Building the Perfect Painkiller

Opioid addiction can be seen as an infinite loop, a bug in the brain’s programming. Take drug. Feel better. Come down. Repeat.

Of the people who use opioid drugs recreationally, between 8 and 23 percent become addicted—sometimes fatally. That’s true whether the opioid drug is strictly prohibited, such as heroin, or a prescription painkiller that people use illegally, such as OxyContin or Vicodin. A smaller proportion of people who take prescription painkillers get hooked—less than 1 percent of people with no prior history of addiction.

In the United States, the world’s largest consumer of all types of drugs, these numbers add up: More than 2 million people are currently addicted to opioids, and nearly 5 million have taken them recreationally in the past month and may be at risk. Consequently, scientists have been searching for a “non-addictive opioid” since the 1800s—desperately seeking a compound that can match these drugs’ peerless pain relief without becoming irresistible.

Some elements of the addictive loop are well understood. The primary factor being that the drugs feel alluring, dreamy, and blissful to a fraction of the people who take them. Meanwhile, about 15 percent strongly dislike them, according to research on healthy volunteers.1

“Some people get nauseated,” says Nora Volkow, director of the National Institute on Drug Abuse. “They hate it.” (Dan Rather, who was given a shot of heroin by police

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