Administered for pain, drugs like OxyContin have taken a massive toll

An advertisement in 1860 extolled Mrs. Winslow's Soothing Syrup for its ability to lull fussy babies to sleep, "restoring the drooping spirits of many mothers." But some babies never woke up. Mrs. Winslow's Soothing Syrup, like many patent medicines of the day, contained a powerful and sometimes fatal opioid. Throughout the late 1800s and early 1900s, doctors prescribed tinctures of opium for anxious women and teething infants. As late as the 1960s, mothers soothed the latter with an opium-based medication called Paregoric. But by the late 20th century, doctors were reluctant to prescribe opioids for routine pain, fearful of the drugs' potential for addiction and misuse. Then came OxyContin.

When Purdue Pharma introduced OxyContin in 1996, the company assured doctors that this drug was different. OxyContin was much safer than other opioid painkillers, the company claimed. Caleb Alexander, now the co-director of the Johns Hopkins Center for Drug Safety and Effectiveness, recalls attending physicians telling him and his fellow residents in the late 1990s that patients who were truly experiencing pain were unlikely to become addicted to OxyContin and similar drugs. "We were taught not to worry about the addictive potential of opioids as long as the patient has true problems," Alexander says. Doctors pointed to a 1986 study in the journal Pain that affirmed what Alexander was hearing from attendings.

Purdue Pharma aggressively marketed OxyContin, especially to primary care doctors. The drug was less likely to be addictive, the pitch went, because it worked for 12 hours, and patients who took fewer pills were less likely to experience the highs and lows that led to dependence. Plus the time-release coating made the drug less attractive for abuse, since it did not produce a quick rush. Where opioids had previously been prescribed mostly for cancer patients or those recovering from surgery or car accidents, now primary care doctors began recommending OxyContin for less severe pain. From 1999 to 2014, sales of legal opioids nearly quadrupled. In 2012, clinicians wrote prescriptions for 259 million bottles of narcotic painkillers—one for every adult in the country, according to the Centers for Disease Control and Prevention.

But there was a problem. Despite Purdue Pharma's claims, OxyContin was indeed both addictive and easily abused. As people needed higher and higher doses over time to get the desired high, they turned to other drugs, such as Fentanyl, the powerful painkiller that killed the rock star Prince. In 2007, Purdue Pharma and three top executives pleaded guilty to misleading regulators, physicians, and patients about OxyContin's hazards and agreed to pay $600 million in fines and damages.

Opioids killed 28,000 people in 2014, more than any year since the CDC started keeping track. That's about one person every 18 minutes. According to the CDC, some 2.6 million people in this country are addicted to opioids, the class of drugs, both natural and synthetic, that resemble morphine. Many people who are addicted to prescription opioids end up switching to heroin, which can be easier and cheaper to obtain: For the cost of a sandwich and coffee, one can get high on black tar heroin, which has infiltrated this country in recent years. "The chemical structure of heroin and OxyContin are remarkably similar," says Alexander, a pharmacoepidemiologist. "You don't have to have a PhD in organic chemistry to see that. But we've treated them so differently in public policy."

The surge in prescription drug abuse has led to unprecedented rates of heroin use, according to the CDC. The number of women using heroin doubled and the number of male users increased 50 percent from 2002 to 2013. Seventy-five percent of these new heroin users said they had become hooked on prescription opioids first, according to a 2014 study published in JAMA Psychiatry. The CDC reported that more than 10,500 people died from heroin overdoses in 2014, a 26 percent increase over the previous year. "Every year, I think it couldn't get much worse, but then the following year, more people die," says Alexander.

This epidemic arrived at a time when the failures of the war on drugs—the prohibitionist mindset that has dominated international law for much of the past century—were becoming difficult to ignore. Johns Hopkins and the medical journal Lancet convened the Johns Hopkins–Lancet Commission on Drug Policy and Health. It published a report this year detailing the global costs of socially destructive mass incarceration, brutal militarized policing in Latin America, and expensive and toxic efforts to wipe out drug crops. But the most glaring evidence of failure is this: More and more people keep using drugs. The number of individuals worldwide using heroin increased by 50 percent from 1998 to 2008, according to the Hopkins–Lancet report.

