Opium, a dried latex collected from the opium poppy, was the original “wonder drug.” It effectively relieved pain and had other medicinal effects—and incidentally produced both euphoria and addiction. There is archaeological evidence that it was used as early as 5700 BC. It was the active ingredient in laudanum and paregoric. For decades, these opiates were readily available without a prescription, and many famous people became addicted, including the poet Elizabeth Barrett Browning and the surgeon William Halsted, a founder of Johns Hopkins Hospital who was considered the “Father of Modern Surgery.” Products such as Mrs. Winslow’s Soothing Syrup were widely given to infants to get them to stop fussing and to relieve the pain of teething. Parents didn’t realize it contained the opium derivative morphine. It worked. It soothed babies, put them to sleep, and relieved frazzled mothers. Unfortunately, there was a risk that it might put babies to sleep permanently.
Morphine was isolated from opium in 1804, and codeine, another component, was identified in 1832. Codeine is metabolized to morphine in the liver. It doesn’t work for everyone; it is not effective in individuals who are poor metabolizers. Opium derivatives are called opiates; synthetic analogues are called opioids. Both are classified as narcotics.
Chemists have invented well over a hundred semisynthetic and synthetic opioids. They were hoping to find a drug that would be less addictive but only succeeded in creating stronger ones. Heroin was originally marketed as a nonaddictive substitute for morphine. That backfired, and it proved to be highly addictive. It soon became illegal but continues to wreak havoc in the modern world. Fentanyl, first synthesized in 1959, is 100 times more potent than morphine and fifty times more potent than heroin; it has recently become a major cause of overdose deaths.
With continued use of opioids, patients develop tolerance: they must increase the dose to get the same effect. That doesn’t mean they are addicted. They are physically dependent on the drug if they have a physiologic need to keep taking it (i.e., withdrawal symptoms if they stop). That’s easily managed by slowly reducing the dose. Drug abuse is when the drug is used outside of societal norms. Addiction goes a step further—it’s a chronic disorder where the drug abuse has a societal impact and there are changes in brain structure and function.
Some people think that anyone who takes an opioid is likely to become addicted; this is not true. Most patients who take an opioid for post-operation or post-trauma pain stop taking it when the pain subsides. The drugs were thought to be powerfully addictive because rats preferred a morphine solution to water and quickly became addicted. But the Canadian psychologist Bruce Alexander suspected the rats’ living conditions were more to blame than the drug. The rats were isolated in individual cages, which is not a natural environment for rats. To test his hypothesis, he set up Rat Park,1 with sixteen to twenty rats of both sexes housed in each cage with food, space, wheels for exercise, and opportunities for play. Lo and behold, the rats in Rat Park preferred water to morphine! Even rats who were already addicted preferred to drink water in Rat Park despite showing signs of dependence and withdrawal. Other studies have confirmed the Rat Park results. In a 2008 study of mice,2 enriching the environment was shown to effectively reverse drug addiction.
Humans are also powerfully influenced by environment. Twenty percent of soldiers in Vietnam became addicted to heroin, but when they left Vietnam and returned to their normal stateside environment, the addiction resolved practically overnight for 90 percent of the addicts.3 Contrast that with the experience of typical drug users who relapse when they graduate from rehab and return to their old environment with plentiful cues, triggers, other addicts, and ready availability of drugs.
The Opioid Epidemic and Overdose Deaths
We are in the midst of an opioid epidemic. Nearly two million Americans either abused or were dependent on opioids as of 2014. From 1999 to 2017, 400,000 people died of opioid overdose; at present, 130 Americans die from it every day.4 The increase in deaths comprised three stages:
- Starting in 1999: deaths from prescription opioids
- Starting in 2010: a rapid increase in heroin deaths
- Starting in 2013: deaths from synthetic opioids, especially illicitly manufactured fentanyl.
There was prescription abuse by the intended patients and also diversion to others, often for profit. Many addicts turned to crime to pay for their habits.
For most post-op pain, a three-day supply of pills is usually sufficient, but patients are often given a week’s supply or more and end up with unused pills in their medicine cabinet that they may be tempted to share with friends or family or even sell. The most widely proposed remedy for the opioid epidemic is to improve prescribing practices, but this can be counterproductive. Dispensing smaller numbers of pills might prevent some addictions but makes it harder for addicts to get the drugs, so more of them turn to heroin, which is illegal but often more readily available and less expensive. The CDC has published guidelines that, among other things, educate prescribers to restrict opioids for chronic pain patients, providing them only for active cancer treatment, palliative care, and end-of-life care.5 For some patients, opioids really are the best or the only option, and it is important not to restrict their access in our zeal to prevent opioid deaths. If a dying patient becomes addicted, that’s not really a problem.
