Well said Jees, I could not agree more. I too feel that this current research will enable us and fellow-psychonauts to clear up the fog and myths around THH.

Ah OK thanks.
That's probably the reason I'm so puzzled about these different substances.

Up til now I only made rue tea so far, which had quite a strange temporal progress (only rue, no DMT). First sets in a quite strong sedating effect. Then after 2-3hours this effects gets a bit less, but a more psychedelic effect sets in. It enhances my "natural patterns" I see in the dark and has more of this pressing high speed character, similar like DMT has, combined with a tinnitus sound.

Could that be because the different alkaloids have their effects at different times during the rush?

Hmm, now I'm curious...Maybe I also once try to separate the ingredients to see their effects alone.

Edit:
Just read in another thread from 69ron that Harmalol could also be a significant player relating to effects.
(https://www.dmt-nexus.me/forum/default.aspx?g=posts&t=8789)

Yes first goes the harmine out while the harmaline keeps going longer.
From here:


I hope to have you on board for some separation fun.

Yep. I think I'm onboard. Already ordered some chems needed for extraction.

But honestly if I read through all this here I'm still a bit puzzled about which tek I now should use. The GC/MS results aren't yet there, am I right?

Also I'm quite interested in the Harmalol effects. E.g. in some paper linked somewhere, it is stated that Harmalol has a very strong MAOI effect (stronger than Harmin or Harmaline).

OTOH Harmalol seems very delicate, as exposition to air seems to kill it.

That's why I currently do my usual rue teas with Vitamin C, in the hope that helps.

I think I will first try the Harmin THH stuff and save the after Manske stuff, as this should contain the Harmalol. Although I have no idea how to extract it from there in a safe way (no exposition to oxygen).

Now we're looking at inert atmospheres, which is a bit more complicated than kitchen level but at the same time not that difficult. Looking at the literature where harmol/harmalol has been isolated should give some idea of the degree of fastidiousness required wrt oxygen exclusion.

Thinking about it, the harmol/harmalol oxygen atom is phenolic thus making the associated hydrogen atom more acidic. This may complicate isolation of such alkaloids somewhat I would think, especially in the case of tetrahydroharmol.

This harmalol idea is cool but where are the seeds that have them sufficiently? Then the unorthodox isolation of harmalol compared to harmine and DHH, it all looks a bit far fetched for me.

Aum_Shanti if you base your manske liquid, all you get is a white slime not able to filter out. It's the quinazolines and supposed harmalol and whatnot but I think it's a real pain to work with that. It would be a different way of working with an unfamiliar branch in the harmalas family, one that deserves an own place/thread if that could ever take off. A daring project I believe. And once more the identification will be very mandatory.

.

The VDS paper has a multitude of angles, then this thread has a bulk of trials with the Zn-salts to get to know it's behavior, it all adds to a bulk. For results, a lot of this thread can/must be put aside but it was all part of the getting-to-know.

Of all the many things the separation narrowed down for me like this:

1 - Make your starting extract very pure (A/B's until the base liquid is clear then followed by many manskes until the manske liquid is 'clear'.) Other methods are fine as long as the result is clean. Dry.
2 - Weight extract to determine a concentration of 15 to 20 mg/ml. Dissolve extract in minimal vinegar (+ some heat helps) and dilute until you come to the desired concentration.
3 - base with ammonia till past the first pH depression (start point + 0.5 pH), collect your harmine, wash, dry
4 - base liquid further till 9 or 10 and collect the harmaline, wash, dry.

A possible step between 1 and 2: dissolve extract in minimal vinegar and boil in activated charcoal. Filter, wash, dry.

Hello guys,

Glad to see you all doing good work here, I noticed earlier someone mentioned the possibility of ascorbic acid acting as a reductant to reduce harmaline to THH. I have wondered about this too, since it has been noted (also debated) long boiling of b. caapi can increase THH content, assuming the natural vitamin C content of caapi, acting as the reductant (or other antioxidants perhaps).
https://www.dmt-nexus.me...aspx?g=posts&t=31699


It have been a discussion on the forum for quite some time now,
It was also attempted but without real evidence to confirm if it was working or not.

https://www.dmt-nexus.me...aspx?g=posts&t=16707



I thought I'd put this to the test once and for all, its simple enough.


50mg of purified freebase harmalas (harmaline enriched) is added to a near boiling solution containing an excess of pharmaceutical grade ascorbic acid (2-3g total).