To understand how the problem got so bad, we first have to look at how we got here— the failed efforts to rein in drug use and the little white tablet that changed the face of opioid addiction.

Decades of international policy have framed drug abuse as something to be eradicated, like smallpox or polio. But there's no vaccine. Abolishing drugs—and the desire to consume them—is infinitely more complex than containing a pathogen. Experimenting with altered states seems to be a fundamental aspect of being human. Fossil evidence shows people cultivated opium poppies 6,000 years ago. Marijuana, nicotine, and psychedelic mushrooms appear to have been part of human culture for millennia. Even some animals seem to seek out intoxicants: Reindeer nibble hallucinogenic mushrooms and Canadian bighorn sheep wear down their teeth scraping psychoactive lichens off rocks.

Image credit: Armando Veve

Opioids are some of the most potent and addictive drugs. They slip into the receptors of neurons in the brain's pleasure pathway, flooding the body with waves of bliss much more intense than any endogenous experience. But once the drugs wear off, people feel depressed and fatigued. As the body grows habituated to opioids, users must take more to feel high. And when a habitual opioid user stops, withdrawal is painful and prolonged.

The late 1990s was a fortuitous time to present a new painkiller. For too long, clinicians had failed to adequately treat pain, causing unnecessary suffering. "There was a powerful sense that we weren't doing enough to help people experiencing acute and chronic pain," says Colleen Barry, co-director of the Johns Hopkins Center for Mental Health and Addiction Policy Research. To address the problem, doctors began writing prescriptions for painkillers more liberally. For wisdom teeth extractions. Backaches. Sciatica. Primary care doctors wrote nearly half of all prescriptions for OxyContin, according to the CDC. But assured that the drug was safe, those doctors rarely warned patients of its potential for dependence, and they often failed to follow up to see whether patients were headed for trouble. "A lot of people who developed addictions were for all intents and purposes following the advice of their physicians and legitimately seeking treatment for pain issues," Barry says.

If doctors or pharmacists cut off OxyContin, those who had become hooked on the drug found new physicians, or booked an appointment at a "pill mill" where doctors were quick to jot out prescriptions for a cash fee. They bought painkillers from street dealers, and, when they started to run out of money, they turned to the cheaper alternative of heroin. Studies show nearly half of young heroin users say they misused prescription opioids before trying heroin, according to the National Institute on Drug Abuse. Once considered a problem of big cities like Baltimore or Philadelphia, heroin seeped out into suburban and rural areas to meet new demand from prescription drug addicts.

As the face of opioid addiction changed, attitudes about drug laws shifted. When heroin ravaged poor and African-American communities in the 1970s and 1980s, political leaders toughened up policing and enacted stiff mandatory minimum sentences, says Bloomberg School of Public Health Professor Susan Sherman. But as opioid addiction moved into predominantly white suburban and rural areas, lawmakers began pushing for better treatment options, she says. The shifting attitudes toward addiction are a troubling testament to the role of race and class in framing policy. "There are two separate and very unequal opioid epidemics," Sherman says.

Bloomberg School Assistant Professor Beth McGinty once conducted an experiment to show how bias shapes the perceptions of drug users. Participants read nearly identical short narratives about a female opioid user with one key difference: the woman's socioeconomic status. McGinty's team found that their subjects were overwhelmingly more sympathetic to the woman when she appeared to be more wealthy.

If there's any silver lining, perhaps it's that greater awareness of drug addiction could bring more empathy for all drug users. Barry hopes that the surge of concern around opioid addiction will bring positive change. The issue has yet to become highly politicized, so there's a good opportunity to change laws, she says. "We're in the midst of a window of opportunity where we could really address some of the terrible damage that has been done to individuals and families and lives," she says.

