Ergine Explained

Ergine, also known as lysergic acid amide and lysergamide, is an ergoline alkaloid that occurs in various species of vines of the Convolvulaceae and some species of fungi. The psychedelic properties in the seeds of ololiuhqui, Hawaiian baby woodrose and morning glories have been linked to ergine and/or isoergine, its epimer, as it is an alkaloid present in the seeds.[1] [2] [3]

Occurrence in nature

Ergine is not a biosynthetic endpoint itself, but rather a hydrolysis product of lysergic acid hydroxyethylamide (LAH), lysergic acid hydroxymethylethylamide (ergonovine), and ergopeptines or their ergopeptam precursors.[4] [5] [6] [7] [8]

Lysergic acid hydroxyethylamide is very vulnerable to this hydrolysis,[9] [10] and many analyses of ergoline-containing fungi show little to no LAH and substantial amounts of ergine.

An ergine analog, 8-hydroxyergine, has also been found in natural products in two studies.[11] [12] Methylergonovine and methylmethylergonovine (methysergide) have also been found in a natural product in only one study;[13] these are documented as semisynthetic chemicals, so the findings need to be repeated for certainty. The aforementioned chemicals are the only natural ergoamides.

LAH & ergine are predominant in Claviceps paspali,[14] [15] [16] but are only found in trace amounts in the more well-known Claviceps purpurea[17] [18] (both are ergot-spreading fungi). The major products of C. purpurea are ergopeptines, but C. paspali does not generate ergopeptines.[19] Ergonovine is the only ergoamide in C. purpurea in a substantial amount.[20]

LAH & 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[21] (ergolines have been identified in 42 of these plants and not all of them contain ergine[22]). Ergonovine is present in Ipomoea tricolor in one-tenth to one-third of the amount of ergine.[23] This variable may account for the varying reports about the psychedelic effect of these seeds.[24]

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

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

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

Psychedelic Effects

Ergine has only been given a miniscule amount of attention. Albert Hofmann and his colleagues self-administered ergine,[50] and it was adminstered in two clinical trials.[51] [52] Synthetic ergine was used in all cases. Albert Hofmann stated that ergine induces a “psychotomimetic” effect with “a marked narcotic component”: “Tired, dreamy, incapable of clear thoughts. Very sensitive to noises which give an unpleasant sensation.” There are parallels between Hofmann's comments and the ones in the two trials:

!Hofmann 1963!Heim 1968!Solms 1956
“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:

“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).”[53]

“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.”[54]

“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.”[55]

Pharmacology

Pharmacodynamics

Affinities of LSA and LSD for various receptors[56]
Receptor Affinity (Ki [nM])
LSA LSD
10 2.5
28 0.87
832 87
891 155
145 25
437 65
141 30
912 60
62 1.0
Notes: 5-HT1A and D1 are for pig receptors.

Ergine interacts with serotonin, dopamine, and adrenergic receptors similarly to but with lower affinity than lysergic acid diethylamide (LSD).[57] The psychedelic effects of ergine can be attributed to activation of serotonin 5-HT2A receptors.[58]

Chemistry

History

Ergine was first obtained by Sidney Smith and Geoffrey Willward Timmis in 1932.[59]

Albert Hofmann was first to identify ergine as a natural constituent of Turbina corymbosa seeds.

Biosynthesis

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.[60] 4-Dimethylallyltyptophan N-methyltransferase (EasF) catalyzes the N-methylation of 4-L-DMAT at the amino of the tryptophan backbone, using S-Adenosyl methionine (SAM) as the methyl source, to form 4-dimethylallyl-L-abrine (4-DMA-L-abrine). The conversion of 4-DMA-L-abrine to chanoclavine-I is thought to occur through a decarboxylation and two oxidation steps, catalyzed by the FAD dependent oxidoreductase, EasE, and the catalase, EasC. The chanoclavine intermediate is then oxidized to chanoclavine-l-aldehyde, catalyzed by the short-chain dehydrogenase/reductase (SDR), EasD.[61]

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

Use of Morning Glory seeds as a drug

History

Albert Hofmann describes ergine as “the main constituent of ololiuhqui”.[62] Ololiuhqui was used by South American healers in shamanic healing ceremonies.[63] 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.[64] [63]

