Editing Ergot (section)

==History==
[[File:Ergot01.jpg|thumb|Ergot on wheat heads]]
[[Ergotism]] is the earliest recorded example of ''mycotoxicosis'', or poisoning caused by toxic molds.<ref name="Bennett Bentley 1999 Story Ergot">{{cite journal |last1=Bennett |first1=J.W. |last2=Bentley |first2=Ronald |title=Pride and Prejudice: The Story of Ergot |journal=Perspectives in Biology and Medicine |volume=42 |issue=3 |pages=333–355 |doi=10.1353/pbm.1999.0026|year=1999 |s2cid=72715889}}</ref>
Early references to ergotism date back as far as 600 BC, an [[Assyria]]n tablet referred to it as a "noxious pustule in the ear of grain."<ref name="Ergot:from witchcraft to biotechnology">{{cite journal |last1=Haarmann |first1=Thomas |last2=Rolke |first2=Yvonne |last3=Giesbert |first3=Sabine |last4=Tudzynski |first4=Paul |title=Ergot:from witchcraft to biotechnology |journal=Molecular Plant Pathology |date=2009 |volume=10 |issue=4 |pages=563–77 |doi=10.1111/J.1364-3703.2009.00548.X |pmid=19523108 |pmc=6640538|bibcode=2009MolPP..10..563H }}</ref> In 350 BC, the [[Parsis|Parsees]] described "noxious grasses that cause pregnant women to drop the womb and die in childbed."<ref name="Ergot:from witchcraft to biotechnology"/> In [[History of Syria|ancient Syria]], ergot was called "Daughter of Blood."<ref name="Wellcome"/> [[Rodulfus Glaber|Radulf Glaber]] described an ailment he called "hidden fire," or ''ignus ocultus'', in which a burning of the limb is followed by its separation from the body, often consuming the victim in one night.<ref name="Wellcome"/> In 1588, Johannes Thallius wrote that it is called "Mother of Rye," or ''rockenmutter,'' and is used to halt bleeding.<ref name="Wellcome"/>

Human poisoning due to the consumption of rye bread made from ergot-infected grain was common in Europe in the [[Middle Ages]]. The first mention of a plague of gangrenous ergotism in Europe comes from [[Germany]] in 857; following this, [[France]] and [[Scandinavia]] experienced similar outbreaks;<ref name="De Costa">{{cite journal |last=De Costa |first=Caroline |title=StAnthony's fire and living ligatures: a short history of ergometrine |journal=The Lancet |date=May 18, 2002 |volume=359 |issue=9319 |pages=1768–1770 |doi=10.1016/S0140-6736(02)08658-0 |pmid=12049883|s2cid=53277037 }}</ref> England is noticeably absent from the historical regions affected by ergotism as its main source of food was wheat, which is resistant to ergot fungi.<ref name="Wellcome">{{cite book |last1=Wellcome |first1=Henry S. |last2=Solomon |first2=Henry |title=From Ergot to Ernutin |date=June 19, 1908 |publisher=Canadian Medical Association |location=Ottawa |isbn=978-1331946151 |pages=1–60}}</ref> In 994, a massive outbreak potentially attributed to ergotism caused 40,000 deaths in the regions of [[Aquitaine]], [[Limousin]], [[Périgord]] and [[Angoumois]] in France.<ref name="Bennett Bentley 1999 Story Ergot"/> In [[Landgraviate of Hesse-Darmstadt|Hesse]], in 1596, Wendelin Thelius was one of the first to attribute ergotism poisoning to grain.<ref name="De Costa"/> In 1778, S. Tessier, observing a huge epidemic in [[Sologne]], France, in which more than 8,000 people died, recommended drainage of fields, compulsory cleaning of grain, and the substitution of potatoes for affected grain.<ref name="De Costa"/>

In 1722, the [[Russia]]n [[Tsar]] [[Peter the Great]] was thwarted in his campaign against the [[Ottoman Empire]] as his army, traveling down the [[Terek River|Terek]] steppe, was struck by ergotism and was forced to retreat in order to find edible grains. A diary entry from the time notes that as soon as people ate the poisoned bread, they became dizzy, with such strong nerve contractions that those who did not die on the first day found their hands and feet falling off, akin to [[frostbite]].<ref name="Bennett Bentley 1999 Story Ergot"/> The outbreak was known as Saint Anthony's fire,<ref name="mia"/> or ''ignis sacer''. 

