Ergine

Ergine is most commonly used as a drug in the form of morning glory seeds, including those of Ipomoea tricolor (tlitliltzin), Ipomoea corymbosa (ololiuhqui), and Argyreia nervosa (Hawaiian baby woodrose). They may be consumed whole and intact, crushed or ground up, or drunk as an extract following soaking of the seeds in water.{{cite journal | vauthors = Halpern JH | title = Hallucinogens and dissociative agents naturally growing in the United States | journal = Pharmacol Ther | volume = 102 | issue = 2 | pages = 131–138 | date = May 2004 | pmid = 15163594 | doi = 10.1016/j.pharmthera.2004.03.003 | url = http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Neuropeptide%20S/Halpern%2004%20PharmacolTher%20Hallucinogens%20in%20plants.pdf | quote = 7. Lysergic acid amide –containing plants LSD is the best-known synthetic hallucinogen and is psychoactive at the microgram level. Although LSD does not occur in nature, a close analogue, lysergic acid amide (LSA, ‘‘ergine’’) is found in the seeds of Argyreia nervosa (Hawaiian baby woodrose) and Ipomoea violacea (morning glory). Hallucinogenic activity of LSA occurs with 2–5 mg, which provides a 4- to 8-hr intoxication that reportedly has quantitative as well as qualitative differences from LSD (Schultes & Hofmann, 1980). Seeds are crushed, germinated, eaten whole, or an extract is drunk after the seeds are soaked in water. Five to 10 seeds of Argyreia nervosa or 150–200 seeds (3–6 g) of Ipomoea violacea yield average doses of LSA (Al Assmar, 1999; Borsutzky et al., 2002). The LSA content of Argyreia nervosa is 0.14% by dry weight of seeds (Chao & Der Marderosian, 1973) and is 0.02% by dry weight in Ipomoea violacea seeds (Miller, 1970).}} A hallucinogenic dose (~0.5–1{{nbsp}}mg) is 150 to 200{{nbsp}}seeds (3–6{{nbsp}}g) of Ipomoea tricolor (0.02% ergine by dry weight) or 5 to 10{{nbsp}}seeds (0.5–1{{nbsp}}g) of Argyreia nervosa (0.14% ergine by dry weight).{{cite report | vauthors = Chen W, De Wit-Bos L | title=Risk assessment of Argyreia nervosa | date=2020 | doi=10.21945/rivm-2019-0210 | page= | quote = (Food supplements with) A. nervosa can be bought on internet as seeds or capsules; an average dose of A. nervosa can vary between 2 to 10 seeds (0.2–1 g) or 1 to 2 capsules (containing 75–300 mg seeds). Based on the assumptions that 1 gram seeds contains between 1.7–16 mg LSA + iso-LSA, this roughly results in an exposure to LSA + isoLSA in the range of 0.35-16 mg (seeds) or 0.13–4.8 mg (capsules). Taken together, this corresponds to 1.9–230 µg/kg bw for an individual weighing 70 kg. [...] Human volunteer studies [...] Heim, Heimann & Lukács (1968) conducted experiments with increasing doses of LSA (0.04 or 0.09 mg/kg bw [3–6 mg total]), iso-LSA (0.03, 0.06 or 0.07 mg/kg bw [2–5 mg total]), or total alkaloids from the drug Ololiuqui (Rivea corymbosa; 0.02, 0.06, 0.08 or 0.10 mg/kg bw) in healthy volunteers. [...] Ingestion of LSA led to nausea, vomiting, an illness-like state with general fatigue, sweating and dizziness, vision problems, slower movements and speech (a state of lethargy and apathy), beginning approximately 45 minutes after ingestion and becoming more pronounced over the next hours. [...] Based on these results, the authors suggest that the vegetative symptoms are probably caused by LSA while iso-LSA leads to impairment of the thinking ability and effects on a persons’ conscious (Heim, Heimann & Lukács, 1968). [...] Heim, E., Heimann, H., & Lukács, G., Die psychische Wirkung der mexikanischen Droge „Ololiuqui“ am Menschen. Psychopharmacologia, 1968. 13(1): p. 35-48. doi:10.1007/BF00401617 | url = https://www.rivm.nl/bibliotheek/rapporten/2019-0210.pdf}} The onset is 0.3 to 3{{nbsp}}hours and the duration is 4 to 10{{nbsp}}hours.

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 2{{nbsp}}mg dose by intramuscular or subcutaneous injection produced relatively weak but significant hallucinogenic effects as well as marked sedation.{{cite journal | vauthors = Soleil J, Lalloz L | title = Les Psychodysleptiques | trans-title = Psychodysleptics | journal = Produits et Problèmes Pharmaceutiques [Prod. Probl. Pharm.] | volume = 26 | issue = 11 | pages = 682–695, 757–767 | language = French | url = https://scholar.google.com/scholar?q=intitle%3A%22PSYCHODYSLEPTICS.+2.%22}}{{cite book | author = Albert Hofmann | chapter = The Discovery of LSD and Subsequent Investigations on Naturally Occurring Hallucinogens | pages = 96–106 | veditors = Ayd FJ, Blackwell B | title = Discoveries in Biological Psychiatry | date = 1970 | publisher = J.B. Lippincott Company | isbn = 978-0-397-59044-5 | chapter-url = https://erowid.org/references/texts/show/5090docid4880 | archive-url = https://catbull.com/alamut/Bibliothek/HOFMANN%20Albert/discovery/lsd.htm | archive-date = 30 March 2025 | url = https://books.google.com/books?id=auBsAAAAMAAJ | quote = Furthermore, the following minor alkaloids were isolated: isolysergic acid amide and isolysergic acid 1-hydroxyethylamide, chanoclavine, elymoclavine and lysergol. [...] Lysergic acid amide, the main component of ololiuqui, had been tested pharmacologically and clinically under the experimental drug designation LA-111 during the course of our investigations on LSD and related compounds long before it was known to be a natural component of a magic Mexican drug. Self-experiment and comparative systematic clinical investigations with Iysergic acid amide (laboratory code name: LA-111) revealed psychotomimetic effects significantly different from those of Iysergic acid diethylamide (LSD-25). The symptoms after oral ingestion of 1 mg to 2 mg of LA-111 were: indifference, decrease of psychomotor activity, tiredness, feeling of sinking into nothingness, and desire to sleep. Isolysergic amide produces similar symptoms. After taking 2.0 mg of isolysergic amide orally, I experienced tiredness, apathy, a feeling of mental emptiness and of the unreality and complete meaninglessness of the outside world.[11] These comparative experiments showed that the psychotomimetic constituents of ololiuqui are 20 to 40 times less active than LSD and that the general picture of activity is characterized by a pronounced depressive and narcotic component.}} Another study described the effects of pure ergine by injection but the doses were not clearly provided (although appeared to be around 0.1–1{{nbsp}}mg).{{cite journal | vauthors = Solms H | title = Relationships between chemical structure and psychoses with the use of psychotoxic substances; comparative pharmacopsychiatric analysis: a new research method | journal = Journal of Clinical and Experimental Psychopathology | volume = 17 | issue = 4 | pages = 429–433 | date = 1956 | pmid = 13406032 | url = https://bibliography.maps.org/resources/download/3888| archive-url = https://web.archive.org/web/20250328215101/https://bibliography.maps.org/resources/download/3888 | archive-date = 28 March 2025 }}{{cite journal | vauthors = Solms H | title = Chemische Struktur und Psychose bei Lysergsäure-Derivaten | trans-title = Chemical structure and lysergic acid derivative psychoses | language = German | journal = Praxis | volume = 45 | issue = 32 | pages = 746–749 | date = August 1956 | pmid = 13359249 | doi = | url = https://bibliography.maps.org/resources/download/20226| archive-url = https://web.archive.org/web/20250328215837/https://bibliography.maps.org/resources/download/20226 | archive-date = 28 March 2025 }} Based on the preceding studies, Alexander Shulgin describes pure ergine as having a dosage of 0.5 to 1{{nbsp}}mg and being 10-fold less potent than LSD, but as being "not hallucinogenic".{{cite book | vauthors = Shulgin AT | chapter=Basic Pharmacology and Effects | pages=67–137 | veditors = Laing RR | title=Hallucinogens: A Forensic Drug Handbook | publisher=Elsevier Science | series=Forensic Drug Handbook Series | year=2003 | isbn=978-0-12-433951-4 | url=https://books.google.com/books?id=l1DrqgobbcwC | chapter-url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 | access-date=1 February 2025 | quote = Table 3.23 Amide analogues and pyrrole derivatives of LSD [...] Code: LA-111. Potency (mg): 0.5–1. Potency (x-LSD): 0.1^a. [...] ^a sedative action or autonomic changes in humans; 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 of 3 to 6{{nbsp}}mg orally and observed toxic-like effects, whereas isoergine at 2 to 5{{nbsp}}mg orally produced notable hallucinogenic effects, including some euphoria, synaesthesia, and altered time perception.{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Indolealkylamines and Related Compounds | pages = 98–144 | title = Hallucinogenic Agents | date = 1975 | publisher = Wright-Scientechnica | location = Bristol | isbn = 978-0-85608-011-1 | oclc = 2176880 | ol = OL4850660M | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1}}

