Ergine has been found in high concentrations of 20μg/g dry weight in the sleepygrass infected with an Acremoniumendophyticfungus together with other ergot alkaloids.[8]
Ergine is a component of the alkaloids contained in the ergot fungus, which grows on the heads of infected rye grasses.
It is also found in the seeds of several varieties of morning glories in concentrations of approximately 10μg per seed, as well as Hawaiian baby woodrose seeds, at a concentration of around 0.13% of dry weight.[9]
History
Ololiuhqui was used by South American healers in shamanic healing ceremonies.[10] 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.[11][10]
Sewell RA. Entheogen Rev. 2008;16:117-25.
Additional reports of the use of ergine were made by Don Thomes MacDougall. He reported that the seeds of Ipomoea violacea were used as sacraments by certain Zapotecs, sometimes in conjunction with the seeds of Rivea corymbosa, another species which has a similar chemical composition, with lysergol instead of ergometrine.[7]
Ergine was assayed for human activity by Albert Hofmann in self-trials in 1947, well before it was known to be a natural compound. Intramuscular administration of a 500 microgram dose led to a tired, dreamy state, with an inability to maintain clear thoughts. After a short period of sleep the effects were gone, and normal baseline was recovered within five hours.[6]
In 1956, the Central Intelligence Agency conducted research on the psychedelic properties of the ergine in the seeds of Rivea corymbosa, as Subproject 22 of MKULTRA.[12]
In 1959, Hofmann was the first to isolate chemically pure ergine from the seeds of Turbina corymbosa, determining that it, and other alkaloids, were acting as the main active components in the seeds.[7] Twenty years prior to its isolation, ergine was first chemically defined by English chemists S. Smith and G. M. Timmis as the cleavage product of ergot alkaloids. Additionally, Guarin and Youngkin reportedly isolated the crude alkaloid in 1964 from morning glory seeds.[13]
While its physiological effects vary from person to person, the following symptoms have been attributed to the consumption of ergine or ergine containing seeds:[7][10][16]
One study found that 2 of 4 human subjects experienced cardiovascular dysregulation and the study had to be halted, concluding that the ingestion of seeds containing ergine was less safe then 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.[17] Another study in mice found that the drug had aphrodisiac properties, inducing increased sexual behavior.[18]
A study gave mice 3000mg/kg with no lethal effects.[citation needed]
Psychedelic component
Ergine is thought to be a serotonergic psychedelic and its psychedelic effects are thought to be due to it being a partial agonist of the 5-HT2A receptor. Though, the reason as to why this may be hallucinogenic remains elusive.
The idea that ergine is the main psychedelic component in ergine containing seeds (morning glory, Hawaiian baby woodrose) is well debated, as the effects of isolated synthetic ergine are reported to be only mildly psychedelic.[9][16] Thus, the overall psychedelic experience after consumption of such seeds has been proposed to be due to a mixture of ergoline alkaloids.
Pharmacology
Pharmacodynamics
Affinities of LSA and LSD for various receptors[20]
The biosynthetic pathway to ergine starts like most other ergoline alkaloid- with the formation of the ergoline scaffold. This synthesis starts with the prenylation of L-tryptophan in an SN1 fashion with dimethylallyl diphosphate (DMAPP) as the prenyl donor and catalyzed by prenyltransferase 4-dimethylallyltryptophan synthase (DMATS), to form 4-L-dimethylallyltryptophan (4-L-DMAT). The DMAPP is derived from mevalonic acid. A three strep mechanism is proposed to form 4-L-DMAT: the formation of an allylic carbocation, a nucleophilic attack of the indole nucleus to the cation, followed by deprotonation to restore aromaticity and to generate 4-L-DMAT.[22] 4-Dimethylallyltyptophan N-methyltransferase (EasF) catalyzes the N-methylation of 4-L-DMAT at the amino of the tryptophan backbone, using S-Adenosyl methionine (SAM) as the methyl source, to form 4-dimethylallyl-L-abrine (4-DMA-L-abrine).[22] The conversion of 4-DMA-L-abrine to chanoclavine-I is thought to occur through a decarboxylation and two oxidation steps, catalyzed by the FAD dependent oxidoreductase, EasE, and the catalase, EasC. The chanoclavine intermediate is then oxidized to chanoclavine-l-aldehyde, catalyzed by the short-chain dehydrogenase/reductase (SDR), EasD.[22][23]
Formation of argoclavine
From here, the biosynthesis diverges and the products formed are plant and fungus-specific. The biosynthesis of ergine in Claviceps 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 argoclavine.[22][23]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 D-lysergic acid.[22] While the specifics of the formation of ergine from D-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.[22][23]
Legal status
The legality of consuming, cultivating, and possessing ergine varies depending on the country.
