Search Results (89)

Adiponectin is adipokine exhibiting beneficial metabolic action through lipid and carbohydrate metabolism stimulation, as well as anti-inflammatory action. We have determined the role of adiponectin in gastroprotection against the formation of acute gastric lesions induced by ischemia–reperfusion (I/R). Gastric lesions evoked by I/R are a serious clinical entity; however, the participation of reactive oxygen species (ROS) and lipid peroxidation products and the involvement of nitric oxide (NO), neuropeptides released from sensory afferent nerves, and the hormone gastrin in the potential gastroprotective action of adiponectin remains unknown. Therefore, we determined the interplay between capsaicin-sensitive afferent nerves, the NO/NOS system, lipid peroxidation products, and the expression of pro-inflammatory and antioxidative factors in the gastroprotective action of adiponectin against gastric I/R. injury. Wistar rats was administered with adiponectin in graded doses (1–40 μg/kg i.v.) with or without: (a) blockade of nitric oxide (NO) activity by L-nitro-L-arginine (L-NNA) and (b) deactivation of sensory nerves by capsaicin (125 mg/kg s.c. 10 days before experiment conduction). They were then exposed to 30 min of ischemia by clamping of the celiac artery followed by 3 h of reperfusion after clamp release. After 3 h, the rats were euthanized with pentobarbital and their gastric blood flow (GBF) was determined by laser Doppler flowmetry, their blood was withdrawn to assess plasma gastrin levels, and the area of gastric lesions was measured by planimetry. Gastric biopsy samples were excised to determine gastric mucosal levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). In separate groups of animals with chronic gastric fistula, the effect of adiponectin on gastric acid secretion was determined. Adiponectin dose-dependently reduced the gastric lesions induced by I/R and this effect was accompanied by an increase in GBF. Blockade of NO-synthase with L-NNA (20 mg/kg i.p.) reversed the protective effect and the rise in GBF induced by this adipokine, and both these effects were restored when L-arginine was added to L-NNA. Capsaicin denervation also impeded the beneficial action of adiponectin in rats, but these effects were in part restored when exogenous CGRP was combined with adiponectin. Adiponectin dose-dependently decreased gastric acid secretion, the expression of mRNA for pro-inflammatory cytokines, and MDA plus 4-HNE content, while significantly increasing SOD, GSH and plasma gastrin increments. We conclude that adiponectin exerts gastroprotection against I/R-induced gastric lesions, through mechanisms involving NO and neuropeptides such as CGRP being released from sensory nerves, a decrease in lipid peroxidation (MDA+4-HNE), an increase of antioxidative factors (SOD, GSH), and the inhibition of gastric acid secretion. Full article

Aim: This study investigated the synergistic therapeutic effects and underlying mechanisms of tetrahydroberberine (THB) combined with protopanaxadiol (PPD) on p-chlorophenylalanine (PCPA)-induced insomnia in rats. Methods: Rats were randomly divided into normal, model, diazepam, THB monotherapy, PPD monotherapy, and THB + PPD combination groups. Evaluations included the pentobarbital sleep test, HE staining, ELISA, 16S rRNA sequencing, metabolomics, and Western blot. Results: Results demonstrated that the THB + PPD combination exhibited significant synergistic effects compared with monotherapies: the combination shortened sleep latency by 56.2% (vs. 44.2% for THB alone and 20.7% for PPD alone) and prolonged sleep duration by 112.8% (vs. 70.2% for THB and 59.6% for PPD) relative to the model group, while effectively restoring body weight gain. Histologically, combined treatment significantly alleviated hippocampal neuronal damage and increased the number of intact neurons in the dentate gyrus. Molecularly, it upregulated brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) levels, restored neurotransmitter balance (serotonin, dopamine, and glutamate), suppressed overactivation of the hypothalamic–pituitary–adrenal (HPA) axis (reducing corticotropin-releasing hormone and corticosterone), and decreased pro-inflammatory cytokine expression. Gut microbiota analysis revealed that the combination restored microbial homeostasis (increasing beneficial bacteria such as *Lactobacillus*) and modulated the glycine–serine–threonine metabolic pathway. Mechanistically, THB + PPD synergistically activated the PI3K/AKT neurotrophic pathway (p-PI3K and p-AKT expression increased by 1.9-fold and 2.5-fold, respectively, vs. model), inhibited the AGE/RAGE pro-inflammatory axis (RAGE expression decreased by 31.8%), and enhanced blood–brain barrier integrity by upregulating tight junction proteins (ZO-1, Occludin). Conclusions: THB combined with PPD exerts synergistic anti-insomnia effects through multi-level regulation of the microbiota–gut–brain axis, neurochemical balance, and key signaling pathways, providing a promising foundation for developing safe natural product-based combination therapies. Full article

