1. Ergotism and witchcraft
Key events in Seventeenth Century colonial America:
1. the founding of Jamestown
2. the voyage of the Pilgrims
3. the first Thanksgiving
4. the establishment of slavery just to name a few.
Another occurrence stands out among the others as a brutal and backward looking mistake in the course of American history--the Salem witch trials of 1692.

2. Ergotism and witchcraft
In medieval times, there were two types of witches:
1. Malefic—a witch that caused misfortunes
causing beer or cheese to spoil,
the family cow to dry up
the death of babies.
2. Theological—witches that had made a covenant with the Devil to acquire their magical powers.
common for these types of witches to be marked with a “witches mark” such as an extra nipple from which familiars of the Devil could nurse.

3. Ergotism and witchcraft
Witchcraft was also a legal concept.
There were laws in most places at that time against “Acts of Conjuracions, Inchantments and Witchcraftes.”
After 1604 the sentence was death, unlike some of the earlier statues where more lenient punishment could have been granted.

4. Salem witchcraft affair of 1692
the worst outbreak of witch persecution in America
It affected not only Salem Village but eight other communities of Essex County, Massachusetts and Connecticut.
It began in the kitchen of the Reverend Samuel Parris, in Salem Village, Massachusetts:
a group of young girls and a slave from the Caribbean named Tituba, were trying to determine what their future husbands would be like.
Utilizing a primitive crystal ball, the girls saw something that terrified them "a specter in the likeness of a coffin.”
Soon the girls began to experience “odd postures,” “foolish, ridiculous speeches,” “distempers,” and “fits, they began blasphemous screaming, had convulsive seizures and were in trance-like states.”
While at first Parris and others sought medical explanations, they soon determined the girls were under the spells of witches.

5. Salem witchcraft affair of 1692
to determine who had bewitched them, a witch cake was baked with the infected girls urine.
Consumption of such a cake would reveal to the girls who had bewitched them.
After consuming the cake, pressure was placed on the girls to reveal the names of the witches, which they did.
The girls initially gave up three names, Tituba, Sarah Good and Sarah Osbourne.
While the others denied the charges, Tituba soon confessed, and the women were locked up.
the girl’s fits did not stop. Sarah Good was hanged for witchcraft and Sarah Osbourne died in Prison.

7. Salem witchcraft affair of 1692
As the spring went on, more people became afflicted, and more people were accused of witchcraft.
The Salem jail began to fill with witches and the social status of the witches began to increase.
With the growing number of prisoners, the accusations began to move out of Salem and into surrounding communities. It was no longer a local affair.
The trials dragged on throughout the summer and when they finally ended in September, due to the direct intervention of several Massachusetts ministers, there had been 141 accusations and twenty people were executed.
Part of the reason that the trials were eventually stopped was that the accusers began to accuse people whose status and piety was so firmly established that people no longer believed them.

8. Historical detectives
This has been the subject of several of books
The problem has been approached from a variety of disciplines and many explanations were provided for the cause.
1. The teenage girls in Salem Village were feigning their symptoms
2. The bewitched were suffering from hysteria

9. Background Typical witches in Salem were:
1. Doctors or herbalists who were trying to help the victims.
2. Middle aged, women
3. Of humble social status
4. Either married or widowed,
5. And often somewhat less fecund than other women.
6. Most had disagreeable or self-assertive personalities

10. Background 7. Many also owned property or stood to own property,
was against the laws that clearly specified male inheritance of property.
There were many conflicts between sons who believed that the real property of their deceased fathers was theirs, and widows who held that property (or whose new husbands held it
it was the cause of a great deal of resentment.
Typical victims in Salem
The victims in Essex County were mainly children and teenagers.

11. Witches in Salam

12. Witches in Salam

13. Background Pattern of Symptoms
The patterns of symptoms was distributed in a nonrandom way in space and time.
Ultimately twenty people were killed in Salem,
over ten thousand people were executed for witchcraft in Europe in the Sixteenth and Seventeenth centuries.

14. Geography of the trials
In Scotland
witch persecution was concentrated in the northeast, along the coast—the country’s main rye-growing area.
Early Modern Europe
most trials were concentrated in:
alpine areas of France and central Europe
in the Rhine Valley.
In all these areas rye was the staple cereal.

