As the opioid crisis continues to ravage U.S. communities, scientists and drug companies have intensified their efforts to develop safer and less addictive pain medications. Now, multiple research groups are claiming progress in devising novel opioids—or alternatives—that seem to offer pain relief with far less risk of addiction or of the opioid-induced respiratory depression that all too commonly leads to death.

Most of these studies have only been done in animals, so the experimental compounds face significant hurdles before they can become approved medications. Yet they are raising tentative hopes among researchers. “It’s encouraging,” says Laura Bohn, a biochemist at Scripps Research in Jupiter, Florida. “There has been a really big push to develop nonopioid pain relievers. But it has been really hard.”

A record 72,000 people in the United States died last year from overdoses, up nearly 10% from 2016, according to a recent estimate by the Centers for Disease Control and Prevention. That rise was driven primarily by an increase in overdoses from highly potent synthetic opioids such as fentanyl and carfentanil. Another 2.1 million Americans are believed to regularly abuse opioids, including natural ones like morphine, semisynthetic compounds such as oxycodone, and the synthetics, and have signs of addiction, such as withdrawal symptoms, if they try to quit.

Robert F. Service/Science