Lysergic acid hydroxyethylamide

Lysergic acid hydroxyethylamide (LSH or LAH), also known as lysergic acid N-(α-hydroxyethyl)amide or as lysergic acid methyl carbinolamide, is a lysergamide alkaloid related to the psychedelic drug lysergic acid diethylamide (LSD). It is found in ergot species such as Claviceps paspali and Claviceps purpurea and in the seeds of morning glory species which contain symbiotic fungi such as Periglandula ipomoeae and Periglandula clandestina.

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. 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." 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, rapidly degrading into ergine, and this 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 ergonovine (ergometrine) as an oxytocic in the isolated guinea pig and rabbit uterus, produces sympathomimetic effects like piloerection, mydriasis, and hyperthermia that are very similar to those of ergine (LSA) in mice and rabbits, and has weak ergotamine-like sympatholytic or antiadrenergic effects but with approximately 200-fold lower potency in comparison. 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 -lysergic acid α-hydroxyethylamide. LSH is also very similar in structure to ergonovine (ergometrine), which is also known as lysergic acid hydroxyisopropylamide.

Natural occurrence Claviceps paspali and Claviceps purpurea are ergot alkaloid-producing fungi that occur as endophytes or pathogens of grasses. Clavicipitaceous fungi of the genus Periglandula are mutualistically associated with, and vertically inherited among, an estimated 450species of Convolvulaceae. Some of them produce LSH, with 42 generating ergolines per Eckart Eich's review. The most well-known plant hosts are Ipomoea tricolor ("morning glory"), Turbina corymbosa (coaxihuitl), and Argyreia nervosa (Hawaiian baby woodrose).

The more well-known analogue, ergine (lysergic acid amide; LSA), is more prominent in analytical results because LSH easily decomposes to ergine. Ergine is only present because of the decomposition of LSH (and ergonovine and ergopeptines or their ergopeptam precursors) and is not otherwise generated. A 2016 analysis found that fresher Ipomoea tricolor seeds contained more LSH than the other two batches analyzed.

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.

Lysergic acid hydroxyethylamide

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