Search Results (559)

Anxiety disorders are characterized by dysregulation of monoaminergic signaling and remain a significant therapeutic challenge due to limitations associated with current pharmacological treatments. In this context, the essential oil of Morisonia flexuosa (Capparaceae) seeds was chemically characterized and evaluated for anxiolytic-like activity in adult zebrafish. Chemical profiling by GC–MS and GC–FID revealed a predominance of isothiocyanates, particularly butyl isothiocyanate (42.60%) and isobutyl isothiocyanate (42.28%). Acute toxicity assessment demonstrated no lethality at the tested doses. Behavioral analyses showed a significant increase in light preference in the light/dark paradigm, with moderate locomotor reduction insufficient to account for the behavioral shift solely by sedation. Pharmacological antagonism assays indicated that the anxiolytic-like effect was predominantly mediated by 5-HT1 and 5-HT2A/2C receptors. Chemometric analyses (PCA, HCA, and heatmap) revealed statistical association between compound abundance and behavioral endpoints, supporting the contribution of major isothiocyanates within the tested model. Notably, the strongest behavioral response was observed at the lowest concentration, suggesting an ideal effective concentration range. Collectively, these findings provide the first evidence that an isothiocyanate-rich essential oil from M. flexuosa exerts serotonergic-involved anxiolytic-like effects in zebrafish and supports further mechanistic investigation of its neuropharmacological potential. Full article

Background/Objectives: Anxiety disorders in people over 65 y of age are common. Treatment of those disorders is often based on studies involving much younger patients. Experience shows that those treatments are regularly ineffective in the elderly, due to differences in physiology and the disparate etiology of the disease. Here, we examine current trends in research to generate data for evidence-based approaches to treat anxiety disorders in the elderly. Our objective was to evaluate the scope, methodological characteristics, and therapeutic focus of current clinical trials for anxiety disorders in the elderly, and to determine whether the existing evidence pipeline is likely to meet the substantial unmet need for effective and well-tolerated treatments. Methods: We searched clinicaltrials.gov for studies addressing “Anxiety disorder” and related readouts and selected those studies that included patients older than 65 y, and that had anxiety measures as primary or secondary endpoints. Results: We find that over 99% of clinical “anxiety” trials exclude patients older than 65 y. Sixty-six trials fulfilled our inclusion criteria. Trials specifically recruiting the elderly are a rare exception. Unexpectedly, only 10 “anxiety” trials are sponsored by the pharmaceutical industry, despite the potential rewards in such investments. Discussion and Conclusions: Although most clinical trials are registered in clinicaltrials.gov., our work is limited by the fact that not all clinical trials carried out world-wide are included in that database. Our findings indicate that ongoing clinical research supporting evidence-based recommendations for the treatment of anxiety in the elderly is scarce. Detailed secondary analysis of clinical trial results for the efficacy and safety of anxiolytics in various age cohorts may at least be a useful instrument for hypothesis generation, to trigger additional clinical research specifically designed to address anxiety treatment in the elderly. Full article

Delta-3-carene (CAR), a monoterpene derived from plant essential oils, exhibits promising biological properties, including anti-inflammatory, antioxidative, anxiolytic, and antimicrobial activities. Therefore, this study aimed to investigate the anti-inflammatory effects of CAR by analyzing the activity of this terpene on leukocyte activation through the evaluation of cell migration in in vitro and in vivo models. Cell viability analysis demonstrated that CAR (3, 10, 30, and 90 μg/mL) exerted no cytotoxic effects and significantly reduced in vitro neutrophil chemotaxis toward N-formylmethionyl-leucyl-phenylalanine (fMLP). Furthermore, CAR decreased phagocytosis in zymosan-stimulated neutrophils in vitro. In Swiss mice, oral CAR treatment, at doses of 25, 50, and 100 mg/kg, reduced inflammatory and antinociceptive parameters in zymosan-induced peritonitis, carrageenan-induced paw edema and mechanical hyperalgesia, and nociception induced by acetic acid and formalin models. In the persistent inflammation model (for 21 days) induced by complete Freund’s adjuvant (CFA), daily CAR treatment (50 mg/kg) reduced paw edema and mechanical hyperalgesia in all evaluated times at 6, 11, 16, and 21 days after CFA-induced inflammation. In conclusion, our data demonstrated that CAR modifies acute and chronic inflammatory responses, highlighting its potential therapeutic application in managing inflammation and pain. Full article