15. Witch trials in Scotland

16. Witch trials in western Europe

17. Geography of the trials
southern France
In 944 AD in 40,000 people died of ergotism.
The absence of persecution is significant.
Ireland
There were few witch trials in Ireland.
The Irish at this time consumed mainly dairy products, potatoes and oats, which may explain why they were not very susceptible to “bewitchment.”

18. Background Food prices were indicative Climate was indicative
The higher the rye prices the more witch persecution trials were held.
Climate was indicative
The colder the spring and summer temperatures, the more witch persecution trials were held.

20. Salem witch trials

21. Background
Outbreaks of witchcraft were often accompanied by central nervous system symptoms:
tremors,
anesthesias
paresthesias (sensations of pricking, biting, ants crawling on the skin)
distortions of the face and eyes
paralysis
spasms
convulsive seizures
muscle contractions
Halucinations
manias
panics
depressions

23. Background
There were also a significant number of gangrene cases and complaints of reproductive dysfunction, especially agalactia (inability of a nursing mother to produce enough milk).
Animals behaved wildly and made strange noises. Cows had agalactia.
Not every victim of “bewitchment” had all the symptoms, but most had abnormal experiences and behaved in abnormal ways.

24. Background
1670
a French physician, Dr. Thuillier put forth the concept that it was not an infectious disease, but one that was due to the consumption of rye infected with ergot that was responsible for the outbreaks of St. Anthony’s Fire.
In 1976 psychologist Linda Caporael proposed that those who displayed symptoms of bewitchment in 1692 were actually suffering from ergotism.

25. Ergot and ergotism
Is a disease of cereals, especially rye (Secale sp.) and occasionally other grasses caused by the fungus Claviceps purpurea.
When ingested by humans or animals in sufficient quantity, ergot produces a disease called “ergotism” which has in serious cases, two variants:
1. convulsive--convulsive ergotism might better be labeled “dystonic ergotism”. It is characterized by nervous dysfunction, such as writhing, tremors, and wry neck, which in the past were frequently reported as “convulsions” or “fits. ”
2. gangrenous--victims of gangrenous ergotism may lose fingers, toes, and limbs to dry gangrene, caused by a vasoconstrictive chemical (such as the alkaloid ergotamine) produced by the ergot fungus.

26. Claviceps purpurea

27. Claviceps purpurea

28. Symptoms of ergotism Cardiovascular system
constriction of arteries and veins
rapid, weak pulse
precordial distress or pain
muscle pain
skin cold
weakness, lameness
gangrene
cardiac arrest

29. Symptoms of ergotism Motor control tremors, spasms, writhing wry neck
eyes awry
loss of speech
muscular paralysis
renal spasm
permanent constrictures

30. Symptoms of ergotism Central nervous system headache dizziness
depression
confusion
drowsiness, unconsciousness
panic
hallucinations
delusions, psychosis

31. Symptoms of ergotism
Gastrointestinal system
nausea
vomiting
diarrhea

32. Symptoms of ergotism Senses unquenchable thirst
depressed or ravenous appetite
sensations of heat (fever) or cold (chills)
blindness
deafness
numbness
feeling of being pinched, choked, suffocated

33. Symptoms of ergotism Skin tingling and itching (formication) jaundice
redness
swelling
blistering

34. Symptoms of ergotism Reproductive system fertility suppression
abortion, stillbirth
agalactia (inability to produce milk)
poisoning of mother’s milk
False convulsions

35. Symptoms of ergotism
It is now known that ergot alkaloids do not produce true convulsions, in which consciousness is lost
some ergot alkaloids interfere with the activity of dopamine in the body
causing muscle spasms as well as confusion delusions and hallucinations.
Psychosis
Ergot might also produce a temporary or permanent psychosis.

36. Symptoms of ergotism Poisoned mother’s milk
Some ergot alkaloids can pass through the mother’s milk and poison the nursing infant who is especially vulnerable.
If lactating domestic animals in a community are also affected, there may be no alternative source of nutrition for human infants.

