For individuals with treatment-resistant depression, ketamine can be an effective fast-acting alternative to conventional antidepressants. It has been hypothesized that it partly exerts its antidepressant effects by modulating the opioid system. In this podcast, Dr. Brandi Quintanilla discusses her study that explored baseline plasma levels of κ-opioid and dynorphin peptides and changes after ketamine infusion. Participants in this randomized trial included individuals with major depressive disorder and healthy volunteers. The results suggest that κ-opioid and dynorphin levels in plasma may not be a major underlying mechanisms of ketamine's therapeutic effects or its dissociative adverse effects. The study, however, may have been underpowered to detect effects, and additional research is needed. Dr. Quintanilla is a psychiatry resident at the University of Texas Health Science Center at Houston and a special research volunteer in the Experimental Therapeutics and Pathophysiology Branch of the National Institute of mental health. The article by Dr. Quintanilla and colleagues is published in the March-April 2023 issue of the Journal of Clinical Psychopharmacology.