St. Anthony’s Fire

1. St. Anthony’s Fire By Nickerson: Kristina Haagsma, Mark Hnatiuk, Jan Kozicky, Justin Ma, Jessica Ng, Josh Plante, Jana Rieger

2. Introduction • Caused by ergot • A filamentous fungus • Genus Claviceps • Parasitic • Found in grains • corn, wheat, barley, oats, rice, and rye • Spread via spores • Transported by wind, rain, insects and other animals, or by plant-to-plant contact

3. Introduction • Infection of plants can be easily overlooked • Mimics the shape of grains • Fungal form is the most dangerous • Causes ergotism • Infection usually follows oral consumption of contaminated food ie/ rye bread

4. Overview • History • Signs & Symptoms • Mechanism of Action • Drug Interactions • Treatment • Therapeutic Uses • LSD

5. History Eleusinian Mysteries • Greek religious cult promising pleasant afterlife • Lasted for almost 200 years, between 1500BC and 396AD • Cult of Demeter and Persephone • Drank ritual drink kykeon before having visions of afterlife, hallucinations • Kykeon likely contained ergotized barley • Extremely secretive, death penalty for revealing secrets and visions

6. Tollund Man • Perfectly preserved body found in Danish peat bog, from 400BC • Rope around neck, likely drowned as ritual sacrifice to earth goddess • Stomach contained porridge with very high levels of ergot in the barley • Ergotised porridge likely taken to induce hallucinations before ritual sacrifice

7. Tollund Man

8. Medieval Ergot Epidemics • Rhine Valley had many ergotism outbreaks recorded between 7th and 17th centuries, rye bread was staple food • Became known as St. Anthony’s Fire as monks of St. Anthony specialized in treatment • Also called Ignis Sacer and Holy Fire • 40 000 deaths in southern France in 944AD

9. Convulsive ergotism called Dancing Mania, St. Vitus’s Dance, as people screamed, babbled, convulsed, and ‘danced’ in streets • shut down Strasbourg in 1418 • Often attributed to demons and madness or divine intervention • Scientific breakthroughs in 1670s • ergotism was connected bread and later to ergotized rye • ergot life cycle identified in 1853

10. Salem Witch Trials • 1692 Salem, Massachusetts had wet harvest, rye bread likely contaminated with ergot • 8 girls in Salem experienced hallucinations, convulsions, burning skin sensations • Pastor’s daughters affected • Immediately accused other women of bewitching them

11. Those accused of witchcraft were mostly unpopular, poor, and non-churchgoing • Over 150 people imprisoned for witchcraft that year • 20 people executed, 5 died in prison

12. Salem Witch Trials

13. Russia • Ergotism very common until 1945 as rye bread was staple food • After 1945, potatoes were planted instead and pesticides/fungicides introduced • 1926, there were 10,000 confirmed cases of ergotism in Russia • Government statistics show that areas with wet weather and rye crops had outbreaks of trembling, confusion, hysteria, and hallucinations

14. Signs and Symptoms • Ergotism can be caused by • Acute ingestion of large amounts of fungus • Chronic ingestion, usually via contaminated food • 2 main categories of symptoms • Gangrenous • Convulsive

15. Gangrenous Symptoms • Dry gangrene caused by tissue necrosis • Fingers and toes are affected first • Followed by arms and legs • Infection may result and can lead to death • Amputation is often the only solution • Happens in livestock as well as in humans

16. Convulsive Symptoms • Includes tingling sensation in the fingers, tinnitus, dizziness, hallucinations, seizures, nausea and vomiting • Mental disturbances such as mania, psychoses and delirium may also be present

17. Kinetics • Many compounds; absorbed to varying degrees from GI tract • Absorption increased in the presence of caffeine (ergotamine) • Extensively metabolized by CYP450 • Cinx in liver failure • Certain drugs inhibit metabolism • Protease inhibitors • Macrolide antibiotics

18. Mechanism of Action • Ergot compounds are structurally similar to the biogenic amines • Dopamine • Serotonin (tryptophan) • Norepinephrine • Serotonergic system particularly affected • Accounts for many of the convulsive symptoms • Similar to symptoms of schizophrenia and epilepsy

19. Mechanism of Action • N/V/D • stimulated serotonin receptors of the GI tract and emetic centres of the brain • LSD • a weak partial agonist at 5HT-2 receptors in the brain • Results in many of the convulsive symptoms

