Opioid drugs like morphine and fentanyl are a mainstay of modern pain medicine. But they also cause constipation, are highly addictive, and can lead to fatal respiratory failure if taken at too high a dose. Scientists have long sought to develop new opioid drugs that can drive away pain without these dangerous side effects, but holes in our understanding of exactly how opioids exert their various effects at a biological level has so far kept this dream at bay.