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.[65]

The Central Intelligence Agency conducted research on the psychedelic properties of Rivea corymbosa seeds for MKULTRA.[66]

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:[3] [63] [67]

One study found that 2 of 4 human subjects experienced cardiovascular dysregulation and the study had to be halted, concluding that the ingestion of seeds containing ergine was less safe then commonly believed. Importantly this may have been a product of other substances within the seeds. The same study also observed that reactions were highly differing in type and intensity between different subjects.[68]

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.[69] Another instance is a death due to falling off of a building after ingestion of Hawaiian baby woodrose seeds and alcohol.[70] A study gave mice 3000 mg/kg with no lethal effects.

A 2016 study showed that penniclavine was the predomiant alkaloid in Ipomoea tricolor seeds. Ergoclavines are known to cause convulsive ergotism,[71] the milder form of ergotism. Gangrenous ergotism is caused by ergopeptines; the complex peptide moiety forces persistance at the receptor sites.[72] Ergopeptines are rare in Convolvulaceae, being found in 10 species,[73] [74] not including the three that are commonly ingested, although Paulke 2014 says analytical evidence suggests that A. nervosa contains ergopeptines.[75] Many people desire purified seed extracts, but the efficacy of this is questionable, as even pure ergine and ergonovine have shown toxic effects.

Ergine:

“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.”

Heim 1968[76]

Ergonovine:

“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,”

Bigwood 1979[77]

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[78] [79] and ergoclavines.[80] Some people even believe that an emetic chemical is purposely added to the seeds to prevent people from ingesting them, but that has never been proven. 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.[81]

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,[82] and Eckart Eich says that they probably don't occur in many Convolvulaceae.[83] There is a similar claim in a publication from 1973, warning about “a strychnine-like alkaloid”,[84] but that is probably just a misapplication of the claim that peyote contains strychnine, which, itself, is a rumor.[85]

Legal status

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

There are no laws against possession of ergine-containing seeds in the United States. However, possession of the pure compound without a prescription or a DEA license would be prosecuted, as ergine, under the name "lysergic acid amide", is listed under Schedule III of the Controlled Substances Act.[86] Similarly, ergine is considered a Class A substance in the United Kingdom, categorized as a precursor to LSD.

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

In Canada, ergine is not illegal to possess as it is not listed under Canada's Controlled Drugs and Substances Act, though it is likely illegal to sell for human consumption.[87]

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.

