Drugs of abuse (DAs) are increasingly detected in surface waters, yet their effects on marine organisms remain poorly understood. This study evaluated the impacts of environmentally relevant concentrations (100 and 1000 ng L[-1]) of cannabinol, codeine, and methamphetamine, individually and in mixtures, on the growth and development of Crassostrea virginica larvae. Eight-day exposures significantly reduced larval survival, impaired growth, and altered swimming behavior, with mixtures producing the strongest effects. At 1000 ng L[-1] , cumulative survival reached zero in mixture and cannabinol groups, while methamphetamine and codeine reduced survival by 74.8% and 56.0%, respectively. Drug mixtures also caused the greatest reduction in larval growth (13.3%) and mean swimming velocity (67.5%) relative to controls, with significant shifts from predominantly rectilinear swimming to circular or motionless behavior. Short-term (24 h) exposures induced changes in the expression of stress-related genes (mapk14, hsp70, sod1, and gst), with hsp70 exhibiting the strongest response (14- to 39-fold upregulation), indicating rapid activation of oxidative stress and detoxification pathways, particularly under mixture conditions. These findings demonstrate that DAs, especially in combination, can disrupt physiological and molecular processes in oyster larvae at concentrations reported in surface waters. Given their persistence, increasing consumption, and documented occurrence near wastewater discharges, DAs warrant consideration as contaminants of emerging concern in coastal ecosystems and should be incorporated into ecological risk assessments that account for mixture effects and early-life stage sensitivity.

Opioid use disorder is characterized by compulsive drug seeking and heightened relapse vulnerability following abstinence, a phenomenon known as incubation of craving. Although preclinical data suggest similar behavioral expression of opioid use between sexes, conclusive evidence on sex differences in craving and relapse across abstinence periods remains lacking. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength, glutamate release probability, and intrinsic excitability of NAcSh medium spiny neurons (MSNs) following 1 (acute) or 14 (prolonged) days of forced abstinence. No sex differences were observed in oxycodone self-administration or somatic withdrawal. However, females exhibited greater cue-induced relapse after prolonged but not acute abstinence. Prolonged abstinence produced comparable increases in PVT-NAcSh synaptic strength and presynaptic glutamate release probability in both sexes, while inhibitory transmission and MSN excitability were largely unaltered. The dissociation between comparable circuit-level plasticity and sex-specific relapse vulnerability suggests that PVT-NAcSh strengthening represents a shared neuroadaptation to oxycodone abstinence, while mechanisms driving heightened relapse in females likely involve additional circuit elements that remain to be identified.

Coated blades have been widely used with ambient ionization mass spectrometry (AIMS) using electrospray as ionization source. This article explores the coupling of commercial blades, containing hydrophilic-lipophilic balance particles (HLB), with soft ionization by chemical reaction in transfer mass spectrometry using a dedicated thermal desorber as interface. Commercial HLB-blades use polyacrylonitrile to embed the sorptive particles in the coating, but this binder is not fully compatible with the high temperatures required to efficiently desorb semivolatile compounds, such as those selected in this work (cocaine, codeine, methadone, and methamphetamine). To overcome this limitation, a micro-solvent-aided soft thermal desorption is proposed. For this purpose, 4 µL of octanol is deposited on the blade before placing it in the desorber, thereby assisting the chemical elution of the analytes and enabling thermal desorption at mild conditions (about 100 °C) in 1.5 min. As proof-of-concept, this strategy has been used to determine the drugs mentioned above in saliva, with detection limits as low as 0.6 µg L[- 1]. The method has been evaluated according to selected ICH M10 criteria to demonstrate its potential fully. As many samples can be extracted simultaneously, this approach provides a high throughput that surpasses the provided by classical liquid chromatography-mass spectrometry analysis. The new approach will permit to extend the application of coated blades to other analytes (e.g. hydrocarbons) that are poorly ionized by ESI.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a well-known cause of systemic hypersensitivity (urticaria, angioedema, and bronchospasm). Ocular involvement is usually described as merely a component of a systemic reaction. It should be distinguished from the local toxicity of topical ocular NSAIDs. To our knowledge, very few cases of isolated allergic conjunctivitis induced by oral NSAIDs have been reported. We report the case of a 24-year-old woman with no history of atopy, who had presented for the past 7 months with recurrent bilateral asymmetric allergic conjunctivitis, predominantly affecting the right eye and strictly coinciding with her menstrual cycle. Examination revealed reduced visual acuity due to conjunctival chemosis and tearing, at 20/25 (LogMAR 0.10) in the right eye and 20/22 (LogMAR 0.05) in the left eye. Allergy testing, including prick tests and eosinophil counts, did not identify a relevant causative allergen explaining the clinical presentation. A detailed medication history revealed a temporal correlation with oral ibuprofen used for severe dysmenorrhea, without any accompanying cutaneous, respiratory, or systemic symptoms. Upon discontinuation of ibuprofen and its replacement with paracetamol and codeine, no recurrence was observed for four consecutive months, and an oral provocation test performed in the fifth month was positive, with mild conjunctivitis confirming the diagnosis. We report a case of isolated allergic conjunctivitis induced by oral NSAIDs and confirmed by an oral provocation test, which highlights the importance of a systematic review of medication history in all cases of recurrent conjunctivitis and that oral NSAIDs should be considered in the diagnosis of recurrent conjunctivitis.

