Ketamine produces rapid antidepressant and antidepressant-like effects in both humans and animal models. However, its therapeutic benefits are tempered by psychoactive side effects, such as hyperlocomotion associated with enhanced dopaminergic activity in the ventral tegmental area (VTA). We tested the therapeutic effect of cannabidiol (CBD) on locomotor activity after systemic (30 mg/kg) or...
Treatment-resistant depression (TRD) remains a major clinical challenge, with inflammation increasingly implicated in its pathophysiology. C-reactive protein (CRP), an accessible biomarker, has emerged as a potential predictor of antidepressant response. While intravenous and intranasal ketamine have shown anti-inflammatory effects, evidence linking inflammation and clinical outcomes remains...
Cocaine and methamphetamine use disorders pose public health concerns due to the high propensity for relapse driven by persistent drug-associated memories. Output from the medial prefrontal cortex (mPFC) regulates relapse and is controlled by parvalbumin (PV) interneurons, which are surrounded by perineuronal nets (PNNs) that support precise PV neuron firing. We previously showed that removal...
Bloy et al. [1] provide an important and methodologically rigorous secondary analysis of the Ketamine for the reduction of Alcoholic Relapse (KARE) trial, examining whether acute psychoactive effects mediate the therapeutic impact of ketamine in alcohol use disorder (AUD). Their finding that dissociative and perceptual effects did not mediate abstinence outcomes is clinically relevant, and...
Recent retrospective analyses have shown that individuals with comorbid Substance Use Disorders (SUDs) are overrepresented among responders to ketamine for Treatment Resistant Depression (TRD). Ketamine is an effective treatment for depression and also a potential substance of misuse. The authors contrast a mechanistic pathway with a possible expectancy effect to account for these findings, and...
Esketamine (ESK), the dextrorotatory enantiomer of ketamine, is an antagonist of the N-methyl-D-aspartic acid (NMDA) receptor. ESK is considered an effective anesthetic because of its ability to mitigate postoperative pain and opioid use. Recently, it has attracted significant research attention for its fast-acting antidepressant effects. Given the advantages of ESK in both perioperative and...
Abstract Ketamine’s rapid neuropsychiatric actions emerge from interactions that span receptors, cells, and circuits, but their net effects on human neuronal population dynamics remain incompletely defined. Here we combine human dorsal forebrain organoids with high-density microelectrode arrays (MEAs) to quantify ketamine’s effects from spikes to networks. In 6-month-old organoids, acute...
Background: Anhedonia and reward-processing deficits are core features of major depressive disorder (MDD) that respond poorly to traditional antidepressants.Ketamine has rapid antidepressant effects, yet its neurofunctional actions within reward circuits remain unclear.We synthesized human neuroimaging evidence on ketamine-related modulation of reward circuitry and implications for...
Background Though esketamine was approved by the Food and Drug Administration (FDA) for treatment-resistant depression in 2019, there is no published research on implementation challenges. Therefore, the aim of this study was to investigate online commentary about these challenges among mental healthcare providers. Methods Using the terms “esketamine” and “Spravato”, the author searched social...
Treatment-resistant depression (TRD) accounts for approximately 30% of major depressive disorder cases and has been characterized by altered functional connectivity within and between the Default Mode (DMN) and Frontoparietal networks (FPN). Ketamine can be an effective treatment for TRD, and its antidepressant response has been associated with alterations in resting state functional...