See also

Further reading

External links

Notes and References

  1. Perrine DM. 2000. Mixing the Kykeon. ELEUSIS: Journal of Psychoactive Plants and Compounds. New Series 4. 9. 2008-05-05. 2019-07-20. https://web.archive.org/web/20190720192225/http://www.psychedelic-library.org/Mixing%20the%20Kykeon%20Final%20Draft.pdf. dead.
  2. Book: Shulgin A . TiHKAL.
    1. 26. LSD-25
    . http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml. Erowid.org. 2012-02-03.
  3. Book: Hofmann A . LSD My Problem Child: Reflections on Sacred Drugs, Mysticism, and Science . 2009 . MAPS.org . 978-0979862229 . 4th.
  4. Flieger M, Sedmera P, Vokoun J, ((R̆ic̄icovā A)), ((R̆ehác̆ek Z)) . 1982-02-19 . Separation of four isomers of lysergic acid α-hydroxyethylamide by liquid chromatography and their spectroscopic identification . Journal of Chromatography A . 236 . 2 . 441–452 . 10.1016/S0021-9673(00)84895-5 . 0021-9673.
  5. Ramstad E . 1968 . Chemistry of alkaloid formation in ergot . Lloydia . 31 . 327–341.
  6. Kleinerová E, Kybal J . Ergot alkaloids. IV. Contribution to the biosynthesis of lysergic acid amides . Folia Microbiologica . 18 . 5 . 390–392 . 4757982 . 10.1007/BF02875934 . September 1973 .
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  8. Book: Panaccione DG . Ergot alkaloids . The Mycota, Industrial Applications . 2nd . Hofrichter M . Springer-Verlag . Berlin-Heidelburg, Germany . 2010 . 10 . 195–214 .
  9. Book: Shulgin A . https://books.google.com/books?id=yt2KcKcJROgC&pg=PA71 . Psychopharmacological agents . Academic Press . 1976 . 978-0-12-290559-9 . Maxwell G . Medicinal Chemistry . 4 . New York . 59–00 . 4. Psychotomimetic Agents.
  10. Book: Schultes RE, Hofmann A . The Botany and Chemistry of Hallucinogens . Charles Thomas . 1973 . 9780398064167 . Springfield, IL.
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    “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).” Results and Discussion, p. 87
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    “On the other hand, methylergometrine, methysergide, and lysergylalanine were detected, which have not yet been reported as compounds of Argyreia nervosa seeds.” 3. Results and Discussion, p. 283
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    Table 4.1 Unambiguously ergoline-positive Ipomoea species (pages 225-227)
    Table 4.4 Unambiguously ergoline-positive Argyreia species (p. 236)
    Table 4.5 Unambiguously ergoline-positive Stictocardia and Turbina species (p. 238)
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    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..
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  44. Panaccione DG, Johnson RD, Wang J, Young CA, Damrongkool P, Scott B, Schardl CL . Elimination of ergovaline from a grass-Neotyphodium endophyte symbiosis by genetic modification of the endophyte . Proceedings of the National Academy of Sciences of the United States of America . 98 . 22 . 12820–12825 . October 2001 . 11592979 . 60137 . 10.1073/pnas.221198698 . free . 2001PNAS...9812820P . 2001-10-23 .
  45. Young CA, Schardl CL, Panaccione DG, Florea S, Takach JE, Charlton ND, Moore N, Webb JS, Jaromczyk J . Genetics, genomics and evolution of ergot alkaloid diversity . Toxins . 7 . 4 . 1273–1302 . April 2015 . 25875294 . 4417967 . 10.3390/toxins7041273 . free . 2015-04-16 . See table 3 on p. 1290.
  46. Shymanovich T, Saari S, Lovin ME, Jarmusch AK, Jarmusch SA, Musso AM, Charlton ND, Young CA, Cech NB, Faeth SH . Alkaloid variation among epichloid endophytes of sleepygrass (Achnatherum robustum) and consequences for resistance to insect herbivores . Journal of Chemical Ecology . 41 . 1 . 93–104 . January 2015 . 25501262 . 10.1007/s10886-014-0534-x . 2015JCEco..41...93S . 2014-12-11 .
  47. Christensen M, Leuchtmann A, Rowan D, Tapper B . 1993-09-01 . Taxonomy of Acremonium endophytes of tall fescue (Festuca arundinacea), meadow fescue (F. pratensis) and perennial ryegrass (Lolium perenne) . Mycological Research . en . 97 . 9 . 1083–1092 . 10.1016/S0953-7562(09)80509-1.
  48. Panaccione DG, Johnson RD, Wang J, Young CA, Damrongkool P, Scott B, Schardl CL . Elimination of ergovaline from a grass-Neotyphodium endophyte symbiosis by genetic modification of the endophyte . Proceedings of the National Academy of Sciences of the United States of America . 98 . 22 . 12820–12825 . October 2001 . 11592979 . 60137 . 10.1073/pnas.221198698 . free . 2001PNAS...9812820P . 2001-10-23 .
  49. Young CA, Charlton ND, Takach JE, Swoboda GA, Trammell MA, Huhman DV, Hopkins AA . Characterization of Epichloë coenophiala within the US: are all tall fescue endophytes created equal? . Frontiers in Chemistry . 2 . 95 . 25408942 . 4219521 . 10.3389/fchem.2014.00095 . 2014-11-04 . free . 2014FrCh....2...95Y .
  50. Hofmann A . The Active Principles of the Seeds of Rivea corymbosa and Ipomoea violacea . Harvard Botanical Museum Leaflets . 20 . 6 . 208–210 . 1963 .
    This plant is now considered to be Ipomoea tricolor..
