Pure Synthetic THH does not activate oral DMT!

[Phlux-]

heh iv been busy with high voltage projects and not spending enough time on the nexus - the old brain must be on the fritz again

 

[Phlux-]

speaking to a friend he said
"
it looks like the reaction is based on the nitrile group , other than the position of the methyl group harmine and harmaline is identical
"
i asked what it reduces to and he said
"
whatever molecule is identical to thh but with the ether and methyl group at another position on the benzine ring
"

care to clarify my confusion ?

 

[Eliyahu]

What do you mean by "activating THH", eli? And how do you know you had any THH to begin with?

Endlessness....it's just a theory I have I suppose. But I have noticed not just with the pure THH (obviously the FV stuff was questionsble or w/e.....)

I have noticed that when I take rue and caapi combined the caapi seems to be more activated and the properties of the caapi come out far more than if I were just to take a whole ton of of caapi, also it's way different than rue on it's own MUCH more visual, loving etc..

Also with the FV thh I noticed that it had no little or no effect on it's own, however
when I took about 70mg of the thh along with 100mg of harmine/harmaline it was much more Ayahusaca like than if I jsut took the harmine/harmaline alone...

At that time the thh I had from FV glowed bright blue under the blacklight, the harmine was green glowing. Not sure this means anything though ...

For example my usual dose is...

100 grams of caapi combined with 75mg of harmine fumerate and 1 gram of syrian rue.

this gives me a really caapi-like experience.. If i take 100gm of caapi on it's own though I get pretty much nothing

 

[moyshekapoyre]

Well, sorry to dig up an old thread I guess.

I've made my own THH via harmaline zinc reduction and it felt just exactly like the THH from FlowingVisions.

I haven't tried mixing dmt with my THH but I did do that with theirs. And it did activate DMT and it was WAY @#$@#$ more intense than if it had been harmine/harmaline ... basically THH does not hypnotize you into accepting the DMT... so it's all apparently up to you whether to let go or not (even tho in reality everything happens automatically with no agents doing anything but..).

I think it's clear that kitchen chemistry THH from harmaline will only get you maybe 80-95% pure THH, with harmaline & harmine contam remaining. So that may be why the home-made stuff did activate DMT so profoundly.

Just be careful tho because yeah, (home-made, impure) THH + DMT is no joke compared to regular ayahuasca...

 

[Infundibulum]

Well, sorry to dig up an old thread I guess.

I've made my own THH via harmaline zinc reduction and it felt just exactly like the THH from FlowingVisions.

I haven't tried mixing dmt with my THH but I did do that with theirs. And it did activate DMT and it was WAY @#$@#$ more intense than if it had been harmine/harmaline ... basically THH does not hypnotize you into accepting the DMT... so it's all apparently up to you whether to let go or not (even tho in reality everything happens automatically with no agents doing anything but..).

I think it's clear that kitchen chemistry THH from harmaline will only get you maybe 80-95% pure THH, with harmaline & harmine contam remaining. So that may be why the home-made stuff did activate DMT so profoundly.

Just be careful tho because yeah, (home-made, impure) THH + DMT is no joke compared to regular ayahuasca...

Very interesting! do you mind sharing some more technical details e.g. where did you get the harmaline for the THH reduction and how much of teh home-made THH you consume. Could it be that you had a mixture of harmine and harmaline (note that harmine does not reduce to THH with zinc), so if you have a fair amount of contaminating harmine then obviously dmt got activated.

 

[Auxin]

I glanced around but didnt see, has anyone developed a kitchen friendly paper chromatography protocol for harmine/harmaline/THH resolution?
Something like X:Y:Z 90% isopropanol:95% ethanol:1M household ammonia. Mark harmine and harmaline under blacklight and stain THH with iodine vapor.
A tek would probably be easy to develop.

