This 1-paragraph letter may have launched the opioid epidemic

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Prescriptions For Opioids Drop Amid Epidemic

Over the past decade, the US has undergone an opioid epidemic. Prescriptions for opioid painkillers like oxycodone, hydrocodone, fentanyl, and morphine have skyrocketed and, with them, the number of overdoses related to opioids.

In 2014, deaths from opioid-related drug overdoses reached a new high of 28,647, according to a January report from the Centers for Disease Control and Prevention (CDC).

But the trend has been decades in the making.

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This 1-paragraph letter may have launched the opioid epidemic

Opioid painkillers capitalize on our body's natural pain-relief system. We all have a series of naturally produced keys ("ligands") and keyholes ("receptors") that fit together to switch on our brain's natural reward system — it's the reason we feel good when we eat a good meal or have sex, for example. But opioids mimic the natural keys in our brain — yes, we all have natural opioids! When they click in, we can feel an overwhelming sense of euphoria.

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Opioid painkillers can have effects similar to heroin and morphine, especially when taken in ways other than prescribed by a doctor.

When prescription painkillers act on our brain's pleasure and reward centers, they can make us feel good. More importantly, though, they can work to reinforce behavior, which in some people can trigger a repeated desire to use.

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You may also feel sleepy.

Opioids act on multiple brain regions, but when they go to work in the locus ceruleus, a brain region involved in alertness, they can make us sleepy. Why? The drugs essentially put the brakes on the production of a chemical called norepinephrine, which plays a role in arousal.

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Your skin may feel flushed and warm.

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You'll begin to feel their effects 10 to 90 minutes after use, depending on whether they're taken as directed or used in more dangerous ways.

Some drugmakers design versions of their medications to deter abuse. Extended-release forms of oxycodone, for example, are designed to release slowly when taken as directed. But crushing, snorting, or injecting the drugs can hasten their effects.

It can also be deadly. Between 2000 and 2014, nearly half a million Americans died from overdoses involving opioid painkillers and heroin, a report from the US Centers for Disease Control and Prevention found. The most commonly prescribed painkillers were involved in more overdose deaths than any other type of the drug.

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Your breathing will slow as well.

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Depending on the method used, the effect can last anywhere from four to 12 hours.

For severe pain, doctors typically prescribe opioid painkillers like morphine for a period of four to 12 hours, according to the Mayo Clinic. Because of their risks, it's important to take prescription painkillers only according to your physician's specific instructions.

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Overdosing can stop breathing and cause brain damage, coma, or even death.

2014 report from the American Academy of Neurology estimates that more than 100,000 Americans have died from prescribed opioids since the late 1990s. Those at highest risk include people between 35 and 54, the report found, and deaths for this age group have exceeded deaths from firearms and car crashes.

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Combining them with alcohol or other drugs — even when taken according to the directions — can be especially deadly.

Since they slow breathing, combining opioid painkillers with other drugs with similar effects can drastically raise the chances of accidental overdose and death.

Yet they're often prescribed together anyway, according to the National Institute on Drug Abuse. "Unfortunately, too many patients are still co-prescribed opioid pain relievers and benzodiazepines [tranquilizers]," the institute said. In 2011, 31% of prescription opioid-related overdose deaths involved these drugs.

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Abusing opioid painkillers has been linked with abusing similar drugs, like heroin.

A CDC report found that people who'd abused opioid painkillers were 40 times as likely to abuse heroin compared with people who'd never abused them. The National Institute on Drug Abuse says that close to half of young people surveyed in three recent studies who'd injected heroin said they'd abused prescription painkillers before they started using heroin.

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You may also develop a tolerance for the drugs so that you need more to get the same effect over time.

Tolerance to opioid painkillers happens when the brain cells with opioid receptors — the keyholes where the opioids fit — become less responsive to the opioid stimulation over time. Scientists think that this may play a powerful role in addiction.

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Suddenly stopping the drugs can result in withdrawal symptoms like shakiness, vomiting, and diarrhea.

Taking prescription painkillers for an extended period increases the likelihood that your brain will adapt to them by making less of its own natural opioids. So when you stop taking the drugs, you can feel pretty miserable. For most people, this is uncomfortable but temporary.

But in people who are vulnerable to addiction, it can be dangerous because it can spurn repeated use.

"From a clinical standpoint, opioid withdrawal is one of the most powerful factors driving opioid dependence and addictive behaviors," Yale psychiatrists Thomas Kosten and Tony George write in a 2002 paper in the Journal of Addiction Science & Clinical Practice.

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This explosion in opioid prescriptions began in the early 1990s with "a big push" from medical groups that doctors were under-treating pain, according to Dr. Ted Cicero, a professor of psychiatry at Washington University in St. Louis and an opiate-use researcher.