  51. Solms H . Relationships between chemical structure and psychoses with the use of psychotoxic substances; comparative pharmacopsychiatric analysis: a new research method . Journal of Clinical and Experimental Psychopathology . 17 . 4 . 429–433 . 1956 . 13406032 .
  52. Heim E, Heimann H, Lukács G . Die psychische Wirkung der mexikanischen Droge „Ololiuqui“ am Menschen . de . Psychopharmacologia . 13 . 1 . 35–48 . 1968 . 5675457 . 10.1007/BF00401617 .
    The quotes on this page were translated w/ Google Translate..
  53. Book: Schultes RE, Hofmann A . The Botany and Chemistry of Hallucinogens . Charles Thomas . 1973 . 9780398064167 . Springfield, IL . 252 . Convolvulaceae.
  54. Book: Hofmann A . LSD, My Problem Child . 1980 . McGraw-Hill . 978-0-07-029325-0 . New York . 3. Chemical Modifications of LSD.
  55. Grof S, Hofmann A . Stanislav Grof Interviews Dr. Albert Hofmann . MAPS Bulletin . 9 . 2 . Fall 2001 . 1984 . 22–35 .
  56. Paulke A, Kremer C, Wunder C, Achenbach J, Djahanschiri B, Elias A, Schwed JS, Hübner H, Gmeiner P, Proschak E, Toennes SW, Stark H . Argyreia nervosa (Burm. f.): receptor profiling of lysergic acid amide and other potential psychedelic LSD-like compounds by computational and binding assay approaches . Journal of Ethnopharmacology . 148 . 2 . 492–497 . July 2013 . 23665164 . 10.1016/j.jep.2013.04.044 .
  57. 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, 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 . Crystal Structure of an LSD-Bound Human Serotonin Receptor . Cell . 168 . 3 . 377–389.e12 . January 2017 . 28129538 . 5289311 . 10.1016/j.cell.2016.12.033 .
  58. Book: Halberstadt AL, Nichols DE . Handbook of the Behavioral Neurobiology of Serotonin. Serotonin and serotonin receptors in hallucinogen action. Handbook of Behavioral Neuroscience. 31. 2020. 843–863. 1569-7339. 10.1016/B978-0-444-64125-0.00043-8. 9780444641250.
  59. Smith S, Timmis GM . 1932 . 98. The alkaloids of ergot. Part III. Ergine, a new base obtained by the degradation of ergotoxine and ergotinine . Journal of the Chemical Society (Resumed) . en . 763 . 10.1039/jr9320000763 . 0368-1769.
  60. Gerhards N, Neubauer L, Tudzynski P, Li SM . Biosynthetic pathways of ergot alkaloids . Toxins . 6 . 12 . 3281–3295 . December 2014 . 25513893 . 4280535 . 10.3390/toxins6123281 . free .
  61. Willingale J, Atwell SM, Mantle PG . 1983-07-01. Unusual Ergot Alkaloid Biosynthesis in Sclerotia of a Claviceps purpurea Mutant. Microbiology. 129. 7. 2109–2115. 10.1099/00221287-129-7-2109. 1350-0872. free.
  62. Book: Wasson RG, Hofmann A, Ruck CA, Webster P . The Road to Eleusis: Unveiling the Secret of the Mysteries . North Atlantic Books . 978-1-55643-752-6 . Forte R . 30th Anniversary . Berkeley, Calif. . November 25, 2008 . 1978 . En .
    “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.” Hofmann, 2. A Challenging Question and My Answer, p. 41.
  63. Sewell RA . 2008. Unauthorized research on cluster headache. . The Entheogen Review . 16 . 4 . 117–125 .
  64. Book: Schultes RE . A Contribution to Our Knowledge of Rivea Corymbosa: The Narcotic Ololinqui of the Aztecs. 1941. Botanical Museum of Harvard University. 1st.
  65. Book: Wasson RG . The Hallucinogenic Fungi Of Mexico: An Inquiry Into The Origins of The Religious Idea Among Primitive Peoples . 1961 . 27 November 2024 . http://web.archive.org/web/20101122083945/http://druglibrary.net/schaffer/lsd/wasson.htm . 22 November 2010.
  66. Web site: Project Mkultra, Subproject 22 (w/attachments) . Central Intelligence Agency.
  67. Ingram AL . Morning Glory Seed Reaction . JAMA . 190 . 13 . 1133–1134 . December 1964 . 14212309 . 10.1001/jama.1964.03070260045019 . 13 .
  68. Kremer C, Paulke A, Wunder C, Toennes SW . Variable adverse effects in subjects after ingestion of equal doses of Argyreia nervosa seeds . Forensic Science International . 214 . 1–3 . e6–e8 . January 2012 . 21803515 . 10.1016/j.forsciint.2011.06.025 .
  69. Cohen S . Suicide Following Morning Glory Seed Ingestion . The American Journal of Psychiatry . 120 . 1 . 1024–1025 . April 1964 . 14138842 . 10.1176/ajp.120.10.1024 .
  70. Klinke HB, Müller IB, Steffenrud S, Dahl-Sørensen R . Two cases of lysergamide intoxication by ingestion of seeds from Hawaiian Baby Woodrose . Forensic Science International . 197 . 1–3 . e1–e5 . April 2010 . 20018470 . 10.1016/j.forsciint.2009.11.017 .
  71. Schardl CL, Panaccione DG, Tudzynski P . Ergot alkaloids--biology and molecular biology . The Alkaloids. Chemistry and Biology . 63 . 45–86 . 2006 . 17133714 . 10.1016/s1099-4831(06)63002-2 . Elsevier . 978-0-12-469563-4 .
    “Clavines are thought to contribute substantially to convulsive ergotism, since C. fusiformis ergots, which possess clavines, but no 1 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).”
    II. Through the Ages: A History of Ergot Alkaloid Use, Abuse, and Poisoning, p. 50 .
  72. Book: Eich E . Solanaceae and convolvulaceae - secondary metabolites: biosynthesis, chemotaxonomy, biological and economic significance: a handbook . Springer-Verlag . 978-3-540-74540-2 . Berlin, Heidelberg . January 12, 2008 . En . 4.2 Ergolines . 10.1007/978-3-540-74541-9 . 195613136.