Background/Objectives: Preoperative anxiety is common in adult patients undergoing oral and dentoalveolar surgical procedures under local anesthesia and may impair cooperation, physiological stability, and overall treatment experience. While intravenous sedation and general anesthesia provide effective anxiolysis, they increase anesthetic exposure and recovery demands. Targeted preoperative anxiolysis offers a less invasive strategy to reduce anxiety while preserving responsiveness. However, approaches vary and standardized protocols are lacking. This systematic review evaluated the efficacy and safety of preoperative anxiolytic interventions—including both pharmacological and non-pharmacological strategies—in adult patients undergoing oral surgical procedures under local anesthesia without general anesthesia or deep sedation. Methods: The review adhered to the PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420261281592). Randomized and quasi-randomized controlled trials published between 2016 and 2026 were identified through structured searches of PubMed/MEDLINE, ScienceDirect, and Springer Nature Link. Eligible studies included adult patients undergoing oral surgery under local anesthesia and evaluated preoperative anxiolysis using validated instruments such as the Dental Anxiety Scale (DAS), State–Trait Anxiety Inventory (STAI), and Visual Analog Scale for Anxiety (VAS-A). Risk of bias was assessed using the Cochrane RoB 2 tool. Owing to methodological heterogeneity, results were synthesized narratively. Results: Eight trials (n = 617) met the inclusion criteria. Interventions included oral benzodiazepines, melatonin, pregabalin, herbal agents, nitrous oxide, and auriculotherapy. Benzodiazepines consistently reduced anxiety scores (p < 0.05) without significant interagent differences. Pregabalin at a dose of 150 mg significantly lowered STAI-S and VAS-A scores (p < 0.001). Passiflora incarnata was comparable to midazolam and superior to placebo, whereas Erythrina mulungu showed no effect. Melatonin results were inconsistent. Hemodynamics remained stable, and adverse events were mild. Conclusions: Preoperative anxiolysis under local anesthesia effectively reduces anticipatory anxiety in oral surgery, with benzodiazepines demonstrating the most consistent efficacy. Further standardized trials are warranted. Full article

Background: Preoperative anxiety and postoperative pain are prevalent and are frequently associated with poor postoperative functional outcomes. Comprehensive postoperative management, including both pharmacological and psychological components, is essential for proper postoperative care and better recovery. While the analgesic effect of traditional non-pharmacological intervention, such as cognitive behavior therapy, has been investigated by other trial studies, the newer innovative methods for delivering psychological interventions for reducing anxiety and pain are extensively being investigated. Virtual reality (VR) has emerged as a novel and promising technology that offers opportunities to mitigate patient perception and cognitive responses, and has been shown to be associated with lower levels of anxiety and pain. The aim of this randomized clinical trial (RCT) is to determine whether delivering the psychological content through virtual reality (VR) along with the standard preoperative and postoperative care results in better anxiety and pain relief outcomes than standard care in patients undergoing spinal surgery. Methods: This study protocol outlines a parallel-group RCT to be conducted in the Department of Neurosurgery at the University Clinical Hospital of Medical University of Lodz. The objective is to assess the efficacy of immersive VR environments in reducing preoperative anxiety and postoperative pain intensity in the following day after surgery. Adult patients (18–70) will be randomly assigned to either (1) standard care before surgery (control group), (2) VR exposure simulating the hospital environment alongside standard care, or (3) VR-based exposure to calming natural landscapes accompanied by soothing background sound along with standard care. In each group, a minimum of 50 patients will be recruited. The primary outcome is the change in preoperative anxiety measured using the State-Trait Anxiety Inventory-State (STAI-S) scale from baseline to immediately after intervention. Secondary outcomes include postoperative pain measured using the Visual Analogue Scale (VAS), postoperative analgesic consumption, patient satisfaction, and VR-related adverse effects. To facilitate a comprehensive understanding of the VR intervention’s impact, the primary outcome will be complemented with measures of the adverse effects, level of immersion, and level of presence in the VR environment. Secondary outcomes of self-reported satisfaction scores and postoperative analgesics from patients’ medical charts will be assessed. Conclusions: This trial will evaluate whether VR-based interventions may reduce preoperative anxiety and postoperative pain in patients undergoing spine surgery. This study may provide evidence supporting the future implementation of VR as a non-pharmacological adjunct in perioperative care. This intervention may hold significant clinical relevance clinically, particularly in patients with high level of preoperative anxiety, by offering an alternative method to pharmacological anxiolytics in the future. Full article