37. Witchcraft and ergotism
Symptoms of bewitchment in Massachusetts
The victims did not have true convulsions because they did not lose consciousness (victims of convulsive ergotism writhe and have spasms but do not lose consciousness.
24/30 victims of bewitchment in 1692 suffered from “fits” and the sensations of being pinched, pricked or bitten, all of which are common symptoms of ergotism.
Temporary blindness, deafness, and speechlessness, burning sensations, visions and the sensation flying through the air (out of body).

38. Witchcraft and ergotism
Three girls said they felt as if they were being torn to pieces and all their bones were being pulled out of joint.
Some victims reported feeling sick to the stomach or weak, sensing a burning in the fingers, swelling and pain in half of the right hand and part o the face, and being lame.

39. Symptoms of ergotism
Epidemics of gangrenous necrosis of the extremities and central nervous abberations swept through the populations of Europe from the ninth through the eighteenth centuries as a result of incorporating ergot-contaminated flour into bread.
Medical use of ergot in obstetrics began in China 5000 years ago and reportedly was prescribed by Hippocrates (ca. 400 B.C.)

40. Ergot alkaloids
Among the known ergot alkaloids with hallucinogenic properties are:
1. Ergine
2. Ergonovine
3. lysergic acid hydroxyethylamide.
It is relatively easy to extract lysergic acid diethylamide (LSD) from lysergic acid, which is the basic ergot alkaloid.
through the action of other fungi, LSD may appear in natural ergot.

41. Rye and ergotism
ergotism began with the cultivation of Secale cereale (Rye)
it is far more common on that host,
but Claviceps purpurea can infect other grains as well.
Rye was a weed grain and occurred wherever wheat was cultivated.
Often it became the dominant plant when wheat fields were abandoned.
wherever civilization became established, Rye would follow it there.
It was not cultivated for food until some time in the early Middle Ages (around the 5th Century), in what is now eastern Europe and western Russia.

42. Rye cultivation England and Wales

43. Alkaloid conc. in Russia

44. St. Anthony’s Fire
The symptoms (but not the cause of the symptoms) were well documented during the Middle Ages.
It was at this time that it came to be called Holy Fire and later St. Anthony’s Fire.
Holy Fire because it caused burning sensations at the extremities from gangrenous ergotism,
St. Anthony’s fire because hospitals were set up, which were dedicated to Saint Anthony, to take care of patients with the disease.

45. St. Anthony

46. Geography of the ergotism
Epidemic-like outbreaks of ergot poisoning have been recorded in most European countries and Russia.
France
many waves of ergotism throughout history.
Between AD the Holy Roman Empire formed by Pope Leo III was one of the areas affected.
The area was populated by the Franks
during this time, the Vikings invaded the Holy Roman Empire. Because of their superior size and fighting ability they easily defeated the Franks who lived along the coastal regions.
Eventually the Holy Roman Empire was split into West Franks (France) and East Franks (Germany).
By 911 the Vikings hold on the northwest coast of France was complete and the king of France ceded to them what would become Normandy.
Through it all the Vikings were unaffected by the ergotism because Rye was not a staple food for them.

47. Current uses for ergot alkaloids
Dihydroergotoxine (Ergoloid Mesylate)--
increases brain metabolism and cerebral brain flow.
Used in age related mental capacity decline.
Ergonovine maleate--
when used after placental delivery, ergonovine increases the strength, duration and frequency of uterine contractions and decreases uterine bleeding.
Used in the prevention and treatment of postpartum and postabortal hemorrhage.

48. Current uses for ergot alkaloids
Ergotamine derivatives--
to prevent or abort vascular headaches such as migraine, migraine variant and cluster headache
suppress fertility or stop lactation.
LSD--treatment of certain mental disorders.
The demand is so great that fields of Rye are now grown by pharmaceutical companies that are purposely infected with Claviceps purpurea in order to harvest the alkaloids.

49. Toxicity of ergots
Grain containing more than 0.3 percent by weight of the grain may not be legally sold and milled for flour and human consumption.
It is also costly and quite often difficult to remove enough sclerotia to meet the legal standards, particularly in poorer countries, and the remaining traces are often toxic to livestock.

