View source for Ergine

{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Watchedfields = verified
| verifiedrevid = 443731816
| image = Ergine.svg
| image_class = skin-invert-image
| width = 175px

<!-- Clinical data -->
| pregnancy_category = X<ref name="Erowid-Morning-Glory">{{cite web | url = http://www.erowid.org/plants/morning_glory/morning_glory_basics.shtml | title = Erowid Morning Glory Basics | publisher = Erowid.org | access-date=2012-02-03}}</ref>
| routes_of_administration = [[Oral administration|Oral]], [[intramuscular injection]], [[subcutaneous injection]]
| class = [[Serotonin receptor agonist]]; [[Serotonergic psychedelic]]; [[Hallucinogen]]; [[Sedative]]
| ATC_prefix = None
| ATC_suffix =

<!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_BR = F2
| legal_BR_comment = <ref name="Anvisa2023">{{cite web | author = Anvisa | author-link = Brazilian Health Regulatory Agency | date = 2023-07-24 | title = RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial | trans-title = Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control | url = https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 | url-status = live | archive-url = https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 | archive-date = 2023-08-27 | access-date = 2023-08-27 | publisher = [[Diário Oficial da União]] | language = pt-BR}}</ref>
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_DE = NpSG
| legal_NZ = <!-- Class A, B, C -->
| legal_UK = Class A
| legal_US = Schedule III
| legal_status = Illegal in France<ref name="LegiFrance2021">{{cite web | date = 20 May 2021 | title = Arrêté du 20 mai 2021 modifiant l'arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants | url = https://www.legifrance.gouv.fr/jorf/id/JORFTEXT000043523554 | website = www.legifrance.gouv.fr | language = fr}}</ref>

<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 
| metabolism = Hepatic
| onset = 0.3–3{{nbsp}}h ([[morning glory|morn. glory]] seeds)<ref name="TittarelliMannocchiPantano2015" /><ref name="Waters2021" />
| elimination_half-life = 
| duration_of_action = 4–10{{nbsp}}h ([[morning glory|morn. glory]] seeds)<ref name="TittarelliMannocchiPantano2015">{{cite journal | vauthors = Tittarelli R, Mannocchi G, Pantano F, Romolo FS | title = Recreational use, analysis and toxicity of tryptamines | journal = Curr Neuropharmacol | volume = 13 | issue = 1 | pages = 26–46 | date = January 2015 | pmid = 26074742 | doi = 10.2174/1570159X13666141210222409 | pmc = 4462041 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=90639cbd4ed3fc89df491868f3276f2288f9b1d2 | quote = Ergine, or lysergic acid amide (LSA), is an alkaloid of the ergoline family closely related to LSD, found in the seeds of Argyreia nervosa (Hawaiian baby woodrose) and Ipomoea violacea (Morning Glories). Hallucinogenic activity of LSA occurs with 4-10 seeds of Argyreia nervosa or with 150–200 seeds (3–6 g) of Ipomoea violacea: seeds could be crushed or eaten whole, or also drunk as an extract, after soaking in water [42]. The onset of the hallucinatory effects, after ingestion of Hawaiian Baby Woodrose, is from 20 to 40 minutes and their total duration is from 5 to 8 hours: the plateau is reached after 4-6 hours and the return to normality is after 1-2 hours from the plateau. [...] However, as regards to the assumption of the Morning Glory seeds, the onset of the hallucinatory effects is from 30 to 180 minutes and they last for 4 to 10 hours. The users reported that they return to normality after about 24 hours [67].}}</ref><ref name="Waters2021" />
| excretion = [[Urine]]<ref name="PaulkeKremerWunder2012">{{cite journal | vauthors = Paulke A, Kremer C, Wunder C, Toennes SW | title = Analysis of lysergic acid amide in human serum and urine after ingestion of Argyreia nervosa seeds | journal = Anal Bioanal Chem | volume = 404 | issue = 2 | pages = 531–538 | date = August 2012 | pmid = 22695498 | doi = 10.1007/s00216-012-6121-5 | url = }}</ref>

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 478-94-4
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 073830XH10
| PubChem = 442072
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 390611
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 4819
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 227213
| synonyms = Lysergic acid amide; LSA; LAA;<ref name="OliverAbneyStrickland1993">{{cite journal | vauthors = Oliver JW, Abney LK, Strickland JR, Linnabary RD | title = Vasoconstriction in bovine vasculature induced by the tall fescue alkaloid lysergamide | journal = Journal of Animal Science | volume = 71 | issue = 10 | pages = 2708–2713 | date = October 1993 | pmid = 7901191 | doi = 10.2527/1993.71102708x }}</ref><ref name="GenestSahasrabudhe1966">{{cite journal | vauthors = Genest K, Sahasrabudhe MR |date=1966 |title=Alkaloids and Lipids of Ipomoea, Rivea and Convolvulus and Their Application to Chemotaxonomy |url=https://www.jstor.org/stable/4252802 |journal=Economic Botany |volume=20 |issue=4 |pages=416–428 |doi=10.1007/BF02904064 |jstor=4252802 |bibcode=1966EcBot..20..416G |issn=0013-0001|url-access=subscription }}</ref><ref name="Genest1966">{{cite journal | vauthors = Genest K | title = Changes in ergoline alkaloids in seeds during ontogeny of Ipomoea violacea | language = English | journal = Journal of Pharmaceutical Sciences | volume = 55 | issue = 11 | pages = 1284–1288 | date = November 1966 | pmid = 5969787 | doi = 10.1002/jps.2600551123 | bibcode = 1966JPhmS..55.1284G }}</ref><ref name="Genest1965">{{cite journal | vauthors = Genest K | title = A direct densitometric method on thin-layer plates for the determination of lysergic acid amide, isolysergic acid amide and clavine alkaloids in morning glory seeds | journal = Journal of Chromatography | volume = 19 | issue = 3 | pages = 531–539 | date = September 1965 | pmid = 5864081 | doi = 10.1016/S0021-9673(01)99495-6 }}</ref><ref name="BrownMalone1978">{{cite journal | vauthors = Brown JK, Malone MH | title = "Legal highs"--constituents, activity, toxicology, and herbal folklore | journal = Clinical Toxicology | volume = 12 | issue = 1 | pages = 1–31 | date = 1978-01-01 | pmid = 343978 | doi = 10.3109/15563657809149579 }}</ref> ᴅ-Lysergic acid amide; ᴅ-Lysergamide, ''d''-Lysergamide; LA-111; "Lacy"; 6-Methyl-9,10-didehydroergoline-8β-carboxamide

<!-- Chemical data -->
| IUPAC_name = (6''aR'',9''R'')-7-methyl-6,6a,8,9-tetrahydro-4''H''-indolo[4,3-fg]quinoline-9-carboxamide
| C=16 | H=17 | N=3 | O=1
| SMILES = O=C(N)[C@@H]1C=C2C3=CC=CC4=C3C(C[C@@]2([H])N(C1)C)=CN4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C16H17N3O/c1-19-8-10(16(17)20)5-12-11-3-2-4-13-15(11)9(7-18-13)6-14(12)19/h2-5,7,10,14,18H,6,8H2,1H3,(H2,17,20)/t10-,14-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GENAHGKEFJLNJB-QMTHXVAHSA-N

