Ergine

Ergine, also known as lysergic acid amide (LSA or LAA) as well as LA-111, is a psychoactive compound of the ergoline and lysergamide families related to lysergic acid diethylamide (LSD).<ref name="Waters2021">Template:Cite journal</ref><ref name="SteinerLeistner2018">Template:Cite journal</ref><ref name="TittarelliMannocchiPantano2015" /><ref name="GrofHofmann1984">Template:Cite journal</ref> Ergine is an ergoline alkaloid found in fungi such as Claviceps paspali (ergot) and Periglandula species,<ref name="SteinerLeistner2018" /> which are permanently connected with many 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">Template:Cite journal</ref><ref name="ChenDeWitBos2020" /><ref name="MoukaddamRuiz2013">Template:Cite book</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">Template:Cite journal</ref><ref name="TiHKAL-LSD">Template:Cite book</ref><ref name="Hofmann2009">Template:Cite book</ref> Morning glory seeds have a history of entheogenic use in Mesoamerica dating back at least hundreds of years.<ref name="SteinerLeistner2018" /><ref name="Hofmann1971">Template:Cite journal</ref><ref name="Schultes1969">Template:Cite journal</ref> They have also since been used by many Westerners.<ref name="Shulgin1976" /> In addition to ergine, morning glory seeds contain other ergolines such as lysergic acid hydroxyethylamide (LSH), lysergic acid propanolamide (ergonovine), and isoergine.<ref name="Hofmann1963">Template:Cite journal</ref><ref name="Hofmann1971" /><ref name="SteinerLeistner2018" /> Some of these compounds are 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">Template:Cite book</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">Template:Cite journal</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 synthesized subsequent to its isolation in the 1930s.<ref name="Hofmann1963" /><ref name="StollHofmann1955">Template:Cite journal</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">Template:Cite book</ref><ref name="HofmannTscherter1960">Template:Cite journal</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 has been widely used since.<ref name="SteinerLeistner2018" /><ref name="HofferOsmond1967" /><ref name="JuszczakSwiergiel2013">Template:Cite journal</ref><ref name="Burillo-PutzeLópezBrizClimentDíaz2013">Template:Cite journal</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</ref><ref name="TittarelliMannocchiPantano2015" /><ref name="Waters2021" /> A hallucinogenic dose (~0.5–1Template:Nbspmg) is 150 to 200Template:Nbspseeds (3–6Template:Nbspg) of Ipomoea tricolor (0.02% ergine by dry weight) or 5 to 10Template:Nbspseeds (0.5–1Template:Nbspg) of Argyreia nervosa (0.14% ergine by dry weight).<ref name="Halpern2004" /><ref name="TittarelliMannocchiPantano2015" /><ref name="Waters2021" /><ref name="Shulgin1976" /><ref name="ChenDeWitBos2020">Template:Cite report</ref> The onset is 0.3 to 3Template:Nbsphours and the duration is 4 to 10Template:Nbsphours.<ref name="Halpern2004" /><ref name="TittarelliMannocchiPantano2015" /><ref name="Waters2021" />

Ergine may be used as a drug in pure or purified form as well, either isolated or synthesized.<ref name="TiHKAL-LSD" /><ref name="Heacock1975" /><ref name="SoleilLalloz1971" /> Albert Hofmann and colleagues found that a 0.5 to 2Template:Nbspmg dose by 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">Template:Cite journal</ref><ref name="Hofmann1970">Template:Cite book</ref> Another study described the effects of pure ergine by injection but the doses were not clearly provided (although appeared to be around 0.1–1Template:Nbspmg).<ref name="Shulgin1976" /><ref name="HofferOsmond1967" /><ref name="Solms1956a">Template:Cite journal</ref><ref name="Solms1956b">Template:Cite journal</ref> Based on the preceding studies, Alexander Shulgin describes pure ergine as having a dosage of 0.5 to 1Template:Nbspmg and being 10-fold less potent than LSD, but as being "not hallucinogenic".<ref name="Shulgin2003">Template:Cite book</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 of 3 to 6Template:Nbspmg orally and observed toxic-like effects, whereas isoergine at 2 to 5Template:Nbspmg orally produced notable hallucinogenic effects, including some euphoria, synaesthesia, and altered time perception.<ref name="ChenDeWitBos2020" /><ref name="BrimblecombePinder1975">Template:Cite book</ref><ref name="HeimHeimannLukács1968" />

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">Template:Cite book</ref><ref name="Cole2013">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</ref> 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" />

Clinical studies of ergine's effects

Hofmann 1963<ref name="Hofmann1963" />	Heim 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:Template:Long quote

