Lysergamides LSI, Ancient LSD, Secret of the Eleusis Kykeon and Vedic SOMA

[donotdothis]

Yes Machine_Elf23, as matter of fact Red22 has done extensive research on how the Greeks could have used wood ash to eliminate the toxic alkaloids in purpurea but be left with non-toxic LSA (then convert to LSI brew). Other than that, there is the non-toxic claviceps paspali which infects barley grass and paspalum grass.

If you look into teotlaqualli, it was very similar.

 

[Allylbenzene]

So what would it [aldehyde] react with? The amide group.
...
Why does it work anyways in that one publication tregar and Allylbenzene like to cite? (https://pubs.acs.org/doi/10.1021/ja01335a085) Because it really only works if you push things enough, by using anhydrous conditions, heat and long reaction times which limits the scope in such a way to (in my opinion)

Allow me to expand the scope on aldehyde–amide rxns, at least some additional literature context, perhaps someone with the appropriate equipment & skillset will investigate the LSA scenario. Originally posted on thevespiary:

Spoiler: amide/aldehyde condensations

The condensation of aldehydes with amides: Part I. The condensation of salicylaldehyde
Proc. Indian Acad. Sci. (Math. Sci.) 7, 361–368 (1938).
doi: 10.1007/BF03045403

The condensations of aldehydes with acid amides have been studied by a very large number of workers and the literature is extensive. Often the condensation is brought about by merely heating the aldehyde with the amide alone, in other cases condensing agents of several kinds have been used, such as, hydrogen chloride, potassium hydroxide, potassium carbonate, diethylamine, triethylamine, sulphuric acid dilute, anhydrous sodium acetate with, or without, acetic anhydride. Frequently, the condensation has been carried out without a solvent.

The condensation of aldehydes with amides: Part II. The condensation of cinnamaldehyde
Proc. Indian Acad. Sci. (Math. Sci.) 7, 376–380 (1938).
doi: 10.1007/BF03045405

As lar as we are aware, there has been only one such condensation reported, and that is by Gupta, of cinnamaldehyde with phenylacetamide, brought about without any condensing or catalytic agent, by merely heating the two together, and resulting in the production of cinnamylidene-bisphenylacetamide. In the present paper, the condensations of this aldehyde are studied with four amides, namely, phenylacetamide, acetamide, propionamide and benzamide, under several different conditions of temperature, molecular proportions and catalytic influences. The condensations in all cases take place and produce the cinnamylidene-bisamides. The yields are fair and at times good, but are not generally as good as were noted with salicylaldehyde in Part 1.

The condensation of aldehydes with amides. Part V. Of p-hydroxybenzaldehyde
Proc. Indian Acad. Sci. (Math. Sci.) 10, 282 (1939).
doi: 10.1007/BF03170451

p-hydroxybenzaldehyde condenses readily with formamide, acetamide, propionamide, benzamide and phenylacetamide, and the products are the corresponding p-hydroxybenzylidene-amides, as in the cases of the o- and m-hydroxybenzaldehydes. The condensations are brought about by heating the aldehyde with the amide for 4-5 hours at 130C, in the presence of absence of a trace of organic bases like pyridine and piperidine. The presence of the base improved the yield only slightly (contrast salicylaldehyde) and compare m-hydroxybenzaldehyde). The yields, however, were uniformly very good, never being less than 60% of the theoretical, and reaching up to 92% as the highest...

The condensation of aldehydes with amides: Part VII. The condensation of piperonal
Proc. Indian Acad. Sci. (Math. Sci.) 14, 18–24 (1941).
doi: 10.1007/BF03049118

Piperonal condenses best when heated without any other condensing reagent, with seven of the common amides, giving characteristic piperonyl bisamides. It does not condense with formamide

Condensation of aldehydes with amides: Part XII. Condensation of benzaldehyde and o-chlorobenzaldehyde
Proc. Indian Acad. Sci. (Math. Sci.) 24, 487 (1946).
doi: 10.1007/BF03176919

The condensation of benzaldehyde and o-chlorobenzaldehyde with several amides has been studied, in the presence as well as in the absence of pyridine. The base slightly increased the yield in many cases. The rise of temperature as well as the prolongation of heating raised the yield more effectively. All the products were the corresponding bisamides. The presence of chlorine on the aromatic ring of the aldehyde, had the expected tendency to increase the yield, particularly in the condensations with benzamide, propionamide and n-heptamide. Condensations with formamide, as has been the general experience, did not give good yields; in all other cases, the yields were good, starting from 30% and reaching up to 86% in some cases.

Condensation of aldehydes with amides: Part XIV. Condensation of n-heptaldehyde
Proc. Indian Acad. Sci. 27, 196 (1948).
doi: 10.1007/BF03174832

In the papers so far published in this series, the condensation and the conditions of condensation of eighteen aldehydes with more or less common amides have been studied. Almost all the aldehydes have been aromatic: cinnamaldehyde and dihydrocinnamaldehyde being the only exceptions, in the sense that, though each contains a benzene ring, the aldehyde group is not situated on the ring but is on the side chain...