<!-- Physical data -->
| melting_point = 135
| melting_notes = Decomposes<ref name="SmithTimmis1932" />
}}

'''Ergine''', also known as '''lysergic acid amide''' ('''LSA''' or '''LAA''') as well as '''LA-111''', is a [[psychoactive drug|psychoactive]] [[chemical compound|compound]] of the [[ergoline]] and [[lysergamides|lysergamide]] families related to [[lysergic acid diethylamide]] (LSD).<ref name="Waters2021">{{cite journal | vauthors = Waters K | title = Pharmacologic Similarities and Differences Among Hallucinogens | journal = J Clin Pharmacol | volume = 61 Suppl 2 | issue = | pages = S100–S113 | date = August 2021 | pmid = 34396556 | doi = 10.1002/jcph.1917 | url = | quote = A study published in 2013 suggests that there may be a resurgence in use [of morning glory seeds] in the United States following its peak in the 1960s, potentially due to the low price, widespread availability, and lack of legal restrictions.45 [...] The mechanism of action of LSA remains unclear; its binding profile has some similarities to that of LSD, but LSA has demonstrated a lower affinity for all receptors.44 Although LSA may produce similar changes in visual perception as elicited by LSD, the psychedelic effects are weaker, likely due to the significantly higher affinity of LSD for 5HT2 receptors.44,45 [...] The seeds of these plants may be ingested whole, ground up, suspended in beverages, or formulated into capsules.11,46 A hallucinogenic dose of LSA ranges from 2 to 5 mg.35 This can generally be obtained from 5 to 10 seeds of Argyreia nervosa (0.14% LSA by dry weight) or 150 to 200 seeds of Ipomoea violacea (0.02% LSA by dry weight).35,47–49 The onset of effects is rapid, and the effects typically last from 4 to 8 hours.35}}</ref><ref name="SteinerLeistner2018">{{cite journal | vauthors = Steiner U, Leistner E | title = Ergot Alkaloids and their Hallucinogenic Potential in Morning Glories | journal = Planta Med | volume = 84 | issue = 11 | pages = 751–758 | date = July 2018 | pmid = 29499587 | doi = 10.1055/a-0577-8049 | bibcode = 2018PlMed..84..751S | url = https://www.thieme-connect.com/products/ejournals/pdf/10.1055/a-0577-8049.pdf}}</ref><ref name="TittarelliMannocchiPantano2015" /><ref name="GrofHofmann1984">{{cite journal | vauthors = Grof S, Hofmann A | title = Stanislav Grof Interviews Dr. Albert Hofmann | journal = MAPS Bulletin | volume = 9 | issue = 2 | date = Fall 2001 | orig-date = 1984 | pages = 22–35 | url=http://www.maps.org/news-letters/v11n2/11222gro.html }}</ref> Ergine is an ergoline [[alkaloid]] found in [[fungi]] such as ''[[Claviceps paspali]]'' (ergot) and ''[[Periglandula]]'' species such as ''[[Periglandula clandestina]]'',<ref name="SteinerLeistner2018" /><ref name="HazelPanaccione2025">{{cite journal | vauthors = Hazel CM, Panaccione DG | title = A new species of Periglandula symbiotic with the morning glory Ipomoea tricolor | journal = Mycologia | volume = 117| issue = 4| pages = 602–614 | date = April 2025 | pmid = 40261263 | doi = 10.1080/00275514.2025.2483634 | pmc = 12197838 | pmc-embargo-date = July 1, 2026 | url = }}</ref> which are permanently connected with many [[convolvulaceae|morning glory]] vines.<ref name="SteinerLeistner2018" /> Ergine induces relatively mild [[psychedelic]] effects as well as pronounced [[sedative]] effects.<ref name="Waters2021" /><ref name="TiHKAL-LSD" /><ref name="Hofmann1963" /><ref name="Hofmann1971" /><ref name="Heacock1975">{{cite journal | vauthors = Heacock RA | title = Psychotomimetics of the Convolvulaceae | journal = Prog Med Chem | series = Progress in Medicinal Chemistry | volume = 11 | issue = | pages = 91–118 | date = 1975 | pmid = 1078534 | doi = 10.1016/s0079-6468(08)70209-1 | isbn = 978-0-7204-7411-4 | url = https://bibliography.maps.org/resources/download/13618 | archive-url = https://web.archive.org/web/20250330055318/https://bibliography.maps.org/resources/download/13618 | archive-date = 30 March 2025 | quote = Hofmann had previously described the action of synthetic ergine (1) as being primarily of a sedative nature [33]. A subcutaneous injection of 0.5-1.0 mg of (1) has been reported to produce a powerful hypnotic action, but a relatively weak psychedelic action [52]. [...] 33. A. Hofmann, Bot. Museum Leafl. Harvard Univ., 20 (1963) 194. [...] 52. J. Soleil and L. Lalloz, Prod. Probl. Pharm., 26 (1971) 682.| url-access = subscription }}</ref><ref name="ChenDeWitBos2020" /><ref name="MoukaddamRuiz2013">{{cite book | vauthors = Moukaddam N, Ruiz P | title=International Handbook of Psychiatry | chapter=Substance Use Disorders | publisher=World Scientific | date=2013 | isbn=978-981-4405-60-7 | doi=10.1142/9789814405614_0011 | pages=260–290 | quote=Hawaiian baby woodrose (Argyreia nervosa) seeds contain d-lysergic acid amide (LSA, also known as d-lysergamide), which is a substance closely related to LSD. LSA can produce mild hallucinogenic effects and is considered a controlled substance in Ireland and the United Kingdom.}}</ref>

