Search Results (194)

In recent years, the issue of drivers under the influence of medications and psychoactive substances as a cause of road accidents has gained increasing importance. This study aimed to assess the prevalence and blood concentration ranges of alcohol and psychoactive substances among drivers in northeastern Poland between 2013 and 2024. To determine the prevalence of medications and psychoactive substances in drivers’ blood, data were collected from 266 blood samples obtained from drivers (251 men and 15 women). Among these, 79 drivers died immediately, 61 drivers survived the accident, and 126 drivers were stopped for roadside checks. The presence of the studied substances was confirmed using gas chromatography combined with mass spectrometry detection (GC-MS) and liquid chromatography combined with mass spectrometry detection (LC-MS). Blood alcohol content was measured using headspace gas chromatography with a flame ionisation detector (HS-GC-FID). Psychoactive substances were detected in 152 of the 266 samples. Drivers testing positive for medications and psychoactive substances were most frequently stopped during roadside controls—67.46%. Among the total positive cases, psychoactive substances used alone or in combination included THC—46.3% (range 0.2–20 ng/mL), alcohol—26.8% (range 0.1–4.1‰), amphetamines—20.7% (range 15–2997 ng/mL), opiates—4.3% (morphine 66.0 ng/mL; methadone 174.0 ng/mL; ranges: tramadol 15.0–600.0 ng/mL; fentanyl 45.0–100.0 ng/mL), benzodiazepines—9.8% (ranges: diazepam 55.0–480.0 ng/mL; midazolam 17.0–1200.0 ng/mL; clonazepam 21.0–36.0 ng/mL), stimulants—6.10% (ranges: amphetamine 15.0–2997.0 ng/mL; cocaine 4.0–30.0 ng/mL; benzoylecgonine 38.0–602.0 ng/mL; PMMA 45.0–360.0 ng/mL; MDMA 20.0–75.0 ng/mL; mephedrone 37.5 ng/mL; alfa-PVP 120 ng/mL), psychotropic drugs—3.1% (carbamazepine 8.0–2100.0 ng/mL; zolpidem 233.0 ng/mL; citalopram 320.0 ng/mL; opipramol 220 ng/mL). The most commonly used substance among car and motorcycle drivers was THC (37.7% of car drivers and 60% of motorcyclists). Among operators of other types of vehicles, alcohol was the most frequently detected substance, present in 35% of cases. The majority of drivers (81.1%) were under the influence of a single substance. Among the drivers, 7.3% consumed alcohol in combination with at least one other substance, and 11.6% used two or more substances excluding alcohol. Among the psychoactive substances most frequently used alone or in combination with others, THC was predominant. Roadside testing, based on effects similar to alcohol intoxication, was mainly conducted on male drivers. Full article

Xylazine, an adulterant found frequently in illicit fentanyl, has been implicated in causing several adverse effects in human recreational users, including skin lesions and complications in the treatment of opiate overdose. Despite these public health concerns, the literature on the basic behavioral effects of xylazine is limited. Recent research has demonstrated that planarians show potential as an emerging and practical animal model for studying the behavioral effects of acute xylazine exposure. The goal of the current investigation was to evaluate the behavioral effects of chronic xylazine administration on negative phototaxis in two planarian species: Girardia tigrina and Schmidtea mediterranea. Three experiments were conducted. Overall, 10 µM of chronic xylazine exposure, arranged according to a multiple-baseline design, impaired negative phototaxis in S. mediterranea but not G. tigrina. An ABA reversal design indicated that behavioral effects in S. mediterranea abated when chronic xylazine was terminated. Finally, a between-group design replicated potential interspecies differences when G. tigrina and S. mediterranea were compared directly, with the latter showing significantly greater susceptibility to drug effects. This work provides evidence of the utility of a planarian model for studying the behavioral effects of xylazine and lays the foundation for further investigation into the chronic effects of the drug. Full article