Condensation of aldehydes with amides: Part XVII. Of 5-chloro- and 3,5-dichlorosalicylaldehydes
Proc. Indian Acad. Sci. (Math. Sci.) 29, 56 (1949).
doi: 10.1007/BF03172438

Usually the highest yields were obtained at 100–110° and in the absence of any condensing agent.

This is a reaction that is not really taught in the standard ochem curriculum because for the most part it is not really relevant. Why? Because the nitrogen electron lone pair in amides is conjugated with the amide carbonyl and thus not available for nucleophilic attack on the aldehyde or ketone carbonyl, making this reaction extremely unlikely.

Clearly someone at the Indian National Science Academy(?) was set on exploring the amide/aldehyde condensation back in the 1930s & 1940s.

Proceedings of the Indian National Science Academy is a peer-reviewed journal, publishing original research and reviews across various scientific disciplines. The journal has a rich history, dating back to its inception in 1935.

 

[Allylbenzene]

Let's not forget the very real possibility of in-vivo rxn/adduct formation; after all, excluding a possible scenario before it's been (dis)proven isn't reasonable.

And besides even if you were able to form these N-acyl hemiaminals (like LSH is one), I'd be surprised of them being pharmacologically relevant as anything but a prodrug as they'd very rapidly degrade in the aqueous soup that is your body.

I think downwardsfromzero (dmt-nexus) outlined it quite well:

This was one of the more visual attempts with natural lysergamide-containing seeds. The experience followed a night involving the consumption of a significant amount of brandy, thus there was an incontestable residue of acetaldehyde in my body.

The seeds themselves, being HBWR, were much more likely to have contained LSA as the principal alkaloid; they will not have been particularly fresh. Although the inference counts as purely anecdotal, I feel it supports at least one of these ideas:

• ...that the 1-acetaldehyde adduct of LSA (or, possibly from what we've learned so far, iso-LSA) is likely to be more of a visionary entheogen than plain LSA itself.
• ...that post-alcoholic acidity in the body promotes the formation of the more visionary iso-LSA from the LSA equilibrium mixture in vivo.
• ...that under physiological conditions, acetaldehyde inhibits the breakdown of LSH such that - in the aforementioned instance - sufficient LSH reached the appropriate receptor sites to produce a mild but significant entheogenic experience.
• ...and/or...:
• ...that, under physiological conditions, acetaldehyde reacts with LSA at the amide nitrogen to (re-)form LSH.

While I consider the last option the least likely, and in the past I have argued against the possibility of it happening, it's still not something I would discount entirely. Still, I wouldn't bank on it and would advise all readers that acetaldehyde conversion of seed extracts containing lysergamide are best carried out in vitro as ethanol and acetaldehyde present health hazards when ingested!

The acetaldehyde adduct would be C2H5O, as CH3COH attached at the indolic nitrogen - another 1-hydroxyethyl group, just like in LSH. From what you describe, this seems like an argument for soaking one's N¹-unsubstituted lysergamides in cold peppermint sherry for a while before consumption. Would this also include tryptamines such as DMT-containing potions for oral consumption, one might wonder? And what about psiloc(yb)in?

As I've mentioned, my most successful plant-derived lysergamide experience - in dreams, of course - albeit with HBWR, coincided with intake of a fairly large quantity of brandy which, in all likelihood, produced a significant level of acetaldehyde within my body, exposing the plant lysergamides to the correct conditions (as reported in the Austin & Fraenkel-Conrat PNAS paper) within my stomach for the putative 1-(1-hydroxyethyl) or, rather, it seems, the 1-(1-ethoxyethyl) derivative to be formed. In this case, the effects were clearly stimulating, unlike the sedative effects usually reported for HBWR. I see that brandy weighs in fairly well on the acetaldehyde content scale as well, btw (post #17)

Looking at the PNAS paper, and the molecular structure "indole after p8441", what we appear to get is a 1-(1-ethoxyethyl)indole, with an ethyl group on the oxygen atom. This would be more lipophilic than the 1-(1-hydroxyethyl) derivative, as would, incidentally, the cinnamaldehyde adduct proposed by 69ron. It is only with the combination of both ethanol and acetaldehyde (EDIT: rather. an alcohol and an aldehyde; see below) that we get a stable product. It would seem likely that under mildly acidic conditions ethanol and cinnamaldehyde (or, we might also surmise, any other sufficiently stable, sterically unhindered aldehyde) would also form a stable adduct.

...
And isovaleraldehyde would lead to the production of a 1-(1-ethoxy-3-methyl-1-butyl)indole derivative under this scheme. That'll have to do for now as I need to sleep. [EDIT: also of interest, we see the following: "Reaction mixtures were also prepared using 1-, 3-, and 4-carbon-chain aldehydes and alcohols. After 24 hr of reaction ... these alternative mixtures were analyzed on the same HPLC system. Reaction products (data not shown) were detected in all cases, except when the aldehyde was formaldehyde, and product retention time increased along with the length of the reagents' carbon chains. The yields decreased with increasing alcohol and aldehyde chain length (methanol/acetaldehyde - butanol/butyraldehyde)."]