    4.2.5.1 Mechanisms of Action and Therapeutic Relevance, p. 249
  73. Book: Eich E . Solanaceae and convolvulaceae - secondary metabolites: biosynthesis, chemotaxonomy, biological and economic significance: a handbook . Springer-Verlag . 978-3-540-74540-2 . Berlin, Heidelberg . January 12, 2008 . En . 4.2 Ergolines . 10.1007/978-3-540-74541-9 . 195613136 .
    Containing ergosine: Argyreia luzonensis, A. mollis, A. obtusifolia, A. philippinensis, A. ridleyi, A. splendens
    Ipomoea argyrophylla (ergosine and ergobalansine)
    See “Table 4.1 Unambiguously ergoline-positive Ipomoea species” (pages 225-227) and “Table 4.4 Unambiguously ergoline-positive Argyreia species” (p. 236).
  74. Beaulieu WT, Panaccione DG, Hazekamp CS, mckee MC, Ryan KL, Clay K . Differential allocation of seed-borne ergot alkaloids during early ontogeny of morning glories (Convolvulaceae) . Journal of Chemical Ecology . 39 . 7 . 919–930 . July 2013 . 23835852 . 10.1007/s10886-013-0314-z .
    Ipomoea amnicola and I. argillicola contain ergobalansine .
  75. Paulke A, Kremer C, Wunder C, Wurglics M, Schubert-Zsilavecz M, Toennes SW . Studies on the alkaloid composition of the Hawaiian Baby Woodrose Argyreia nervosa, a common legal high . Forensic Science International . 249 . 281–293 . April 2015 . 25747328 . 10.1016/j.forsciint.2015.02.011 .
    “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) .
  76. Heim E, Heimann H, Lukács G . Die psychische Wirkung der mexikanischen Droge „Ololiuqui“ am Menschen . de . Psychopharmacologia . 13 . 1 . 35–48 . 1968 . 5675457 . 10.1007/BF00401617 .
    3. Results, pages 38-39.
  77. Bigwood J, Ott J, Thompson C, Neely P . Entheogenic effects of ergonovine . Journal of Psychedelic Drugs . 11 . 1-2 . 147–149 . January 1979 . 522166 . 10.1080/02791072.1979.10472099 .
  78. Book: Chemistry in Botanical Classification: Medicine and Natural Sciences: Medicine and Natural Sciences . Elsevier . 978-0-323-16251-7 . Bendz G, Santesson J . 2013-10-14 . en .
    “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.” The Chemistry of Resin Glycosides of the Convolvulaceae Family (H. Wagner), p. 235 . 1973 .
  79. Ono M . Resin glycosides from Convolvulaceae plants . Journal of Natural Medicines . 71 . 4 . 591–604 . October 2017 . 28748432 . 6763574 . 10.1007/s11418-017-1114-5 .
    “Resin glycosides are well known as purgative ingredients,” (Abstract) .
  80. Schardl CL, Panaccione DG, Tudzynski P . Ergot alkaloids--biology and molecular biology . The Alkaloids. Chemistry and Biology . 63 . 45–86 . 2006 . 17133714 . 10.1016/s1099-4831(06)63002-2 . Elsevier . 978-0-12-469563-4 .
    “Clavines are thought to contribute substantially to convulsive ergotism, since C. fusiformis ergots, which possess clavines, but no 1 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).”
    II. Through the Ages: A History of Ergot Alkaloid Use, Abuse, and Poisoning, p. 50 .
  81. Ingram AL . MORNING GLORY SEED REACTION . Jama . 190 . 13 . 1133–1134 . December 1964 . 14212309 . 10.1001/jama.1964.03070260045019 .
    “It has been suggested6 that the insecticide coating on the morning glory seed might be promoting adverse side effects that have been noted. The majority of commercial seeds are treated with N-tri-chlorete which is a fungicide and seed protectant having a tolerance of 100 parts per million.8 Thus, this is quite an inocuous product from the toxicologic point of view and would require ingestion of quantities beyond the capacity of the stomach to absorb, in amounts found as a seed coater, to be considered lethal.9 Symptoms involving the nervous system would be lacking if we were dealing only with the effects of this fungicide. Formerly, compounds containing mercury were used extensively as fungicides and there is the possibility that some seeds so treated might pose a toxicologic danger if ingested. This is considered unlikely as the newer seed protectants have been in use for a considerably longer period than the current morning glory fad.”
    “It would seem then, that both the psychological and physiological effects observed in the ingestion of the seed of the morning glory reside in the alkaloids of the seed and not the seed protectant. The LSD-like reaction is most likely due to the LSD-like alkaloids for no pure LSD has as yet been isolated from the seed. As all compounds occurring in the morning glory seed have not been studied intensively enough to inspire confidence in their respective roles, they cannot yet be considered for scientific experimental use much less be used irresponsibly in excitement-seeking self-experimentation.” (Comment, p. 1134) .
    6. Cohen S . Suicide Following Morning Glory Seed Ingestion . The American Journal of Psychiatry . 120 . 1024–1025 . April 1964 . 14138842 . 10.1176/ajp.120.10.1024 .
    8. Book: Frear DE . Pesticide Handbook . State College, Pa . College Science Publishers . 1963 . 8 .
  82. Peter Jordan. Re: Woodrose vs Ipomoea. alt.drugs, UseNet, 10/1/1994

