Harmine, harmaline and THH from Syrian Rue. Verification and finetuning of the VDS-protocols

[An1cca]

OK, padawan, it's a good thing I was wrong there . Jees' experiment convincingly showed the THH to be stable.

 

[Sabnock1990]

Yes, very interesting ShamensStamen. Found this quote from tapatalk:

Limonene is responsible for the "universal love" feel mediated by 5-HT1A activity.

p.s. above 2011 paper by Ray is backed up by 1988 paper on last paragraph of post, same findings of lack of anti-serotonin properites for dmt. MAOI's, harmmine and harmaline have been found to have zero activity in blocking serotonin.

There's still more sources for DMT having 1A agonism though than there is for it not having 1A agonism. Also, MAO-A inhibitors have been found to activate 1A receptors, as they raise Serotonin which then activates the 1A receptor which then has an anti-serotonin effect, apparently. So yes, MAO-A inhibition in itself does have 1A agonism through Serotonin increase, as 1A agonism is said to be a huge part in the therapeutic/medicinal effects of MAOI's, SSRI's, Tryptophan/5-HTP supplementation and so on.

And once again i'd like to mention that if DMT doesn't have 1A agonism, and MAO-A inhibition isn't enough for 1A agonism, then i really don't think it matters considering all i've gotten from oral DMT using Rue/Harmalas, still dissolved filters/barriers of the mind, still had ego death/dissolution, still got so much out of it that frankly if DMT doesn't have 1A agonism then it doesn't seem to matter really.

 

[GordoTEK]

Back to the THH reduction, I had success with this, using a very fine zinc powder but I must say, double coffee filter did not filter that excess zinc dust out very well. However after letting the post-filter solution sit in a cool spot overnight, all the zinc seemed to stick to the bottom glass like glue. After the decant I was left with a very clear solution. But I was wondering if anyone has had success with this process using larger zinc granules?

Examples:

https://www.ebay.com/itm/50g-weight-high-purity-zinc-particles-99-999-pure-Zn-grain-zincum-grains/372046422693

https://www.ebay.com/itm/ELEMENT-30-ZINC-PELLETS-99-99-PURE-SAMPLE-9-GM-FROM-USA/113594950886

https://www.ebay.com/itm/100-gram-3-52-oz-100g-High-Purity-99-99-Pure-Zinc-Zn-Metal-Granular/272973585158

These all CLAIM higher purity like 99.99 or even 99.999 and would not have the problem of getting past filters. But obviously the contact surface area would be greatly reduced. I would love to know if anyone has tried it this way and what the results were (did hydrogen gas bubbles form at all? how long did the process take if it completed?)

 

[blue.magic]

But I was wondering if anyone has had success with this process using larger zinc granules?

I don't have experience with ganular zinc, but I use fine zinc dust without issues (particles 2 micrometers. see image).

What does the trick for me is prepare small amount of food grade diatomaceous earth in water, then filter this with aid of vacuum using any filter - the DE will form a "bed" which traps even very fine particles. Then you wash the bed by passing just water through it, discard the milky filtrate and then filter your zinc suspension.

Another method that might work is to simply mix the diatomaceous earth into your THH/zinc mixture and filter that.

You might need vacuum to promote filtration, but there are cheap vacuum filtration sets on eBay (for filtering wine) that can be used as you need just a little but of vacuum. Water aspirators work fine, too.

You can also try higher grade lab filters that are made of membranes or glass fiber filters - there are more expensive but work way better than coffee filters.

Finally, you can use a large syringe as a ghetto pressure pump - placing filter disc onto the syringe or cut a small piece and place it inside. Maybe even cotton ball + Celite (diatomaceous earth) might do the job.

 

[An1cca]

I had success using galvanised nails (not for consumption). So I don't think the particle size is that crucial :d . Using a file on a piece of Zn-metal will give you some very reactive zinc-powder as well.

