Nature's Pharmacopeia: A World of Medicinal Plants
A poppy flower.
The poppy is an herbaceous annual plant that produces upright flowering stems up to 1.5 meters in height and leaves with toothed edges that grow close to the ground.1 Each flowering stem is tipped by a single flower that bears (usually) four large, thin petals. Poppy flowers are white, red, or purple. The flowers give rise to spherical seed pods known as capsules. Each poppy capsule matures to contain hundreds to thousands of small black, gray, or white seeds. These nutritious seeds have been used in European and western Asian cuisine since antiquity, pressed for oil and baked into bread and pastries.2 Domesticated poppy, recognized by its larger capsule and tendency to retain mature seeds for harvest, was propagated from a wild ancestor, probably in the European western Mediterranean region.3 The plant tolerates a range of temperate and tropical climates (at elevation in the latter) and now grows on all inhabited continents.
ANCIENT USE IN THE MEDITERRANEAN REGION
Archaeological evidence supports the notion that the poppy was widespread in Europe and the Near East in ancient times. Among the earliest finds are poppy seeds at a 7700-year-old Neolithic settlement in northern Italy and dried poppy capsules associated with woven baskets at a burial cave in southern Spain dated to 2200 B.C.E. A number of Swiss, German, Polish, Czech, and other sites throughout northern and central Europe have turned up remains of poppy dating back 4000 or more years. Such botanical relics indicate that the poppy was collected, probably for use as food, across a vast expanse of Europe. Artifacts also demonstrate the poppy’s significance to ancient peoples. For example, Mycenaean Greek (1550–1100 B.C.E.) jewelry items from modern-day Greece and Turkey depict what appear to be poppy capsules.4Artifacts such as poppy capsule–shaped juglets hint that poppy may have been prepared as a drug as early as the sixteenth century B.C.E. (figure 5.1).
While it is unknown when the poppy’s medicinal properties were discovered, by the time of the Egyptian Ebers papyrus of 1550 B.C.E., the herb was documented as a pharmaceutical substance of great strength.5 For example, the plant figures in a prescription for a “remedy to stop the crying of a child.” This recipe requires “pods-of-the-poppy-plant” mixed with “fly-dirt-which-is-on-the-wall,” eaten for four days. According to the text, “it acts at once!”6
The Greeks and Romans left extensive records detailing the uses of the poppy in cuisine and pharmacy.7 The early Greek botanist Theophrastus (371–287 B.C.E.) mentioned the plant in Enquiry into Plants, and the influential herbalist Pedanius Dioscorides (ca. 40–90) noted that “its seed is baked into bread to use in a health-inducing diet.” He also recommended the boiled leaves and capsule to help one sleep and ground seeds consumed in wine to treat diarrhea and gynecological infections. Furthermore, he explained that the opos (juice) expressed from a cut plant was a particularly potent medicine. “It is analgesic, soporific [sleep-inducing], helpful for digestion, and it comes to the aid of coughs and abdominal conditions,” Dioscorides wrote.8 Galen (129–ca. 216) agreed that the “seed of the cultivated poppy is useful as a seasoning spread on bread, just like sesame seed.” As a plant with a cooling property, according to Galen, “it is soporific and, if taken to excess, causes lethargy.”9 In these and many other passages, classical physicians documented some key pharmacological properties of what modern-day medicinal chemists recognize to be an important class of plant active principles: the opiates. The opiates, including morphine and codeine, are poppy-derived alkaloid compounds grouped together because of their shared numbing effects. In his detailed treatment of the poppy, Dioscorides noted the pain-relieving, sleep-inducing, cough-suppressing, and antidiarrheal effects of the herb. The only major medicinal effect not described is the feeling of pleasure it gives to those who consume it.