20. Mechanism of Action • All ergot compounds exhibit some vasospastic properties • Effects on serotonin and alpha adrenergic receptors in blood vessels • St. Anthony’s Fire • Body feels extremely warm due to constriction of peripheral vessels

21. Mechanism of Action • Results in myocardial or peripheral ischemia • Gangrene, infection, amputation, death • Cinx in CAD, PAD, uncontrolled HTN • Uterine smooth muscle is also affected by serotonergic and alpha adrenergic effects • Contractions may lead to miscarriage or preterm birth

22. Treatment • 16th and 17th century folk remedies • “green ointment of herbs,  earthworms stamped in vinegar, swan or goose dung stamped with the white or yolk of the egg, or doves dung in salad oil” • Later remedies • “British Oil” originally containing bitumen, • later preparations with oil of turpentine, oil of rosemary and Barbados tar

23. Treatment • Modern-Day Treatment • Early detection and immediate discontinuation of exposure vital • Severe ischemia may be irreversible • If overdose is detected early • Activated charcoal • Gastric lavage if patient is conscious

24. Treatment • Treatment of hallucinations • Stopping exposure to toxin usually effective • Intracranial injection of combination serotonin and cholinergic drugs successful treatment in mice

25. Treatment • Treatment for ischemia • Vasodilators • Nitroprusside, nifedipine, captopril, prostaglandins • Anticoagulants • Dextrin, heparin • In extreme cases of ischemia • Regional sympathectomy • Hyperbaric oxygen chamber • Hydrostatic dilation with balloon catheters

26. Medicinal Uses • Bromocriptine • Stimulates D2 receptors in the brain • Treatment for Parkinson’s • female infertility, abnormal lactation, amenorrhea, hypogonadism, and acromegaly • Effective in cocaine withdrawal • Diabetes and Obesity

27. Medicinal Uses • Pergolide • Anti-Parkinson • 1000x more potent than Bromocriptine • Inhibits Prolactin Release • Effects on Leutinizing and Growth Hormone

28. Medicinal Uses • Methysergide • Prophylactic migraine treatment • Activation of 5HT-1D receptors in cranial blood vessels • vasoconstriction • Linked to retroperitoneal fibrosis

29. Medicinal Uses • Ergotamine • Intermittent treatment of migraines • Similar MOA as Methysergide • Cinx in pregnant women • Migraine treatments are non-selective • Overdose or drug interaction may result in ergotism • Replaced by safer -triptans

30. Medicinal Uses • Methylergonovine • Used after delivery • Initiates strong contractions of uterine smooth muscle • Contract the uterus, prevent hemorrhage, promote placental passage

31. Drug-Drug Interactions • SSRI’s will potentiate the effects of ergot derivatives which are partial 5-HT agonists • Ex. Fluoxetine • LSD has sympathomimetic effects; therefore, stimulants will worsen adverse effects like tachycardia and hypertension

32. Drug-Drug Interactions • Since LSD is metabolized by CYP enzymes, CYP inhibitors may lead to toxicity • Ex. Antiretrovirals (ritonavir), Macroglide antibiotics (erythromycin), Grapefruit juice • LSD should not be combined with other hallucinogens • Ex. Psilocybin, Mescaline

33. LSD • Synthesized by Albert Hoffman in 1938 • Accidentally dosed himself • Had the first ‘acid trip’ • Hallucinations, synesthesias, emotionality, body distortions • Used as a psychoanalytic drug • Was thought to elicit repressed memories • Given to alcoholics as part of counselling process

34. LSD • Believed to be helpful in treating schizophrenia • Tried to map out a ‘model psychoses’ using animals • Later realized that schizophrenia and acid trips are very different • Therapeutic use discontinued in the ’60s

35. LSD • CIA • Attempted to use it for mind control • Cold War, Russian spies • Tested it on unsuspecting civilian and military ‘volunteers’ • Caused mental trauma and suicides in subjects • No real use was found for it

36. LSD • Eventually became accessible to the public • Counterculture committed to social change and cultural liberation • Timothy Leary’s League of Spiritual Discovery was a church in the ’70s based on LSD use • Widespread stories of bad trips and flashbacks decreased its use • Legislation was imposed prohibiting LSD

37. LSD • Today it is part of the ‘party drug’ scene • Along with ecstasy and mushrooms

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