Does THH suppress the effects of DMT?

[Jagube]

I drank a controlled dose of 100mg THH and 150mg of (presumably) nearly pure harmine, with MHRB tea.
I felt the rootbark quite strongly, with visual and other effects. I had two servings of that.

Then I zinc-reduced a full, unseparated harmine/harmaline mix (at the original and unknown ratio) and decided to give that a try with MHRB.
I drank 300mg of that harmine/THH mix, having assuming the ratio would be roughly 50:50. This was followed by a similar dose of MHRB to that in the first bioassay.
I had a wonderful, beautiful, profound experience, but it wasn't visual and it seemed like the DMT didn't shine through. I also didn't feel too cold, didn't have lose bowels or onset anxiety.
For the second serving, I had 150mg harmine, 100mg THH and a standard dose of MHRB. Still, no clear DMT effects.

This led me to suspect the ratio in the original harmala mix was actually in favor of harmaline, and - after the reduction - THH, and the received dose of THH was on the high side, which somehow suppressed the DMT. That's the most obvious parameter that was different from the first bioassay.
I don't think it was insufficient MAOI from the harmine levels being too low, because the second glass had 150mg harmine, which usually does the trick for me.

 

[Elrik]

THH•HCl, taken as 150 mg 1 hour prior or two 100 mg pills per session taken at both 1 and 2 hours prior [I'm trying to decide which I like better] has never reduced visuals from ACRB refined alks in me. I never tried it with simple bark tea, or with simultaneous THH/ACRB dosing.
One question, though, was your MHRB tea a portion of known potency frozen stock or was it a fresh batch? It could have been a quirky tea batch?

 

[Jagube]

One question, though, was your MHRB tea a portion of known potency frozen stock or was it a fresh batch? It could have been a quirky tea batch?

It was a fresh batch, shaken before pouring and mixing.

I don't know how much THH I consumed, quite possibly it may have been in the order of 400mg or more in the single session. I couldn't sleep until 8am (having started at 8pm; and that only thanks to melatonin), and felt high the whole following day.

 

[Jagube]

THH inhibits serotonin uptake, as a result there is more serotonin floating about. And the DMT has to compete with that excessive serotonin for the same receptors, right?

 

[tregar]

From Dr Callaway & Dennis Mckenna: Erowid Ayahuasca Vault : Scientific Investigation of Ayahuasca, McKenna, Callaway, Grob 1998

There is some evidence, however, that tetrahydroharmine (THH), the second most abundant ß-carboline in the beverage, acts as a weak 5-HT uptake inhibitor and MAOI. Thus, THH may prolong the half-life of DMT by blocking its intraneuronal uptake, and hence, its inactivation by MAO, localized in mitochondria within the neuron. On the other hand, THH may block serotonin uptake into the neuron, resulting in higher levels of 5HT in the synaptic cleft; this 5-HT, in turn, may attenuate the subjective effects of orally ingested DMT by competing with it at post-synaptic receptor sites (Callaway, et al., 1997).

In my opinion, the 1st sentence is true: THH may prolong the half-life of DMT by blocking its intraneuronal uptake, and hence, its inactivation by MAO, localized in mitochondria within the neuron.

I agree with Elrik, in that there is no lessening, but rather the opposite: dreamed over fifty experiences with lots of brew heavy in thh mixed together with moderate amounts of psychotria leaf from Hawaii (30 to 35 grams of hot filtered leaf brew)...then reduced down to 2oz....experiences have always been very intense on the light or leaf side and long-lasting (90 minutes of super strong activity) followed by 90 minutes of strength that is easier to handle. Definately no weakening of the leaf effects, if anything made the leaf effects stroger and longer lasting by "preventing the breakdown of dmt by blocking it's intaneuronal uptake and inactivation by mao in the mitochondria in the neurons."

