Excellent work downwardsfromzero! Chemical diagramming genius

Some people have been asking me who the girl in post #61 is...she is one of my favorite DJ's at frisky radio.com, Really great mixes over here, my favorite house radio channel...check it out:

https://www.friskyradio.com/

Thank you Downwardsfromzero & Benzyme. I've read that study before, claviceps Paspali strain makes LSH just like the morning glory. Yes Benzyme, that wikipedia article is clueless.

This is the dream summary...

I know nobody wants to hear this, but the 2014 Forensics study by Paulke (you can download the complete 9 page paper from this thread) saids that HBWR contains NO LSH, but only found LSA & iso-LSA (83-84%) & ergometrine (10-17%) & rest: lysergol, elymoclavine & chanoclavine. Whereas fresh morning glory contains very high amounts of LSH and penniclavine according to 2016 Polish mg study. LSH was discovered by Hofmann in the seeds around 1967, he put color pics of it in his book "LSD, my problem child" and apparently even told Owsley it was very "LSD like".

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Thanks downwardsfromzero for drawing what the 1-acetaldehyde penniclavine would look like.

Since you mention the 1-acetaldehyde adduct of penniclavine [1-(1-hydroxyethyl)penniclavine], attached is a picture of the molecule, for your viewing pleasure
(Note that the the substituents at position 8 - hydroxy and hydroxymethyl - can be in one of two positions. When the hydroxy is below the hexagonal ring and the hydroxymethyl above when viewing the molecule as in the diagram below we have penniclavine. When the hydroxy is above and the hydroxymethyl below, we have isopenniclavine. These two bear the same relationship as lysergic acid and isolysergic acid.)

EDIT: It also occurs to me that the two oxygen atoms can themselves, under acidic conditions, combine with a further molecule of acetaldehyde to form a cyclic ether or acetal (spirodioxolane!) and both the 1-hydroxyethyl group and this 8-spirodioxolane can exist as optical isomers - in the case of the spirodioxolane, because of its methyl group.

EDIT2: This spirodioxolane starts to resemble the space-filling and electron densities of LSH. I wonder if this could be significant too?



[Coleus can grow into small bushes if protected from cold over the winter. I've had mine for about 10 years.]

Here I've attached space-filling models of the LSH-hemiaminal (first picture) and the penniclavine-hemiaminal-spirodioxolane - "PHSD" (second picture). Note that there is absolutely no evidence whatsoever that this latter compound even exists in morning glories, but it's a common chemical reaction for a glycol (like penniclavine) to form a dioxolane by reacting with an aldehyde. I suspect that there's no enzyme to support the formation of PHSD; this is purely a chemistry-based observation derived from the context of the discussion.

Thanks downwardsfromzero! Absolutely amazing models of the LSH-hemiaminal (top picture) and the penniclavine-hemiaminal-spirodioxolane (bottom pic) - "PHSD".

Psychotomimetics of the Convolvulaceae pg 93:

Jonathan Ott "Pharmacotheon":

Hmm, that graph is a bit confusing with its superposed bumps and duplicated colours. It also leaves me wondering what further analyses of the 'alchemical coaxihuitl tea' there might be out there, if any.

I've also had a further (small) look into what is known about how LSH is actually synthesized in the plant. It turns out in feeding studies that labelled lysergylalanine gets metabolised to ergometrine, but not LSH! At least, this appears to be the case for Claviceps species. Actual biosynthesis studies for Ipomoea are much harder to find. So the exact pathway of Ipomoea LSH biosynthesis is either still a mystery or buried somewhere in a paper I haven't found yet.

The route from elymoclavine to LSH appears to have lysergaldehyde (perhaps as the enol-CoA ester) rather than lysergic acid as an intermediate.

One can only hope some further research has been done in the past 36 or so years.

References: Basmadjian et al., Chem Commun., 418 (1969); Minghetti and Arcamone, Experientia 25, 926 (1969)

Other finds:
https://pubmed.ncbi.nlm.nih.gov/27215547/
Gröger & Floss - The Alkaloids, Chapter 5 - The biochemistry of ergot alkaloids (dedicated to Albert Hofmann on his 90th birthday)

P.S. I love chocolate. Chocolate is the food of the gods. In 1753, Linnaeus designated the tree Theobroma cacao, which translates to “cacao, food of the gods.”.

I discovered that I can eat only the Dove promise chocolates (pure milk chocolate & dark chocolates) by the handful day after day and not gain a lb...I have been doing this for weeks...but if it's a butter finger or anything else I gain 4 lbs of water weight overnight...but with the pure chocolates I can eat entire handfuls of it day after day and not gain anything...give it a shot, several of my friends have tried the same, and also found no weight gain. I read about the fat burning properties of "pure chocolates" even if it has sugar in the latest issue of Muscular Development.

https://livehealthy.chro...educing-weight-5330.html

1. Improves metabolism, decreases insulin resistance
2. Controls appetite, reduces digestion & absorption of fats and carbs.
3. Enhances your sense of well being,
4. Dark chocolate contains anandamide, a type of lipid known as "the bliss chemical."
5. Dark chocolate has more antioxidant activity, polyphenols and flavanols than any other fruits tested, which included blueberries and acai berries.
6. The Aztecs believed cacao seeds had so much value they were used as a form of currency. The great Aztec king Montezuma himself reportedly drank about 50 cups of cocoa every single day.

