While the opioid epidemic continues kill more than 40 Americans every day, researchers and health experts are frantically searching for ways to curtail use of the highly addictive, pain-quenching drugs. In March, the Centers for Disease Control and Prevention even released new guidelines directing doctors to simply refrain from prescribing opioids. But if a new study holds up, the health agency may be able to reverse course.

According to a report in the Proceedings of the National Academy of Sciences, an opioid drug referred to as BU08028 was able to alleviate pain in a dozen monkeys just as well as other opioid painkillers, such as morphine. Yet, unlike every other opioid drug, BU08028 showed no signs of being addictive. Even at high dose—at which other opioid drugs inhibit the respiratory and cardiovascular system, which can be fatal—BU08028 was harmless.

"Based on our research, this compound has almost zero abuse potential and provides safe and effective pain relief," Mei-Chuan Ko, a professor of physiology and pharmacology at Wake Forest Baptist Medical Center and lead author of the study, said in a statement. "This is a breakthrough for opioid medicinal chemistry that we hope in the future will translate into new and safer, non-addictive pain medications."

In pain experiments, which involved dipping monkeys' tails into hot water, BU08028 was a potent pain-killer. A single dose relieved pain for up to 30 hours. Next, in experiments in which the monkeys were trained to self-medicate, BU08028 proved no more habit-forming than a control dose of saline. Scientists forced one group of monkeys to take BU08028, while another group was forced to take morphine. When the drugs were taken away, the monkeys who had taken BU08028 showed no withdrawal symptoms, unlike the monkeys who had blazed on morphine.

BU08028's lack of nasty side-effects may hinge on its dual-action biochemistry. Like other opioids, it controls pain by targeting the nervous system's classic μ-opioid peptide receptors, called MOP receptors. But BU08028 also targets “nonclassical” opioid receptors, called NOP receptors for nociceptin receptors, in the nervous system. These receptor proteins generally don’t interact with opioid drugs, yet they share similarities with the receptors that do. NOP receptors regulate pain, like their MOP counterparts, but they are also involved in a host of other brain functions, such as memory, cardiovascular functions, and anxiety.

“To our knowledge, the present study provides the first functional evidence in nonhuman primates that BU08028 with mixed MOP/NOP agonist activities is an effective and safe analgesic without apparent abuse liability or other opioid-associated side effects,” the authors conclude.

Next, the researchers hope to test BU08028 at treating chronic pain without risks of addiction or overdoses. Regardless of BU08028's fate in subsequent trials, the researchers are hopeful that the strategy of co-activating NOP and MOP receptors will eventually lead to a safer painkiller.

Proceedings of the National Academy of Sciences, 2016. DOI: 10.1073/pnas.1605295113 (About DOIs).