 

[endlessness]

Are you talking about preparative paper chrom to separate or just for analytical purposes? If its the second case, with TLC I´ve been using methanol:25%ammonia in a 60:1.5ml ratio , but I´ve tried other mixes that worked just fine. Here´s a related thread:

THH isomers - Synthetic and Natural THH differences? - Plant Analysis and Substance Testing - Welcome to the DMT-Nexus

 

[Auxin]

Yup, I was thinking analytical for verifying home THH prep success. [That way people could experiment around with zinc, magnesium, acidic brews in aluminum pots, etc and obtain a reportable result]
Good related thread, glad to see THH is nice and visible at 365 nm- no staining needed

 

[moyshekapoyre]

Well, sorry to dig up an old thread I guess.


Very interesting! do you mind sharing some more technical details e.g. where did you get the harmaline for the THH reduction and how much of teh home-made THH you consume. Could it be that you had a mixture of harmine and harmaline (note that harmine does not reduce to THH with zinc), so if you have a fair amount of contaminating harmine then obviously dmt got activated.

MOD EDIT TO REMOVE SOURCING INFORMATION From his tests he has found that the harmine content of the harmaline was about 5%.

I'd say the chance of a small amount of non-THH harmalas activating DMT to that extent is pretty much zero, for me anyway, based on my experience.

I have since done further experiments using THH that I've made via Mg and HCl reduction (which seems to fully reduce all harmaline to THH--even harmine to THH, from what I see in the microscope), with many test subjects. It is now what I would call a fact that THH produced via reduction of other harmalas is a super powerful MAOI... and by that I mean, the dose of 200mg is required for someone who requires 200mg of harmine to inactivate their MAO, but the effect of that 200mg THH when combined with DMT is far stronger than if 200mg harmine were used.

So now I'm trying to figure out why Trips (the OP) got no MAOI effects from his synthetic THH. Shulgin theorized that synthetic THH was racemic, vs natural THH being dextrorotary. Not sure if that explains the difference fully. Too bad Trips never responded about what isomer he had.

 

[Jagube]

I think I've read on here that zinc reduction produces racemic THH.
If a certain dose of plant-extracted THH orally activates DMT, then twice that dose of racemic THH should do so at least as strongly, right?

 

[endlessness]

Several papers report THH as a poor MAOI.. And by poor it means, it will not have any noticeable MAOI properties at the dosages we consume harmalas

http://www.neip.info/downloads/Sci-Inv%20of%20aya-HR-DJMk.pdf

Another point worthy of remark is that the activity of THH in hoasca is apparently more a function of its inhibition of 5-HT uptake than to its action as an MAOI. THH is a poor MAOI compared to harmine (EC50 = 1.4 x 10-5M vs 8 x 10-8M for harmine), and while the plasma levels for harmine are well above the EC50 values, those for THH are well below the EC50 value for this compound as an MAOI

https://wiki.dmt-nexus.me/w/images/2/26/Pharmacokinetics_of_hoasca_in_healthy_humans.pdf

Due to its weak affinity, and in the presence of high harmine concentrations, THH may not play a significant role in the inhibition of MAO. Instead, THH may contribute psychoactivity indirectly by inhibiting the uptake of 5-HT in platelets and presynaptic neurons (Airaksinen et al., 1980), further increasing extracellular 5-HT levels over those seen from MAO inhibition alone, as significant amounts of this alkaloid are known to occur in B. caapi (Rivier and Lindgren 1972; Callaway et al., 1996). The pharmacokinetic profile of THH (Fig. 2) and related parameters (Table 2) also suggests some independence from interactions between harmine and MAO. It is possible that the activity of THH may even be potentiated by
MAO inhibition.

moyshekapoyre, I'm not sure if you can trust microscopic appearance of crystals as an indication of purity. If you still have samples, we can get it tested.

