Objective The molecular mechanisms driving esketamine (ESK) efficacy in the pain-depression dyad (PDD) remain incompletely understood. This study investigated the effects of a sub-anesthetic ESK regimen on cortical expression profiles and exploratory signaling markers within the anterior cingulate cortex (ACC). Methods Male Sprague-Dawley rats were randomized into Sham, PDD, and PDD + ESK...
Stroboscopic light stimulation (SLS) and psilocybin each induce altered states whose phenomenology and neurophysiology partly overlap, including posterior alpha-band changes and visual imagery. The two states engage the alpha band through different operations - pharmacological suppression under psilocybin and frequency-selective visual drive under SLS. We formalize their possible interaction...
There is considerable interest in the concept that psychedelic compounds might facilitate reorganization of emotional processing with therapeutic benefit; in particular, amelioration of excessive focus on past, current and potential-future aversive events, a dominant emotional-cognitive state in stress-related affective disorders. Translational animal models can advance understanding of...
Background Major depressive disorder (MDD) is associated with multiple pathophysiological mechanisms, including dysregulation of monoaminergic systems, excessive glutamatergic activity, reduced neurotrophic support, inflammation, and oxidative stress. The combination of dextromethorphan, an N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, with bupropion, a...
Background Disruptions in the gut-brain-microbiota axis are increasingly linked to psychiatric disorders. While cannabinoids possess immunomodulatory and neuroprotective properties, their impact on the microbial architecture during critical neurodevelopmental periods remains poorly understood. This exploratory study investigated whether adolescent treatment with delta-9-tetrahydrocannabinol...
Background: Postoperative depressive symptoms may impair recovery and quality of life in patients undergoing breast cancer surgery. Esketamine has shown potential antidepressant and analgesic effects in the perioperative setting. This meta-analysis evaluated the efficacy and safety of perioperative esketamine for postoperative depressive symptoms in patients undergoing breast cancer surgery....
There is a need for characterizing more efficacious therapeutic strategies for glioblastoma multiforme to overcome treatment resistance to the standardized use of temozolomide as well as to better treat its debilitating comorbidities like depression. In this context, combination therapies, particularly cannabidiol with temozolomide exhibited additive or synergistic anti-tumor effects, capable...
Background: Traumatic brain injury (TBI) can result in prolonged post-concussive syndrome and chronic hypoxic-ischemic brain injury (HIBI) sequelae remains therapeutically challenging with the persistence of significant neurological and cognitive impairments. While conventional treatments often provide limited relief, emerging research explores alternative therapeutic interventions, including...
The rapid evolution of the novel psychoactive substances market has blurred the boundaries between synthetic “designer drugs” and other emerging psychoactive products distributed outside traditional regulatory frameworks. Recently, increasing recreational and self-therapeutic interest in Amanita muscaria has led to its growing presence within the broader landscape of substances used in patterns...
Major Depressive Disorder (MDD) is a highly prevalent and disabling psychiatric disorder, representing a major global health burden across all age groups. Increasing evidence indicates that its pathophysiology involves a complex interplay between chronic stress, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, immune activation, and neuroinflammation. Persistent HPA axis...
psychiatric disorders, beta-carbolines, trace amine, phosphoproteomics, social hierarchy. Scientific interest in psychedelic substances has re-emerged, offering new perspectives on the treatment of neuropsychiatric and neurological disorders.Historically, psychedelics have been associated with a wide spectrum of positive and negative effects, encompassing ritualistic and spiritual use,...
Neuropsychiatric disorders affect nearly one billion people worldwide, yet many existing psychopharmacological treatments are limited by adverse effects, drug interactions, and variable efficacy. Ethnopharmacological knowledge embedded in Indigenous health systems offers important perspectives for understanding mental and neurological distress and for informing future research on central...
Objective To evaluate outcomes of different doses of esketamine in postoperative patient-controlled intravenous analgesia (PCIA) combined with preoperative intercostal nerve block (ICNB) analgesia protocol for acute postoperative pain (APP) relief in patients undergoing thoracoscopic lobectomy. Materials and methods A total of 360 patients scheduled for thoracoscopic lobectomy at Xuzhou Central...
