Papaver somniforum—literally, 'sleep-bringing poppy'—is the scientific name for the type of poppy that produces opium, which humanity has relied on since before history was even a concept. Along with wheat, the opium poppy is one of the world's oldest cultivated plants, with some estimates suggesting that humans have been growing it for 10,000 years or more. It's been cultivated so widely we don't even know where it originates. Some think it's indigenous to the Eastern Mediterranean or the Swiss Alps, but frankly nobody really knows. What's clear, though, is that the relationship between humans and this strange and hardy plant (it can grow basically anywhere) goes beyond curiosity and into the realm of symbiosis.
There's a line from Lars Von Trier's Antichrist: "Nature is Satan's church," and perhaps there's no better example of the curious and uncanny relationships that form across species and time than the one between humans and the poppy. Opioids, the chemicals produced by papaver somniforum, somehow fit perfectly into the human body's opioid receptors, which are scattered throughout the brain, spinal cord, and digestive system, and this precise fit makes them exceptionally effective at suppressing pain. The geometry is so exact that some experts theorize that the opium plant and our neural architecture is the result of symbiotic co-evolution (some even think opium poppies shaped the development of human consciousness). The mystical pain-dampening plant on the one hand, the upright ape on the other.
So when we talk about today's opioid crisis, we're really talking about just the latest chapter in an inter-species relationship that spans millennia. That's important to remember because for all their potential harms, opioids are a critical part of human civilization given their unique capacity to numb our pain. The issue, then, isn't so much how we stop people from using opioids, but instead how we make sure that these drugs bring us the most benefits with the fewest harms.
Unfortunately, over the past few decades it seems that the harms of opioids are increasingly outweighing their benefits in North America, to the point where governments are declaring public health emergencies in response to epidemics of opioid overdose deaths. In Ontario, one in eight deaths among young adults are the result of opioid overdoses, while drug overdose —driven primarily by opioids—is the leading cause of accidental death in the United States. But how did we get here? The answer is a cautionary tale about the power of Big Pharma, the unintended consequences of government intervention, and the tenacity of drug markets.
OxyContin has been widely hailed as a wonder drug and in many ways, it is. A prescription drug with billions in R&D behind it, OxyContin was put on the market in 1996 as a fast-acting, controlled release formulation of oxycodone, which is an opioid used to treat moderate to severe pain, and which was originally designed to treat cancer patients. In its first year on the market, OxyContin sales reached $48 million (USD); in 2000—just four years later—annual sales had reached almost $1.1 billion, representing an increase of roughly 2,200 percent. It remained among the top 20 best-selling drugs in the US until 2013, when it was taken off the market. By the conventional metrics of the pharmaceutical industry, then, OxyContin was a massive and highly profitable success.
Part of that success, though, wasn't just a natural result of OxyContin's effectiveness as an opioid painkiller. Purdue Pharma, the pharmaceutical giant that developed the drug, also threw millions behind marketing the drug to its key customer base: medical doctors. This meant, for instance, holding over 40 all-expense-paid conferences for over 5,000 attendees and paying out $40 million in bonuses to Purdue sales reps in the first five years OxyContin was on the market. In some cases, the marketing strategies verged into the ridiculous, as with Purdue Pharma's creation of a promotional song—"Get in the Swing with OxyContin"—to try to entice doctors to prescribe the drug.
Other strategies went further. One of the major breakthroughs in expanding the number of OxyContin prescriptions came with Purdue Pharma's decision to switch focus from marketing OxyContin as a drug to manage cancer-related pain—a relatively stable market— and instead promote it as an effective and safe treatment for the more nebulous class of "chronic non-malignant pain" (aka, non-cancer pain), a market that was exploding in the late 1990s. It was a masterstroke, and it paid off: between 1997 and 2002, there was a near tenfold increase in OxyContin prescriptions in the US for chronic non-malignant pain, from 670,000 to 6.2 million annually. It was the opening up of a massive new market for opioids that would prove incredibly profitable: Purdue Pharma made nearly $3 billion in revenues from OxyContin in the first five years it was on the market.
The true genius, though, was Purdue Pharma's use of granular geographic data to identify doctors with the highest OxyContin prescribing patterns in specific area codes, and then targeting those clinicians with marketing materials that included patient coupons for free 30-day trials of OxyContin prescriptions (as laid out in a American Journal of Public Health review.) The idea was that these techniques would help identify doctors with the highest number of chronic pain patients. Of course, it also opened up the possibility, if not the probability, that Purdue Pharma was pushing doctors who were already over-prescribing OxyContin to ramp their prescriptions up even further.
In some cases, Purdue Pharma's marketing verged on the sinister and even crossed into the illegal. Nowhere was this more obvious than in the pharmaceutical giant's downplaying of the addictive potential of OxyContin, which it did in a multitude of ways. In 2010, two doctors at St. Michael's Hospital, a teaching hospital affiliated with the University of Toronto's medical school (and where I hold a position), started voicing concerns about pharmaceutical industry involvement in a pain management course that was part of U of T's med school curriculum. It turned out that the lecturer for the course, Dr. Roman Jovey, was a member of Purdue Pharma's speakers' bureau and was paid by the company to lecture. Worse, a book on pain management that was co-authored by Dr. Jovey and funded by Purdue had been used as a textbook within the class. In the book, free copies of which were given to U of T medical students, oxycodone (the active agent in OxyContin) was described as a moderate-intensity opioid despite the fact that it is twice as potent as morphine. It was also characterized as having a low risk for addiction among non-malignant pain patients, despite the fact that at the time, rates of opioid dependence among patients prescribed OxyContin were soaring.
