The cognitive neuroscience of ketamine in major depression.
Brain : a journal of neurology June 30, 2025 Sara Costi, Chloe Wigg, Erdem Pulcu et al. 3 citations
Ketamine, long used as an anesthetic, was first identified in 2000 as a fast-acting antidepressant. A single dose alleviates depressive symptoms, including anhedonia, within hours, and effects last for days. Research in animals indicates ketamine rapidly influences brain regions involved in punishment and reward processing, reverses negative affective biases in memories, and promotes stress resilience. Translating these findings to humans is ongoing, with emerging evidence suggesting similar mechanisms in healthy volunteers and patients. Clinical use is limited by acute side effects and unknown long-term safety. Understanding ketamine's mechanisms may guide development of safer rapid-acting antidepressants.