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.{{cite book | vauthors = DeKorne J |title=Psychedelic shamanism: the cultivation, preparation and shamanic use of psychotropic plants |publisher=Loompanics Unlimited |isbn=978-1-55950-110-1 |location=Port Townsend, Wash |page=81 |chapter=8. d-Lysergic Acid Amide: Morning Glory Seeds, Stipa robusta|date=1994 }}{{cite web | vauthors = Cole KA |date=17 August 2013 |title=Ergot Wine Revisited - YouTube |url=https://www.youtube.com/watch?v=IHWX0H8FIDo |publisher=Neurosoup|archive-url= https://web.archive.org/web/20210723133609/https://www.youtube.com/watch?v=IHWX0H8FIDo|archive-date=23 July 2021}}

Ergine has only been given a minuscule amount of attention. Albert Hofmann and his colleagues self-administered ergine. In addition, it was assessed in two clinical studies by other researchers.{{cite journal | vauthors = Heim E, Heimann H, Lukács G | title=Die psychische Wirkung der mexikanischen Droge "Ololiuqui" am Menschen | trans-title=Psychotomimetic effects of the mexican drug “Ololiuqui” | journal=Psychopharmacologia | volume=13 | issue=1 | date=1968 | issn=0033-3158 | doi=10.1007/BF00401617 | pages=35–48 | pmid=5675457 | language=de | url=https://bitnest.netfirms.com/external/10.1007/BF00401617}} Synthetic ergine was used in all of these cases. Hofmann stated that ergine induces a "psychotomimetic" effect with "a marked narcotic component": "Tired, dreamy, incapable of clear thoughts. Very sensitive to noises which give an unpleasant sensation." There are parallels between Hofmann's comments and the ones in the two trials:

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:{{Long quote | date = March 2025}}

"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."{{cite book | vauthors = Hofmann A |title=LSD, My Problem Child |date=1980 |publisher=McGraw-Hill |isbn=978-0-07-029325-0 |location=New York | url = https://www.shaman-australis.com/~pic/cs/lsdmyproblemchild.pdf | quote = A substance very closely related to LSD, the monoethylamide of lysergic acid (LAE23), 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 of this substance 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. [...] Lysergic acid amide was described for the first time by the English chemists S. Smith and G. M. Timmis as a cleavage product of ergot alkaloids, and I had also produced this substance synthetically in the course of the investigations in which LSD originated. Certainly, nobody at the time could have suspected that this compound synthesized in the flask would be discovered twenty years later as a naturally occurring active principle of an ancient Mexican magic drug. After the discovery of the psychic effects of LSD, I had also tested lysergic acid amide in a self-experiment and established that it likewise evoked a dreamlike condition, but only with about a tenfold to twenty-fold greater dose than LSD. This effect was characterized by a sensation of mental emptiness and the unreality and meaninglessness of the outer world, by enhanced sensitivity of hearing, and by a not unpleasant physical lassitude, which ultimately led to sleep. This picture of the effects of LA-111, as lysergic acid amide was called as a research preparation, was confirmed in a systematic investigation by the psychiatrist Dr. H. Solms.}}

"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."

While its physiological effects vary from person to person, the following symptoms have been attributed to the consumption of ergine or ergine containing seeds: sedation, visual hallucinations, auditory hallucinations, euphoria, loss of motor control, nausea, vasoconstriction, delusions, anxiety, paranoia, and irregular heartbeats.{{cite journal | vauthors = Kremer C, Paulke A, Wunder C, Toennes SW | title = Variable adverse effects in subjects after ingestion of equal doses of Argyreia nervosa seeds | journal = Forensic Science International | volume = 214 | issue = 1–3 | pages = e6–e8 | date = January 2012 | pmid = 21803515 | doi = 10.1016/j.forsciint.2011.06.025 }}

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.