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).<ref name="SteinerLeistner2018" /><ref name="Perrine2000">{{cite journal|vauthors=Perrine DM|date=2000|title=Mixing the Kykeon|url=http://www.psychedelic-library.org/Mixing%20the%20Kykeon%20Final%20Draft.pdf|journal=ELEUSIS: Journal of Psychoactive Plants and Compounds|volume=New Series 4|pages=9|access-date=2008-05-05|archive-date=2019-07-20|archive-url=https://web.archive.org/web/20190720192225/http://www.psychedelic-library.org/Mixing%20the%20Kykeon%20Final%20Draft.pdf|url-status=dead}}</ref><ref name="TiHKAL-LSD" /><ref name="Hofmann2009">{{cite book| vauthors = Hofmann A |title=LSD My Problem Child: Reflections on Sacred Drugs, Mysticism, and Science |date=2009 |publisher=MAPS.org |isbn=978-0979862229 |edition=4th}}</ref> Morning glory seeds have a history of [[entheogen]]ic use in [[Mesoamerica]] dating back at least hundreds of years.<ref name="SteinerLeistner2018" /><ref name="Hofmann1971">{{cite journal | vauthors = Hofmann A | title = Teonanácatl and Ololiuqui, two ancient magic drugs of Mexico | journal = Bulletin on Narcotics | volume = 23 | number = 1 | pages = 3–14 | date = January–March 1971 | url = https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1971-01-01_1_page003.html | archive-url = https://web.archive.org/web/20250328194118/https://bibliography.maps.org/resources/download/19394 | archive-date = 28 March 2025}}</ref><ref name="Schultes1969">{{cite journal | vauthors = Schultes RE | title = Hallucinogens of plant origin | journal = Science | volume = 163 | issue = 3864 | pages = 245–254 | date = January 1969 | pmid = 4883616 | doi = 10.1126/science.163.3864.245 | bibcode = 1969Sci...163..245E | url = https://bibliography.maps.org/resources/download/15068| archive-url = https://web.archive.org/web/20250328203841/https://bibliography.maps.org/resources/download/15068 | archive-date = 28 March 2025 | url-access = subscription }}</ref> They have also since been used by many [[Western people|Westerner]]s.<ref name="Shulgin1976" /> In addition to ergine, morning glory seeds contain other ergolines such as [[lysergic acid hydroxyethylamide]] (LSH), [[ergonovine|lysergic acid propanolamide]] (ergonovine), and [[isoergine]].<ref name="Hofmann1963">{{cite journal | vauthors = Hofmann A | title=The Active Principles of the Seeds of Rivea Corymbosa and Ipomoea Violacea | journal=Botanical Museum Leaflets, Harvard University | publisher=Harvard University Herbaria | volume=20 | issue=6 | year=1963 | issn=0006-8098 | jstor=41762231 | pages=194–212 | doi=10.5962/p.168542 | doi-access=free }}</ref><ref name="Hofmann1971" /><ref name="SteinerLeistner2018" /> Some of these compounds are [[pharmacology|pharmacologically active]] and are thought to contribute to the effects of the seeds as well.<ref name="Hofmann1963" /><ref name="Hofmann1971" /><ref name="SteinerLeistner2018" /><ref name="Ripinsky-Naxon1993">{{cite book | vauthors = Ripinsky-Naxon M |title=The Nature of Shamanism: Substance and Function of a Religious Metaphor |publisher=State University of New York Press |year=1993 |isbn=9781438417417 |location=Albany, NY |page=146 }}</ref><ref name="HeimHeimannLukács1968" /> There has been debate about the role of ergine in causing the psychedelic effects of morning glory seeds.<ref name="TiHKAL-LSD" /><ref name="Shulgin2003" /><ref name="EntheogenReview1999">{{cite journal | vauthors = | title = More Stipa Robusta | journal = Entheogen Review | date = Winter 1999 | volume = 8 | number = 4 | pages = 136– | url = http://www.entheogenreview.com/recentback-issue.html | archive-url = https://archive.today/20250328210244/http://psyvault.net/viewtopic.php?t=868#selection-591.0-576.16 | archive-date = 28 March 2025 | quote = In The Botany and Chemistry of Hallucinogens by SCHULTES and HOFMANN, lysergic acid amide (ergine) is described as a strong tranquilizer with very little psychoactivity. HOFMANN should know; he is the “father of LSD” and did extensive research on related compounds. Ergine is not useful as an entheogen, but it’s great for insomnia! Yet individuals persist in trying to use it as a vision-inducing material, simply because it is structurally related to LSD. — B. GREEN [...] This letter and the previous one bring up an interesting point. It is assumed by some that ergine is the primary visionary component in Ipomoea violacea and Argyreia nervosa. However, this may not be the case. K. TROUT has found that some morning glories are very LSD-like, and others are not (both within commercially available “heavenly blue” strains for example). There may be something else at work here that has not been adequately examined. It appears that HOFMANN did not evaluate all of the different chemicals found in I. violacea, and at least one that he did evaluate may have been visionary at doses higher than he took; he evaluated isoergine only up to the 2 mg level, and found it to be predominantly sedative without visual effects. JONATHAN OTT has pointed out that this compound might be psychoptic at higher levels (OTT 1993). We simply do not know at this point. It is also worth noting that lysergic acid-L-2-propanolamide, or ergonovine, has been reported as having mild visionary effects (as well as producing lassitude and leg cramps) in doses of 2–10 mg (HOFMANN 1978; BIGWOOD et al. 1979), and this compound is found in both Argyreia nervosa and Ipomoea violacea (CHAO & DER MARDEROSIAN 1973, listed under MOIR & DUDLEY’S synonym ergometrine), as is elymoclavine, which OTT has stated is “evidently psychoptic” (OTT 1993). Other possible players include the N-(1-hydroxyethyl)-amides of ergine and/or isoergine. The Botany and Chemistry of Hallucinogens notes: [...] Ergine may not be the psychoptic agent in morning glories that are active, or if it is then it is likely not the only player involved in producing visual activity. Between 1972 and 1983, K. TROUT ate Ipomoea violacea seeds or seed-extract several dozen times with wildly varying results ranging from powerfully colorful visuals to sedative effects. [...] }}</ref><ref name="ChenDeWitBos2020" />

