THE PERNICIOUS OPIUM POPPY

Opium poppy (Papaver somniferum)

PAPAVERACEAE, Poppy Family

The opium poppy (Papaver somniferum), an annual herb 3-5 feet tall with gorgeous white to pink or purple flowers, has had a powerful impact on human affairs as a medical blessing and a societal curse. This plant produces copious amounts of a viscous latex, which is loaded with strong alkaloids. The latex is collected by incising the immature capsule with a single or multibladed knife and subsequently scraping off the coagulated latex into a bowl. The dry, darkened, slightly sticky latex mass is called opium, from the Greek opos, which means juice. Mature seeds lack alkaloids and are used on rolls and other pastry goods.

Opium poppy has been broadly associated with cultures of the Near East, e.g., Turkey. Nonetheless, recent studies of archaeological and written records suggest that the plant originated elsewhere. In fact, it now appears that the species is native to southern France, Spain, and northwestern Africa. There is a cave site in southern Spain, dated at 5500 B.C., in which intact capsules of opium poppy were found in a religious artifact. Much later, in the Early Bronze Age (3000 B.C.) in the Swiss Lake dwellings caches of poppy seeds and presscake have been found along with parts of flax (Linum), barley (Hordeum), and einkorn, emmer, and bread wheat (Triticum spp.). The evidence is unclear whether this poppy was a semicultivated weed or a true cultivar. The Swiss Lake dwellings were located in the Swiss Foreland between the Alps and the Jura Mountains; this is where rivers from the mountains drained into lowlands, forming lakes and the heads of major European rivers, the Rhine, the Rhone and Po, and the Danube. Nobody knows by what route the peoples or poppies came from Iberia to Switzerland, but a northward course along the Rhone seems likely, and farming peoples probably also came from the Balkans via the Danube. It seems likely that over time this plant was cultivated in Switzerland so that large numbers of seeds could be harvested to press for oil and to be ground for flour (dough). There is no indication that in early western Europe these poppies were smoked or used for medicine.

From 1600 to 1200 B.C., P. somniferum was apparently involved in northern Europe amber and tin trade routes, and thereby spread eastward from Switzerland, and perhaps intentionally or as a weed also into the eastern Mediterranean. Then in the Late Bronze Age poppies are finally seen in the records of the Greek realm, including Homer's Iliad, where they were revered as potent medicinal plants (Theophrastus and Dioscorides). Here poppies and pomegranates (Punica) were used extensively in artwork and jewelry; the two fruits, which have a similar outline, have often been misinterpreted. From the Greek city states, poppies spread successively into the cultures of Crete, Egypt, the Middle East, and finally the Near East, where the plant became used heavily as a narcotic, opium. In ancient Crete, there appears to have been a poppy goddess that wore a crown with three capsules.

Narcotic comes from the Greek "benumbing or deadening." Ancient peoples considered this a sacred plant of medicine and a sleep potion (Hypnos = Greek God of Sleep; Morpheus = Greek God of Dreams; Somnus = Roman God of Sleep). Pliny the Elder warned of the dangers of opium; however, its use as a medicine created addicts, such as the Roman Emperor Marcus Aurelius, and the great Arabic physician Avicenna died of an unintentional overdose of opium in wine. Later addicts included Elizabeth Barrett Browning, Dumas, Edgar Allen Poe, and Samuel Taylor Coleridge. So feared was addiction that France prohibited the sale of opium in 1718 and 1735. Opium smoking in China was forbidden in the 1690s, but the British East India Company smuggled opium into China and promoted its importation. Eventually this precipitated the Opium Wars between China and Britain and France (1839-1842, 1856) , which reshaped the history of that region. In the 1840s, England was given as one concession the island of Hong Kong, which on 1 July, 1997, was returned to Chinese rule. Chinese laborers of the 19th Century promoted use of opium in the western United States when they were imported to build the railroads.

The opium poppy contains up to 50 alkaloids, and the most famous is morphine. Crystalline morphine was first isolated from opium in 1803 by Jean-François Derosne, a fashionable Parisian pharmacist. In 1804-05 Friedrich Wilhelm Sertürner isolated an organic acid from opium; this acid had no effect on dogs, but when ammonia was added to mother's milk of these dogs, the crystals that formed were narcotic to the dogs. Sertürner published his findings and named this substance "principium somniferum." These results were overlooked until they were translated into French and republished; then the findings were appreciated and praised by Gay-Lussac as the discovery of a new group of salt-forming organic alkali. Gay-Lussac proposed that N-containing alkalis should have the "ine" suffix (morphium became morphine), and thus began the standardization of names in organic chemistry. In 1818, Wilhelm Meissner proposed the name alkaloid for this class of salts. Morphine, therefore, was the first nitrogenous base to be crystallized from a living source, but its correct chemical structure was not made until 1925 (Sir Robert Robertson and Gulland).