 

[GordoTEK]

I had success using galvanised nails (not for consumption). So I don't think the particle size is that crucial :d . Using a file on a piece of Zn-metal will give you some very reactive zinc-powder as well.

When you used the galvanized nails, how long did the total reduction take? Did you observe those tell tale hydrogen gas bubbles like you do with the fine zinc dust/powder? If this works I don't know why anyone would want to use the dust/fine powder, it should be much cleaner and easier to use the larger granules. To compensate for the reduced surface area, did you greatly increase the quantity of material (for example instead of 3g zinc dust, use I don't know, 30g of galvanized nails (or course granules)? I would have to do a whole new extraction to put this to the test at this point since I just reduced all of my harmaline, but it sounds pretty good to me (although I wouldn't recommend using galvanized metal from a hardware store, as they use extra lead in that process).

Another question - more of a curiosity really, in several of the descriptions written by chemists, for the precipitation step, they specifically state they used slow (dropwise) addition of ammonia. I am just curious if this is actually something that was only done because these guys are in uncharted territory and wanted to measure/record precise pH levels when various precipitations were observed, so it was done more for documentation purposes - or if doing it very slowly like this is actually required or desired for optimal results? For example if some guy sees that it took 75ml of 10% ammonia to precipitate everything (harmine & THH) and instead of doing a slow careful dropwise addition with a pH meter, he just dumped it all in at once (maybe not even using a pH meter) - would he end up with the same result (only everything just crashing out at once)?

 

[Jees]

...Another question - more of a curiosity really, in several of the descriptions written by chemists, for the precipitation step, they specifically state they used slow (dropwise) addition of ammonia. I am just curious if this is actually something that was only done because these guys are in uncharted territory and wanted to measure/record precise pH levels when various precipitations were observed, so it was done more for documentation purposes - or if doing it very slowly like this is actually required or desired for optimal results? For example if some guy sees that it took 75ml of 10% ammonia to precipitate everything (harmine & THH) and instead of doing a slow careful dropwise addition with a pH meter, he just dumped it all in at once (maybe not even using a pH meter) - would he end up with the same result (only everything just crashing out at once)?

Hi GordoTEK,
We've played with that a bit and some results were posted in

Harmine, harmaline and THH from Syrian Rue. Verification and finetuning of the VDS-protocols - Collaborative Research Project - Welcome to the DMT-Nexus

This one was mostly about separating Harmine from Harmaline and the speed of executing that titration.

 

[An1cca]

Hi Gordotek, the nails were used as a proof-of-concept experiment with perhaps 100mg of THH in a test-tube. I did observe the bubbles and the solution was completely reduced according to the blue color. I wouldn't use galvanized material for ingestible alkaloids because the zinc-layer is of unknown purity and is rather thin, so after a while other metals get into the solution as well....

When doing separations, dropwise addition is necessary because the solution takes some time to stabilize. If you only want to precipitate the only alkaloid in solution, you can just crash it out with excess base. You should use ammonia when doing this with THH.

 

[GordoTEK]

Another question - I'm trying to figure out, if you start with a harmine/harmaline mix (never doing any separation), then do the THH reduction and precipitation, again doing no separation, should a person expect something likely close to 50% harmine, 50%THH and 0% harmaline? Or is there some expectation of there still being some harmaline left and if so, what would be best guess on final percentage of each of the 3?

Compare:

2.7 Zinc-acetic acid reduction of mixed harmine-DHH freebases and pH-specific separation with ammonia
3,002g of mixed harmala-freebases from experiment 2.2 were dissolved in 100ml of acetic acid 7%. To this solution, 3g of zinc powder were added and the reaction vessel was left to stand at room temperature for 17 hours. Then, the solution was filtered and the unreacted zinc was discarded. After washing, the total volume of filtrate was 159ml (A).
To 53ml of this solution (A1), ammonia 12% solution was progressively added until the pH read 7,75 (7ml was needed). At that moment, pH-depression and clouding of the solution was observed. The suspension was filtered to give residue R1A1. To the filtrate more ammonia was added until clouding and pH-depression was again observed at pH 9,45 (6ml was needed). The suspension was once again filtered to give residue R2A1. Now, 15ml of ammonia 12% were added to the filtrate that brought the pH to 10,15. No clouding or pH-depression was observed.

