Lysergic acid hydroxyethylamide

Use and effects

According to Albert Hofmann, Alexander Shulgin, and other researchers, LSH might be a psychedelic drug and might contribute to or be substantially responsible for the hallucinogenic effects of morning glory seeds. Relatedly, per Shulgin in his 1997 book TiHKAL (Tryptamines I Have Known and Loved), both ergine (lysergic acid amide; LSA) and isoergine (iso-LSA) are "probably correctly dismissed" as not contributing to the effects of morning glory seeds. However, LSH has not been studied in humans and this hypothesis has not been tested or confirmed. LSH is said to be extremely chemically unstable, and rapidly degrades into ergine, which has made its investigation difficult.

Interactions

Pharmacology

Pharmacodynamics

The pharmacology of LSH has been very limitedly studied. It has about 30 to 50% of the potency as ergometrine as an oxytocic in the isolated guinea pig and rabbit uterus, produces sympathomimetic effects (including piloerection, mydriasis, and hyperthermia) very similar to those of ergine in mice and rabbits, and has weak ergotamine-like sympatholytic or antiadrenergic effects (1/200 the potency of ergotamine). These effects are potentially indicative of LSH having LSD-like activity. However, LSH is not known to have been tested in humans. LSH may simply function as a prodrug of ergine.

Chemistry

The structure of LSH is similar to that of LSD, with the N,N-diethylamide group replaced by an N-(1-hydroxyethyl)amide in D-lysergic acid α-hydroxyethylamide. LSH is also very similar in structure to ergonovine (ergometrine), which is also known as lysergic acid hydroxyisopropylamide.

Natural occurrence

C. paspali and C. purpurea are ergot-spreading fungi. Periglandula, Clavicipitacepus fungi, are permanently symbiotically connected to an estimated 450species of Convolvulaceae and thus generate LAH in some of them (42 generate ergolines, by Eckart Eich's review). The most well-known ones are Ipomoea tricolor (“morning glory”), Turbina corymbosa (coaxihuitl), and Argyreia nervosa (Hawaiian baby woodrose). LAH is structurally similar to ergonovine, which is also known as lysergic acid hydroxymethylethylamide.

The more well-known analogue, ergine (lysergic acid amide; LSA), is more prominent in analytical results because LAH easily decomposes to ergine. Ergine is only present because of the decomposition of LAH (and lysergic acid hydroxymethylethylamide and ergopeptines or their ergopeptam precursors); it is not generated. Indeed, a 2016 analysis found that fresher I. tricolor seeds contained more LAH than the other two batches analyzed (another interesting finding is that penniclavine was the predominant ergoline.)

History

LSH was first described in the scientific literature in 1960. It was isolated from Claviceps paspali.

Society and culture

Legal status

Canada

LSH is not a controlled substance in Canada.

France

LSH is illegal in France.

United States

LSH is not an explicitly controlled substance in the United States. However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

References

References

1. (20 May 2021). "Arrêté du 20 mai 2021 modifiant l'arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants".
2. (July 1960). "Production of lysergic acid derivatives by a strain of Claviceps paspali Stevens and Hall in submerged culture". Nature.
3. (April 1970). "Biosynthesis of N-(alpha-hydroxyethyl) lysergamide, a metabolite of Claviceps paspali Stevens and Hall". The Biochemical Journal.
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9. {{CiteTiHKAL https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml "LA-111, Ergine, d-Lysergamide. This is an active compound and has been established as a major component in morning glory seeds. It was assayed for human activity, by Albert Hofmann in self-trials back in 1947, well before this was known to be a natural compound. An i.m. administration of a 500 microgram dose led to a tired, dreamy state with an inability to maintain clear thoughts. [...] The epimer, inverted at C-8, is isoergine or d-isolysergamide, and is also a component of morning glory seeds. Hofmann tried a 2 milligram dose of this amide, and as with ergine, he experienced nothing but tiredness, apathy, and a feeling of emptiness. Both compounds are probably correctly dismissed as not being a contributor to the action of these seeds. It is important to note that ergine, as well as lysergic acid itself, is listed as a Schedule III drug in the Controlled Substances Act, as a depressant. This is, in all probability, a stratagem to control them as logical precursors to LSD. [...] Although there are many other chemical treasures in the ergot fungal world, I would like to wrap this commentary up with a return to the topic of morning glory seeds. Four additional alkaloids of the ergot world must be acknowledged as being potentially participating factors in the MGS story. [...] These structures in effect define absolute obscurity, and most probably do not contribute to the morning glory intoxication state. But the others, some present is sizable amounts, may someday help explain why the pharmacology of these seeds is so different than that of the major isolates, the ergines."
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