ergot

krauterbuch 1582

In the history of mankind there were popularity ups and downs of materia medica representatives. Plant and animal raw materials were (and still are) commonly used in medicine, pharmacy, and other economic sectors. But fungal raw materials are out of the scope of interest. It is hard not to appreciate the significance of Sacharomyces cerevisiae (brewer’s yeast, baking yeast – with biotechnology it is possible to produce various drugs with cultures of the above species).

Things are a bit different with sclerotia of Claviceps purpurea (ergot) – a source with unknown origins and unknown ancient history. Across the ages, this medicinal fungus was unambiguously connected with gynecology and obstetrics. But it is only the beginning.

We do not know if the Ancients knew rye. Possibly this species was used in Trace and Macedonia to bake bread. About 600 BC, an Assyrian tablet alluded to a “noxious pustule in the ear of grain” (ergot?). In classical Latin, this grain was called secale. Then during the medieval period rye was called siligo. A large number of Poaceae representatives are being infected by fungi belonging to the Claviceps genus. But the most important from both historical and economical points of view is Claviceps purpurea (ergot)causing damage to rye, wheat, and barley.

But first we need to have a look at the nonobvious nomenclature of this species.

Mycological nomenclature of ergot

Theatrum Botanicum Sive Historia Plantarum bauhin 1658

For centuries a lot of scientists had problems with the classification of an ergot. In 1816 Augustin Pyramus de Candolle (Swiss botanist who specialized in economic botany and agronomy) described Secale Cornutum as a fungus and baptised this species as Sclerotium Clavis. Another Swiss — Elias Magnus Fries (professor of botany and applied economics at Uppsala University, father of modern fungal taxonomy), denominated it Spermoedia Clavus. What is crucial E. J. Queckett (botanist, surgeon, and microscopist) called it Ergotoetia abortifaciens (abortifaciens — Latin term for a substance that induces abortion) In 1839 he wrote:

“I adopted the term abortans […] is it probable that I ever should have proposed […] name as being fitted to form the specific one of the newly discovered genus”?

M. J. Berkley (Anglican clergyman interested in plant pathology) was also conscious of the specific effect of the above fungus, therefore he called it Oidium abortifaciens. In 1853 Edmond Tulasne (French mycologist and botanist) introduced his views on the development cycle of the ergot. From then on this fungus is called Claviceps purpurea.

In pharmaceutical sources the ergot was called Clavus siliginis, Calcar, Secalis mater, Secale luxurians, Secale cornutum and Grana secalis degeenerata.

Ethnomycology of ergot

Parke, Davis & Company, Standardized products (1911)

We have no clues when the secale cornutum (ergot) was first introduced into medicinal use. The true western history of ergot is the great unknown. But the eastern history is probably more clear. Alexander Tschirch (pharmacist and pharmacognosist who lived at the turn of the 20th century) stated, that Chou Kung (Chinese philosopher and physician) has written about ergot circa 1100 BC. According to this man of science, this source was used as an obstetrical remedy – the application unknown in Europe until the 17th or 18th century! On the other hand, the further works associated with botany e.g., Thousand Golden Remedies of Sun Ssii-mho written in the seventh century, Pen Ts’ao Kang Mu written in the 16th century by Li Shih-Chen (he complied 11,091 prescriptions used throughout the centuries; these are listed in 52 volumes describing 443 animal substances and 1,074 plant material) does not mention ergot. It may be true, that the Chinese did not know ergot at all.

Galen (Galenos – Greek physician and philosopher born circa 129 BC) wrote that some people make the black bread with an unpleasant odour called Briza. Indeed, ergot could cause the above organoleptic features. Galenos also stated that the grains could be transformed into black ones, and these are very dangerous for our health. The Greeks during Eleusinian Mysteries used a cryptic mixture called Kykeon. Some scholar state that this substance was prepared by mixing wine, various herbs, water, and barley infected with Claviceps spp. The latter ingredient was the essential one – it could cause a “hallucinogenic trip” during the above religious rite.

Rye was primarily cultivated by the Teutons classified as Germanic tribe, so it should not be surprising that the first medicinal mention of ergot as a drug comes from German sources. Adam Lonicer was a German botanist and physician of the city of Frankfurt. He is also an author of the “Kreuterbuch” – one of the most notable herbal in the history of herbalism and pharmacy. In 1582 4th edition of the above work was published. In the chapter about agricultural crops and grains (in rye subchapter) he wrote that sometimes long, black grains outstand from the spike, like long nails. This description unambiguously indicates that Lonicer knew the ergot. What is more, he wrote beneath that women use three sclerotia of Claviceps to induce a strong uterine contraction. This is the oldest clear evidence of Secale cornutum application in gynecology and obstetrics.

The oldest known illustration (woodcut) of ergot is located in the book titled Theatrum Botanicum Sive Historia Plantarum (Botanical theatre or the history of plants) from 1656 edited by the son of Caspar Bauhin. This author was a Swiss botanist, who proposed binominal system of plant nomenclature, later improved by Linnaeus.

It is also worth mentioning that medieval chroniclers mention years in which the mysterious disease called ignis sacer or ignis plaga was prevalent. In Europe, it occurred last time on a larger scale in 1771 in Westphalia, Hanover, and Lauenburg where in some villages only 5 out of 120 people survived. It is implied that ergot may be responsible for well-known choreomania (dancing plague) – the phenomenon when villagers in the medieval period in Europe were falling into an involuntary dance trance.

