahuasca (that would be oral DMT + MAOI) it is only something like 1 h. So indeed the story of your friend sounds actually quite similar to my own experiences, but this time I had a MAOI incorporated :?

In your big DMT analysis you say no Juremamamine detected for your various spices, that it only exists in cold water process extracts

Well it is indeed for sure not present in hot acidic boils, but the source where it was reported to be extracted from Jurema used cold Methanol. Very likely that it wont be extracted in cold water, unless you add an acid and then it is also possible destroyed, like it is for sure when applying heat additionally. In the original paper of 2005 (where it was first isolated) it was stated it would be destroyed by strong bases, but their proposed chemical structure was wrong (as seen later in 2015) so not sure if indeed the base step of extractions are the point where it gets broken up.

But regarding transformation into DMT, thats not quite likely, molecules can break down by heat into a wide variety of compounds, so one would have to analyze that with a Yuremamine sample to see whats the outcome, but I think its very unlikely that it will exactly split into DMT and that other substance. Bondings with heteroatoms (O, N) are more likely to break first and this would not cause a release of DMT. Also maybe the concentration of Yuremamine is quite low and so it is more something like an "oddity" than something that really has an effect on the actual outcome of an extraction. :surprised
Maybe there are other compounds that incorporate DMT in their structure and can indeed release it upon heating, but I'm not sure if there are some reported. Nevertheless I think the concensus is that nearly all the DMT gathered from extraction is originally present also as DMT in the bark.
Strictly speaking, yuremamine is not a 'complexed' form of DMT. The DMT is chemically bound to a flavanol moiety. (A relevant analogy might be the C-C bonding in certain flavonoid glycosides, such as vitexin and orientin.)

Since we have no particular evidence of the pharmacological activity of yuremamine, nor whether it decomposes into DMT at extremes of pH, clearly there is some more research to be done. 12mg yuremamine were recovered from 2.265 g of root bark (0.53% w/w) so it seems likely that the compound may make a contribution to the pharmacology of jurema.

For fans of systematic nomenclature, one possibility for yuremamine is 4-(3-(2-dimethylaminoethyl)indol-2-yl-2-(3,4,5-trihydroxyphenyl)-7-hydroxy-2,3-dihydro-4H-benzopyran 😁.

Brennendes Wasser said:
Oh well it was late at night, I wanted to write Bioactivity :? 😁
Ah, bioavailability!

Nature Boy said:
Hi, all:
I read numerous journal articles and papers on using HPBCD to complex vitamins, steroids, antimetabolites and antibiotics following which I successfully complexed 25i-NBOMe and laid it on blotter at precisely 550 mcg / tab. It was a successful venture and an amazing experience.

It subsequently occurred to me that the only reason MAOI's are needed in conjunction with DMT fumarate or DMT freebase taken ORALLY, is to get around the inhibition in the gut. After all, an MAOI is completely unnecessary when vaporized, administered IV, or even rectally. I then began to consider a sublingual ROI for DMT freebase using HPBCD complexed DMT - and >>NO<< MAOI.

One MAJOR question remains before an attempt can be made. Shockingly few molecules of DMT are probably required for detectable effects. Assuming for the moment that the proposed experiment is a rousing success at introducing DMT into the bloodstream...HOW MUCH COMPLEXED DMT SHOULD CONSTITUTE A FIRST TEST DOSE??? 1 milligram? 10 milligrams??? I have a goodly supply of both materials. I'm scared to try for fear of success without some opinions on a starting dosage attempt, being a conservative psychonaut and a bit of a coward. The complexed DMT would be in ~ 1/2 cc of distilled WATER..


Complexing DMT freebase for sublingual administration - Otherhttps://www.dmt-nexus.me › ... › Other
Feb 20, 2012 · 20 posts · 14 authors
Hi, all: I read numerous journal articles and papers on using HPBCD to complex vitamins, steroids, antimetabolites and antibiotics following ...

So I had some recent trials with DMT after I was again into testing Salvia Extracts with HPBCD. But as I wrote in that Salvia Thread, the mechanism of complexation will probably not work for Salvinorin, as I cannot find a way to disperse it unimolecular in an aqueous HPBCD solution. Anyways for DMT it's possible like this:

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 mixed 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.

Because of this I'm quite sure that approaches like this wont work:

Orion said:
I'm the guinea pig I guess:

10mg Freebase DMT
5ML Isopropanol

- DMT dissolves right away, HPBCD very little or not at all, solution is cloudy.