 

[tregar]

Link from endlessness:

THH in hoasca is apparently more a function of its inhibition of 5-HT uptake

This is very true, tetrahydroharmine is a potent 5-ht or serotonin inhibitor. Even though most likely no one at this forum needs an explanation, I thought it would be helpful to post some technical scientific explanations for why Ayahuasca and/or traditional Amazonian snuffs are so very different from smoked dmt. One critical difference is that Ayahuasca and the traditional snuffs used in the Amazon both contain potent serotonin (5-ht) inhibitors. This accounts for over 80% of the brain's serotonin filters!...while dmt is only stimulating the other 20% of brain 5-ht.

DMT smoked or used orally has no serotonin blocking action (0.00 in chart below at 5-ht1a), but when combined with the components of Caapi for example, you get the classic serotonin blocking action of THH combined with the outstanding activation of all the other receptor sites by Dmt, important team work going on then. Notice the outstanding serotonin blocking action of LSD, mescaline, psilocin, and 5-meo-dmt in the 5ht1a column below. Ayahuasca does the same with the THH in caapi, and then when the dmt is added, you have the full monty.

Nichols: "LSD has very strong potency in blocking the action of serotonin. The morpholide lysergamide cousin had only about 1/10th the potency in blocking serotonin. Of the 5 diferent dialkylamides we studied LSD was the most potent and specific serotonin antagonist. " [page 2 & 3 of 8 in attached paper].

Thomas S. Ray, Psychedelics and the Human Receptorome (2010):

Psychedelics and the Human Receptorome

We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT2A (and possibly 5-HT2C) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these two receptors. This manuscript is a reference...

journals.plos.org

hxxp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0009019

Breadth of Receptor Binding, 4.00=max, 0.00=min

LSD: 5ht1a = 3.73, DMT: = 0.00, psilocin = 2.88, mescaline = 3.61, 5-meo-DMT: = 4.00 (make up >80% of brain 5-ht)
LSD: 5ht1b = 4.00, DMT: = 0.00, psilocin = 2.19, mescaline = 0.00, 5-meo-DMT: = 2.41
LSD: 5ht1d = 3.70, DMT: = 3.91, psilocin = 3.40, mescaline = 0.00, 5-meo-DMT: = 3.48
LSD: 5ht1e = 2.62, DMT: = 3.28, psilocin = 3.03, mescaline = 3.16, 5-meo-DMT: = 1.72
LSD: 5ht2a = 3.54, DMT: = 2.58, psilocin = 2.14, mescaline = 0.00, 5-meo-DMT: = 0.98
LSD: 5ht2b = 3.11, DMT: = 3.91, psilocin = 4.00, mescaline = 3.97, 5-meo-DMT: = 0.69
LSD: 5ht2c = 3.11, DMT: = 3.42, psilocin = 2.52, mescaline = 0.00, 5-meo-DMT: = 1.55
LSD: 5ht5a = 3.64, DMT: = 3.16, psilocin = 2.83, mescaline = 0.00, 5-meo-DMT: = 1.84
LSD: -5ht6 = 3.75, DMT: = 3.35, psilocin = 2.82, mescaline = 0.00, 5-meo-DMT: = 2.73
LSD: -5ht7 = 3.77, DMT: = 4.00, psilocin = 2.82, mescaline = 0.00, 5-meo-DMT: = 3.69
LSD: ---D1 = 2.34, DMT: = 3.51, psilocin = 3.37, mescaline = 0.00, 5-meo-DMT: = 2.38
LSD: -A-2A = 2.93, DMT: = 2.75, psilocin = 1.36, mescaline = 2.92, 5-meo-DMT: = 0.00
LSD: -A-2B = 0.00, DMT: = 3.53, psilocin = 1.57, mescaline = 0.00, 5-meo-DMT: = 0.86
LSD: -A-2C = 0.00, DMT: = 3.53, psilocin = 1.03, mescaline = 4.00, 5-meo-DMT: = 1.57

As we go thru day to day life, the brain serotonin filters are in place so that we will not be overwhelmed by the perception of the way things would appear to an un-filtered mind, or "Mind at Large" as Aldous Huxley describes it in "Doors of Perception" as "infinite or eternal". He also referred to the visions as coming from "the other world" in his book "Moksha". I prefer to think of it in similar terms as well "the spirit world" or "the other world". 5-ht1a inhibition theoretically causes this filter system to be lifted, and the infinite mind to manifest in combination with dmt for example.

