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Chloral hydrate

Category: Medicines

Type

Involuntary

Introduction and description

 

Chloral hydrate - Aquachloral; Noctec; Welldorm; Knockout Drops -  is one of the oldest sedative-hypnotics.

The active ingredient in Hall’s formula for epilepsy was chloral hydrate, first reported and used as a sleeping medication in 1869;  although mainly a hypnotic, chloral was also used for a range of  convulsive disorders, which included tetanus, chorea, rabies, strychnine poisoning, toxemia of pregnancy [sic], and alcoholic delirium tremens.

History

 

Chloral hydrate was discovered in 1832 by Justus von Liebig in Gießen.

Its sedative properties were first published in 1869 and subsequently, because of its easy synthesis, its use was widespread. 

No doubt if they had known the word it would have been 'novel' too, novelty being the most important thing to any pharmaceutical researcher and if you do not believe us type in 'novel' and 'drug' into google.  There is little mention of safety or efficacy [sorry for our cynicism here].

In the various editions of the authoritative Dispensatory of the United States of America under various editors we may find several declarative statements:

Although known for decades, chloral was first discovered to be a soporific in 1869, coming into wide medical use shortly after.
William Whitty Hall lauded the THE NEW ANODYNE -  The medical world is delighted with the discovery of a new medicine, and the newspapers abound with advertisements, setting forth the peculiar advantages of each preparation, every man claiming that his own is the best. It is called CHLORAL HYDRATE. The object of taking this medicine is to promote sleep, and thus far, when administered pure and in a proper manner, it has advantages above all others known hitherto, whether in the form of Opium, Morphine, Laudanum, or Paregoric. This Chloral Hydrate is in white crystals; almost every liquid dissolves it; hence it is largely advertised in the shape of syrups, anodynes, and various fluid mixtures.... (339-40)

 

Squire’s 1871 edition of A Companion to the British Pharmacopoeia also cited its use as an “excellent hypnotic, producing sound and placid sleep,” but also used against chorea, delirium tremens, “nervous disturbances and restlessness.” (85).

The 1880 edition of the Dispensatory of the United States of America discusses chloral’s role against convulsions due to various causes, but relegates it to secondary  status against classic epilepsy:

Perhaps no medicine has come so rapidly into extensive use as that now under consideration.... It is simply as a soporific that chloral is most efficient and most employed.... In spasms chloral is often useful, though generally inadequate to the cure of the more violent and obstinate of these affections.... (266, 270-71)

The text mentions tetanus, hydrophobia, chorea and epilepsy, but, “[I]n the latter it is at best but an occasional palliative.” (271)

It was widely used ‘recreationally’ and widely misprescribed in the late 19th century.

 

Chloral hydrate is soluble in alcohol, readily forming concentrated solutions. A solution of chloral hydrate in alcohol called "knockout drops" was used to prepare a Mickey Finn - a drink designed to render someone unconscious.

Side-effects

High doses can depress respiration and blood pressure. 

Long-term use of chloral hydrate is associated with a rapid development of tolerance to its effects and addiction.

Then there are the terrifying hallucinations and visions and the 'psychosis' often misdiagnosed as manic depression and schizophrenia and treated with yet more drugs.  Thee are as many hallucinations and entries into darker realms from withdrawal as there are entry into it, whether you are coming or going it is just as appalling.

Other adverse effects include rashes, gastric discomfort and severe renal, cardiac and hepatic failure. 

Overdose is characterized by nausea, vomiting, confusion, convulsions, slow and irregular breathing, cardiac arrhythmia, and coma. 

And death.

The victims

A whole host of very unfortunate people have used chloral hydrate in the past as a sedative:

  • Anna O - Sigmund Freud's patient Anna O, was treated for severe cough, paralysis of the extremities on the right side of her body, and disturbances of vision, hearing, and speech, as well as hallucinations and loss of consciousness. She was diagnosed with 'hysteria'.  However what was somewhat overlooked was that the problems only started on the death of her father when she was prescribed Chloral hydrate  to sedate her and help her sleep.  This then made her psychotic.  Our entry provides more detail.
  •  Ernest Dowson's father - In August 1894 Dowson's father, who was in the advanced stages of tuberculosis, died of an overdose of chloral hydrate.
  •  
    Marilyn Monroe  - died from chloral hydrate. On August 5, 1962, at 4:25 a.m., LAPD sergeant Jack Clemmons received a call from Dr. Ralph Greenson, Monroe's psychiatrist, saying that Monroe was found dead at her home in Brentwood, Los Angeles, California.  She was 36 years old.  At the subsequent autopsy, eight mg/dL of chloral hydrate and 4.5 mg/dL of Nembutal were found in her system, both prescribed by her doctor.  Despite calls of 'foul play', Dr. Thomas Noguchi of the Los Angeles County Coroners office recorded cause of death as "acute barbiturate poisoning", resulting from a "probable suicide".
  • Friedrich Wilhelm Nietzsche - became addicted to chloral hydrate plus a number of other drugs prescribed by his doctors.  By 1882, Nietzsche was taking huge doses of opium and laudanum.  In 1883, while staying in Nice, he was also writing out his own prescriptions for the sedative chloral hydrate, signing them 'Dr Nietzsche'.
  • John Boyle O'Reilly - In his later years, O'Reilly became prone to illness, and suffered from bouts of insomnia. Late in the evening of 9 August 1890, while suffering from insomnia, he took some of his wife's sleeping medicine, which contained chloral hydrate. In the early hours of the morning, he was found dead. There remains some doubt as to the cause of death. Public announcements attributed O'Reilly's death to heart failure, but the official death register claims "accidental poisoning".
  • Dante Gabriel Rossetti - was a regular user of chloral hydrate, originally against insomnia. He is quoted as saying to his friend Hall Caine: "Everyone has skeletons in their cupboards, and this is mine."  The savage reaction of critics to Rossetti's first collection of poetry contributed to a mental breakdown in June 1872, and although he joined Jane at Kelmscott that September, he "spent his days in a haze of chloral and whisky".  Toward the end of his life, he sank into a morbid state, darkened by his drug addiction to chloral hydrate and increasing mental instability. He spent his last years as a recluse at his home in Cheyne Walk.  On Easter Sunday, 1882, he died at the country house of a friend, where he had gone in a vain attempt to recover his health, which had been destroyed by chlorate.
  • Hank Williams  - came under the spell of a man calling himself "Doctor" Toby Marshall (actually a paroled forger), who often supplied him with prescriptions and injections of chloral hydrate, which Marshall claimed was a pain reliever, to deal with the pain from Williams' lifelong severe back problems.