Image credit: Armando Veve

The trick is figuring out how to prevent more people from starting to use opioids in the first place, and to better treat those already addicted.

Daniel Webster, director of the Johns Hopkins Center for Gun Policy and Research, recalls listening to stories from his brother, a pharmacist in their hometown in Kentucky. Stories about lines of patients stretching around the block. Cash payments for appointments. Doctors who prescribed and dispensed bottles of narcotics in a matter of minutes. Drug Enforcement Agents passing through the family pharmacy would share tales of sham clinics they had busted.

Webster started thinking about how pills flowed through communities, beginning at doctors' offices and ending in the hands of people who abused them. Much like guns, they were first purchased legally and then moved into the black market. Webster knew that a small number of gun shops—as few as 1 to 5 percent—provide the guns used in more than three-quarters of crimes. He also knew that when authorities shut down these problem dealers, gun violence dropped dramatically in the surrounding area. So Webster wondered: Could the same model be applied to opioids?

He examined the effects of a crackdown in Florida, once considered the hub of the pill mill industry. In 2010 and 2011, DEA and state officials closed some of the most notorious pill mills. New laws curtailed one of the practices that characterized these operations—doctors dispensing bottles of pills straight from their offices—and limited the amount of narcotics that could be prescribed. Before writing a new opioid prescription, physicians were now required to consult a database to consider the patient's prescription history.

Would the new laws cut down on overdose deaths from prescription painkillers? Or would they simply lead to more people using heroin? Webster compared Florida's overdose rates with those in North Carolina, which had comparable patterns of drug use. He found that prescription opioid overdoses did fall substantially in Florida. And, while there was a short-term increase in heroin use, that too dropped during the period that Webster studied. "The enforcement and greater regulation of pill mills saved roughly 1,000 lives over three years," Webster says. (However, heroin overdoses surged again in Florida in 2014, for reasons not understood.) Other states that have been hit hardest by the epidemic, including Texas, Ohio, and Tennessee, have passed similar laws.

Bloomberg School Associate Professor Lainie Rutkow looked at the Florida laws through a different lens. An attorney who also holds a doctorate in public health, Rutkow determined that the new laws slashed the number of opioid prescriptions written. Physicians who had previously written the most prescriptions—presumably including some pill mill doctors—showed the biggest drop.

Rutkow has also studied another legislative tool: the database that enables physicians and pharmacists to see how many prescription opioids patients have received over a period of time. In theory, the data should tip off medical professionals if a patient is developing an addiction or shopping around for painkillers. Forty-nine states have such a database, but many states do not actually require physicians and pharmacists to use them. (Missouri's legislature has repeatedly shot down efforts to create a state database.) She also found that only about three-quarters of primary care doctors knew their state had a database, and only half of them actually used it. That is beginning to change; more states now require practitioners to use the tool. Rutkow is looking into whether these databases, when used, actually work as intended.

Of course, physicians wouldn't need to use such data if someone found better and safer treatments for pain. How can they help people who are suffering without creating more problems down the road?

Steven Cohen sees people in terrible pain. As the director of medical education for the Pain Management Division at Johns Hopkins Medicine and the director of pain research for Walter Reed National Military Medical Center, Cohen treats soldiers maimed by explosions and civilians suffering from complex conditions. But he prescribes opioids only as a last resort. "When people benefit from opioids, they show moderate benefits. When people are harmed by opiates, the results could be catastrophic. They could die," he says.

Opioids are not only dangerous; they often aren't even the best painkillers, according to Cohen. Some studies have shown that people are actually more sensitive to pain after using opioids, a condition called hyperalgesia. Rats that were given morphine for five days showed an increased sensitivity to pain for 12 weeks after stopping the drug, according to a study from University of Colorado Boulder neuro­scientists recently published in Science. Because opioids appear to amplify the body's pain signals, patients require higher and higher doses to manage their pain.

