CHAPTER 1
GOD’S OWN MEDICINE
“Of pain you could wish only one thing: that it should stop. Nothing in the world was so bad as physical pain. In the face of pain there are no heroes.”
The first civilization produced the first medicine.
About 6,000 years ago, around the time of Abraham, the Sumerians migrated from Persia (now Iran) and settled between the Tigris and Euphrates Rivers. They invented cuneiform writing, producing more than 400,000 clay tablets. They invented farming, growing barley, wheat, dates, apples, plums, and grapes. And they discovered a plant that would eventually cause more pleasure and more suffering than any other plant in history. They called it hul gil, “the plant of joy.” Carl Linnaeus, an 18th-century Swedish botanist, called it Papaver somniferum. Today, we call it the opium poppy.
Opium was so powerful that ancient cultures reasoned it could only have come from the gods. The Sumerians believed it was a gift from Isis, who gave it to the sun god, Ra, to treat his headache. In India, enthusiasts believed it had come from Buddha, who had cut off his eyelids to prevent sleep. When the eyelids touched the ground, they became the beautiful flower that would provide sleep and dreams for all eternity. Thomas Sydenham, a 17th-century English physician said, “Among the remedies which it has pleased the Almighty God to give man to relieve his sufferings, none is so universal and efficacious as opium.” The characterization of opium as divine persisted into the 20th century. In the early 1900s, William Osler, arguably the most distinguished physician of his day and a founder of Johns Hopkins Hospital, called opium “God’s own medicine.”
THROUGHOUT HISTORY, the opium poppy has been accommodating, growing in many different types of soils and locations. It’s also naturally resistant to insects and fungi. For these reasons, even countries with limited resources can grow and harvest the plant. (Today, the opium poppy is the leading cash crop of Afghanistan.) The money is in the seedpod, which contains a milky white liquid that hardens into a dark gum. The gum (opium) contains five biologically active ingredients: morphine, the most powerful pain-relieving (analgesic) medicine known to man; codeine (methylmorphine), a mild analgesic and cough suppressant; alpha-narcotine and papaverine, which are muscle relaxants; and thebaine, which, starting in the late 1990s, formed the basis of a drug that is now killing about 20,000 Americans a year.
SINCE THE DAYS OF ANCIENT GREECE, doctors have used opium to treat pain as well as a vast array of other illnesses.
Hippocrates, the father of modern medicine, used it to treat insomnia. Galen, the last of the great Greek physicians, used it to treat headaches, vertigo, deafness, epilepsy, apoplexy (stroke), poor sight, bronchitis, asthma, coughs, hemoptysis (coughing up blood), colic, jaundice, hardness of the spleen, kidney stones, urinary complaints, fever, dropsy (swelling of the limbs, caused by heart failure), leprosy, menstrual problems, and melancholy. Neither Hippocrates nor Galen was aware of opium’s snare. Rather, it was a relatively unknown physician named Diagoras of Melos who was the first to realize that many of his fellow Greeks had become hopelessly addicted to the drug. As a consequence, he became the first person in history to argue against its use, declaring that it was better to suffer pain than to become addicted to opium. His warnings have been ignored for the last 2,500 years.
The Romans were also smitten with the opium poppy, which was emblazoned on their coins and honored by Somnos, their god of sleep. But the Romans also understood that opium could be a powerful poison. In 183 B.C., the Carthaginian general Hannibal used it to kill himself. And the emperor Claudius’s wife, Agrippina, used it to poison her 14-year-old stepson, Britannicus, so that her son, Nero, could become emperor.
A reference to opium can even be found in the New Testament. As described in Matthew 27:34, when Jesus was hanging on the cross, his followers offered him something to dull the pain: “They gave him vinegar to drink mingled with gall; and when he had tasted thereof, he would not drink.” Because it was bitter, opium was often mixed with wine or beer to make it more palatable. Biblical scholars have theorized that gall, which means “something bitter,” was probably opium.
Neither the Greeks nor the Romans traded in opium. Rather, opium commerce was the province of Arab merchants, who brought the drug to China—where it enslaved a nation.
OPIUM FIRST MADE ITS WAY TO China in the seventh century A.D., where it was used primarily for medicinal purposes, although sometimes it was added to sweets and cakes. At first, opium was a pleasant distraction. But when the Portuguese brought the smoking pipe to China, everything changed. Chinese citizens couldn’t get enough of the drug.
In 1660, British-owned companies shipped 1,350 pounds of opium from India to China; by 1720, 33,000 pounds; and by 1773, 165,000 pounds. About three million Chinese citizens were addicted. In response, the Chinese government banned opium smoking. It didn’t work. By 1839, the British were exporting a startling 5,600,000 pounds. At least 25 percent of the Chinese population was addicted to opium; in some regions, the addiction rate was as high as 90 percent. Chinese society was on the verge of collapse. In response, the Chinese government pleaded with British officials to stop exporting opium from India. When they refused, Chinese officials, desperate to end the massive epidemic of addiction and crime that had overtaken their country, took the next step.