Background/Objectives: Baichuan Baile (BCBL), a novel functional dietary formula, has been shown to exert antidepressant-like effects through modulation of the 5-HT system in our prior studies. Given the close neurobiological connections between depression and insomnia, along with its pharmacodynamic profile guided by TCM theory and nutritional assessments, BCBL is likely to possess beneficial effects against insomnia. However, this hypothesis and its underlying mechanisms require further validation. Methods: The chemical constituents of BCBL were analyzed by UPLC-Q-TOF-MS, and network pharmacology was applied to predict potential sleep-relevant targets and pathways. Subsequently, BCBL was evaluated for sedative-hypnotic effects using pentobarbital-induced hypnosis, locomotor activity, and polysomnography (EEG/EMG). Its therapeutic efficacy was further assessed in insomnia models induced by environmental stress, serotonin depletion, and rotarod-based sleep deprivation. The rotarod-induced chronic model was selected for mechanistic studies due to its sustained insomnia-like phenotype. Finally, key network-predicted targets were validated in this model through histopathology, Western blotting, and ELISA. Results: Pharmacological evaluation confirmed that BCBL significantly promoted sleep at both behavioral and EEG levels, confirming its sedative-hypnotic properties. BCBL mitigated environmental stress-triggered impairments in NREM sleep continuity and duration, and exerted protective effects against body weight loss and sleep disturbances in a serotonin depletion-induced insomnia model. In the rotarod sleep deprivation model, BCBL treatment increased spontaneous alternation rates and recognition indices, ameliorated hippocampal pathological alterations, and reduced hippocampal levels of HIF-1α, TNF-α, and IL-1β. Furthermore, BCBL elevated the p-GSK3β/GSK3β ratio and enhanced SIRT₁ expression in the hypothalamus. It also modulated the activity of key sleep–wake neurotransmitters/neuromodulators (serotonin, dopamine, adenosine, and glutamate) and key circadian rhythm regulators (BMAL₁, PER₂, and CLOCK) in this region. Conclusions: BCBL exhibits significant therapeutic efficacy against insomnia, indicating its potential as a dietary supplement for managing insomnia. Its mechanisms appear to involve anti-inflammatory effects, rebalancing of neurotransmitters/neuromodulators, and stabilization of circadian rhythm gene expression. Full article

The Acronicta major larva is a toxic agricultural pest that poses severe ecological management challenges. This study presents a sustainable strategy to valorize this hazardous biological waste into functional nanotherapeutics for insomnia by leveraging its unique intrinsic chemical composition. Carbon dots derived from Acronicta major larva (AM-CDs) were synthesized via one-step pyrolysis, which facilitated the natural molecular pre-assembly of N,S-codoping. Their physicochemical properties and cytotoxicity were evaluated using a series of characterizations and the CCK-8 assay. The sedative and hypnotic effects were assessed in mice with PCPA-induced insomnia through hot plate, Open Field and pentobarbital-induced sleep tests, and their potential mechanism was explored via neurotransmitter detection. The thermal process effectively eliminated intrinsic toxicity while retaining bioactivity via in situ heteroatom doping. AM-CDs exhibited favorable biocompatibility and significant sedative–hypnotic activity, reducing anxiety-related agitation without motor impairment. Mechanistically, AM-CDs effectively restored the GABA/5-HT/glutamate axis. Unlike direct central receptor binding, our findings suggest that this therapeutic effect is likely mediated through a systemic or peripheral regulatory pathway. This study demonstrates the conversion of toxic pests into safe and intrinsically bioactive nanomaterials, providing a dual solution for ecological pest management and novel neuroactive agent development, and validating the “Waste-to-Wealth” concept in biomedicine. Full article