Ergine was first described by Sidney Smith and Geoffrey Timmis after they isolated it from ergot in 1932.<ref name="SmithTimmis1932" /> It was first [[chemical synthesis|synthesized]] subsequent to its isolation in the 1930s.<ref name="Hofmann1963" /><ref name="StollHofmann1955">{{cite journal | vauthors = Stoll A, Hofmann A | title=Amide der stereoisomeren Lysergsäuren und Dihydro-lysergsäuren. 38. Mitteilung über Mutterkornalkaloide | trans-title=Amides of the stereoisomeric lysergic acids and dihydrolysergic acids. 38. Report on ergot alkaloids | journal=Helvetica Chimica Acta | volume=38 | issue=2 | date=1955 | issn=0018-019X | doi=10.1002/hlca.19550380207 | pages=421–433 | bibcode=1955HChAc..38..421S | url=https://bibliography.maps.org/resources/download/11726| archive-url=https://web.archive.org/web/20250328223302/https://bibliography.maps.org/resources/download/11726 | archive-date=28 March 2025 | url-access=subscription }}</ref> [[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.<ref name="TiHKAL-LSD" /><ref name="Hofmann1963" /><ref name="HeimHeimannLukács1968" /><ref name="Hofmann1980" /> He and his colleagues also isolated ergine from morning glory seeds in 1960.<ref name="HofferOsmond1967">{{cite book | author1=[[Abram Hoffer]] | author2=[[Humphrey Osmond]] | chapter=Chapter II A d-Lysergic Acid Diethylamide | pages=83–236 | chapter-url=https://bitnest.netfirms.com/external/Books/TheHallucinogens#page=91 | title=The Hallucinogens | publisher=Elsevier | date=1967 | isbn=978-1-4832-3296-6 | doi=10.1016/B978-1-4832-3296-6.50005-7 | lccn=66030086 | oclc=332437 | ol=OL35255701M  | url=https://bitnest.netfirms.com/external/Books/TheHallucinogens | quote=The psychological properties of lysergic acid amide (LA) were compared to LSD and to lysergic acid monoethylamide (LAE) by Solms (1956). About 0.1-1.0 mg of LA given to male subjects, chiefly physicians and chemists, were required to produce a typical LA response. This dose was similar to the dose of LAE required. But LA produced more indifference, a decrease in motor activity and more sleepiness than LAE. The subjects fell asleep after 1 hour and if not aroused they slept about 2 hours. Higher doses caused autonomic changes, emesis, diarrhea and dizziness but no hallucinations. Subjects were sometimes irritable and depressed. Thus, when the methyl groups were removed and LA produced instead of LSD, the alkaloid had much less hallucinogenic and psychomotor activity and more sedative activity. [...] R. corymbosa is only one of a large number of morning glory varieties. After it was shown that LA and other ergot alkaloids were present, it became apparent to many investigators and to many more curious nonprofessionals that morning glory plants native to North America might also be active. Before long many varieties were sampled and it became generally known that certain varieties aptly named "Heavenly Blue," "Pearly Gates" and "Wedding Bells" were especially active psychologically. According to Cohen (1963) these discoveries initiated a wave of purchases of seeds from feed and seed stores. Federal agents seized many pounds of seeds in single raids. Psychotherapists who had used LSD for psychotherapy turned to the morning glory seeds when cut off from their normal sources. Stories appeared in the daily press and before long it became widely known how to obtain LSD-like experiences cheaply without having to get LSD.}}</ref><ref name="HofmannTscherter1960">{{cite journal | vauthors = Hofmann A, Tscherter H | title=Isolierung von Lysergsäure-Alkaloiden aus der mexikanischen Zauberdroge Ololiuqui (Rivea corymbosa (L.) Hall. f.) | trans-title=Isolation of lysergic acid alkaloids from the Mexican magic drug Ololiuqui (Rivea corymbosa (L.) Hall. f.) | journal=Experientia | volume=16 | issue=9 | date=1960 | issn=0014-4754 | doi=10.1007/BF02178840 | doi-access=free | pages=414 | pmid=13715089 | url=https://link.springer.com/content/pdf/10.1007/BF02178840.pdf | language=de | access-date=28 March 2025}}</ref><ref name="Hofmann1963" /><ref name="SteinerLeistner2018" /> Morning glory seeds started to become frequently used as a [[recreational drug]] that same year<ref name="Shulgin1976" /> and have been widely used since.<ref name="SteinerLeistner2018" /><ref name="HofferOsmond1967" /><ref name="JuszczakSwiergiel2013">{{cite journal | vauthors = Juszczak GR, Swiergiel AH | title = Recreational use of D-lysergamide from the seeds of Argyreia nervosa, Ipomoea tricolor, Ipomoea violacea, and Ipomoea purpurea in Poland | journal = Journal of Psychoactive Drugs | volume = 45 | issue = 1 | pages = 79–93 | date = 2013-01-01 | pmid = 23662334 | doi = 10.1080/02791072.2013.763570 | s2cid = 22086799 }}</ref><ref name="Burillo-PutzeLópezBrizClimentDíaz2013">{{cite journal | vauthors = Burillo-Putze G, López Briz E, Climent Díaz B, Munné Mas P, Nogue Xarau S, Pinillos MA, Hoffman RS | title = Drogas emergentes (III): plantas y hongos alucinógenos | trans-title = Emergent drugs (III): hallucinogenic plants and mushrooms | journal = Anales del Sistema Sanitario de Navarra | volume = 36 | issue = 3 | pages = 505–518 | date = 2013-09-01 | pmid = 24406363 | doi = 10.4321/s1137-66272013000300015 | doi-access = free }}</ref> Recreational use of morning glory seeds may be increasing due to their inexpensiveness, widespread availability, and lack of legal restrictions.<ref name="Waters2021" /><ref name="HofferOsmond1967" /> Ergine has been encountered as a novel [[designer drug]] in [[Europe]].<ref name="Europol2008">{{cite web | title=EMCDDA–Europol 2008 Annual Report on the implementation of Council Decision 2005/387/JHA | website=Europol | date=2008 | url=https://www.europol.europa.eu/cms/sites/default/files/documents/2008_implementation_report_281411_2.pdf | access-date=28 March 2025 | quote = 9. LSA ((8β)-9,10-didehydro-6-methyl-ergoline-8-carboxamide) – 29 October 2008 – Bulgaria}}</ref> Ergine, though not morning glory seeds, has become a [[controlled substance]] in various places in the world.<ref name="Erowid-LSA" /><ref name="USDOJ2021" />

==Use==
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).<ref name="SteinerLeistner2018" /> They may be consumed whole and intact, crushed or ground up, or drunk as an extract following soaking of the seeds in water.<ref name="Halpern2004">{{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).}}</ref><ref name="TittarelliMannocchiPantano2015" /><ref name="Waters2021" /> A [[hallucinogen]]ic 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).<ref name="Halpern2004" /><ref name="TittarelliMannocchiPantano2015" /><ref name="Waters2021" /><ref name="Shulgin1976" /><ref name="ChenDeWitBos2020">{{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}}</ref> The [[onset of action|onset]] is 0.3 to 3{{nbsp}}hours and the [[duration of action|duration]] is 4 to 10{{nbsp}}hours.<ref name="Halpern2004" /><ref name="TittarelliMannocchiPantano2015" /><ref name="Waters2021" />

Ergine may be used as a drug in [[chemical purification|pure or purified]] form as well, either [[chemical isolation|isolated]] or [[chemical synthesis|synthesized]].<ref name="TiHKAL-LSD" /><ref name="Heacock1975" /><ref name="SoleilLalloz1971" /> [[Albert Hofmann]] and colleagues found that a 0.5 to 2{{nbsp}}mg dose by [[intramuscular injection|intramuscular]] or [[subcutaneous injection]] produced relatively weak but significant hallucinogenic effects as well as marked [[sedation]].<ref name="TiHKAL-LSD" /><ref name="Hofmann1963" /><ref name="Hofmann1980" /><ref name="Shulgin1976" /><ref name="Heacock1975" /><ref name="SoleilLalloz1971">{{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}}</ref><ref name="Hofmann1970">{{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.}}</ref> 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).<ref name="Shulgin1976" /><ref name="HofferOsmond1967" /><ref name="Solms1956a">{{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 }}</ref><ref name="Solms1956b">{{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 }}</ref> 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 [[potency (pharmacology)|potent]] than LSD, but as being "not hallucinogenic".<ref name="Shulgin2003">{{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<sup>a</sup>. [...] <sup>a</sup> sedative action or autonomic changes in humans; not hallucinogenic}}</ref> Hofmann also stated that ergine was 10- to 40-fold less potent than LSD and that it had qualitatively different effects.<ref name="Hofmann1980" /><ref name="Hofmann1970" /> [[Robert Oberlender]] has stated that ergine is about 30-fold less potent than LSD in humans.<ref name="Oberlender1989" /> Heim and colleagues assessed ergine at higher doses of 3 to 6{{nbsp}}mg [[oral administration|orally]] and observed [[toxic]]-like effects, whereas [[isoergine]] at 2 to 5{{nbsp}}mg orally produced notable hallucinogenic effects, including some [[euphoria]], [[synaesthesia]], and [[time dilation|altered time perception]].<ref name="ChenDeWitBos2020" /><ref name="BrimblecombePinder1975">{{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}}</ref><ref name="HeimHeimannLukács1968" />