In 1839, Commissioner Lin Tse-hsu seized and destroyed 2,600,000 pounds of British opium. War ensued. Between 1839 and 1860, China and Britain fought two Opium Wars. China lost both times. As a consequence, China had to open more ports for opium importation, pay Britain $21 million in reparations, and cede Hong Kong to British rule (which, by treaty, wasn’t returned to China until 1997). Eventually, China legalized the drug. By 1900, China was importing 8,600,000 pounds of opium and had more than 13 million opium addicts.
While the Chinese were smoking opium, Americans—thanks to a European inventor—were drinking it.
IN THE EARLY 16TH CENTURY a Swiss alchemist, physician, astrologer, and philosopher named Paracelsus mixed opium with brandy, calling his concoction laudanum, from the Latin verb laudare, meaning, “to be praised.” “I possess a secret remedy which I call laudanum and which is superior to all other heroic remedies,” he said. Liquid opium swept through Europe. Victorian women, who found it unacceptable to frequent bars and saloons, turned to laudanum; they also gave it to their babies to help them sleep. British physicians used laudanum to treat coughs, diarrhea, dysentery, and gout.
Americans also embraced liquid opium. Louisa May Alcott and George Washington used laudanum; Mary Todd Lincoln was addicted to it. By the late 1800s, about 200,000 opium addicts lived in the United States; three-quarters were women. Unlike opium smokers in China, women in Europe and the United States who drank laudanum were considered to have a gentle, harmless addiction. In Harper Lee’s To Kill a Mockingbird, set in a small Alabama town, Mrs. Henry Lafayette Dubose is addicted to laudanum, the picture of decay. But Atticus Finch—the lawyer who takes the town to task for its racist beliefs—praises Dubose for her courageous attempt to fight her addiction and die with dignity. Finch sees Dubose as a sympathetic, not pathetic, character.
Opium was also a staple of the patent medicine craze. Medicines like Stott’s Unique Fruit Cordial, which contained 3 percent opium, and Chlorodyne, which contained opium, cannabis, and chloroform, were easily purchased over the counter. And Mrs. Winslow’s Soothing Syrup, Mother Bailey’s Quieting Syrup, and Hooper’s Anodyne were all spoon-fed to “quiet the cranky child.” The American Medical Association later called opium-containing preparations “baby killers.”
The opium poppy also made a cameo appearance in L. Frank Baum’s best-selling book, The Wizard of Oz.
[Dorothy’s] eyes closed in spite of herself and she forgot where she was and fell among the poppies, fast asleep.
“What shall we do?” asked the Tin Woodsman.
“If we leave her here she will die,” said the Lion. “The smell of the flowers is killing us all. I myself can scarcely keep my eyes open and the dog is asleep already.”
UNLIKE THE EUROPEANS, Americans eventually banned opium use. They did it because of a series of events triggered by the California gold rush.
Between 1850 and 1870, about 70,000 Chinese citizens entered the United States to mine gold and work on the railroads, bringing their opium pipes with them. They came through the port of San Francisco. Initially, opium smoking was limited to Chinese immigrants. But, starting in the 1870s, opium dens became a popular haunt for actors, gamblers, prostitutes, and criminals, spreading to almost every major American city, including Los Angeles, New York, Chicago, and Miami. Opium addiction became so widespread and so perverse that in 1875 San Francisco city officials passed the Opium Den Ordinance, prohibiting public smoking of opium. Other cities followed. Then, the United States government stepped in. In 1909, Congress passed the Opium Exclusion Act, banning importation. But it was too late. Many Americans were already addicted to the drug. And, as reflected by a new American lexicon, people addicted to opium were no longer sympathetic figures. They were called junkies, because they often sifted through junkyards to find salable items. Or hop heads, from the Cantonese phrase ha peen, meaning “bird or cow manure.”
In 1914, the United States Congress passed the Harrison Act, forcing doctors to register and maintain records of all narcotic prescriptions. (In addition to relieving pain, opium is a narcotic, a word derived from the Greek narkoun, meaning “to make numb.” All narcotics, by definition, suppress the central nervous system, causing drowsiness, stupor, and occasionally coma.) In 1919, the U.S. Supreme Court extended the act, making it clear that doctors were prohibited from prescribing narcotics to maintain an addiction. Almost a hundred years would pass before doctors were held accountable for violating this law.
Opium was now restricted by state legislatures and reviled by the American public. But the enslavement of Americans by opium and its derivatives was just getting started.
