Thursday, July 12, 2012

The Risk of Never Waking Up at All


     In 1996, the American Medical Association recognized sleep (and the lack of sleep, insomnia) as a medical speciality. But the history of sleeplessness has been with the human race for tens and probably hundreds of thousands of years. The earliest cavemen likely suffered from sleep disturbances, associated with the worries about what they would eat the next day, how to keep the carve warm or how to avoid the many predators that were wandering around.
Complications of Insomnia

     The word 'insomnia' was first used in 1623, in the third known English Language dictionary, written by Henry Cockeram. Cockeram defined insomnia as 'Insomnie (the 'anglicized' form of the Latin 'insomnia'): 'Watching, want of power to sleepe'.
     Insomnia (the absence of sleep) is intricately related to the night and the absence of light. Insomnia is considered by some to be a 'double negative' -  the absence of unconsciousness (a lack of sleep when there is lack of light).
     The descriptive history of insomnia dates far back. The Babylonian Atrahasis epic (about 2000 B.C.), describes a war among the gods at the end of which the lead troublemaker is killed and his remains used to create human beings.
Epic of Gilgamesh

     But these humans, set to work at manual labour, reproduce so rapidly that their noise keeps the god Enil from sleeping. In the real world, ancient peoples were kept from sleep by wars, moonlight, love and lust, anxiety, hunger noise...making insomnia a real and probably daily problem.
     In Greece, around 400 B.C, the father of western medicine, Hippocrates wrote his theory of sleep in 'Corpus Hippocraticum'.
     The oldest known literary work (The Epic of Gilgamesh) tells the story of the oldest human hero, the Mesopotamian Gilgamesh. Gilgamesh becomes mortal by making a transition from constant wakefulness to sleeplessness to knowledge, on the way, experiencing significant insomnia due to all the energy he possessed for work and celebration.
King Wu

     As in other ancient tales, sleeplessness and sleep play on the fault line between mortality and immortality. The 'devil' was to blame for the inability to fall asleep, a punishment from the gods. Others in the ancient world knew sleeplessness because of hunger, worry, and love sickness or—in the case of the Chinese King Wu—because he could not sleep as long as he had not secured heaven’s support'.
     Inhabitants of medieval Europe did not seem to have been worried when they woke up in the middle of the night - a worry that concerns insomniacs today. At that time, interrupted nocturnal sleep was a common experience, the culprits behind insomnia included bedbugs and fear of arson, robbery, and political conspiracy.
     But most worrisome of all were the Devil and his minions (see post: Devils and Demons): According to some, the Devil himself was an insomniac, a fact which required vigilance on the part of Christians.
     In the 1300s, public clocks and bells triggered a heightened awareness of insomnia (or, perhaps became a major cause of it). In Shakespeare’s plays, insomnia was often a condition that affected 'the unsettled mind'.

     With the emergence of the mercantile economy in modern Europe, new forms and ideas of insomnia began to predominate. Wasting one’s time became a serious sin and time was increasingly counted and calculated. New notions about sleep and the stresses of life arose: sleeplessness was secondary to anxiety and that anxiety came from putting faith in material things. Dutch Calvinists demanded moderation in both sleep and consumption. English preachers of the seventeenth century moulded the concept of sleep into the equivalent of 'moral disorder'. Sleeping in was a bad thing and morally condemned.
     In the 19th century, there were many schools of thought for the cause of sleep (and the lack of it). One  idea was that sleep was related to the blood vessels, that sleep was due either to congestion or pressure of blood in the brain, or a lack of blood in the brain.
     Two chemical approaches were also thought to be possible concepts for the cause of sleep. The chemical approach implied that sleep was caused by either a lack of oxygen to the brain or an accumulation of toxic substances, such as cholesterol, carbon dioxide, 'urotoxins' or 'leucomaines'.  With the build-up of these toxins during the day, sleep eventually ensued. As one slept, these same toxins slowly drained away.
     With a new understanding of the central nervous system, the demonstration of the electrical activity of the nervous system, and the newly named neuron (the nerve cell), neural theories for the cause of sleep came into vogue. One type of neural theory was that neurons were paralyzed during sleep, preventing communication between other nerve cells.