5Ml water

- HPBCD dissolves, solution stirred and completely clears. Stirred for a few minutes and then poured onto flat glass dish. Fanned to evaporate.

An amorphous clear solid remains. It's very brittle and shatters everywhere, so I lose some product.

A way to verify if the route of Orion would work could be drying the product completely down and redissolving it. If there is a brown residue, then the complexation did not work, because the Freebase was just precipitating before Cyclodextrin was doing so, as the evaporation will slowly increase the content of water and keeps Cyclodextrin in solution. Even more: Alltogether I am quite sure as long as both substances are indeed dissolved there will be no complexation at all, because a DMT Molecule fully solvated in a solvent is much more preferred entropy-wise than being stuffed into the HPBCD, which would result in less degrees of freedom. You can think of this more like a liquid-liquid extraction with the DMT forming its own phase. It must be immiscible with water to enter the HPBCD instead of just staying dissolved in the mix. But as both are in opposite phases, phase contract has to be maximized. Therefore a stirrer would be much more efficient as mixing by hand.

Now let's see if it will work that way. In contrast to 69rons mentioning I used excess HPBCD as I thought it will speed up the complexation by alot.

So here is the experiment:

1. 1000 mg HPBCD dissolved in 3 ml Water
2. Heated up to 80 °C
3. 50 mg DMT placed on top, it will melt and form a brown layer.
4. Start stirrer, DMT will be dragged into the water, but not mix until vortex hits the ground
5. With Vortex at maximum (> 800 RPM) stirr for 5 min
6. Stop Stirring and see if brown layer re-appears

Tada - no brown layer. DMT was successfully complexed. Note that the vortex has to hit the ground, otherwise DMT will just always stay on top = actual mixing nearly zero.


> HPBCD in high concentration
> DMT molten --> unimolecular dispersed
> no organic solvent - just water
> stirred to maximize phase contact ("DMT Phase" to HPBCD in water)

= Complexation works

Now let's make a test to verify that this truly is complexation by repeating upon same conditions and NOT put any HPBCD into the water:


= Complexation doesnt work.

DMT is stuck at the stirring bar at the end, possibly because it's the coldest surface in that glass.

What happens if you dont disperse the DMT unimolecular = dont melt it?

... not shown ... just stirring crystals for ages

= Complexation doesnt work.

If you would have a nanometer-microscope you would see giant ice-bergs of DMT stirred throughout the HPBCD. How would they ever get into the HPBCD barrels as solitary molecules?

Because of this I am kind of convinced that complexation will only work if you melt a hydrophobe drug and then stirr like crazy in a HPBCD water solution. If you can achieve this unimolecular dispersion by another way, maybe it will work too. But at least precipitation did not work (for Salvinorin A), as it probably starts to immediately form small crystallites, which will not ever break free again and enter any HPBCD pores. The solution will just look milky due to the crystallites being too small to ever form visible for your human eye. Still they are not unimolecular anymore. This can be even explained by physics: Salvinorin as an example is colourless. A cloudy solution of freshly precipitated Salvinorin catches the milky colour due to small crystals causing a light refraction inside the water. To refract light they have to be solid, which can only form by aggregation of molecules. Complexation impossible ...

Until a way to overcome this is found I guess complexation will not work with

- Harmalas
- Bufotenin
- Salvinorin

But it will work with any "classic" Tryptamine.

What would be interesting now is if complexation even survives Freezing and removal of water and addition again. In both cases the solution must stay homogeneous and clear at all times. Also if complexation is just as fast if the ratio is closer to 1:1, that would shrink down the needed water volume by far. But actually the most important question might still be: Is bioavailability indeed better now? :? :?

[What is wondering me: Why is complexed DMT-HPBCD-solution still brown? I thought the brown colour would come from Pi-Stacking which should be impossible now. Only solution would be also 2 DMT molecules can enter the HPBCD pore?]
More HPBCD experiments:

1. Does 1:1 of DMT:HPBCD indeed work?

Can you indeed complex DMT with a lower ratio of DMT:HPBCD? In that experiment above I used excess to speed things up, but if molten it is super fast anyways. So I tried only 50 mg DMT + 400 mg HPBCD (1 : 1,1) in 600 µl water. Much more concentrated for lesser volume and nearly 1:1 regarding host-guest interaction. Mixture was heated to 80 °C, stirred for 5 min and indeed everything complexed.