Morphine [7,8-didehydro-4,5-epoxy-17-methyl(5alpha,6alpha)-morphinan-3,6-diol] is made by the plant from tyrosine or phenylalanine, two of the common 20 amino acids. The resultant alkaloid is an analgesic, a compound that alleviates or abolishes pain without inducing the loss of consciousness. Morphine, which effects especially the central nervous system but also induces drowsiness and can depress respiration, is a medicine that has high physical dependency and low oral activity--taken orally, it is relatively weak. Another alkaloid in the latex of poppy and related species (P. bracteatum) is codeine. Codeine has one-seventh the biological activity of morphine, has less physical dependency, and has oral activity, hence its use in prescription cough medicine and drops. Other poppy alkaloids may also be physiologically active.

Opium, and especially morphine, was an important painkiller during the Civil War, but its use created many addicts. The invention of the hypodermic syringe by Dr. Alexander Wood (1853, based on a design by Sir Christopher Wren) to replace quills, was intended to reduce opium addiction but, of course, it actually made matters much worse because morphine injected into the blood is more powerful. Morphine taken orally is metabolized in the intestinal walls and made into a harmless water-soluble glucuronide in the liver, never reaching the central plasma.

In 1898, E. Merck of Darmstadt marketed the ethyl ether of morphine, called 'Dionin', which was the first semisynthetic morphine derivative, to serve as a cough sedative. That same year Heinrich Dreser of Friedrich Bayer and Company introduced diacetylmorphine (acetylated morphine) as the "heroic drug," having the ability of morphine to relieve but being "safer." Under the proprietary name 'Heroin' (diamorphine), this drug quickly became popular worldwide (Bayer had a very large painkilling business with Heroin and Aspirin!). The very strong heroin was widely prescribed and could be purchased by mail order through the Sears, Roebuck catalog. By 1900, there were an estimated 1,000,000 opiate addicts in the United States, often addicted by accident. So even though it was initially hailed as a nonaddictive morphine substitute, heroin actually was metabolized twice as fast, and 6-monoacetylmorphine, the first breakdown product of heroin, is four times more potent, yielding a combined effect of both chemicals and a drug with very high physical dependence capacity, in fact, actually one of the most addictive drugs ever used in medicine. Governments, under pressure, were compelled to introduce laws on dangerous drugs, and responsible companies stopped using and supplying opiates. In the U.S. opium was eventually placed under federal restrictions by the Harrison Act of 1914. Finally, in 1929 the Rockefeller Foundation and government agencies began a research program to find nonaddictive morphine-like chemicals and analgesics.

In 1973, research first reported that opiates work with specific receptor sites in the brain, replacing naturally produced opiate peptides in the brain, called enkephalins, endorphins, and dynophins. These chemicals inhibit pain messages from being read by the brain cortex, but endorphins are also euphorics, involved in "runner's high." Within weeks of daily use, the body becomes physically dependent on this external supply and stops making its own opiate messages in nerve cells. Opiate neurotransmitters act as blockers by changing the receptor sensitivity and membrane biochemistry and structure to depress spontaneous or glutamine-driven firing activity. Pregnant mother users ensnare the developing fetus, which is affected by smaller size, retarded motor functions, hyperactivity, reduced number of nerve cells in the brain, and a decrease in glia cells. Withdrawal symptoms are related to this fight to restore body functions, and the body cannot return to pristine condition, while receptors are permanently altered. Withdrawal includes a horrible syndrome of limbic and brain stem problems.

Codeine, isolated from the poppy in 1832, is a milder alkaloid, but still is physically addictive, as are all of the synthetic opiates such as Methadone, Demerol (meperidine), and Vicodin (hydrocodone). Meperidine was synthesized in 1939 by Eislab and Shaumann, and is now one of the most widely used analgesics, especially commonly used during labor for child birth, painful skeletal conditions, and severe migraine attacks. Vicodin and the same drug under other names is commonly prescribed for patients after painful dental surgery and those suffering recurrent migraine or cluster headaches. Methadone was invented by the Nazis during World War II as a painkiller for soldiers and in 1963 was used in clinical trial to replace heroin addiction; as an oral dosage, it assuages craving without producing a large euphoric effect, so if administered daily can yield a potentially more useful victim. Newer morphine-like alternative, such as LAAM, have been adopted, which can be administered fewer times per week, cost less, is less likely to reinforce the drug habit, and requires hours longer to produce psychoactive effect.

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