Some historical events, such as the [[Great Fear]] in France at the outset of the [[French Revolution]], have been linked to ergot poisoning.<ref>Matossian, Mary Kilbourne, ''Poisons of the Past: Molds, Epidemics, and History''. New Haven: Yale, 1989 (reedited in 1991) {{ISBN|0-300-05121-2}}{{page needed|date=October 2016}}</ref> 

===Saint Anthony's fire and the Antonites===
[[Anthony the Great|Saint Anthony]] was a 3rd Century Egyptian ascetic who lived by the [[Red Sea]] and was known for long fasting in which he confronted terrible visions and temptations sent from the [[Devil]].<ref name="De Costa"/> He was credited by two noblemen for assisting them in recovery from the disease; they subsequently founded the [[Hospital Brothers of St. Anthony|Order of St. Anthony]] in his honor.<ref name="Wellcome"/> Anthony was a popular subject for art in the Middle Ages, and his symbol is a large blue "[[Tau|T]]" sewn onto the shoulder of the order's monks, symbolizing the crutch used by the ill and injured.<ref name="Nemes"/>

The Order of St. Anthony, whose members were known as Antonites, grew quickly, and hospitals spread through France, Germany and Scandinavia and gained wealth and power as grateful patrons bestowed money and charitable goods on the hospitals.<ref name="Wellcome"/> By the end of the Middle Ages, there were 396 settlements and 372 hospitals owned by the order,<ref name="Nemes"/> and pilgrimages to such hospitals became popular, as well as the donation of limbs lost to ergotism, which were displayed near shrines to the saint.<ref name="Wellcome"/> These [[Hagiotherapy|hagiotherapeutic]] centers were the first specialized European medical welfare systems, and the friars of the order were knowledgeable about treatment of ergotism and the horrifying effects of the poison.<ref name="Nemes">{{cite journal |last=Nemes |first=C.N. |title=The medical and surgical treatment of the pilgrims of the Jacobean Roads in medieval times Part.1 |journal=International Congress Series |date=1 December 2018 |volume=1242 |pages=31–42 |doi=10.1016/S0531-5131(02)01096-8}}</ref> The sufferers would receive ergot-free meals, wines containing [[Vasodilation|vasodilating]] and analgesic herbs, and applications of Antonites-balsam, which was the first [[transdermal therapeutic system]] (TTS) in medical history.<ref name="Ergot:from witchcraft to biotechnology"/> These medical recipes have been lost to time, though some recorded treatments still remain.<ref name="Nemes"/> After 1130, the monks were no longer permitted to perform operations, and so barber surgeons were employed to remove gangrenous limbs and treat open sores.<ref name="Nemes"/> Three barbers founded a hospital in [[Memmingen]] in 1214 and accepted those who were afflicted with the gangrenous form of ergotism. Patients were fed and housed, with the more able-bodied individuals acting as orderlies and assistants. Patients with the convulsive form of ergotism, or ''ergotismus convulsivus'', were welcomed for only nine days before they were asked to leave, as convulsive ergotism was seen as less detrimental. Though the sufferers often experienced irreversible effects, they most often returned to their families and resumed their livelihoods.<ref name="Nemes"/>

An important aspect to the Order of St. Anthony's treatment practices was the exclusion of rye bread and other ergot-containing edibles, which halted the progression of ergotism.<ref name="Wellcome"/> There was no known cure for ergotism itself; however, there was treatment of the symptoms, which often included blood constriction, nervous disorders and/or hallucinations; if the sufferer survived the initial poisoning, his limbs would often fall off, and he or she would continue to improve in health if he or she halted consumption of ergot.<ref name="De Costa"/> The trunk of the body remained relatively untouched by the disease until its final stages, and the victims, not understanding the cause of their ailment, would continue to imbibe ergot-laden food for weeks until the condition reached their digestive system.<ref name="Nemes"/> It is believed that the peasantry and children were most susceptible to ergotism, though the wealthy were afflicted as well, as, at times, entire villages relied on tainted crops for sustenance, and during times of famine, ergotism reached into every house.<ref name="Ergot:from witchcraft to biotechnology"/> Ergot fungus is impervious to heat and water, and thus it was most often baked into bread through rye flour; though other grasses can be infected, it was uncommon in [[Medieval Europe]] to consume grasses other than rye.<ref name="Wellcome"/> The physiological effects of ergot depended on the concentration and combinations of the ingested ergot metabolites, as well as the age and nutritional status of the afflicted individual.<ref name="Bennett Bentley 1999 Story Ergot"/> The Antonites began to decline after physicians discovered the genesis of ergotism and recommended methods for removing the [[sclerotium]] from the rye crops. In 1776, the cloisters of the Antonites were incorporated into the Maltese [[Knights Hospitaller]], losing much of their medical histories in the process and losing the ergotism cures and recipes due to lack of use and lack of preservation.<ref name="Nemes"/>