We could do a much better job of identifying and treating individuals with opioid use disorders. Punishing addicts with jail time doesn’t work. Based on the Rat Park studies, we could change our focus from detox and rehab to long-term support of recovered patients focused on improving their environment.
One simple stopgap measure is to supply injectable naloxone (Narcan) to first responders and anyone else who might encounter someone who has overdosed. It reverses the opioid effect. Where this policy has been implemented, it has already saved lives.
Several studies have found that opioids are no better than non-opioid analgesics for chronic non-cancer pain.6 A well-designed 2018 study of children with post-op pain showed no difference between ibuprofen and oral morphine. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen may work as well as opioids without the risk of addiction and may have fewer adverse side effects. Opioids can actually cause pain through the phenomenon of opioid-induced hyperalgesia. Chronic use can make patients more sensitive to pain. People who have used opioids in the past may have increased pain responses to procedures such as having blood drawn. Opioids are effective for cancer pain, but up to 20 percent of patients will have intolerable side effects requiring a change in treatment.
Big Pharma Malfeasance
Purdue Pharma makes one of the most widely prescribed opioid drugs, OxyContin. A study published in The American Journal of Public Health examined the commercial triumph and public health tragedy resulting from Purdue’s deceptive and aggressive marketing tactics.7 Pharmaceutical representatives were instructed to tell doctors that the risk of addiction was less than 1 percent, although this was not supported by any acceptable evidence. Purdue claimed the drug was more effective than other opioids; it wasn’t. They claimed the slow-release formulation lasted twelve hours; it actually wore off sooner, encouraging drug abuse. Purdue doubled the number of sales representatives and paid them lucrative incentives (bonuses averaged $71,000 and went as high as $240,000). They collected prescriber profiling data, targeted high-volume prescribers, and encouraged them to prescribe even more. They offered free coupons. They made a deceptive educational video that was not approved by the FDA. They ignored increasing evidence of drug abuse, diversion, and overdose deaths. They ignored marked geographical variations, with some counties filling five to six times as many prescriptions per capita as the national average. The excesses could often be traced to unscrupulous doctors and “pill mills.”
The Sackler family, who controls the company, for years systematically ignored warnings and deceived doctors to increase sales. Dr. Richard Sackler was the chief executive. Documents disclosed during legal proceedings showed how he forcefully pushed employees to increase sales of OxyContin and suppressed concerns that might limit those ambitions. He left the Purdue board in July 2018. He denies any wrongdoing and still does not accept that the company had any role in causing the opioid epidemic. He blames the abusers, not the drugs. In a 2001 email, he said, “We have to hammer on the abusers in every way possible … . They are the culprits and the problem. They are reckless criminals.”8
Purdue’s business model covered both ends: selling addictive drugs and selling drugs to treat opioid addiction. They promoted the misconception that OxyContin was weaker than morphine. They maintained a list of doctors suspected of abuses but continued to sell to them. The Sackler family’s net worth is $13 billion. It is well known for philanthropy, and the Sackler name is on many museums and galleries, including the Metropolitan Museum of Art in New York. Thanks to the OxyContin publicity, these institutions are now refusing Sackler donations.
Purdue Pharma has been sued many times.9 In May 2007, they pled guilty to misleading the public and paid $600 million in one of the largest pharmaceutical settlements in history. Three individuals also pled guilty and paid individual fines, and three top executives charged with a felony were sentenced to 400 hours of community service. In the settlement, the company agreed to monitor suspicious patterns of sales but then failed to do so.
In 2015, they settled a lawsuit with Kentucky for $24 million. In 2019, they settled an Oklahoma lawsuit for $270 million. By January 2019, they were being sued by thirty-six states as well as by the city of Everett and others. The House Oversight Committee is investigating. The company is considering filing for bankruptcy.
Purdue appears to be the biggest offender, but several other companies are also being sued. In all, more than a thousand cities, counties, tribes, and states have sued drug makers, distributors, and pharmacies. Hundreds of lawsuits have been consolidated to facilitate prosecution.
Opioids are good when used appropriately to relieve pain. They are bad when they lead to addiction, crime, and overdose deaths. They become ugly when unscrupulous people exacerbate misuse by spreading misinformation and marketing drugs aggressively simply to increase their own profit.