An example of the importance of adding the serotonin reuptake inhibition properties of 5-meo-dmt for example to dmt (which totally lacks 5-ht1 reuptake properites on it's own) is shown below. This is the same way the snuff's are used in the amazon, as they naturally combine dmt with additives which cause the reuptake of 5-ht like bufotenin for example.

Oroc's experiment of combining 5-meo-dmt with DMT sounds imho very much like a short beautiful transcendental Ayahuasca experience, from his book "Tryptamine Palace":

Oroc: DMT + 5-meo-dmt:

As an experiment (and in a foreign land) I smoked the last of the Bufo alvarius venom (the story of whose collection is described within the pages of Tryptamine Palace) with some ‘regular’ DMT (extracted from Jurema Preta.). In the vast majority of my early nigerine (DMT) experiences, I encountered visual fields of ‘dots’ that would come together to form images, much like the pointillism style of painting developed by Georges Seurat or the Australian Aboriginal song-line paintings.

** With the addition of the 5-MeO-DMT containing toad-venom to the DMT however, the visual characteristic was completely different and totally unique to my experiences so far. On this occasion there was a complete lack of ‘dots’ or ‘points’ of any kind, the fine lines of the constantly changing imagery were like those painted with a single-hair brush on Tibetan thangkas and due to the overwhelming artistry of what I was seeing, I could only think of the vaulted ceiling of the Sistine Chapel in comparison.

Sistene Chapel: This was without a doubt the most ‘visionary’ experience I have ever been fortunate enough to encounter and I lay there with my eyes shut watching the most fantastic parade of the Collective Unconsciousness imaginable, wishing that it would never end, and as I sit here now I can not even describe one tiny corner of it, since every image in the multitude of imagery was in such constant motion that they defied all but a glimpse. And then moments later, like a tent collapsing when its ropes are cut, the vision is gone. Leaving only a struggle of words to explain it, since nothing before or after has come close to this experiences visual majesty.

This experience leads to the interesting question of selectively combining DMT and 5-MeO-DMT for a more visionary and somewhat less overwhelmingly transcendental experience. (Or for the other way around). This combining of the two endogenous entheogens is being tested in changa blends (reportedly at a 90% DMT to 10% 5-MeO-DMT ratio), while many Pharmahuasca urban-shamans are also adding 5-MeO-DMT to their ayahuasca-analogues to transform and deepen that experience. It seems likely to me that the combining of DMT and 5-MeO-DMT in various ratios and manners will only become more popular as the exponentially increasing number of psychonauts search for new psychological terrain to explore.

Oroc's combining of DMT with trace amounts of 5-meo-dmt resulted in a breath-taking experience that was so very different from all of his past dmt only smoked experiences that he wrote about it. This is how the snuff's are in the Amazon: they combine dmt with minute amounts of 5-meo-dmt or bufotenin, both very potent 5-ht1a serotonin reuptake inhibitors. This resulted in a beautiful short lasting transcendental "Ayahuasca experience" for him, for the 1st time in his life. Ayahuasca is the exact same way, it contains oral serotonin reuptake inhibitors as well: so the "infinite mind can manifest" away from it's normal booted "survival mode" for day to day living.