 

[Allylbenzene]

In any case, just tossing some questionable aldehyde source with some acid and stirring in non-anhydrous conditions will lead to zero conversion ... besides even if you were able to form these N-acyl hemiaminals (like LSH is one), I'd be surprised of them being pharmacologically relevant...

Here user flickedbic describes various adducts. I used to participate on the same forum as flickedbic, his contributions were always well reasoned and mature.

Flickedbic writes:

• Cinnamaldehyde makes a speedy adduct that carries much more visual strength (and side effects- keep a handy bronchodilator like Cannabis). This one should be dosed lower.
• Acetaldehyde to (re)form LSH adduct (fresh peppermint, cwe coffee, sherry that smells like apples) is a more traditional trip, not as visual with open eye but blissful and more giggly/trippy than the speedy but visual Cinnamaldehyde adduct.
• Perhaps my favorite; cuminaldehyde. I make a cumin tincture then shake it with the filtered acidified LSA CWE over ice, and then strain. A much more serene and zen, meditative trip: very peaceful but also very enjoyable.
...
I've probably done adduct formation from LSA a dozen times using various aldehydes.
...
Very cold, strong agitation of the aldehyde in the CWE is needed to form the adduct.

Here he describes things in more detail:

I have done experiments with adduct formation and talked with many others who have also. There are definite distinct timelines, effects, and side-effects for the various adducts.

My understanding of this reaction in a nutshell:
— "LSA" + the aldehyde + low PH (4) + cold agitation = an adduct with modified effect.

Alcohol may facilitate the reaction.
...
Detailed adduct differentiation:

Acetaldehyde adduct: Great euphoria, classical psychedelic mentally. Offers light visual effects such as haloes, tracers, increased brightness and color saturation.
— The Acetaldehyde adduct gives me vasoconstriction, but no bronchial constriction.

---

Cinnamaldehyde adduct: Short duration, high energy, occasional OEV's: a rapidly expanding white "bubble-ring" (like the kind dolphins make and play with) shoots out from a Persian rug towards me.
— The Cinnamaldehyde adduct gave me bronchial constriction, so keep a bronchodilator like THC handy.

This is the only adduct that has given me actual OEV; and with half my usual dose at that! While it is the most stimulating adduct I've tried, it's the least uplifting.
More on the Cinnamaldehyde adduct: https://www.shroomery.org/forums/showflat.php/Number/22081081#22081081

---

Cuminaldehyde adduct: Good mood; centered. Fair energy. Long duration. Presents visual effects from soft "breathing" to "rubber objects" (or seeing things how a video camera does after the lens is splash and water goes into streams across the lens).
— Thinking is unclouded, not on overdrive, but zen. Feels almost holy. While the cuminaldehyde adduct may be slightly less euphoric than the acetaldehyde one, it is still very nice!

Here's my post on Cuminaldehyde written during and after trying it, "hbwr cumin mix kicks ass"*: https://www.shroomery.org/forums/showflat.php/Number/21168265#21168265

The user Lysurgeon (from dmt-nexus) reports that the vanillin and benzaldehyde adducts aren't recommended (unpleasant). Lysurgeon also explored other aldehydes including cinnamaldehyde, he was one of the early pioneers of this mysterious "rxn".

Lysurgeon writes (Kash also comments in this thread):

I'm extremely excited about this, especially after receiving the rave reviews of this combo. I did have an experience involving being accidentally fingertip dosed during the preparation of heavenly blue cwe/sassafras root tincture (contains 2 different substituted cinnamaldehydes, 3-meo-4-oh and 3,4-MD). It was definitely not a "placebo". Blindsided by the realization that I'm tripping, but...I didn't eat anything. Indicates intense potency potential given just the right conditions and plant matter.
— https://forum.dmt-nexus.me/threads/lysergic-research.311082/post-3379729

Flickedbic writes (same thread):

Shook only the 400 HBMG CWE, ocassionally; for 6 hrs maybe 5 times, before the third shake; he added 6 drops of Cinnamon bark essential oil.
...
12:30 MG drink was finished. There was some muck which was sucked on and held sublingual. Swallowed...
...
1:30 Feeling like the breath cannot be caught. Does LSC constricts the airways? Start searching for information online; and the screen keeps rippling, making it difficult. Anxious; not enjoying the effect much. Then another psychedelic wave hits.

1:40 Focuse on breathwork and feel great. Slight nausea coming and going.

2:00 Experience visual alterations; a shimmering/waving in the rug patterning (definitely more than is usual). It seemed to be playful/intelligent and powerful also. See a glistening 3-d rippling circle burst outwards from the carpet, as if a rock was dropped in a pond; from corner of the eye.
— https://forum.dmt-nexus.me/threads/lysergic-research.311082/post-3929335

I don't really have the same confidence in the method working beyond (delusion-induced) placebo
...
But the adduct hypothesis is just way too flimsy to be considerable.

It's an incredible delusion-induced placebo for sure. It would be interesting to eventually discover what is truly going on with this LSA/aldehyde saga. It's been going on [online] for what, since the 90s?