In 2007, during a time when the dangers of OxyContin over-prescribing were starting to become clear to public health experts, three top executives at a subsidiary of Purdue Pharma pled guilty to fraud and paid $600 million for "misbranding" OxyContin as a result of the company's claims that the drug was less addictive than other comparable opioid-based drugs like Percocet or Vicodin. In internal Purdue Pharma documents dating to before OxyContin was marketed, company officials expressed concerns that they would face resistance from medical doctors concerned about the potential for patients to become addicted. Despite these doubts, Purdue Pharma went full steam ahead in marketing the drug as having a "reduced-risk" for addiction; in the court case, it was found that this constituted fraudulent and deceptive marketing, and in a guilty plea, Purdue Pharma agreed, with the company stating that "[w]e accept responsibility for those past misstatements and regret they were made."
By the time public health experts started sounding the alarm about the addictive potential of OxyContin, the damage was done. Beginning in the early 2000s the infusion of billions of OxyContin pills into the drug market had caused a seismic shift in drug use patterns, with increases in heroin use and injection drug use among working-class white people in suburban and rural communities across North America for the first time in decades. Purdue Pharma had wedged open a massive new market of people seeking to numb their pain, aided and abetted by a legion of clinicians without the requisite knowledge about the drug's dangers and a lack of expertise in managing the associated risks. But now, the market was out of control. The alarm had been sounded. It was time to act.
There's a phenomenon to describe the ways that trying to intervene in one part of a drug market can make things worse elsewhere. It's called the Balloon Effect, for the way that squeezing one part of a balloon causes other parts to expand, and it's surprisingly common in the history of the drug war. When the US tried to stop cocaine production by eradicating coca leaf cultivation in Colombia, for instance, all that the aerial spraying and destruction of millions of hectares of farmland did was spread production to Colombia's neighbours, Bolivia and Peru. When a sudden drop in the availability of heroin in Australia occurred in 2001,the number of heroin users plummeted, but was offset by a similar increase in the number of people using cocaine and amphetamines. The problem is, basically, that if you don't first reduce demand for a drug, trying to control supply in a global economy only incentivizes drug traffickers to find new supply routes or new drugs to bring to the market.
So it has gone with efforts to control North America's opioid problem, and why it is that we are now facing an even graver crisis than in the era when OxyContin prescriptions were at their peak. Instead of meaningfully scaling up effective treatment for people who became addicted to OxyContin, the major policy change was the removal of OxyContin by Purdue Pharma from the North American market in 2012 and its replacement with OxyNEO, which the company claims is tamper-resistant (i.e., harder to crush up, snort, or inject). The timing of this swap out, though, caused some experts to grow suspicious: in Canada, OxyNEO was introduced just a few months before the patent on OxyContin was set to expire, meaning that it was also an effective way for Purdue Pharma to protect its market share.
Worse, efforts by government agencies and medical associations to reduce opioid prescribing failed to make a meaningful dent.. How could it, given that doctors had been acculturated into believing that drugs like OxyContin weren't actually that dangerous, and chronic pain patients had grown accustomed—and in many cases, dependent on—a steady supply of opioids? Instead, with OxyContin's removal, fentanyl, an opioid painkiller 50 to 100 times more powerful than morphine and which carries an even higher risk of overdose, became the opioid of choice to fill the prescription void.
And this is where the Balloon Effect comes into play: without expanded access to treatment, the demand for opioids hasn't gotten smaller. Reducing the supply of opioids like OxyContin, has only served to shift the market to more dangerous ones like fentanyl. As a second wave of alarm has spread about fentanyl, some doctors have become unwilling to treat chronic pain patients at all. The result? The market—this time, contraband fentanyl and lesser known carfentanil (developed as an elephant tranquilizer and 10,000 times more powerful than morphine)—have been filling the void, with deadly but predictable results. The question is, of course, where continuing along this path will get us. If beer was taken off the market, people would drink wine. If wine was taken off, people would drink hard liquor. If hard liquor was taken off, people would drink industrial alcohol. So it goes with opioids, and why we've moved from OxyContin (1.5 times as strong as morphine) to fentanyl (50-80 times more powerful) to carfentanil (10,000 times more powerful).
So how does this cycle stop? Sadly, there is no quick fix when it comes to opioids. Simply banning painkillers would doom hundreds of thousands of people who are legitimately suffering with pain to a barbaric and excruciating existence. And when the problem was caused by a billion-dollar fraud perpetrated on an unsuspecting public via one of the most trusted pillars—medical doctors—the solution is just too damn big to be easily dealt with. What's clear though, is that the cycle of squeezing the supply without addressing the demand for opioids will only get us into increasingly more dangerous territory. Instead, we need a broad recognition that the pharmaceutical market is just one part of a larger drug market that includes illegal drugs and regulated substances like alcohol, and that intervening on supply in one part of this larger market will have ripple effects across the whole enterprise. If we fail to come to this realization, we'll be dooming ourselves to the opioid overdose epidemic becoming a permanent fixture of our society. Do we really want to live in a world where we have to worry about one tiny grain of carfentanil killing kids who are experimenting with drugs? In the long history of our symbiotic relationship with opioids, that would be the saddest ending of all.
Dr. Daniel Werb is an epidemiologist and policy analyst with expertise in the fields of HIV, addictions, and drug policy.
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