     Based on earlier experiments, behavioral theories for the cause of sleep were presented in the late 1800s, theories which proposed the existence of an 'inhibitory reflex' as the cause of sleep; sleep occurred as the result of something being turned off or removed. This inhibitory theory was expanded to state that a loss of wakefulness was based on a loss of stimulation to the senses. By the end of the century, this theory was refuted with the finding of the role of the brainstem in sleep and wakefulness.
     An experiment performed by two neuro-anatomists in the early 1800s, revealed the anatomy of sleep and wakefulness to some degree. In 1809,
Anatomy Museum of Luigi Rolando (Turin)

     Luigi Rolando noted that a permanent state of sleepiness occurred after he removed the cerebral hemispheres in the brains of birds. Marie Jan Pierre Flourens repeated the same experiment in pigeons in 1822.
     Human beings always attempt to'correct' what they deem to be an abnormal state. With lack of sleep (insomnia) judged as an abnormal state, sleeping remedies were invented.
     Evidence of the earliest forms of sleeping remedies are found in ancient Greece and Egypt.
     The most common form of sleep aid used in the ancient world was opium, a very effective antidote to sleeplessness. The Greek God of sleep, Hypnos, was usually shown holding a poppy flower in paintings and sculpture.

Hypnos

     Other sleeping aids of the ancient world included lettuce juice, the bark of mandrake (mandragora), the seeds of a herb called henbane, and, of course wine. The juice of lettuce was also used to induce sleep. As early as 300 B.C. , Greek doctors were known to prescribe concoctions of all these different plant derivatives. Similar prescriptions were also apparently known throughout the Arab world.
     Plant-based sleep aids were all that were available up until the nineteenth century. Apothecaries of the Middle Ages in Europe stocked 'spongia somnifera' a sponge soaked in wine and various herbs. Other mixtures were known in England in the Middle Ages and the Renaissance as 'drowsy syrups'.
Mandrake (Mandragora)
     In 1805, the chemist, Fredrick Setumer synthesized opium for the first time (see post: Ancient remedies), followed by new research into synthesized sedatives to be used as sleeping remedies. By the 1850s two new sleep aids had emerged as the most successful and were being commonly used around the world.
     Chloral hydrate, developed in the early 1830s in Germany (by Justus von Liebig who used dry chlorine on ethylic alcohol, creating chloroform) was a very fast acting depressant of the central nervous system and  extremely effective for inducing sleep quickly (especially when mixed with alcohol).
     Chloral hydrate became known as 'knock out drops', 'Mickey Finn' or 'Mickeys' whence the saying 'slip a Mickey into his drink'. The new drug was introduced in Berlin as a surgical anesthetic and began to be used for insomnia, in lieu of opiates. The problem was that in many cases people overdosed, especially if any amount of alcohol was consumed, and never woke up after using these 'sleep aids'.

Justus von Liebig

     The other extremely popular sleep aid of the nineteenth century was pills made of a combination of bromides  - sodium bromide, potassium bromide, and ammonium bromide, which all act as central nervous system depressants -  invented in 1857 by an English chemist, Sir Charles Locock. These were originally designed as a (rather ineffective) treatment for epilepsy.
     In 1864, however, a German doctor, Otto Behrend, discovered that potassium bromide was a useful sedative. From that point on, the various bromides be-came popular as sleep aids in the late nineteenth and early twentieth century. Although bromides could make someone fall asleep very easily, these drugs came with a variety of side effects and like chloral hydrate, could also cause overdose.
     In the early twentieth century, the most popular sleeping pills were the barbiturates. The barbiturates comprise a class of drugs with more than 25,000 known compounds.

Adolf von Baeyer

     A Prussian chemist, Adolf von Baeyer, is credited with discovering barbituric acid in 1864, creating the acid out of a compound of malonic acid and urea. In 1903, a student of Baeyer's produced a new compound out of barbituric acid and a diethyl derivative and gave the new chemical (diethyl-malonyl) the commercial name Veronal.
     The most widely used was phenobarbital. Other pharmaceutical companies created new barbiturates in the 1920s and 1930s - Eli Lilly produced Amytal and Seconal; Abbott Laboratories invented Pentothal.
     As with chloral hydrate and the bromides, the barbiturates were effective sleep aids but also dangerous. Barbiturates were shown to be addictive, could have a variety of unpleasant side-effects and, when taken with alcohol, were often lethal either through accidental overdose or planned suicide.