"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">Template:Cite book</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 hallucinations, auditory hallucinations, euphoria, loss of motor control, nausea, vasoconstriction, delusions, anxiety, paranoia, and irregular heartbeats.<ref name="Hofmann2009" /><ref name="Sewell2008" /><ref name="Ingram1964" /><ref name="KremerPaulkeWunder2012">Template:Cite journal</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" /> Ergoclavines are known to cause convulsive ergotism,<ref name="SchardlPanaccioneTudzynski2006">Template:Cite journal</ref> the milder form of ergotism. Gangrenous ergotism is caused by ergopeptines: the complex peptide moiety forces persistence at the receptor sites.<ref name="Eich2008" /> Ergopeptines are rare in Convolvulaceae, being found in 10 species,<ref name="Eich2008">Template:Cite book</ref><ref name="BeaulieuPanaccioneHazekamp2013">Template:Cite journal</ref> not including the three that are commonly ingested, although Paulke 2014 says analytical evidence suggests that A. nervosa contains ergopeptines.<ref name="PaulkeKremerWunder2015">Template:Cite journal</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 cm³ 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">Template:Cite journal</ref>

Like other psychedelics, ergine is not considered to be addictive. Additionally, there are no known deaths directly associated with pharmacological effects of ergine consumption. All associated deaths are due to indirect causes, such as self-harm, impaired judgement, and adverse drug interactions. One known case involved a suicide that was reported in 1964 after ingestion of morning glory seeds.<ref name="Cohen1964">Template:Cite journal</ref> Another instance is a death due to falling off of a building after ingestion of Hawaiian baby woodrose seeds and alcohol.<ref name="KlinkeMüllerSteffenrud2010">Template:Cite journal</ref> A study gave mice 3000Template:Nbspmg/kg with no lethal effects.Template:Citation needed

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">Template:Cite book</ref><ref name="Ono2017">Template:Cite journal</ref> and ergoclavines.<ref name="SchardlPanaccioneTudzynski2006" /> SomeTemplate:Who even believe that an emetic chemical is purposely added to the seeds to prevent people from ingesting them, but that has never been proven.Template:Citation needed 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">Template:Cite journal</ref><ref name="Cohen1964" /><ref name="Frear1963">Template:Cite book</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">Template:Cite book</ref> but that is probably just a misapplication of the claim that peyote contains strychnine, which, itself, is a rumor.<ref name="Pendell2010">Template:Cite book</ref>

Overdose

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

Interactions

The interactions of ergine and of morning glory seeds have been discussed.<ref name="ChenDeWitBos2020" />

Pharmacology

Pharmacodynamics

LSA and LSD activities

Receptor	Affinity (Ki, nM)		Ratio
	LSA	LSD
5-HT1A	73	1.6	46:1
5-HT2A	28–132 (Ki) 1.1–58 (Template:Abbrlink) 47–82% (Template:Abbrlink)	0.87–1.1 (Ki) 0.52–3.6 (Template:Abbr) 60–86% (Template:Abbr)	32–120:1 2–16:1 0.78–0.95:1
5-HT2B	54–115 (Template:Abbr) 40–55% (Template:Abbr)	0.68–34 (Template:Abbr) 62–73% (Template:Abbr)	3–79:1 0.65–0.75:1
5-HT2C	798	7.8	102:1
D1 (pig)	832	87	10:1
D2L	891	155	6:1
D2S	145	25	6:1
D3	437	65	7:1
D4.4	141	30	5:1
α1	912	60	15:1
α2	62	1.0	62:1
Notes: All proteins are human unless otherwise specified. Sources: <ref name="PaulkeKremerWunder2013">Template:Cite journal</ref><ref name="WackerWangMcCorvy2017">Template:Cite journal</ref><ref name="McCorvy2013">{{#invoke:citation/CS1|citation				CitationClass=web }}</ref>

Ergine interacts with serotonin, dopamine, and adrenergic receptors similarly to but with lower affinity than lysergic acid diethylamide (LSD).<ref name="PaulkeKremerWunder2013" /><ref name="WackerWangMcCorvy2017" /> It is known to act as an agonist of the serotonin 5-HT_2A and 5-HT_2B receptors similarly to LSD, albeit much less potently and with reduced activational efficacy.<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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="CerlettiDoepfner1958">Template:Cite journal</ref> The psychedelic effects of ergine can be attributed to activation of serotonin 5-HT_2A receptors.<ref name="HalberstadtNichols2020">Template:Cite book</ref><ref name="KelmendiKayePittenger2022">Template:Cite journal</ref><ref name="Nichols2018">Template:Cite book</ref>

Chemistry

Ergine, also known as lysergic acid amide (LSA) or as lysergamide, is a ergoline and lysergamide. It is the simplest lysergamide and is the parent structure of this family of compounds. Hence, all lysergamides are derivatives of ergine. Lysergic acid diethylamide (LSD) is the analogue of ergine with two ethyl groups substituted on its amide moiety.