 

  • William S. Burroughs  - was expelled from school for experimenting with chloral hydrate along with another pupil. The incident is detailed in the writer's foreword to Junkie.
  • Mary Todd Lincoln  - was given chloral hydrate for sleep problems. 
  • André Gide (1869–1951)  - was given chloral hydrate as a boy for sleep problems by a physician named Lizart. Gide states in his autobiography, If It Die... that "all my later weaknesses of will or memory I attribute to him."
  • Antonin Artaud -  In January 1948, Artaud was diagnosed with colorectal cancer. He died shortly afterwards on 4 March 1948, alone in the psychiatric clinic. It was suspected that he died from a lethal dose of the drug chloral hydrate, although it is unknown whether he was aware of its lethality..
  • Oliver Sacks  - is said to have abused chloral hydrate in 1965 as a depressed insomniac. He found himself taking fifteen times the usual dose of chloral hydrate every night before he eventually ran out, causing violent withdrawal symptoms.

Given the link between this class of chemicals, brain damage and manic depression, Marilyn Monroe’s problems may have been brought on or exacerbated by the substance.

One of the more famous cases is that of Anna O. who hallucinated and became ‘psychotic’ from taking the drug.  She was then treated by Sigmund Freud, who became famous for the treatment.  What is not mentioned is that she fled Freud and after having escaped got better by herself.

Hist Psychol. 2003 Aug;6(3):239-50.

Revisiting Anna O.: a case of chemical dependence - Ramos Sde P.;  Psychiatry department, Universidad Federal de São Paulo, Brazil. serramos@terra.com.br

The famous clinical case of Anna O./Bertha Pappenheim, who was treated by Breuer from 1880 to 1882 and whose pathology was discussed by him and Freud in an 1895 article (J. Breuer & S. Freud, 1895/1955), is reviewed based on biographical information regarding the patient, which appeared from 1953 onward.  The objective of this article is to show that, in order to better understand the case, the diagnosis of chloral hydrate .... has to be taken into account. PMID: 14506815

 

Its status today

Chloral hydrate isn't as 'novel' anymore, so those doctors and researchers who get a thrill from novelty have lost interest in it and moved on to other newer drugs without the stigma attached to them - yet.

But rather extraordinarily given its history, it is still used for the short-term treatment of insomnia.  And it is used as a sedative before minor medical or dental treatment. It is also still used, and I quote, as  "a sedative prior to EEG procedures, as it is one of the few available sedatives that does not suppress epileptiform discharges". At which point one should ask why a sedative is needed at all.

And they give it to children in hospital - see the observations.

But there are a few brave souls who fight the good fight, and quite a number of them have said that the use of the substance should be discontinued completely.  But then they have been saying this for well over one hundred years, and repeating it and repeating it and repeating it   ........

Med J Aust. 1988 Dec 5-19;149(11-12):686-8.  Overdose with chloral hydrate: a pharmacological and therapeutic review.  Graham SR, Day RO, Lee R, Fulde GW.
St. Vincent's Hospital, Darlinghurst, NSW.

The purpose of this review is to highlight the toxicity of chloral hydrate and to review the management of overdoses with chloral hydrate.
Three patients are presented in whom life-threatening cardiac arrhythmias dominated the clinical presentation. These arrhythmias were resistant to standard antiarrhythmic therapy.
Also, we have reviewed selected features in eight patients who took overdoses of chloral hydrate who were admitted to an intensive care unit between 1981 and 1988. The pharmacology and toxicology of chloral hydrate are discussed with particular reference to the cardiac arrhythmias that are seen with overdosage.
A case may be made for the discontinuation of the usage of chloral hydrate.

PMID: 3059159

 but here I quote

Chloral hydrate is not now approved by the FDA in the United States or the EMA in the European Union for any medical indication and is on the list of unapproved drugs that are still prescribed by clinicians

May God save us all.

 

 

References and further reading

Chloral hydrate page of website Erowid.org

Related observations