ALTHOUGH OPIUM WAS CLEARLY addictive to individuals and destructive to society, its pain-relieving properties were undeniable. No other drug could match it. Scientists were desperate to find a way to retain opium’s analgesic properties while jettisoning its addictive properties. In the early 1800s, a young German chemist became the first to try.
In 1803, Friedrich Sertürner, a 20-year-old chemist’s apprentice, isolated opium’s most abundant and most active ingredient. He named it morphium after the Greek god of dreams: Morpheus. Later, the name was changed to morphine. Sertürner never trained at a university, never earned a degree, had no professional standing, made his own laboratory equipment, and tested the effects of his newfound product on the only person he could find to do it: himself. A shy and solitary man, this remarkably young chemist’s apprentice would soon change the face of medicine.
Sertürner found that morphine was about six times more powerful than opium, causing almost immediate euphoria followed by depression and dependence. When he finished his studies, he was addicted to the drug. Worried that he had created a monster, Sertürner warned, “I consider it my duty to attract attention to the terrible effects of this new substance I called morphium in order that calamity may be averted.” Sertürner’s warning went unheard. By 1827, the German pharmaceutical company Merck began mass-producing the drug. European doctors soon prescribed morphine for a variety of illnesses, including alcoholism, inadvertently shifting the addiction from alcohol to morphine.
Then a medical invention changed the face of narcotic addiction.
In 1853, a doctor in Edinburgh, Scotland, named Alexander Wood attached a syringe to a needle, allowing morphine to be injected directly into the bloodstream. (Morphine was the first intravenous drug.) Wood reasoned that if morphine were injected instead of ingested, people wouldn’t develop an “appetite” for the drug. He believed that he had found a way to separate morphine’s analgesic properties from its addictive properties. By 1880, almost every physician in the United States owned a hypodermic needle and began instructing patients on how to inject morphine on their own. Wood’s wife would later die from a morphine overdose—the first recorded patient to die from an injectable drug.
With the invention of the hypodermic syringe, morphine became the addict’s drug of choice. By 1900, more than 300,000 people in the United States were addicted to morphine. When laws were passed to prohibit its sale, the demographics of addiction quickly shifted. No longer were addicts the frail, sympathetic, laudanum-drinking women of To Kill a Mockingbird; they were poor urban males like Frankie Machine, the hustling, pool-playing junkie in Nelson Algren’s best seller The Man with the Golden Arm. (Frank Sinatra played Machine in the 1955 movie.)
It was back to the drawing board. Was it possible to invent a pain-relieving medicine that had the power of opium—and its principal component, morphine—without causing the addiction and dependence that invariably accompanied the drug? At this point, scientists had used only products found in nature. Surely, there must be a way to use modern chemistry to synthesize a nonaddictive painkiller. In the late-1800s, one scientist believed he had discovered it: the holy grail of pain relief.
IN 1874, A PHARMACIST in London named C. R. Alder Wright boiled morphine with the reactive form of acetic acid (vinegar) on a stove for several hours, producing diacetylmorphine. (This process is called acetylation.) Convinced that he had finally created a nonaddictive pain reliever, Wright fed the gray-white powder to his dog, who became frighteningly hyperactive, violently ill, and almost died. After throwing away the powder, he published his findings in the Journal of the Chemical Society in London. Although Wright would soon become a Fellow of the prestigious Royal Society, nobody paid attention to what he had written.
Twenty-one years passed.
In the late 1800s, Heinrich Dreser, a young chemistry professor working for a struggling pharmaceutical company in the Rhineland, discovered Alder Wright’s article. Like Wright, Dreser wanted to rid morphine of its addictive properties. He was impressed by Wright’s paper. Dreser knew that by acetylating morphine, the drug could enter the brain more quickly. Therefore, much less morphine would be required for pain relief. With so little drug required to induce a biological effect, Dreser reasoned that people would be much less likely to become addicted to the drug. At last, a safe, effective pain reliever.
In 1895, Dreser instructed his assistant, Felix Hoffmann, a postdoctoral student, to acetylate morphine. This was nothing new to Hoffmann, who had recently acetylated another chemical, sodium salicylate, which had been used as an anti-inflammatory drug to treat rheumatism. The problem with sodium salicylate was that it damaged the lining of the stomach, causing gastritis, bleeding, and occasionally ulcers. Hoffmann found that by acetylating sodium salicylate, resulting in acetyl salicylic acid, the gastritis problem virtually disappeared. In 1899, Dreser and Hoffmann’s company—which was named for its founder, Friedrich Bayer—marketed its new drug, calling it Bayer Aspirin.
Now, Dreser and Hoffmann were ready to see if their success with aspirin would carry over to morphine. So they fed diacetylmorphine to a few rats and rabbits that appeared to love it. Then they fed the gray powder to four workmen in the company who also loved it; indeed, the workers were anxious to repeat the experiment. Then they tried the drug on a few local patients.