One of the primary justifications for this increase, used by doctors, pharmaceutical companies, and researchers alike was a single paragraph printed in the January 10, 1980 issue of the New England Journal Of Medicine:


To the Editor: Recently, we examined our current files to determine the incidence of narcotic addiction in 39,946 hospitalized medical patients' who were monitored consecutively. Although there were 11,882 patients who received at least one narcotic preparation, there were only four cases of reasonably well documented addiction in patients who had a history of addiction. The addiction was considered major in only one instance. The drugs implicated were meperidine in two patients, Percodan in one, and hydromorphone in one. We conclude that despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction.



Boston Collaborative Drug

Surveillance Program

Boston University Medical Center

Waltham, MA 02154

The analysis mentioned in the letter, which was authored by Dr. Hershel Jick, was not included.

In the years that followed, the letter was used by pain specilaists, nurses, and pharmaceutical representatives in conventions, seminars, and workshops as evidence that opiate painkillers had the low risk of addiction.

Jick's analysis proved no such thing. The study analyzed a database of hospitalized patients at Boston University Medical Center who were given small doses of opioids in a controlled setting to ease suffering from acute pain. These patients were not given longterm opioid prescriptions which they'd be free to administer at home.

Nevertheless, medical groups like the American Pain Society and the American Pain Foundation used the letter as a jumping off point and began calling pain the "fifth vital sign" that doctors should attend to. Pharmaceutical companies like Purdue Pharma introduced powerful new painkillers such as MS Contin and Oxycontin, extended-release pills with a very large dose of morphine or oxycodone respectively that is designed to be released slowly into a person's body over a 12 or 24-hour period. Major pain specialists began encouraging doctors to prescribe opioids liberally to their pain patients, despite long-held fears of addiction.

As detailed by investigative journalist Sam Quinones in "Dreamland: The True Tale of America's Opiate Epidemic," his investigation into the causes of the heroin crisis, the Porter and Jick letter was referenced repeatedly to justify the increase in liberal prescriptions of opioid painkillers, including in the following:

  • A 1990 article in Scientific American, where it was called "an extensive study;"
  • A 1995 article in Canadian Family Physician, where it was called "persuasive;"
  • A 2001 Time Magazine feature, which said it was a "landmark study" demonstrating that the "exaggerated fear that patients would become addicted" to opiates was "basically unwarranted;"
  • A 2007 textbook Complications in Regional Anesthesia and Pain Medicine, which said it was "a landmark report" that "did much to counteract" fears that pain patients treated with opioids would become addicted.
  • A 1989 monograph for the National Institutes of Health which asked readers to "consider the work [of Porter and Jick]."

As of May 24, 2016, the Porter and Jick letter has been cited 901 times in scholarly papers, according to a Google Scholar search.

The most influential citation of the Porter and Jick letter was in a 1986 paper on the "chronic use of opioid analgesics in non-malignant pain" by Dr. Russell Portenoy and Kathy Foley in Pain, the official journal of the American Pain Society. In the paper, Portenoy and Foley reviewed the cases of 38 cancer patients with chronic pain who used opioids. Only two became addicted.

"We conclude that opioid maintenance therapy can be a safe, salutary and more humane alternative to the options of surgery or no treatment in those patients with intractable non-malignant pain and no history of drug abuse." Portenoy and Foley wrote.

Portenoy and Foley's paper, bolstered by the Porter and Jick letter, became an even broader justification for doctors to prescribe opioids liberally for common injuries such as back pain.

russell portenoyAbid Katib/Getty Images

Over time, the Porter and Jick letter, and its claim that "less than 1%" of opioid users became addicted, became "gospel" for medical professionals, Dr. Marsha Stanton told Quinones.

"I used [Porter and Jick] in lectures all the time. Everybody did. It didn't matter whether you were a physician, a pharmacist, or a nurse; you used it. No one disputed it. Should we have? Of course we should have," Stanton said.

In 1996, the American Pain Society and the American Academy of Pain Management issued a "landmark consensus," written in part by Portenoy, saying that there is little risk of addiction or overdose in pain patients. The consensus cited both the "less than 1 percent" addiction figure and the Porter and Jick letter.

In an interview released by Physicians for Responsible Opioid Prescribing in 2011, Portenoy admitted that he used the Porter and Jick letter, along with other similar studies on opioid use, to encourage more liberal prescribing of opioids:

None of [the papers] represented real evidence, and yet what I was trying to do was to create a narrative so that the primary care audience would look at this information in toto and feel more comfort about opioids in a way they hadn't before. In essence this was education to destigmatize [opioids] and because the primary goal was to destigmatize, we often left evidence behind.

Here's the full video:

When asked by Quinones years later about the letter, Jick called it "an amazing thing."

"That particular letter, for me, is very near the bottom of a long list of studies that I've done. It's useful as it stands because there's nothing else like it on hospitalized patients. But if you read it carefully, it does not speak to the level of addiction in outpatients who take these drugs for chronic pain."

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