Anandamide's effects are mediated primarily by CB1 cannabinoid receptors in the central nervous system, and CB2 cannabinoid receptors in the periphery. The name anandamide is taken from the Sanskrit word Ananda, which means "joy, bliss, delight", and amide.

P.S. Ideal time to pick is when the seed pod just lost its green, as then they have the best LSH/LSA ratio and being overall the most potent.

Interesting, I'll look into Aum Shanti's claim for LSH biosynthesis this way; it could be the case that it's true for the vine even if LSH is made another way in, say, Claviceps paspali. But having a good look at the references is something I'll do anyway. I've been pondering this question for the past few days, in the light of what information was to be found. Thus, I've dropped by to share my current thought for what might happen in the elymoclavine → LSH, if it proceeds differently from the lysergic acid/ergometrine route (as some evidence might appear to suggest):
elymoclavine → enollysergaldehyde-CoA [ + NH3 + pyruvate] → LSH [ + CoA + CO2]



I'm totally with you on the other aspects of MGS as we encounter it at harvest.

(On chocolate, our opinions will have to diverge. For one thing, the brand that you so treasure is not available in the country I live in. For another, my main issue has been in gaining and maintaining weight rather than losing it!)

(And is that your friend, Penny Clavine in your new avatar pic? )

downwardsfromzero said:

Yes, the one and only Penni Clavine.

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anandamide is hydrolyzed by FAAH, and rendered inactive. It has a half-life of 3.5 s., so the bliss is fleeting.

While there is very little anandamide in cacao, there are 2 important chemicals found in much higher concentrations in cacao that are more than likely the reason why we notice the mood elevating effects from cacao: N-oleolethanolamine (OEA), a known inhibitor of weight gain in mice, and N-linoleoylethanolamine (18:3 NAE), a known anti-inflammatory molecule — like anandamide — via the TRPV1 receptor.

These two structural cousins of anandamide both inhibit the metabolic breakdown of anandamide and could potentially inhibit the breakdown of other cannabinoids including THC and CBD causing these compounds to stick around longer, providing even more benefits

All of these mood-enhancing benefits are compounded by theobromine, the primary stimulant in chocolate. Theobromine is a known vasodilator that acts as a “driver” of nutrients and chemicals into the tissues. It could also be responsible for amplifying the effects of the anandamide found in chocolate as it is also a mood enhancer.

In addition to anandamide and theobromine, cacao has serotonin, Phenylethylamine, and dopamine, all of which help us to feel more optimistic and peaceful. Serotonin & dopamine cannot cross the blood brain barrier however, but phenylethylamine can. All of these combined provide us with an overall sense of well being while providing gentle, natural, long-lasting energy.

The reasons to love chocolate are many.

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PEA is another trace amine with a short half-life (~4 s), oxidized by the oxidireductase CYP3A4...the same that metabolizes caffeine and theobromine. to my knowledge, chocolate lacks any RIMA of subtype A and B. Before I formally studied metabolism,
I thought xocolatl infusions would potentiate the mushroom experience; I asked dr. strassman, and he said he didn't know.
There must've been another ingredient added (besides chile peppers).

The late (and wonderful) Dale Pendell covered this, in his own way, in the second volume of his Pharmako* trilogy, PharmakoDynamis. One associated plant that comes up as an admixture with unanswered questions attached has the Latin name Quararibea funebris, but besides this unusual ingredient and the aforementioned chillies, the commonest flavourings were allspice (Pimenta racemosa) and vanilla. Pendell wrote plenty more on the cacahuatl preparation methods of the Aztecs but this tangent has continued long enough lest I reproduce Pendell's entire Theobrome cacao chapter here.

One more relevant point he raises, however, is that chocolate "contains two related compounds, in greater quantities, that inhibit the natural degradation of anandamide in the body." This, to me, suggests some kind of FAAH inhibitor which surely must be pharmacologically relevant. Considering phytochemical compounds in isolation is prone to errors of emission in this respect - which brings me to a further point: bearing in mind that PEA is metabolized by, amongst other things, CYP3A4, and that purine alkaloids found in chocolate are also substrates for this enzyme, we can also surmise that the half-life of PEA likely will also be prolonged (slightly) through competitive inhibition.

Add to that the abundant flavonoids and catechins found in (good quality) chocolate and their metabolic effects and we might start to see a broader picture. It would be reasonable to suspect that flavonoids would modulate the metabolism of Psilocybe fungal alkaloids, for example.

https://www.researchgate...sis_in_Theobroma_cacao_L (lists some significant cacao flavanoids)

In "The Simple Plant Isoquinolines", Shulgin & Perry list 4,6-dihydroxy-2-methyltetrahydroisoquinoline [1], longimammidine (8-hydroxy-2-methylTHIQ) [1] and salsolinol (6,7-dihydroxy-1-methylTHIQ) [2] in association with Theobroma cacao. Whether any of these compounds have any bearing on the subjective effects of commercial chocolate remains to be seen. Their occurrence might be restricted to the roots, for example.

References:
[1] Lloydia 41, 130 (1978)
[2] J. Agric. Food Chem. 24, 900 (1976)

Do we know that the function of cacaobeans and peppers in the brew was to potentiate the effects of mushrooms?

The fact that theobromine is a vaso and broncholidator could also be an explanation for why it was used in conjunction with magic mushrooms. You can take larger quantities that way, without experiencing these side effects.