Background: Despite increasing opioid use in Brazil, the national epidemiological profile of opioid-related poisonings remains insufficiently characterized. Objective: To characterize opioid-notified poisonings reported in the Sistema de Informações sobre Agravos de Notificação (SINAN-Notifiable Diseases Information System), accessed through Departamento de Informática do Sistema Único de Saúde (DATASUS-Department of Informatics of the Unified Health System), between 2019 and 2025. Methods: This retrospective descriptive study used secondary national surveillance data from publicly accessible databases. Records of exogenous poisonings related to medications and drugs of abuse were screened, and notifications involving opioid analgesics were identified and standardized. Descriptive analyses were performed for demographic, clinical, and exposure-related variables. Bivariate analyses and multivariable logistic regression, regression models were conducted for selected outcomes. Incidence rates were estimated by year and federative unit, and temporal trends were assessed using generalized linear mixed models. Results: Between 2019 and 2025, 1,127,265 poisonings related to medications and drugs of abuse were reported in Brazil, of which 12,645 involved opioids. The opioids most frequently implicated in notifications were codeine (38.65%), tramadol (33.98%), and morphine (17.86%). Most cases occurred in women (70.3%), in individuals aged 26-50 years (47.8%), and in residences (85.6%). Digestive exposure predominated (92.3%), and suicide attempt was the main circumstance (73.5%). Most patients recovered without sequelae (75.1%), whereas 1.6% died due to exogenous intoxication. Co-exposure information was classifiable in 9573 records, most commonly involving opioids and medications. In multivariable analyses, suicide attempts were associated with female sex (aOR = 1.98; 95% CI: 1.68-2.34), residence-based exposure (aOR = 8.95; 95% CI: 6.29-12.72), and co-exposure (aOR = 2.17; 95% CI: 1.82-2.60). Hospitalization was less likely among females (aOR = 0.83; 95% CI: 0.75-0.91) and more likely with co-exposure (aOR = 1.14; 95% CI: 1.02-1.27). Serious outcomes were associated with older age (aOR = 1.017; 95% CI: 1.009-1.026), while residence-based exposure and suicide attempt showed lower odds. A significant increasing temporal trend was identified, with higher reported notification rates observed in the South and Southeast regions. Discussion: The predominance of suicide attempts and residential digestive exposures suggests that the notification profile captured by SINAN/DATASUS is predominantly shaped by intentional self-poisoning and household medication availability, while still representing a broader toxicovigilance scenario involving abuse, habitual use, adverse reactions, and other exposure contexts. The contrast between the most frequent notification profile and the profile associated with serious outcomes indicates that occurrence and severity may follow different epidemiological patterns. Therefore, these findings should be interpreted as a toxicovigilance signal reflecting multiple exposure contexts rather than as evidence of a single opioid-use pattern. Conclusions: Reported opioid-notified poisonings in Brazil increased over the study period and were predominantly associated with domestic exposure, suicide attempts, and co-exposure to other substances. These findings highlight the clinical and public health relevance of opioid-notified poisonings and support the need for strengthened surveillance, improved reporting quality, and preventive strategies addressing both opioid use and mental health. Limitations: Underreporting, missing data, regional reporting differences, and possible misclassification in SINAN/DATASUS records; therefore, associations, temporal increases, and projections should be interpreted as exploratory, and hypothesis generating.

Combination analgesic therapy is commonly used to improve pain control, yet conventional molecular docking approaches typically evaluate individual ligands and provide limited insight into potential intermolecular associations between co-administered drugs. In this study, paracetamol, codeine, and their proposed 1:1 and 2:1 non-covalent assemblies were investigated using lipophilicity analysis, molecular docking, short molecular dynamics relaxation, electrostatic potential surface mapping, and HOMO-LUMO analysis. Docking simulations were performed against cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and the μ-opioid receptor (MOR). The proposed assemblies produced docking scores that differed from those of the individual compounds, with the most pronounced differences observed for the cyclooxygenase targets. The 2:1 assemblies generally exhibited the most favorable docking scores, whereas the predicted interaction profiles at MOR appeared to be more dependent on molecular orientation. Molecular dynamics relaxation and electronic structure analyses further revealed differences in the energetic and electronic characteristics of the investigated configurations. These findings support the theoretical feasibility of distinct interaction patterns among the proposed paracetamol-codeine assemblies within the applied computational framework. However, the reported docking scores represent relative computational values rather than experimentally validated binding affinities, and the short-timescale molecular dynamics simulations provide only preliminary information regarding conformational stability. Furthermore, the existence and biological relevance of the proposed assemblies under physiological conditions remain to be established. This study provides a computational basis for future investigations of intermolecular associations in multicomponent drug systems.

Misuse of over-the-counter (OTC) and prescription-only medicines (POMs) is increasingly recognised as a public health and medicine-safety concern. Although specialist substance misuse services (SMS) increasingly support people affected by OTC/POM misuse, little is known about how SMS staff perceive the characteristics, challenges, and treatment needs of this population. This study explored the experiences of SMS staff to address this evidence gap and inform pharmacy practice and service development. Confidential semi-structured interviews were conducted with staff across five community adult English SMS. Audio recordings were transcribed verbatim and analysed thematically using NVivo[®]. Twenty interviews with varied professionals achieved data saturation. Three overarching themes emerged: (1) characteristics of OTC/POM misuse; (2) staff-perceived patterns among people who misuse OTC/POM; and (3) negative experiences and concerns. Dependence on orally administered opioids (particularly codeine-containing products), benzodiazepines and gabapentinoids predominated. Polypharmacy including illicit substance use was also reported. Withdrawal symptoms frequently perpetuated misuse, and abrupt supply cessation created additional risks. Routine enquiry about OTC/POM misuse and provision of tailored harm-reduction interventions are essential. The findings suggest that pharmacists may have an important role in early identification of problematic OTC/POM use, harm-reduction interventions, medicine review and facilitating referral into appropriate treatment pathways. Further research should examine whether dedicated OTC/POM pathways are required and explore differences in demographic and treatment needs across medicine types.