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Ergine, also known as lysergic acid amide ( LSA or LAA) as well as LA-111, is a psychoactive compound of the ergoline and lysergamides families related to lysergic acid diethylamide (LSD). Ergine is an ergoline alkaloid found in fungi such as Claviceps paspali (ergot) and Periglandula species such as Periglandula clandestina, which are permanently connected with many convolvulaceae vines. Ergine induces relatively mild psychedelic effects as well as pronounced sedative effects. (2026). 9789814405607, World Scientific. ISBN 9789814405607
The most common sources of ergine for use as a drug are the seeds of morning glory species including Ipomoea tricolor (tlitliltzin), Ipomoea corymbosa (ololiuhqui), and Argyreia nervosa (Hawaiian baby woodrose). (2026). 9780979862229, MAPS.org. ISBN 9780979862229 Morning glory seeds have a history of use in Mesoamerica dating back at least hundreds of years. They have also since been used by many Western people. In addition to ergine, morning glory seeds contain other ergolines such as lysergic acid hydroxyethylamide (LSH), ergonovine (ergonovine), and isoergine. Some of these compounds are pharmacology and are thought to contribute to the effects of the seeds as well. (1993). 9781438417417, State University of New York Press. ISBN 9781438417417 There has been debate about the role of ergine in causing the psychedelic effects of morning glory seeds.
Ergine was first described by Sidney Smith and Geoffrey Timmis after they isolated it from ergot in 1932. It was first synthesized subsequent to its isolation in the 1930s. Albert Hofmann, the discoverer of LSD's psychedelic effects in 1943, evaluated the effects of ergine in humans in 1947 and described the results many years later. He and his colleagues also isolated ergine from morning glory seeds in 1960. Morning glory seeds started to become frequently used as a recreational drug that same year and have been widely used since. Recreational use of morning glory seeds may be increasing due to their inexpensiveness, widespread availability, and lack of legal restrictions. Ergine has been encountered as a novel designer drug in Europe. Ergine, though not morning glory seeds, has become a controlled substance in various places in the world.
Ergine may be used as a drug in pure or purified form as well, either isolated or synthesized. Albert Hofmann and colleagues found that a 0.5 to 2mg dose by intramuscular or subcutaneous injection produced relatively weak but significant hallucinogenic effects as well as marked sedation. Another study described the effects of pure ergine by injection but the doses were not clearly provided (although appeared to be around 0.1–1mg). Based on the preceding studies, Alexander Shulgin describes pure ergine as having a dosage of 0.5 to 1mg and being 10-fold less potent than LSD, but as being "not hallucinogenic". Hofmann also stated that ergine was 10- to 40-fold less potent than LSD and that it had qualitatively different effects. Robert Oberlender has stated that ergine is about 30-fold less potent than LSD in humans. Heim and colleagues assessed ergine at higher doses of 3 to 6mg orally and observed toxic-like effects, whereas isoergine at 2 to 5mg orally produced notable hallucinogenic effects, including some euphoria, synaesthesia, and time dilation.
Per Shulgin in his 1997 book TiHKAL ( Tryptamines I Have Known and Loved) however, both ergine and isoergine are "probably correctly dismissed" as not contributing to the effects of morning glory seeds.
"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." The poorly-stable lysergic acid hydroxyethylamides (LSHs) might alternatively be involved in the psychedelic effects of morning glory seeds per Shulgin.
Sleepy grass ( Achnatherum robustum) and Claviceps paspali (ergot) have similar ergoline constituents as morning glory seeds and have also been used to produce psychoactive effects, albeit rarely. (1994). 9781559501101, Loompanics Unlimited. ISBN 9781559501101
Heim 1968 also noted "paraesthesia", "synesthesia" and an "overestimation of the time that had passed" (isoergine), but also concluded, "our experiments with ᴅ-lysergic acid amide also confirm the results that Sᴏʟᴍꜱ had made with this substance, namely a predominantly sedative intoxication." Hofmann emphasized this sedative effect:
"Furthermore there is not only a quantitative difference between the principles of Ipomoea tricolor and Turbina corymbosa and LSD; there is likewise a qualitative one, LSD being a very specific hallucinogen, whereas the psychic effects of lysergic acid amide and the total alkaloids of these two plants are characterized by a pronounced narcotic component (Hofmann, 1968)."