In September 1898, Heinrich Dreser presented his findings at the 70th Congress of German Naturalists and Physicians. Dreser claimed that diacetylmorphine could treat colds, sore throats, and headaches, as well as severe respiratory infections like pneumonia and tuberculosis—two leading causes of death. Further, diacetylmorphine was five times more potent than morphine and completely non–habit forming. (At this point, Dreser had tested the drug on only a handful of people for about four weeks.) Dreser believed that he had found the perfect drug to treat morphine addiction. Attendees at the conference gave him a standing ovation.
Dreser didn’t have to work hard to convince Bayer executives to launch the new drug. But first they had to come up with a name. Some of the workers wanted to call it wunderlich, meaning miracle. But Dreser preferred the name heroisch, meaning heroic. In 1898, Bayer launched their new drug, calling it heroin. Aspirin, which physicians worried might cause gastritis, could be obtained by prescription only. Heroin, which was believed to be much safer, could be purchased over the counter.
In 1900, Eli Lilly, working in collaboration with Bayer, began distributing heroin without prescription in the United States, promoting it side by side with aspirin as a treatment for colds and the flu. Lilly claimed that the drug could be given safely not only to children, but also to infants and pregnant women.
Heroin sales took off. First, the military administered the drug intravenously to its soldiers in the field during World War I. Then, citizens bought heroin in the form of cough lozenges or as an elixir mixed in glycerin. Millions of doses were sold in England and the United States. In the early 1900s, the philanthropic Saint James Society launched a campaign to send free heroin to morphine addicts.
Heroin became a standard of care. In 1906, the Journal of the American Medical Association stated that heroin was “recommended chiefly for the treatment of diseases of bronchitis, pneumonia, consumption [tuberculosis], asthma, whooping cough, laryngitis, and certain forms of hay fever.”
IT DIDN’T TAKE LONG TO REALIZE that heroin wasn’t what it was claimed to be.
By 1902, at least a dozen cases of addiction and some infant deaths had been reported. By 1905, the evidence was overwhelming. Because heroin crosses the placenta, infants born to heroin addicts suffered symptoms of severe withdrawal. Traces of heroin could also be found in breast milk. In 1906, the Council on Pharmacy and Chemistry stated, “The habit is readily formed and leads to the most deplorable results.” By 1910, doctors were fully aware of the dangers of heroin, and its use declined. Bayer, on the other hand, didn’t stop advertising the drug as safe until 1913. By 1918, more than 200,000 people living in New York City alone were addicted to heroin.
In 1924, Congress passed the Heroin Act, making manufacture and sale of the drug illegal. As a consequence, heroin went underground. In the 1920s and early 1930s, heroin’s principal distributors were mobsters Meyer Lansky, Dutch Schultz, and Legs Diamond. (Because all three were Jewish, heroin was often called “smack,” from the Yiddish word schmecher, meaning “addict.”) In the mid-1930s the Italian Mafia took over, specifically, Charles “Lucky” Luciano, who established the “French connection.” Opium grown in French Indochina or Turkey was shipped to Lebanon where it was converted to morphine and then shipped to the French port city of Marseille where it was processed into high-quality heroin and smuggled into the United States.
Initially, heroin abuse was confined to a poor, urban underclass. By the 1940s, however, heroin addiction had spread to the Harlem jazz scene, and by the 1950s—through the writings of Jack Kerouac and William Burroughs—to the beat generation. By the mid-1960s, more than 500,000 Americans were addicted to heroin. Virtually all major U.S. cities, as well as countries like Britain, France, and Germany, were caught in heroin’s snare.
The U.S. government took action, pressuring Turkey to stop producing opium and eliminating importation of heroin from France. (This success was dramatized in the 1971 movie The French Connection, starring Gene Hackman and Roy Scheider.)
By the 1970s, opium production had moved to an area in the highlands of Laos, Thailand, and Burma (now Myanmar), known as the Golden Triangle. No group suffered this switch in opium production more than American soldiers in Vietnam, about 15 percent of which became addicted to heroin.
In the summer of 1971, President Nixon declared an “all-out war on drugs.” “America has the largest number of heroin addicts of any nation in the world,” he said. “If we cannot destroy the drug menace in America, then it will surely in time destroy us.” Nixon chose Elvis Presley to be the public face of his war on drugs. Ironic, given that at the time of Presley’s death in 1977, Valium, methaqualone, morphine, codeine, and barbiturates were found in his bloodstream. Presley wasn’t the only celebrity to die from a drug overdose: Janis Joplin died in 1970, John Belushi in 1982, Chris Farley in 1997, and Philip Seymour Hoffman in 2014, all from heroin overdoses.