Background/Objectives: Recent studies have identified some concerns related to the occurrence of eye disorders in offspring of opioid-prescribed mothers, and especially so in those exposed to methadone. The aim here was to investigate, from a pharmacovigilance point of view, the association between opioid exposure during pregnancy and reported eye disorders in children. Methods: The FDA Adverse Event Reporting System (FAERS) was searched for the following: reports of eye disorders in children aged 0–17 years exposed during pregnancy to either methadone or buprenorphine; top 20 medications administered during pregnancy and associated with eventual occurrence of eye disorders in children; and reports of eye disorders in children from mothers prescribed with a range of psychotropics. Results: For 190 methadone and 79 buprenorphine cases, occurrence of eye disorders was registered as the consequence of having been exposed to these drugs in utero. After data cleaning, residual cases for methadone and buprenorphine were 17 and 15, respectively. Overall, in comparing the odds of eye disorders given methadone exposure to the odds of eye disorders given buprenorphine exposure, which represents a relative Reporting Odds Ratio (ROR) between two drugs, the relative ROR between methadone and buprenorphine was 0.59, suggesting lower odds of eye disorders for methadone compared to buprenorphine in children 0–17 years old antenatally exposed to either methadone or buprenorphine. Conversely, the ROR values resulting from a comparison of methadone- or buprenorphine-related data versus all other psychotropic drugs resulted in 0.27 (95% CI 0.16–0.48) and 0.47 (95% CI 0.26–0.85), respectively, indicating lower reporting odds of eye disorders for these molecules versus the pooled non-opioid comparator group. Medications prescribed during pregnancy which were most frequently related to the occurrence of eye disorders included the following: dupilumab (126 reports), valproate (69 reports), and ibuprofen (52 reports). Indeed, no opiates/opioids appeared among the top 20 drugs linked to eye disorders. A total of 25 and 11 unique cases were associated either with benzodiazepines or antipsychotics, respectively. Conclusions: No potential disproportionality safety signal for eye disorders associated with prenatal opioid exposure was identified. Specifically, the relative ROR indicated lower reporting odds for methadone compared to buprenorphine. The interpretation of these results is complicated by common co-exposures, polydrug interventions, and underlying maternal comorbidities, which introduce substantial confounding in real-world pharmacovigilance data. Overall, these findings highlight the importance of continued systematic post-marketing surveillance. Full article

Diamorphine (DIM, heroin) is a semi-synthetic opioid that undergoes rapid conversion to 6-monoacetylmorphine and morphine, producing short-lived biomarkers that are difficult to capture during the process. This review critically explores the evolution of analytical techniques for quantitative DIM analysis in biological matrices from 1980 to 2025. It synthesizes findings across blood, plasma, urine, hair, sweat, and postmortem samples, emphasizing matrix-specific challenges and forensic applicability. Unlike previous opioid reviews that primarily focused on metabolites, this work highlights analytical methods capable of successfully detecting diamorphine itself alongside its key metabolites. This review examines 32 studies spanning three decades and compares three core analytical methods: gas chromatography–mass spectrometry (GC–MS), high-performance liquid chromatography (HPLC) with optical detection and liquid chromatography–mass spectrometry (LC–MS). Key performance metrics include sensitivity, sample preparation workflow, hydrolysis control, metabolite coverage, matrix compatibility, automation potential and throughput. GC–MS remains the workhorse for hair and sweat ultra-trace screening after derivatization. HPLC with UV, fluorescence or diode-array detection enables robust quantification of morphine and its glucuronides in pharmacokinetic and clinical settings. LC–MS facilitates the multiplexed analysis of DIM, its ester metabolites and its conjugates in a single, rapid run under gentle conditions to prevent ex vivo degradation. Recent advances such as high-resolution mass spectrometry and microsampling techniques offer new opportunities for sensitive and matrix-adapted analysis. By integrating validation parameters, forensic applicability, and evolving instrumentation, this review provides a practical roadmap for toxicologists and analysts navigating complex biological evidence. Full article