FIGURE 5.1 An earthenware vessel from Cyprus believed to have contained opium, ca. 1600–1400 B.C.E. The shape resembles an upside-down poppy capsule, and the groove opposite the handle might represent a cut made for opium harvesting. (Science Museum, London. Wellcome Images, L0058861)
The method of preparation affects its pharmacological properties. The aerial portion of the plant (leaves and stems) is known as the poppy herb, and it accumulates relatively little opiate content. Dioscorides recommended poppy herb lozenges for coughs and abdominal conditions.10 The poppy seeds contain edible oils and are rich in protein, making them a nutritious element of cuisine.11 They have only a minuscule level of opiates.12 Ancient poppy growers must have noticed that the capsule was more medicinal than the rest of the plant and that its thick, milky latex (the fluid exuded from wounds) was more potent still (figure 5.2). Dioscorides described a method to obtain this substance, called opium, in a form still practiced today.13 “It is necessary to scratch all around the capsule with a knife in a way as not to pierce through its inner part, and to make superficially straight cuts at the side of the capsule,” he explained, “then wipe up the tear that flows with the finger into a spoon.”14 By allowing the latex to flow and harden, then carefully collecting it after several hours, cultivators accumulated significant quantities of a potent, sticky, solid opium product (figure 5.3). To obtain the medicinal effect desired, people ate this thickened poppy latex alone or mixed it with foods or drinks. While the ability of opiates to soothe discomfort earned the poppy its prominent role in the classical materia medica, the dangers of opium and its concentrated active principles reminded physicians then (as in the modern day) that the line between medical benefit and toxic effect can be simply a matter of dose. Dioscorides was well aware of this risk, as he warns of opium, “but when too much of it is drunk, it plunges into a coma and it is deadly.”15
An opaque, milky fluid that exudes from certain plants when cut
FIGURE 5.2 Latex exuding from incised poppy capsules. (Photograph by Toni Kutchan, Donald Danforth Plant Science Center; from Marion Weid et al., “The Roles of Latex and the Vascular Bundle in Morphine Biosynthesis in the Opium Poppy, Papaver somniferum.” Proceedings of the National Academy of Sciences USA 101 : 13957–13962. © 2004 National Academy of Sciences USA)
FIGURE 5.3 A man in Turkish dress preparing opium. (Woodcut from Angelo Sala, Opiologia ; Wellcome Library, London, M0010469)
Such lethal effects intrigued those whose intents were to harm rather than heal. Poppy proved itself a subtle agent of death. Pliny the Elder (23–79), writing in Rome, relayed the story of an elderly man with an incurable illness who took his own life with an overdose of opium, his “malady having rendered existence quite intolerable to him.”16 Opium served in assassination as well. Mixed with the victim’s food, opium might be undetected until the target fell into a deep, permanent sleep. It is thought that the Emperor Claudius’s wife, Agrippina, in 55 C.E. put opium in the wine of her fourteen-year-old stepson, Britannicus, to procure the throne for her own son, Nero.17
The Greek and Roman period saw widespread use of the poppy for food, for its medicinal properties, and for its symbolism in artifacts and mythology. For example, the Greek goddess Demeter (Roman Ceres), representing fertility and agriculture, is often depicted holding stems of poppies along with stalks of grain. Worshippers are said to have made offerings of poppy to her in hopes of a bountiful harvest.18The Greek Hypnos (Roman Somnus), the god of sleep, is frequently portrayed holding a bunch of poppies, highlighting the plant’s potency as a sleep inducer.19 The brother of Hypnos, tellingly, is Thanatos (Roman Mors), the god of death.
