A brief history of opiates, opioid peptides, and opioid receptors.

It is hard to decide when and where the opium poppy was first cultivated. It may have been grown for its seeds before people discovered how to prepare mekonion from the leaves and fruits of the plant or opium (from "opos," the Greek word for juice) from the liquid that appears on the unripe seed capsule when it is notched. The use of written records to decipher the early history of opium use and abuse is hard because descriptions of drugs by ancient authors are often ambiguous. The preparation described by Homer-given by Helen, the daughter of Zeus, to Telemachus and his friends to help them forget their grief over Odysseus' absence-was attributed to Homer's imagination by Theophrastus (300 B.C.) who was himself aware of the method used to produce opium. Other writers (e.g., Diskourides, A.D. 60) have argued that the drug alluded to by Homer contained henbane, the active ingredient of which is scopolamine. Most modem pharmacologists including Schmiedeberg (1) and Lewin (2) feel that Helen administered opium to the men. Indeed, Kritikos and Papadaki (3) have suggested that Telemachus may not have experienced any of the toxic effects ofopium because he and his contemporaries used it habitually. Despite difficulties in interpreting ancient writings and archeological data, a picture of opium use in antiquity does emerge from them. There is general agreement that the Sumerians, who inhabited what is today Iraq, cultivated poppies and isolated opium from their seed capsules at the end of the third millenium B.C. They called opium "gil," the word forjoy, and the poppy "hul gil," plant ofjoy. It appears that opium spread from Sumeria to the remainder of the old world. At first opium may have been employed as a euphoriant in religious rituals, taken by mouth or inhaled from heated vessels (4). Knowledge of its use may initially have been confined to priests representing gods who healed the sick and gods of death as well. It was given along with hemlock to put people quickly and painlessly to death, and it came to be used medicinally. The Ebers Papyrus (ca. 1500 B.C.), for example, includes the following description of a "remedy to prevent excessive crying of children" (see ref. 2, p. 35): "Spenn, the grains of the spenn (poppy)-plant, with excretions of flies found on the wall, strained to a pulp, passed through a sieve and administered on four successive days. The crying will stop at once." This remedy and others containing opium (such as spongia somnifera, sponges soaked in opium used to relieve pain during surgery) were dangerous because they varied in potency and rate of absorbance. Consequently, many physicians were wary of using them. Most authors* agree that, as early as the eighth century A.D., Arab traders brought opium to India (6) and China (7) and that between the tenth and thirteenth centuries opium made its way from Asia Minor to all parts of Europe. With the drug came addiction. Starting in the sixteenth century, manuscripts can be found describing drug abuse and tolerance in Turkey, Egypt, Germany, and England. Nowhere was the problem of addiction greater than in China where the practice of smoking opium began in the midseventeenth century after tobacco smoking was banned. Efforts to suppress the sale and use of opium failed because the British, laterjoined by the French, forced the Chinese to permit opium trade and consumption. In 1806, Serturmer (8, 9) isolated the active ingredient in opium and named it morphine after the god of dreams, Mor-