Opioid-use disorder (OUD) poses a growing global health crisis, with chronic opioid exposure linked not only to addiction but also to enduring neurological impairments. While traditional research has focused primarily on neuronal alterations, emerging evidence underscores the pivotal role of astrocytes, abundant glial cells in the central nervous system, and their secreted extracellular vesicles (EVs) in opioid-mediated neuropathology. This review delineates the mechanistic roles of astrocytes and astrocyte-derived EVs (ADEVs) across a spectrum of opioids, including morphine, heroin, fentanyl, codeine, tramadol, buprenorphine, and methadone. Opioids disrupt astrocytic homeostasis by impairing glutamate regulation, altering the redox balance, and activating pro-inflammatory signaling pathways. In response, astrocytes release EVs enriched with neurotoxic cargo, including amyloidogenic proteins, cytokines, microRNAs, and long non-coding RNAs, that propagate neuroinflammation, compromise blood–brain barrier (BBB) integrity, and exacerbate synaptic dysfunction. Preclinical models and in vitro studies reveal drug-specific astrocytic responses and ADEV profiles, implicating these vesicles in modulating microglial function, neuroimmune signaling, and neuronal viability. Notably, morphine-induced ADEVs promote amyloidosis and inflammatory signaling, while heroin and fentanyl affect glutamatergic and inflammasome pathways. Even opioids used in therapy, such as buprenorphine and methadone, alter astrocyte morphology and EV cargo, particularly during neurodevelopment. Collectively, these findings advance a neuro-glial paradigm for understanding opioid-induced brain injury and highlight ADEVs as both biomarkers and mediators of neuropathology. Targeting astrocyte-EV signaling pathways represents a promising therapeutic avenue to mitigate long-term neurological consequences of opioid exposure and improve outcomes in OUD. Full article

Dried matrix spot (DMS) techniques have gained increasing attention in bioanalytical and forensic toxicology for the detection of opiates and opioids, offering minimally invasive sampling, enhanced sample stability, and simplified storage and transport. This review provides a critical overview of recent methodological advances and applications of DMS across multiple biological matrices, including blood, plasma, urine, and oral fluid. Particular focus is given to sample preparation protocols, extraction strategies, analytical instrumentation, and method performance. Dried blood spots (DBS) remain the most established format; however, alternative matrices such as dried plasma, urine, and saliva spots (DPS, DUS, DSS) are expanding the scope of DMS, particularly in decentralised and point-of-care contexts. Despite clear advantages, such as reduced biohazard risk and compatibility with high-throughput workflows, several limitations persist, including low sample volumes, matrix-specific recovery issues, and lack of standardised procedures. Future efforts should aim to optimise paper substrates, improve solvent–matrix compatibility, and integrate DMS workflows with automated or miniaturised mass spectrometry platforms. Overall, DMS techniques represent a versatile and evolving analytical platform with strong potential for reliable opioid monitoring in both clinical and forensic settings. Full article

Several plants produce toxic and hallucinogenic metabolites, posing risks when misused due to a lack of botanical knowledge. Improper or accidental use of these plants poses a public health risk and has been associated with forensic cases involving poisoning, suicide, or drug-facilitated crimes. This review identified eight species of forensic interest that grow in southern Chile and analyzed their active compounds, mechanisms of toxicity, and documented clinical and legal cases. These selected species included both native and introduced taxa, whose main toxic agents are tropane alkaloids (atropine, scopolamine), piperidine (coniine), taxane pseudoalkaloids, and natural opiates (morphine, codeine). Most reported cases involved unintentional poisoning, mainly in children, highlighting the lack of regulation and awareness. This review revealed the need for improved forensic and clinical documentation of plant-based intoxications in Chile and greater public education regarding the toxicological risks posed by these botanical species. Full article

