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| Other names | LAH; LSH; Lysergic acidN-(α-hydroxyethyl)amide; Lysergic acid α-hydroxyethylamide; Lysergic acid methyl carbinolamide;N-(1-Hydroxyethyl)lysergamide;N(HOE)-LA; 9,10-Didehydro-N-(1-hydroxyethyl)-6-methylergoline-8-carboxamide |
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| ECHA InfoCard | 100.020.079 |
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| Formula | C18H21N3O2 |
| Molar mass | 311.385 g·mol−1 |
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Lysergic acid hydroxyethylamide (LSH orLAH), also known aslysergic acidN-(α-hydroxyethyl)amide or aslysergic acid methyl carbinolamide, is alysergamidealkaloid related to thepsychedelic druglysergic acid diethylamide (LSD). It is found inergot species such asClaviceps paspali[2][3][4] andClaviceps purpurea[5][6] and inmorning glory species.[7]
According toAlbert Hofmann,Alexander Shulgin, and other researchers, LSH might be apsychedelic drug and might contribute to or be substantially responsible for thehallucinogenic effects ofmorning glory seeds.[8][9][10][11] However, the drug has not been studied in humans and this hypothesis has not been tested or confirmed.[8][11] LSH is extremelychemically unstable, and rapidly degrades intoergine (lysergic acid amide; LSA), which has made its investigation difficult.[8][9][10][11]
Thepharmacology of LSH has been very limitedly studied.[10][8][11] It has about 30 to 50% of thepotency asergometrine as anoxytocic in the isolated guinea pig and rabbituterus, producessympathomimetic effects (includingpiloerection,mydriasis, andhyperthermia) very similar to those ofergine in mice and rabbits, and has weakergotamine-likesympatholytic orantiadrenergic effects (1/200 the potency of ergotamine).[10][11] These effects are potentially indicative of LSH havingLSD-like activity.[10][8][11] However, LSH is not known to have been tested in humans.[8][11] LSH may simply function as aprodrug of ergine.[8][10]
Thestructure of LSH is similar to that ofLSD, with theN,N-diethylamide group replaced by anN-(1-hydroxyethyl)amide inD-lysergic acid α-hydroxyethylamide. LSH is also very similar in structure toergonovine (ergometrine), which is also known as lysergic acid hydroxyisopropylamide.[12]
C. paspali andC. purpurea are ergot-spreading fungi.Periglandula,Clavicipitacepus fungi, are permanently symbiotically connected to an estimated 450 species ofConvolvulaceae[13] and thus generate LAH in some of them (42 generate ergolines, by Eckart Eich's review[14]). The most well-known ones areIpomoea tricolor (“morning glory”),Turbina corymbosa (coaxihuitl), andArgyreia nervosa (Hawaiian baby woodrose). LAH is structurally similar toergonovine, 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.[10][15] Ergine is only present because of the decomposition of LAH (andlysergic acid hydroxymethylethylamide and ergopeptines or their ergopeptam precursors); it is not generated.[16][17][18][19][20] Indeed, a 2016 analysis found that fresher I. tricolor seeds contained more LAH than the other two batches analyzed[21] (another interesting finding is that penniclavine was the predominant ergoline.)