I like the way professor8 describes THH here from "THH Harmala holy grail": THH - Harmala Holy Grail - Harmalas - Welcome to the DMT-Nexus

professor8 (11/1/2010, he writes like a poet with special powers of imagination & expression):

THH has the ability to raise your vibration in a most powerful, yet subtle way. It brings a crystalline prismy texture to spice and adds a super clear watery dimension to Aya, like looking down through 10meters of shimmering Caribbean Sea on clear blue day. It brings a dimension of pure light to the entheogenic experience and encourages entities & intelligences of only the Highest Order. If one is not accustomed to perceiving these experiences with a spiritual perspective most of the nuances & subtleties THH brings on are overlooked and remain unseen and one would better enjoy Harmaline as a house painter chooses a roller over a brush, its about preference & choice.

Trips (from this forum here on 12/2/2011, and the one who started this topic, loved all of his old classic posts, he will be remembered always):

As to how the THH altered the experience -> I find rue extract+DMT to be very similar to mushrooms. I found the THH added to the rue+DMT to shift the experience to a state much closer to that provided by LSD. It was more clear, more energetic, more euphoric, more focused, and when confusion struck it was definitely more "acid-like".

Professor8 and trips were both way ahead of their time. They seemed to have managed THH synthesis/extractions way before there was any interest and posted beautiful encounters of their experiences...they lead the way in a sense, if you were into that kind of thing. They were the game changers.

 

[tregar]

But anyhow, back to the topic: from Tetrahydroharmine (CAS 17019-01-1)

tetrahydro-Harmine (THH) is a fluorescent indole alkaloid extracted from B. caapi, a woody vine that is used to produce a psychoactive beverage, ayahuasca, which has been ritually ingested for medicoreligious purposes throughout South America since pre-Columbian times.1

THH inhibits monoamine oxidase (MAO)-A and MAO-B with much weaker potency (IC50s = 74 nM and >100 μM, respectively) compared to the companion harmala alkaloids also found in B. caapi: harmaline (Item No. 10995; IC50s = 2.5 nM and 25 μM, respectively) and harmine (Item No. 10010324; IC50s = 2 nM and 20 μM, respectively).2,3

There is virtually no mao inhibition worth noting at normal caapi/harmala doses, just as trips and endlessness note.

 

[endlessness]

Taking those numbers tregar mentioned, and considering ic50 is inversely proportional to the amount of inhibition, THH is about 30 times less potent than harmine/harmaline to inhibit MAO-A. That means to have the same MAOI effect as 200mg harmine, you'd need to take 6g of THH.

 

[tregar]

Endlessness said:

Taking those numbers tregar mentioned, and considering ic50 is inversely proportional to the amount of inhibition, THH is about 30 times less potent than harmine/harmaline to inhibit MAO-A. That means to have the same MAOI effect as 200mg harmine, you'd need to take 6g of THH.

Thanks endlessness, in the past had said 200mg was equivalent to around between 5 and 10mg of harmine inhibition, so was not far off, pretty much exactly the numbers I came up with as well. Should also mention that from the paper I have seen, tetrahydroharmine's inhibition of 5-ht1a receptors (which make up over 80% of brain 5-ht) are completely balanced by it's counter stimulation of adrenal receptors. Mescaline and dmt are other potent stimulators of the adrenal receptors. Nature seems to have made DMT to be extremely potent at all the "other" brain 5-ht receptors, just looking at the chart, you find nothing else as potent at all 3 adrenal receptors for instance, but in order for DMT to be like this, it must give up stimulation of 5-ht1a, it just can't "do it all", so in my opinion, that's why it was meant to "team up" with caapi or the harmalas in a sense, to achieve the "full Monty" of receptor stimulation, becoming the world's most potent hallucinogen, and achieving infinite-mind spiritual other-worldliness in the process, just like cactus, mushrooms, or LSD.