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.<ref name="TiHKAL-LSD">{{CiteTiHKAL}} https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml "LA-111, Ergine, d-Lysergamide. This is an active compound and has been established as a major component in morning glory seeds. It was assayed for human activity, by Albert Hofmann in self-trials back in 1947, well before this was known to be a natural compound. An i.m. administration of a 500 microgram dose led to a tired, dreamy state with an inability to maintain clear thoughts. [...] The epimer, inverted at C-8, is isoergine or d-isolysergamide, and is also a component of morning glory seeds. Hofmann tried a 2 milligram dose of this amide, and as with ergine, he experienced nothing but tiredness, apathy, and a feeling of emptiness. Both compounds are probably correctly dismissed as not being a contributor to the action of these seeds. It is important to note that ergine, as well as lysergic acid itself, is listed as a Schedule III drug in the Controlled Substances Act, as a depressant. This is, in all probability, a stratagem to control them as logical precursors to LSD. [...] Although there are many other chemical treasures in the ergot fungal world, I would like to wrap this commentary up with a return to the topic of morning glory seeds. Four additional alkaloids of the ergot world must be acknowledged as being potentially participating factors in the MGS story. [...] These structures in effect define absolute obscurity, and most probably do not contribute to the morning glory intoxication state. But the others, some present is sizable amounts, may someday help explain why the pharmacology of these seeds is so different than that of the major isolates, the ergines."</ref> The poorly-stable [[lysergic acid hydroxyethylamide]]s (LSHs) might alternatively be involved in the psychedelic effects of morning glory seeds per Shulgin.<ref name="Shulgin1972">{{cite book | veditors=Mulé, SJ, Brill H | vauthors = Shulgin AT | chapter=Hallucinogens, CNS Stimulants, And Cannabis | title=Chemical and Biological Aspects of Drug Dependence | publisher=CRC Press | date=1972 | isbn=978-0-87819-011-9 | doi=10.1201/9780429260629-16 | pages=163–176 | chapter-url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=8d86c9d6e58771ccef891e76483b86fceee153f8 | url=https://books.google.com/books?id=-edsAAAAMAAJ | quote = The major alkaloids present were found to be ergine (d-Lysergic acid amide, Figure 2; R1, R2, R3 = H) and the enantiomorph isoergine (d-Isolysergic acid amide, identical with ergine, but with the opposite epimeric configuration on the carbon atom that carries the amide carbonyl group). These two compounds have been shown to have some activity in man, but it is possible that their presence in the natural seed as the extremely labile acetaldehyde condensates (the hydroxyethylamides) may explain the activity of the seed compared to the lack of activity of the ergot isolates.8 [...] 8. Hofmann, A., Teonanacatl and Ololiuqui, two ancient magic drugs of Mexico, Bull. Narc., 23, 3, 1971.}}</ref>

[[Achnatherum robustum|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.<ref name="DeKorne1994">{{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 }}</ref><ref name="Cole2013">{{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}}</ref>

==Effects==
===Subjective effects===
Ergine has only been given a minuscule amount of attention. [[Albert Hofmann]] and his colleagues self-administered ergine.<ref name="Hofmann1963" /> In addition, it was assessed in two clinical studies by other researchers.<ref name="Solms1956a" /><ref name="HeimHeimannLukács1968">{{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| url-access=subscription }}</ref> [[Synthetic compound|Synthetic]] ergine was used in all of these cases.<ref name="Solms1956a" /><ref name="Hofmann1963" /><ref name="HeimHeimannLukács1968" /> 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."<ref name="Hofmann1963" /> There are parallels between Hofmann's comments and the ones in the two trials:<ref name="Hofmann1963" />

{| class="wikitable"
|+ Clinical studies of ergine's effects
! Hofmann (1963)<ref name="Hofmann1963" />
! Heim et al. (1968)<ref name="HeimHeimannLukács1968" />
! Solms (1956)<ref name="Solms1956a" /><ref name="Solms1956b" />
|-
|
| "dysphoria"
| "irritative depressive moods"
|-
| "incapable of clear thoughts"
| "impairment of concentration"
"clouding of consciousness"
| "impaired concentration"
"clouding of consciousness"

"With middle to strong doses in 1 subject work became increasingly difficult after 30 minutes"
|-
| "Desire to lie down and sleep. Genuine physical and mental tiredness, which is not experienced as an unpleasant sensation. Slept for 3 hours."
| "test subject SB [...] had to go to bed after an antineoplastic injection and did not recover until the following day."
"In the fourth and fifth study periods, however, they appeared to be sufferingly exhausted and even sleepy and dazed." [isoergine]
| "and an immediate desire to sleep, after which he slept for three hours during the day".
|-
| "a feeling of mental emptiness and of the unreality and complete meaninglessness of the outside world". [isoergine]
| "In the test subject PS (5 mg), severe nausea with a drop in blood pressure suddenly occurred after 3½ hours, which was controlled with analeptics and antinausea after about 30 minutes. At the same time, the test subject experienced a feeling of total annihilation and fear of death, which subsided after vomiting about 60 minutes later, but only completely subsided during the course of the night." [isoergine]

"In the fourth and fifth study cross-sections, they complained of difficulty in thinking and a lack of ideas." [isoergine]
| "Indifference"

"a feeling of sinking into nothing"
|}

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)."<ref name="SchultesHofmann1973" />

"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."<ref name="Hofmann1980">{{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.}}</ref>

"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."<ref name="GrofHofmann1984" />

===Physiological effects===
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 hallucination]]s, [[auditory hallucination]]s, [[euphoria]], [[motor incoordination|loss of motor control]], [[nausea]], [[vasoconstriction]], [[delusion]]s, [[anxiety]], [[paranoia]], and [[irregular heartbeat]]s.<ref name="Hofmann2009" /><ref name="Sewell2008" /><ref name="Ingram1964" /><ref name="KremerPaulkeWunder2012">{{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}}</ref>

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.<ref name="KremerPaulkeWunder2012" />

==Side effects==
A 2016 study showed that [[penniclavine]] was the predominant alkaloid in ''[[Ipomoea tricolor]]'' seeds.<ref name="NowakWoźniakiewiczKlepacki2016" /> [[Ergoclavine]]s are known to cause [[convulsion|convulsive]] [[ergotism]],<ref name="SchardlPanaccioneTudzynski2006">{{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''). }}</ref> the milder form of ergotism. Gangrenous ergotism is caused by [[ergopeptine]]s: the complex [[peptide]] [[moiety (chemistry)|moiety]] forces persistence at the receptor sites.<ref name="Eich2008" /> Ergopeptines are rare in Convolvulaceae, being found in 10 species,<ref name="Eich2008">{{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 [...]}}</ref><ref name="BeaulieuPanaccioneHazekamp2013">{{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 [...]}}</ref> not including the three that are commonly ingested, although Paulke 2014 says analytical evidence suggests that [[Argyreia nervosa|''A. nervosa'']] contains ergopeptines.<ref name="PaulkeKremerWunder2015">{{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) [...]}}</ref> 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 cm<sup>3</sup> of Cyclicinum hydrochloricum. In addition, sensations of heat, sweating, dizziness, a feeling of heaviness and general tiredness were observed."<ref name="HeimHeimannLukács1968" />

