Current Neuropharmacology
January 1, 2025
Wei Zheng, Limei Gu, Jianqiang Tan et al.
1 citation
Repeated intravenous ketamine infusions rapidly reduce anhedonia in both younger and older adults with major depressive episodes, but older patients show a weaker response. In a study of 135 patients (116 younger, 19 older) receiving six ketamine infusions over 12 days, anhedonia scores dropped significantly in both age groups within 4 hours of the first infusion, with effects maintained throughout treatment. By day 26, younger patients had lower anhedonia scores than older patients. The antianhedonic response rate was 51.7% in younger patients versus 31.6% in older patients, and remission occurred in 24.1% of younger patients but none of the older patients.
Current Neuropharmacology
June 30, 2026
Jiaying Wang, Rui Zhang, Yuanyuan Ma et al.
Prenatal exposure to ketamine or its analog 2-fluorodeschloroketamine disrupts mitochondrial energy production in developing brain cells, increasing the risk of neurological damage. Using human cerebral organoids and single-cell RNA sequencing of 83,436 cells, the study found that both substances altered gene networks controlling mitochondrial oxidative phosphorylation in cortical cells. Experiments in fetal mouse neurons confirmed that exposure increased mitochondrial fragmentation and oxidative stress while reducing ATP production capacity. These energy disruptions during rapid brain development can make offspring more vulnerable to neurological issues. The results provide direct evidence of neurodevelopmental toxicity from these substances and identify mitochondrial dysfunction as a probable primary molecular mechanism.
Current Neuropharmacology
April 28, 2026
Hongshuang Wang, Xiaobing Li, Feng Yu et al.
Combining psychedelics with music in therapy may improve mental health outcomes by acting on specific brain mechanisms. Psychedelics like psilocybin activate 5-HT2A receptors and BDNF-TrkB signaling, increase neural plasticity, and desynchronize the default mode network, while music guides emotional processing and amplifies psychological insights. This synergy shows promise for treating depression, PTSD, and addiction. The review provides a mechanistic framework for understanding these interactions and identifies neurobiological targets for optimizing future therapeutic protocols.
Current Neuropharmacology
April 16, 2026
Xiangying Wei, Shan Xu, Zhaoqiong Zhu
General anesthetics such as ketamine, propofol, isoflurane, and certain opioids show rapid and sustained antidepressant effects in both preclinical and clinical settings, offering a new therapeutic avenue for treatment-resistant depression, which affects about one-third of patients. These effects go beyond traditional monoamine regulation, involving modulation of glutamate and GABA signals and restoration of synaptic plasticity in damaged brain circuits. Despite the promise, balancing benefits against risks and establishing consistent treatment guidelines remain critical for developing new rapid-acting antidepressants for patients who do not respond to standard care.
Current Neuropharmacology
March 4, 2022
Radharani Benvenutti, Matheus Gallas‐lopes, Matheus Marcon et al.
NMDAR antagonists like MK-801 and ketamine induce behavioral changes in zebrafish that model schizophrenia symptoms, including social interaction and memory deficits, but results for locomotor and exploratory behaviors are mixed. A review of 44 studies found that zebrafish are a suitable alternative to rodents for studying these drug-induced phenotypes, though more research is needed to understand species differences.
Current Neuropharmacology
January 1, 2016
George T Taylor, Francesca Manzella
Opioids, long known for pain and addiction, are now recognized as central to mood regulation, potentially shifting focus from monoamine neurotransmitters to opioid systems in depression. Dynorphin, the last major endogenous opioid discovered, and its kappa receptor have distinct, often opposite effects from mu-receptor opioids like beta-endorphin and morphine. This review examines dynorphin/kappa neurobiology in relation to major depressive disorder (MDD). Salvinorin A, a plant-based kappa agonist, shows a complex pharmacological profile beyond kappa agonism, making it a promising candidate for MDD treatment research.