Breadth of Receptor Binding, 4.00=max, 0.00=min

LSD: 5ht1a = 3.73, DMT: = 0.00, psilocin = 2.88, mescaline = 3.61, 5-meo-DMT: = 4.00 (5-ht1a makes up > 80% of brain 5-ht)
LSD: 5ht1b = 4.00, DMT: = 0.00, psilocin = 2.19, mescaline = 0.00, 5-meo-DMT: = 2.41
LSD: 5ht1d = 3.70, DMT: = 3.91, psilocin = 3.40, mescaline = 0.00, 5-meo-DMT: = 3.48
LSD: 5ht1e = 2.62, DMT: = 3.28, psilocin = 3.03, mescaline = 3.16, 5-meo-DMT: = 1.72
LSD: 5ht2a = 3.54, DMT: = 2.58, psilocin = 2.14, mescaline = 0.00, 5-meo-DMT: = 0.98
LSD: 5ht2b = 3.11, DMT: = 3.91, psilocin = 4.00, mescaline = 3.97, 5-meo-DMT: = 0.69
LSD: 5ht2c = 3.11, DMT: = 3.42, psilocin = 2.52, mescaline = 0.00, 5-meo-DMT: = 1.55
LSD: 5ht5a = 3.64, DMT: = 3.16, psilocin = 2.83, mescaline = 0.00, 5-meo-DMT: = 1.84
LSD: -5ht6 = 3.75, DMT: = 3.35, psilocin = 2.82, mescaline = 0.00, 5-meo-DMT: = 2.73
LSD: -5ht7 = 3.77, DMT: = 4.00, psilocin = 2.82, mescaline = 0.00, 5-meo-DMT: = 3.69
LSD: ---D1 = 2.34, DMT: = 3.51, psilocin = 3.37, mescaline = 0.00, 5-meo-DMT: = 2.38
LSD: -A-2A = 2.93, DMT: = 2.75, psilocin = 1.36, mescaline = 2.92, 5-meo-DMT: = 0.00 (A2A adrenal receptor)
LSD: -A-2B = 0.00, DMT: = 3.53, psilocin = 1.57, mescaline = 0.00, 5-meo-DMT: = 0.86 (A2B adrenal receptor)
LSD: -A-2C = 0.00, DMT: = 3.53, psilocin = 1.03, mescaline = 4.00, 5-meo-DMT: = 1.57 (A2C adrenal receptor)

The stimulation of the A2A, A2B, and A2C adrenal receptors are responsible for alot of the "aesthetic quality" that is dreamed on cactus or dmt trips, and why LSD seems to have less "aesthetic artistic quality" in comparison to mescaline/dmt but is more analytical in a sense. THH stimulates these same adrenal receptors as well, it's agonization of those receptors are a counterbalance to it's 5-ht1a inhibition, a fine balancing act. This counterbalancing is necessary to keep these psychedelics safe as well. The man-made 25 i-nbome molecules are so dangerous because they have no counterbalance to their extreme 5-ht2a agonization. You see this same balancing act with LSD, mescaline, mushrooms, and to a lesser extent 5-meo-dmt (which is more lopsided to 5-ht1a inhibition only) and why more precautions are needed to dream it safely.

 

[Jagube]

That's interesting information about how these molecules interact with the different receptors.

One question though. A few days ago I took 100mg THH with 75ug 1P-LSD. This one experiment is not enough data points to draw conclusions from, but I couldn't help but feel that the THH weakened the effects of the 1P-LSD. Could their action have countered each other, or was it just me (my set and setting, possibly some tolerance - I had drank Aya analogs with THH, but hadn't taken anything else in a while).

 

[tregar]

Thanks Jagube. Yes, I don't think thh will improve the operation of any of the natural entheogens or the semi-synthetic LSD due to all of those entheogens already having significant 5-ht1a inhibition in balance with the other 5-ht receptors, just as you found out. The THH no doubt theoretically improves the operation of the dmt molecule in the "infinite or un-filtered mind, as Huxley defines it" as dmt totally lacks the 5-ht1a inhibition (which makes up over 80% of brain 5-ht) which THH makes up for. Reading Oroc's account above in post #32 of 5-meo-dmt traces in combination with dmt also reveal the power of 5-ht1a inhibition in combination with dmt (like a shorter acting brief Ayahuasca).