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, [...]".<ref name="BigwoodOttThompson1979">{{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| url-access = subscription }}</ref>

Like other psychedelics, ergine is not considered to be [[addiction|addictive]]. Additionally, there are no known [[death]]s directly associated with [[Pharmacology|pharmacological]] effects of ergine consumption. All associated deaths are due to indirect causes, such as [[self-harm]], [[Judgement|impaired judgement]], and adverse [[drug interaction]]s. One known case involved a [[suicide]] that was reported in 1964 after [[ingestion]] of [[morning glory]] [[seeds]].<ref name="Cohen1964">{{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}}</ref> Another instance is a death due to [[Falling (accident)|falling off]] of a [[building]] after ingestion of [[Argyreia nervosa|Hawaiian baby woodrose]] [[seed]]s and [[alcohol (drug)|alcohol]].<ref name="KlinkeMüllerSteffenrud2010">{{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 }}</ref> A study gave mice 3000{{nbsp}}mg/kg with no lethal effects.{{Citation needed | date = February 2024}}

===Chemical coatings on seeds===
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<ref name="BendzSantesson2013">{{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}}</ref><ref name="Ono2017">{{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}}</ref> and ergoclavines.<ref name="SchardlPanaccioneTudzynski2006" /> 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.<ref name="Ingram1964">{{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 suggested<sup>6</sup> 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.<sup>8</sup> 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.<sup>9</sup> 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.)}}</ref><ref name="Cohen1964" /><ref name="Frear1963">{{cite book | vauthors = Frear DE | title = Pesticide Handbook | location = State College, Pa | publisher = College Science Publishers | date = 1963 | page = 8}}</ref>

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,<ref name="Jordan1994">Peter Jordan. Re: Woodrose vs Ipomoea. alt.drugs, UseNet, 10/1/1994 https://erowid.org/plants/hbw/hbw_info1.shtml</ref> and Eckart Eich says that they probably don't occur in many Convolvulaceae.<ref name="Eich2008" /> There is a similar claim in a publication from 1973, warning about "a strychnine-like alkaloid",<ref name="Mann1973">{{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.}}</ref> but that is probably just a misapplication of the claim that peyote contains strychnine, which, itself, is a rumor.<ref name="Pendell2010">{{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.}}</ref>

==Overdose==
Cases of [[overdose]] of ergine and morning glory seeds and associated [[toxicity]] have been reported.<ref name="ChenDeWitBos2020" />

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

The [[drug interaction|interaction]]s of ergine and of morning glory seeds have been discussed.<ref name="ChenDeWitBos2020" />

==Pharmacology==
===Pharmacodynamics===
{| class="wikitable floatright"
|+ Ergine (LSA) and LSD activities
|-
! rowspan="2" | Receptor !! colspan="2" | Affinity (K<sub>i</sub>, nM) !! rowspan="2" | Ratio
|-
! Ergine (LSA) !! LSD
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 73 || 1.6 || 46:1
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 28–132 (K<sub>i</sub>)<br />1.1–58 ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}})<br />47–82% ({{Abbrlink|E<sub>max</sub>|maximal efficacy}}) || 0.87–1.1 (K<sub>i</sub>)<br />0.52–3.6 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />60–86% ({{Abbr|E<sub>max</sub>|maximal efficacy}}) || 32–120:1<br />2–16:1<br />0.78–0.95:1
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 54–115 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />40–55% ({{Abbr|E<sub>max</sub>|maximal efficacy}}) || 0.68–34 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />62–73% ({{Abbr|E<sub>max</sub>|maximal efficacy}}) || 3–79:1<br />0.65–0.75:1
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 798 || 7.8 || 102:1
|-
| [[D1 receptor|D<sub>1</sub>]] (pig) || 832 || 87 || 10:1
|-
| [[D2L receptor|D<sub>2L</sub>]] || 891 || 155 || 6:1
|-
| [[D2S receptor|D<sub>2S</sub>]] || 145 || 25 || 6:1
|-
| [[D3 receptor|D<sub>3</sub>]] || 437 || 65 || 7:1
|-
| [[D4.4 receptor|D<sub>4.4</sub>]] || 141 || 30 || 5:1
|-
| [[α1-Adrenergic receptor|α<sub>1</sub>]] || 912 || 60 || 15:1
|-
| [[α2-Adrenergic receptor|α<sub>2</sub>]] || 62 || 1.0 || 62:1
|-
| colspan="4" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' All proteins are human unless otherwise specified. '''Sources:''' <ref name="PaulkeKremerWunder2013">{{cite journal | vauthors = Paulke A, Kremer C, Wunder C, Achenbach J, Djahanschiri B, Elias A, Schwed JS, Hübner H, Gmeiner P, Proschak E, Toennes SW, Stark H | title = Argyreia nervosa (Burm. f.): receptor profiling of lysergic acid amide and other potential psychedelic LSD-like compounds by computational and binding assay approaches | journal = Journal of Ethnopharmacology | volume = 148 | issue = 2 | pages = 492–497 | date = July 2013 | pmid = 23665164 | doi = 10.1016/j.jep.2013.04.044 }}</ref><ref name="WackerWangMcCorvy2017">{{cite journal | vauthors = Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, Lansu K, Schools ZL, Che T, Nichols DE, Shoichet BK, Dror RO, Roth BL | title = Crystal Structure of an LSD-Bound Human Serotonin Receptor | journal = Cell | volume = 168 | issue = 3 | pages = 377–389.e12 | date = January 2017 | pmid = 28129538 | doi = 10.1016/j.cell.2016.12.033 | pmc = 5289311 | url = }}</ref><ref name="McCorvy2013">{{cite web | vauthors = McCorvy JD | title=Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics | website=Purdue e-Pubs | date=16 January 2013 | url=https://docs.lib.purdue.edu/dissertations/AAI3545320/ | archive-url=https://bitnest.netfirms.com/external/Theses/McCorvey2012 | archive-date=25 March 2025 | quote=Table 5.2 Binding affinities using 3 H-LSD at 5-HT2A EL2 mutants [...] Table B.1 Binding affinities for 5-HT2A, 5-HT2C, 5-HT1A receptors using 3 H-LSD [...]}}</ref>
|}

Ergine interacts with [[serotonin receptor|serotonin]], [[dopamine receptor|dopamine]], and [[adrenergic receptor]]s similarly to but with lower [[affinity (pharmacology)|affinity]] than [[lysergic acid diethylamide]] (LSD).<ref name="PaulkeKremerWunder2013" /><ref name="WackerWangMcCorvy2017" /> It is known to act as an [[agonist]] of the [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub>]] and [[5-HT2B receptor|5-HT<sub>2B</sub> receptor]]s similarly to LSD, albeit much less [[potency (pharmacology)|potently]] and with reduced [[receptor activation|activational]] [[maximal efficacy|efficacy]].<ref name="WackerWangMcCorvy2017" /> The drug has about 4.3% of the [[antiserotonergic]] activity of LSD in the isolated rat [[uterus]] ''[[in vitro]]''.<ref name="Oberlender1989">{{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. [...]}}</ref><ref name="CerlettiDoepfner1958">{{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 [...]| url-access = subscription }}</ref> The psychedelic effects of ergine can be attributed to activation of serotonin 5-HT<sub>2A</sub> receptors.<ref name="HalberstadtNichols2020">{{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}}</ref><ref name="KelmendiKayePittenger2022">{{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}}</ref><ref name="Nichols2018">{{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}}</ref>

==Chemistry==
{{See also|Lysergamides}}

Ergine, also known as lysergic acid amide (LSA) or as lysergamide, is a [[substituted ergoline|ergoline]] and [[substituted lysergamide|lysergamide]]. It is the simplest lysergamide and is the [[parent compound|parent structure]] of this family of compounds. Hence, all lysergamides are [[chemical derivative|derivative]]s of ergine. [[Lysergic acid diethylamide]] (LSD) is the [[structural analog|analogue]] of ergine with two [[ethyl group]]s substituted on its [[amide]] [[moiety (chemistry)|moiety]].

