The Antioxidant Activity of Ketamine: Threshold-Dependent Mechanism in Treatment-Resistant Depression?
Research Square February 17, 2026 Zofia Winczewska, Magdalena Górska‐ponikowska, Wiesław Jerzy Cubała
Ketamine at 25 ng/mL increased the viability of mouse hippocampal HT22 neuronal cells exposed to hydrogen peroxide, but only at the highest concentration tested (1000 µM H₂O₂). At that level, cell viability rose from 12% (±1.63%) without ketamine to 38% (±9.12%) with ketamine. This suggests a protective, nonlinear effect that depends on the intensity of oxidative stress, activating only at critical H₂O₂ overload typical of severe depression. The findings indicate a threshold antioxidant mechanism that may contribute to ketamine's antidepressant action and inform future predictive models for individualized treatment.