Ketamine-From an Anesthetic to a Psychiatric Drug: Mechanisms of Action, Clinical Applications and Potential Risks.

Ketamine, originally developed as an anesthetic, also provides potent pain relief by blocking NMDA receptors, which helps reduce chronic and neuropathic pain. It shows promise for treating substance use disorder by disrupting maladaptive reward memories and promoting neuroplasticity. Additionally, S-ketamine produces rapid antidepressant effects in treatment-resistant depression, likely through increased glutamatergic signaling and synaptic plasticity. This broad therapeutic profile makes ketamine a unique agent spanning anesthesia, pain management, addiction medicine, and psychiatry, though further research into its mechanisms and long-term effectiveness is needed.

Study at a glance

Abstract

Ketamine, originally developed as an anesthetic, is gaining increasing attention due to its multifaceted pharmacological properties. In addition to its use in anesthesia, ketamine exerts potent analgesic effects via N-methyl-D-aspartate (NMDA) receptor antagonism, modulating pain perception and reducing central sensitization, particularly in chronic and neuropathic pain conditions. Emerging evidence also supports ketamine's potential in the treatment of substance use disorder, where it may disrupt maladaptive reward-related memories and promote neuroplasticity which facilitates behavioral change. Moreover, in recent years, S-ketamine has shown rapid and potent antidepressant effects, especially in treatment-resistant depression (TRD), probably due to increased glutamatergic signaling, synaptic plasticity and the release of neurotrophic factors. This heterogeneous therapeutic profile positions ketamine as a unique agent at the interface of anesthesia, pain management, addiction medicine and psychiatry, warranting further exploration into its mechanism and long-term effectiveness.