"A substance very closely related to LSD, the monoethylamide of lysergic acid (LAE-32), in which an ethyl group is replaced by a hydrogen atom on the diethylamide residue of LSD, proved to be some ten times less psychoactive than LSD. The hallucinogenic effect is also qualitatively different: it is characterized by a narcotic component. This narcotic effect is yet more pronounced in lysergic acid amide (LA-111), in which both ethyl groups of LSD are displaced by hydrogen atoms. These effects, which I established in comparative self-experiments with LA-111 and LAE-32, were corroborated by subsequent clinical investigations."
"The experience had some strong narcotic effect, but at the same time there was a very strange sense of voidness. In this void, everything loses its meaning. It is a very mystical experience."
One study found that two of four human subjects experienced cardiovascular dysregulation and the study had to be halted, concluding that the ingestion of seeds containing ergine was less safe than commonly believed. Importantly this may have been a product of other substances within the seeds. The same study also observed that reactions were highly differing in type and intensity between different subjects.
The side effects of ergine have been described as follows: "The expression and behavior of the test subjects changed just 45 minutes after taking the substance: the test subjects appeared to be suffering, their facial expressions were deteriorating as if they had suffered a serious illness, and their movements were noticeably slower. ... In the self-reports of both test subjects, complaints about vegetative symptoms predominated: unpleasant, flu-like feeling of illness, nausea, sudden onset of nausea, with vomiting that could be stopped with 2 cm3 of Cyclicinum hydrochloricum. In addition, sensations of heat, sweating, dizziness, a feeling of heaviness and general tiredness were observed."
And the side effects of ergonovine have been described as follows: "Walking in this dreamy state was difficult due to leg cramps and slight incoordination. There was always a great desire to lie supine. ... One of us (J.B.) felt the cramping in the legs as painful and debilitating. ... We all had a slight hangover the following morning. ... The mild entheogenic effects of ergonovine are similar to those of LSD. However, in dramatic contrast to LSD, the somatic effects of ergonovine greatly overshadow its psychic effects, so much so that we had no wish to ingest more than 10.0 mg, ...".
Like other psychedelics, ergine is not considered to be addiction. Additionally, there are no known directly associated with Pharmacology effects of ergine consumption. All associated deaths are due to indirect causes, such as self-harm, Judgement, and adverse . One known case involved a suicide that was reported in 1964 after ingestion of morning glory seeds. Another instance is a death due to falling off of a building after ingestion of Argyreia nervosa and alcohol. A study gave mice 3000mg/kg with no lethal effects.
A related rumor is that the seeds contain cyanogenic glycosides. The UseNet post on which this is based contains two references, but neither of them support that claim,
Ergine interacts with serotonin, dopamine, and adrenergic receptors similarly to but with lower affinity than lysergic acid diethylamide (LSD). It is known to act as an agonist of the serotonin 5-HT2A and 5-HT2B receptors similarly to LSD, albeit much less potently and with reduced activational maximal efficacy. The drug has about 4.3% of the antiserotonergic activity of LSD in the isolated rat uterus in vitro. The psychedelic effects of ergine can be attributed to activation of serotonin 5-HT2A receptors.
The extraction of ergine from morning glory seeds has been described.
LSH is very vulnerable to this hydrolysis,
An ergine analog, 8-hydroxyergine, has also been found in natural products in two studies. Methylergonovine and methysergide (1-methylmethylergonovine) have also been found in a natural product in one study; these are documented as semisynthetic compounds, so the findings need to be repeated for certainty. The aforementioned chemicals are the only natural lysergamides.
LSH and ergine are predominant in Claviceps paspali, but are only found in trace amounts in the more well-known Claviceps purpurea.
LSH and ergine are also found in the related fungi, Periglandula, which are permanently connected with Ipomoea tricolor, Ipomoea corymbosa, Argyreia nervosa ("morning glory", coaxihuitl, Hawaiian baby woodrose), and an estimated over 440 other Convolvulaceae
Other fungi that have been found to contain LSH and/or ergine:
All of these fungi are related to Claviceps fungi. Aspergillus is considered to be a more distant relative of Claviceps.
Other fungi that possibly contain ergine (i.e. they have been found to contain ergonovine and/or ergopeptines):
/ref> and Eckart Eich says that they probably don't occur in many Convolvulaceae. There is a similar claim in a publication from 1973, warning about "a strychnine-like alkaloid", but that is probably just a misapplication of the claim that peyote contains strychnine, which, itself, is a rumor. (2010). 9781556438042, North Atlantic Books. ISBN 9781556438042
Overdose
Cases of overdose of ergine and morning glory seeds and associated toxicity have been reported.