===Usage in gynaecology and obstetrics===
Midwives and very few doctors in Europe have used extracts from ergot for centuries: 
# In a [[Nürnberg]] manuscript of 1474, powdered ergot was prescribed together with [[Laurus nobilis#Alternative medicine|Laurel-fruits]] and [[rhizome]]s of [[Polygonatum multiflorum|Solomon's seal]]s to cure ''permutter'' or ''heffmutter,'' which refers to pain in the lower abdomen caused by 'uprising of the womb'<ref>Cod. Pal. germ. 545, Blatt &nbsp;70v [http://digi.ub.uni-heidelberg.de/diglit/cpg545/0144 (Digitalisat)]</ref>
# In a printed book of 1582, the German physician [[Adam Lonicer]] wrote, that three sclerotia of ergot, used several times a day, were used by midwives as a good remedy in case of the "uprising and pain of the womb" (''auffſteigen vnd wehethumb der mutter'')<ref>Adam Lonitzer. Kreuterbuch ... Egenolff, Frankfurt 1582, Blatt CCLXXXVr ({{Digitalisat|MDZ=11200293_00589}}). In the 1578 edition [http://bildsuche.digitale-sammlungen.de/index.html?c=viewer&bandnummer=bsb00086989&pimage=598&v=100&nav=&l=de (Digitalisat)] ergot is not mentioned.</ref>
# [[Joachim Camerarius the Younger]] wrote in 1586, that sclerotia of ergot held under the tongue, would stop bleeding<ref>Herbal of [[Pietro Andrea Mattioli]] enlarged by J. Camerarius. Frankfurt am Main 1586, page 109-, [http://bildsuche.digitale-sammlungen.de/index.html?c=viewer&bandnummer=bsb00091089&pimage=00238&v=100&nav= (Digitalisat)]</ref>

To prove that ergot is a harmless sort of grain, in 1774, the French pharmacist [[Antoine-Augustin Parmentier]] edited a letter he had received from Madame Dupile, a midwife of [[Chaumont-en-Vexin]]. She had told him that if uterine contractions were too weak in the [[Childbirth#Second stage: fetal expulsion|expulsion stage of childbirth]], she and her mother gave peeled ergot in an [[Thimble|amount of the filling of a thimble]] dispersed in water, wine or broth. The administration of ergot was followed by a mild childbirth within 15 minutes.<ref>Journal de Physique, 1774, S. 144–155 [https://archive.org/details/journaldephysiq03unkngoog/page/n157 (Digitalisat)]</ref> The French physician Jean-Baptiste Desgranges (1751–1831) published in 1818, that in 1777 he had met midwives in [[Lyon]], who successfully treated feeble uterine contractions by administering the powder of ergot. Desgranges added this remedy to his therapeutic arsenal. From 1777 to 1804, he was successful in alleviating childbirth for more than twenty women  by the administration of the powder of ergot. He never saw any side-effect of this treatment.<ref>Jean-Baptiste Desgranges (1751–1831). ''Sur la propriété qu'a le Seigle ergoté d'accélérer la marche de l'accouchement, et de hâter sa terminaison''. In: ''Nouveau Journal de Médecine'', Paris, I (1818), S. 54–61 [https://archive.org/details/BIUSante_90147x1818x01/page/n53 (Digitalisat)]</ref>

In the [[United States]], in 1807 Dr. [[John Stearns, 1770|John Stearns]] of [[Saratoga County, New York]] wrote to a friend that he had used, over several years, a ''pulvis parturiens'' with complete success in patients with "lingering [[Uterine contraction#Childbirth|parturitation]]". This ''pulvis parturiens'' consisted of ergot, that he called a "spurious groth of rye". He boiled [[Apothecaries' system#Metrication in countries using the troy and avoirdupois systems|"half a drachm"]] (ca. 2g) of that powder in half a pint of water and gave one third every twenty minutes, till the pains commenced.<ref name="auto">{{Cite web |title=The Medical repository Hexade 2, v. 5 (1808). |url=https://babel.hathitrust.org/cgi/pt?id=nyp.33433011578865&view=1up&seq=324 |access-date=2024-10-24 |website=HathiTrust |language=en}}</ref> In 1813, Dr. [[Oliver Prescott#Son|Oliver Prescott]] (1762–1827) of [[Newburyport, Massachusetts]] published a dissertation "on the natural history and medical effects of the secale cornutum", in which he described and analysed the experience he had gathered over five years while using ergot in cases of poor uterine action in the second stage of labour in childbirth.<ref name="auto"/>

