Opioids: A Brief History
August 30, 2018
by Amy Givler, MD
This is the story of how opioids became a problem in every community in America, including yours. And it is the story of how opioid addiction has overwhelmed and devastated some communities, maybe yours.
If you were practicing medicine in the 1990s, you already know some of this story. Maybe you remember when, in 1996, the American Pain Society coined the term, “Pain: The Fifth Vital Sign,” and urged doctors to ask all patients during every visit how much pain they were experiencing. Maybe you remember when OxyContin first came out—also in 1996—and maybe you listened to Purdue’s drug reps insisting that because it was a slow release drug, it didn’t have the peaks and troughs of immediate-release oxycodone and therefore wasn’t addictive. Maybe you remember hearing a speaker, sometime in that decade, saying it was okay to prescribe opioids liberally for chronic pain because in the presence of actual pain, the opioids don’t produce euphoria, and thus are unlikely to lead to addiction. I remember all these things.
Nobody wants to go back to the days before palliative care was developed 40 years ago. From the 1930s through the 1970s, opioids were rarely used medically in the U.S., even for cancer pain. That is because patent medicines containing them had exploded in popularity, addicting millions, from 1860 to 1914, at which point the Harrison Narcotic Tax Act was passed, limiting their use to medical prescriptions. But during the next decade, police starting arresting doctors for prescribing them to addicts, so doctors became leery of using them at all. Cancer patients enduring their last months of life bore the painful cost.
Humans have grown poppies, the source of opium, at least as early as 3000 BC when the people of Sumer grew it, naming it the “joy plant.” The ancient civilizations of Assyria, Egypt, Greece, Rome, India and Arabia all produced and traded opium. Its abilities to numb pain and induce sleep have been well known for millennia, as well as its potential to addict or poison the user.
Opium comes from slicing and draining the goo that comes from the poppy’s pod. But could opium be further refined to molecules that emphasizes its positive qualities and de-emphasizes its negative ones? That hunt began 200 years ago. In the early 1800s a German scientist isolated morphine, naming it after Morpheus, the Greek god of sleep and dreams. It induces sleep more readily than opium and is a more potent painkiller. In 1898, in an ill-fated attempt to find a non-addictive opioid, Bayer Laboratory developed heroin. Heroin pills were marketed by Bayer to cure coughs, diarrhea and menstrual cramps. Other molecules initially thought to be the solution to the problem of addiction include oxycodone (1917), hydrocodone (1920), methadone (1937) and tramadol (1977).
The quest for a non-addictive derivative of opium may be doomed from the start. The problem seems to be intrinsic to the way opioids work on the mu-opioid receptors found throughout our nervous systems. When we experience pleasure, or are in need of natural analgesia, our brain produces endorphins that plug into these receptors. But the connection is weak and fleeting. When the morphine molecule is introduced, however, it grabs that receptor in a vice grip, creating a far more intense euphoria. Does everyone exposed to this molecule become an addict? No, but a few people seem to be genetically predisposed to developing intense drug-seeking behaviors after even a single dose. And many others will be hooked if the opioid exposure continues.
What is the risk of misuse (continuing to use past the point of pain relief) or abuse (continuing to use despite harm)? After five days of continued opioid use, the risk of converting to a substance use disorder rises. And the risk keeps increasing, spiking higher after 30, and then plateauing at 90 days of use. After receiving an initial prescription for an opioid, if patients get a refill authorized, one in seven of them will be on opioids a year later. Of all Americans taking opioids, approximately one in four misuses, and one in 10 abuses.
U.S. opioid prescriptions doubled to 200 million from 1998 to 2012. Because there are so many opioids being prescribed, this adds up to a massive number of eventually-addicted people. In 2015, two million Americans were abusing prescription opioids, and 600,000 were abusing heroin.
Yes, heroin. When I was a teenager in the 1970s, heroin was only associated with inner city drug dens and street gangs. But heroin has moved to the suburbs.