Dihydrosanguinarine (DHSA) is a naturally occurring benzo[c]phenanthridine alkaloid primarily isolated from plants of the Papaveraceae family. DHSA exhibits broad pharmacological activities, including antitumor, anti-inflammatory, hypoglycemic, neuroprotective, analgesic, anxiolytic, antiarrhythmic, and antimicrobial effects. Mechanistically, DHSA regulates multiple signaling pathways and molecular targets, including TMEM16A, p53, Ras/Raf/MEK/ERK, PI3K/AKT, NF-κB, PPARγ, GABA_A receptors, and voltage-gated sodium channels. Compared with its biosynthetic precursor sanguinarine (SA), DHSA exhibits a comparatively favorable safety profile while retaining considerable biological activity. Pharmacokinetic studies further suggest that DHSA possesses acceptable membrane permeability, gastrointestinal absorption potential, enterohepatic circulation characteristics, and sustained systemic exposure. In addition, structure–activity relationship (SAR) and electrostatic surface potential (ESP) analyses indicate that the chemically accessible C6 position may provide opportunities for rational structural optimization. Nevertheless, the clinical translation of DHSA still faces several challenges. Therefore, this review systematically summarizes the physicochemical properties, pharmacological activities, molecular mechanisms, SAR characteristics, ESP distribution, toxicity, pharmacokinetic behavior, and clinical prospects of DHSA, aiming to provide a theoretical basis for its future drug development and translational application. Full article

Background/Objectives: Anshen Bunao Oral Liquid (ABOL) is a traditional medicinal formula comprising Cornu Cervi Pantotrichum, Radix Polygoni Multiflori Preparata and other ingredients. It replenishes essence, nourishes qi and blood, and soothes the spirit. It is used in clinical practice to treat neurasthenia and insomnia (emotion-related symptoms), and its key component, glycyrrhizin, exhibits anxiolytic properties. This aligns with the holistic approach of traditional Chinese medicine (TCM) to regulating neuropsychiatric disorders. The aim of this study is to evaluate the anxiolytic efficacy of ABOL in rats with anxiety induced by chronic restraint stress (CRS), and to clarify its mechanism by focusing on modulation of the gut–brain axis (microbiota and metabolism). Methods: Sprague-Dawley rats underwent three hours of restraint per day for 28 days to induce anxiety. ABOL was administered intragastrically in three doses. Anxiety-like behaviours were assessed using OFT, EPM and SPT. Serum, tissue and faecal samples were analysed using ELISA, histopathology, immunohistochemistry, non-targeted metabolomics, 16S rRNA sequencing and RT-qPCR. Results: CRS induced anxiety-like behaviours, impaired weight gain and perturbed the balance of neurotransmitters (decreasing 5-HT, GABA, NE and DA, while increasing CORT), inducing inflammation/oxidative stress, hippocampal neuronal injury, intestinal barrier dysfunction and gut microbiota/metabolic dysregulation. ABOL effectively reversed these abnormalities by restoring the balance of neurotransmitters and the HPA axis, suppressing inflammation and oxidation, protecting neurons and the intestinal barrier, remodelling the gut microbiota (enriching Akkermansia and balancing Firmicutes/Bacteroidota) and regulating sphingolipid and glycerophospholipid pathways. The interaction between the gut microbiota and metabolites may contribute to this pharmacological effect. Conclusions: ABOL exerts anxiolytic effects by modulating the gut–brain axis at multiple targets, involving microbiota remodelling, regulation of lipid metabolism and improvement of pathology. This validates its ethnopharmacological value, linking traditional Chinese medicine to the development of modern anxiolytics. Full article

Background: Anxiety is a frequent clinical problem that becomes disabling when excessive or persistent. Cyclitols are naturally occurring polyhydroxy compounds, and inositols are the most abundant cyclitols in eukaryotic cells; several stereoisomers have been proposed as candidates for CNS-relevant effects. Methods: A narrative review was conducted using a structured search of biomedical bibliographic databases. The search was centered on myo-inositol, scyllo-inositol, and D-chiro-inositol in relation to anxiety-related outcomes. Results: The retrieved literature suggests some biological plausibility for anxiolytic effects of selected inositol stereoisomers through pathways related to intracellular signaling and neurotransmission. However, the available evidence is uneven and remains limited. The most informative findings concern myo-inositol and include both preclinical and clinical studies, whereas data on scyllo-inositol and D-chiro-inositol are scarce, particularly in relation to anxiety-related outcomes. Conclusions: Current evidence suggests a possible anxiolytic role of selected inositol stereoisomers; however, the existing data are limited and heterogeneous, and do not allow for definitive clinical conclusions. Further research is required. Full article