So at that point 69ron was right that equimolar amounts can be used, but mixing with tools would probably take quite longer than with automated stirrer.

Next question would be, how stable is that complexation? In solution the HPBCD might form a hydrophobe cavity for the DMT, but maybe upon conformational changes DMT could be kicked out, most likely provoked if the the water needed for HPBCD solvation is manipulated.

2. Does DMT-Complexation survive Freezing?

Will the guest be kicked out of the host at any stage of the water stopping being in liquid form? Maybe the conformation of HPBCD will drastically change and show DMT the door (HPBCD is cone-shaped so there should be indeed only 1 door).

Same DMT-HPBCD-water sample from above (1:1 Ratio) was frozen and thawed. No brown oily layer on top - no white precipitation at bottom - everything stayed homogeneous.


Therefore I believe everything is still complexed.

3. Does DMT-Complexation survive water-removal?

Similar to above this could induce a conformational change that will kick DMT out of its shell.


Same DMT-HPBCD-water sample from above (Freeze-Thaw cycle test) was placed inside of a drying chamber, air light, filled with CaCl2 (drying agent). After 24 h the water was mostly evaporated, a solid residue remained. This was still waxy, as it will still have a lot of water attached. Actually with heat you can remove much more water, until it will be rock solid. But as the HPBCD was not dissolved anymore it was enough for me. 2 ml of water was put on top and heated to 80 °C. Everything dissolved with no brown oily layer on top - no whiteprecipitation at bottom - everything stayed homogeneous.

No picture here, but well it looks just as after Freeze-Thaw ...

Therefore I believe everything is still complexed.

4. Can DMT indeed be only complexed when molten?

So above I wrote this theoretical explanation of why melting DMT for complexation might be necessary:

What happens if you dont disperse the DMT unimolecular = dont melt it?
... not shown ... just stirring crystals for ages

= Complexation doesnt work.

If you would have a nanometer-microscope you would see giant ice-bergs of DMT stirred throughout the HPBCD. How would they ever get into the HPBCD barrels as solitary molecules?

Actually I did not really stirr for ages of course. So I just wanted to be super sure and repeated it while actually stirring for ages to just prove if it indeed never complexes when still crystalline.

1000 mg HPBCD
50 mg DMT
3 ml Water

stirred and stirred and stirred ...

And guess what happened? It complexed after 5 h :shock: :shock: Also check how the solution is completely colorless and not brown like when using molten DMT.

So apparently I need to correct whatever theory I wrote above there. When you just stirr for ages, it will indeed also complex. That stirrer was set to 800 RPM and stirred 5 h straight so it might take forever when doing by hand. But it indeed vanished! Obviously I then also needed to make a blind sample to see if that will not also just happen with regular plain water with no HPBCD added. Both shown afterwards, DMT after 5 h fully complexed without any heating (left) and after 24 h nothing happens if no HPBCD is added (right):


No HPBCD would indeed let it stirr forever without anything happening. With HPBCD after some hours it's also complexed ... Now that it indeed works to complex DMT without making some unimolecular dispersion I tried it with Bufotenin. Same procedure with also 50 mg:

Left: Bufotenin in HPBCD solution before mixing
Middle: Bufotenin in HPBCD solution after 20 min stirring without heating
Right: Bufotenin in 100 % water after 24 h


As you can see also Bufotenin is complexed without any heating, directly from Freebase Crystals. Note how the colour of the water gets yellow upon. As a blind check Bufotenin in just water without HPBCD will not vanish at all even after 24 h ...


So apparently all that huge text wall above seems not entirely true. You can indeed complex Tryptamines straight from the Freebase Crystals into HPBCD solution. But how would that work? Now just again some speculation, that might explain this, while still fitting quite well to the results:

Probably a heterogeneous process like DMT molecules migrating directly from a crystal lattice into the HPBCD is quite unlikely. They have to first be dispersed into the medium to be able to be picked up by HPBCD. Now why it still could work this way is that solubility of any Tryptamines will never be truly 0 in water. There is always a really small fraction of molecules that get dissolved. Normally that is negligibly low and we dont notice it. Also while stirring as hell there would be a constant migration of Freebase DMT into water, it just would normally stop immediately as solubility of Freebase in water is obviously still close to 0. But upon dissolving due to the high concentration of HPBCD it gets absorbed into the HPBCD nearly instantly. Therefore that process can never reach equilibrium of DMT Freebase dissolved in the water. Therefore as DMT is constantly removed (by HPBCD) it means more and more DMT will be dissolved - and complexed sequentially - over time. After 5 h that process run to a complete and with 100 % complexed DMT.

