Sleeping potions were some of the earliest drugs discovered, and sleep aids are still among the most widely used drugs today. The ancient Greeks and Egyptians used the extract of the opium poppy to induce sleep. The Greek god of sleep, Hypnos, was usually depicted holding a poppy flower. The juice of the poppy contains chemicals known as opiates, from which morphine and heroin are distilled. Ancient Greeks and Romans knew several other herbal sleep-inducers. The bark of mandrake, or mandragora, was used as a sleep aid, as were the seeds of an herb called henbane. The juice of lettuce was also used to induce sleep. As early as 300 B.C., Greek doctors were known to prescribe concoctions of these different plant derivatives. Similar prescriptions were also apparently known throughout the Arab world. 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." Plant-based sleep aids were all that were available up until the nineteenth century. The chemist Frederick Setumer synthesized opium in 1805, and other advances in sleep drugs followed by the middle of the century.
Two drugs used in the nineteenth century to induce sleep were bromides and chloral hydrate. Chloral hydrate was synthesized in 1832 by a German chemist, Justus von Liebig. Chloral hydrate is a central nervous system depressant that acts very rapidly. Chloral hydrate alone could send a person into deep sleep in about half an hour. Chloral hydrate works much more quickly in combination with alcohol. Slipped into whiskey, it was the "knockout drops" of the underworld, also called a "Mickey Finn." The class of sleeping drugs called bromides were invented in 1857 by an English chemist, Sir Charles Locock. There are several bromide salts, including sodium bromide, potassium bromide, and ammonium bromide, which all act as central nervous system depressants. Locock first used bromides as an anticonvulsant to treat epileptics. A German doctor, Otto Behrend, discovered in 1864 that potassium bromide was a useful sedative. The various bromides be-came popular as sleep aids in the late nineteenth and early twentieth century.
The most popular sleeping pills of the early twentieth century were the barbiturates. The barbiturates comprise a huge class of drugs with at least 25,000 known compounds. Of these compounds, about 50 were or are marketed as prescription drugs. The forebear of the barbiturates was actually discovered in the mid-nineteenth century. A Prussian chemist, Adolf von Baeyer, is credited with inventing and naming barbituric acid in 1863 or 1864. He created the acid out of a compound of malonic acid and urea. On the day of his discovery, Baeyer is said to have gone to a nearby tavern to celebrate. Some sources say it happened to be the feast of St. Barbara that day; others say the barmaid was named Barbara. In any case, he named the compound barbituric acid. In itself, barbituric acid was useless. In 1903, a student of Baeyer's, along with another German chemist, produced a new compound out of barbituric acid and a diethyl derivative. The new chemical, given the trade name Veronal, was an excellent sedative and sleep aid. Other researchers came up with more barbituric acid derivatives. The most widely used was phenobarbital. Many European and American pharmaceutical companies came up with new barbiturates in the 1920s and 1930s. The Eli Lilly Company produced the widely used Amytal and Seconal, and Abbott Laboratories invented Pentothal.
Though the barbiturates were effective sleep aids, they also proved dangerous. Barbiturates are addictive, can have a variety of unpleasant side-effects, and their effectiveness is greatly increased when taken with alcohol. Barbiturate sleeping pills taken with alcohol can quickly bring on death, whether through accidental overdose or planned suicide. Scientists developed safer sleeping pills in the 1970s, the benzodiazepines. Early benzodiazepine drugs shared problems with barbiturates. They were addictive and had side effects such as memory impairment. Improved benzodiazepines were developed in the late 1970s and early 1980s. In the 1990s, non-benzodiazepine drugs were developed, which leave the body much more quickly than the older drugs.
The barbiturates and benzodiazepines are ingredients in prescription drugs, given out by a doctor. Until the 1970s, ingredients in over-the-counter sleep medications were not closely regulated in the United States. The FDA began reviewing over-the-counter drugs in the early 1970s, and by 1978 had approved one active ingredient for an over-the-counter sleep aid. This was the antihistamine doxylamine succinate. In 1982, the FDA approved two more antihistamines for non-prescription hypnotics. These are diphenhydramine HICI and diphenhydramine citrate. These three drugs are the only active ingredients approved for non-prescription sleep aids in the United States. Though it is possible to overdose on these drugs, they are not nearly as strong as prescription sleep aids, and in most cases can be used safely when the directions are followed.