By the mid-1990s, heroin—which had become cheaper and purer—could be liquefied on tinfoil and its vapors inhaled (called “chasing the dragon”). Now more women started to use the drug. By 1995, more than 600,000 Americans were addicted to heroin. In addition to the Golden Triangle, the Medellin cartel in Colombia also produced large quantities of the drug. The Drug Enforcement Agency, which now had more than 75 offices in 50 countries, was spending more than $13 billion a year trying to keep heroin out of the country.
By 2003, the number of Americans addicted to heroin had decreased from 600,000 to a little more than 100,000. This decrease wasn’t because Americans had lost interest in narcotics. It was because they had again replaced one addiction with another.
SCIENTISTS HAD HOPED that morphine could treat opium addiction. Then they had hoped that heroin could treat morphine addiction. It was time to try something else. Again, they would synthetically modify a drug to separate pain relief from addiction. And again, they would fail. This time, spectacularly.
To find the next wonder drug, scientists turned to another component of opium: thebaine, named for Thebes, a town in ancient Egypt where the opium poppy was grown. The first synthetic version of thebaine was produced in 1916 by two German chemists working at the University of Frankfurt. They called it oxycodone.
In the early 1950s, oxycodone made its American debut. Initial preparations were combined with a variety of other drugs. For example, there was Percodan, a combination of oxycodone and aspirin; Combunox, a combination of oxycodone and ibuprofen, a nonsteroidal anti-inflammatory; and Percocet, a combination of oxycodone and acetaminophen (Tylenol). But the single most powerful, and eventually most addictive and most abused preparation, was OxyContin, pure oxycodone uncut by other drugs. OxyContin’s manufacturer, Purdue Pharma, marketed the drug as a first-line agent for arthritis. In OxyContin, Purdue Pharma had struck gold—the drug would eventually account for more than 80 percent of its business.
Later, Purdue combined OxyContin with an acrylic that allowed for a slower, timed release of the drug, eliminating its need to be taken several times a day. Addicts soon found that by chewing the tablet or crushing it, they could bypass the timed-release mechanism and enjoy the immediate rush of as much as 160 milligrams of oxycodone, logarithmically greater than any other product on the market. Now addicts had the capacity to ingest a potentially lethal dose of the drug. (On a weight-by-weight basis oxycodone is actually more powerful than morphine.)
When OxyContin first came onto the market in 1996, the label read, “Delayed absorption, as provided by OxyContin tablets, is believed to reduce the abuse liability of the drug.” Officials from the Food and Drug Administration (FDA) would soon regret this label. In the end, there was nothing controlled about the controlled-release form of OxyContin.
PHYSICIANS WERE INITIALLY wary of oxycodone. They had been burned by morphine in the 1800s, heroin in the 1900s, and opium since the beginning of recorded history. They didn’t want to be burned again. So they were slow to prescribe the next opium-derived miracle. By the mid-1980s, however, all of that would change.
On April 20, 1948, Cicely Saunders, a nurse, joined St. Luke’s Hospital for the Dying in East London. Saunders believed that patients with terminal illness shouldn’t have to spend their last few weeks crying out in pain. Rather, they should die a dignified death—one as pain-free as possible. Saunders reasoned that it was better to prevent pain than to treat it. So, in 1967, she founded the hospice movement, providing dying patients with large quantities of addictive, pain-relieving medicines. Saunders’s movement crossed the ocean. In 1984, the United States Congress passed the Compassionate Pain Relief Act, making it legal to treat terminally ill patients with heroin. In 1986, Wisconsin launched the first state-based pain management program for cancer patients. Other states followed.
For many patients suffering from terminal illnesses, vigorous pain management was a godsend. But a door had now been opened for doctors to prescribe long-term, high-dose narcotics. Initially, use was limited to patients with terminal cancer. Then a respected doctor from New York City took the liberal use of narcotics one ill-fated step farther.
IN 1986, RUSSELL PORTENOY, a 31-year-old New York City pain specialist, published a paper in the journal Pain. Portenoy believed it was time for American physicians to get over their fear of painkillers, what he called “opiophobia.” Portenoy reported the stories of 38 people who were on high-dose pain medicines (12 were on OxyContin). Only 2 of the 38 had become addicted to their drugs, and both had had a history of addiction. Portenoy argued that his findings weren’t unique; three previously published studies had also shown that less than one percent of patients on chronic painkillers had become addicted to them. Portenoy reasoned that, “opioid maintenance therapy can be a safe, salutary and more humane alternative [for] patients with intractable non-malignant pain and no history of drug abuse.” Russell Portenoy believed that the compassion Cicely Saunders showed for patients with terminal cancer should be extended to all patients. Pain, argued Portenoy, should now be the fifth vital sign (in addition to temperature, blood pressure, heart rate, and respiratory rate). No one should be allowed to suffer. (One note on nomenclature: When Russell Portenoy used the term opioid, he was referring to synthetic forms of opium, like oxycodone. Morphine and codeine, which can be purified directly from opium without modification, are called opiates.)
