Researchers found direct structural evidence that ketamine binds to and partially activates all three major human opioid receptors, alongside its established NMDA receptor action.

A team led by Tao Che at Washington University School of Medicine found that ketamine binds to and activates mu, kappa and delta opioid receptors, with stronger effects at mu and kappa. Cryo-electron microscopy showed ketamine occupying the receptors’ primary binding pocket. The findings may help explain ketamine’s effects and inform its clinical use, but do not establish that opioid activity causes its antidepressant effects.