A kind of cautious proof could be the Bufotenin experiment:

Because of that 5-OH-group solubility in water is way higher. Still negligible in neutral medium, but it will dissolve much faster. While also being absorbed instantly by the HPBCD, it means the speed of that hypothetical process would be much faster. And indeed: After 20 min all Bufotenin was already complexed, in contrast to the 5 h of DMT.

Obviously now while all that is still more something for scientific curiousity and rather has no direct usage, that process would be extremely interesting for Salvinorin, to finally make a non-smoking route that is not quidding. Spoiler Alert: It does not work ... Maybe Solubility of Salvinorin is even way lower and therefore that process is infinitely slow or HPBCD is not big enough for Salvinorin, needing more like HP-gamme-CD.

5. Bioassay:

Now that's quite sad and therefore the question remains, what does all that help with Tryptamines? Is their bioavailability indeed better? Would it have any improvement on the pharmacokinetics? Obviously it only makes sense when you know what to compare to. I have just 1x made some nasal 50 mg I believe, effect was not too strong and it was burning uncomfortably ... Then I did 70 mg of DMT Fumarate in a Nosespray and it was rather the same. 30 min duration with 20 min of annoying nose-burn. That's the only stuff I can compare too :?

DMT-HPBCD Nosespray:

- 50 mg DMT
- 400 mg HPBCD
- 600 µl water

- complexed at 80 °C
- diluted to 1200 µl for better dosage
- filled into Nosespray, which is ~ 73 mg water per spray = 73 µl
- 1,2 ml = 16x Spraying, with 3 mg complexed DMT per spray


Actually effects are feeled only 5 seconds after spraying easily. Also it still burned quite a LOT initially ... but most of the burning fades really fast. I would say first 15 seconds are really strong burning, but then the residual time burning is on like 10-20 % of that strength. Not the best, but definetly not too uncomfortable.

8 x Sprays = 25 mg
strong body high

10 x Sprays = 30 mg
very strong body high, like on Ketamine
still not much OEV / CEV

Nose felt like a little glued together, like a film making a stiff coating on your nose. Still with a finger it does not feel sticky.

I was impatient and did all the 16 x Sprays ...
16 x Sprays = 50 mg
visual distortions started and I had to lay back and felt a little bit sedated and like I had to close my eyes.
Still CEVs were not toooo strong ...

At T + 15 min nose started to not feel any burning anymore

At T + 20 min whole experience was nearly over


Well not too sure what to conclude. Did it have an effect? YES and not too bad. Probably stronger than the 70 mg Fumarate that I did back in the days. But ... that is definetly not enough to really distinguish between those 2 experiences.

Burning in the nose is strong when administered directly ... I can just say it I had the feeling it was fading faster than with the Fumarate. So IF the complexation has an effect, maybe it speeds up transportation of DMT to the mucus membranes, that will take up the Spice and therefore stop its irritation to the mucus membrane.

About effect strength, as I said not sure if bioavailability therefore indeed was raised? Just burning ceased faster. Still if I would extrapolate the effects to a really high level experience, then the nose-burn would indeed be more than annoying and make it impossible to really enjoy that experience. Obviously that is just a problem of the nose-spray method and sublingual would not have this problem. But as I was interested in checking nose-spray possibilities, that was my way of testing.

If burning would have not been a thing - like when sublingually administered, then it might have actually quite cool. But still dont know if strength would have been just equal if doing without HPBCD. Maybe will check that sublingual method both ways in future ...
What is wondering me quite much now:

Colorless white DMT crystals being absorbed into the HPBCD
= Colorless white solution

Yellow Bufotenin (its natural colour) crystals being absorbed into the HPBCD
= Yellow solution


Colorless white DMT crystals molten to brown oil being absorbed into the HPBCD
= slightly brown solution

I thought consens was that brown colour is always what you get when melting any Tryptamine because the molecules now released from their crystal grid will stack over each other with that Indol-units = Pi-Stacking and this creates a colour = brown.

So if DMT is truly absorbed into the HPBCD ... then why is the colour still remaining? Only explanation would be DMT is entering the sugar not alone, but in 2 or even 3 maybe?
And complexation definetly happened, the solution would just stay opaque with clouds / oil if no HPBCD is added ... :?
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