Charismatic, bright, and persuasive, Russell Portenoy became the media’s “go-to” guy for pain management, frequently appearing in newspapers and popular magazines. His academic success was also meteoric; Portenoy wrote or co-wrote more than 140 papers in medical and scientific journals and 15 book chapters. When Russell Portenoy talked, doctors listened. Portenoy had now given doctors permission to come back to opium derivatives. This time, he assured them, there would be little addiction and death. The days of opium, morphine, and heroin were behind them. Drugs like oxycodone had finally solved the problem of pain relief without addiction. Richard Nixon’s war on drugs had become Russell Portenoy’s war on the war on drugs.
IN LATE 1995, at the same time that Russell Portenoy was urging American physicians to get over their fear of painkillers, the FDA approved Purdue Pharma’s timed-released version of OxyContin. Purdue’s sales force promoted the drug for the treatment of lower back pain, arthritis, trauma, fibromyalgia, dental procedures, broken bones, sports injuries, and pain resulting from surgery. In other words: everything. And they constantly repeated Portenoy’s mantra that less than one percent of patients would become addicted to the drug.
In 1996, more than 300,000 prescriptions for OxyContin were written for a net profit to Purdue Pharma of $44 million. Realizing it had created the right drug at the right time, Purdue doubled its sales force, offered coupons for a free 7- to 30-day supply of the drug (34,000 coupons were redeemed), increased its yearly advertising budget to $200 million, and paid $40 million in incentive bonuses. In 2001, Purdue reaped $1.45 billion from the sale of OxyContin, the highest retail sale of any named pharmaceutical product, including Viagra.
SALES OF OXYCONTIN also benefited from a vigorous black market.
More than 70 percent of recreational OxyContin users had procured the drug from friends or relatives; 5 percent from drug dealers on the Internet. Sometimes users stole the drug from pharmacies; 90 percent of robberies in Pulaski, Virginia, were due to OxyContin abuse, and half of the inmates in Hazard, Kentucky, were incarcerated for OxyContin-related crimes. Sometimes, to supplement their meager Social Security checks, the elderly poor used Medicare or Medicaid to acquire a bottle of a hundred 80-milligram tablets of OxyContin and sold them on the street for $1.00 per milligram, netting an $8,000 profit for the seller. Teenagers stole OxyContin from their parents. (One street name for OxyContin was “kiddie dope.”) Prescriptions were forged. Women turned to prostitution to feed their habit. Pharmacists diverted the drug and sold it on the side. Before he was arrested, one Pennsylvania pharmacist had illegally sold hundreds of thousands of dollars worth of prescription painkillers, mainly OxyContin, over a three-year period, netting him $900,000 (which he later lost in the stock market).
Doctors took advantage of the OxyContin gold rush, selling prescriptions for money or sex. Dr. Randolph W. Lievertz of Indianapolis wrote more than $1 million in prescriptions paid for by the state’s Medicaid program; $130,000 of that total was written for one female patient who was part of a drug ring that sold OxyContin on the street. To honor the prescription, the woman would have had to ingest 31 tablets every 12 hours instead of the one tablet recommended by the manufacturer. Lievertz wasn’t alone. Pill mills sprang up across the country. One eastern Kentucky doctor saw 150 patients a day, writing prescriptions for painkillers after spending less than three minutes with each patient. Florida alone was home to hundreds of these facilities.
Doctors were arrested and charged with manslaughter and murder. Some were jailed. No case, however, drew more national media attention than that of Dr. James Graves, a 55-year-old Florida physician who was charged with manslaughter in the overdose deaths of four of his patients. Graves’s prescription mill was widely known among addicts. “The word spread that he was the go-to doctor to get pills,” said Russ Edgar, the assistant state attorney. Edgar argued in court that Graves had bragged that writing prescriptions for painkillers was a “gold mine” because he had rarely examined patients and didn’t have to fill out medical records. Edgar also claimed that Graves had ignored the pleas of pharmacists and parents to change his prescribing habits. Indeed, Graves’s parking lot often resembled scenes more commonly found at sporting events. Patients would eat, work on their cars, and give each other high-fives when they emerged with their OxyContin prescriptions. “You’ve got to realize something’s wrong when outside your office people are having tailgate parties,” said Edgar.