     The benzodiazepines were developed as safer sleeping pills in the 1970s (Valium, Xanax, Ativan) but these chemicals still shared some of the problems seen with barbiturates (addiction and memory impairment).
     In 1978, the US Food and Drug Administration (FDA) approved one active ingredient for an over-the-counter sleep aid - the antihistamine doxylamine succinate and, in 1982 approved two more antihistamines for non-prescription hypnotics (diphenhydramine HCL and diphenhydramine citrate).

St. John's Wort Flower

     Today's 'natural' sleeping remedies are more advanced than opium and lettuce juice used in ancient times. Most modern natural sleep aids use combinations from a variety of herbs and herbal extracts from all over the world. These herbal extracts include St. Johns Wort and nardostchya jatamanshi and valeriana wallichi which are mild sedatives.
     Aside from Gilgamesh and the ancient Greeks and Egyptians, many famous people in more recent times have suffered from sleep disturbances. Insomnia is not a modern problem. Insomnia is a fact of life and always has been.

Sir Isaac Newton

     Sir Isaac Newton (see post: Doomsday in Modern Culture) suffered from a severe case of depression and, consequently, had trouble sleeping.
     Some famous insomniacs felt that their nocturnal wakefulness was connected with the beds in which they were sleeping.
     Benjamin Franklin insisted on having bed-sheets that had low temperature as this would help him sleep.
     Sir Winston Churchill had two beds and if he couldn’t sleep in one, he would lie down in the second.

Thomas Edison

     Thomas Edison was unable to have a normal night sleep pattern so he started catnapping during the day.
     Charles Dickens believed that the position he had in bed and the position of the bed itself were factors in getting a good sleep and he placed his bed facing north and slept exactly in the middle of the mattress. He used to check this by extending both his arms out sideways and then wriggling until he was exactly in the centre. Only after this ritual could he begin to enjoy his slumber.
     Marcel Proust used Barbital to trick his insomnia.
     Napoleon was unable to sleep more than three hours every night but it seemed that this was enough for him.
     One of the most creative insomniacs was Alexandre Dumas who produced enough words to fill 1,200 volumes and claimed to have fathered 500 children.
Alexandre Dumas

     The English writer, Arthur Evelyn St. John Waugh, consumed huge amounts of bromides to the point that he suffered hallucinations but still could not get the sleep he wanted.
     The Earl of Rosebery, the Prime Minister of England for one year, between 1894 and 1895 was forced to resign due to chronic insomnia. He had become a chronic user of Sulphonal.
     Margaret Thatcher stated that 'sleep is for wimps'.
     Richard Nixon, American president from 1969 to 1974 was a known chronic insomniac, often binge drinking when under stress. In 1968, Nixon was given an anti-convulsant medication (Dilantin) by his financier friend Jack Dreyfus (who had used the drug to treat his depression).
Margaret Thatcher

     The president then used the drug an on-going basis, resulting in slurred speech, dizziness, at times mental confusion and, increased insomnia during his final months in office before his resignation.
     Human beings always strive to correct 'abnormal' states and with the invention of 'sleeping  pills' as a 'correction', complications ensued.
     A white, crystalline powder called Sulphonal (dimethyl sulphone dimethyl methane) was developed in Germany in 1886 and marketed as a 'sleeping draught'. Within a short time, it became evident that use of Sulphonal on a regular basis resulted in hallucinations and addiction.
     Paraldehyde is a colourless liquid, soluble in water and highly soluble in alcohol. Paraldehyde slowly oxidizes in air, turning brown and producing an odour of acetic acid (vinegar). The drug was synthesized in 1829 and  introduced into clinical practice in the UK by an Italian physician in 1882. It has been used to treat epilepsy as well as a sedative and sleep medication. It is one of the safest hypnotics and was regularly given at bedtime in psychiatric hospitals and to the elderly up until the 1960s.

Richard Nixon
     Today, paraldehyde is sometimes used to treat unresponsive seizures (status epilepticus). Paraldehyde was the last injection given to Edith Alice Morrell in 1950 by the suspected serial killer Dr. John Bodkin Adams (see post: Death by Physician).
     An American survey of 107 physicians taken in 1880, reported 135 patients with 'chloral cravings'.
     The German writer, Karl Gutzkow became addicted to the drug and died in a fire from an over turned oil lamp while in a chloral stupor. The philosopher, Friedrich Nietzsche used large doses of chloral for his sleep problems.