Presumably, the official usage of ergot in gynecology started in 1747 in Holland. It was subsequently used in France until it was interdicted by the legislative act in 1774. In the 1st decade of the 19th century in the state of Washington there was the high-profile case of a Scottish woman, who tried the ergot medications in obstetrics practice with fatal results.

In 1807 in USA a clinical trial net of obstetricians was established who used ergot in their practice in form of powder and decoction. In 1813 the results were published in the New-England Journal of Medicine and Surgery. They met with general approbation. What is important, some of the physicians described the cases of still-born children, after ergot application. It is not surprising — C. purpurea is a very potent medication.

It is important to remark that usage of ergot was limited to cases that were hazardous for the life of both mother and child. In this case, the risk was legitimate. Taking this into consideration, in 1807 dr John Stearns created a list of observations regarding the use of ergot:

It should never be administered during the continuance of one’s labour, in larger quantities than thirty grains by decoction in a half-pint of water.
Three grains, with a grain of opium, steeped in a gill of water and a tea-spoonful given every ten minutes, have succeeded in reproducing the interrupted pains of regular labour.
The ergot is indicated and may be administered […] when in lingering labours a child has descended into the pelvis. […] When pains are transferred from the uterus to other parts of the body, or to the whole muscular system.

Another important remark on ergot was made by Dr John Paterson who was specialised in midwifery. In 1840 he wrote:

“I consider the ergot more to be depended on, as to its particular effects on the uterus than almost any other specific in the Pharmacopoeia”.

This scientist also mentioned that he had never seen any side effects of ergot application. It is rather unobvious because a single dose could cause symptoms like vomiting, colic, pains, headache, hallucinations…

In the late 19th century use of ergot was limited to eye diseases, those associated with the neural system, such as paralysis, headaches, mental apathy, but also in turbinated hypertrophy, various internal haemorrhages, and induction of premature labour.

Considering the above side effects a lot of pharmacists, physicians, herbalists tried to compound an ergot-based drug which a small number of bad effects and all good effects. Dr. Rees’s ethereal solution seems to be the best choice. According to “The retrospect of practical medicine and surgery” from 1840:

“The ethereal solution, the properties of which you have so well tested, was prepared by digesting 4 ounces. of the powdered ergot in 4 fluid ounces of ether during seven days. The result was a solution of the fatty matters contained in the drug: this was poured off, evaporated to dryness, and the residue again dissolved in 2 fluid ounces. of ether”.

One part of the above preparation was an equivalent of two parts of ergot. Both aether and Claviceps has a narcotic potential, so usage of the ethereal solution was highly risky.

According to D. Allen and G. Hatfield (ethnobotanists), only a solitary contemporary folk record of procuring abortions (in Norfolk) has been traced, but it may have been as well a widespread practice down the centuries.

Ergot in contemporary medicine and pharmacy

The contemporary history of ergot starts in 1906 when Barger and Carr isolated the ergotoxine and Dale discovered the adrenolytic activity of Secale cornutum. But we had to wait for the isolation of pure active compounds until 1918 when Stoll isolated ergotamine – first chemically pure ergot alkaloid. From this point forward the discoveries accelerated and in 1961 the total synthesis of this main active compound was developed by Hoffmann, Frey, and Ott.

Ergot exerts a remarkable effect on the human system. One or more sclerotia have long been known to have the effect of bringing on uterine contractions in pregnant women of sufficient severity to expel the fetus. Ergot derivatives have consequently long been in use officially for inducing or speeding labour and inhibiting postpartum bleeding as well as unofficially for procuring abortions.

The European Pharmacopoeia contains monographs of the following ergot alkaloids: ergotamine mesylate, ergotamine tartrate, dihydroergotamine mesylate, dihydroergotamine tartrate, and dihydroergocristine mesylate. In 2013 EMA (European Medicines Agency) recommended reducing the use of drugs containing ergot alkaloid derivatives.

Despite this, the main ergot alkaloid – ergotamine is used these days in the prevention and control of vascular headaches, including migraine headaches and cluster headaches (dose 2-4 mg per day). In the case of postpartum haemorrhage ergot alkaloids can be administered (ergometrine, methylergometrine, ergotamine) which have similar efficacy to oxytocin in spite of a lower safety profile.

The author wishes to thank Piotr Czerwik for the review.

Aleksander K. Smakosz (Poland) is a pharmacist (MPharm, M.Sc.) and ethnopharmacologist. He specializes in the identification, interpretation, and re-creation of former drugs (15th-19th century) from apothecary recipes and formulas. His other areas of expertise are: economic botany, ethnobotany, ethnopharmacology, pharmacognosy, plant toxicology, natural history of spices and crude drugs and herbalism. From childhood, he was interested in the history of alchemy, and the impact on branches of science. In research, he combines contemporary phytochemical and pharmacological knowledge with traditional and historical methods of world exploration. In his free time develop his collection of antique apothecary bottles and preparing herbarium specimens. In 2021 he became editor-in-chief of the Pharmacopola – Polish-language journal focused on interactions between biomedical sciences, humanities, cultural property, and religion. Currently, he is working on two books: about the natural history of spices from the economic botany and pharmaceutical side, and about the potential action of unguentum lamiarum – witches’ ointment. http://www.gulosus.pl/ https://www.instagram.com/alexander_gulosus/

The article is published to bring the medical history of Ergot as part of Invisibledrum´s 2nd Symposium on Spiritual Technologies – Ethnobotany within Witch Trials and the Capitalization of Health. 8–10 April 2021, Kunsthall Trondheim and online.