A 2016 study showed that penniclavine was the predominant alkaloid in Ipomoea tricolor seeds. Ergoclavines are known to cause convulsive ergotism,{{cite journal | vauthors = Schardl CL, Panaccione DG, Tudzynski P | title = Ergot alkaloids--biology and molecular biology | journal = The Alkaloids. Chemistry and Biology | volume = 63 | pages = 45–86 (50) | date = 2006 | pmid = 17133714 | doi = 10.1016/s1099-4831(06)63002-2 | publisher = Elsevier | isbn = 978-0-12-469563-4 | quote = Clavines are thought to contribute substantially to convulsive ergotism, since C. fusiformis ergots, which possess clavines, but no [lysergic acid] or lysergyl amides, cause convulsive symptoms (26). However, the ergopeptines are known to produce similar symptoms, and are also thought to cause gangrenous ergotism (6). The occurrence of convulsive ergotism without dry gangrene suggests that other clavine or lysergyl alkaloids are involved, or that individual effects of specific ergopeptines may give clinically different syndromes (6). }} the milder form of ergotism. Gangrenous ergotism is caused by ergopeptines: the complex peptide moiety forces persistence at the receptor sites. Ergopeptines are rare in Convolvulaceae, being found in 10 species,{{cite book | vauthors = Eich E |url=https://link.springer.com/book/10.1007/978-3-540-74541-9 |title=Solanaceae and convolvulaceae - secondary metabolites: biosynthesis, chemotaxonomy, biological and economic significance: a handbook |publisher=Springer-Verlag |isbn=978-3-540-74540-2 |location=Berlin, Heidelberg |date=January 12, 2008 |language=En |chapter=4.2 Ergolines |doi=10.1007/978-3-540-74541-9 |oclc=195613136 |pages=225–227,236,238,249,274|quote=Containing ergosine: Argyreia luzonensis, A. mollis, A. obtusifolia, A. philippinensis, A. ridleyi, A. splendens [...] Ipomoea argyrophylla (ergosine and ergobalansine) [...] Table 4.1 Unambiguously ergoline-positive Ipomoea species [...] Table 4.4 Unambiguously ergoline-positive Argyreia species [...]}}{{cite journal | vauthors = Beaulieu WT, Panaccione DG, Hazekamp CS, mckee MC, Ryan KL, Clay K | title = Differential allocation of seed-borne ergot alkaloids during early ontogeny of morning glories (Convolvulaceae) | journal = Journal of Chemical Ecology | volume = 39 | issue = 7 | pages = 919–930 | date = July 2013 | pmid = 23835852 | doi = 10.1007/s10886-013-0314-z | bibcode = 2013JCEco..39..919B | quote = Ipomoea amnicola and I. argillicola contain ergobalansine [...]}} not including the three that are commonly ingested, although Paulke 2014 says analytical evidence suggests that A. nervosa contains ergopeptines.{{cite journal | vauthors = Paulke A, Kremer C, Wunder C, Wurglics M, Schubert-Zsilavecz M, Toennes SW | title = Studies on the alkaloid composition of the Hawaiian Baby Woodrose Argyreia nervosa, a common legal high | journal = Forensic Science International | volume = 249 | pages = 281–293 | date = April 2015 | pmid = 25747328 | doi = 10.1016/j.forsciint.2015.02.011 | quote = On the other hand, methylergometrine, methysergide, and lysergylalanine were detected, which have not yet been reported as compounds of Argyreia nervosa seeds. Furthermore, some high molecular weight ergot alkaloid derivatives and hydroxyalanine derived ergopeptide fragments could be observed at various retention times (c.f. chapter 3.1). Altogether, lysergylalanine, the high molecular weight ergot alkaloids and the hydroxyalanine derived ergopeptide fragments strongly suggest the presence of ergopeptides in Argyreia nervosa. However, due to the disadvantage of the applied APCI technique for peptide analysis (c.f. chapter 3.1) additional research (e.g. ESI-HRMS/MS) will be necessary to verify this assumption and to elucidate the structure of the ergopeptides." (3. Results and discussion, p. 283) [...]}} Many people desire purified seed extracts, but the efficacy of this is questionable, as even pure ergine and ergonovine have shown toxic effects.

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, [...]".{{cite journal | vauthors = Bigwood J, Ott J, Thompson C, Neely P | title = Entheogenic effects of ergonovine | journal = Journal of Psychedelic Drugs | volume = 11 | issue = 1–2 | pages = 147–149 | date = January 1979 | pmid = 522166 | doi = 10.1080/02791072.1979.10472099 | url = https://bibliography.maps.org/resources/download/12845| archive-url = https://web.archive.org/web/20250328185507/https://bibliography.maps.org/resources/download/12845 | archive-date = 28 March 2025 }}

Like other psychedelics, ergine is not considered to be addictive. Additionally, there are no known deaths directly associated with pharmacological effects of ergine consumption. All associated deaths are due to indirect causes, such as self-harm, impaired judgement, and adverse drug interactions. One known case involved a suicide that was reported in 1964 after ingestion of morning glory seeds.{{cite journal | vauthors = Cohen S | title = Suicide Following Morning Glory Seed Ingestion | journal = The American Journal of Psychiatry | volume = 120 | issue = 1 | pages = 1024–1025 | date = April 1964 | pmid = 14138842 | doi = 10.1176/ajp.120.10.1024 }} Another instance is a death due to falling off of a building after ingestion of Hawaiian baby woodrose seeds and alcohol.{{cite journal | vauthors = Klinke HB, Müller IB, Steffenrud S, Dahl-Sørensen R | title = Two cases of lysergamide intoxication by ingestion of seeds from Hawaiian Baby Woodrose | journal = Forensic Science International | volume = 197 | issue = 1–3 | pages = e1–e5 | date = April 2010 | pmid = 20018470 | doi = 10.1016/j.forsciint.2009.11.017 }} A study gave mice 3000{{nbsp}}mg/kg with no lethal effects.{{Citation needed | date = February 2024}}

Garden seeds, in general, may be coated with fungicides et. al. (e.g. neonicotinoids, Thiram, and ApronMaxx). It is rumored that this is the cause of the severe adverse effects that have been observed, but the seeds, themselves, contain toxins, specifically glycoresins{{cite book |url=https://books.google.com/books?id=yr_PznYrdEUC |title=Chemistry in Botanical Classification: Medicine and Natural Sciences: Medicine and Natural Sciences |publisher=Elsevier |isbn=978-0-323-16251-7 | veditors = Bendz G, Santesson J |date=2013-10-14 |language=en | page=235 | quote=Among the most striking characteristics of the family is the occurrence of rows of secretory cells with milky, resinous contents. Resin glycosides are among the most important chemical characteristics of the family. The occurrence of tropine alkaloids in Convolvulus species and lysergic acid type alkaloids in Ipomoea and Rivea species as well as a wide distribution of cinnamic acid derivatives and coumarins are also noteworthy. The last two groups of compounds are common to both the Convolvulaceae and Solanaceae families. |orig-date=1973 }}{{cite journal | vauthors = Ono M | title = Resin glycosides from Convolvulaceae plants | journal = Journal of Natural Medicines | volume = 71 | issue = 4 | pages = 591–604 | date = October 2017 | pmid = 28748432 | pmc = 6763574 | doi = 10.1007/s11418-017-1114-5 }} and ergoclavines. Some{{Who|date=March 2025}} even believe that an emetic chemical is purposely added to the seeds to prevent people from ingesting them, but that has never been proven.{{Citation needed|date=March 2025}} One 1964 article states that reported adverse effects must come from the seeds, as the stated insecticide is too "inocuous" to humans to be responsible.{{cite journal | vauthors = Ingram AL | title = Morning Glory Seed Reaction | journal = JAMA | volume = 190 | issue = 13 | pages = 1133–1134 | date = December 1964 | pmid = 14212309 | doi = 10.1001/jama.1964.03070260045019 | quote = It has been suggested⁶ that the insecticide coating on the morning glory seed might be promoting adverse side effects that have been noted. The majority of commercial seeds are treated with N-tri-chlorete which is a fungicide and seed protectant having a tolerance of 100 parts per million.⁸ Thus, this is quite an inocuous product from the toxicologic point of view and would require ingestion of quantities beyond the capacity of the stomach to absorb, in amounts found as a seed coater, to be considered lethal.⁹ Symptoms involving the nervous system would be lacking if we were dealing only with the effects of this fungicide. Formerly, compounds containing mercury were used extensively as fungicides and there is the possibility that some seeds so treated might pose a toxicologic danger if ingested. This is considered unlikely as the newer seed protectants have been in use for a considerably longer period than the current morning glory fad. [...] It would seem then, that both the psychological and physiological effects observed in the ingestion of the seed of the morning glory reside in the alkaloids of the seed and not the seed protectant. The LSD-like reaction is most likely due to the LSD-like alkaloids for no pure LSD has as yet been isolated from the seed. As all compounds occurring in the morning glory seed have not been studied intensively enough to inspire confidence in their respective roles, they cannot yet be considered for scientific experimental use much less be used irresponsibly in excitement-seeking self-experimentation.) }}{{cite book | vauthors = Frear DE | title = Pesticide Handbook | location = State College, Pa | publisher = College Science Publishers | date = 1963 | page = 8 }}