These experiences were so strong leaf active wise, could only sit still in dreams for the 1st 90 minutes and close my eyes in an attempt to slow down the visuals and visions, which were extremely bright and rapidly changing, any attempt to move more than an inch up and down or side to side would result in hundreds of new visuals forming. Closing eyes was an attempt to find a happy place in the super intense sessions, as the effects can be frightening and even overwhelming when the leaf dose is too much. Open eyes effects were super intense with objects leaving tracers without even moving that went backwards into infinity, colors super saturated with colors that don't even exist, these colors given off by objects would even fill the entire room at peak effects. Beauty intensity mind-boggling of artistic creations, female form, nature. Not only was sound heightened and intensified, but sounds and music very different from normal and music intense in beauty.

With the proper leaf dose, the effects are very euphoric and easier to handle. There is most definately no lessening of the effects, these sessions were super-intense visually and divine in nature with open eyes, revealing infinite beauty for hours. Closed eye visions at peak included beautiful naked women spinning in front of slowly spinning marble pillars, scenes of Atlantis, beautifully decorated elephants from India, traveling thru spinning vortex of blue color dropping me off on distant islands to view the inhabitants and their artwork made out of wood (tikis), a Polynesian woman then gesturing to show that these tikis marked the boundaries of their sacred sites. The phenemonology of the experiences otherworldly & divine in nature.

Also recall that LSD, mescaline, 5-meo-dmt and psilocin are all potent 5-ht reuptake inhibitors just like THH (inhibit 5-ht1a which makes up over 80% of brain 5-ht) while dmt has zero activity at 5-ht1a...and thus must be combined with thh for this to happen (important teamwork going on then with Ayahuasca). See chart below.

Thus, 5-ht reuptake inhibiton appears to be a very important feature of all the natural oral entheogens found in nature along with the semi-synthetic LSD. Also recall the snuffs in the Amazon which all combine dmt with bufotenin and/or 5-meo-dmt which also greatly increases it's visual propensity.

For the fact that lsd, mescaline, shrooms, and THH (tetrahydroharmine) all inhibit 5-ht definately does not take away from it's visionary properties, but actually enhances it.

DMT is super-potent at the other 20% of brain 5-ht, but can only "do so much" which is why it requires THH teamwork in caapi to fill in for the missing 5-ht1a inhibition (makes up the other 80% of brain 5-ht). Just look at the potency of dmt at all 3 adrenal receptors below, nothing else comes close, but in doing this, it gives up potency at 5-ht1a, and looks for caapi to fill in for what it must miss at becoming so potent everywhere else.

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)

Inhibition of 5-ht (serotonin) by thh, lsd, mescaline, shrooms, & 5-meo-dmt/bufotenin lift the barriers or serotonin built up survival filters in the brain (80% of brain 5-ht) so that "mind at large" as coined by Aldous Huxley can rain free. Ayahuasca is teamwork between thh, harmine/harmaline and dmt.

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.

 

[Jagube]

Thanks for that, tregar. You say the THH in Ayahuasca is crucial for completeness, but do we know the harmine or harmaline in Rue don't inhibit 5-ht1a? When I worked with Rue or its extracts without THH, I always felt rather complete, like my receptors had been 'cleansed' and reset.
THH, on the other hand, leaves a crazy long, warm and fuzzy afterglow, but when I don't feel DMT I still feel incomplete and 'unreset'.

The only explanation for why I didn't feel the DMT so much is that I didn't consume sufficient harmine for full gut MAOI.

 

[Sabnock1990]

Thanks for that, tregar. You say the THH in Ayahuasca is crucial for completeness, but do we know the harmine or harmaline in Rue don't inhibit 5-ht1a? When I worked with Rue or its extracts without THH, I always felt rather complete, like my receptors had been 'cleansed' and reset.
THH, on the other hand, leaves a crazy long, warm and fuzzy afterglow, but when I don't feel DMT I still feel incomplete and 'unreset'.

The only explanation for why I didn't feel the DMT so much is that I didn't consume sufficient harmine for full gut MAOI.

