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.

Opioid use disorder (OUD) is an emerging public-health challenge in Nigeria, driven largely by non-medical use of tramadol and codeine and compounded by limited access to evidence-based care. This narrative review synthesises evidence on the epidemiology, patterns, harms and treatment gaps for OUD in Nigeria and identifies priorities for policy and research. We searched PubMed/MEDLINE, Embase, PsycINFO, the Cochrane Library, African Journals Online, Google Scholar and grey literature from 2005 to 2024 for Nigerian data on non-medical opioid use, clinical harms, opioid agonist therapy (OAT) services, barriers and community supports. Findings were thematically synthesised using Braun and Clarke's framework, with quality appraisal using Joanna Briggs Institute tools and the SANRA scale. Thirty studies were included. The 2019 national drug use survey estimated past-year opioid use at 4.7% (approximately 4.6 million people), with institution-based surveys reporting high lifetime misuse among undergraduates. Reported harms included overdose, seizures, psychiatric comorbidity and injectable pentazocine dependence with severe soft-tissue infections. OAT availability remains highly centralised, with limited community recovery infrastructure. Nigeria's OUD burden is substantial but unevenly characterised, highlighting the need to decentralise OAT, integrate addiction training, strengthen surveillance and expand community supports.

Objective: To evaluate the effects of oxycodone naloxone prolonged-release tablets on bowel function, analgesic control, quality of life, and safety in patients with severe cancer pain and opioid-induced constipation (OIC). Methods: This study is an interim analysis of a prospective, multicenter, single-arm trial. Patients with severe cancer pain and OIC from nine medical institutions in China between April 2025 and January 2026 were enrolled and treated with oxycodone naloxone prolonged-release tablets for 4 weeks. The primary endpoint was bowel function improvement assessed by the Bowel Function Index (BFI). Secondary endpoints included analgesic effect (Brief Pain Inventory-Short Form, BPI-SF), defecation status (Complete Spontaneous Bowel Movement, CSBM), quality of life (Patient Assessment of Constipation Quality of Life, PAC-QOL), and safety (adverse events). One-way repeated measures analysis of variance was used to compare the above measures between different post-treatment time points and baseline. The Lan-DeMets α-spending function (with O'Brien-Fleming adjustment) was applied to adjust the α level for the interim analysis, yielding an interim analysis boundary value of 0.000 6 (two-sided) and a final analysis boundary value of 0.049 8. Results: Planned enrollment was 203 patients; by January 2026, 78 patients were actually enrolled. The modified full analysis set (mFAS) comprised 64 patients, and the safety analysis set (SAS) comprised 77 patients. In the mFAS group, BFI scores decreased significantly after treatment (F=36.39, P<0.001). The change from baseline in BFI score at week 4 was -26.7 (-39.2, -10.0) points (P<0.001). BPI-SF scores at all post-treatment time points were lower than baseline, and CSBM at all time points increased compared with baseline, and the PAC-QOL score at all time points decreased compared with baseline (all P<0.001). In the SAS group, the daily opioid dose was [M(Q1, Q3)] 40.0 (20.0, 65.5) mg. The overall incidence of adverse events was 54.5% (42/77), with the most common being nausea (15.6%, 12/77) and vomiting (14.3%, 11/77). The incidence of serious adverse events was 6.5% (5/77). Conclusion: Oxycodone naloxone prolonged-release tablets improve bowel function and defecation in Chinese patients with severe cancer pain and OIC, do not compromise analgesic effect, enhance constipation-related quality of life, and demonstrate acceptable safety.

Polymer materials are widely used as sorptive phase due to their great availability, variety and widely modification possibilities. The latter includes the introduction of different interactions between the sorbent and analytes or the enhancement of existing ones, thus increasing the extraction efficiency, selectivity, or both. This article describes a simple one-step modification of commercial polyvinyl chloride (PVC) to introduce sulfonic groups into its structure. As a result, the modified particles acquired mixed-mode sorption capacity (combination of cation-exchange and hydrophobic interactions), being confirmed by X-ray fluorescence and infrared spectroscopy. Modified PVC particles were immobilized on a stainless-steel sheet using double-sided adhesive tape, and the resulting sorptive phase was used to extract opioids (codeine, methadone, oxycodone, and tramadol) from saliva samples. During the study, key parameters affecting the extraction process (sample pH, eluent type, stirring speed, and extraction and elution times) were optimized. The procedure was combined with direct infusion tandem mass spectrometry and validated, yielding satisfactory results in terms of precision (intra-day relative standard deviation ≤ 13.4 %, inter-day relative standard deviation ≤ 9.7 %) and accuracy (intra-day relative recovery in the range of 82-111 %, inter-day relative recovery between 82 and 104 %). The scope of the developed method covers concentrations of the tested opioids found in actual saliva samples, which makes it suitable for use in drug monitoring and abuse control programs.

Maternal use of oral opioids during breastfeeding can cause infant drowsiness, which may progress to rare but severe central nervous system depression.[1,2] Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. If the mother of a newborn requires codeine, it is not a reason to discontinue breastfeeding; however, once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of oral codeine to 2 to 3 days at a low dosage with close infant monitoring, especially in the outpatient setting.[2-4] If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.[5] Excessive sedation in the mother often correlates with excess sedation in the breastfed infant. Following these precautions can lower the risk of neonatal sedation.[6] Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. Numerous professional organizations and regulatory agencies recommend that other agents are preferred over codeine or to avoid codeine completely during breastfeeding;[7-11] however, a large population study did not find codeine to be more dangerous than other opioids that have been studied less and may not be safer.[12-14]