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,Peter Jordan. Re: Woodrose vs Ipomoea. alt.drugs, UseNet, 10/1/1994 https://erowid.org/plants/hbw/hbw_info1.shtml 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",{{cite book |title=The First Book of Sacraments of the Church of the Tree of Life: A Guide for the Religious Use of Legal Mind Alterants |publisher=Tree of Life Press |year=1973 | veditors = Mann J |location=San Francisco, CA |page=13 |quote=The standard procedure is to scrape or singe the white layer from the seed coat before grinding. This layer is believed to contain a strychnine-like alkaloid which may cause undesirable symptoms.}} but that is probably just a misapplication of the claim that peyote contains strychnine, which, itself, is a rumor.{{cite book | vauthors = Pendell D |title=Pharmako/Gnosis: Plant Teachers and the Poison Path |publisher=North Atlantic Books | date = 28 September 2010 |isbn=9781556438042 |edition=Revised and Updated |pages=106 |orig-date=2005 |quote=To put one persistent myth to rest, there is no strychnine in peyote. The white fuzz that is usually removed from the buttons before ingestion can be a gastroirritant, but it does not contain strychnine. However, lophophorine, accounting for about 0.18% of the dry weight of the buttons, can cause some symptoms similar to strychnine poisoning, such as a sickening feeling in the back of the head, and hotness and blushing of the face. Lophophorine causes violent convulsions when injected into rabbits at concentrations of 12 milligrams per kilogram of body weight.}}

Cases of overdose of ergine and morning glory seeds and associated toxicity have been reported.

{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

The interactions of ergine and of morning glory seeds have been discussed.

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-HT_2A and 5-HT_2B receptors similarly to LSD, albeit much less potently and with reduced activational efficacy. The drug has about 4.3% of the antiserotonergic activity of LSD in the isolated rat uterus in vitro.{{cite web | vauthors = Oberlender RA | title=Stereoselective aspects of hallucinogenic drug action and drug discrimination studies of entactogens | publisher=Purdue University | website=Purdue e-Pubs | date=May 1989 | url=https://bitnest.netfirms.com/external/Theses/Oberlender1989#page=49 | quote=Table 2. Relative potency values for lysergic acid amides. [...]}}{{cite journal | vauthors = Cerletti A, Doepfner W | title = Comparative Study on the Serotonin Antagonism of Amide Derivatives of Lysergic Acid and of Ergot Alkaloids | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 122 | issue = 1 | pages = 124–136 | date = January 1958 | pmid = 13502837 | doi = 10.1016/S0022-3565(25)11933-2 | url = https://bibliography.maps.org/resources/download/19096 | archive-url = https://web.archive.org/web/20250325115812/https://bibliography.maps.org/resources/download/19096 | archive-date = 25 March 2025 | quote = TABLE 1 Antiserotonin. potency of 16 amide-derivatives of d-lysergic acid [...]}} The psychedelic effects of ergine can be attributed to activation of serotonin 5-HT_2A receptors.{{cite book| vauthors = Halberstadt AL, Nichols DE |title=Handbook of the Behavioral Neurobiology of Serotonin|chapter=Serotonin and serotonin receptors in hallucinogen action|series=Handbook of Behavioral Neuroscience|volume=31|year=2020|pages=843–863|issn=1569-7339|doi=10.1016/B978-0-444-64125-0.00043-8|isbn=9780444641250}}{{cite journal | vauthors = Kelmendi B, Kaye AP, Pittenger C, Kwan AC | title = Psychedelics | journal = Curr Biol | volume = 32 | issue = 2 | pages = R63–R67 | date = January 2022 | pmid = 35077687 | pmc = 8830367 | doi = 10.1016/j.cub.2021.12.009 | bibcode = 2022CBio...32..R63K | url = https://www.cell.com/action/showPdf?pii=S0960-9822%2821%2901685-7}}{{cite book | vauthors = Nichols DE | title = Chemistry and Structure-Activity Relationships of Psychedelics | series = Current Topics in Behavioral Neurosciences | volume = 36 | pages = 1–43 | date = 2018 | pmid = 28401524 | doi = 10.1007/7854_2017_475 | isbn = 978-3-662-55878-2 | url = https://bitnest.netfirms.com/external/10.1007/7854_2017_475}}

{{See also|Lysergamides}}

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 structure of this family of compounds. Hence, all lysergamides are derivatives of ergine. Lysergic acid diethylamide (LSD) is the analogue of ergine with two ethyl groups substituted on its amide moiety.

The extraction of ergine from morning glory seeds has been described.{{cite journal | vauthors = Shanks KS | title = Clandestine Extraction of Lysergic Acid Amide (LSA) From Morning Glory Seeds | journal = Journal of the Clandestine Laboratory Investigating Chemists Association | volume = 11 | number = 2 | date = April 2001 | pages = 15–17 | url = https://bitnest.netfirms.com/external/JCLIC/11.2.15-17}}{{cite web | author = Soma Graphics | title = Simple Extraction Methods of LA-111 From Argyreia and Ipomoea Species | date = January 1996 | publisher = Soma Graphics | url = https://bibliography.maps.org/resources/download/13338| archive-url = https://web.archive.org/web/20250328221536/https://bibliography.maps.org/resources/download/13338 | archive-date = 28 March 2025 }}