Recent bioassay studies have unexpectedly supported the high (computationally predicted) binding affinities of angiotensin receptor blockers (ARBs) at α-adrenergic receptors (αARs) in isolated smooth muscle. Computational predictions from ligand docking studies are consistent with very low concentrations of ARBs (e.g., sartans or bisartans) that partially reduce (20–50%) the contractile response to phenylephrine, suggesting that some ARBs may function as partial inverse agonists at αARs. Virtual ligand screening (docking) and molecular dynamics (MD) simulations were carried out to explore the binding affinities and stabilities of selected non-peptide ligands (e.g., ARBs and small-molecule opioids) for several G-protein coupled receptor (GPCR) types, including angiotensin II (AngII) type 1 receptor (AT₁R), α1AR, α2AR, and μ-(µOR) and ժ-opioid receptors (ժOR). Results: All ligands docked preferentially to the binding pocket on the cell surface domain of the GPCR types investigated. Drug binding was characterized by weak interactions (hydrophobic, hydrogen bonding, pi-pi) and stronger ionic and salt-bridge interactions (cation-pi and cation-anion interactions). Ligands specific to each GPCR category showed considerable cross-binding with alternative GPCRs, with small-molecule medications appearing less selective than their peptide or ARB functional equivalents. ARBs that exhibit higher affinities for AT₁R also demonstrate higher affinities for µORs and ժORs than opiate ligands, such as fentanyl and naltrexone. Moreover, ARBs had a higher affinity for αARs than either alpha agonists (epinephrine and phenylephrine) or inhibitors (prazosin and doxazosin). MD simulations of membrane-embedded ARB-GPCR complexes proved stable over nanosecond time scales and suggested that some ARBs may behave as agonists or antagonists depending on the GPCR type. Based on the results presented in this and related investigations, we propose that agonists bind to the resting A-site of GPCRs, while inverse agonists occupy the desensitizing D-site, which partial agonists like morphine and fentanyl share, contributing to addiction. ARBs block both AngII and alpha receptors, suggesting that they are more potent antihypertensive drugs than ACE inhibitors. ARBs have the potential to inhibit morphine tolerance and appear to disrupt receptor desensitization processes, potentially by competing at the D-site. Our results suggest the possible therapeutic potential of ARBs in treating methamphetamine and opiate addictions. Full article

Objective: The aim of this study is to determine if protein intake, diet quality, or engagement in physical activity mediate the relationship between sleep quality or duration and handgrip strength. Methods: The sample consisted of 2171 middle-aged persons examined in the 2013–2017 Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) prospective cohort study. Those with sleep apnea (n = 222) and missing data were excluded, resulting in an analytical sample of 1308. Handgrip strength, an objectively measured variable, was determined using a Jamar Hydraulic Hand Dynamometer and expressed relative to body mass index (based on measured height and weight). Sleep quality and duration were measured using the Pittsburgh Sleep Quality Index questionnaire. Protein intake was calculated from two 24 h recalls collected using the USDA Automated Multiple-Pass Method and expressed as g per kg of body weight. Diet quality was assessed using the Healthy Eating Index (HEI) and the energy-adjusted Dietary Inflammatory Index (e-DII). Physical activity was self-reported and expressed as meeting the Life Simple 7 criterion (≥150 min/week, 0–149 min/week, 0 min/week). Mediation analysis was conducted using the Hayes PROCESS macro, model #4, for SPSS Version 4.2. Adjustment for the self-reported covariates of age (years); sex at birth (male, female); race (African American, White); poverty status (<125% or >125% US HHS Poverty Guidelines); current cigarette smoker (yes, no); marijuana, opiate, and/or cocaine user (yes, no); medical conditions including diabetes, hypertension, and/or metabolic syndrome (yes, no); and mean energy (kcal, only protein model) was performed. Results: Protein intake, expressed as g per kg of body weight, mediated the relationship between sleep quality and sleep duration and handgrip strength (indirect effect = −0.0017 ± 0.0006, CI 95% (−0.0030, −0.0006, p < 0.05); indirect effect = 0.0057 ± 0.0019, CI 95% (0.0023, 0.0098, p < 0.05, respectively)). Diet quality, as measured using the HEI, mediated the relationship between sleep duration and handgrip strength (indirect effect = 0.0013 ± 0.0007, CI 95% (0.0001, 0.0030, p < 0.05). Conclusions: Protein intake and a healthy diet mediate the relationship between sleep and handgrip strength, suggesting that these factors may play a role in preserving muscle strength. Full article