During the trial, Edgar argued that, “Mother after mother after mother called the defendant’s office and asked him to quit giving their children drugs or they would die. The defendant did not quit and they continued to overdose.” Graves countered that no one would have died if patients had simply used the drugs as prescribed. And he railed against the prosecutor, whom he considered ungodly, telling the judge, “I pray to God something will change and somehow he will come to know Christ.” James Graves was sentenced to 63 years in prison for manslaughter. He was the first physician to be found guilty of manslaughter or murder in connection with the irresponsible prescribing of a painkiller.
NO AREAS SUFFERED THE NIGHTMARE of OxyContin pill mills more than rural Appalachia and the Ohio Valley.
OxyContin abuse first surfaced in rural Maine in the late 1990s, then spread down the East Coast to include West Virginia, Kentucky, and southern Ohio. (Another name for OxyContin was “hillbilly heroin.”) From 1995 to 2001, the number of patients treated for oxycodone abuse in Maine increased 460 percent, and in eastern Kentucky, 500 percent. In West Virginia, six new drug treatment clinics treated more than 3,000 addicts. Southwestern Virginia opened its first drug treatment center in 2000; within three years more than 1,400 patients were being treated; by 2003, the region had experienced an 830 percent increase in deaths from oxycodone abuse. By 1999, deaths from oxycodone use in Allegheny County in western Pennsylvania outnumbered car fatalities.
Appalachian emergency department physicians became experts in recognizing the symptoms of drug withdrawal, which included anxiety, runny nose, sweating, yawning, insomnia, loss of appetite, gooseflesh (the source of the phrase “going cold turkey”), back pain, abdominal pain, tremors, and occasional involuntary thrusting of the legs (the source of the phrase “kicking the habit.”)
IN 2003, 17 YEARS AFTER Russell Portenoy published his paper claiming that long-term use of oxycodone was relatively harmless and nonaddictive, Jane Ballantyne published a paper in the New England Journal of Medicine claiming exactly the opposite. Ballantyne showed that long-term use of drugs like OxyContin induced tolerance (larger and larger doses of the drug were required to induce the same effect), hyperesthesia (pain experienced while using painkillers was actually worse than the original pain), hormonal changes (specifically, a decline in production of cortisol, an important regulatory hormone), changes in the immune system, and a reduction in fertility, libido, and sex drive. Ballantyne concluded, “Whereas it was previously thought that unlimited dose escalation was at least safe, evidence now suggests that prolonged, high-dose opioid therapy may be neither safe nor effective.”
Ballantyne’s paper wasn’t news to the FDA, which had already changed the label on OxyContin. No longer did the label state that the timed-release formulation made it less likely for abuse; now it stated that the formulation made it more likely for abuse, addiction, overdose, and death. The warning wasn’t written in fine print; rather, the FDA issued its most strident alert—the so-called “black box” warning.
But it was too little, too late.
In 2002, a survey at a rural Michigan high school showed that 98 percent of students had heard of OxyContin and 9.5 percent had tried it; of those who had tried it, 50 percent had taken it more than 20 times. By April, 1,300 deaths caused by OxyContin had been reported to the FDA; in most cases, doctors had prescribed the drug. By the end of 2002, Purdue Pharma was selling more than $30 million worth of OxyContin every week, and sales had exceeded more than $2 billion a year.
In 2003, Rush Limbaugh, a conservative radio commentator who often railed against drug abusers for being morally bankrupt, admitted that he was addicted to OxyContin.
In 2004, three million people were using OxyContin—now the most prevalent prescription painkiller in the United States.
In 2007, 14,000 people died from overdoses of prescription painkillers, and health care and criminal justice system costs exceeded $55 billion.
In 2008, 15,000 people died from prescription painkillers—the leading cause of accidental death in 30 states.
In 2009, health insurers spent $72 billion in direct health care costs related to prescription painkillers.
By 2010, 22 million people had misused prescription painkillers, and more people had died from these drugs than from heroin and cocaine combined. Enough painkillers were now being prescribed to medicate every adult living in the United States around the clock for a month.
In 2012, 12 million Americans aged 12 and older reported the recreational use of prescription painkillers; 16,000 of those users died from overdoses. Painkillers were now the most widely prescribed class of drugs in the United States; every 19 minutes someone died from an overdose. (OxyContin overdoses were indistinguishable from overdoses of opium, morphine, or heroin, all of which suppress the rate and depth of respiration. Patients breathe as few as four times a minute; blood pressure begins to drop, body temperature falls, and the skin becomes cold and clammy. Because the brain isn’t getting enough oxygen, the patient seizes and eventually dies from respiratory failure.)
In 2014, U.S. retail pharmacies dispensed 245 million prescriptions for opioid pain relievers. About 2.5 million adults were addicted to the drug.