    https://erowid.org/plants/hbw/hbw_info1.shtml

  83. Book: Eich E . Solanaceae and convolvulaceae - secondary metabolites: biosynthesis, chemotaxonomy, biological and economic significance: a handbook . Springer-Verlag . 978-3-540-74540-2 . Berlin, Heidelberg . January 12, 2008 . En . 4.2 Ergolines . 10.1007/978-3-540-74541-9 . 195613136 .
    See 6.2 Cyanogenic Glycosides, p. 274.
  84. Book: The First Book of Sacraments of the Church of the Tree of Life: A Guide for the Religious Use of Legal Mind Alterants . Tree of Life Press . 1973 . Mann . John . San Francisco, CA . 13 .
    “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.” (OLOLUIQUE and related sacraments in the Morning Glory (Bindweed) family, p. 13).
  85. Book: Pendell, Dale . Pharmako/Gnosis: Plant Teachers and the Poison Path . North Atlantic Books . 28 September 2010 . 9781556438042 . Revised and Updated . 106 . 2005 .
    “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.” (Peyote: Lophophora williamsii).
  86. Web site: Initial schedules of controlled substances (Schedule III), Section 812. www.deadiversion.usdoj.gov. 2020-01-17. 2021-11-04. https://web.archive.org/web/20211104092917/https://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm. dead.
  87. Web site: Erowid LSA Vault : Legal Status. erowid.org. 2020-05-05.

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