Background: Tapentadol is an atypical opioid with a dual mechanism as a mu agonist and norepinephrine reuptake inhibitor. This study characterized tapentadol use in the United States (US) using three databases. Methods: Drug distribution data from 2010 to 2020 were extracted from the Drug Enforcement Administration (DEA)’s Automated Reports and Consolidated Orders System (ARCOS), including use per region (mg/person) and business activity (i.e., pharmacy). Tapentadol prescription claims from the Medicare and Medicaid programs for 2010–2020 were also examined. Results: The distributed amount of tapentadol was 3.5 tons in 2020. Distribution was over twice as high in southern (South Atlantic = 29.0 mg/person, East South Central = 28.8) relative to Pacific (12.9) or New England (12.8) states. Tapentadol use decreased nationally between 2012 and 2020 by −53.8%. Adult diabetes prevalence was significantly associated with tapentadol distribution in 2012 (r(50) = +0.44, p < 0.01) and 2020 (r(50) = +0.28, p < 0.05). Tapentadol prescribing to Medicaid patients declined −55.2% from the peak year, 2011, until 2020. Tapentadol prescribed by Nurse Practitioners accounted for over one-sixth (18.0%) of 2019 in Medicare. Conclusions: There has been a substantial decline over the past decade in tapentadol distribution and prescribing. However, the substantial regional differences may warrant further attention by opioid stewardship programs. Full article

Background: Chronic cough is a common symptom in patients with interstitial lung diseases (ILDs), which significantly affects health-related quality of life (HRQoL). The prevalence of chronic cough varies from 30% to almost 90% in different ILDs, with the highest rate in patients with idiopathic pulmonary fibrosis. However, the pathophysiology of cough in ILDs remains poorly understood, with multiple proposed mechanisms contributing to its development. This knowledge gap complicates both clinical assessment and treatment, as current therapeutic strategies target general cough mechanisms rather than ILD-specific pathways. This review synthesizes existing data to clarify distinct cough mechanisms across ILD subtypes and identify opportunities for more targeted therapeutic strategies in this challenging patient population. Moreover, cough can be a clinical marker of disease severity and a predictor of ILD progression and transplant-free survival. Effective cough-specific therapeutic options that consider potential mechanisms, comorbidities, and individual effects on HRQoL are needed for cough associated with ILD. Therefore, the aim of this review was to analyze the prevalence, the impact on HRQoL, the pathophysiology, and the management of chronic cough in ILDs. Methods: We performed a comprehensive search in PubMed, MEDLINE, Embase, and the Cochrane Library. This review included randomized clinical trials, observational studies, systematic reviews, and meta-analyses in adults with chronic cough comparing ILD types. The following were excluded: commentaries, letters, case reports and case series, conference abstracts, and studies and publications lacking cough-specific outcomes. Results: Several approaches to reduce cough frequency and severity were described: antifibrotic agents, neuromodulators, opiates, inhaled local anesthetics, oxygen, speech therapy, and anti-reflux therapy. Some therapeutic approaches, such as oral corticosteroids and thalidomide, can cause significant side effects. Novel agents, such as P2X3 receptor antagonists, which are in phase III trials (COUGH-1/2), show promising results for refractory cough and may benefit ILD-related cough. Conclusions: Thus, a comprehensive assessment of cough is required for effective cough treatment in patients with ILDs considering possible mechanisms and individual impact on QoL. Full article

Background: “Chemsex” involves the intake of a range of drugs (e.g., synthetic cathinones, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), ketamine, methamphetamine, “poppers”, type V phosphodiesterase (PDE) inhibitors, MDMA/ecstasy, cocaine, cannabis, and occasionally a few other molecules as well, to enhance and prolong sexual experiences. This paper aims to provide an overview of the clinical pharmacology of the vast range of drugs that are being used for chemsex with a focus on both the medical and psychopathological disturbances that they can produce. Methods: A narrative literature review was conducted using Pubmed, Scopus, and Web of Science databases. A total of 273 papers published up to January 2025 were screened; articles were selected based on relevance to chemsex/sexualized used behaviour and related substances. Both human and preclinical studies were considered. Results: The use of stimulants is likely related to the need to increase as much as possible both sexual arousal and performance but also to increase social interactions. Furthermore, the empathogenic/entactogenic activities of some MDMA-like “love drugs” facilitate the occurrence of “feeling closer/more intimate” emotional sensations, and GHB/GBL may provide the user with a subjective sensation of disinhibition, hence facilitating condomless meetings with a higher number of random partners. Conversely, ketamine may be used to both enjoy its psychotropic dissociative characteristics and facilitate the potentially painful receptive anal intercourse and/or fisting experiences. Most typically, these drugs are consumed in combination, with polydrug exposure possibly facilitating the occurrence of serotonergic syndrome, seizures, drug–drug pharmacokinetics’ interaction, and sympathomimetic overstimulation. Following these polydrug exposures, a range of psychopathological conditions have at times been reported. These issues may lead to misuse of opiates/opioids, gabapentinoids, and/or antipsychotics. Conclusions: Further actions should aim at reducing the stigma that prevents individuals from accessing necessary healthcare and support services. A multidisciplinary approach that combines medical, psychological, and social support remains key to managing the complex challenges posed by chemsex-related drug use. Full article