OPIUM AS WORLD MEDICINE
Apparently, the Romans did not participate in long-range trade in poppy, and after the fall of their empire, very little record exists of the poppy’s role as a major medicinal or economic plant.20 However, among the Muslims, whose influence began to spread during the eighth through tenth centuries, commerce in opium was an important component of their cultural domain. Poppy was cultivated in Persia, Anatolia, and elsewhere in the Islamic world and traded from Moorish Spain through North Africa, the Middle East, and Asia. The Islamic physicians (many of whom, such as Abu Ali al-Husayn ibn Abd Allah ibn Sina [Avicenna, 980–1037], were widely respected in Europe and Asia for centuries) incorporated the poppy into their medical textbooks as painkillers and sleep inducers, much as the Greeks and Romans had. The Arab and Persian caravans and trading vessels brought the poppy to India and Southeast and East Asia, where cultivation yielded opium as a valuable medical commodity.21
While knowledge of opium had not totally disappeared during the European Middle Ages, its prominence certainly faded. The European Crusaders of the eleventh through thirteenth centuries also learned more of the poppy’s medicinal values from the Muslims against whom they fought.22 As the Venetian merchant mariners developed an extensive and profitable Mediterranean trade in the fifteenth century, they sought sources of opium for importation. At first, the Arabs supplied Venice with opium and spices, goods that the Venetians traded throughout Europe. Eventually, the Portuguese eclipsed Venice by sailing around Africa and purchasing opium directly from dealers in India. It was during this time that opium regained an important role in the European medicine chest.23
Keenly aware of its capacity to alleviate their patients’ suffering, many physicians came to view opium as an essential weapon in their therapeutic arsenal. In time, they developed new formulations of opium. In its original state, opium is the gummy, brownish dried exudate of the poppy capsule, and various men came up with inventive admixtures and concoctions to offer their patients. The radical Swiss doctor Paracelsus (1493–1541) is credited with having invented a type of opium tablet that he named laudanum, from the Latin word laudare (to praise).24 By the early seventeenth century, laudanum was reformulated as an alcoholic tincture (opium dissolved in alcohol) containing various medicinal plant extracts, sometimes mixed with honey and spices for ease of ingestion.25 Over time, laudanum was standardized to contain simply opium dissolved in alcohol.26 The unquestioned effectiveness of opium against pain and its increasingly popular, simple-to-take formulations led many to praise its usefulness—the patriarch of English medicine Thomas Sydenham (1624–1689) said that “medicine would be a cripple without it”—but led some to recognize a growing dependence on its soothing yet barbed hold.27 The combination of physical tolerance and opium’s activation of pleasure pathways in the brain gave rise to many long-term (probably addictive) relationships between patients and the poppy.
To the British physician George Young (1692–1757), opium’s overuse posed significant risks to the public, not from acute toxicity but from the consequences of chronic abuse. “Opium is a poison by which great numbers are daily destroyed; not, indeed, by such doses as kill suddenly, for that happens very seldom,” he wrote, “but by its being given unseasonably in such diseases and to such constitutions for which it is not proper.”28 Another eighteenth-century writer noted that patients taking opium often require increased doses over time, advising physicians to consider “the constitution and habit of the patient” when prescribing the drug.29
While opium and its derivatives have had striking effects on all the societies in which they were used and abused, the story of opium in China is particularly poignant.
OPIUM IN CHINA
The poppy probably reached China via Arab traders over the Silk Road by the eighth century, and it saw use for centuries as a medicinal herb.30 During the Tang dynasty (618–907), it was cultivated in the southwestern Chinese province of Sichuan, and descriptions of the poppy flowers appear in poetry of the era.31 By the time of the Song dynasty (960–1279), Chinese scholars recommended the seeds, capsules, and herb of the poppy as powerful medicines. For example, a book of pharmacy from 973 declared that “its seeds have healing powers,” especially suggested to counteract the toxic effects of mercury-containing drugs.32 Later, the government official and poet Su Shi (1037–1101) praised the convenience of poppy in medicinal herbal teas useful against sunstroke, writing, “even a child can prepare the yingsu [poppy] soup.”33 Other texts recommended the poppy capsule to treat dysentery and pain.34
By the fourteenth century, the poppy had become integrated into medical practice and was considered useful against a broad range of ailments. However, its dangers had also become apparent. In a passage reminiscent of the warning expressed by the Greek herbalist Dioscorides, writing many centuries earlier, the physician Zhu Zhenheng (1282–1353) explained: “The poppy capsule is used extensively for cough at the present time in the case of those who are weak and consumptive. It is employed to take away the cough. It is used also for diarrhea and dysentery accompanied with local inflammation. Though its effects are quick, great care must be taken in using it because it kills like a knife.”35
It is not clear when the Chinese began using the poppy in its dried-latex opium form, but during the Yuan dynasty (1271–1368) and afterward, opium was undoubtedly used as a tribute good and reached China from nearby nations.36 Produced in China and imported from vassal states in Southeast Asia, opium was increasingly available throughout the country during the fourteenth and subsequent centuries.