Background: Severe traumatic brain injury (TBI) often leads to elevated intracranial pressure (ICP) that requires aggressive management. Inducing burst suppression with deep sedation is an established therapy for refractory intracranial hypertension. Traditionally, barbiturate coma has been used to achieve burst-suppression EEG in TBI patients, but alternative sedative agents (propofol, midazolam, ketamine, dexmedetomidine) are increasingly utilized in modern neurocritical care. This review compares barbiturates with these alternatives for inducing burst suppression in adult TBI, focusing on protocols, mechanisms, efficacy in controlling ICP, safety profiles, and impacts on neurological outcomes. Methods: A search of the literature was performed, including clinical trials, observational studies, and guidelines on deep sedation for ICP control in adult TBI. Studies comparing high-dose barbiturates to other sedatives (propofol, midazolam, ketamine, dexmedetomidine) in the context of burst suppression or severe TBI management were included. Data on sedative protocols (dosing and EEG targets), mechanisms of action, ICP-lowering efficacy, complications, and patient outcomes were extracted and analyzed qualitatively. Results: High-dose barbiturates (e.g., pentobarbital or thiopental) and propofol are both effective at inducing burst-suppression EEG and reducing ICP via cerebral metabolic suppression. Barbiturate coma remains a third-tier intervention reserved for ICP refractory to other treatments. Propofol infusion has become first-line for routine ICP control due to rapid titratability and shorter half-life, though it can also achieve burst suppression at high doses. Midazolam infusions provide sedation and seizure prophylaxis but yield less metabolic suppression and ICP reduction compared to barbiturates or propofol, and are associated with longer ventilation duration and delirium. Ketamine, once avoided for fear of raising ICP, has shown neutral or lowering effects on ICP when used in ventilated TBI patients, thanks to its analgesic properties and maintenance of blood pressure; however, ketamine alone does not reliably produce burst-suppression patterns. Dexmedetomidine offers sedative and anti-delirium benefits with minimal respiratory depression, but it is generally insufficient for deep burst-suppressive sedation and has only a modest effect on ICP. In comparative clinical evidence, propofol and barbiturates both effectively lower ICP, but neither has demonstrated clear improvement in long-term neurological outcome when used prophylactically. Early routine use of barbiturate coma may increase complications (hypotension, immunosuppression), and thus, current practice restricts it to refractory cases. Modern sedation protocols emphasize using the minimal necessary sedation to maintain ICP < 22 mmHg, with continuous EEG monitoring to titrate therapy to a burst-suppression target (commonly 2–5 bursts per minute) when deep coma is employed. Conclusions: In adult TBI patients with intracranial hypertension, propofol-based sedation is favored for first-line ICP control and can achieve burst suppression if needed, whereas high-dose barbiturates are reserved for ICP crises unresponsive to standard measures. Compared to barbiturates, alternative agents (propofol, midazolam, ketamine, dexmedetomidine) offer differing advantages: propofol provides potent, fast-acting metabolic suppression; midazolam adds anticonvulsant sedation for prolonged use at the cost of slower wake-up; ketamine supports hemodynamics and analgesia; dexmedetomidine aids lighter sedation and delirium control. The choice of agent is guided by the clinical scenario, balancing ICP reduction needs against side effect profiles. While all sedatives can transiently reduce ICP, careful monitoring and a tiered therapy approach are essential, as no sedative has conclusively improved long-term neurological outcomes in TBI. EEG monitoring for burst suppression and meticulous titration is required when employing barbiturate or propofol coma. Ongoing research into optimal combinations and protocols may further refine sedation strategies to improve safety and outcomes in severe TBI. Full article

Background/Objectives: As a non-medicinal part resource of Ziziphus jujuba, this study focuses on the total flavonoids from Ziziphus jujuba mesocarp (TFZJM), aiming to optimize the extraction process and explore its sedative and hypnotic effects. Methods: The extraction process of TFZJM was optimized by using single-factor experiments and the Box-Behnken response surface design method. The material basis of TFZJM was analyzed using Ultra-Performance Liquid Chromatography-Quadrupole-Time of Flight-Mass Spectrometry (UPLC-Q-TOF-MS). The mouse insomnia model was induced by intraperitoneal injection of PCPA, and the effects of TFZJM on this model and its potential mechanism were evaluated using multiple methods, such as sleep enhancement induced by pentobarbital sodium, HE staining of tissue sections, ELISA, RT-PCR, WB, and serum metabolomics. Results: The results showed that by optimizing the extraction conditions, a solid-liquid ratio (SLR) of 1:25 g·mL⁻¹, ethanol concentration of 60%, extraction time of 60 min, and extraction rate of 1.98% were achieved. The common chemical basis of the 10 flavonoid components was identified using UPLC-Q-TOF-MS analysis. Compared with the model group, the high-dose TFZJM (TFZJM-H) group had the most significant effect, followed by the medium-dose (TFZJM-M) and low-dose (TFZJM-L) groups. Conclusions: Metabolomic analysis revealed that TFZJM regulates pathways related to the metabolism of phenylalanine, tyrosine, cytochrome P450, and alanine. This lays the foundation for further exploration of the active substances and mechanisms of action of TFZJM in sedation and hypnosis. Full article

