Ketamine and Evolving Neuroplasticity.
Clinical drug investigation June 13, 2026 Angel Prabakar
Ketamine provides rapid antidepressant effects for treatment-resistant depression by blocking NMDA receptors, which triggers glutamatergic signaling that promotes synaptic plasticity and neurogenesis. This review synthesizes preclinical and clinical evidence on how these neuroplastic changes unfold over hours to days, linking molecular mechanisms like BDNF signaling and mTOR pathway activation to improvements in mood, motivation, cognition, and functional outcomes. It emphasizes the temporal trajectory of ketamine's effects and offers a plasticity-centered model to integrate neuroscience with clinical psychiatry, while identifying gaps in translational research for optimizing fast-acting antidepressants.