The Potential Role of the Endogenous Opioid System in the Antidepressant Effect of Ketamine

Abstract

The noncompetitive NMDA receptor blocker ketamine provides significant improvement to patients suffering from depression but its mechanistic pathways are not fully understood. The endogenous opioid system is known to be dysregulated in patients with depression. Ketamine is known to interact with the opioid system either directly or indirectly through the release of endogenous opioids. In this review, I am discussing the potential role that might be played by the endogenous opioid system in conferring the antidepressant effect of ketamine and emphasizing that the modulation of the opioid system by ketamine warrants in-depth investigation for potential antidepressant effect.