There’s a direct link from prescription opioid use to heroin use. Four out of five heroin users began with a prescription. Heroin is becoming purer and cheaper, and deaths are spiking. There were 13,000 deaths in the U.S. due to heroin in 2015, a 20 percent jump from the year earlier. Heroin is smuggled in from Asia (white powder), Columbia, Pakistan and Afghanistan (brown powder), as well as Mexico (black tar). Reading Dreamland: The True Tale of America’s Opiate Epidemic was eye opening. It describes a new kind of drug cartel, one largely without guns and street crime. Small amounts of high quality, black tar heroin produced in the tiny Mexican state of Nayarit are carried by family members—usually young sugar-cane farmers—to suburban communities in a dozen U.S. states. There each pusher develops a clientele by passing out cards with his phone number, and then he responds to calls by driving a nondescript car to meet upper- or middle-class addicts in public parking lots. He carries a dozen tiny balloons in his cheek, each with a tenth of an ounce of heroin. If police stop him, he swallows the balloons. If he is deported, another young family member takes his place within the week. And so the supply continues unchecked, and families and communities are destroyed.
The problem of chronic non-cancer pain (from now on I’ll just call it “chronic pain”) is immense. All medical professionals see chronic pain patients, although the burden of addressing this problem is generally on the shoulders of primary care doctors. Pain specialists cannot possibly see all of the nearly 50 million Americans who suffer either daily or intermittently from chronic pain. So what can we do if we are not writing opioid prescriptions?
As I’ve written before, nine months ago, there are many good options for helping people with chronic pain. Briefly, they include: daily exercise, adequate sleep, psychological support, non-opiate medications and physical therapy. But all of these treatments take time—time to explain them to the patient, and lots of elapsed time before they take good effect. And if the patient has taken opioids in the past, you can double the amount of time it will take to explain why you think opioids are not currently a good idea.
The more you know about the dangers of opioids, the easier it is to choose to use other treatments for chronic pain. We want to help our patients. But it also helps to know that opioids are no more effective for chronic pain than the other treatments I listed. In a review of meta-analyses on the subject, published in the British Journal of Pharmacology, the authors conclude, “even though sponsors and authors have likely identified the optimal scenarios for improvement of the (randomized controlled trials’) participants during the last two decades, there is no evidence to support the sole or preferential use of opioids.”
As if addiction or misuse isn’t enough to worry about, it looks like opioids actually enhance the very pain they are supposed to relieve. This phenomenon is called “opioid induced hyperalgesia” and is distinct from the process of tolerance. Although its exact mechanism isn’t understood, and it may not happen in all users, it has been demonstrated in studies of methadone users, post-op patients and normal volunteers. By giving opioids, we may be making pain worse.
If at all possible, we want to relieve pain. But as followers of Jesus, we also know pain is often used by God to get people’s attention. That is, to point people to Himself. Caring for patients means just that—caring. We have compassion for our patients’ suffering, regardless of whether their own choices were the cause. And pain can be the pathway to maturity. As Timothy and Kathy Keller write, “there is seldom real growth without life’s difficulties, its blows and wounds. People who have led completely charmed lives are often superficial and unable to sympathize with others, and usually have an unrealistically high estimation of their own endurance, patience, and strength."
Christians aren’t the only ones who know this. I previously mentioned Dreamland: The True Tale of America’s Opiate Epidemic, which is a masterful piece of investigative reporting by Sam Quinones. I have no inkling whether Mr. Quinones is a man of faith, but in his book characterized by straightforward facts, he took a rare detour for wise reflections on the underlying reason addicts stay addicted:
“In heroin addicts, I had seen the debasement that comes from the loss of free will and enslavement to what amounts to an idea: permanent pleasure, numbness, and the avoidance of pain. But man’s decay has always begun as soon as he has it all, and is free of friction, pain, and the deprivation that temper his behavior.”
Stemming the flood of current opioid users will not be a simple process because it didn’t have a simple beginning. Clinicians, pharmaceutical companies, accrediting organizations, Mexican drug cartels and public expectations have all played a part. But those of us who care for patients need to be part of the solution, however tiny that contribution may be.
It’s time to take a hard look at our own prescribing habits of opioids for patients with chronic pain. At the very least, we must strive to “do no harm.”