     The guilt ridden Dante Gabriel Rossetti (whose wife had overdosed on laudanum in 1862) avoided opiates but became hooked on chloral hydrate for his insomnia to the point he suffered paranoid delusions.
     A total of 376,000 kilograms of barbiturates were produced in the USA in 1946 (equivalent to 5 million people taking 1 sleeping pill each day for a full year). Patients taking barbiturates for longer than 4-6 weeks become depressed and anxious, develop tolerance and, if the drug is stopped are unable to sleep.

Paraldehyde
     Barbiturates have been used for murder as well as suicide. The death of an English widow in 1956 led to the arrest of her physician, Dr. John Bodkin Adams (see post: Death by Physician) who had a habit of prescribing large doses of heroin and other lethal drugs to elderly woman who had named him as beneficiary in their wills (see above).
     The American poet, Anne Sexton overdosed several times on Nembutal (a drug she dubbed her 'kill-me' pills) in the 1950s before finally carrying out a successful suicide by breathing in the exhaust from her car.

Virginia Woolf
     Author Virginia Woolf attempted suicide by overdosing on Veronal in 1913
     Marilyn Monroe took up to 20 Phenobarbital daily hoping she could get some sleep. On August 5, 1962, she was found dead in her hotel room. Her death was ruled to be 'acute barbiturate poisoning' by the Los Angeles County Coroner's Office; a 'probable suicide' at age 36 although numerous conspiracy theories have been proposed, suggesting that her death was actually murder.
     Her internist had refilled Monroe's prescription for the barbiturate Nembutal a day earlier and the actress may very well have ingested enough Nembutal throughout the day such that it would lethally react with the chloral hydrate given to her later on.
     On June 22, 1969, Judy Garland was found dead in the bathroom of her rented house in London. Her blood contained the equivalent of 970 mg Seconal capsules. According to the coroner, the cause of death was an 'incautious self-overdosage of barbiturates' ('unintentional' suicide).
     Jimi Hendrix died of an overdose in London in 1970 (see post: Last Songs from the Opium Den), probably heroin but he had also taken 9 tablets of a sleeping medication called Vesparax, a combination tablet containing 50 mg brallobarbital, 150 mg secobarbital and 50 mg hydroxyzine (the antihistamine Atarax).

Jimi Hendrix
     The death of American rock star Michael Jackson in 2011 at 50 years of age, was one of the most high profile 'insomnia-related' deaths in recent history.
      Jackson  suffered from a long history of insomnia and had been under physician care for this problem for years. He died on June 25, 2009 of propofol intoxication after suffering a respiratory arrest at his home in Los Angeles.
     Propofol (marketed as Diprivan by pharmaceutical firm AstraZeneca) is a short-acting, intravenously administered hypnotic agent, used for induction and maintenance of general anesthesia. Chemically, propofol is unrelated to barbiturates but has replaced the barbiturate Pentothal for anesthetic induction.
     Jackson had used a number of aliases (Omar Arnold and Jack London) to secure prescription drugs. He was said to have used propofol several times before his death, as well as alprazolam (a benzodiazepine), sertaline (an antidepressant), hydromorphone and hydrocodone (opioid pain killers) as well as a number of other prescription medications (omeprazole, paroxetine, carisopradol), all for insomnia. Jackson had been reported to be taking up to 40 alprazolam pills every night.
Michael Jackson

     Jackson's death was ruled a homicide. His personal physician, Conrad Murray, had administered propofol as well as two benzodiazepines (lorazepam and  midazolam) to his patient that same evening in Jackson's home.  Murray was convicted of involuntary manslaughter and sentenced to four years in prison.

     The ancient Mesopotamians, Greeks and Egyptians had perhaps only one really powerful medication to treat insomnia, one which was powerful enough to kill (opium). Today, modern society has hundreds of these lethal drugs and, with this plethora of 'cures' for the ill of sleeplessness, comes the risk of never waking up at all.
 
     *Insomnia and sleep deprivation: subject of research for the novel The Judas Kiss - Amazon Kindle

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