Ergine is not a biosynthetic endpoint itself, but rather a hydrolysis product of lysergic acid hydroxyethylamide (LSH), lysergic acid propanolamide (ergonovine), and ergopeptines or their ergopeptam precursors.{{cite journal | vauthors = Flieger M, Sedmera P, Vokoun J, ((R̆ic̄icovā A)), ((R̆ehác̆ek Z)) |date=1982-02-19 |title=Separation of four isomers of lysergic acid α-hydroxyethylamide by liquid chromatography and their spectroscopic identification |url=https://linkinghub.elsevier.com/retrieve/pii/S0021967300848955 |journal=Journal of Chromatography A |volume=236 |issue=2 |pages=441–452 |doi=10.1016/S0021-9673(00)84895-5 |issn=0021-9673}}{{cite journal | vauthors = Ramstad E |date=1968 |title=Chemistry of alkaloid formation in ergot |journal=Lloydia |volume=31 |pages=327–341}}{{cite journal | vauthors = Kleinerová E, Kybal J | title = Ergot alkaloids. IV. Contribution to the biosynthesis of lysergic acid amides | journal = Folia Microbiologica | volume = 18 | issue = 5 | pages = 390–392 | pmid = 4757982 | doi = 10.1007/BF02875934 | date = September 1973 }}{{cite journal | vauthors = Panaccione DG, Tapper BA, Lane GA, Davies E, Fraser K | title = Biochemical outcome of blocking the ergot alkaloid pathway of a grass endophyte | journal = Journal of Agricultural and Food Chemistry | volume = 51 | issue = 22 | pages = 6429–6437 | pmid = 14558758 | doi = 10.1021/jf0346859 | bibcode = 2003JAFC...51.6429P | date = 1 October 2003}}{{cite book | vauthors = Panaccione DG | chapter = Ergot alkaloids | title = The Mycota, Industrial Applications | edition = 2nd | veditors = Hofrichter M | publisher = Springer-Verlag | location = Berlin-Heidelburg, Germany | date = 2010 | volume = 10 | pages = 195–214 }}

LSH is very vulnerable to this hydrolysis,{{cite book | veditors=Gordon M | title=Psychopharmacological Agents: Use, Misuse and Abuse | series=Medicinal Chemistry: A Series of Monographs | volume=4 | vauthors = Shulgin AT | chapter=Psychotomimetic Agents | date=1976 | isbn=978-0-12-290559-9 | doi=10.1016/b978-0-12-290559-9.50011-9 | pages=59–146 | publisher=Academic Press | url=https://bitnest.netfirms.com/external/10.1016/B978-0-12-290559-9.50011-9 | quote=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. [...] The human pharmacology of ergine, interestingly, predates its discovery as a major component in the Convolvulaceae. Following the discovery of the high potency of LSD, a large number of analogs were prepared at the Sandoz Laboratories, and many of these assayed in limited clinical experiments. Hofmann (1963a) has described the psychopharmacology of both ergine and isoergine. Following an i.m. 500-μg dose of ergine there was nausea, followed by a narcotic-like physical and mental fatigue with a high sensitivity to noises. These effects developed in about an hour, and were followed by a period of sleep; in 5 hours there was complete return to the normal state. A similar sedative-hypnotic course of activity was reported by Solms (1956a,b) in which his subjects displayed a decrease of psychomotor activity, a feeling of sinking into nothingness, a desire to sleep, followed by sleep itself. [...] It appears that the agents that are responsible for the human activity of these plants are ergine and isoergine, and possibly the corresponding α-hydroxyethylamides of lysergic acid which could serve as metabolic precursors. [...] It was in the summer of 1963 that the biological potential of morning glory seeds became widely broadcast throughout a very drug-conscious youth group, and within weeks every major news vehicle gave this “new problem” wide coverage. There were a number of notes in medical journals in the following months concerning toxicity cases, but in general, the fad quickly died out.}}{{cite book | vauthors = Schultes RE, Hofmann A |title=The Botany and Chemistry of Hallucinogens |publisher=Charles Thomas |year=1973 |isbn=9780398064167 |location=Springfield, IL |pages=246,252 |quote=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.}} and many analyses of ergoline-containing fungi show little to no LSH and substantial amounts of ergine.

An ergine analog, 8-hydroxyergine, has also been found in natural products in two studies.{{cite journal | vauthors = Flieger M, Linhartová R, Sedmera P, Zima J, Sajdl P, Stuchlík J, Cvak L |title=New Alkaloids of Claviceps paspali |url=https://pubs.acs.org/doi/abs/10.1021/np50065a014 |journal=Journal of Natural Products |language=en |date=September 1, 1989 |volume=52 |issue=5 |pages=1003–1007 |doi=10.1021/np50065a014 |bibcode=1989JNAtP..52.1003F |issn=0163-3864}}{{cite journal | vauthors = Petroski RJ, Powell RG, Clay K | title = Alkaloids of Stipa robusta (sleepygrass) infected with an Acremonium endophyte | journal = Natural Toxins | volume = 1 | issue = 2 | pages = 84–88 | pmid = 1344912 | doi = 10.1002/nt.2620010205 | date = March–April 1992 | quote = 8-Hydroxylysergic acid amide was isolated with difficulty as it was present as only a minor alkaloid in endophyte-infected sleepygrass (0.3 pg/g dry wt).}} 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,{{cite journal | vauthors = Arcamone F, Bonino C, Chain EB, Ferretti A, Pennella P, Tonolo A, Vero L | title = Production of lysergic acid derivatives by a strain of Claviceps paspali Stevens and Hall in submerged culture | journal = Nature | volume = 187 | issue = 4733 | pages = 238–239 | date = July 1960 | pmid = 13794048 | doi = 10.1038/187238a0 | bibcode = 1960Natur.187..238A }}{{cite journal | vauthors = Castagnoli N, Corbett K, Chain EB, Thomas R | title = Biosynthesis of N-(alpha-hydroxyethyl) lysergamide, a metabolite of Claviceps paspali Stevens and Hall | journal = The Biochemical Journal | volume = 117 | issue = 3 | pages = 451–455 | date = April 1970 | pmid = 5419742 | pmc = 1178946 | doi = 10.1042/bj1170451 }}{{cite journal | vauthors = Basmadjian G, Floss HG, Gröger D, Erge D |date=1969 |title=Biosynthesis of ergot alkaloids. Lysergylalanine as precursor of amide-type alkaloids |url=https://xlink.rsc.org/?DOI=C29690000418 |journal=J. Chem. Soc. D |language=en |issue=8 |pages=418–419 |doi=10.1039/C29690000418 |issn=0577-6171}} but are only found in trace amounts in the more well-known Claviceps purpurea.{{cite book | vauthors = Schultes R |title=The Botany and Chemistry of Hallucinogens |publisher=Charles Thomas |year=1973 |isbn=9780398064167 |location=Springfield, IL |language=En | chapter = 4. Plants of Hallucinogenic Use / The Fungi | page = 37 }}{{cite book | vauthors = Wasson RG, Hofmann A, Ruck CA, Webster P |url=https://books.google.com/books?id=7JC7EAAAQBAJ&pg=PA42 |title=The Road to Eleusis: Unveiling the Secret of the Mysteries |publisher=North Atlantic Books |isbn=978-1-55643-752-6 | veditors = Forte R |edition=30th Anniversary |location=Berkeley, Calif. |date=November 25, 2008 |orig-date=1978 |language=En | pages=42,44}} Both are ergot-spreading fungi. The major products of C. purpurea are ergopeptines, but C. paspali does not generate ergopeptines.{{cite book | vauthors = Panaccione DG | chapter = Ergot alkaloids | title = The Mycota, Industrial Applications | edition = 2nd | veditors = Hofrichter M | publisher = Springer-Verlag | location = Berlin-Heidelburg, Germany | date = 2010 | volume = 10 | pages = 195–214 }} Ergonovine is the only lysergamide in C. purpurea in a substantial amount.