There are a host of more specific—and more effective—treatments for chronic pain, Cohen says. For example, at the Johns Hopkins Blaustein Pain Treatment Center, he and other physicians might treat sciatica with a steroid injection or relieve back pain through radiofrequency ablation—destroying the nerve that causes the sensation of pain. Antidepressants are effective painkillers, Cohen says, because they increase the body's ability to modulate pain on its own. So are anti-seizure medications, which stop pain nerves from firing. Exercise, healthy eating, and talk therapy can help, too, he says.

The military is particularly interested in treating pain with alternatives such as acupuncture, chiropractic care, and massage, Cohen says. The risks attendant with opioid use—fatigue, confusion, and the possibility of dependence—are simply too high for members of the military.

But if clinicians prescribe fewer opioids, will more people suffer? "That's a false dichotomy," Alexander says. "There's no conflict between reducing opioid use and improving the quality of care for patients in pain. There's little to no evidence to show that opioids are effective in treating pain, except in cancer."

Opioids may reduce acute pain, but they do not address the root causes of chronic pain. OxyContin might dull back pain, but to reduce it permanently, you might need to lose weight, see a physical therapist, and exercise. In other words, a bottle of OxyContin no more heals an aching back than a lollipop heals a skinned knee. It's an easy and fast temporary solution to a complex problem.

At another clinic on Johns Hopkins' East Baltimore campus, scores of people arrive each day to receive methadone, talk with counselors, and work through problems in group therapy. "We're not just giving a medicine that helps people stop using a drug," says Kenneth Stoller, the director of the Johns Hopkins Broadway Center for Addiction. "We're helping them build a life with things that provide them with meaning."

About 170 people are in treatment at Stoller's clinic at any given time. The clinic dispenses opioid agonists—methadone or buprenorphine—which lock into the same brain receptors. Patients also receive case management and individual and group counseling to help them deal with their addiction.

Many have mental health problems, particularly those who started using as teenagers and lost important years of social and emotional growth, Stoller says.

He wants the federal government to invest more money in treating patients like these. While there has been an uptick in programs to increase access to Narcan, a lifesaving drug that reverses overdoses, funding to help overdose survivors has remained level, he says. He would also like to see an increase in cooperative drug treatment programs such as those he runs with nearby clinics. Under Stoller's guidance, the clinics' primary care doctors are authorized to prescribe methadone and buprenorphine. This makes it easier for patients to receive treatment for their addiction while getting care for other medical issues.

Another treatment program, at Johns Hopkins Bayview Medical Center, serves between 350 and 400 patients annually, most from the surrounding neighborhoods. "The clinic is filled with stories of people who had things and lost them," says Michael Kidorf, the associate director of Addiction Treatment Services at Bayview. "They've lost relationships, contact with family, material things that were important to them, a house or a car. They've lost jobs. They've lost their freedom in many ways."

The job of Kidorf, Stoller, and others who treat people with addictions is to help them learn to keep things again: appointments, commitments, and, most importantly, getting treatment. Once patients are established on methadone therapy, they're likely to continue it for the rest of their lives, though doctors can help taper their dosage.

"Leaving treatment is almost always a bad thing," Kidorf said. "Our job is really to keep them in this kind of treatment program for as long as they can do it."

The sweeping windows in Chris Beyrer's office on the seventh floor of the Bloomberg School look out onto one of the poorest areas in Baltimore, according to city health department data. In the Perkins-Middle East neighborhood, the median income is $18,500, about half the median for the city as a whole. Six out of 10 children arrive in kindergarten unprepared to learn.

Beyrer, director of the Bloomberg School's Center for Public Health and Human Rights, believes that the nation's drug policies have created as much harm as the drugs themselves. "We have demonized substance use and substance users, and these communities have paid a terrible price," he says. "For all the effects of licit and illicit drugs, it's drug policy that has ravaged Baltimore. And drug policy is something that we can reform."