vs:

2.5 Conversion of DHH freebase to THH
2002mg of DHH was dissolved in 100ml of acetic acid 7%. To this solution, 3008mg zinc powder was added. This mixture was left to stand at room temperature for several hours under regular stirring. It was observed under UV-light that the solution's fluorescent color changed from yellow-green to deep blue in the course of 3 hours. The mixture was left to react for an additional 6 hours. Then it was filtered giving residue RA1 and the recipient was washed with water that was poured over the unreacted zinc in the filter and was thereby added to the filtrate. This brought the total volume of filtrate to 200ml.
Under continuous pH-measurement, a solution of ammonia 12% was added dropwise. The starting pH was 3,88. When the pH reached 5,42 after adding 16ml of base, a very fine mist appeared in the solution that did not augment during the further addition of base. At pH 7,25 (21,5ml of ammonia added in total), the solution was filtered again to give residue RA2.
More ammonia was added and after the total addition of 33ml of ammonia 12% (pH 8,77), clouding once again appeared in the solution and the pH declined steadily to 8,62. At this point the solution was filtered again and precipitate RA3 was obtained.
The addition of ammonia was continued, but no more clouding nor pH-depression was observed up to a pH of 9,64. At that moment, 4ml of ammonia 12% were added that gave rise to clouding at a pH of 9,76. The solution was filtered again to give residue RA4

What was this RA2 from experiment 2.5? (Note, there are 4 different and unrelated "RA2" precipitates in this paper, and the results section of the paper doesn't identify which one it is referring to when it comes to the melting points and weights tables, it would be great if this could be reorganized for clarification (use different designations for the different experiments and note what experiment is being referred to in the results/discussion/tables)

Also note that in experiment 2.7 THH reduction from mixed harmalas (harmine/harmaline) he did NOT note 3 precipitations at different pH levels as in 2.5, no note of a fine mist around pH 5. It seems when he started with harmine/DHH mix (2.7), he ends up with harmine & THH, but when he starts with only DHH (2.5), he ends up with at least 2 (maybe 3) distinct outputs, this seems like a contradiction, but either way, I'm having trouble figuring out what the 3 outputs were and how much each weighed.

 

[An1cca]

Not unlike this thread, the VDS-article is indeed very lengthy. I find it difficult to read the results-section because of the need for switching to the methods-section every paragraph. It could have been better organised. Nevertheless, all the products that are referred to follow the logic that e.g. 'RA2' from results-section 3.x was synthesized in method-section 2.x .

Concerning RA2 from 3.5: In my own experiments, but also post 173 (Jees) and some posts after (Ijahdan), we all encountered the 'mist' that VDS filtered off (small fraction by the way: 4% of total precipitate). However, If you just keep on adding ammonia, it redissolves (gets complexed by the ammonia?). This is the reason why ammonia should be used and not sodium carbonate, for then the mist will not redissolve. Precipitate RA4 from 2.5 by the way seems to be the same as RA3 (same THH melting point), although it precipitated in two times.

As fot the completeness of reduction and separation: it is very important that during reduction and especially during basification, constant stirring is applied and the base is added slowly enough for pH-levels to stabilize.

 

[endlessness]

An1cca,

Thanks for all the work you've made so far and help you provided on this!

I seem to remember asking you guys to sum up a bit what was found, or the general recommendations like you just did in your last post. To be honest I can't remember the answer if there was any, so forgive me if Im repeating myself here but...

Would you mind summing up a bit what was found in your experiments, what you'd recommend regarding harmala separation and THH synthesis, and editing it into the first post? That way it wont be lost if this thread gets a few more pages..