In addition to its use in treating pain, cough, and intestinal problems, opium transitioned to a role in spiritual-sexual health. By the early fifteenth century, opium was being offered by herbalists as both yao (medicine) and chunyao (spring medicine, or aphrodisiac).37 In the Grand Materia Medica of 1596, the landmark medical book by Li Shizhen (1518–1593), opium was listed to treat diarrhea and to “help control the essence of men; ordinary people use it for the art of sex.”38 In the medical interpretation of the era, opium was useful to control the male sexual response, as retention of ejaculate was thought to regenerate the spirit.39 It is not surprising, then, that even the Chinese emperors indulged frequently in such medicine. In fact, the Ming emperor who ruled as Wanli from 1573 to 1619 was long suspected to have been addicted to opium.40 In a report published in 1997, the Chinese Ministry of Public Security confirmed that the emperor’s bones contained high levels of the opium compound morphine.41
Until the sixteenth century, the Chinese took opium much as the Europeans did: by eating the opium paste or mixing it with water or alcohol to drink. After contact increased with Europeans, especially in coastal cities, the Chinese learned to smoke, and they applied that knowledge to the consumption of opium.
Sometime during the second half of the sixteenth century, tobacco (Nicotiana spp.) entered China through trade with the Spanish or Portuguese.42 By the 1620s and 1630s, Chinese writers noted that smoking tobacco extended through all strata of society, and many individuals in the government and military were frequent users.43 The Chinese acquired pipes and soon innovated all varieties of smoking instruments, including water pipes, pipes with long stems, and short pipes for tobacco consumption. While opium was typically prepared in soups and as pills to be swallowed until the seventeenth century, during the seventeenth and eighteenth centuries smoking opium—through the Chinese-conceived long pipes—became commonplace. Among the lower classes, bamboo pipes substituted for the more elegant devices employed by the nobles.44
Opium prepared for smoking is specially processed to promote its rapid vaporization under the heat of a lamp. First, the raw opium is boiled and strained to remove traces of poppy herb. In the process, the opiates become concentrated in a dark paste. Then, a small bead of smoking opium is teased apart with small needles and worked, under heat, into a ball that fills the minute cavity of a porcelain or an earthenware bowl at the end of the long pipe. By placing the bowl directly over an oil flame, the smoker more easily vaporizes and inhales the opium.45 By the eighteenth century, opium smoking was widespread through China and among its Asian trading partners.
FIGURE 5.4 Workers rolled Indian opium into balls and dried them on large wooden racks before export. (Lithograph after Walter S. Sherwill, The Stacking Room, Opium Factory at Patna, India [ca. 1850]; Cornell University Library, RMC_2005_0215)
Much of the opium smoked in China was cultivated in India, a territory gradually entering British trade domination during the late eighteenth century. With the assistance of the British government, the British East India Company obtained a monopoly on the Indian opium trade (figure 5.4). With that, the East India Company was able to sell its Indian opium in exchange for silver to merchants, ostensibly independent agents who shipped the product to stations off the coast of China for distribution. At the same time, the East India Company used the silver to purchase Chinese tea for delivery to Great Britain.46 By the nineteenth century, the East India Company employed thousands in the processing and packaging of Indian opium and held monthly opium auctions in the cities of Calcutta and Bombay to supply largely Chinese wholesalers. The Chinese elite continued to promote the health-restoring virtues of opium use, and this philosophy permeated the urban centers, from the seafaring south to the Qing (1644–1912) court in Beijing. And while the Qianlong emperor (r. 1736–1799) did issue an edict to ban opium, little could be done to enforce it in a culture of booming trade and consumption.47
FIGURE 5.5 Opium smoking as a Chinese cultural practice: (left) two men smoking opium; (right) upper-class (Manchu) woman smoking opium, ca. 1900. ([left] From George Morrison, An Australian in China ; [right] Library of Congress, Prints and Photographs Division, LC-USZ62–25834)
The British, for their part, tried to exert diplomatic pressure to open up China’s vast market to free trade. In 1793, and again in 1817, representatives of the Crown visited Beijing demanding an embassy, access to the Chinese market, and a concession of land for foreign merchants. Both visits were graciously accommodated, but the Qing emperors refused the requests. Official policy notwithstanding, the smuggling trade of opium from India to China grew from 4244 chests in 1820, to 18,956 in 1831, to 40,200 in 1839.48 The opium-smoking habit in China originated as an imperial medicinal-recreational sex aid and spread through cities among government officials and merchants, from the urban port areas of the east and south to areas north, west, and inland (figure 5.5). Members of the lower classes emulated their elite contemporaries in this trendy practice, and, coupled with prostitution, smoking seduced millions.