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{{cite book | vauthors = Leistner E, Steiner U | chapter = The Genus Periglandula and Its Symbiotum with Morning Glory Plants (Convolvulaceae) |date=February 3, 2018 | veditors = Anke T, Schüffler A | title = Physiology and Genetics |pages=131–147 |chapter-url= http://link.springer.com/10.1007/978-3-319-71740-1_5 |access-date=2024-11-21 |place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/978-3-319-71740-1_5 |isbn=978-3-319-71739-5 }} (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.{{cite journal | vauthors = Nowak J, Woźniakiewicz M, Klepacki P, Sowa A, Kościelniak P | title = Identification and determination of ergot alkaloids in Morning Glory cultivars | journal = Analytical and Bioanalytical Chemistry | volume = 408 | issue = 12 | pages = 3093–3102 | date = May 2016 | pmid = 26873205 | pmc = 4830885 | doi = 10.1007/s00216-016-9322-5 | postscript = 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.

Other fungi that have been found to contain LSH and/or ergine:

• Unidentified Acremonium species that infects sleepy grass (C. purpurea also infects sleepy grass{{cite journal | vauthors = Alderman SC, Halse RR, White JF | title = A Reevaluation of the Host Range and Geographical Distribution of Claviceps Species in the United States | journal = Plant Disease | volume = 88 | issue = 1 | pages = 63–81 | date = January 2004 | pmid = 30812458 | doi = 10.1094/PDIS.2004.88.1.63 | bibcode = 2004PlDis..88...63A }}).
• Unidentified Acremonium species that infects drunken horse grass{{cite journal | vauthors = Miles CO, Lane GA, di Menna ME, Garthwaite I, Piper EL, Ball OJ, Latch GC, Allen JM, Hunt MB, Bush LP, Min FK |date=1996-05-16 |title=High Levels of Ergonovine and Lysergic Acid Amide in Toxic Achnatherum inebrians Accompany Infection by an Acremonium -like Endophytic Fungus |url=https://pubs.acs.org/doi/10.1021/jf950410k |journal=Journal of Agricultural and Food Chemistry |language=en |volume=44 |issue=5 |pages=1285–1290 |doi=10.1021/jf950410k |bibcode=1996JAFC...44.1285M |issn=0021-8561}}
• Acremonium coenophialum (infects Festuca arundinacea){{cite book | vauthors = Petroski RJ, Powell RG |chapter=Preparative Separation of Complex Alkaloid Mixture by High-Speed Countercurrent Chromatography | veditors = Hedin PA |title=Naturally Occurring Pest Bioregulators |date=1991-01-09 |publisher=American Chemical Society |isbn=978-0-8412-1897-0 |series=ACS Symposium Series |volume=449 |pages=426–434 |location=Washington, DC |language=en |doi=10.1021/bk-1991-0449.ch031 }}
• Epichloë gansuensis var. inebriens (infects drunken horse grass){{cite journal | vauthors = Chen L, Li X, Li C, Swoboda GA, Young CA, Sugawara K, Leuchtmann A, Schardl CL | title = Two distinct Epichloë species symbiotic with Achnatherum inebrians, drunken horse grass | journal = Mycologia | volume = 107 | issue = 4 | pages = 863–873 | pmid = 25911697 | doi = 10.3852/15-019 | date = July 2015 }}
• Metarhizium brunneum{{cite journal | vauthors = Leadmon CE, Sampson JK, Maust MD, Macias AM, Rehner SA, Kasson MT, Panaccione DG | title = Several Metarhizium Species Produce Ergot Alkaloids in a Condition-Specific Manner | journal = Applied and Environmental Microbiology | volume = 86 | issue = 14 | date = July 2020 | pmid = 32385081 | pmc = 7357478 | doi = 10.1128/AEM.00373-20 | bibcode = 2020ApEnM..86E.373L | veditors = Alexandre G }}
• Metarhizium acridum
• Metarhizium anisopliae
• Metarhizium flavoviride
• Metarhizium robertsii
• Aspergillus leporis{{cite journal | vauthors = Jones AM, Steen CR, Panaccione DG | title = Independent Evolution of a Lysergic Acid Amide in Aspergillus Species | journal = Applied and Environmental Microbiology | volume = 87 | issue = 24 | pages = e0180121 | date = November 2021 | pmid = 34586904 | pmc = 8612279 | doi = 10.1128/AEM.01801-21 | bibcode = 2021ApEnM..87E1801J | veditors = Atomi H }}
• Aspergillus homomorphus
• Aspergillus hancockii

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):