The [[chemical extraction|extraction]] of ergine from morning glory seeds has been described.<ref name="Shanks2001">{{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}}</ref><ref name="SomaGraphics1996">{{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 }}</ref>

==Natural occurrence==
Ergine is not a [[biosynthesis|biosynthetic]] endpoint itself, but rather a [[hydrolysis]] [[metabolic product|product]] of [[lysergic acid hydroxyethylamide]] (LSH), [[ergonovine|lysergic acid propanolamide]] (ergonovine), and [[ergopeptine]]s or their [[ergopeptam]] [[precursor (biochemistry)|precursor]]s.<ref name="FliegerSedmeraVokoun1982">{{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|url-access=subscription }}</ref><ref name="Ramstad1968">{{cite journal | vauthors = Ramstad E |date=1968 |title=Chemistry of alkaloid formation in ergot |journal=Lloydia |volume=31 |pages=327–341}}</ref><ref name="KleinerováKybal1973">{{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 }}</ref><ref name="PanaccioneTapperLane2003">{{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}}</ref><ref name="Panaccione2010">{{cite book | vauthors = Panaccione DG | chapter = Ergot alkaloids | title = The Mycota, Industrial Applications | edition = 2nd | veditors = Hofrichter M | publisher = Springer-Verlag | location = Berlin-Heidelberg, Germany | date = 2010 | volume = 10 | pages = 195–214 }}</ref>

LSH is very vulnerable to this hydrolysis,<ref name="Shulgin1976">{{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.}}</ref><ref name="SchultesHofmann1973">{{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.}}</ref> and many analyses of [[ergoline]]-containing products 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.<ref name="FliegerLinhartováSedmera1989">{{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|url-access=subscription }}</ref><ref name="PetroskiPowellClay1992">{{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).}}</ref> [[Methylergonovine]] and [[methysergide]] (1-methylmethylergonovine) have also been found in a natural product in one study;<ref name="PaulkeKremerWunder2015" /> 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]]'',<ref name="ArcamoneBoninoChain1960">{{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 }}</ref><ref name="CastagnoliCorbettChain1970">{{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 }}</ref><ref name="BasmadjianFlossGröger1969">{{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|url-access=subscription }}</ref> but are only found in trace amounts in the more well-known ''[[Claviceps purpurea]]''.<ref>{{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 }}</ref><ref name="WassonHofmannRuck2008">{{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}}</ref> Both are [[ergot]]-spreading fungi. The major products of ''C. purpurea'' are ergopeptines, but ''C. paspali'' does not generate ergopeptines.<ref name="Panaccione2010" /> Ergonovine is the only lysergamide in ''C. purpurea'' in a substantial amount.<ref name="WassonHofmannRuck2008" />

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]]''<ref>{{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 }}</ref> (ergolines have been identified in 42 of these plants and not all of them contain ergine).<ref name="Eich2008" /> Ergonovine is present in Ipomoea tricolor in one-tenth to one-third of the amount of ergine.<ref name="NowakWoźniakiewiczKlepacki2016">{{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 }} 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.</ref> This variable may account for the varying reports about the psychedelic effect of these seeds.<ref name="Ripinsky-Naxon1993" />

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

{{Div col|colwidth=20em}}
* Unidentified ''Acremonium'' species that infects [[Achnatherum robustum|sleepy grass]] (''C. purpurea'' also infects sleepy grass<ref name="AldermanHalseWhite2004">{{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 }}</ref>).<ref name="PetroskiPowellClay1992" />
* Unidentified ''Acremonium'' species that infects drunken horse grass<ref name="MilesLanediMenna1996">{{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|url-access=subscription }}</ref> 
* ''Acremonium coenophialum'' (infects ''Festuca arundinacea'')<ref name="PetroskiPowell1991">{{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 }}</ref> 
* ''Epichloë gansuensis'' var. ''inebriens'' (infects drunken horse grass)<ref name="ChenLiLi2015">{{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 }}</ref> 
* ''Metarhizium brunneum''<ref name="LeadmonSampsonMaust2020">{{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 | article-number = e00373-20 }}</ref> 
* ''Metarhizium acridum''<ref name="LeadmonSampsonMaust2020" /> 
* ''Metarhizium anisopliae''<ref name="LeadmonSampsonMaust2020" /> 
* ''Metarhizium flavoviride''<ref name="LeadmonSampsonMaust2020" /> 
* ''Metarhizium robertsii''<ref name="LeadmonSampsonMaust2020" /> 
* ''Aspergillus leporis''<ref name="JonesSteenPanaccione2021">{{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 | date = November 2021 | pmid = 34586904 | pmc = 8612279 | doi = 10.1128/AEM.01801-21 | bibcode = 2021ApEnM..87E1801J | veditors = Atomi H | article-number = e01801-21 }}</ref> 
* ''Aspergillus homomorphus''<ref name="JonesSteenPanaccione2021" /> 
* ''Aspergillus hancockii''<ref name="JonesSteenPanaccione2021" />
{{Div col end}}

''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):