[photo1]

The dissolved orange solution was kept at boiling for 1.5hr , adding a small scoop of ascorbic acid every 15-20minutes.

[photo2]

An aliquot was removed by pipette and added to solution of 10% NaOH, and shaken with EtOAc.

[photo3]

This solution was tested side by side with the harmala starting material by TLC.


MeOH:EtOAc:10%aqNH3 | 40:10:1

Left side is starting material, right side is post- ascorbic acid reduction

[Photo4]

As you can see, there was no visible change from the lower spot, camera doesn't pick it up that well, but by eye it was quite obvious there was not even a hint of THH.

For reference, compare it to the successful reduction seen here:

https://www.dmt-nexus.me...aspx?g=posts&t=72092

Most interesting, thank you.

@Mindlusion:
Interesting indeed. Although I didn't mean to use the Vit C for this,but rather as a protection for the Harmalol.

BTW: Did anyone on the Nexus yet tried the conversion of Harmaline to Harmine?
If I remember correctly Shulgin did this with Aqua regia.

@Jees: What do you think is the minimal amount of rue to start with, for a practical extraction, to go the Harmine+THH way?
First I would rather like to test a bit the tek.
Is it really that important for the THH conversion to have the product very pure?
What happens if one does it, with not such a pure product?

Edit:
Hmm, about the Harmaline -> Harmin conversion.

Manske said (The Alkaloids: Chemistry and Physiology, Vol 8, p50):

and


Anybody an idea, what would be the simplest way for that? Is H2O2 too aggressive for that?
Sorry, if this is too offtopic, please tell, then I will start a new thread about this conversion.

I just have the feeling, that if one would want to copy the Caapi, then the conversion DHH -> THH would yield a mix with Harmine with too much THH. But one would have to test if this isn't beneficial.
But if OTOH one could easily convert the DHH to Harmine, one could make two batches, convert one to THH, the other to Harmine and mix them again...

Hmm, probably I'm overthinking this...

Edit2:
Just read on the forum, that some people think boiling it or heating it generally oxidizes the Harmaline to Harmin. If this is the case, then one should probably not boil for extraction if a THH conversion should be done.

Edit3:
Here I just read the opposite:
https://www.dmt-nexus.me/forum/default.aspx?g=posts&t=31699
So I give up making any sense of this...LOL

Edit4:
Hmm, now I think I understood it. Boiling in acid reduced them, boiling/heating in non-acid oxidizes them.
What I think is also interesting is, that according to Manske Sodium immediately reduces Harmine and Harmaline to THH.
Hmm...wouldn't that mean that this should also work with an electrolysis of NaCl Water?

Many new aspects, all interesting, thanks.

There's coming more suggestions how to form THH which is all glory in itself (if it works ) and their mentioning here is very valuable. Yet the eventual deeper deployment of such alternatives might be best served with a specific dedicated thread to empower it. I'm all won for cross referencing between the THH covering threads

Personally I've never been interested in oxidizing because the harmine comes so easy on itself I feel no need to offer DHH for it, I'd rather do THH with it.

Aum_S how much rue to start: I think if you can process 100 gr rue seeds then I'd favor that. Super clean should give 4% or 4 grams mixed extract. One could end with 50% harmine 50% DHH for Iranian commercial seeds, and if you convert the 2 gr of DHH to THH at a 80% yield (my best yet) then you would have 2 gr harmine and 1.6 gr THH.

For making the separation a la VDS and favoring 15mg/ml on 4 gr is 266 ml. VDS would do it in 24mg/ml so in 166 ml. We discussed concentrations before. You can play between 166 and 266 ml no problem. Do you have the tools for that volumes, I guess they're quite ideal volumes to work with in a kitchen. You need a pH meter, strips aren't sensitive enough. A 0.00 display resolution is good to have.

But coming back at your question about harmine - THH ratios, if you put your harmine + THH together, this ratio is immediately the right ratio for caapi copy. How convenient is that

Btw that Manske sodium trick sounds exotic! Any tips welcome.

Still digesting Mindlusions post...

Thanks.

Didn't know that PH measurements had to be that accurate. For that I would need a new PH meter. I have such an el cheapo not really accurate thing...

Will probably first just do the conversion to THH, and then test the Harmine+THH in vivo. To see the difference to Harmine and Harmaline alone.


Manske just says to use sodium in ethanol (has to be pure!!!) to reduce Harmine and DHH into THH. (Na is here, where I live available for $40 per 100g, but getting anhydrous EtOH is another thing...)
I guess it's just the development of atomic hydrogen which does the trick. If this is the case, then IMHO other methods should also work. (but I'm certainly not a chemist, so please don't stone me!)

