Diprenorphine couldbe used as an improved overdose reversal agent due to its quick onsetand its effectiveness in reversing fentanyl- and morphine-inducedrespiratory depression.2 However, whileoften described as a MOR, KOR, and DOR opioid antagonist, diprenorphineshows partial agonist activity at both KOR and DOR;6 the former is substantial enough to cause psychotomimeticeffects in humans,7 limiting its utility.Therefore, an improved rescue medication should retain diprenorphine’sMOR antagonism, rapid onset, and potency versus fentanyl but withreduced KOR agonist activity. Here, OPRK1 is linked to major depressive disorder.