The opiates are unrivalled in their ability to relieve pain. Opium is the dried milky exudate obtained from the unripe seed pods of the opium poppy plant (Papaver somniferum), which grows naturally throughout most of Turkey. Of the 20 or more alkaloids found in opium, only a few are pharmacologically active.
The important constituents of opium are morphine (10 percent), papaverine (1 percent), codeine (0.5 percent), and thebaine (0.2 percent). (Papaverine is pharmacologically distinct from the narcotic agents and is essentially devoid of effects on the central nervous system.)
About 1804 a young German apothecary’s assistant named F.W.A. Sertürner isolated crystalline morphine as the active analgesic principle of opium. Codeine is considerably less potent (one-sixth) and is obtained from morphine. Diacetylmorphine—or heroin—was developed from morphine by the Bayer Company of Germany in 1898 and is 5 to 10 times as potent as morphine itself. Opiates are not medically ideal. Tolerance is developed quite rapidly and completely in the more important members of the group, morphine and heroin, and they are highly addictive.
In addition, they produce respiratory depression and frequently cause nausea and emesis. As a result, there has been a constant search for synthetic substitutes: meperidine (Demerol), first synthesized in Germany in 1939, is a significant addition to the group of analgesics, being one-tenth as potent as morphine; alphaprodine (Nisentil) is one-fifth as potent as morphine but is rapid-acting; methadone, synthesized in Germany during World War II, is comparable to morphine in potency; levorphanol (Levo-Dromoran) is an important synthetic with five times the potency of morphine.
These synthetics exhibit a more favourable tolerance factor than the more potent of the opiates, but in being addictive they fall short of an ideal analgesic. Of this entire series, codeine has the least addiction potential and heroin has the greatest.
History of opiates
The narcotic and sleep-producing qualities of the poppy have been known to humankind throughout recorded history. Sumerian records from ancient Mesopotamia (5000 to 4000 BCE) refer to the poppy, and medicinal reference to opium is contained in Assyrian medical tablets. Homer’s writings indicate Greek usage of the substance at least by 900 BCE. Hippocrates (c. 400 BCE) made extensive use of medicinal herbs including opium.
The Romans probably learned of opium during their conquest of the eastern Mediterranean. Galen (130–200 CE) was an enthusiastic advocate of the virtues of opium, and his books became the supreme authority on the subject for hundreds of years. The art of medicinals was preserved by the Islamic civilization following the decline of the Roman Empire. Opium was introduced by the Arabs to Persia, China, and India. Paracelsus (1493–1541), professor at the University of Basel, introduced laudanum, a tincture of opium. Le Mort, a professor of chemistry at the University of Leyden (1702–18), discovered paregoric, useful for the control of diarrhea, by combining camphor with tincture of opium.
There is no adequate comprehensive history of the addictive aspects of opium use in spite of the fact that it has been known since antiquity. Because there were few alternative therapeutics or painkillers until the 19th century, opium was somewhat of a medical panacea. Thus, although at least one account, in 1701 by a London physician named Jones, spoke of an excessive use of opium, there appears to have been no real history of concern until recent times, and opiates were easily available in the West in the 19th century—for instance, in a variety of patent medicines. Physicians prescribed them freely, they were easy to obtain without prescription, and they were used by all social classes.
At one time the extensive use of these medicines for various gynecological difficulties probably accounted for high addiction rates among women (three times the rate among men). The invention of the hypodermic needle in the mid-19th century and its subsequent use to administer opiates during wartime produced large numbers of addicted soldiers (about 400,000 during the U.S. Civil War alone); it was thought mistakenly that if opiates were administered by vein, no hunger or addiction would develop, since the narcotic did not reach the stomach.
Toward the end of the 19th century, various “undesirables” such as gamblers and prostitutes began to be associated with the use of opiates, and narcotics became identified more with the so-called criminal element than with medical therapy. By the turn of the 20th century, narcotic use had become a worldwide problem, and various national and international regulatory bodies sought to control opium traffic in China and Southeast Asia. In the 20th century, narcotic use was largely associated with metropolitan slums, principally among the poor and culturally deprived. Narcotic use eventually spread to middle-class youth.
Physiological effects of opiates
The various opiates and related synthetics produce similar physiological effects. All are qualitatively similar to morphine in action and differ from each other mainly in degree. The most long-lasting and conspicuous physiological responses are obtained from the central nervous system and the smooth muscle of the gastrointestinal tract. These effects, while restricted, are complex and vary with the dosage and the route of administration (intravenous, subcutaneous, oral). Both depressant and stimulant effects are elicited.
The depressant action involves the cerebral cortex, with a consequent narcosis, general depression, and reduction in pain perception; it also involves the hypothalamus and brain stem, inducing sedation, the medulla, with associated effects on respiration, the cough reflex, and the vomiting centre (late effect).
The stimulant action involves the spinal cord and its reflexes, the vomiting centre (early effect), the tenth cranial nerve with a consequent slowing of the heart, and the third cranial nerve resulting in pupil constriction. Associated effects of these various actions include nausea, vomiting, constipation, itchiness of the facial region, yawning, sweating, flushing of skin, a warm sensation in the stomach, fall in body temperature, diminished respiration, and heaviness in the limbs.
The most outstanding effect of the opiates is one of analgesia. All types of pain perception are affected, but the best analgesic response is obtained in relieving dull pain. The analgesic effects increase with increasing doses until a limit is reached beyond which no further improvement is obtained. This point may fall just short of complete relief.
Depression of cortical function results in a euphoric response involving a reduction of fear and apprehension, a lessening of inhibitions, an expansion of ego, and an elevation of mood that combine to enhance the general sense of well-being. Occasionally in pain-free individuals the opposite effect, dysphoria, occurs, and there is anxiety, fear, and some depression. In addition to analgesia and associated euphoria, there is drowsiness, mental and physical impairment, a clouding of consciousness, poor concentration and attention, reduced hunger or sex drive, and sometimes apathy.
Apart from their addiction liability, respiratory depression leading to respiratory failure and death is the chief hazard of these drugs. All of the more potent opiates and synthetics produce rapid tolerance, and tolerance to one member of this group always is associated with tolerance to the other members of the group (cross-tolerance). The more potent members of the group have a very great addiction liability with the associated physical dependence and abstinence syndrome.