Pregnancy Category C

Uses. This substance is the first synthetic central nervous system depressant, created in the 1830s. After that creation, however, several decades passed before chloral hydrate's medical usage as a sleep inducer began. The anesthetic chloroform is produced from it. Chloral hydrate has also been used against pain of rheumatism. In the nineteenth century the drug was popular among middle-class women and middle-aged men for reducing anxiety.

In former times chloral hydrate was routinely administered to produce anesthesia, but such use is tricky; the difference between an effective dose and a poisonous one is so close that the drug has been replaced by other substances for human anesthesia, although chloral hydrate is still used for that purpose in animals. The substance has been largely superseded by barbiturates but still has medical applications as a sedative and to induce sleep. Chloral hydrate is also used to treat seizures caused by fever and is a secondary choice for controlling the seizures of status epilepticus (an emergency in which persons keep having epileptic seizures, one after another, with little or no letup). Medical caregivers sometimes administer chloral hydrate to help withdrawal from heroin and GHB dependence and to help alcohol addicts withstand delirium tremens during withdrawal. The famed "Mickey Finn" drug used by criminals to knock out victims was a combination of chloral hydrate and alcohol, but animal and human experiments have failed to demonstrate that the combination worked as advertised.

Drawbacks. Chloral hydrate users may act drunken and confused. An experiment found reduction in abilities needed to drive an automobile. The same research, however, also showed that if the product was taken to induce sleep the night before, persons performed better the next day after the drug had worn off, presumably because they were better rested than usual. At normal doses gastrointestinal distress may occur, and persons suffering from stomach irritation are supposed to avoid the compound. A case report notes a deliberate overdose that destroyed part of a patient's stomach. Heart attack has occurred from chloral hydrate overdose, but that is unusual. In high quantities the compound interferes with heart rhythm and reduces blood pressure and breathing; seizures are possible. Experiments using chloral hydrate on rats and mice have injured the liver, and inhaling the drug's vapor has caused lung damage in mice. Human physical contact with the compound can irritate the skin, lungs, and eyes. The substance is suspected of causing kidney damage and colon cysts and of aggravating a disease called porphyria. Reduction may occur in the number of white blood cells. Although the substance is a depressant, some persons are stimulated by the drug.

Abuse factors. In the 1800s a number of prominent persons became addicted to chloral hydrate: English poet and painter Dante Gabriel Rossetti, German literary figure Karl Ferdinand Gutzkow, and renowned German philosopher Friedrich Wilhelm Nietzsche. Such addiction grew uncommon in the twentieth century as the drug itself grew less common. As is so often the case with drug abuse, chloral hydrate addicts were typically polydrug abusers, often using alcohol, opium, or morphine as well. Today chloral hydrate does not seem to be a popular recreational intoxicant, quite possibly because the kind of person who would enjoy chloral hydrate may instead be attracted to barbiturates, a type of drug that was unavailable in the nineteenth century.

No dependence developed after experimenters gave chloral hydrate to monkeys twice a day for six weeks, but tolerance and dependence can develop in humans. The most common origin of dependence is medical usage. Chloral hydrate withdrawal symptoms include tremors, worry, sleeping difficulty, confusion, delirium, hallucinations, and convulsions. Some authorities describe the syndrome as delirium tremens. Withdrawal may have a fatal outcome.

Drug interactions. Actions of anti-blood clotting medicines may be temporarily boosted by chloral hydrate, but the amount of change and its medical significance are disputed. The drug may reduce blood levels of the epilepsy medicine phenytoin, thereby impeding phenytoin's therapeutic actions. In mice experimentation chloral hydrate had inconsistent impact on alcohol blood level (sometimes raising it, sometimes reducing it) but extended the time that intoxication lasted. In humans the combination produces changes in heart rate and blood pressure that might harm cardiac patients (the face and neck of one volunteer turned reddish purple from the combination). Alcohol and chloral hydrate are both depressants, and taking them together is like taking an extra dose of one or the other. Injecting marijuana's main active ingredient THC (tetrahydrocannabinol) into animals increases chloral hydrate's potency.

Cancer. Lab tests of chloral hydrate's potential for causing cancer have produced mixed results. The compound has increased the liver cancer rate in mice, but skepticism exists about human relevance of those mice results because dosage was long term and so high as to be poisonous—circumstances not at all similar to an occasional normal therapeutic dose. Experimenters administered the substance to hundreds of rats every day for over two years without evidence developing that the drug causes cancer. The cancer-causing potential in humans is uncertain.

Pregnancy. Chloral hydrate passes from a pregnant woman into the fetus but is not considered a cause of birth defects. Infants born to such women are, however, more likely to have a condition called hyperbilirubinemia, which can lead to jaundice. Some investigators also believe that administering the drug to infants after birth causes hyperbilirubinemia. The compound passes into the milk of a nursing mother, enough to slightly sedate the infant. Additional scientific information may be found in:

Butler, T.C. "The Introduction of Chloral Hydrate into Medical Practice." Bulletin of the

History of Medicine 44 (1970): 168-72. Miller, R.R., and D.J. Greenblatt. "Clinical Effects of Chloral Hydrate in Hospitalized

Medical Patients." Journal of Clinical Pharmacology 19 (1979): 669-74. Robinson, J.T. "A Case of Chloral Hydrate Addiction." International Journal of Social

Psychiatry 12 (1966): 66-71. Sellers, E.M., et al. "Interaction of Chloral Hydrate and Ethanol in Man. II. Hemodynamics and Performance." Clinical Pharmacology and Therapeutics 13 (1972): 50-58. Sourkes, T.L. "Early Clinical Neurochemistry of CNS-Active Drugs. Chloral Hydrate."

Molecular and Chemical Neuropathology 17 (1992): 21-30. Steinberg, A.D. "Should Chloral Hydrate Be Banned?" Pediatrics 92 (1993): 442-46.

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