Thanks a lot!

 

[GordoTEK]

An1cca thanks so much for those clarifications, it all makes sense now. One more thing I question about the VDS paper, in 3.1 he says he pulled out 18.953g raw alkaloids then in 3.2 he says "The final harmine- and DHH-freebases were left to dry and weighed 36.4g or 48% of the total extracted alkaloid mass" . 48% of 18.953 is 9.097, its not possible to end up with twice as much harmine/DHH as raw starting alkaloids. I didn't see this mentioned in the thread. Am I missing something?

Would you mind summing up a bit what was found in your experiments, what you'd recommend regarding harmala separation and THH synthesis, and editing it into the first post? That way it wont be lost if this thread gets a few more pages..

Endlessness, good idea. I should also point out that I've been working on documenting the harmala extraction and THH conversion procedures both in video and written forms, based largely on this thread and the VDS paper. The first part is already published, the THH reduction video is in editing right now. I'm not sure if I'm allowed to post links to videos here or not? But here is what I have so far:

Content Index:

1:50 Background on Peganum Harmala

3:00 Review of modern research on harmine

5:05 What’s wrong with rue tea?

7:50 Dr. Van Der Sypt’s paper on harmala extraction

9:10 Things you will need for the extract

12:18 How to build a magnetic stirrer

13:37 How to make a vacuum filtration system

16:36 EXTRACT BEGINS: Ground seed acid boil 6x

30:10 First basing

40:25 Salt crystallization 5x

48:02 Final basing

49:58 Ammonia wash removes salt

52:08 Storage

52:24 Dosage Guidelines

53:23 Dangerous Interactions

 

[An1cca]

Nope, I think you found an error there. The different extracts all add up to 18.95g and in the results-section he also mentions that the total mass of alkaloids is 7,6% of the mass of seeds (251,9g) which is 19g. So the 36,4g should be 9,097g I agree.

In your video (wow, nice work! :thumb_up: ), you mention 'flaws' in the VDS-paper. Are there any more like this you know of?

Since you did a good job in reviewing the paper and this thread, your video might be the conclusive document Endlessness refers to. I can't seem to find your written tek. Has it got pictures as well? This might be more in line with current Nexus-practices...

 

[GordoTEK]

The flaws from the VDS paper I noticed were:

1) Incorrect total in 3.2
2) Image 6 was misidentified as harmine (it is harmaline)
3) The initial raw alkaloid extract is very inefficient and incomplete but I realize that was not the focus of the paper, but still as far as a "TEK" goes its a flaw. (Note: I am not actually certain yet of what the most efficient way to do this is, as far as I'm concerned, this is another area that badly needs further research, which I will happily do when I get the time).
4) Again, not at all the fault of the paper, but VDS tries things many different ways, which is great, but this too makes it problematic when it comes to devising an actual TEK.
5) Too much salt used in the manske. I'm not actually 100% certain about this yet (I may have done something wrong), but I saw some criticism of this in this thread, and I and another person I've been working with both encountered problems because of this, I could not reproduce the result in the paper at all using a saturated salt solution but had success using a much lower salt concentration as described in my video. If it works with less salt, that means less salt contamination as well, so this seems like a flaw in the paper to me.
6) Failure to address the contamination issues (zinc salts and heavy metals) associated with the THH reduction and in particular how choice of base is an important consideration for safety and purity.
7) The paper says "DHH is a much stronger MAO-inhibitor than harmine [Herraiz et al., 2010]" however I thoroughly reviewed this citation and found no such conclusion (refer to Figure 3 of said paper, where DHH is depicted as only modestly stronger than harmine for MAOI).