Numerous historical, economic, and social factors converged in the Chinese government’s ill-fated effort to exert control over a rapidly degenerating opium and foreign trade situation.49 The Daoguang emperor (r. 1821–1850) sent agents to enforce the prohibition, seizing and destroying a large quantity of British-owned opium. A number of skirmishes ensued, culminating in the arrival of a British expeditionary force in June 1840 that was victorious over the Chinese opposition. The Treaty of Nanjing (1842) ended this First Opium War (known as a “War of Free Trade” in Britain). In China’s defeat, Britain received an indemnity, access to five ports for trade, and Hong Kong. Although the treaty obligations did not legalize the opium trade, after the first war, Qing officials only sporadically enforced its ban.50
The Opium Wars
FIRST OPIUM WAR (1839–1842)
China ceded Hong Kong to British; opened five treaty ports for international trade; indemnity.
SECOND OPIUM WAR (1856–1860)
China opened ten more treaty ports; allowed unimpeded access to European missionaries; indemnity.
Under constant pressure from Western diplomatic forces, China acceded to demands from the French and Americans for access to trade. In October 1856, Chinese officials boarded a Hong Kong–registered vessel in southern China in search of smugglers and pirates, an affront to the British colonial authorities.51 The British retaliated by attacking Guangzhou and were joined by the French after a missionary was assaulted. This Second Opium War resulted in strikes on major cities of the south and on Beijing’s imperial palaces. In 1860, China ratified the Treaty of Tianjin, agreeing to open ten more ports of free trade, grant unimpeded access to the country by Western missionaries, legalize opium importation, and pay a substantial indemnity to Britain and France.52
The Opium Wars brought about an increased trade in opium, both imported and of domestic production, since even the large volume of Indian opium was insufficient to meet domestic demand, and Chinese farmers saw the poppy as a lucrative cash crop.53 The ports of free trade—including British Hong Kong and the concessions to Western powers in Shanghai—provided one avenue for the drug to reach markets, and Chinese merchants effectively met the inland demand for opium.
The treaty port of Shanghai, with its booming trade and foreign population, became the center of a drug-recreation culture that soon spread worldwide. During the mid-nineteenth century, the opium shop transitioned from one where the average person could purchase opium for consumption at home to a veritable “flower-smoke house” (opium den), where opium and sex could be cheaply and easily purchased.54In the second half of the nineteenth century, China—battered by two asymmetrical wars, impoverished by unbalanced foreign trade, and increasingly dependent on narcotics—saw itself drawn into a period defined in great part by a rampant opium lifestyle.55
It is difficult to estimate the effect of opium on Chinese society during this period. Statistics of opium use are available only in the subjective diaries of witnesses, so there is no way to be certain how extensive opium consumption really was. A British government official estimated that 15 to 20 percent of the adult population in Xiamen, along the southeastern Chinese coast, smoked opium in 1870.56 Other estimates for the era ran as low as one in 166 to as high as nine in ten opium users.57 Among Westerners, some of the strongest critics of opium were missionaries. In 1900, one English writer lamented, “I hold that the opium vice is the most colossal in its pernicious effects that the world has ever known.”58
OPIUM IN NINETEENTH- AND TWENTIETH-CENTURY WESTERN MEDICINE
As opium entered mainstream Chinese culture, it also became further established in the pharmacopeias of Europe and the United States. As a painkiller of unequaled power, with the singular ability to calm persistent coughs, ease the belly, and provide rest, opium and its alcoholic formulation, laudanum, had been extolled since the Renaissance by doctor and patient alike (figure 5.6). Yet opium’s extensive use led some to require ever-increasing doses to meet their addiction. There was little effort, though, during much of the time that opium reigned as the frontline medicine for the challenges of a difficult existence, to identify the particular chemical compounds responsible for its effects.
As the study of pharmacy grew more empirical during the late eighteenth century, scientists began to investigate the chemical makeup of medicines.59 In isolating chemicals from medicinal plants and testing their effects (on animals and people), these pioneer researchers sought the specific chemicals that caused physiological effects in humans. In these particular chemical compounds, isolated from all the other chemicals present in plants—the active principles—researchers hoped to discover the material basis of the actions of medicinal plants.
FIGURE 5.6 Opium in alcohol (laudanum) was an important medicine until the early twentieth century. Paregoric is a weaker, camphorated opium solution, here sold alongside laudanum by mail order from Sears, Roebuck and Company, 1897.