{{Div col|colwidth=20em}}
* ''Claviceps hirtella''<ref name="LorenzHaarmannPazoutová2009">{{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 }}</ref>
* ''Neotyphodium lolii''<ref name="FleetwoodScottLane2007" />
* Unidentified ''Epichlöe'' and ''Neotyphodium'' (asexual forms of ''Epichlöe'') species<ref name="SchardlLeuchtmannSpiering2004">{{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 }}</ref>
* ''Aspergillus fumigata''<ref name="Kozlovsky2006">{{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 }}</ref> 
* ''Aspergillus flavus''<ref name="Kozlovsky2006" />
* ''Botritis fabae''<ref name="Kozlovsky2006" />
* ''Curvularia lunata''<ref name="Kozlovsky2006" />
* ''Geotrichum candidum''<ref name="Kozlovsky2006" />
* ''Balansia cyperi''<ref name="Kozlovsky2006" /> 
* ''Balansia claviceps''<ref name="Kozlovsky2006" /> 
* ''Balansia epichloë''<ref name="Kozlovsky2006" />
* ''Epichloë amarillans''<ref name="SchardlYoungHesse2013">{{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 |article-number=e1003323 | pmid = 23468653 | pmc = 3585121 | doi = 10.1371/journal.pgen.1003323 | date = 2013-02-28 | doi-access = free | veditors = Heitman J }}</ref>
* ''Epichloë cabralii'' (H)<ref name="CharltonCravenAfkhami2014">{{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 }}</ref>
* ''Epichloë canadensis'' (H)<ref name="SchardlYoungPan2013">{{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}}</ref><ref name="CharltonCravenMittal2012">{{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 }}</ref>
* ''Epichloë coenophiala'' (H)<ref name="SchardlYoungPan2013" /><ref name="TakachMittalSwoboda2012">{{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 }}</ref><ref name="HaniganRicketts1993">{{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 }}</ref><ref name="YoungCharltonTakach2014" />
* ''Epichloë festucae''<ref name="SchardlYoungHesse2013" />
* ''Epichloë festucae'' var. ''lolii''<ref name="FleetwoodScottLane2007">{{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}}</ref><ref name="FlootwoodKhanJohnson2011">{{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 }}</ref>
* ''Epichloë festucae'' var. ''lolii'' x ''E. typhina'' (H)<ref name="SchardlYoungPan2013" /><ref name="PanaccioneJohnsonWang2001">{{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}}</ref>
* ''Epichloë inebriens''<ref name="SchardlYoungHesse2013" />
* ''Epichloë glyceriae''<ref name="SchardlYoungHesse2013" />
* ''Epichloë mollis''<ref name="SchardlYoungPan2013" />
* ''Epichloë typhina''<ref name="Kozlovsky2006" />
* ''Epichloë typhina'' ssp. ''poae''<ref name="SchardlYoungHesse2013" /><ref name="CharltonCravenAfkhami2014" />
* ''Epichloë typhina'' ssp. ''clarkii''<ref name="YoungSchardlPanaccione2015">{{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.</ref>
* ''Epichloë''{{nbsp}}sp. AroTG-2(H)<ref name="ShymanovichSaariLovin2015">{{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}}</ref>
* ''Epichloë'' sp. FaTG-2(H)<ref name="SchardlYoungPan2013" /><ref name="TakachMittalSwoboda2012" /><ref name="YoungCharltonTakach2014" /><ref name="ChristensenLeuchtmannRowan1993">{{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|url-access=subscription }}</ref><ref name="PanaccioneJohnsonWang2001"/>
* ''Epichloë'' sp. FaTG-4(H)<ref name="SchardlYoungPan2013" /><ref name="YoungCharltonTakach2014">{{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 }}</ref>
* ''Hypomyces aurantius''<ref name="Kozlovsky2006" />
* ''Sepedonium'' sp.<ref name="Kozlovsky2006" />
* ''Cunnigbamella blakesleana''<ref name="Kozlovsky2006" />
* ''Mucor biemalis''<ref name="Kozlovsky2006" />
* ''Rhizopus nigricans''<ref name="Kozlovsky2006" />
{{Div col end}}

===Biosynthesis===
[[File:Ergine_biosynthesis_part_1_(fixed).png|border|center|800x800px|class=skin-invert-image|Biosynthesis of the ergoline scaffold]]

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.<ref name="GerhardsNeubauerTudzynski2014">{{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 }}</ref> 4-Dimethylallyltyptophan [[N-methyltransferase|''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).<ref name="GerhardsNeubauerTudzynski2014" /> The conversion of 4-DMA-L-abrine to [[Chanoclavine|chanoclavine-I]] is thought to occur through a decarboxylation and two oxidation steps, catalyzed by the [[FAD dependent oxidoreductase family|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.<ref name="GerhardsNeubauerTudzynski2014" /><ref name="WillingaleAtwellMantle1983">{{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}}</ref>

[[File:Ergine_biosynthesis_part_2.png|border|center|650x650px|class=skin-invert-image|Formation of agroclavine]]

From here, the biosynthesis diverges and the products formed are plant and fungus-specific. The biosynthesis of ergine in [[Claviceps purpurea|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.<ref name="GerhardsNeubauerTudzynski2014" /><ref name="WillingaleAtwellMantle1983" /> [[Cytochrome P450 monooxygenase]]s (CYP<sub>450</sub>) 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 CYP<sub>450</sub> monooxygenase. Paspalic acid then undergoes [[isomerization]] of the C-C double bond in conjugation with the acid to form [[Lysergic acid|D-lysergic acid]].<ref name="GerhardsNeubauerTudzynski2014" /> While the specifics of the formation of ergine from [[Lysergic acid|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.<ref name="GerhardsNeubauerTudzynski2014" /><ref name="WillingaleAtwellMantle1983" />

[[File:Ergine_biosynthesis_part_3.png|border|center|850x850px|class=skin-invert-image]]

==History==
Ergine was first obtained by Sidney Smith and Geoffrey Willward Timmis in 1932.<ref name="SmithTimmis1932">{{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|url-access=subscription }}</ref>

[[Albert Hofmann]] was first to identify ergine as a natural constituent of ''[[Turbina corymbosa]]'' seeds.<ref name="Hofmann2009" />

Albert Hofmann describes ergine as "the main constituent of ''ololiuhqui''".<ref name="WassonHofmannRuck1978">{{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''.}}</ref> ''Ololiuhqui'' was used by South American healers in shamanic healing ceremonies.<ref name="Sewell2008">{{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 }}</ref> Similarly, ingestion of [[morning glory]] seeds by [[Mazatec]] tribes to "commune with their gods" was reported by [[Richard Evans Schultes|Richard Schultes]] in 1941 and is still practiced today.<ref name="Schultes1941">{{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}}</ref><ref name="Sewell2008" />

According to the ethnobotanist [[R. Gordon Wasson]], Thomas MacDougall and Francisco Ortega ("Chico"), a [[Zapotec peoples|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.<ref name="Wasson1961">{{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}}</ref>

The [[Central Intelligence Agency]] conducted research on the psychedelic properties of ''Rivea corymbosa'' seeds for [[MKULTRA]].<ref name="CIA1956">{{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}}</ref>

{{blockquote|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 (<nowiki>=</nowiki>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<ref name="Ott1996">{{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}}</ref>}}

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.<ref name="BrimblecombePinder1975" />

==Society and culture==
===Legal status===
The legality of consuming, cultivating, and possessing ergine varies depending on the country.

====Australia====
In most Australian states, the consumption of ergine containing materials is prohibited under state legislation.

====Canada====
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.<ref name="Erowid-LSA">{{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}}</ref>

====New Zealand====
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.

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

====United States====
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]].<ref name="USDOJ2021">{{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}}</ref>

==See also==
* [[Substituted lysergamide]]
* [[Isoergine]] (isolyergic acid amide; iso-LSA; isolysergamide)
* [[Aztec use of entheogens#Ololiuqui and Tlitliltzin|Aztec use of entheogens § Ololiuqui and Tlitliltzin]]
* [[Morning glory#Chemistry and ethnobotany|Morning glory § Chemistry and ethnobotany]]
* [[List of entheogens]]
* [[List of psychoactive plants]]

==References==
{{Reflist}}

==External links==
* [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]
* [https://tripsitter.com/psychedelics/lysergamides/#11_LSA LSA - Lysergamide Psychedelics - TripSitter]

{{Ergolines}}
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