Yeah for me personally using Rue things have always felt full, whole/complete, i find no necessary reason for THH being in the mix. You can already change/alter/flavor things by the addition of admixture plants/oils/supplements, so at least for me, while i haven't yet tried THH aside from Caapi, i don't find THH to be necessary. It may indeed add something beneficial to the mix, but you can probably do better with admixture plants. I think a lot of people hype up THH a lot and make it seem like THH makes or breaks the Aya experience, it may be useful but the lack of THH hasn't ever been a concern for me, Rue/Harmalas work just fine and i already get so much out of this stuff that while i wouldn't mind investigating THH, it's not really a concern. I certainly have no complaints about Rue and Acacia/Mimosa for me personally, especially with 4 grams of Lemon Balm in the mix which cleans things up quite nicely. I'd much rather go for admixture plants to further the potential of Aya than to focus on THH. There's literally many possible alterations/flavors of the Aya experience/medicine so i really don't think THH would make much difference compared to what all else there is out there that can be mixed with Aya.

And this is why i advocate for a broader understanding of the technology that is Ayahuasca, whether using traditional plants or analog plants, it's the same technology, just different plants/flavors, which can be further flavored through admixture plants. So i don't think Caapi is so special, both Rue and Caapi imo/ime are equally as valuable, useful, and special, same technology, different plants/flavors.

 

[tregar]

It's all in what you prefer, yes. The whole psychedelic trip is a very personal individual thing. Like trips used to say, rue and dmt is like mushrooms, as you still get a bit of 5-ht1a inhibition from harmine and harmaline (similar to what happens with psilocin at 2.88 5-ht1a inhibition). Adding thh to the mix will make it more like LSD or mescaline (which both have >3.6 5-ht1a inhibition), as the chart above shows. THH with the rue or caapi's harmine/harmaline reminds one of a shorting acting LSD or cactus trip, only further out there at a2b, as Ayahuasca is the world's most potent psychedelic no doubt, it really attacks all the available 5-ht receptor sites.

Unlike LSD, the trip is more adrenal based, as dmt has all the elements of mescaline's incredible adrenal activity (see chart above at a2a, a2b and a2c) which really brings out the feelings of love/empathy/beauty while LSD is more analytical. But don't forget that along with this high adrenal activity is a combo of very strong 5-ht1a or serotonin inhibition ingrained in cactus, lsd, or thh (caapi) based Ayahuasca. The THH will also theoretically extend the half-life of the dmt in the psychotria as it slows down the mitrochondria from killing it off early.

Ayahuasca has it all, it's just a shorter journey (no more than 3 hours long typically). But if you take a 2nd dose hours later, things can get really crazy and visions can last into the rest of the night (upwards of 6+ hours). Ron used to speak about how 5-meo-dmt used to remind him of LSD, as you can see from the chart above, 5-meo-dmt is the world's strongest 5-ht1a inhibitor, and has strong serotonin inhbition just like LSD or mescaline at 5-ht1a.

Trips (from this forum here on 12/2/2011):

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".

Like you mentioned Jagube, you most likely just didn't have enought harmine in you or the timing was off somehow. I've never liked mushrooms much (confusing, darker and not as euphoric) and so that is why I prefer THH heavy rue/caapi brews--they remind me of shorter acting cactus/lsd style trips. It's all individual and no one can choose for you but yourself.

 

[Sabnock1990]

I agree Tregar. Though while i understand that THH may come in handy, i do wonder about all the possible admixture plants/oils/supplements that could be useful as well, perhaps even more useful than THH, or that can do similar things as THH. There's many ways to go about this imo and there's a lot of potential in synergistic herbal combinations. But yeah i'm quite sure it's possible to make DMT/Aya feel more LSD or Mescaline-like through the use of admixture plants, though if THH can indeed do that then that's interesting too.

For me, the DMT part seems to last a full 4 to 5 hours from come up to afterglow, and the Harmalas usually last about 8 full hours from consumption till i'm back down, 6 hours if i'm using a lighter Harmala/Rue dosage.

I also agree that DMT is quite Adrenergic, quite a few times i've even taken 1 to 3 capsules of Mimosa root powder, and at 1 capsule it felt a bit like a "psychostimulant" (i've always liked that word) in a way, and at 3 capsules especially with Moclobemide it's Adrenergic effects were quite apparent, so even low dosages of Mimosa/DMT can still be quite intense, much more so than Psilocin (mushrooms or 4-ACO-DMT) or LSD has been for me so far. DMT is indeed quite strong/powerful lol, but it's my favorite Psychedelic/Entheogen thus far.