The 1836 ''Dispensatory of the United States'' recommended "to a woman in labour fifteen or twenty grains [ca. 1 to 1.3g] of ergot in powder to be repeated every twenty minutes, till its peculiar effects are experienced, or till the amount of a drachm [ca. 3.9g] has been taken".<ref>''The Dispensatory of the United States of America'', third edition Philadelphia 1836, p. 588 [https://archive.org/details/dispensatoryofun00wood/page/588 (Digitalisat)]</ref>

In 1837, the French ''Codex Pharmacopee Francaise'' required ergot to be kept in all pharmacies.<ref>''Codex, pharmacopée française 1837'', p. 215 : ''Poudre de seigle ergoté'' [http://archive.org/details/codexpharmacopef00univ/page/214 (Digitalisat)]
</ref>

Low to very low evidence from clinical trials suggests that prophylactic use of ergot alkaloids, administered by intravenous (IV) or intramuscular (IM) in the third stage of labor, may reduce blood loss and may reduce the risk of moderate to severe hemorrhage following delivery, however this medication may also be associated with higher blood pressure and higher pain.<ref name=":0">{{Cite journal |last1=Liabsuetrakul |first1=Tippawan |last2=Choobun |first2=Thanapan |last3=Peeyananjarassri |first3=Krantarat |last4=Islam |first4=Q. Monir |date=2018 |title=Prophylactic use of ergot alkaloids in the third stage of labour |journal=The Cochrane Database of Systematic Reviews |volume=2018 |issue=6 |pages=CD005456 |doi=10.1002/14651858.CD005456.pub3 |issn=1469-493X |pmc=6513467 |pmid=29879293}}</ref> It is not clear if oral ergot alkaloids are beneficial or harmful as they have not been well studied.<ref name=":0"/> A 2018 Cochrane Systematic Review concluded that other medications such as oxytocin, syntometrine and prostaglandins, may be preferred over ergot alkaloids.<ref name=":0"/>

Though ergot was known to cause abortions in [[cattle]] and humans, this was not a recognized use for it as abortion was illegal in most countries, thus evidence for its use in abortion is unknown.<ref name="Bennett Bentley 1999 Story Ergot"/> Most often, ergot was used to speed the process of parturition or delivery, and was not used for the purpose of halting postpartum bleeding, which is a concern of childbirth.<ref name="De Costa"/> However, until [[anesthesia]] became available, there was no antidote or way of controlling the effects of ergot. So if the fetus did not move as expected, the drug could cause the uterus to mold itself around the child, rupturing the uterus and killing the child. [[David Hosack]], an American physician, noted the large number of stillbirths resulting from ergot use and stated that rather than ''pulvis ad partum'', it should be called ''pulvis ad mortem''.<ref name="De Costa"/> He began advocating for its use to halt postpartum bleeding. Eventually, doctors determined that the use of ergot in childbirth without an antidote was too dangerous. They ultimately restricted its use to expelling the [[placenta]] or stopping hemorrhage. Not only did it constrict the uterus, ergot had the ability to increase or decrease blood pressure, induce hypothermia and emesis, and influence pituitary hormone secretions.<ref name="Bennett Bentley 1999 Story Ergot"/> In 1926, Swiss psychiatrist Hans Maier suggested to use ergotamine for the treatment of vascular headaches of the migraine type.<ref name="Miedaner and Hartwing"/>

In the 1930s, [[abortifacient]] drugs were marketed to women by various companies under various names such as Molex pills and Cote pills. Since birth control devices and abortifacients were illegal to market and sell at the time, they were offered to women who were "delayed". The recommended dosage was seven grains of ergotin a day. According to the [[United States]] [[Federal Trade Commission]] (FTC)<ref>{{cite journal |author=Federal Trade Commission |title=Federal Trade Commission Decisions |journal=Federal Trade Commission Decisions |volume=30 |pages=800 |year=1941}}</ref> these pills contained ergotin, aloes, [[Helleborus niger|Black Hellebore]] and other substances. The efficacy and safety of these pills are unknown. The FTC deemed them unsafe and ineffective and demanded that they [[cease and desist]] selling the product. Currently, over a thousand compounds have been derived from ergot ingredients.<ref name="Miedaner and Hartwing"/>