• Claviceps hirtella{{cite journal | vauthors = Lorenz N, Haarmann T, Pazoutová S, Jung M, Tudzynski P | title = The ergot alkaloid gene cluster: functional analyses and evolutionary aspects | journal = Phytochemistry | volume = 70 | issue = 15–16 | pages = 1822–1832 | pmid = 19695648 | doi = 10.1016/j.phytochem.2009.05.023 | series = Evolution of Metabolic Diversity | bibcode = 2009PChem..70.1822L | date = 2009-10-01 }}
• Neotyphodium lolii
• Unidentified Epichlöe and Neotyphodium (asexual forms of Epichlöe) species{{cite journal | vauthors = Schardl CL, Leuchtmann A, Spiering MJ | title = Symbioses of grasses with seedborne fungal endophytes | journal = Annual Review of Plant Biology | volume = 55 | issue = 1 | pages = 315–340 | pmid = 15377223 | doi = 10.1146/annurev.arplant.55.031903.141735 | date = 2004-06-02 | bibcode = 2004AnRPB..55..315S }}
• Aspergillus fumigata{{cite book | vauthors = Kozlovsky AG |title=Ergot: The Genus Claviceps |publisher=Harwood Academic Publishers |year=2006 |isbn=978-90-5702-375-0 | veditors = Křen V, Cvak L |series=Medicinal and aromatic plants - industrial profiles |location=London |language=En |chapter=18. Producers of ergot alkaloids out of Claviceps genus }}
• Aspergillus flavus
• Botritis fabae
• Curvularia lunata
• Geotrichum candidum
• Balansia cyperi
• Balansia claviceps
• Balansia epichloë
• Epichloë amarillans{{cite journal | vauthors = Schardl CL, Young CA, Hesse U, Amyotte SG, Andreeva K, Calie PJ, Fleetwood DJ, Haws DC, Moore N, Oeser B, Panaccione DG, Schweri KK, Voisey CR, Farman ML, Jaromczyk JW, Roe BA, O'Sullivan DM, Scott B, Tudzynski P, An Z, Arnaoudova EG, Bullock CT, Charlton ND, Chen L, Cox M, Dinkins RD, Florea S, Glenn AE, Gordon A, Güldener U, Harris DR, Hollin W, Jaromczyk J, Johnson RD, Khan AK, Leistner E, Leuchtmann A, Li C, Liu J, Liu J, Liu M, Mace W, Machado C, Nagabhyru P, Pan J, Schmid J, Sugawara K, Steiner U, Takach JE, Tanaka E, Webb JS, Wilson EV, Wiseman JL, Yoshida R, Zeng Z | title = Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the clavicipitaceae reveals dynamics of alkaloid loci | journal = PLOS Genetics | volume = 9 | issue = 2 | pages = e1003323 | pmid = 23468653 | pmc = 3585121 | doi = 10.1371/journal.pgen.1003323 | date = 2013-02-28 | doi-access = free | veditors = Heitman J }}
• Epichloë cabralii (H){{cite journal | vauthors = Charlton ND, Craven KD, Afkhami ME, Hall BA, Ghimire SR, Young CA | title = Interspecific hybridization and bioactive alkaloid variation increases diversity in endophytic Epichloë species of Bromus laevipes | journal = FEMS Microbiology Ecology | volume = 90 | issue = 1 | pages = 276–289 | date = October 2014 | pmid = 25065688 | doi = 10.1111/1574-6941.12393 | bibcode = 2014FEMME..90..276C }}
• Epichloë canadensis (H){{cite journal | vauthors = Schardl CL, Young CA, Pan J, Florea S, Takach JE, Panaccione DG, Farman ML, Webb JS, Jaromczyk J, Charlton ND, Nagabhyru P, Chen L, Shi C, Leuchtmann A | title = Currencies of mutualisms: sources of alkaloid genes in vertically transmitted epichloae | journal = Toxins | volume = 5 | issue = 6 | pages = 1064–1088 | date = June 2013 | pmid = 23744053 | pmc = 3717770 | doi = 10.3390/toxins5061064 | doi-access = free}}{{cite journal | vauthors = Charlton ND, Craven KD, Mittal S, Hopkins AA, Young CA | title = Epichloe canadensis, a new interspecific epichloid hybrid symbiotic with Canada wildrye (Elymus canadensis) | journal = Mycologia | volume = 104 | issue = 5 | pages = 1187–1199 | pmid = 22675049 | doi = 10.3852/11-403 | date = Sep–Oct 2012 }}
• Epichloë coenophiala (H){{cite journal | vauthors = Takach JE, Mittal S, Swoboda GA, Bright SK, Trammell MA, Hopkins AA, Young CA | title = Genotypic and chemotypic diversity of Neotyphodium endophytes in tall fescue from Greece | journal = Applied and Environmental Microbiology | volume = 78 | issue = 16 | pages = 5501–5510 | date = August 2012 | pmid = 22660705 | pmc = 3406137 | doi = 10.1128/AEM.01084-12 | bibcode = 2012ApEnM..78.5501T }}{{cite journal | vauthors = Hanigan MH, Ricketts WA | title = Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase | journal = Biochemistry | volume = 32 | issue = 24 | pages = 6302–6306 | date = June 1993 | pmid = 8099811 | doi = 10.1021/bi00075a026 }}
• Epichloë festucae
• Epichloë festucae var. lolii{{cite journal | vauthors = Fleetwood DJ, Scott B, Lane GA, Tanaka A, Johnson RD | title = A complex ergovaline gene cluster in epichloe endophytes of grasses | journal = Applied and Environmental Microbiology | volume = 73 | issue = 8 | pages = 2571–2579 | date = April 2007 | pmid = 17308187 | pmc = 1855613 | doi = 10.1128/AEM.00257-07 | bibcode = 2007ApEnM..73.2571F}}{{cite journal | vauthors = Fleetwood DJ, Khan AK, Johnson RD, Young CA, Mittal S, Wrenn RE, Hesse U, Foster SJ, Schardl CL, Scott B | title = Abundant degenerate miniature inverted-repeat transposable elements in genomes of epichloid fungal endophytes of grasses | journal = Genome Biology and Evolution | volume = 3 | pages = 1253–1264 | pmid = 21948396 | pmc = 3227409 | doi = 10.1093/gbe/evr098 | date = 2011-01-01 }}
• Epichloë festucae var. lolii x E. typhina (H){{cite journal | vauthors = Panaccione DG, Johnson RD, Wang J, Young CA, Damrongkool P, Scott B, Schardl CL | title = Elimination of ergovaline from a grass-Neotyphodium endophyte symbiosis by genetic modification of the endophyte | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 22 | pages = 12820–12825 | date = October 2001 | pmid = 11592979 | pmc = 60137 | doi = 10.1073/pnas.221198698 | doi-access = free | bibcode = 2001PNAS...9812820P}}
• Epichloë inebriens
• Epichloë glyceriae
• Epichloë mollis
• Epichloë typhina
• Epichloë typhina ssp. poae
• Epichloë typhina ssp. clarkii{{cite journal | vauthors = Young CA, Schardl CL, Panaccione DG, Florea S, Takach JE, Charlton ND, Moore N, Webb JS, Jaromczyk J | title = Genetics, genomics and evolution of ergot alkaloid diversity | journal = Toxins | volume = 7 | issue = 4 | pages = 1273–1302 | date = April 2015 | pmid = 25875294 | pmc = 4417967 | doi = 10.3390/toxins7041273 | doi-access = free}}

See table 3 on p. 1290.

• Epichloë{{nbsp}}sp. AroTG-2(H){{cite journal | vauthors = Shymanovich T, Saari S, Lovin ME, Jarmusch AK, Jarmusch SA, Musso AM, Charlton ND, Young CA, Cech NB, Faeth SH | title = Alkaloid variation among epichloid endophytes of sleepygrass (Achnatherum robustum) and consequences for resistance to insect herbivores | journal = Journal of Chemical Ecology | volume = 41 | issue = 1 | pages = 93–104 | date = January 2015 | pmid = 25501262 | doi = 10.1007/s10886-014-0534-x | bibcode = 2015JCEco..41...93S | url = http://libres.uncg.edu/ir/uncg/f/S_Faeth_Alkaloid_2015.pdf}}
• Epichloë sp. FaTG-2(H){{cite journal | vauthors = Christensen M, Leuchtmann A, Rowan D, Tapper B |date=1993-09-01 |title=Taxonomy of Acremonium endophytes of tall fescue (Festuca arundinacea), meadow fescue (F. pratensis) and perennial ryegrass (Lolium perenne) |url=https://linkinghub.elsevier.com/retrieve/pii/S0953756209805091 |journal=Mycological Research |language=en |volume=97 |issue=9 |pages=1083–1092 |doi=10.1016/S0953-7562(09)80509-1}}{{cite journal | vauthors = Panaccione DG, Johnson RD, Wang J, Young CA, Damrongkool P, Scott B, Schardl CL | title = Elimination of ergovaline from a grass-Neotyphodium endophyte symbiosis by genetic modification of the endophyte | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 22 | pages = 12820–12825 | date = October 2001 | pmid = 11592979 | pmc = 60137 | doi = 10.1073/pnas.221198698 | doi-access = free | bibcode = 2001PNAS...9812820P}}
• Epichloë sp. FaTG-4(H){{cite journal | vauthors = Young CA, Charlton ND, Takach JE, Swoboda GA, Trammell MA, Huhman DV, Hopkins AA | title = Characterization of Epichloë coenophiala within the US: are all tall fescue endophytes created equal? | journal = Frontiers in Chemistry | volume = 2 | pages = 95 | pmid = 25408942 | pmc = 4219521 | doi = 10.3389/fchem.2014.00095 | date = 2014-11-04 | doi-access = free | bibcode = 2014FrCh....2...95Y }}
• Hypomyces aurantius
• Sepedonium sp.
• Cunnigbamella blakesleana
• Mucor biemalis
• Rhizopus nigricans