Nearly two years ago, Beyrer enlisted public health experts from around the world to form the Johns Hopkins–Lancet Commission. In a meticulously researched report published this year, the commission called out the failures of the War on Drugs and called for a global revolution in drug policy.

International drug laws "are portrayed by policymakers to be necessary to preserve public health and safety, and yet they directly and indirectly contribute to lethal violence, disease, discrimination, forced displacement, injustice, and the undermining of people's right to health," the commission wrote. The report urges global leaders not to prohibit drug use but to minimize the risks associated with it. It calls for decriminalizing the use, possession, and sales of small quantities of drugs, avoiding aggressive police tactics, widening access to needle exchange programs and medical therapies, and ensuring care for injection drug users who have HIV or hepatitis C. In short, the commission wrote, drug laws that do more harm than good should be abolished. "The laws were implemented in the name of public health, but they have undermined public health," Beyrer says.

He and the other commissioners believe an important part of solving the drug problem is to stop sending so many people to jail.

"Law enforcement says they're going after the big guys, but 83 percent of the people worldwide incarcerated for drugs are there for possession." The United States incarcerates far more people than any other country. In 2014, 2.2 million people were in prison or jail, and one out of every 36 adults was under some sort of criminal supervision, according to the Bureau of Justice Statistics. Nearly half of all people currently in federal custody are there for drug offenses.

The country's focus on arresting people involved in drugs has led to generations of poverty and broken families, Beyrer says. "If you have a felony conviction, you become a marginal person. You can't get a passport. You can't vote."

African-Americans have suffered the brunt of the nation's drug laws. They are five times more likely to go to prison for drug offenses, though people of all races use drugs at similar rates, according to the Hopkins–Lancet report, which notes that women are also unfairly penalized. While women are less likely than men to be involved in the drug trade, they're more likely to go to jail if they do. That's because women tend to have lower rank in drug organizations and therefore have less information to swap for a plea deal, according to the Hopkins–Lancet report.

As if that weren't enough, the report notes that rates of HIV and hepatitis C soar when people continue to inject drugs behind bars. And those who get clean in prison are more likely to overdose when they get out.

The Bloomberg School's Susan Sherman is part of an experimental effort to help Baltimore drug offenders avoid jail and put their lives back together. The program, called LEAD, is modeled after an initiative that has helped drug users in Seattle's Belltown neighborhood. Under LEAD, police don't arrest people suspected of low-level drug offenses. Instead, they refer them to a caseworker who can connect them to a raft of social services, including drug treatment, legal advice, housing, and job training. Seattle's program, which was launched in 2011, has been very effective, says Sherman, who also served on the Hopkins–Lancet commission. "Not only does it have an effect on people in the program, but it also changes the perception of cops," she says. Baltimore is set to roll out its LEAD program next year around Lexington Market. If it's a success there, the project could grow to other neighborhoods, Sherman says.

Another solution is to provide clinics where people can inject drugs under medical supervision. Last year Beyrer toured a Canadian supervised injection clinic, called Insite. It was, as Hemingway wrote, a "clean, well-lighted place," Beyrer says. "You'd think it would be wild, but it's kind of quiet." Clients bring their own drugs but pick up clean syringes, tourniquets, and cookers at the facility. If a patient overdoses, nurses rush to help. More than 18,000 people have visited Insite some 3.4 million times since it opened 13 years ago, according to the clinic's website. And while there have been 5,000 overdoses, no one has died. Those wishing to stop using can check into a medically supervised withdrawal clinic on the second floor of the building. The third floor is a transitional housing program for those in recovery.

Beyrer, who just completed a term as president of the International AIDS Society, has seen some hopeful signs that officials in this country are beginning to treat drug use as a public health crisis. Earlier this year, the federal government lifted its decades-long ban on funding for needle exchange programs.

"That's something I've been fighting for my whole career and they finally did it," Beyrer says. "A rational, evidence-based policy—that's what we're calling for."