===Speculated cause of hysterics and hallucinations===
It has been posited that [[Kykeon]], the beverage consumed by participants in the [[Ancient Greece|ancient Greek]] [[Eleusinian Mysteries]] cult, might have been based on [[hallucinogen]]s from [[ergotamine]], a precursor to the potent hallucinogen LSD, and [[ergonovine]].<ref name="Miedaner and Hartwing"/><ref>{{cite journal |url=http://www.psychedelic-library.org/Mixing%20the%20Kykeon%20Final%20Draft.pdf |title=Mixing the ''Kykeon'' |journal=ELEUSIS: Journal of Psychoactive Plants and Compounds |volume=New Series 4 |year=2000 |access-date=2008-07-31 |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>{{Cite web |last=Carod-Artal |first=F. J. |date=2013 |title=Psychoactive plants in ancient Greece |url=https://nah.sen.es/en/130-journals/volume-1/issue-1/241-psychoactive-plants-in-ancient-greece |access-date=2021-02-17 |website=nah.sen.es}}</ref>

An article appearing in the July 23, 1881 edition of ''[[Scientific American]]'' entitled "A New Exhilarating Substance" denotes cases of euphoria upon consuming [[tincture]] of ergot of rye, particularly when mixed with [[Sodium phosphates|phosphate of soda]] and sweetened water. In rainy years, it was thought rye bread exceeded 5% ergot.<ref>{{Cite book |url=https://books.google.com/books?id=YIE9AQAAIAAJ |title=Scientific American |date=1881-07-23 |publisher=Munn & Company |pages=51 |language=en}}</ref>

British author John Grigsby contends that the presence of ergot in the stomachs of some of the so-called 'bog-bodies' ([[Iron Age]] human remains from peat [[bog]]s of northeast Europe, such as the [[Tollund Man]]) is indicative of use of ''[[Claviceps purpurea]]'' in ritual drinks in a prehistoric fertility cult akin to the Greek Eleusinian Mysteries. In his 2005 book ''Beowulf and Grendel'', he argues that the [[Anglo-Saxon]] poem ''[[Beowulf]]'' is based on a memory of the quelling of this fertility cult by followers of [[Odin]]. He writes that Beowulf, which he translates as ''barley-wolf'', suggests a connection to ergot which in German was known as the 'tooth of the wolf'.<ref>{{cite book |last=Grigsby |first=John |title=Beowulf & Grendel: The Truth Behind England's Oldest Legend |year=2005 |publisher=Watkins Publishing |isbn=978-1-84293-153-0}}{{page needed |date=July 2014}}</ref>

[[Linnda R. Caporael]] posited in 1976 that the [[Salem witch trials#Medical theories about the reported afflictions|hysterical symptoms of young women]] that had spurred the [[Salem witch trials]] had been the result of consuming ergot-tainted rye.<ref>{{cite journal |last=Caporael |first=Linnda R. |author-link=Linnda R. Caporael |date=April 1976 |title=Ergotism: the satan loosed in Salem? |url=http://web.utk.edu/~kstclair/221/ergotism.html |url-status=dead |journal=Science |volume=192 |issue=4234 |pages=21–6 |bibcode=1976Sci...192...21C |doi=10.1126/science.769159 |pmid=769159 |archive-url=https://web.archive.org/web/20080511154621/http://web.utk.edu/~kstclair/221/ergotism.html |archive-date=2008-05-11|url-access=subscription }}</ref> However, Nicholas P. Spanos and Jack Gottlieb, after a review of the historical and medical evidence, later disputed her conclusions.<ref>{{cite journal |vauthors=Spanos NP, Gottlieb J |s2cid=41615273 |title=Ergotism and the Salem Village witch trials |journal=Science |volume=194 |issue=4272 |pages=1390–4 |date=December 1976 |pmid=795029 |doi=10.1126/science.795029 |bibcode=1976Sci...194.1390S }}</ref> Other authors have likewise cast doubt on ergotism as the cause of the Salem witch trials.<ref name="Woolf">{{cite journal |last=Woolf |first=Alan |year=2000 |title=Witchcraft or mycotoxin? The Salem witch trials |journal=Clinical Toxicology |volume=38 |issue=4 |pages=457–60 |doi=10.1081/CLT-100100958 |pmid=10930065 |s2cid=10469595}}</ref>