The extraction of ergine from morning glory seeds has been described.<ref name="Shanks2001">Template:Cite journal</ref><ref name="SomaGraphics1996">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Natural occurrence

Ergine is not a biosynthetic endpoint itself, but rather a hydrolysis product of lysergic acid hydroxyethylamide (LSH), lysergic acid propanolamide (ergonovine), and ergopeptines or their ergopeptam precursors.<ref name="FliegerSedmeraVokoun1982">Template:Cite journal</ref><ref name="Ramstad1968">Template:Cite journal</ref><ref name="KleinerováKybal1973">Template:Cite journal</ref><ref name="PanaccioneTapperLane2003">Template:Cite journal</ref><ref name="Panaccione2010">Template:Cite book</ref>

LSH is very vulnerable to this hydrolysis,<ref name="Shulgin1976">Template:Cite book</ref><ref name="SchultesHofmann1973">Template:Cite book</ref> and many analyses of ergoline-containing fungi show little to no LSH and substantial amounts of ergine.

An ergine analog, 8-hydroxyergine, has also been found in natural products in two studies.<ref name="FliegerLinhartováSedmera1989">Template:Cite journal</ref><ref name="PetroskiPowellClay1992">Template:Cite journal</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">Template:Cite journal</ref><ref name="CastagnoliCorbettChain1970">Template:Cite journal</ref><ref name="BasmadjianFlossGröger1969">Template:Cite journal</ref> but are only found in trace amounts in the more well-known Claviceps purpurea.<ref>Template:Cite book</ref><ref name="WassonHofmannRuck2008">Template:Cite book</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>Template:Cite book</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">Template:Cite journal</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:

• Unidentified Acremonium species that infects sleepy grass (C. purpurea also infects sleepy grass<ref name="AldermanHalseWhite2004">Template:Cite journal</ref>).<ref name="PetroskiPowellClay1992" />
• Unidentified Acremonium species that infects drunken horse grass<ref name="MilesLanediMenna1996">Template:Cite journal</ref>
• Acremonium coenophialum (infects Festuca arundinacea)<ref name="PetroskiPowell1991">Template:Cite book</ref>
• Epichloë gansuensis var. inebriens (infects drunken horse grass)<ref name="ChenLiLi2015">Template:Cite journal</ref>
• Metarhizium brunneum<ref name="LeadmonSampsonMaust2020">Template:Cite journal</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">Template:Cite journal</ref>
• Aspergillus homomorphus<ref name="JonesSteenPanaccione2021" />
• Aspergillus hancockii<ref name="JonesSteenPanaccione2021" />

All of these fungi are related to Claviceps fungi. Aspergillus is considered to be a more distant relative of Claviceps.

Other fungi that possibly contain ergine (i.e. they have been found to contain ergonovine and/or ergopeptines):

• Claviceps hirtella<ref name="LorenzHaarmannPazoutová2009">Template:Cite journal</ref>
• Neotyphodium lolii<ref name="FleetwoodScottLane2007" />
• Unidentified Epichlöe and Neotyphodium (asexual forms of Epichlöe) species<ref name="SchardlLeuchtmannSpiering2004">Template:Cite journal</ref>
• Aspergillus fumigata<ref name="Kozlovsky2006">Template:Cite book</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">Template:Cite journal</ref>
• Epichloë cabralii (H)<ref name="CharltonCravenAfkhami2014">Template:Cite journal</ref>
• Epichloë canadensis (H)<ref name="SchardlYoungPan2013">Template:Cite journal</ref><ref name="CharltonCravenMittal2012">Template:Cite journal</ref>
• Epichloë coenophiala (H)<ref name="SchardlYoungPan2013" /><ref name="TakachMittalSwoboda2012">Template:Cite journal</ref><ref name="HaniganRicketts1993">Template:Cite journal</ref><ref name="YoungCharltonTakach2014" />
• Epichloë festucae<ref name="SchardlYoungHesse2013" />
• Epichloë festucae var. lolii<ref name="FleetwoodScottLane2007">Template:Cite journal</ref><ref name="FlootwoodKhanJohnson2011">Template:Cite journal</ref>
• Epichloë festucae var. lolii x E. typhina (H)<ref name="SchardlYoungPan2013" /><ref name="PanaccioneJohnsonWang2001">Template:Cite journal</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">Template:Cite journal