This study investigated the effects of lemon verbena extract (LVE) on sleep regulation using both a pentobarbital-induced sleep model and an EEG-based sleep assessment model in mice. To elucidate its potential mechanisms, mice were randomly assigned to five groups: control, positive control (diazepam, 2 mg/kg b.w.), and three LVE-treated groups receiving 40, 80, or 160 mg/kg b.w. via oral administration. In the pentobarbital-induced sleep model, mice underwent a two-week oral administration of LVE, followed by intraperitoneal pentobarbital injections. The results demonstrated that LVE significantly shortened sleep latency and prolonged sleep duration compared to the control group. Notably, adenosine A1 receptor expression, both at the mRNA and protein levels, was markedly upregulated in the brains of LVE-treated mice. Furthermore, LVE’s administration led to a significant increase in the mRNA expression of gamma-aminobutyric acid type A (GABA_A) receptor subunits (α2 and β2) in brain tissue. In the electroencephalography (EEG)/electromyogram (EMG)-based sleep model, mice underwent surgical implantation of EEG and EMG electrodes, followed by one week of LVE administration. Quantitative EEG analysis revealed that LVE treatment reduced wakefulness while significantly enhancing REM and NREM sleep’s duration, indicating its potential sleep-promoting effects. These findings suggest that LVE may serve as a promising natural sleep aid, improving both the quality and duration of sleep through the modulation of adenosine and GABAergic signaling pathways. Full article

Background: This study aimed to develop a model for understanding stress-induced sleep disturbances and to explore the potential interactions between sleep disturbances and mood disturbances. Methods: The chronic unpredictable mild stress (CUMS) group was established using the CUMS method, while the CUMS+Noise group was subjected to an additional 8-h exposure to noise in conjunction with the CUMS protocol. Each group was tested for anxiety and depressive-like behavior using the open-field, elevated plus maze, tail suspension, and forced swimming tests in male C57BL/6J mice. Subsequently, we assessed sleep status using sleep recordings and a standardized scoring system alongside the pentobarbital sodium-induced sleep test. Results: The mice in both model groups exhibited anxiety-like behavior. Sleep disturbances observed in the CUMS+Noise group were characterized by disruptions in sleep duration and circadian rhythm. This observation was supported by a marked reduction in multiple sleep time intervals and single sleep duration, as well as a significant increase in sleep duration at the final time interval of ZT23-24. To further investigate the potential mechanisms of interaction, we conducted an analysis of hub genes present in the hippocampal sequencing data utilizing weighted gene co-expression network analysis (WGCNA). Pearson correlation analysis revealed a significant association between the hub genes Alb, P2rx1, and Npsr1 and key phenotypic traits. However, PCR experiments indicated that only Alb showed a significant difference, which aligns with the sequencing results. Conclusions: Albumin is a crucial transporter protein for thyroid hormones and plays a vital role in their metabolism. The interaction between sleep disorders and anxiety-like behavior may be closely linked to the dysfunctional transportation of thyroid hormones by albumin. Full article

Ziziphi Spinosae Semen saponins (ZSSS) show sedative–hypnotic activity but have very low bioavailability, potentially due to their conversion into bioactive metabolites by gut microbiota. In this study, the biotransformation of ZSSS by gut microbiota from healthy humans and patients with insomnia in vitro was analyzed. A total of 21 prototype compounds and 49 metabolites were identified using UHPLC-Q-Orbitrap-MS. Deglycosylation, deoxygenation, dehydration, and deacylation were detected in both healthy individuals and insomniacs. However, oxidation and hydrogenation were uniquely observed in insomniacs. ZSSS can enhance beneficial bacteria, such as Veillonella, Dialister, and Bacteroides. ZSSS can promote the synthesis of short-chain fatty acids (SCFAs), especially acetic acid, propionic acid, and butyric acid. Furthermore, it was found that the sedative–hypnotic activity of ZSSS was enhanced after biotransformation, as determined by a sodium pentobarbital-induced sleeping test (SPST), open-field behavior test (OFBT), and molecular docking experiment (MDE). These results collectively offer valuable insight into the mechanism of action of ZSSS. Full article