But first things first, and I would probably then open up a new thread for this, as also for the Harmaline->Harmin conversion.

There's basically one potential advantage I would see in a DHH->Harmine and Harmine,DHH -> THH conversion. You would end up with pure Harmine and pure THH without the need of any separation steps.

Aum_Shanti, Jees, pH-meters don't need to be that accurate if you're willing to sacrifice a small amount of alkaloids to a 'mixed fraction'. Let me explain: first you'll notice a drop in pH at a pH not much above 7. If you follow VDS's experimental technique in paragraph 2.3, the depression would start at around 7,2. Actually, it doesn't matter at all at what pH the depression starts, the fact that it depresses is the main focus. Then, after having added a certain amount of base (you can get an order of magnitude from the protocol in VDS's article), you will see the pH rising again. Starting from lets's say 6,3 to around 7,0. At this point, most of the harmine has precipitated. Between 6,5 and 7,5 only 10% of the harmine needs further basification. And between 7,0 end 7,5, this amount gets completely negligable. This can be clearly observed on graph 3.3.3.

So this means that even if your pH-meter is accurate to only 0,5pH, you'll be able to selectively precipitate between 90 and 99% of your harmine (that could have been precipitated considering inevitable loss of about 5% through the reprecipitation-process) if you stop basifying at pH 7,0 (confidence interval 6,5-7,5). So first precipitation will start, and most likely yor meter will first have turned to 7,0ph before showing 6,5. If not, no problem, just continue basifiying slowly under constant stirring and from the moment the meter reads 7,0, stop the addition of base. Wait until the pH reads 6,5 again under occasional stirring. As long as the pH returns to 6,5, keep adding base in small increments until the pH stabilizes for more than an hour at 7,0. Filter of harmine, add more base to bring the pH to 9 or 10 and filter off your DHH. Optionally, you can isolate a mixed fraction by slowly adding base to solution stabilized at pH 7 until a definite amount of precipitation starts and a depression of 0,5pH or more is seen.

If your meter is accurate to 0,1pH, the amount of 'mixed fraction' that is not separated and mainly consists of DHH, can be kept to 2% (page 19 of article). In fact, the separation becomes so complete, that one can skip the isolation of this mixed fraction completely. Then one just stops at about 7,5 (or as Jees suggested: 0,5pH higher than the starting pH of the depression), filters of the harmine fraction and base further to precipitate the DHH. For all practical reasons, this is the way to go. However, if you don't want any trace amount of harmine in your DHH, go and isolate the mixed fraction (between pH 7,5 and the first sign of precipitation + pH-depression). This won't take more than an extra 10 minutes.

When reading the article, I thought about using 'accurate' pH-strips (0,2pH). Well, I ordered some but found out that the color of the alkaloid-solution strongly influenced and deteriorated the reading of the pH-value. I also tried to dissolve some relevant pH-indicator (nitrazine and thymol blue) into the solution. Only to find out that the indicator was caught in the precipitating alkaloids. Now that I think about it, it might just work if you only add the indicator near the expected end-point. Then there's practically no more alakaloid to 'wash out' the indicator during the accompanying strong pH rise. Hmm, interesting...

BTW, Aum-Shanti, this pH-specific separation-process is very fast. I did my third in about half an hour. And it should be effective as well, given the peculiar pH-curve, the microscopical characteristics and VDS's narrow melting points. We'll get definite evidence on the effectiveness of this technique when the results of the LC/MS come in.

So, all this just to let you know that even a cheap pH-meter with a minimal accuracy of 0,5pH is sufficient for effective and efficient separation of harmine + DHH. A meter accurate to 0,1pH provides more control over the process and even further increases yield by minimising the mixed fraction. Good luck!

Typically sodium reductions are more about the readily available electrons from the sodium. Nobody believes in "nascent hydrogen" any more.

"Mechanistic understanding of such reactions is now available, and the concept of nascent hydrogen is discounted, even ridiculed."

"[...] studies have shown that this reaction proceeds via electron-transfer from metallic sodium to the ester substrate followed by protonation of the reduced intermediate. The evolution of hydrogen by the reaction of sodium and alcohol is purely a competitive reaction, the sole benefit being that in the presence of sufficient alkoxide, the sodium/alcohol reaction slows."

This suggests it would be advantageous to allow the sodium to react in the ethanol for a while before adding harmine/DHH.