50. LSD
Albert Hofmann-inventor of LSD at Sandoz labs in Switzerland–1930’s
Isolated an alkaloid called ergotoxine, which was thought not to be pure, but was really a mixture.
Isolated Lysergic acid as one of the base alkaloids.
He began to do a series of experiments where he combined lysergic acid with a variety of amines to make pharmaceutically important lysergic acid compounds.
The first was lysergic acid + prolamine; the result was ergonovine was a very useful uterotonic- hemostatic compound valuable in obstetrics.
Lysergic acid + butanolamine; the result was the compound with the trade name Methergine which today is the leading medicine for obstetrics.

51. LSD
1938–He produced the twenty-fifth substance in this series of lysergic acid derivatives:
lysergic acid diethylamide (LSD-25, Lyserg-saure-diathylamid).
This compound, from its structure, was planned as a circulatory and respiratory stimulant.
In tests it was found that a strong effect on the uterus was established that amounted to 70% of ergonovine.
It was also noted in passing that the experimental animals became restless during the narcosis.
LSD-25 aroused no speical interest and testing was discontinued.
Usually in the lab this would have been the end of LSD-25 because finding no pharmacological uses it would normally have been discarded as nothing useful.

52. LSD
Hofmann did resynthesize more LSD-25 about five years later –in the process he absorbed some through his skin
“Last Friday, April 16, 1943, I was forced to interrupt my work in the laboratory in the middle of the afternoon and proceed home, being affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away. If LSD-25 had indeed been the cause of this bizarre experience, it must be a substance of extraordinary potency.”

53. LSD on Monday he began a series of self-experiments
16:20: taken 0.25 mg in 10 cc water (tasteless)
17:00: Beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh.
Here the notes in his laboratory journal cease.
He then asked his laboratory assistant to escort him home.
They went by bicycle, no automobile being available because of wartime restrictions on their use. On the way home, his condition began to assume threatening forms. He recalls everything becoming distorted and having to work very hard to pump the bicycle up very steep hills to his house. The road to his house was perfectly level.

54. LSD
The dizziness and sensation of fainting became so strong at times that I could no longer hold myself erect, and had to lie down on a sofa. My surroundings had now transformed themselves in more terrifying ways. Everything in the room spun around, and the familiar objects and pieces of furniture assumed grotesque, threatening forms. They were in continuous motion, animated, as if driven by an inner restlessness. The lady next door, whom I scarcely recognized, brought me milk - in the course of the evening I drank more than two liters. She was no longer Mrs. R., but rather a malevolent, insidious witch with a colored mask.

55. LSD
Even worse than these demonic transformations of the outer world, were the alterations that I perceived in myself, in my inner being. Every exertion of my will, every attempt to put an end to the disintegration of the outer world and the dissolution of my ego, seemed to be wasted effort. A demon had invaded me, had taken possession of my body, mind, and soul. I jumped up and screamed, trying to free myself from him, but then sank down again and lay helpless on the sofa.
I was taken to another world, another place, another time. My body seemed to be without sensation, lifeless, strange. Was I dying? Was this the transition? At times I believed myself to be outside my body, and then perceived clearly, as an outside observer, the complete tragedy of my situation.

56. LSD
By the time the doctor arrived, the climax of my despondent condition had already passed. My laboratory assistant informed him about my self-experiment, as I myself was not yet able to formulate a coherent sentence. He shook his head in perplexity, after my attempts to describe the mortal danger that threatened my body. He could detect no abnormal symptoms other than extremely dilated pupils. Pulse, blood pressure, breathing were all normal. He saw no reason to prescribe any medication. Instead he conveyed me to my bed and stood watch over me. Slowly I came back from a weird, unfamiliar world to reassuring everyday reality. The horror softened and gave way to a feeling of good fortune and gratitude, the more normal perceptions and thoughts returned, and I became more confident that the danger of insanity was conclusively past.

57. LSD
Now, little by little I could begin to enjoy the unprecedented colors and plays of shapes that persisted behind my closed eyes. Kaleidoscopic, fantastic images surged in on me, alternating, variegated, opening and then closing themselves in circles and spirals, exploding in colored fountains, rearranging and hybridizing themselves in constant flux. It was particularly remarkable how every acoustic perception, such as the sound of a door handle or a passing automobile, became transformed into optical perceptions. Every sound generated a vividly changing image, with its own consistent form and color.

60. Kapok