 

[Jagube]

I've now separated my harmine:THH mix. The THH is still drying and I don't know what the losses were, but assuming 100% separation and no loss, it would seem the ratio was around 1:3 (my original assumption was 1:1). With my 300mg consumed per serving, that would be 75mg harmine and 225mg THH. No wonder I didn't feel the DMT! Also, I drank that dose twice, spaced ~3 hours apart, which would mean a whopping 450mg THH consumed in a session. My head still feels incredibly clear 24 hours later and I feel peace, as if the THH were still in my system.

Edit: After the THH dried, the loss turned out to be ~20% and the pre-reduction harmine : harmaline (or post-reduction harmine : THH) ratio 1:2 rather than 1:3.

 

[tregar]

Well said Shamanstamen as usual, I also agree with you...nice to hear about your mimosa experiences and possible admixture topics. Glad to hear Jagube! Let us know how it goes in the future one day, will stay tuned. Always had dreamed actual reduced down Hawaiian psychotria brew as knew a grower in Hawaii. Never failed to work strongly and long-lasting when caapi mixed together with psychotria leaf and reduced down to 2oz of hot filtered liquid. For some reasons we may never understand (and just like Palmer states in his book), the actual liquid form of the tea from psychotria at 30 to 35 grams (which I dreamed) is equivalent to around 70mg dmt, but is quality wise different from the xtal form in this liquid plant form tea--the salt liquid form of the leaf in this state is extremely powerful perhaps due to dynamics of digestion and packs a wicked punch that is strong for hours and mind-blowing encompassing. The words he writes below give credit to the actual plant liquid form (see * below) of the brew from the psychotria leaf or other plants containing the "light":

From "Articulations, On the Utilisation and Meanings of Psychedelics" (2015) by Julian Palmer:

Modern day researchers, spearheaded by people such as myself, have realized that Jonathan Ott's calculations fall short of what most explorers need for a truly visionary experience. Even with a strong harmine/Banisteriopsis caapi dosage, 30-60mg of dmt is not sufficient to produce significant visionary effects in most people. So if fact, a dosage of 30-40mg of dmt is where tryptamine-like effects just begin to occur for most people, and 10-25mg dmt is not really noticeable above the gentle psychoactive effects of the harmine.

Each person is different and for some rare individuals, 30-40mg may be about as much dmt as they wish to take--but most people need at least 60-80mg for sufficient psychoactive effects and even at this dosage, you generally cannot expect a full-blown visionary experience, even when using a strong dose of 4 grams of syrian rue or 100 grams of strong caapi vine. Also, it should be pointed out that going beyond 4 grams of syrian rue (around 200-280mg of harmaline) or 100 grams of strong caapi vine (150--250mg of harmine) can increase the negative effects of these beta-carbolines--which include a feeling of heaviness, pressure in the head, inability to walk properly, more purging and perhaps more of an emphasis on bodily processes.

An oral dosage of 100mg of dmt is where the visionary qualities really begin to occur, for most people say when they are taking 3 grams of syrian rue or 80 grams of strong vine, and in context, 40-60 grams of strong vine is enough to fully mao inhibit most people.

I would say to neophyte explorers to tread carefully, and to slowly increase your dmt dosage in increments: perhaps starting at 60mg, going to 100mg, then 150mg. Some people are going to find 100mg of dmt to be exceedingly strong, and it will perhaps give them an experience they did not feel ready for.

* It came to my attention after an embarrassing number of years, that taking freebase crystal DMT orally was not as potent, colourful, or clear as taking the equivalent amount of DMT in a tea that was brewed from the plant. For many years, I couldn't see how there could be a difference, but after doing some comparisons, it was obvious that the tea was much better, and the experiences resulting from the crystalline extract were inferior.

* You could take twice or even three times as much DMT crystal as the equivalent in brew, and the experience from the crystal would never be as bright or full as that from the tea. Why could this be?