 

[tregar]

Amazing work An1cca & Gordotek & all contributors. I have nothing to add as I just like to talk theory, but just wanted to add some info from a stuy found on-line that gives typical amounts of thh found in Vegetal Ayahuasca brews. Ron69 once mentioned that 300mg of THH is a "good amount" but not above that, I believe he was on to something. When I dreamed vegetal brews from Santo Daime (around 1.5 brews spread out over several hours) this was probably around 300mg of thh, and I concur the visions are really spectacular at that amount for several hours. Notice all the Santo Daime brews contain no harmaline probably due to extensive boiling. It was at these points that I remember having the following visions (over different sessions). There were many other visions beyond what I write below, but only have time to list a few.

Drinking Ayahuasca is like entering a University as Shanon used to say (author of Antipodes of the Mind), the teaching begins once the mysterious tea is drank, enduring the foul few oz taste of the brew is the price of admission. It's very strong...like handling a high speed sports car, just as he said. for 90 minutes it is of very strong strength, then reduces down to a strength that is easier to handle.

Example 1: was shown an overhead view of the lost city of Atlantis, zoomed in for a bird's eye view of the entire complex (it really existed).

Example 2: flew over what looked like Los Angles, as I had a bird's eye view of all the homes and swimming pools below, this went on for at least 1 to 2 minutes, absolutely breathtaking.

Example 3: was taken on a tour of a distant island's tiki's...as a young beautiful native island girl waved her hand to show me that these tikis marked the boundaries of their sacred spaces...then was shown snapshots of the amazing waterfalls on the island.

Example 4: have seen the most beautiful naked female forms (like a comic but way beyond) with dazzling detail, color, and breath taking beauty, exceeds anything an artist could ever paint. 4k has nothing on this, the visions are like infinite k or what say 100k hdtv would look like. In one of these visions, 3 of the naked female women danced and spiraled around rotating marble pillars. Caapi + psychotria is the bomb, but other natural entheogens are also capable of the exact same thing, this is not limited to Ayahuasca.

With other "single brews" that were more sedating (had decent amounts of harmaline say 20 to 30mg) with decent amounts of thh (around 175mg +) the same type of visions would manifest as above. I think there is some kind of multiplying effect when all 3 alkaloids are present, and that when dreamy harmaline is not present, the thh is able to manifest the same type of visions at higher doses as would be a combo of harmaline + thh. This is just my subjective dream experience. These single mixed brews would give around 45 minutes of strong closed eye visions: a ship on the ocean, perfect natural gardens, beautiful women from the renaissance period, a detached alluring woman's face with freckles, typical things of the many I remember seeing.

From study attachment:
2005: Brew from study is 100ml or 3.3oz, simply multiply each figure x 100 to get the mg amount, examples:

entry #1 from UDV is 183mg tetrahydroharmine, 9mg harmaline, 172mg harmine.
entry #22 from Santo Daime is 168mg tetrahydroharmine, 0mg harmaline, 198mg harmine.
entry #29 from Shuar Indian is 163mg tetrahydroharmine, 0mg harmaline, 180mg harmine.

 

[GordoTEK]

Tregar, I remember looking at that paper a while back, but ignored it because the results were only shown as mg/ml and did not seem to align with other published numbers. For example the high value the found for DMT was 14.15 mg/ml, so the stated minimum dose would contain 708 mg of DMT! Yikes, I would not want to be in that ceremony! Haha. For THH the high mark was 12.79 mg/ml, or minimum dose of 640mg of THH! For harmine it was 6.25, or 625mg from the mentioned mimimum dosage.

You will find much more reasonable measurements in:

Phytomedicine. 1998 Apr;5(2):87-96. doi: 10.1016/S0944-7113(98)80003-2.
Effects of Ayahuasca on the human EEG.
Don NS1, McDonough BE, Moura G, Warren CA, Kawanishi K, Tomita H, Tachibana Y, Böhlke M, Farnsworth NR.