There are no laws against possession of ergine-containing seeds in the United States. However, possession of the pure compound without a prescription or a DEA license would be prosecuted, as ergine, under the name "lysergic acid amide", is listed under Schedule III of the Controlled Substances Act.[24] Similarly, ergine is considered a Class A substance in the United Kingdom, categorized as a precursor to LSD.
In most Australian states, the consumption of ergine containing materials is prohibited under state legislation.
In Canada, ergine is not illegal to possess as it is not listed under Canada's Controlled Drugs and Substances Act, though it is likely illegal to sell for human consumption.[25]
In New Zealand, ergine is a controlled drug, however the plants and seeds of the morning glory species are legal to possess, cultivate, buy, and distribute.
Lysergic acid diethylamide, commonly known as LSD, and known colloquially as acid or lucy, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages, LSD manifests primarily mental, visual, and auditory hallucinations. Dilated pupils, increased blood pressure, and increased body temperature are typical.
Convolvulaceae, commonly called the bindweeds or morning glories, is a family of about 60 genera and more than 1,650 species. These species are primarily herbaceous vines, but also include trees, shrubs and herbs. The tubers of several species are edible, the best known of which is the sweet potato.
Ipomoea corymbosa is a species of morning glory, native throughout Latin America from Mexico as far south as Peru and widely naturalised elsewhere. Its common names include Christmasvine, Christmaspops, and snakeplant.
Ergot or ergot fungi refers to a group of fungi of the genus Claviceps.
Morning glory is the common name for over 1,000 species of flowering plants in the family Convolvulaceae, whose current taxonomy and systematics are in flux. Morning glory species belong to many genera, some of which are:
Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of these are implicated in the condition ergotism, which can take a convulsive form or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives.
Lysergic acid, also known as D-lysergic acid and (+)-lysergic acid, is a precursor for a wide range of ergoline alkaloids that are produced by the ergot fungus and found in the seeds of Turbina corymbosa (ololiuhqui), Argyreia nervosa, and Ipomoea tricolor.
Ergotamine, sold under the brand names Cafergot and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitters, and it acts as a vasoconstrictor.
Argyreia nervosa is a perennial climbing vine native to the Indian subcontinent and introduced to numerous areas worldwide, including Hawaii, Africa, and the Caribbean. Though it can be invasive, it is often prized for its aesthetic and medicinal value. Common names include Hawaiian baby woodrose, adhoguda अधोगुडा or vidhara विधारा (Sanskrit), elephant creeper and woolly morning glory. Its seeds are known for their powerful entheogenic properties, greater or similar to those of Ipomoea species, with users reporting significant psychedelic and spiritual experiences. The two botanical varieties are A. n. var. nervosa described here, and A. n. var. speciosa, which are used in Ayurvedic medicine for their medicinal value.
Amides of lysergic acid are collectively known as lysergamides, and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine receptors. Lysergamides contain an embedded tryptamine structure, and as a result can produce similar, often psychedelic, effects to those of the true tryptamines.
D-Lysergic acid α-hydroxyethylamide, also known as D-lysergic acid methyl carbinolamide, is a Lysergamide and alkaloid of the Ergoline family, it is present in higher concentrations in the parasitic fungi species "Claviceps", mainly the Claviceps paspali, also in Claviceps Purpurea. This fungi grows in various species in the Convolvulaceae family like the Ipomoea violacea, the Rivea corymbosa (Ololiuhqui), and the Argyreia nervosa. Heavenly Blue Morning Glory and Hawaiian Baby Woodrose especially contain high amounts of LSH, with content varying between species and by how fresh the seeds are. LSH is a psychoactive Ergoline and has effects similar to LSD due to similarity in the structure and is the main psychoactive compound found in Claviceps Paspali and in (fresh) Heavenly Blue Morning Glory Seeds. LSH is unstable and breaks down into LSA quickly, so old seeds often only contains LSA and iso-LSA. When the seeds are fresh, they contain significantly higher amounts of LSH.
Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.
Lysergol is an alkaloid of the ergoline family that occurs as a minor constituent in some species of fungi, and in the morning glory family of plants (Convolvulaceae), including the hallucinogenic seeds of Rivea corymbosa (ololiuhqui), Argyreia nervosa and Ipomoea violacea. Lysergol is not a controlled substance in the USA. Its possession and sale is also legal under the U.S. Federal Analog Act because it does not have a known pharmacological action or a precursor relationship to LSD, which is a controlled substance. However, lysergol is an intermediate in the manufacture of some ergoloid medicines.
Ipomoea violacea is a perennial species of Ipomoea that occurs throughout the world with the exception of the European continent. It is most commonly called beach moonflower or sea moonflower as the flowers open at night.
Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.
Ergocryptine is an ergopeptine and one of the ergoline alkaloids. It is isolated from ergot or fermentation broth and it serves as starting material for the production of bromocriptine. Two isomers of ergocryptine exist, α-ergocryptine and β-ergocryptine. The beta differs from the alpha form only in the position of a single methyl group, which is a consequence of the biosynthesis in which the proteinogenic amino acid leucine is replaced by isoleucine. β-Ergocryptine was first identified in 1967 by Albert Hofmann. Ergot from different sources have different ratios of the two isomers.