With extracted dmt, with chemicals used it would appear that some dimensions and qualities of the tryptamine molecules are compromised. Also, there is the factor of isolating the alkaloids from the rest of the plant. For example, there are very few people who say that extracted pure mescaline from the cactus is as potent of full bodied compared to when they take the tea made from the cactus flesh.

When making a tea from the whole plant, you are extracting the essence of the plant intelligence from its very flesh, not just isolating the alkaloids. In the alchemic method "Spagyrics" developed by Paracelsus, often considered the father of modern medicine, the ashes of the plant are commonly burnt and then blended back into an alcohol-extracted tincture. Friends who have experimented with this procedure report that a Spagyric tincture of Ayahuasca is much more potent than a normal tea prepared from the same amount of Ayahuasca vine.

p.s. Even though dmt plants with just harmine or harmaline journeys are commonly compared to mushrooms, by viewing the chart above, you easily see that dmt is two to three times stronger at the receptor sites (except for 5-ht1a) as compared to psilocin, so this will create a journey that is quite different from mushrooms, and even though dmt plants with the harmalas + THH are commonly compared to lsd, it is perhaps better explained as a journey that is like nothing else, as LSD would be like child's play when compared with full blown Ayahuasca. There is truly nothing else like Ayahuasca, it is in a league of it's own.

 

[Jagube]

After the separation I tried the following:
180mg harmine, 120mg THH, 30mg harmaline and 30mg other Rue alkaloids in combination with 3.3g ACRB in crude tea form.

It was great, I felt the ACRB strongly and it lasted a good 5-6 hours. This suggests THH doesn't suppress DMT and my previous attempts failed due to insufficient MAOI.

Now I know my Rue seeds have 1:2 harmine to harmaline and I know how to prepare my harmalas from Rue at the right ratios. The only problem is that this leaves me with excess THH, which I don't know what to do with. After my last extraction I'm left with spare 2.6g freebase THH. Plus another 2g or so from the previous extraction. I love THH, but not when it's more prevalent in my drink than harmine.

 

[downwardsfromzero]

this leaves me with excess THH, which I don't know what to do with.

Sounds like you'll just have to extract more harmala alkaloids and mix the spare THH into those.

Spare THH, sheesh, what a bummer! :lol:

 

[Jagube]

Sounds like you'll just have to extract more harmala alkaloids and mix the spare THH into those.

The point was that my seeds' natural harmine:harmaline (or harmine:THH post-zinc-reduction) ratio of 1:2 is too high on harmaline/THH, i.e. higher than in Caapi and higher than what I like. Since my main use case is making a Caapi copy from Rue, every time I'll be left with spare THH, unless I intentionally discard the harmaline (which could save me some ammonia) or skip the zinc reduction and accept the high harmaline content.

 

[downwardsfromzero]

It should be relatively simple to convert the harmaline into harmine.

Other than what I've quoted below, it's not possible for me to point you towards a known method in this precise moment. I get the feeling it should be straightforward enough under OTC domestic conditions.

Under the appropriate conditions, harmaline could disproportionate to form harmine and THH. At the very least, prolonged boiling should encourage the oxidation (in the sense of dehydrogenation by dissolved/atmospheric oxygen) of harmaline to harmine, as is thought by some to occur in caapi brews.

And Shulgin observed that a very old harmaline sample contained virtually all harmine, suggesting (but not proving!) that harmaline spontaneously dehydrogenates very slowly. Equally, the sample could have been bunk from the start.

Anyhow, it seems like work on a harmaline to harmine conversion would be fruitful.

My outline thoughts are that ascorbic acid (vitamin C) could act as a hydrogen transfer agent by shuttling between the reduced state and dehydroascorbic acid. Certain metal ions or catalytic metals could assist in this process.

A few calculations and some experimentation would need to be done to test this hunch. It's something I've been visualising on a molecular level for quite some time now. I mean, it could be rather wide of the mark in practice but it's clearly energetically favourable from a chemistry point of view.

Having checked the literature a bit about this, so far not much has come up.

Voltammetric determination of harmaline in natural food products using boron-doped diamond electrode :? Electrolytic oxidation, perhaps?

