St. Anthony‟s Fire

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

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

Overview

History

Signs & Symptoms

Mechanism of Action

Drug Interactions

Treatment

Therapeutic Uses

LSD

History Eleusinian Mysteries

Religious cult between 1500BC and 396AD

Cult of Demeter and Persephone promising

pleasant afterlife

Drank ritual drink kykeon before having

visions of afterlife, hallucinations

Kykeon likely contained ergotized barley

Extremely secretive, death penalty for

revealing secrets and visions

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

Tollund Man

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

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 when ergotism was connected bread and later to ergotized rye; ergot life cycle identified in 1853

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

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

Salem Witch Trials

Russia

Ergotism very common until 1945

Rye bread was staple food in Russia until 1945, when potatoes were planted instead and pesticides/fungicides introduced

Government statistics show that areas with wet weather and rye crops had outbreaks of trembling, confusion, hysteria, and hallucinations

1926, there were 10,000 confirmed cases of ergotism in Russia

Ergot Scare: Pont-Saint-Esprit

1951, French town of Pont-Saint-Esprit had 200 people suffering from confusion, hallucinations, „madness‟, and cold extremities

7 deaths and 50 people interred in insane asylums

Linked to bread

Misidentified as ergotism, later proved to be mercury poisoning

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

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

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

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

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

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

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

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

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

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

Treatment

Treatment of hallucinations

Stopping exposure to

toxin usually effective

Intracranial injection of

combination serotonin

and cholinergic drugs

successful treatment

in mice

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

Medicinal Uses

Bromocriptine

Stimulates D2 receptors in the brain

• Treatment for Parkinson‟s

female infertility, abnormal lactation,

amenorrhea, hypogonadism, and acromegaly

• D2 stimulation

Effective in cocaine withdrawal

Opiate weaning?

Medicinal Uses

Pergolide

Anti-Parkinson

1000x stronger than bromocriptine

Inhibits prolactin

Effects on leutinizing and growth hormone

Medicinal Uses

Methysergide

Prophylactic migraine treatment

Activation of 5HT-1D receptors in cranial

blood vessels

• vasoconstriction

Linked to retroperitoneal fibrosis

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

Triptans are a safer new alternative for

migraine treatment

Medicinal Uses

Methylergonovine

Used after delivery

Initiates strong contractions of uterine smooth

muscle

Contract the uterus, prevent hemorrhage,

promote placental passage

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

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

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

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

LSD

Today it is part of the „party drug‟ scene

Along with ecstasy and mushrooms

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