See table 3 on p. 1290.</ref>

• EpichloëTemplate:Nbspsp. AroTG-2(H)<ref name="ShymanovichSaariLovin2015">Template:Cite journal</ref>
• Epichloë sp. FaTG-2(H)<ref name="SchardlYoungPan2013" /><ref name="TakachMittalSwoboda2012" /><ref name="YoungCharltonTakach2014" /><ref name="ChristensenLeuchtmannRowan1993">Template:Cite journal</ref><ref name="PanaccioneJohnsonWang2001">Template:Cite journal</ref>
• Epichloë sp. FaTG-4(H)<ref name="SchardlYoungPan2013" /><ref name="YoungCharltonTakach2014">Template:Cite journal</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" />

Biosynthesis

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">Template:Cite journal</ref> 4-Dimethylallyltyptophan N-methyltransferase (EasF) catalyzes the N-methylation of 4-L-DMAT at the amino of the tryptophan backbone, using S-Adenosyl methionine (SAM) as the methyl source, to form 4-dimethylallyl-L-abrine (4-DMA-L-abrine).<ref name="GerhardsNeubauerTudzynski2014" /> The conversion of 4-DMA-L-abrine to chanoclavine-I is thought to occur through a decarboxylation and two oxidation steps, catalyzed by the FAD dependent oxidoreductase, EasE, and the catalase, EasC. The chanoclavine intermediate is then oxidized to chanoclavine-l-aldehyde, catalyzed by the short-chain dehydrogenase/reductase (SDR), EasD.<ref name="GerhardsNeubauerTudzynski2014" /><ref name="WillingaleAtwellMantle1983">Template:Cite journal</ref>

Formation of argoclavine

From here, the biosynthesis diverges and the products formed are plant and fungus-specific. The biosynthesis of ergine in Claviceps purpurea will be exemplified, in which agroclavine is produced following the formation of chanoclavine-l-aldehyde, catalyzed by EasA through a keto-enol tautomerization to facilitate rotation about the C-C bond, followed by tautomerization back to the aldehyde and condensation with the proximal secondary amine to form an iminium species, which is subsequently reduced to the tertiary amine and yielding argoclavine.<ref name="GerhardsNeubauerTudzynski2014" /><ref name="WillingaleAtwellMantle1983" /> Cytochrome P450 monooxygenases (CYP₄₅₀) are then thought to catalyze the formation of elymoclavine from argoclavine via a 2 electron oxidation. This is further converted to paspalic acid via a 4 electron oxidation, catalyzed by cloA, a CYP₄₅₀ monooxygenase. Paspalic acid then undergoes isomerization of the C-C double bond in conjugation with the acid to form D-lysergic acid.<ref name="GerhardsNeubauerTudzynski2014" /> While the specifics of the formation of ergine from D-lysergic acid are not known, it is proposed to occur through a nonribosomal peptide synthase (NRPS) with two enzymes primarily involve: D-lysergyl peptide synthase (LPS) 1 and 2.<ref name="GerhardsNeubauerTudzynski2014" /><ref name="WillingaleAtwellMantle1983" />

File:Ergine biosynthesis part 3.png

History

Ergine was first obtained by Sidney Smith and Geoffrey Willward Timmis in 1932.<ref name="SmithTimmis1932">Template:Cite journal</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">Template:Cite book</ref> Ololiuhqui was used by South American healers in shamanic healing ceremonies.<ref name="Sewell2008">Template:Cite journal</ref> Similarly, ingestion of morning glory seeds by Mazatec tribes to "commune with their gods" was reported by Richard Schultes in 1941 and is still practiced today.<ref name="Schultes1941">Template:Cite book</ref><ref name="Sewell2008" />

According to the ethnobotanist R. Gordon Wasson, Thomas MacDougall and Francisco Ortega ("Chico"), a Zapotec guide and trader, should be credited for the discovery of the ceremonial use of Ipomoea tricolor seeds in Zapotec towns and villages in the uplands of southern Oaxaca. The seeds of both Ipomoea tricolor and Rivea corymbosa, another species which has a similar chemical profile, are used in some Zapotec towns.<ref name="Wasson1961">Template:Cite book</ref>

The Central Intelligence Agency conducted research on the psychedelic properties of Rivea corymbosa seeds for MKULTRA.<ref name="CIA1956">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

See also

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

External links

• d-Lysergamide (Ergine; LA-111; LAA; LSA) - Isomer Design
• Angel’s Trumpets and Morning Glories—An Ethnobotanical Survey of Psychoactive Perennials Part 2: Ipomoea - God Among Men
• LSA - PsychonautWiki
• LSA - Erowid
• The Big & Dandy Hawaiian Baby Woodrose Seeds / Morning Glory Seeds / LSA Thread - Bluelight
• LSD-25: LA-111, ergine, d-lysergamide - TiHKAL - Erowid
• LSD-25: LA-111, ergine, d-lysergamide - TiHKAL - Isomer Design
• LSA (Lysergic Acid Amide): Naturally-Occurring Acid With Sedative Qualities - Tripsitter