Interactions
The drug interaction of ergine and of morning glory seeds have been discussed.
Pharmacology
Pharmacodynamics
+ Ergine (LSA) and LSD activities 46:1 32–120:1
2–16:1
0.78–0.95:13–79:1
0.65–0.75:1102:1 10:1 6:1 6:1 7:1 5:1 15:1 62:1 Notes: All proteins are human unless otherwise specified. Sources: (2026). 9780444641250 ISBN 9780444641250
Chemistry
Ergine, also known as lysergic acid amide (LSA) or as lysergamide, is a ergoline and lysergamide. It is the simplest lysergamide and is the parent compound of this family of compounds. Hence, all lysergamides are derivatives of ergine. Lysergic acid diethylamide (LSD) is the analogue of ergine with two substituted on its amide moiety.
Natural occurrence
Ergine is not a biosynthesis endpoint itself, but rather a hydrolysis product of lysergic acid hydroxyethylamide (LSH), ergonovine (ergonovine), and or their ergopeptam precursors.
(1973). 9780398064167, Charles Thomas. ISBN 9780398064167 and many analyses of ergoline-containing products show little to no LSH and substantial amounts of ergine.
(1973). 9780398064167, Charles Thomas. ISBN 9780398064167 Both are ergot-spreading fungi. The major products of C. purpurea are ergopeptines, but C. paspali does not generate ergopeptines. Ergonovine is the only lysergamide in C. purpurea in a substantial amount.
(2018). 9783319717395, Springer International Publishing. ISBN 9783319717395 (ergolines have been identified in 42 of these plants and not all of them contain ergine). Ergonovine is present in Ipomoea tricolor in one-tenth to one-third of the amount of ergine. See Table 3. ... 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. This variable may account for the varying reports about the psychedelic effect of these seeds.
(1991). 9780841218970, American Chemical Society. ISBN 9780841218970
See table 3 on p. 1290.
(2026). 9789057023750, Harwood Academic Publishers. ISBN 9789057023750
From here, the biosynthesis diverges and the products formed are plant and fungus-specific. The biosynthesis of ergine in C laviceps purpurea will be exemplified, in which agroclavine is produced following the formation of chanoclavine-l-aldehyde, catalyzed by EasA through a keto-enol tautomerization to facilitate rotation about the C-C bond, followed by tautomerization back to the aldehyde and condensation with the proximal secondary amine to form an iminium species, which is subsequently reduced to the tertiary amine and yielding agroclavine. Cytochrome P450 monooxygenases (CYP450) are then thought to catalyze the formation of elymoclavine from argoclavine via a 2 electron oxidation. This is further converted to paspalic acid via a 4 electron oxidation, catalyzed by cloA, a CYP450 monooxygenase. Paspalic acid then undergoes isomerization of the C-C double bond in conjugation with the acid to form Lysergic acid. While the specifics of the formation of ergine from Lysergic acid are not known, it is proposed to occur through a nonribosomal peptide synthase (NRPS) with two enzymes primarily involve: D-lysergyl peptide synthase (LPS) 1 and 2.
Albert Hofmann was first to identify ergine as a natural constituent of Turbina corymbosa seeds.
Albert Hofmann describes ergine as "the main constituent of ololiuhqui". Ololiuhqui was used by South American healers in shamanic healing ceremonies. Similarly, ingestion of morning glory seeds by Mazatec tribes to "commune with their gods" was reported by Richard Schultes in 1941 and is still practiced today.
According to the ethnobotanist R. Gordon Wasson, Thomas MacDougall and Francisco Ortega ("Chico"), a Zapotec peoples guide and trader, should be credited for the discovery of the ceremonial use of Ipomoea tricolor seeds in Zapotec towns and villages in the uplands of southern Oaxaca. The seeds of both Ipomoea tricolor and Rivea corymbosa, another species which has a similar chemical profile, are used in some Zapotec towns.
The Central Intelligence Agency conducted research on the psychedelic properties of Rivea corymbosa seeds for MKULTRA.
Hofmann's discovery of ergine and related compounds in morning glory seeds, which are closely structurally related to LSD, was said to have initially been met with "a state of disbelief bordering on accusations of scientific fraud", but was soon confirmed by other researchers.
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