Insomnia seriously affects people’s health and daily life. There is a growing interest in sleep-promoting agents from natural sources. Nelumbinis Plumula (NP), a traditional Chinese medicine with dual food-medicine homology, has the effects of clearing the heart and calming the mind, showing promising efficacy in treating insomnia. In this study, the effects of NP extract, total alkaloid extract of NP, and crude polysaccharide of NP were measured in para-chlorophenylalanine-induced insomnia rats combined with the pentobarbital sodium experiment. The results indicated both total alkaloid extract and NP total extract could improve insomnia in rats, with the total alkaloid extract demonstrating a stronger effect than NP total extract. Total alkaloid extract significantly prolonged sleep duration and shortened sleep latency. Therefore, total alkaloids in NP appeared to be the main pharmacological substances that exerted sedative effect. Simultaneously, total alkaloid extract could increase the GABA level and reduce the DA level as well as affect the activities of GABRA1, DRD2, 5-HT1A, and AChE proteins. This study can lay an experimental foundation for the further development and application of NP as a remedy for treating insomnia. Full article

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus; oxidative stress plays a key role in the pathogenesis of DN. The objective of this study was to evaluate the antioxidant effect of vitamin E on diabetic nephropathy. A control group and three groups of rats with streptozotocin-induced diabetes mellitus (untreated diabetic rats and diabetic rats treated with vitamin E 250 and 500 mg/kg) were studied. After 4 weeks of treatment, the kidneys were removed under anesthesia with sodium pentobarbital. The kidneys were weighed, the AT₁ and AT₂ receptor expression was measured by Western blot, and the activities of glutathione peroxidase, catalase, and superoxide dismutase were determined in the renal cortex. Rats with diabetes mellitus had hyperglycemia, increased food and water consumption, and higher urinary volume than control rats. In diabetic rats (DM), kidney hypertrophy was observed and measured by kidney weight, protein/DNA ratio in the renal cortex, and proximal tubular cell area; proteinuria and reduced creatinine clearance were observed. AT₁ and AT₂ receptor expression in the kidney cortex of DM rats increased significantly compared to normoglycemic rats; antioxidant enzyme activities were decreased; treatment with vitamin E reversed kidney hypertrophy and reduced proteinuria; reduction in expression of AT₁ and AT₂ receptors was associated with increased antioxidant activity. Thus, treatment with vitamin E slows the progress of DN. Full article

Background/Objectives: The misuse of veterinary drugs is a growing concern, with increasing evidence of their presence in illicit drug markets and their use as alternatives to traditional substances. Methods: This study explores Reddit discussions on the misuse of veterinary drugs on Reddit, focusing on xylazine, carfentanil, medetomidine, pentobarbital, phenylbutazone, and acepromazine. Reddit was utilised for its abundant real-time data on users’ thoughts and experiences with substance misuse. Through a combination of manual and Artificial Intelligence (AI)-driven thematic analysis, we examined posts and comments to explore patterns of misuse. Results: The themes analysed included adverse effects, polysubstance misuse, routes of administration, motivations for misuse, and methods of obtaining these drugs. Our findings revealed that xylazine, medetomidine, carfentanil, and pentobarbital exhibit significant potential for misuse, while phenylbutazone and acepromazine are not widely misused. Despite this, phenylbutazone and acepromazine have been identified as adulterants in the illicit drug supply in the United States. The most discussed themes included motivations for misuse, followed by public experiences and perceptions, as well as adverse effects. Conclusions: The dual-method approach of combining manual interpretation with AI analysis allowed for a comprehensive understanding of social media discussions. This research highlights the importance of monitoring online platforms for early indicators of emerging drug trends, offering valuable insights to inform public health policies and intervention strategies. Impact Statement: This research highlights the growing public health risk posed by veterinary drug misuse, underscoring the need for enhanced monitoring, regulatory frameworks, and education to address their diversion into illicit markets. By leveraging social media as an early detection tool for emerging drug trends, our findings can inform targeted interventions. Full article