Introduction: Effective perioperative management in cesarean section remains essential to optimize maternal outcomes. Melatonin (M) has been proposed as a potential adjunct due to its analgesic, anxiolytic, and antiemetic properties; however, evidence from randomized controlled trials (RCTs) remains inconsistent. This meta-analysis aimed to evaluate the efficacy and safety of preoperative melatonin compared with placebo in women undergoing cesarean section. Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane from inception to 15 March 2026 for studies evaluating pregnant women undergoing elective cesarean section receiving preoperative melatonin versus placebo (P) (PROSPERO “CRD420261355468”). Heterogeneity was assessed using the I² statistic and Cochrane Q test. Risk ratios (RRs) and standardized mean differences (SMDs) were computed using a restricted maximum-likelihood estimator random-effects method. Trial Sequential Analysis (TSA) was performed to assess the robustness and sufficiency of the evidence. Results: Seven RCTs were included with 552 patients (melatonin: 278; placebo: 274). Preoperative melatonin significantly reduced opioid consumption in the overall pooled analysis (RR 0.31, 95% CI 0.12 to 0.80; p = 0.030; I² = 50%), and TSA supported the robustness of this opioid-sparing finding under the selected assumptions. Postoperative pain scores were also significantly lower in the melatonin group (SMD −2.10, 95% CI −2.43 to −1.78; p < 0.01; I² = 22%). The incidence of postoperative nausea showed a trend toward reduction in the conventional meta-analysis (RR 0.49, 95% CI 0.23–1.04; p = 0.057; I² = 34%); although TSA suggested a possible benefit, this finding should be considered exploratory. No significant difference was observed in intraoperative blood loss (SMD −0.33, 95% CI −1.53 to 0.88; p = 0.60; I² = 94%). Conclusions: Preoperative melatonin may be a promising adjunct in cesarean section, particularly for reducing postoperative pain and overall opioid consumption. TSA findings support the opioid-sparing result under selected assumptions, while the possible effect on postoperative nausea remains exploratory. Further high-quality trials are warranted before routine clinical implementation can be recommended. Full article

Background/Objectives: Based on the central nervous system-related activity potential of 1,3,4-thiadiazole derivatives, novel 1,3,4-thiadiazole compounds were synthesized, and their possible antidepressant-like and anxiolytic-like effects were investigated. Methods: The chemical structures of the compounds were elucidated using several spectroscopic techniques. Antidepressant-like effects of compounds were evaluated using the tail suspension and the modified forced swimming tests, while anxiolytic-like effects were assessed using the hole board, elevated plus maze, and open field tests in male Balb/c mice. Motor activities of the animals were examined using the activity-meter device. Mechanistic and computational in silico studies were also performed. Results: The results demonstrated that compounds 4e–4i exhibited antidepressant-like effects, whereas only compound 4e showed an anxiolytic-like effect. None of the compounds produced significant alterations in motor activities of animals, indicating that the observed behavioral effects were specific. The antidepressant-like effects of compounds 4e–4i were abolished by p-chlorophenylalanine methyl ester (PCPA) and α-methyl-para-tyrosine methyl ester (AMPT) pre-administration indicating that the antidepressant-like effects of these test compounds are related to both serotonergic and catecholaminergic mechanisms. Furthermore, the anxiolytic-like effect of compound 4e was reversed by flumazenil and NAN-190 pre-administrations, indicating the participation of the GABA-A benzodiazepine receptor complex and 5-HT_1A receptors in its pharmacological activity. Computational in silico studies revealed that compounds have good ADME profiles; compounds 4e–4i interact with the serotonin transporter; compound 4e shows affinity for GABA-A and 5-HT_1A receptors; and all interactions remain stable under dynamic conditions. Conclusions: These findings supported the previous papers reporting the antidepressant-like and anxiolytic-like effects of 1,3,4-thiadiazole derivatives. Full article

Benzodiazepines (BZDs) are among the most widely prescribed psychotropic drugs in modern healthcare, primarily used as anxiolytics, hypnotics, anticonvulsants, and muscle relaxants. However, rising global consumption and prolonged use raise significant concerns about safety and dependence. Recent studies report that up to 35.8% of patients continue BZD therapy beyond three months, with long-term use observed in over 5% of the general population. These patterns highlight the need for evidence-based strategies to improve prescribing practices. BZDs are recommended primarily for short-term management of severe anxiety or transient insomnia, typically limited to 2–4 weeks. In anxiety disorders, SSRIs and SNRIs are first-line treatments. BZD use is particularly discouraged in older adults due to increased risks of cognitive impairment, falls, and dependence. Rational prescribing requires individualized assessment, minimal effective dosing, gradual withdrawal protocols, and patient education. Enhanced regulatory oversight and improved access to psychotherapy are essential for safer benzodiazepine use. Full article

