(iStock)

When the emergency team arrived, it was already too late. The 24-year-old man, who had a history of opioid addiction, was not breathing and lacked a pulse. His case report, recently published in the Annals of Emergency Medicine, includes an unusual detail along with this all-too-typical tragedy: The responders found a half-dozen boxes of loperamide — a popular anti-diarrhea medication, sold over the counter as Johnson & Johnson’s Imodium or Medique’s Diamode — all completely empty.

Long considered an innocuous drug — the Centers for Disease Control recommends it for travelers who find themselves abroad with the runs — loperamide has been swept up in America’s ongoing opioid epidemic. Four in 10 Americans say they know someone addicted to opioid painkillers such as hydrocodone and oxycodone, not to mention those who are addicted to illegal opioids such as heroin. In a 2014 Senate testimony, the director of the National Institute on Drug Abuse, Nora D. Volkow, said that 2.1 million people in the United States were abusing or addicted to pain relievers.

Some of these people, pharmacists fear, are now turning to loperamide to reduce their symptoms. Or to achieve euphoria.

“Loperamide’s accessibility, low cost, over-the-counter legal status and lack of social stigma all contribute to its potential for abuse,” William Eggleston, an author of the case study and a pharmacist at Upstate New York Poison Center, said in a news release. Timed with their report, Eggleston and his colleagues released a searing statement against loperamide abuse on Tuesday, calling it “dumb and dangerous.”

The active ingredient in loperamide is an opioid, as is the active ingredient in Vicodin, Oxycontin and Percocet. But unlike the latter trio of drugs, loperamide is not used as a painkiller. Humans have opioid receptors in our guts and in our brains. Typical opioids can access both types of receptors. In fact, because painkillers can induce constipation when they interact with the intestine — and because so many Americans now take opioids — an ad for opioid relief made it to the commercials during the Super Bowl.

AstraZeneca's 2016 super bowl ad features a man looking for relief from constipation due to opioid use. (AstraZeneca)

But loperamide seemed to be different: all gut, no brain. A membrane called the blood-brain barrier, the popular thinking went, prevented the drug from stimulating the receptors in our heads.

The Food and Drug Administration approved loperamide in the 1970s, and early pharmacological trials left experts feeling confident the likelihood of addiction was low. “Loperamide poses little threat of potential abuse,” concluded one 1980 study in the journal Clinical Pharmacology and Therapeutics; the researchers reported that men randomly given codeine, a placebo or loperamide rarely reported loperamide as “dope” and “‘liked’ little or not at all.”

A few decades later, as the number of Americans addicted to opioids rises, loperamide’s fate changed. By 2013, reports of loperamide being used recreationally had circled the Web long enough for loperamide to pick up a nickname: “poor man’s methadone.”

A 2012 study of nearly 1,300 posts on online drug forums determined that people were dosing themselves with 70 to 100 milligrams of loperamide. The maximum recommended dose for diarrhea relief is 16 milligrams a day. As Eggleston put it: “People looking for either self-treatment of withdrawal symptoms or euphoria are overdosing on loperamide with sometimes deadly consequences.”

Just how significant a problem loperamide poses is uncertain. Eggleston and his colleagues believe that the Web-forum data, coupled with an influx of calls to poison-control centers, indicate loperamide abuse is on the rise. Between 2011 and 2014, according to their statement, U.S. poison-control calls reflected a 71 percent increase in people dosing themselves with high amounts of loperamide.

That doesn’t mean everyone should abstain from taking anti-diarrhea medication. In the recommended doses, the pharmacists note, loperamide is safe.

But it does indicate that the potential for abuse is real. Eggleston and his co-authors conclude their paper by urging the FDA to limit the sales of loperamide, in the same way that Sudafed and other over-the-counter cold medicines containing pseudoephedrine are sold only in small batches. “This is another reminder that all drugs, including those sold without a prescription,” he said, “can be dangerous when not used as directed.”

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