Opium and its alkaloids

American Journal of Pharmaceutical Education, Summer 2002 by Schiff, Paul L Jr

PROLOGUE

This manuscript reviews the history and pharmacognosy of opium, and describes the chemistry, pharmacology, and therapeutic uses of the major opium alkaloids. An abbreviated form of the material found in this paper is presented in a three-hour lecture format to third year PharmD students as part of their study of analgesics and related compounds in the modular offering entitled Neurology/Psychiatry (Pharm 5319).

Students at the University of Pittsburgh receive an introduction to pharmacognosy and natural products during their first professional year in an introductory course in Drug Development (Pharm 5119). The role of natural products as both historical and continuing sources of drugs, as well as sources of precursors for semisynthetic modification and sources of probes for yet undiscovered drug moieties, is emphasized. This curricular dialog with pharmacognosy and natural products continues in courses in the second professional year [Pharmacotherapy of Infectious Disease 1 and 2 (Pharm 5214, 5215), Cardiology (Pharm 5216), Critical Care (Pharm 5221)] and the third professional year [Oncology (Pharm 5315), [Pulmonology/Rheumatology (Pharm 5316), Neurology/Psychiatry (Pharm 5319)].

HISTORY

Sumeria and Assyria

The opium poppy, Papaver somniferum L. (Papaveraceae), is one of the oldest medicinal plants in recorded history. It is believed that the plant originated in Asia Minor, but the exact time and place of discovery are unknown. The Sumerian culture flourished between the Tigris and Euphrates Rivers in southern Iraq from 4000-3000 BC, and the first mention of the opium poppy is found on Sumerian clay tablets inscribed in Cuneiform script in about 3000 BC. These tablets were found at Nipper, a spiritual center of the Sumerians located south of Baghdad, and described the cultivation of the opium poppy, including the collection of poppy juice in the early morning, with the subsequent production of opium. The Sumerians named opium "Gil," ("happiness"), a term still applied to opium in certain world cultures today, and produced an ideogram of the opium poppy known as "Gil Hul" ("joy plant"). The Assyrians subsequently named poppy juice "aratpa-pal", and it has been speculated that the Latin word "Papaver" (botanical genus of the opium poppy) is derived from this etymological origin. The Assyrians, like the Sumerians, also collected poppy juice early in the morning (via scraping the poppy capsule with an iron scoop) and placed these collections in earthen pots. After the conquest of Assyria and Babylonia by the Persians, mention of the cultivation of the opium poppy and preparation of opium subsequently appeared in the sixth century BC(1-8).

Egypt

The ancient Egyptians cultivated opium poppies, however the use of opium was generally restricted to priests, magicians, and warriors, and was associated with religious cultism. Thoth, the Egyptian god of letters, invention and wisdom was said to have instructed mortal beings about opium preparation, while the goddess Isis was to have used opium as a headache remedy for the god Ra. In fact, the terms "opium thebaicum" and "thebaine" (an opium alkaloid) are derived from Egyptian "Thebes" (an ancient Egyptian city on the Nile River close to modern day Luxor). Opium became a well known drug of Egypt, with its various preparations being concentrated in certain geographic regions(I-3,5,6-8).

Greece, Rome

The word "opium" has been postulated to be of Greek origin, deriving from "opos" (juice) and "opion" (poppy juice). Opium likely came into Greece from Asia Minor and the ancient Greeks associated various divinities with opium, including Hypnos (sleep), Morpheus (dreams), Nyx (night) and Thanatos (the twin brother of Hypnos) (death). Opium is frequently mentioned in Greek mythology, and Homer (850 BC) cites the drug as an intoxicating, pain-relieving and sleepinducing substance in both "The Iliad" and "The Odyssey," while Virgil also mentions it in "The Aeneid." Ancient Greeks regarded opium as a symbol of consolation and oblivion, and crowned all of their nocturnal gods with a wreath of poppy blossoms. This was in concert with their belief that sleep was the greatest of all physicians and the most powerful consoler of humanity. Poppy juice in opium wine was mentioned in the writings of Hippocrates (460-377 BC), the Greek physician and father of medicine. The life-terminating properties of opium were well known, and opium and hemlock were a commonly used combination for the execution of condemned individuals. The Romans continued in the use of opium as a medicinal and as a poison, and according to Pliny (50 AD) the imperator Nero was an ardent user of various plant poisons, including opium, to eliminate enemies. The actual collection of crude opium was described in the first century AD by Dioscorides who accompanied Roman armies throughout the known world of that day(1-9).

Arabia

The Arabs formerly called the opium poppy "Abou-elnoum" ("father of sleep"), and during the seventh century AD when the Arabs ruled Egypt, the preparation became widely spread throughout the Arab Empire. The well-noted Arabian physician and philosopher Avicenna (Abu-Ali-Ibn-Sina) (10th century AD) wrote a famous thesis about opium, but later died of opium intoxication. As the cultivation of the opium poppy flourished, the product was exported to both Europe and India( -9).