Ergot and Lycanthropy [One of an occasional series of essays by MegaDog]

How many of you ever thought of your local bakery as a possible cause of werewolves?

Or as a source of hallucinogenic drugs?

In medieval times, it could have been both.

Ergot, Claviceps purpurea, is a parasitic fungus that can be found growing on rye or other cereal grasses. Rye grass is by far the most widespread species parasitized, though wheat and barley are also commonly affected. The 'ergots' appear as a blackish-purple club- shaped growth [sclerotia] on the tops of the rye where the seeds are, and are referred to as "heads of ergot"; from these heads sprout the Claviceps purpurea fungal fruiting bodies. They have long stems with bulbous heads when seen under a strong glass or microscope.

Fig.1 - Ergot sclerotia.

Ergot naturally produces a wide range of chemical compounds, the ones of relevance here are collectively known as the "Ergot Alkaloids", and include ergotamine, ergosine and beta-ergosine, ergonine, ergovaline, ergostine, ergotine and beta-ergotine, ergocornine, ergocristine, ergocryptine and beta-ergocryptine. These compounds all have some degree of psychoactivity; indeed LSD was first synthesized from ergot compounds. Their other major medical effect is vasoconstriction [narrowing of blood vessels], which, if severe, can lead to gangrene of the extremities.

Fig.2 - Ergotamine.

Ergotamine has medical uses; for example it is frequently prescribed [often in combination with caffeine] as a therapy for migraine headaches - see below for a description of the mechanism of action.

Ergot was a widespread parasite of cereal grains in Europe in the middle-ages, growing particularly well during excessively damp summers. The psychoactive components of ergot are *not* broken down by heat, so it is fair to assume that they would be present in bread baked from flour milled from ergotized grains. There was a significant outbreak of ergot-poisoning in France in the early 1950's; this outbreak gives a good insight into what may have been experienced in medieval times.

Symptoms of ergot poisoning include hallucinations [the 1950's French victims reported 'being chased or attacked by horrible beasts', 'terror of the dark', and 'feeling that my body was not mine'] together with tingling/burning sensations in the extremities & the scalp.

It is not hard to imagine how an outbreak of ergot-poisoning, or, IMHO, more likely, an ongoing low level of ergotisation, could lead to the development of a werewolf-legend, the 'pursuit by horrible beasts' hallucination being probably the most likely cause, however the 'tingling & loss of sensation in the extremities' effect could possibly have been interpreted as shapeshifting? For those interested in more detail of such things, see references [2] and [3].

Epidemics of Ergot poisoning have occurred, and still occur, when contaminated grain is used for food. The symptoms produced include mental disturbances, and intensely painful peripheral vasoconstriction, leading ultimately to gangrene, which came to be known in the Middle ages as St. Anthony's Fire, because it was normally cured by a visit to the shrine of St. Anthony, which happened to be in an ergot-free region of France. Ergot contains many active substances, and it was a preoccupation with their complex pharmacological properties that led Dale to many important discoveries concerning acetylcholine, histamine and catecholamines.

Ergot alkaloids (fig.1 - see above) are molecules based on a complex aromatic acid, Lysergic acid , and the different compounds in this group display many different types of pharmacological action. Chemically, they fall into two major categories, according to whether they posess an amine or an amino-acid side chain.

Compounds with an amine side-chain include Lysergic acid diethylamide (LSD), Methysergide, and Ergometrine. Compounds with an amino-acid side chain include ergotamine, which acts on alpha-adrenopceptors, dihydroergotamine, and a semisynthetic compound, bromocriptine, which acts selectively on dopamine receptors. Ergometrine, which has a simple aliphatic side-chain, acts selectively on the smooth muscle of the uterus. Many ergot alkaloids are agonists or antagonists at 5-HT receptors.

The ergot alkaloids all cause stimulation of smooth muscle, some being relatively selective for vascular smooth muscle, and others acting mainly on the uterus. In addition, the amino-acid alkaloids affect catecholamine and 5-HT receptors in various ways.

Ergotamine and dihydroergotamine are respectively a partial agonist and an antagonist of alpha-adrenoceptors; bromocriptine acts as an agonist on dopamine receptors, particularly in the central nervous sysetem; methysergide is an antagonist of 5HT2 receptors. The main pharmacological actions of these drugs are summarised in table [A]. As one would expect of drugs with so many actions, their physiological effects are complex, and rather poorly understood.

The main physiological effects of ergotamine are as follows:-

Vascular effects

When injected into an anaesthetized subject, ergotamine causes a sustained rise in blood-pressure, caused by vasoconstriction. The effect is blocked by pure alpha-receptor antagonists such as phentolamine. At the same time as causing a rise in blood pressure, ergotamine reverses the pressor effect of adrenaline. The adrenaline reversal was discovered accidentally by Dale when, at the end of a long day, he tried to carry out a bioassay on the adrenal gland extract by measuring its' pressor effect on a cat into which he had previously injected ergot. It occurs because the alpha-receptors with which adrenaline normally combines are occupied, leaving the beta-receptor-mediated vasodilation unopposed. The same effect can be produced by any alpha-receptor antagonist. The vasoconstrictor effect of ergotamine is responsible for the peripheral gangrene and tingling sensations (incipient necrosis of nerve-endings) in St. Anthony's fire, and also probably for some of the effects of ergot on the central nervous system.

Other actions

Ergotamine causes uterine contraction, similar to the effects of ergometrine, and may also produce nausea aand vomiting, an anction shared with bromocriptine, and probably caused by stimulation of central Dopamine receptors. It is also a partial agonist on certain 5-HT receptors, an effect which may contribute to its' vascular actions.

Clinical use

The main use of ergotamine is in the treatment of migraine, for which it is effective as a prophylactic, as is methysergide. It is unclear at present whether this effect is due to an interaction with alpha-adrenoceptors, or with 5-HT receptors, or both.

Unwanted effects

Nausea and vomiting are troublesome side effects, and ergotamine must be avoided in patieonts with peripheral vascular disease because of its' vasoconstrictor action. An analogue, dihydroergotamine produces an equal benefit with fewer side-effects.

WARNING

If any of you are thinking of experimenting with Ergot at home, I would discourage this most strongly! To back this up, here is an abstract from a medical toxicology file I just happened to have to hand... Ergotamine: Acute effects: May be fatal if inhaled, swallowed, or absorbed through the skin.

Exposure can cause: Nausea, dizziness and headache, stomach pains, vomiting, diarrhea.

Other symptoms include: Thirst, changes in blood pressure and heart rate, tingling in the extremities and confusion. Chronic effects: An Oxytocic; in pregnant women may result in abortion or fetal harm. Can cause menstrual dysfunction and sterility. Other effects include peripheral circulatory disturbances and gangrene. Possible mutagen.

References:-

[1]Morten Lange and F. Bayard Hora: Collins Guide to Mushrooms and Toadstools 1978 Description of characteristics of ergot, its distribution & life cycle.

[2]Fuller, John Grant, The Day of St Anthonys Fire, NY: Macmillan, 1968. This is a look at outbreaks of hallucinations and other bizarre behavior believed to have been caused by ergot infections.

[3]Matossian, Mary Kilbourne, Poisons of the Past: Molds, Epidemics & History, New Haven: Yale Univ Press, 1989. This book covers more ground, from the Middle Ages to witchcraft scares in Europe. She has charts, maps and graphs to illustrate her findings.