The process of identifying and characterizing the pharmacologically active chemicals in plant medicines is one of the key steps in understanding their physiological roles. Through such studies, medicine has gained insight into the function of the nervous system and attained safer dosing regimens. The isolation of active principles is also an important step in purifying and distributing such drugs for therapeutic (and illicit) use.
The first to tease out the active principle from the poppy—the first plant active principle to be so studied—was the German organic chemist Friedrich Sertürner (1783–1841), who accomplished the task in 1803.60 Many more alkaloids were later determined from a wide range of medicinal plants by chemists working in Europe and elsewhere. Sertürner named the chemical he extracted from poppy morphine, after Morpheus, the Greek god of dreams (figure 5.7).61
Following the chemical isolation of morphine, European and American firms began to produce large quantities of it to meet the medical demand.62 In the form commonly prepared during the nineteenth century, morphine consisted of a powder that could be added in precise amounts to alcohol or water for ingestion by patients seeking help sleeping, relief from pain, or alleviation of myriad other concerns.63 With the invention of a practical hypodermic syringe in the 1850s, a quicker route of administration of morphine was available, useful for intense pain such as that faced during surgery.64 Doctors or their patients dissolved morphine powder in water and injected it directly into the tissue or bloodstream, which resulted in faster pain relief than offered by the oral route.65 Thus morphine ascended as a key anesthetic in Western medicine. During the Civil War (1861–1865), both opium and morphine administered by mouth and probably (to a lesser extent) morphine administered by injection were used to treat the pain of war wounds, diarrhea associated with dysentery, malarial fevers, and other battlefield afflictions.66 While both orally administered opium and injected morphine had the capacity to produce dependence in its users, the direct route of administration delivered the active principle more quickly to the brain, producing a more intense feeling of reward and therefore a higher risk of addiction.
During the second half of the nineteenth century, opium and morphine were components of numerous patent medicines, drugs advertised to cure any number of ailments but whose ingredients remained secret. As a result, countless women fed their children morphine-laced syrups to calm their teething pains, many men used such products to help them sleep at night, and all took these medicines to ease the pain of a difficult life. Indeed, the morphine in these patent medicines made them enjoyable to take and deviously addictive.67 As an American physician commented in 1871, “the popular nostrums of the day, the cholera-drops, the pain-killers, the lung-troches and other pectorals, draped as they are in a flaunty incognito … owe whatever inherent virtue (if any) they possess to the omnipresent leaven, opium. The stereotyped cautionary phrase, Caveat Emptor, should be the statutory appendix to every one of their trade-marks.”68 It is not known how many middle-class, small-town families became dependent on patent-medicine morphine during the nineteenth century, but the number is no doubt very large.69
FIGURE 5.7 Opium-derived drugs: the principal opiate morphine; the opiate codeine; the semisynthetic opioid heroin.
In morphine, physicians discovered a new, sure way to alleviate their patients’ troubles, and armed with a hypodermic syringe, many could at last offer something beyond the violent purges and bloodletting that persisted in some medical circles in nineteenth-century North America and Europe.70 Morphine soothed those suffering from coughing diseases and helped agitated patients find calm and rest. However, morphine was a more effective painkiller than it was a cough suppressant, and it was highly addictive at therapeutic doses. Therefore, chemists sought to produce or isolate opiate compounds that treated pain or cough without the addictive properties.
Codeine, a compound in poppy latex less abundant than morphine, is composed of the morphine chemical structure with an additional small carbon-containing methyl group (see figure 5.7). This drug is a useful painkiller and cough suppressant, both slower acting and less addictive than morphine.71 In the modern day, it often is prescribed for postoperative pain, for example, in combination with the anti-inflammatory drug acetaminophen.
The industrial era of the late nineteenth and early twentieth centuries saw a population explosion in crowded city districts characterized by cramped quarters and poor sanitation, fertile grounds for the spread of the bacterial lung disease tuberculosis. Morphine elixirs were somewhat useful to combat this scourge by suppressing the intense coughing that spread the bacteria in aerosolized sputum, yet the risk of drug dependence led chemists to develop new molecules with more potent painkilling and cough-suppressing effects and less potential for addiction. Chemists in London in the 1870s and researchers at Bayer Laboratories in Germany in the 1890s added two simple acetyl groups (just a few more carbon, hydrogen, and oxygen atoms) to the structure of morphine. The molecule they produced, in chemical terms diacetylmorphine, turned out to be a much more potent analgesic than morphine, and to the German pharmaceutical firm a heroisch (“mighty” or “powerful”) medicine.72 Bayer marketed the drug as heroin (see figure 5.7).