LSD-Pip is a compound from the ergoline family, related to LSD but with the N,N-diethyl substitution replaced by a piperidine group. It is more potent than the corresponding pyrrolidine and morpholine analogues, but is still several times less potent than LSD as a 5-HT2A agonist. Early studies suggested this compound to be inactive as a psychedelic in humans, though this does not seem to have been confirmed by any more recent work.
Elymoclavine is an ergot alkaloid. It can be produced from C. fusiformis from Pennisetum typhoideum. It is a precursor in the biosynthesis of D-(+)-lysergic acid. Ergot alkaloids are natural products derived from L-tryptophan. They are often toxic for humans and animals. Despite that they are also well known for their pharmacological activities.
Argyreia cuneata is a perennial climbing shrub which is native to the Indian subcontinent and is related to Argyreia nervosa.
Periglandula are a genus of fungi in the family Clavicipitaceae. They live as epibionts, in a symbiotic relationship with two species of plant, Ipomoea asarifolia and Ipomoea corymbosa. They are known to produce ergot alkaloids related to lysergic acid.
↑ Smith S, Timmis GM (1932). "98. The alkaloids of ergot. Part III. Ergine, a new base obtained by the degradation of ergotoxine and ergotinine". Journal of the Chemical Society (Resumed): 763. doi:10.1039/jr9320000763.
↑ Perrine DM (2000). "Mixing the Kykeon"(PDF). ELEUSIS: Journal of Psychoactive Plants and Compounds. New Series 4: 9. Archived from the original(PDF) on 2019-07-20. Retrieved 2008-05-05.
1 2 Alexander Shulgin, "#26. LSD-25", TiHKAL, Erowid.org, retrieved 2012-02-03
1 2 3 4 Hofmann A (2009). LSD My Problem Child: Reflections on Sacred Drugs, Mysticism, and Science (4thed.). MAPS.org. ISBN978-0979862229.
↑ Schultes RE (1941). A Contribution to Our Knowledge of Rivea Corymbosa: The Narcotic Ololinqui of the Aztecs (1sted.). Botanical Museum of Harvard University.
↑ Der Marderosian AH, Guarino AM, De Feo JJ, Youngken Jr HW (1964). "A Uterine Stimulant Effect of Extracts of Morning Glory Seeds". Pschedelic Review: 317–323.
↑ Cohen S (April 1964). "Suicide Following Morning Glory Seed Ingestion". The American Journal of Psychiatry. 120 (1): 1024–1025. doi:10.1176/ajp.120.10.1024. PMID14138842.
↑ Klinke HB, Müller IB, Steffenrud S, Dahl-Sørensen R (April 2010). "Two cases of lysergamide intoxication by ingestion of seeds from Hawaiian Baby Woodrose". Forensic Science International. 197 (1–3): e1–e5. doi:10.1016/j.forsciint.2009.11.017. PMID20018470.
1 2 3 4 5 Marneros A, Gutmann P, Uhlmann F (October 2006). "Self-amputation of penis and tongue after use of Angel's Trumpet". European Archives of Psychiatry and Clinical Neuroscience. 256 (7): 458–9. doi:10.1007/s00406-006-0666-2. PMID16783491. S2CID9261722.
1 2 3 Paulke A, Kremer C, Wunder C, Achenbach J, Djahanschiri B, Elias A, etal. (July 2013). "Argyreia nervosa (Burm. f.): receptor profiling of lysergic acid amide and other potential psychedelic LSD-like compounds by computational and binding assay approaches". Journal of Ethnopharmacology. 148 (2): 492–497. doi:10.1016/j.jep.2013.04.044. PMID23665164.
↑ Halberstadt AL, Nichols DE (2020). "Serotonin and serotonin receptors in hallucinogen action". Handbook of the Behavioral Neurobiology of Serotonin. Handbook of Behavioral Neuroscience. Vol.31. pp.843–863. doi:10.1016/B978-0-444-64125-0.00043-8. ISBN9780444641250. ISSN1569-7339.
Sydney S, Timmis GM (1932). "98. The Alkaloids of Ergot. Part III. Ergine, a New Base obtained by the Degradation of Ergotoxine and Ergotinine". J. Chem. Soc.1932: 763–766. doi:10.1039/JR9320000763.
Juszczak GR, Swiergiel AH (2013-01-01). "Recreational use of D-lysergamide from the seeds of Argyreia nervosa, Ipomoea tricolor, Ipomoea violacea, and Ipomoea purpurea in Poland". Journal of Psychoactive Drugs. 45 (1): 79–93. doi:10.1080/02791072.2013.763570. PMID23662334. S2CID22086799.
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.