Esketamine, the S-enantiomer of ketamine, is a rapid-acting antidepressant approved for treatment-resistant depression (TRD) when used in combination with an oral antidepressant. Identifying reliable clinical or genetic predictors of treatment response remains a critical unmet need. This study aimed to evaluate the impact of selected clinical and genetic variables on esketamine response in a...
This study systematically evaluated the safety profile of esketamine for treatment-resistant depression through a meta-analysis, focusing on dose-dependent adverse events and associated risk factors to inform precision dosing. PubMed, Embase, the Cochrane Library, the Mainland China Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI) and Wanfang databases...
In humans, empathy is expressed through various prosocial behaviours between individuals that may be enhanced after intake of the synthetic entactogen MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") as the behavioural expression of the so-called entactogenic syndrome. Rodents may also exhibit empathy-like behaviours, such as social interaction and helping behaviour. In this regard, while...
Classical serotonergic psychedelics (e.g., LSD, psilocybin, DMT) alter perception and neuroplasticity primarily via 5-HT2A receptor activation and downstream Ca2+-dependent signaling cascades. Here we propose a speculative yet falsifiable pharmacological hypothesis that these drug-induced biochemical cascades might interface with quantum-mechanical processes in the brain. We focus on nuclear...
N-Cyclohexyl butylone and N-cyclohexyl methylone are cathinones found on the street that produce morbidity and mortality, but are not yet legally controlled, and there has been little or no pharmacological testing of these compounds. Both compounds have a large moiety on the N-position that may alter their pharmacological effects. Locomotor stimulant effects of N-cyclohexyl butylone and...
The serotonin 2A receptor (5-HT2A) is a Gq/11-coupled receptor implicated in reward processing, neuropsychiatric disorders, and the actions of serotonergic psychedelics. Although 5-HT2A activation has been shown to engage endocannabinoid (eCB) signaling in several brain regions, its role in inhibitory synaptic plasticity within the nucleus accumbens (NAc) remains poorly understood. Here, we...
This article proposes that ibogaine’s induction of GDNF, modulation of glutamate and dopamine signaling, and reopening of plasticity represent a unified mechanism capable of restoring reward system fidelity across disorders. This includes addiction, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and eating disorders, amongst others. These conditions are labelled as...
As a therapy for postoperative analgesia, esketamine shows relatively favorable efficacy in pain control and is associated with a lower risk of postpartum depression. However, this result is unstable. Furthermore, esketamine may increase the risk of dizziness in pregnant women aged over 30 years. Since all the experiments in this study are conducted in China, there are certain regional...
Background 4-substituted 2,6-dimethoxyphenethylamines and the corresponding amphetamines (so-called pseudo [Ψ] derivatives) are a hitherto mostly unexplored group of psychedelics. Still, preliminary investigations indicate that these derivatives are promising and potent psychedelics in humans. In this study, we examined the monoamine receptor and transporter interaction properties of several...
Introduction Metabolic and gut microbiota (GM) disturbance play a significant role in the complex pathogenesis of substance dependence. Although levo-tetrahydropalmatine (l-THP) demonstrates therapeutic potential in drug addiction, the underlying mechanism remains elusive. Methods The efficacy of l-THP was assessed using a conditioned place preference (CPP) paradigm. In this research, we...
This trial aims to provide Level I evidence comparing the respiratory depression risk between esketamine-based and fentanyl-based analgesia during HHNB-guided liver ablation. Should esketamine prove to be demonstrably superior in terms of respiratory safety, HHNB-esketamine has the potential to be a viable treatment option.
In recent years, psychiatry has witnessed a renaissance in the investigation of psychedelic compounds, a broad class of psychoactive substances that induce altered states of consciousness, often characterized by changes in perception, mood, and cognition, which were largely shelved following regulatory crackdowns in the 1970s. The renewed interest is driven by a mounting crisis in mental health...