A white powder, heroin can be mixed with water and injected, formulated into pills for oral consumption, snorted into the nose, or vaporized and smoked. Heroin’s rapid action is attributable to its acetyl adornments, which render the molecule more fat soluble and therefore more readily taken up into the brain from the bloodstream. Effects of a dose of heroin, particularly when injected, are felt intensely within seconds. Contrary to the English and German chemists’ predictions, their modified morphine was far more addictive than any of the other opiates. Heroin was briefly marketed as a more effective alternative to morphine for pain relief and cough suppression in the late 1890s and early 1900s but soon fell out of favor in mainstream medical practice as its human toll became clear (figure 5.8).73 Yet its relative simplicity of manufacture and unequalled euphoriant effects have assured its persistence as a recreational drug into the twenty-first century.
OPIUM CULTURE IN THE UNITED STATES
Americans had access to the opium-based alcoholic medicine laudanum from the early years of the colonies, but its use for medicine and recreation was probably limited by cost and availability.74 The American experience with opium was shaped strongly by a wave of Chinese immigration to the United States and by homegrown demand for patent medicines and morphine that mounted during the mid-nineteenth century. During the 1850s and later, thousands of Chinese men left their ancestral villages, mostly in the south of China, to seek employment in American mines and railroads. Others found their way to cities along the West Coast and further inland, eventually settling in cities such as San Francisco, Seattle, Chicago, and New York. The men were usually poor and rarely brought their families, but some did bring with them the habit of opium smoking.75 Chinese entrepreneurs, some of whom had originally immigrated for the purpose of prospecting for gold or working railroad jobs, established opium dens in the Chinese quarters of American cities and offered their clientele an experience inspired by the decadent establishments of their homeland.76 Attracting Chinese, Americans, and visitors alike, opium dens developed a reputation of exoticism that, along with the opium and other pleasures they offered, fueled their business during the late nineteenth century.77
FIGURE 5.8 A trade-card advertisement for heroin, early twentieth century. (Wellcome Library, London, L0064712)
A typical opium den consisted of rooms with beds or mats that allowed smokers to lie on their side while smoking. The clients smoked through long pipes with a small bowl at one end where the opium paste was heated. They inhaled the smoke through the length of the tube, which was packed with grass, hair, wood shavings, or other material to reduce the harshness of the smoke. After a long session, smokers made use of the padded floor or bed to experience a prolonged euphoria and sleep.
Over the course of the last few decades of the nineteenth century, the opium den’s mythologized association with the underworld and its renown as a place where the races and sexes commingled earned it a place in the crosshairs of anti-opium crusaders (figure 5.9). Bans on smoking opium (that is, the form of opium specially prepared for the pipe) and opium dens were instituted in various localities during the 1870s, 1880s, and later, with some small effect.78 Ultimately, the first federal legislation in U.S. history targeting any drug was written specifically to restrict the form of opium preferred by the Chinese and went into effect in 1909.79 While the drug’s physical effects on the body and economic toll loomed large in the effort to restrict it, there was undoubtedly also a moral and racial motivation behind the antiopium movement. As Hamilton Wright (1867–1915?), a U.S. delegate to the International Opium Commission wrote, “One of the most unfortunate phases of the habit of opium smoking in this country is the large number of women who have become involved and were living as common-law wives of or cohabiting with Chinese in the Chinatowns of our various cities.”80
MECHANISM OF ACTION
Opium’s principal psychoactive compound, morphine, comprises approximately 10 percent of the raw poppy latex; codeine makes up about 0.5 percent.81 Absorption of morphine and other opiates is slow and incomplete through the gastrointestinal tract. The effect of morphine is more rapid and pronounced when injected or smoked. Morphine can also be administered rectally.82 Because of the semisynthetic opioid heroin’s capacity to cross from the blood into the brain quickly, it produces the most immediate effects.