Objectives: Mucositis is a debilitating side effect of cancer therapy that adversely affects quality of life, cost of care, and the outcome of cancer therapy. Oral mucositis-related pain may be treated with numerous modalities but often includes opioids. The effects of opiate treatment on painful UM and its overall influence on the burden of illness (BOI) in cancer patients remain unknown. Methods: This study utilized the 2017 United States (US) National Inpatient Sample (NIS) database. The exposure was opioid treatment for chemo-induced ulcerative mucositis (UM), oral mucositis-induced pain, and the main outcomes included in-hospital mortality and BOI, length of hospital stays (LOS), and total hospital charges. Multivariable regression analysis was used to examine the relationship between outcomes and the key independent variable, opioid use, adjusting for propensity scores. Results: In the propensity score-adjusted analysis, UM patients with opioid treatment had 0.51 times lower total charges (95% CI: 0.42–0.76) and 0.67 times shorter LOS (95% CI: 0.51–0.87) than the UM patients without opioid treatment. However, there was no association between opioid treatment and in-hospital mortality. In the sensitivity analysis, the effect estimates were comparable in the propensity score-adjusted analysis, the decile-adjusted model, and the full model with the non-propensity score estimated method. Conclusions: Cancer patients with chemotherapy-induced UM-prescribed opioid analgesics for treating pain are associated with a lower BOI. Opioid pain medications are commonly provided to cancer survivors; estimating the BOI among them is crucial in supportive care research. Full article

The word opium derives from the ancient Greek word ὄπιον (ópion) for the juice of any plant, but today means the air-dried seed capsule latex of Papaver somniferum. Alkaloid chemistry began with the isolation of morphine from crude opium by Friedrich Wilhelm Adam Sertürner in 1804. More than a century later, Hungarian pharmacist János Kabay opened new perspectives for the direct isolation of morphine from dry poppy heads and straw without the labor-intensive harvesting of opium. In 2015, Kabay’s life and achievements obtained official recognition as constituting a «Hungarikum», thereby entering the national repository of matters of unique cultural value. To this day, the study of Papaver alkaloids is a focus of medicinal chemistry, the (perhaps unstated) aspiration of which is to obtain an opioid with lesser abuse potential and side effects, while retaining good analgesic properties. We begin this review with a brief account of opiate biosynthesis, followed by a detailed presentation of semisynthetic opioids, emphasizing the efforts of the Alkaloida Chemical Company, founded in 1927 by János Kabay, and the morphine alkaloid group of the University of Debrecen. Full article

The misuse of opioids and opiates has remained a persistent issue since the 19th century. The recent resurgence of non-fentanyl synthetic opioids, such as U-type opioids and nitazenes, has further exacerbated the ongoing crisis. Identifying these synthetic opioids presents many challenges, including the emergence of new substances, the lack of standards, and the presence of structural isomers. This highlights the need for a robust structural characterisation strategy in forensic laboratories. To address these challenges, we developed a methodology to identify a U-type opioid sample received by Kosmicare from the European Union-funded SCANNER project, which was suspected to be either U-48800 or U-51754. Our innovative approach combined gas chromatography coupled with mass spectrometry (GC-MS), nuclear magnetic resonance spectroscopy (NMR), and molecular dynamics to characterise the questioned sample unequivocally. While the GC-MS analysis suggested a potential match with the mass spectrum of U-51754 and its structural isomer U-48800, NMR analysis confirmed the presence of U-48800 in the sample, which was further validated through molecular dynamics experiments. These experiments provided additional insights, confirming the structural features underlying the obtained NMR profile. The presented methodology offers a valuable solution for cases involving the identification of isomers, which are currently one of the most significant challenges in identifying new psychoactive substances. Full article