Dilute nitric acid isn't so OTC but it's what Perkin and Robinson reported in 1912:

Harmaline, C13H14ON2, differs from harmine, C13H12ON2, by two atoms of hydrogen, and that the two alkaloids are closely related and that harmaline is dihydroharmine is indicated by the fact that harmaline may be converted into harmine by oxidation with dilute nitric acid. The reverse change has, however, not been effected, since harmine, on reduction with sodium and alcohol, yields tetrahydroharmine, C13H110N2, a substance which is also produced from harmaline by treatment with zinc dust and hydrochloric acid (0. Fischer, Ber., 1889, 22, 637).

(But they got the structures wrong, which was commonplace in those days.)

 

[Jagube]

Thanks, this is a worthwhile quest indeed, in light of the high harmaline to harmine ratio in the most viable natural source of harmala alkaloids known to man. This topic may warrant its own thread.

Under the appropriate conditions, harmaline could disproportionate to form harmine and THH. At the very least, prolonged boiling should encourage the oxidation (in the sense of dehydrogenation by dissolved/atmospheric oxygen) of harmaline to harmine, as is thought by some to occur in caapi brews.

That's new to me, I had only ever come across the hypothesis that the opposite may be true, i.e. that prolonged boiling may convert harmine to harmaline (and that on to THH). Experiments failed to confirm it though.

My knowledge of chemistry is very limited and I feel like leaving this pioneering work (especially the theoretical part) to those with more knowledge and experience, but simple experiments like mixing aqueous harmaline acetate with ascorbic acid and waiting a week, then doing ammonia harmine/harmaline separation to check the weights of each, is something I could do.

 

[downwardsfromzero]

I had only ever come across the hypothesis that the opposite may be true, i.e. that prolonged boiling may convert harmine to harmaline (and that on to THH). Experiments failed to confirm it though.

Where did you hear this? I'm not surprised to hear that it didn't work. From my understanding of chemistry, the reaction in the direction of harmine seems more favourable. However, I do recall reading that the reaction was pH dependent, and that low pH favoured the reduction of harmaline to THH, whereas high pH favoured the oxidation of harmaline to harmine. This may have been in Shulgin & Shulgin's "TIHKaL".

Considering zinc won't reduce harmine - dissolving sodium is needed for that reaction - it seems very doubtful that harmine would be reduced merely by boiling.

From Ott's "Ayahuasca analogues", p.42:

Evidently [...] the prolonged heating, in the case of well-cooked ayahuasca, causes destruction of harmaline, although harmine and/or leptaflorine [THH] are possibly degradation products.

Your experiment sounds like a promising start although I would suggest at least keeping the solution simmering in a crockpot, and then maybe only for 24 hours. If the reaction which could be written as "2DHH -> THH + H" occurs in "well-cooked ayahuasca", it would be worth replicating the temperature of the reaction, at least.

Of course, plant brews are far more complex than boiling a purified alkaloid so it could well be that there are vital components of the reaction missing - components that would participate in the transfer of protons and electrons to or from harmaline. My other hunch here is that certain flavonoids and maybe even chlorophyll would play a role here, to name very few. (This is, of course, speculation, albeit slightly informed guesswork.)

Here's what K. Trout reports on the DHH -> H conversion:

Converting Harmaline to Harmine​

Synthetic harmine can be prepared by nitric acid oxidation of commercial harmaline using procedure of Iyer & Robinson 1934.
See also Shulgin & Shulgin 1997, p. 455.

Dr. Shulgin found that an old sample of harmaline (commercial reference material) had evidently decomposed into a 1:2 mixture of harmine and harmaline. [Ott 1994 and Shulgin 1994 (lecture; BPC seminar, Maui.)]

Published analyses of old samples of plant material have also suggested a conversion of harmaline into harmine over time.

It is also claimed by Shulgin and many others that, whether from synthetic sources or via botanical purification, it is virtually impossible to obtain harmine that is completely free of harmaline.