These differences in route of administration account, in part, for the varying levels of addictiveness of poppy compounds. When ingested, opium or opium-containing laudanum produces mild and sustained euphoria. However, when smoked or injected, the opium (or morphine) euphoria begins more quickly and reaches a higher level, and it is thus more likely to lead to physical dependence. The euphoria of injected heroin is more intense still.
FIGURE 5.9 Many white American men feared the consequences of their wives, sisters, and daughters frequenting opium dens in urban Chinatowns. (Caricature from Frank Leslie’s Illustrated Newspaper, April 24, 1878)
PHARMACOLOGICAL EFFECTS OF THE OPIATES
Relaxation and sleep
Reduced intestinal motility
Decrease in body temperature
Constriction of the pupils
Morphine is administered in the modern-day clinical setting as an analgesic for severe or chronic pain, and its side effects include sleepiness, constipation, nausea, flushing of the skin, itching, and respiratory depression.83 Morphine blocks the transmission of pain sensations from the periphery to the brain, which is why anesthesiologists sometimes inject it directly to the surface of the spinal cord (epidural) to reduce the pain of labor and delivery.84 This treatment allows women to remain alert and maintain normal vital signs while experiencing less pain. The locally acting morphine does not reach the brain and therefore does not produce systemic effects.
Morphine, codeine, and other opiates exert their analgesic effects by binding as agonists to opioid receptors in the brain and at the interface between sensory neurons and the spinal cord. They reduce the sensation of pain and increase the tolerance for pain. Synthetic chemicals that have similar effects (called opioids) are widely prescribed. They also come with a significant risk of addiction and are subject to overprescription and diversion into the illicit drug market.85 Some of them are based closely on the structure of morphine, such as hydrocodone (sold as Vicodin) and oxycodone (sold in a slow-release tablet as OxyContin). Oxycodone is also combined with the analgesic anti-inflammatory drugs acetaminophen (sold as Percocet) and aspirin (sold as Percodan).86 Other synthetic molecules have structures that differ from morphine’s but that nonetheless act as agonists at opioid receptors. Examples are meperidine (sold as Demerol), methadone, and fentanyl.87
Morphine and its chemical cousins also induce drowsiness and a state of tranquility, which leads to a shallow sleep. Opiates and opioids produce a feeling of euphoria through opioid neuronal connections to the dopamine network in the brain’s limbic system. Opioid receptors located on presynaptic terminals of neurons respond to agonist binding by inhibiting the release of GABA, a neurotransmitter among whose functions is the suppression of dopamine signaling.88 The decrease of GABA in the synaptic cleft in turn increases dopamine’s presence there, which results in a sense of extreme pleasure and reward. Long-term use gives rise to tolerance, which requires increased doses to maintain the initial pleasurable state and can accompany addiction. Withdrawal symptoms (including dysphoria, pain, diarrhea) also become increasingly severe after continued, high-dose use.89
As antidiarrheals, opiates and opioids activate opioid receptors at the interface of the peripheral nervous system with the smooth muscle of the intestine, where they slow the rate of intestinal muscle contraction (peristalsis) and decrease intestinal secretions, resulting in a greater level of fluid reabsorption.90 Synthetic drugs such as loperamide (sold as Imodium) and diphenoxylate (sold as Lomotil) are used to treat gastrointestinal symptoms.91 Diphenoxylate generally does not produce central effects except at very high dosage, and loperamide’s chemical structure prevents it from reaching the central nervous system in any significant concentration. Therefore, it has no painkilling or euphoriant properties.
From its origins in the Mediterranean region to worldwide distribution as a clinically important source of medicine, the poppy has long entwined itself in human history. It is one of the earliest documented medicinal herbs, having helped the Romans face pain and the Chinese combat diarrhea. Its active principle, morphine, was the first effective painkiller in a new era of biochemical medicine, but its use—and abuse—also led countless individuals, captured by the drug’s euphoriant effects, to addiction and ruin. Europeans waged wars in China that boosted its commercial success, as it meanwhile spread through the West as laudanum and emerged in many cities at the end of a pipe. Even today, the poppy remains a lucrative cash crop, yielding many tons of the potent, simple, and seductive morphine derivative heroin for the illicit trade. Since ancient times, the poppy has exercised its gentle force over humanity.