Mindlusion, great that you tried the vitamin C reduction although I would suggest using non-metallic vessels as iron interferes with the action of vit C, IIRC. Taking this a step further would imply exclusion of atmospheric oxygen also. So, a glass reaction flask would be worth a try. I would do this except I've no extracted harmala alkaloids to play with right now!

Edit: would you rather I posted most of this in the harmala-sodium/EtOH reduction thread?

Yes exactly, this is why amalgamated sodium metal is used, to slow the reaction between Na and EtOH. It also uses less sodium, and gives more surface area for the electron transfer to occur.
But of course, it contaminates with mercury. IRCC, Manske got a better yield with amalgamated sodium than he did with pure metal. But working with these materials are undesired for our purposes. I didn't get any conversion using pure sodium metal in EtOH, but like I said, it wasn't optimized. Just a throw and go, to see what happens.




Yeah heh, I tried to be home friendly and use the kitchen pot. Could be though. Could try a reflux under argon.. but with the excess that I used, and not seeing even a hint of conversion, im not optimistic.

Yes I think it would be a good idea to take this conversation to the Na/EtOH reduction thread.

BTW, it could be possible to reduce harmine, not just harmaline, with NaBH4 as well, if a large excess is used. But that's only based on heard it from a friend of a friend who tried it. Intuitively I doubted that NaBH4 could reduce the fully aromatic molecule, but boron always behaves strangely, beta-carbolines too.

---

Regarding oxidation, I think ill make a thread on this too. It can be done easily by reflux in a high bp non-polar solvent, like xylene, some air (O2) with a bit of a metal catalyst like Pd/C. But i'm investigating a few different home friendly metal-free methods, potentially with H2O2, sulfur, or just plain activated carbon. Ill keep you posted.

You're right and I did not say 'necessary' but 'good to have' because it shows better.

I've had a pH meter with tiny button cells as batteries, and felt that it needed a time after startup to settle it's reading, it had the tendency to drift after startup. I believe that the little batteries had to find their selves a stable voltage under load, hence the time needed.
My recent meter has a 9V block battery, and reading is very quick and stable immediately because, I think, this battery has a much more stable voltage after startup.
If I'm right, for this I'd recommend meters with cells like 9V or AA or AAA.

And the question why the purity: I've found impurities to sabotage the pH depression phenomena. Where this effect exactly begins I've not tested, but clean products LoVe to make pH depressions

a bit ot, but anyway, i just noticed that the p. harmala related publications are immense in number, referring to alkaloids and whatnot compounds i never heard of. so for the hardcore researchers in this thread, perhaps they could find papers of interest at the following addr
http://booksc.org/s/?q=peganum+harmala&t=0

there's a lot in those seeds, thank you.
I suppose the manske treatment is a firm diet in the seeds ingredients.

@exquisitus:

Wow, thanks for that link. That's a lot of info...
IMHO interesting that in one paper a chemists states that Harmala red is a weak acid, which forms salts with bases. And that it forms in Ethanol if you add Ammonia.

Also interesting the Ionopheresis tek for separation of alkaloids.

But I'm getting too offtopic sorry. Again thanks for the link!

Finally got round to reducing the harmaline which I had separated before xmas using sodium carb/sodium bicarb.

I started with 1.3 grams of fairly pure, cream coloured harmaline. Dissolved in vinegar, added a few grams of zinc powder and left to react for 24 hours before filtering.

I then carefully added ammonia solution drop by drop while stirring continuously.

At some point (no pH meter so dont know exactly) a precipitate (presumably zinc salts) started forming. A few more drops of ammonia and the solution became clear again as expected (zinc salts redissolving).

Still more ammonia was added until a second precipitation began. Some of this was a fine tan coloured powder, but a darker brown goo also formed and stuck to the spoon I was using to stir. This had during previous attempts too.

I filtered this precipitate and dried it. Lots more ammonia was added to the solution but no more precipitation occurred.

So I now had a very fine powder and some dried brown goo which was easily crushed down to powder too. Problem was that the total weight was now only 250mg, so a huge loss.

I bioassayed some (about 50mg) by smoking it sandwiched between non psychoactive herbs, with no additives, and no real effect to speak of. Tried sublingually and again nothing much. Tasted bitter like harmaline. The harmine from the same separated batch of alks, on the other hand is very potent when ingested in a similar way, as was the harmaline before reduction.

Well, Ive got no more harmaline now till I boil some more seeds up. Any ideas what went wrong?