While it is unclear how far it is directly applicable to the alkaloids in ayahuasca, the papers of Cassady and associates [1], investigating Virola cuspidata, may be of interest. In it they described experiments in which refluxing 6-Methoxytetrahydroharman in water for 8 hours and concentrating resulted in partial conversion to 6-Methoxyharman and 6-Methoxy-harmalan.

The fully aromatic compound has greater activity than the other two and it has been proposed that the prolonged boiling observed in the snuff preparation may play a role in this regard.

Such facile interconversion between such related β-carbolines has been mentioned as a potential source of misidentification during plant analysis.

Anyhow, I look forward to hearing of your results. An easy disproportionation of harmaline to harmine and THH would be pretty useful!

 

[Jagube]

I had only ever come across the hypothesis that the opposite may be true, i.e. that prolonged boiling may convert harmine to harmaline (and that on to THH). Experiments failed to confirm it though.

Where did you hear this? I'm not surprised to hear that it didn't work.

For one, the title of the thread
Conversion of Harmine->Harmaline->THH by simple boiling (and storage?) suggests that.

From my understanding of chemistry, the reaction in the direction of harmine seems more favourable. However, I do recall reading that the reaction was pH dependent, and that low pH favoured the reduction of harmaline to THH, whereas high pH favoured the oxidation of harmaline to harmine.

Do you have an idea of what that high pH would be: is it close to neutral, or is it alkaline and does freebase harmaline oxidize to harmine more readily than its salts?

 

[Mindlusion]

Anyhow, it seems like work on a harmaline to harmine conversion would be fruitful.

My outline thoughts are that ascorbic acid (vitamin C) could act as a hydrogen transfer agent by shuttling between the reduced state and dehydroascorbic acid. Certain metal ions or catalytic metals could assist in this process.

A few calculations and some experimentation would need to be done to test this hunch. It's something I've been visualising on a molecular level for quite some time now. I mean, it could be rather wide of the mark in practice but it's clearly energetically favourable from a chemistry point of view.

Don't you mean harmaline to THH conversion?

ascorbic acid is a reducing agent, hydrogen transfer is by definition a reduction.
Unless im missing some key umplong reactivity here going on with ascorbic acid, i've used it countless times to reduce metal salt to their base metal like copper or elemental iodine to iodide.

A more powerful hydrogen transfer agent, but the same mechanistically ascorbic acid is a reagent called DDQ (strongly electron-withdrawing quinone REMOVES hydrogens from target molecule, rather than transferring them), which is typically used for this kind of dehydrogenation/aromatization. Though I believe this transformation, harmaline to harmine, should be accomplished with sulfur as an oxidizing agent, refluxing in toluene or xylene is a standard condition. That or Pd/C or palladium black.

 

[downwardsfromzero]

The thinking here was that *perhaps* dehydroascorbic acid (= oxidising form) would serve to shuttle the hydrogen away from the harmaline, and the ascorbic acid (= reducing form) obviously transferring hydrogen to the harmaline to produce THH - thereby catalysing a disproportionation of harmaline to harmine and THH. I'm not saying it'll be quick though - nor even that it would work. Like I said, it was just one of those hunches. Most of my thoughts about this are already outlined above.

Maybe ayahuasca, as it seems, has other hydrogen transfer molecules such as flavonoids so the ascorbic acid idea is too over-simplified to work. Practical experimentation has been inconclusive and as for the molecular orbital number-crunching required for a theoretical approach - that would take me rather a while from my present starting point

Don't you mean harmaline to THH conversion?

Depending on the circumstances, both are desirable. Getting the harmaline to disproportionate would be quite handy for making (harmaline-rich) rue brews a bit more caapi-like.

If dehydroascorbic acid (which is at least a dione) could act in a capacity similar to DDQ, well, I'd rather not have DDQ in my kitchen This is entirely thought of as food-grade kitchen chemistry, much like ayahuasca brewing is (largely) food-grade.


Jagube - sorry, I can't answer your pH question because I don't know, although high pH should be taken to mean something more basic than neutral. But it's pretty clear that direct reduction of harmine to harmaline is difficult.

How this all relates to changes in alkaloid content during ayahuasca brewing, and the alkaloid content of raw caapi, is a little foggy to say the least.