Ketamine, a dissociative anesthetic, induces behavioral and molecular alterations associated with psychosis-like phenotypes. However, the epigenetic mechanisms bridging its cellular effects with behavioral outcomes are poorly defined. Here, we report that ketamine induces histone H3 Ser10 phosphorylation in both hippocampal neurons (HT22 cells) and the mouse hippocampus, an effect primarily...
Background: Treatment-resistant depression (TRD) is associated with substantial functional impairment, suicide risk, and health-care costs. Ketamine and its S-enantiomer, esketamine, have emerged as rapid-acting glutamatergic treatment options for TRD. Aim: This review aims to synthesize current evidence on the different ketamine administration routes for TRD, with a focus on acute and...
Ketamine has emerged as a promising rapid-acting treatment for mood disorders and suicidality. Notwithstanding its replicated antidepressant efficacy, ketamine-associated risk for abuse, dependence, and misuse remain. We conducted a systematic review of clinical and preclinical studies from database inception to August 2025, including randomized and observational trials, open-label extensions,...
This study aimed to investigate a set of pharmacodynamic biomarkers reflecting acute, delayed and sustained central nervous system effects of S-ketamine, used as a tool compound for rapid-acting antidepressant activity, with the goal of informing biomarker strategies for delayed antidepressant effects. In this randomized, double-blind, double-dummy, placebo-controlled, 4-way crossover study in...
Background Methamphetamine use disorder (MAUD) is associated with substantial psychiatric and physical morbidity, and current treatment options remain limited. Ketamine-assisted psychotherapy (KAP) has shown promise in substance use disorders, but little is known about how individuals experience and interpret this intervention, particularly in MAUD. Qualitative investigation may provide insight...
Protective Effects of Gallic Acid on Oxidative and Inflammatory Markers in the Hippocampus and Prefrontal Cortex of a Ketamine-Induced Schizophrenia-like Model.
Introduction and purpose. Major depressive disorder is a serious clinical problem. Current treatments are often unsuccessful, and many patients do not achieve full remission. In a reanalysis of the STAR*D study, the cumulative remission rate after up to four treatment steps was about 41%, which highlights the limitations of currently available antidepressant strategies[1]. In recent years,...
Ketamine offers rapid relief for treatment-resistant depression and severe pain in the clinic, providing immediate benefits that traditional medications often fail to deliver. While its antagonistic action at the N-methyl-D-aspartate receptor (NMDAR) is a key mechanism, ketamine's dual nature as both a promising treatment and a drug with abuse potential suggests its therapeutic effects extend...
Background: In HT-22 cells, 500 μM NMDA was used as a high-concentration oxidative stressor rather than a classical NMDA receptor-mediated excitotoxic stimulus. Because HT-22 cells lack functional ionotropic NMDA receptors, this model cannot test NMDA receptor antagonist-mediated pharmacology. Methods: HT-22 cells and C8-D1A astrocytes were examined in a Transwell co-culture system. CCK-8...
Major depressive disorder (MDD) is a leading cause of disability worldwide, and currently available antidepressants remain limited by delayed onset of action, incomplete response, and adverse effects. Ketamine is a rapid-acting antidepressant, whereas xanomeline, an M1/M4 muscarinic receptor agonist, may represent a mechanistically distinct non-monoaminergic strategy. However, the molecular...