Regional Blood Flow Signatures of Opioidergic Modulation of Ketamine in Major Depressive Disorder: A Randomized Crossover Study

This study aimed to investigate whether modulation of the opioid system with naltrexone affects ketamine's acute impact on regional cerebral blood flow (rCBF) in individuals with major depressive disorder (MDD). The findings revealed that ketamine increased rCBF in specific brain regions regardless of naltrexone pretreatment, and that the relationships between rCBF changes and subjective and clinical outcomes were disrupted by naltrexone. These results suggest intricate interactions among glutamatergic, opioidergic, and GABAergic systems in the context of ketamine's antidepressant effects.