Few insurance companies did much to discourage abuse. Before OxyContin burst onto the scene, chronic pain was treated with a combination of psychotherapy, biofeedback, exercise, and physical therapy. The goal was to leave the painkillers at the door. Although several studies had showed that this multidisciplinary approach to relieving pain worked just as well if not better than chronic drug use, the fact remained that the drugs were less expensive than the therapies. Unfortunately, many insurance companies encouraged the drugs. At best, this was shortsighted. Workers who took high doses of painkillers were out of work three times longer than those with similar injuries who took lower doses of the drugs.
ON MAY 10, 2007, Purdue Pharma, along with three company executives, pleaded guilty to one count of “misbranding” OxyContin. The court ruled that Purdue had minimized risks, made unsubstantiated claims, and failed to include clear warnings about how, under certain conditions, the drug could be fatal. Just as Bayer had continued to market heroin when it was evident that the drug was causing harm, Purdue had been slow to inform the public about the potential dangers of OxyContin. The three executives were fined $34.5 million (which Purdue paid), barred from working for any company that sold medical products for the next 12 years, and required to perform 400 hours of community service in drug-treatment centers. Purdue also paid an additional $634 million penalty. Many of the parents whose children had died from OxyContin were present during the sentencing. “Our children were not drug addicts; they were typical teenagers,” said one woman, whose 19-year-old son had died. “We’ve been given a life sentence.” Judge James P. Jones, who presided over the trial, said he would have liked to have sent company executives to prison, but was bound by the plea bargain.
IN AUGUST 2010, Purdue replaced their timed-release form of OxyContin with a “tamper-resistant” product. The new version formed a thick, sticky gel that made it more difficult to crush. Two years later, a study in the New England Journal of Medicine examined the impact of this new formulation. Researchers found that although OxyContin abuse had decreased, 24 percent of users had found a way to defeat the tamper-resistant properties and 66 percent had just switched to another drug, mainly heroin. Despite the reformulation, yearly sales of OxyContin still topped $2 billion.
IN 2012, Russell Portenoy, who had become chairman of pain medicine and palliative care at Beth Israel Medical Center in New York City, recanted: “I gave innumerable lectures in the late 1980s and ’90s about addiction that weren’t true,” he said. “We didn’t know then what we know now.” During the previous decade, more than 100,000 people had died from overdoses of painkillers. Steven Passik, a psychiatrist who had worked closely with Portenoy, recalled the war on pain: “It had all the makings of a religious movement,” he said. “It had a kind of spirit to it.”
In the end, OxyContin was one of the most addictive narcotics ever sold. And Russell Portenoy’s war on pain was one of modern medicine’s biggest mistakes.
ON JANUARY 16, 2016, an article written by Gina Kolata and Sarah Cohen in the New York Times stated: “The rising death rates for young white adults make them the first generation since the Vietnam War years of the mid-1960s to experience higher death rates in early adulthood than the generation that preceded it.” Opioid overdoses were now the leading cause of accidental deaths in the United States.
On March 15, 2016, the Centers for Disease Control and Prevention (CDC) finally offered guidelines for the sensible use of prescription painkillers, stating that doctors should prescribe them: (1) only after nonprescription painkillers like ibuprofen and physical therapies had failed; (2) in quantities not to exceed a three-day supply for short-term pain and rarely longer than seven days (typically, patients are given two weeks or a month worth of pills); and (3) only when improvement was significant. The guidelines did not apply to patients who were receiving painkillers for cancer or end-of-life treatment. The American Academy of Pain Management—a group that receives funds from Purdue and Teva Pharmaceuticals—and the Washington Legal Foundation, which frequently represents pharmaceutical company interests in court, opposed the new guidelines. After all, painkillers were now a $9 billion a year industry. Robert Twillman, executive director of the academy, didn’t like the three- to seven-day dosing recommendation. “The numbers are still arbitrary,” he said. But Tom Frieden, director of the CDC, had had enough. “For the vast majority of patients with chronic pain,” he countered, “the known, serious, and far too often fatal risks far outweigh the transient benefits. We lose sight of the fact that prescription opioids are just as addictive as heroin.” Today, 80 percent of the world’s opioid prescriptions are written in the United States, even though only 5 percent of the world’s population lives there.
THE LESSON FROM THE ILL-FATED WAR on pain is a simple one: It’s all about the data. When Friedrich Sertürner feared that in morphine he had opened up a Pandora’s box and let loose a monster, his warnings were ignored. When Heinrich Dreser claimed that heroin was safe, he had only tested it on a handful of people for a few weeks. And when Russell Portenoy launched a national campaign promoting opioid use, he based his claims on 38 patients, 12 of whom had taken OxyContin. As Clara Peller said in her now iconic television commercial for Wendy’s hamburgers, “Where’s the beef?” If you’re going to medicate a nation, at the very least you should base your recommendations on a mountain of evidence, not a molehill.