Molecules of Witchcraft By: Tanja Thompson & Justin Reale

Digitalis purpurea

Common Names Common foxglove Foxglove Long purples Dead men’s fingers Toxic Amounts Therapeutic dose if 1.5g of powered leaf in an adult 800 to 1600mg is toxic to adults [1].

History It is a cultivated flower so most of the recorded accounts of human poisonings come from reports of accidental ingestion of Digitalis purpurea that were gathered from gardens or from tea made from the leaves [1].

Cardiac glycosides and Witchcraft Those branded for witchcraft often used cardiac glycosides derived from plants and animals such as toads in their "magic potions” Cardiac glycosides caused individuals to "come back from the dead” these effects were often blamed on the local herbalist AKA a witch [3].

Human Toxicity Initially nausea and vomiting Hyperkalemia The cardiac effects include electrocardiogram changes Prolonged P-R interval S-T segment depression Bradycardia Heart block Ventricular tachycardia Mental confusion Lathargic Flashing of lights Halos around objects [1]

Chemically Glycosides are hydrolyzed to yield the secondary glycosides: Digitoxin Gitaloxin More specifically digitoxin Considered a cardiac glycoside 2 Types of cardiac glysosides

Cardiac glycosides (Pharmaceutical Class) 1. Cardenolides are the most prevalent and are C23 steroids with an ,  - unsaturated 5-membered lactone ring on C-17 Examples digitoxin, convallatoxin, and evonoside

Cardiac glycosides (Pharmaceutical Class) 2. Bufadienolides are C24 steroids with a double unsaturated 6-membered lactone ring on C-17 Examples convallamarin, scillaren, A and B, and hellebrin [1].

Mechanism of Action Digitalis and related glycosides Inhibition (or interference with pump) of the enzyme Na, K- ATPase, results in high intracellular levels of sodium and potassium. The increased Na leads to the subsequent increase in calcium levels with leads to over stimulation of muscle and cardiac tissue [1].

Case Example “A 70-year-old man mistook Digitalis purpurea leaves for comfrey leaves in preparing an herbal tea. He consumed one liter of tea over several days. He was admitted with a 2-day history of vomiting, diarrhea, confusion, and seeing flashing lights. The EKG demonstrated bradycardia and complete heart block, which reverted to first-degree block after four days. The potassium level was 6.8 mEq/l. He was treated with activated charcoal, atropine, and insulin. A temporary pacemaker was required. The EKG was normal after ten days [1].”

Claviceps purpurea

Common names Ergotamine Ergot of Rye Holy fire Saint Anthony’s fire Occult fire and Saint Vitus’ dance Ergot is a parasitic fungus that forms on the head of the grain of the Claviceps purpurea. The fungus produces a dark purple fruiting body called the sclerotium that is then consumed along with the grain [2].

Background History The “fire” relates to the terrible searing pain and blackened extremities caused by the progression of gangrene. The “dance” refers to twitching and convulsive contortions due to the neurological effects of some ergot alkaloid. 16th century used to strengthen uterine contractions [3].

A Little More History 600 B.C. The Assyrians who noted “a noxious pustule in the ear of grain.” 400 B.C. - record of “noxious grasses” causing miscarriages in cattle in Persia. 944 A.D thousand deaths in France [3].

Witchcraft of Ergot Alkaloid Older women who lived on the outskirts of the community, many of which were herbalist or unable to afford flour, thus would have saved a woman from ergotism and the rest of the community was effected by the infected wheat. Many of these individuals were accused of being witches and casting spells on the whole community [3].

Witchcraft Continued May have been responsible for the Salem witch trials of 1692 because of the moist and wet conditions during the spring and summer allowing for ideal conditions for the fungi to grow in the community’s grain. 250 people, mostly women were accused, 19 were hung and stoned to death [3].

Human Toxicity Nausea, vomiting, diarrhea, severe thirst, tingling of skin, skin hypoerfusion, and chest pain. Headache, fixed mitosis, hallucinations, delirium, hemiplegia, and convulsions may occur. Hemorrhagic vesiculations, prutius, formications, and gangrene can occur. Hallucinogenic episodes [2].

Current Uses Ergotamine tartrate plus caffeine is administered to relieve migraine headaches. Ergononvine has been used to treat postpartum hemorrhage. Ergot derivatives are used to manage amenorrhea and an adjunct in the treatment of Parkinson’s disease. Hydrogenated ergot alkaloids have been used for symptoms of idiopathic mental decline in elderly patients [2].

Exposure Pathway Consumption of contaminated grain (especially rye flour) Acute poisoning in humans is rare and generally associated with overdosage with ergotamine tartrate medications. Ergot-containing mixtures has been associated with attempts to induce abortion. Animal poisoning consumption of contaminated pasture grasses and grains. Last known human death was in 1951 [2].

Chemically A mixture of ergot alkaloids Ergotamine Ergocistine Ergocornine α- ergocryptine β-ergocryptine [2].

Toxicokinetics Poorly absorbed orally The majority of the xenobiotic is eliminated by phase I biotransformation in the liver. Symptoms begin approximately 4hrs after ingestion Half-life of metabolism ranges from hrs [2].

Mechanism of Action Interaction with Tryptaminergic, dopaminergic, and α-adrenergic receptors Pharmacological effects interference with α-adrenergic receptors producing pressor, uterotonic, and emetic effects Hypothermia is induced by action at dopamine and serotonin receptors Ergot amine poisoning may be attributed to localized vascular insufficiency [2].

Works Cited [1.] Spoerke, D. G., S. C. Smolinske. (1990). CRC toxicity of houseplants. Florida: CRC Press, Inc 11-13, [2.] Wexler, P. (1998). Encylocopedia of toxicology: Erogt. Academic Press Vol. I, [3.] Le Couteur, P., J. Burreson. (2003). Napoleon’s buttons: Great molecules in history. New York: Tarcher/Putnam, ,