LSH was first described in thescientific literature in 1960.[22] It was isolated fromClaviceps paspali.[22]
LSH is unscheduled and uncontrolled in the United States, but possession and sales of it for human consumption could potentially be prosecuted under theFederal Analog Act because of its structural similarities toLSD. Although doubtful as it breaks down into LSA which is a Schedule 3 drug and therefore not applicable to theFederal Analog Act.[citation needed]
"Whereas ergine, lysergic acid hydroxyethylamide, and lysergyl L-valine methylester occur in ergot of rye only in trace amounts, ergonovine (synonyms ergometrine, ergobasin), which is the specific oxytocic factor of a ergot, is often found in remarkable quantities. In contrast, ergine and hydroxyethylamide of lysergic acid are the main constituents of certain ergot growing on wild grasses, e.g. Paspalum distichum." 4. Plants of Hallucinogenic Use / The Fungi, p. 37
"We analyzed ergot of wheat and ergot of barley in our laboratory and they were found to contain basically the same alkaloids as ergot of rye, viz. alkaloids of the ergotamine and ergotoxine group, ergonovine, and sometimes also traces of lysergic acid amide. As I said before, ergonovine and lysergic acid amide, both psychoactive, are soluble in water whereas the other alkaloids are not." Albert Hofmann, 2. A Challenging Question and my Answer, p. 42
d-Lysergic acid N-(1-hydroxyethyl)amide (16b), and d-isolysergic acid N-(1-hydroxyethyl)amide (17b) are hydrolyzed very easily to the corresponding amides and acetaldehyde (186). This could also occur in the organism. d-Lysergic acid N-(1-hydroxyethyl)amide induces contractions in the isolated uterus of the guinea pig and in the rabbit uterus in situ, showing about 30—50 % of the activity of ergometrine. In mice and rabbits it produced the syndrome of central sympathetic stimulation, such as piloerection, mydriasis, and hyperthermia, which suggests that it could have an LSD-like activity, but this hypothesis has not yet been verified by experiments on humans (193).
The major alkaloids present were found to be ergine (d-Lysergic acid amide, Figure 2; R1, R2, R3 = H) and the enantiomorph isoergine (d-Isolysergic acid amide, identical with ergine, but with the opposite epimeric configuration on the carbon atom that carries the amide carbonyl group). These two compounds have been shown to have some activity in man, but it is possible that their presence in the natural seed as the extremely labile acetaldehyde condensates (the hydroxyethylamides) may explain the activity of the seed compared to the lack of activity of the ergot isolates.8 [...] 8. Hofmann, A., Teonanacatl and Ololiuqui, two ancient magic drugs of Mexico, Bull. Narc., 23, 3, 1971.
"These compounds, although well documented as components in the Convolvulaceae, are possibly lost in several of the analyses of alkaloid composition. They are extremely unstable, and are very readily degraded into acetaldehyde and the corresponding amide, ergine or isoergine." (p. 72) [...] "Lysergic acid hydroxyethylamide appears, in uterus response studies of the guinea pig and rabbit (Glasser, 1961), to be about half as potent as its homolog ergometrine, and in mice and rabbits it shows a sympathomimetic response very similar to that described for ergine. This is indicative of potential LSD-like activity."
[...] the new naturally occurring alkaloid ᴅ-lysergic acid methyl carbinolamide has powerful ergometrine-like oxytocic action and weak ergotamine-like adrenergic blocking actions. It must be included, on the basis of pharmacological evidence, in the ergometrine group of ergot alkaloids. Ergometrine, however, is less toxic and more active than the new alkaloid. Results suggest that it could have a lysergic acid diethylamide-like activity, but this hypothesis must be checked by experiments on humans.
[...] lysergic acid hydroxyisopropylamide—ergonovine maleate, U.S.P. (Ergotrate Maleate, Lilly) [...]
{{cite book}}: CS1 maint: postscript (link)"Later, it was found that ergine and isoergine were present in the seeds to some extent in the form of lysergic acid N-(1-hydroxyethyl) amide and isolysergic acid N-(1-hydroxyethyl) amide, respectively, and that, during the isolation procedure, they easily hydrolize to ergine and isoergine, respectively, and acetaldehyde." 4. Plants of Hallucinogenic Use / Convolvulaceae, p. 246
"As has been demonstrated in this study, LSH is a labile compound, and therefore the variances in its concentration may be due to different age and storage conditions of the seeds rather than difference in plant metabolism. Indeed, seeds IT-HB2, which express highest concentration of LSH, were bought directly from the producer, whereas seeds IP-HB1 were purchased in retail stores." (Analysis of different Ipomoea seeds)
See Table 3 under "Analysis of different Ipomoea seeds".
Concentration values for "LSH", "Lyzergol/isobars", penniclavine, and chanoclavine can be obtained by dividing the concentration values of ergine or ergometrine by their relative abundance values and multiplying that number by the relative abundance value of the specified chemical.
[...] Neither the two isomers of lysergic acid amide [(LSA)] nor those of lysergic acid methyl carbinolamide [(LSH)] have previously been reported to occur in Nature.