Background: Sleep, a process physiologically vital for mental health, faces disruptions in various sleep disorders linked to metabolic and neurodegenerative risks. Zizyphus seed (Zizy) has long been recognized for its diverse pharmacological attributes, including analgesic, sedative, insomnia, and anxiety alleviation. Objectives: In this study, the sleep-prolonging effects of Zizy extract (100, 200 mg/kg), along with their characterizing compounds jujuboside A (JuA) (5, 10 mg/kg), were evaluated in a mouse model under a pentobarbital-induced sleep. Additionally, the efficacy of Zizy extract was examined on caffeine-induced insomnia in mice. Methods: To confirm the efficacy of Zizy extract on the structure and quality of sleep, an electroencephalogram (EEG) analysis of rats was performed using the MATLAB algorithm. Additionally, Western blot analysis and measurement of intracellular chloride influx were performed to confirm whether these effects acted through the gamma-aminobutyric acid (GABA)ergic system. Administration of Zizy extract showed no effect on the locomotor performance of mice, but the extract and their characteristic compounds significantly prolonged sleep duration in comparison to the pentobarbital alone group in the pentobarbital-induced sleep mouse model. Furthermore, this extract alleviated caffeine-induced insomnia in mice. Results: The administration of Zizy extract extended non-rapid eye movement sleep (NREMS) duration without inducing significant changes in the brain wave frequency. Zizy extract regulated the expression of GABA_A receptor subunits and GAD65/67 in specific brain regions (frontal cortex, hippocampus, and hypothalamus). JuA increased intracellular chloride influx in human SH-SY5Y cells, and it was reduced by GABA_A receptor antagonists. These results suggest that the sleep-maintaining effects of Zizy extract may entail GABAergic regulation. In summary, Zizy extract demonstrated sleep-prolonging properties, improved insomnia, and regulated sleep architecture through GABAergic system modulation. Conclusions: These findings suggest that Zizy extract has potential as a therapeutic agent for stress-related neuropsychiatric conditions such as insomnia. Full article

Background/Objectives: With increasing interest in plant-based compounds that can enhance sleep quality without the side effects of caffeine, Alpinia galanga (AG) has emerged as a promising herbal supplement for improving mental alertness. This study assessed the impact of water-soluble AG extract on sleep quality; the activity of GABAergic, glutamatergic, and serotonergic receptors; and concentrations of dopamine and serotonin in the brains of mice. Methods: The study employed two experimental models using BALB/c mice to examine the impact of pentobarbital-induced sleep and caffeine-induced insomnia. In the first model, a set of 20 mice was assigned to four groups to assess the effects of pentobarbital (42 mg/kg) or pentobarbital with AG extract on sleep induction, with observations made 45 min post-administration. In the second model, 20 mice were divided into four groups to evaluate the impact of caffeine (25 mg/kg) alone or caffeine with varying doses of AG extract (61.25 or 205.50 mg/kg administered orally) on brain activity along with additional analyses on receptor proteins and neurotransmitters. Results: A higher dose of AG extract (205.50 mg/kg) significantly increased total deep sleep duration compared to the caffeine group (p < 0.0001). Furthermore, this dose extended sleep latency and suppressed GABAergic and glutamatergic receptor activity compared to the lower AG dose (p < 0.05). Additionally, the 205.50 mg/kg dose elevated serotonin and dopamine levels compared to caffeine (p < 0.0001), suggesting improved sleep quality alongside enhanced wakefulness. Conclusions: Our data indicate that a higher dose of AG extract improved sleep latency and duration by regulating GABAergic and glutamatergic receptors through the GABAergic/serotonergic pathway in mice. Full article

Introduction: Evidence suggests an increasing misuse of veterinary medicines by humans. This study aims to analyse Adverse Events (AEs) associated with selected veterinary products using the Food and Drug Administration Adverse Events Reporting System (FAERS). Methods: A descriptive pharmacovigilance analysis was conducted on AEs related to 21 drugs approved for human and/or animal use. Results: A total of 38,756 AEs, including 9566 fatalities, were identified. The United States reported the highest number of cases (13,532), followed by Canada (2869) and the United Kingdom (1400). Among the eight drugs licenced exclusively for animals, levamisole, pentobarbital, and xylazine were most frequently reported. Reports predominantly involved males (57%) from the 18–64 age group, with incidents related mainly to overdose, dependence, and multi-agent toxicities. Unmasking techniques revealed ‘intentional overdose’ as the primary reaction. Polysubstance use was evident in 90% of the drugs, with benzodiazepines/Z-drugs and opioids as common co-used classes. Conclusions: Veterinary medications are increasingly infiltrating the illicit drug market due to their pharmacological properties. This trend highlights the need for heightened vigilance and awareness to prevent further public health risks associated with the adulteration of illicit substances with veterinary products like xylazine and pentobarbital. Full article