N-methyl-D-aspartate Receptors and Depression: Linking Psychopharmacology, Pathology and Physiology in a Unifying Hypothesis for the Epigenetic Code of Neural Plasticity.

Uncompetitive NMDAR (N-methyl-D-aspartate receptor) antagonists restore impaired neural plasticity, reverse depressive-like behavior in animal models, and relieve major depressive disorder (MDD) in humans. This review integrates recent findings from in silico, in vitro, in vivo, and human studies of uncompetitive NMDAR antagonists into the extensive body of knowledge on NMDARs and neural plasticity. Uncompetitive NMDAR antagonists are activity-dependent channel blockers that preferentially target hyperactive GluN2D subtypes because these subtypes are most sensitive to activation by low concentrations of extracellular glutamate and are more likely activated by certain pathological agonists and allosteric modulators.

Pharmacological characterization of cannabidiol as a negative allosteric modulator of the 5-HT receptor.

Promising clinical evidence suggests that psychedelic compounds, like lysergic acid diethylamide (LSD), have therapeutic value for treatment of psychiatric disorders. However, they often produce hallucinations and dissociative states, likely mediated by the serotonin (5-HT) receptor 5-HT, raising challenges regarding therapeutic scalability. Given the reported antipsychotic effects of cannabidiol (CBD) and its promiscuous binding at many receptors, we assessed whether CBD could modulate 5-HT signalling.

Genomics and pharmacogenomics of cluster headache: implications for personalized management? A systematic review.

The role of genetic factors in cluster headache etiology, suggested by familial and twin studies, remains ill-defined, with the exact pathophysiological mechanisms still largely elusive. This systematic review aims to synthesize current knowledge on cluster headache genetics and explore its implications for personalized treatment and prediction of treatment response. Thus, we searched PubMed, Scopus, and the Cochrane Library databases and reference lists of identified research articles, meta-analyses, and reviews to identify relevant studies up to 10 July 2024.

The clock is ticking on schizophrenia: a study protocol for a translational study integrating phenotypic, genomic, microbiome and biomolecular data to overcome disability.

Background: Shared biological factors may play a role in both the cognitive deficits and the increased prevalence of metabolic syndrome observed in individuals with Schizophrenia (SCZ). These factors could entail disturbances in tryptophan (Trp) to both melatonin (MLT) and kynurenine (Kyn) metabolic pathways, as well as inflammation and alterations in the gut microbiome composition.

Methods: The present research project aims to investigate this hypothesis by recruiting 170 SCZ patients from two different recruitment sites, assessing their cognitive functions and screening for the presence of metabolic syndrome.

Melatonin, Melatonin Receptors and Sleep: Moving Beyond Traditional Views.

Sleep, constituting approximately one-third of the human lifespan, is a crucial physiological process essential for physical and mental well-being. Normal sleep consists of an orderly progression through wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, all of which are tightly regulated. Melatonin, often referred to as the "hormone of sleep," plays a pivotal role as a regulator of the sleep/wake cycle and exerts its effects through high-affinity G-protein coupled receptors known as MT1 and MT2.