Affective disorders, including anxiety, depression, and bipolar disorder (BD), represent a global mental health burden with complex, multifactorial etiopathogenesis. Increasing evidence implicates neuroinflammation, oxidative stress, and dysregulation of neurotrophic and neurotransmitter systems as central mechanisms driving these conditions. Flavonoids, a structurally diverse class of plant-derived polyphenolic compounds abundantly found in fruits, vegetables, tea, and other dietary sources, have emerged as promising modulators of these pathophysiological pathways. This narrative review synthesizes current preclinical and clinical evidence on the role of flavonoids and related natural compounds in modulating neuroinflammation and affective disorders. We describe the major flavonoid subclasses—flavones, flavonols, isoflavones, anthocyanins, flavanones, and flavan-3-ols—and analyze their mechanisms of action, including inhibition of the NF-κB/NLRP3 axis, reduction in pro-inflammatory cytokines, attenuation of oxidative stress via Nrf2 pathway activation, modulation of monoaminergic and GABAergic neurotransmission, promotion of Brain-Derived Neurotrophic Factor (BDNF)-mediated neuroplasticity, and regulation of the microbiota–gut–brain axis. Preclinical studies consistently demonstrate anxiolytic and antidepressant effects for compounds such as quercetin, luteolin, apigenin, and chrysin; however, clinical evidence remains limited and methodologically heterogeneous. Future research should prioritize bioavailability-enhanced formulations, standardized clinical trials, and biomarker-guided stratification to fully establish the therapeutic potential of flavonoids in affective disorders. Full article

Excitotoxicity is one of the factors that participates in neurodegeneration, impairing neuronal and glial cells’ function, and leading to the development of chronic neurodegenerative diseases. The main mechanism of action lies in the overstimulation of excitatory receptors, especially the NMDA (N-methyl-D-aspartic acid) receptor, by glutamate, which promotes a massive influx of Ca²⁺ that is not sufficiently buffered by the intracellular machinery, or not released by mechanisms such as Ca²⁺ ATPase and plasma membrane Ca²⁺/Na⁺ exchanger promoting, among other toxic effects, mitochondrial damage and an increase in reactive oxygen species (ROS). Notably, many cases reported of long COVID-19 describe significant brain alterations and neuropsychiatric disorders, including delirium, depression, etc., and patients required increased use of antidepressant or anxiolytic drugs, for example. In addition, emerging evidence links neurodegeneration as a potential long-term sequelae associated with an increased number of patients with cognitive disorders. This review analyzes data from the literature regarding brain alterations associated with post-COVID-19 syndrome and explores a potential link to the excitotoxicity pathways, due to its participation in neurodegeneration by homeostatic failure, and it is clearly present in various brain conditions, such as Alzheimer’s and Parkinson’s diseases. Full article

(1) Background: Clinopodium pulchellum (Kunth) Govaerts (Panizara) is an aromatic Andean medicinal plant traditionally used in Peru to manage nervous disorders, insomnia, and digestive complaints; however, its neuropharmacological properties remain poorly validated. This study aimed to evaluate the anxiolytic- and antidepressant-like effects of C. pulchellum and to characterize its phytochemical profile as supportive evidence. (2) Methods: The essential oil was obtained by hydrodistillation and analyzed using GC–MS and GC–FID. (3) Results: Fifteen volatile compounds were identified based on retention indices and mass spectral data, with β-caryophyllene (22.9%) and linalool (19.1%) as the most representative constituents, while other compounds were tentatively identified. The aqueous extract showed total phenolic and flavonoid contents of 34.15 mg GAE/g and 29.44 mg QE/g, respectively, and moderate antioxidant activity (DPPH = 2.36 mg TE/g; ABTS = 3.33 mg TE/g). In vivo assays revealed that EOCP at 200 mg·kg⁻¹ significantly increased open-arm exploration in the elevated plus maze and reduced immobility time in the CUMS–forced swim test by 37% compared with the stress group, although the effect was lower than that of reference drugs. Molecular docking analysis indicated favorable binding affinities of β-caryophyllene, humulene, and aromandendrene with serotonergic and ion channel targets, while ADMET predictions suggested suitable pharmacokinetic properties. (4) Conclusions: These findings indicate that the observed neuropharmacological effects may be associated with the presence of bioactive terpenoids typical of Lamiaceae, supporting the traditional use of C. pulchellum. However, further studies are required to confirm the identity of uncommon constituents and to elucidate the mechanisms underlying its biological activity. Full article