File:Ergine_biosynthesis_part_1_(fixed).png

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.{{cite journal | vauthors = Gerhards N, Neubauer L, Tudzynski P, Li SM | title = Biosynthetic pathways of ergot alkaloids | journal = Toxins | volume = 6 | issue = 12 | pages = 3281–3295 | date = December 2014 | pmid = 25513893 | pmc = 4280535 | doi = 10.3390/toxins6123281 | doi-access = free }} 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). 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.{{cite journal| vauthors = Willingale J, Atwell SM, Mantle PG |date=1983-07-01|title=Unusual Ergot Alkaloid Biosynthesis in Sclerotia of a Claviceps purpurea Mutant|journal=Microbiology|volume=129|issue=7|pages=2109–2115|doi=10.1099/00221287-129-7-2109|issn=1350-0872|doi-access=free}}

File:Ergine_biosynthesis_part_2.png

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. 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. 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.

File:Ergine_biosynthesis_part_3.png

Ergine was first obtained by Sidney Smith and Geoffrey Willward Timmis in 1932.{{cite journal | vauthors = Smith S, Timmis GM |date=1932 |title=98. The alkaloids of ergot. Part III. Ergine, a new base obtained by the degradation of ergotoxine and ergotinine |url=https://xlink.rsc.org/?DOI=jr9320000763 |journal=Journal of the Chemical Society (Resumed) |language=en |pages=763–766 |doi=10.1039/jr9320000763 |issn=0368-1769}}

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".{{cite book | vauthors = Wasson RG, Hofmann A, Ruck CA, Webster P |url=https://books.google.com/books?id=7JC7EAAAQBAJ&pg=PA42 |title=The Road to Eleusis: Unveiling the Secret of the Mysteries |publisher=North Atlantic Books |isbn=978-1-55643-752-6 | veditors = Forte R |edition=30th Anniversary |location=Berkeley, Calif. |date=November 25, 2008 |orig-date=1978 |language=En |quote=This was an experiment performed without attention to 'set and setting' but it proves that ergonovine possesses a psychotropic, mood-changing, slightly hallucinogenic activity when taken in the same amount as [an] effective dose of lysergic acid amide, the main constituent of ololiuhqui.}} Ololiuhqui was used by South American healers in shamanic healing ceremonies.{{cite journal| vauthors = Sewell RA |date=2008|title=Unauthorized research on cluster headache. |journal=The Entheogen Review |volume=16 |issue=4 |pages=117–125 | url = http://psychonautdocs.com/docs/sewell_2009_unauthorized_research_on_cluster_headache.pdf }} 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.{{cite book| vauthors = Schultes RE |title=A Contribution to Our Knowledge of Rivea Corymbosa: The Narcotic Ololinqui of the Aztecs|date=1941|publisher=Botanical Museum of Harvard University|edition=1st}}

According to the ethnobotanist R. Gordon Wasson, Thomas MacDougall and Francisco Ortega ("Chico"), a Zapotec 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.{{cite book | vauthors = Wasson RG |title=The Hallucinogenic Fungi Of Mexico: An Inquiry Into The Origins of The Religious Idea Among Primitive Peoples |date=1961 |url=https://www.druglibrary.net/schaffer/lsd/wasson.htm |access-date=27 November 2024 |archive-url=http://web.archive.org/web/20101122083945/http://druglibrary.net/schaffer/lsd/wasson.htm |archive-date=22 November 2010}}

The Central Intelligence Agency conducted research on the psychedelic properties of Rivea corymbosa seeds for MKULTRA.{{cite web | title = Project Mkultra, Subproject 22 (w/attachments) | url = https://www.cia.gov/readingroom/document/0000707674 | website = Central Intelligence Agency | date = 3 November 1956}}

{{quote|My chemical investigations of Ololiuhqui seeds led to the unexpected discovery that the entheogenic principles of Ololiuhqui are alkaloids, especially lysergic acid amide, which exhibits a very close relationship to lysergic acid diethylamide (=ʟsᴅ). It follows therefrom that ʟsᴅ, which hitherto had been considered to be a synthetic product of the laboratory, actually belongs to the group of sacred Mexican drugs.|author=Albert Hofmann, Burg i.L., Switzerland, November 1992{{cite book | vauthors = Ott J |title=Pharmacotheon: Entheogenic Drugs, Their Plant Sources and History |publisher=Natural Products Co. |isbn=9780961423490 |edition=2nd Edition, Densified |date=1996 |pages=13 |chapter=Foreword |orig-date=1993-07}}}}

The legality of consuming, cultivating, and possessing ergine varies depending on the country.

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.{{cite web|title=Erowid LSA Vault : Legal Status|url=https://erowid.org/chemicals/lsa/lsa_law.shtml|website=erowid.org|access-date=2020-05-05}}

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.

Ergine is considered a Class A substance in the United Kingdom, categorized as a precursor to LSD.

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.{{cite web | title = Initial schedules of controlled substances (Schedule III), Section 812 | url = https://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm | website = www.deadiversion.usdoj.gov | access-date = 2020-01-17 | archive-date = 2021-11-04 | archive-url = https://web.archive.org/web/20211104092917/https://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm | url-status = dead}}

• Isoergine (isolyergic acid amide; iso-LSA; isolysergamide)
• Aztec use of entheogens § Ololiuqui and Tlitliltzin
• Morning glory § Chemistry and ethnobotany
• List of entheogens
• List of psychoactive plants

{{Reflist}}

• [https://isomerdesign.com/pihkal/explore/5309 d-Lysergamide (Ergine; LA-111; LAA; LSA) - Isomer Design]
• [https://www.godamongmen.com/journal/angels-trumpets-and-morning-glories-part-2 Angel’s Trumpets and Morning Glories—An Ethnobotanical Survey of Psychoactive Perennials Part 2: Ipomoea - God Among Men]
• [https://psychonautwiki.org/wiki/LSA LSA - PsychonautWiki]
• [https://www.erowid.org/chemicals/lsa/lsa.shtml LSA - Erowid]
• [https://www.bluelight.org/xf/threads/258723 The Big & Dandy Hawaiian Baby Woodrose Seeds / Morning Glory Seeds / LSA Thread - Bluelight]
• [http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml LSD-25: LA-111, ergine, d-lysergamide - TiHKAL - Erowid]
• [https://isomerdesign.com/pihkal/read/tk/26 LSD-25: LA-111, ergine, d-lysergamide - TiHKAL - Isomer Design]
• [https://tripsitter.com/lsa/ LSA (Lysergic Acid Amide): Naturally-Occurring Acid With Sedative Qualities - Tripsitter]

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