When America saw the first signs of an opioid addiction epidemic in the mid 1990s, one major mystery began to fester. Pharmacology research has long suggested that drugs that take effect slowly and last for a long time are likely to be less addictive than those that hit fast and crash faster. In fact, that's at least part of why FDA officials felt like they were on safe ground when they approved Oxycontin—the first long-acting form of the opioid oxycodone—in 1995.
But the explosion of addictions after that suggested there was a glaring problem with this perspective. Most Oxycontin addictions struck recreational drug users who snorted or injected it—which bypasses the time-release mechanism and makes it into a short-acting, fast-hitting drug. But even people who swallowed the stuff seemed overly likely to get hooked. Anti-opioid activists began arguing that the previously unquestioned principle trumpeting long-acting drugs as less addictive was mere propaganda from the pharmaceutical industry.
That is until earlier this month, when the LA Times seemed to reveal the missing piece of the puzzle: According to an investigation published May 5, while manufacturer Purdue Pharma has long claimed that Oxycontin's effects last for at least 12 hours, some of the company's own studies showed that for many people, the drug wears off way faster than that.
This means pharmacologists actually are right about the relationship between how long drugs last and the risk of addiction. It could also help explain why some pain patients have faced a higher risk for addiction than they should have, helping produce a jump in addictions that's led to an unprecedented number of overdose deaths in America.
It might seem paradoxical to think that a drug that lasts for a long time would be less addictive than a shorter-acting one, rather than the other way around. After all, people who like intoxication should want to stay high as long as possible—not to mention that this would mean they'd need to pay for drugs less frequently. But this isn't actually how getting high works.
As the term "high" itself implies, there's a relationship at play. You can't just be high—you have to be high relative to a lower state. Part of what causes addiction, then, is the contrast between the high and your normal state of consciousness. If you just go up and stay up, you are naturally going to be less aware of this contrast. (Also, if you start from lower, you'll feel much higher—which is part of why people in emotional distress are much more likely than others to get addicted.)
Basically, addiction can't occur unless your brain learns that a drug improves your state of mind somehow—typically by intensifying and accelerating experience (think stimulants like methamphetamine or cocaine) or slowing and numbing it (think depressants like alcohol and opioids). The more frequently you associate a drug with feeling better, the more that learning gets internalized. This means a short-acting drug, one that produces a series of highs and lows, will be more addictive due to repetition alone than a longer-acting one will be. And the relative intensity of the up-and-down experience will also increase risk.
This helps explain why shooting drugs is generally more addictive than swallowing them and why smoking crack or shooting cocaine powder are both more addictive than snorting it. In most cases*, injecting drugs gets them to the brain fastest, followed by smoking, snorting, and eating.
The reduced addiction risk that comes from staying in a steady state is also the principle on which the use of maintenance drugs—the only treatment that cuts the death rate from opioid addiction—relies. Indeed, when pain is treated with opioids, the vast majority of patients do not become addicted. This fact—widely promoted by a great deal of pharmaceutical advertising—led doctors to become less cautious about prescribing during the 90s and early 00s. (And that indirectly made the drugs more available to the people who are at high risk of addiction, like teens and young adults, who generally get them from family medicine cabinets, friends, and dealers).
In pain treatment, the idea that longer-acting drugs are less addictive relied on the same principle observed in studies on recreational use. The fewer ups and downs patients experience, the less likely they are to feel a "rush" and develop a strong association between the drug and relief. Keeping pain levels steady and low—rather than waiting to take drugs until the last dose wears off—is the goal. And abundant marketing assured doctors this could be achieved for 12 hours with Oxy.
Unfortunately, according to the LA Times, Purdue Pharma, the manufacturer of Oxycontin, has known from the start that for many people, the drug doesn't last nearly that long. The paper described what happened to one Oxycontin patient, a 42-year-old plant scientist named Elizabeth Kipp who had back pain beginning when she was thrown from a horse at age 14. She would suffer in agony for hours between Oxy doses, but her doctor insisted she stay on the 12-hour regimen.
"You want a description of hell?" the patient recalled. "I can give it to you."
Kipp should have been at low risk for addiction: She was past her teens and 20s, which is the peak period of risk. She was also taking the drug exactly as prescribed. But because Purdue apparently misled doctors about Oxy's true length of effectiveness, her risk increased dramatically. And she remained hooked until she eventually went to rehab. Sadly, hers is not at all an isolated case. (In a lengthy response to the paper, a Purdue Pharma spokesperson said, "Scientific evidence amassed over more than 20 years, including more than a dozen controlled clinical studies, supports the FDA's approval of 12-hour dosing for OxyContin.")
So what should we do now? For one, it's good to know pharmacology texts don't need changing: Addiction really is less likely if you "go slow and stay low." And steady pain relief (rather than waiting to take drugs at longer intervals) is still a good idea. Secondly, if there is anyone who doesn't already think that Big Pharma needs to be better regulated and made to pay for severe ethical violations that go beyond fines he or she can simply write off as a "cost of doing business," this should make him or her think again.
America needs to ban direct-to-consumer advertising, massively raise fines for misleading marketing, and give the National Institutes of Health the funding and responsibility for most human clinical trials, rather than drug companies. And the government should refuse to allow companies that repeatedly violate the law to continue to do so.
Medical science relies on trust and good data. The story of Oxycontin continues to undermine it. Pain patients, people with addiction, and human beings everywhere deserve better.
By Maia Szalavitz - Vice/May 16, 2016
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