(See the attached PDF)

 

[Elrik]

Guys, it really helps to actually read the paper! In that 2005 study those doses were not all 100 ml, it specifically says that the UDV brews were dosed from 100-200 ml, the shuar brews were dosed at 20-30 ml, and the santo daime brews were dosed at 50-100 ml. They didnt report the paste dosage, just that it was so nasty that no one managed to overdose. You can not assume that all ayahuasca doses are 100 ml!
After reading that paper I tried several higher dose trials to match some of those values, for instance in one trip I used 500 mg THH•HCl, 475 mg harmine•HCl, 300 mg DMT base, 25 mg harmaline•HCl [keep in mind that the paper was reporting as freebase weights, for the harmalas multiply hydrochloride dose by 0,75 to obtain the freebase dose or multiply freebase by 1,33 to get hydrochloride]. My only complaint was that on such a high THH dose I have to stay lying down in the dark extra long after the peak or I get this psychedelic vertigo where the edges of my vision become very disorienting shimmering waves. I can tolerate 350 mg THH•HCl much better, which equates to 263 mg THH base, or a 20 ml shuar brew containing 13 mg THH per ml, which was close to average for the shuar brews.
I mentioned the odd effect half of a gram of THH•HCl has on me, too much harmaline is overly sedating and can make the trip depressing, too much DMT can just make me feel like a balloon filled with rainbows about to pop from being sat on, while I've used half gram doses of pure harmine•HCl in various scenarios never to any ill effect.
Doses can go quite a bit higher than the usual pharma values if harmaline is kept to reasonable values, but don't misread a single paper and take things in 2 gram doses! :lol:

tregar, I really envy your trips

 

[GordoTEK]

Elrik, what is your source for and logic behind "keep in mind that the paper was reporting as freebase weights for the harmalas multiply hydrochloride dose by 0,75 to obtain the freebase dose or multiply freebase by 1,33 to get hydrochloride"?

Regarding the Callaway paper, when I originally read it, I felt like he didn't quite finish the work, meaning a mg/ml value is not helpful as anyone can simply boil their brew down more and have a more concentrated result, so measuring actual dosage amounts is required, and while you are right that he did provide "loose guidance" for 3 out of the 4 religious groups (one is completely unknown but looks similar to his "Santo Daime" numbers), even that is not really sufficient - you need dosing for each and every individual brew, it is also quite apparent that these did not come from a single shaman from each group, but from multiple locations and multiple brewers. I still think this paper was poorly done, but I appreciate having something vs. nothing. Here is my attempt at improving the table plus adding averages, I can attach the excel if anyone wants to play around with it (but keep in mind, these numbers are still unreliable for the reasons I've mentioned, and these values are around 2-3 times higher than what other researchers have reported. I'm thinking one explanation could be that his samples dried out somewhat either in storage or in transit before he even got his hands on them):

 

[endlessness]

I agree with GordoTek that without the average dose for each individual brew it is hard to estimate what people would be ingesting. I know often they give different doses to different people, and it depends what kind of ceremony it is, if there is any specific purpose, if its for an inner circle of experienced people or for general ceremonies eetc. That being said they should still have asked about each brew's average dosage imo even if it varies.

Gordo, maybe try doing median value too, not just mean, it might help eliminate the outliers... Or remove top and bottom results. Because i think the values ended up a bit schewed. Say for example these daime samples with super high dmt, that isnt imo representative of average daime brews at all,they are generally much more mild. Id imagine those are concentrates ( " mel " ) given in small amounts, not the normal diluted daime dose.

Also, as posted before, just to help with further info, here are some other values for aya alkaloid content from different sources... These are all more typical 50-100ml dosage brews, if you want to add to the calculation

 

[GordoTEK]

OK I added the median (above). I still think the numbers are highly suspect even for the median.

Other sources:
Phytomedicine. 1998 Apr;5(2):87-96. doi: 10.1016/S0944-7113(9Cool80003-2.
Effects of Ayahuasca on the human EEG.
Don NS1, McDonough BE, Moura G, Warren CA, Kawanishi K, Tomita H, Tachibana Y, Böhlke M, Farnsworth NR.

Endlessness' data: