Search Results (1,015)

Methamphetamine (METH)-induced cardiomyocyte injury is the leading cause of mortality beyond acute intoxication. METH abuse often occurs in crowded, poorly ventilated environments, and even moderately high ambient temperatures exacerbate METH-related cardiovascular emergencies. However, the underlying mechanisms by which environmental factors drive the progression of cardiac diseases remain poorly understood. This study modeled the real-world scenario in vivo by exposing mice to METH under normothermic condition (NC, 22 °C) or subthreshold thermal stress (STS, 28 °C, a mild thermal challenge for mice) conditions, and in vitro by using H9c2 cardiomyocytes exposed to METH at 37 °C or 39 °C. STS significantly potentiated METH-induced cardiac dysfunction, mitochondrial ultrastructural damage, and oxidative stress (p < 0.05). Mechanistically, the co-exposure impaired mitochondrial respiratory chain complex I and led to excessive mitochondrial ROS (mtROS) production, activating the pro-apoptotic protein BAX, causing mitochondrial outer membrane (MOM) permeabilization and the cytosolic release of mitochondrial DNA (mtDNA). Cytosolic mtDNA-mediated NLRP3 inflammasome activation subsequently executed cardiomyocyte pyroptosis via caspase-1/Gasdermin D (p < 0.05). Crucially, the mitochondria-targeted antioxidant mitoquinone (MitoQ) substantially attenuated the aggravated cardiotoxicity by scavenging the initial mtROS (p < 0.05), thereby preventing the activation of the downstream BAX/mtDNA/NLRP3 axis. These findings provide evidence for a defined signaling basis for this drug-environment interaction and highlight mitochondrial redox modulation as a potential therapeutic strategy for psychostimulant-associated cardiovascular injury. Full article

Background: The 2-benzylbenzimidazoles or nitazenes are an evolving class of highly potent mu-opioid receptor agonists. Nitazenes were originally developed in the late 1950s for pharmaceutical use as analgesics; however, due to their extreme potency and the risk of adverse health outcomes, pharmaceutical research was discontinued. Since 2019, nitazenes have emerged as illicit drugs of abuse, causing significant concern. From 2021, they have been detected in both coronial and clinical casework in Victoria, Australia. This study examined nitazene-related coronial casework in Victoria from 2021 to 2025 to explore the trends and characteristics of nitazene-related deaths. Methods: Relevant cases were identified from the Victorian Institute of Forensic Medicine’s (VIFM’s) case management system. Data were collated and analysed from all coronial cases where a nitazene was detected by a toxicological analysis between 1 January 2021 and 31 December 2025. Trend comparisons were made with nitazene detections reported in other countries. Results: Nitazenes were detected in 23 deaths from a total of approximately 33,108 coronial cases admitted to the VIFM for investigation over the time period. The age range was 17–45 years, with a median of 32 and with 87% of the deaths being male. The nitazenes detected were protonitazene (n = 14), metonitazene (n = 5), isotonitazene (n = 2), N-pyrrolidino etonitazene (n = 2), N-desethyl isotonitazene (n = 1), methylenedioxynitazene (n = 1) and etodesnitazene (n = 1). Two cases contained more than one nitazene; both involved protonitazene, one involved metonitazene, and the other involved N-desethyl isotonitazene and methylenedioxynitazene. The timeline of detection of these nitazenes displays similarities with emergence trends in other countries. The nitazene concentrations ranged from 0.1 to 33 ng/mL. Broad polydrug usage was evident in all cases, with other drugs co-detected in the blood including stimulants (particularly, methylamphetamine (48%) and cocaine (44%)) as well as pharmaceutical benzodiazepines (43%) and pharmaceutical opioids (22%), and 13% had 6-monoacetylmorphine detected in either blood or urine. Novel benzodiazepines (39%) were also common, including bromazolam, which was co-detected in 35% of cases. Nineteen deaths were attributed solely to nitazene-related mixed-drug toxicity, while the remaining four cases were attributed to cardiac- and pulmonary-related disease, with polydrug use deemed a contributing factor. Conclusions: This novel case series adds comprehensive toxicological information to the body of evidence reinforcing the high risk of harm associated with the use of nitazenes. It is imperative that toxicology services continue to monitor for nitazenes to promote community awareness against nitazene-related harm. Full article

In recent years, there has been an unprecedented upsurge in opioid prescriptions for pain management. Consequently, the widespread availability of these medicines has led to an increase in misuse and abuse. This has led to a greater number of overdose-related deaths. The high prevalence of drug misuse was born of multiple and complex societal factors. However, from a medical perspective, critical contributors to the dire consequences of the crisis have been the need for chronic pain relief, as well as mental health issues within communities. Chronic pain coupled with psychological distress exacerbates patients’ predicaments and thus further fuels the crisis. Anxiety and depression have bidirectional and complex relationships with pain. The somatic symptoms associated with anxiety potentially worsen pain, whilst pain emanating from a chronic condition worsens anxiety. The same relational dynamic applies to depression and pain. Thus, these psychopathological states may be major contributors to the opioid abuse epidemic. Thus, psychosocial management as a first-line treatment instead of starting with drug treatments seems an enlightened approach to this problem. Cognitive behavioral therapy (CBT) has been proven to be effective in managing specific symptoms associated with chronic pain. Similarly, patient education has been shown to be a viable alternative to drugs for certain aspects of chronic pain treatment. We consider that the opioid crisis could be addressed with a greater reliance and emphasis on non-pharmacological approaches to managing chronic pain patients. This mini-review examines non-pharmaceutical and monitoring-based interventions to reduce opioid misuse risk among adults prescribed opioids for chronic non-cancer pain. Studies were identified through PubMed/MEDLINE, Scopus, and Google Scholar using terms related to chronic pain, prescription opioid misuse, opioid use disorder, cognitive behavioral therapy, patient education, prescription drug monitoring programs, digital health, telehealth, and non-pharmacological interventions. Studies were included if they focused on adults with chronic pain who were prescribed opioids or at risk of misuse, and evaluated interventions aimed at reducing unsafe opioid use, misuse risk, or opioid-related harm. Evidence was synthesized narratively to identify key intervention approaches, limitations, and clinical implications. Full article

The abuse of γ-hydroxybutyric acid (GHB) and its precursors, γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), has increased in recent years, with these substances frequently being illicitly added to beverages. GHB is colorless and odorless and exhibits anesthetic and hypnotic psychoactive effects, which are often exploited in drug-facilitated sexual assault, posing a significant public safety concern. Chromatography–tandem mass spectrometry is a conventional analytical approach for narcotic drug determination due to its high sensitivity and accuracy; however, its large instrumentation footprint and high operational cost limit its suitability for on-site rapid screening. In response to the growing demand for field-deployable analytical tools, rapid detection technologies for GHB have progressively evolved. This review summarizes and compares the advantages and limitations of current rapid detection methods for GHB and discusses their potential future developmental trends, with the aim of providing a reference for researchers and relevant authorities. Full article

Maternal consumption of alcohol and drugs during pregnancy can compromise neural development with long-lasting impact on individuals’ health. The inhibitor of growth (ING) family of proteins is an epigenetic regulator that plays a central role in fetal brain development, contributing to neural stem cell maintenance, neuronal differentiation, and the regulation of genes involved in brain morphogenesis. Given the susceptibility of the developing nervous system to epigenetic dysregulation induced by alcohol and drugs, this narrative study aims to summarize literature evidence with the hypothesis that ING proteins may represent a critical but understudied mechanistic link between maternal substance dependence and adverse neurodevelopmental outcomes in newborns. We conducted a comprehensive literature search across three databases (PubMed, Scopus, and Web of Science) up to February 2026 to identify relevant studies. Search terms included combinations of “ING proteins”, “neural development”, “alcohol”, “drugs”, “epigenetic”, “oxidative stress” and “neuroinflammation”. The inclusion criteria were limited to original studies published in English that examined neural development in newborns; the exclusion criteria encompassed non-English publications, letters, editorials, and case reports, and those not directly addressing the specified topics. We identified 55 papers; six were excluded per the exclusion criteria, leaving 49 works discussed in this review. ING proteins are epigenetic regulators essential for embryonic and neural development, including neural stem cell fate and neurogenesis, while substances of abuse are disruptors of the essential pathways necessary for the right fetal brain development. Furthermore, substance abuse creates oxidative stress environments and activates pathways that require ING-mediated chromatin regulation. ING proteins likely act as mediators linking oxidative stress, neuroinflammation, and transcriptional reprogramming in the developing brain. Meanwhile, alcohol and drugs induce epigenetic reprogramming that may disrupt ING-mediated chromatin control. There is little evidence directly linking prenatal exposure (e.g., alcohol and drugs) to ING changes during fetal development. However, we hypothesize that ING proteins function as epigenetic stress response regulators whose disruption by oxidative stress, inflammation, and chromatin alterations induced by prenatal alcohol or drug exposure may contribute to impaired fetal neurodevelopment. Although direct experimental evidence remains limited, this could be a promising and relatively unexplored research area. Full article

Background/Objectives: This study aimed to evaluate the frequency and predictors of adverse drug events (ADEs) related to medication abuse, misuse, and dependence, along with serious adverse events (SAEs), and to develop machine learning models to detect serious abuse, misuse, and dependence cases. Methods: This study included 455,415 ADE reports involving medications with high dependence potential reported to the Korea Adverse Event Reporting System (KIDS KAERS DB) between 2013 and 2022. Multivariate logistic regression was used to identify predictors. Three machine learning algorithms, random forest (RF), support vector machine, and eXtreme Gradient Boosting, were developed and evaluated. Results: Higher reporting likelihood of abuse-, misuse-, and dependence-related ADEs was observed with concomitant use of acetaminophen (OR 3.60, 95% CI 2.40–5.39), antidepressants (OR 1.75, 95% CI 1.17–2.61), antipsychotics (OR 4.97, 95% CI 3.21–7.17), and anticonvulsants (OR 3.42, 95% CI 2.42–4.81). Reports from the general public were associated with higher odds of abuse, misuse, and dependence than those from healthcare professionals (OR 4.59, 95% CI 3.04–6.94). Ketamine (ROR 14.03) and bromazepam (ROR 13.02) showed the highest likelihood of being classified as SAEs. Cardiovascular (ROR 30.36) and respiratory disorders (ROR 17.03) demonstrated the highest SAE reporting likelihood. RF model demonstrated the best predictive performance (AUC-ROC 0.928; accuracy 94.4%), with reporter type identified as a key feature. Conclusions: RF model demonstrated optimal predictive performance, with reporter type as the most important feature for detecting serious cases. This study emphasizes the importance of incorporating patient-reported data and polypharmacy surveillance to facilitate early detection of serious cases. Full article

Toxicological testing for drugs of abuse (DOAs) is an essential tool for healthcare practitioners and law enforcement agencies. Oral fluid (OF) is an alternative biological fluid for detecting recent DOA intake and is widely employed in forensic investigations. In the current study, a relatively novel and “green” fabric phase sorptive extraction (FPSE) procedure for sample preparation was coupled to liquid chromatography–tandem mass spectrometry (LC–MS/MS) to provide simplicity, cost-effectiveness, rapidity, low solvent consumption, and high analytical performance for the quantitative determination of ten commonly encountered DOAs and metabolites: amphetamine, benzoylecgonine, cocaine, codeine, ecgonine methyl ester, methadone, methamphetamine, 3,4-methylenedioxyamphetamine, 6-monoacetylmorphine, and morphine. The FPSE procedure was optimized by testing different filters, pH, extraction time, and solvents. The validated method demonstrated excellent linearity for all analytes, selectivity, acceptable precision, and high sensitivity (ranges for limits of detection (LODs) and quantification (LOQs) were 0.01–2 ng/mL and 0.03–6 ng/mL, respectively). Autosampler and short-term freeze stability exceeded 95% and 90% for all analytes, respectively. Overall, the combination of FPSE with LC–MS/MS provided a sensitive, selective, and environmentally friendly innovative analytical approach for the determination of DOA in OF and is suitable for both screening and confirmatory forensic and clinical applications. Full article

School dropouts remain a complex challenge for educational systems globally, with economic, social and psychological consequences for the individual and society at large. Evidence from the literature supports the high prevalence of school dropouts in rural communities, resulting in teenage pregnancy, exposure to drugs, and early marriage, among others. The study employed an exploratory approach to contribute to existing knowledge on the challenges of school disengagement through the lenses of community and peer-influence among high school students in rural South Africa. A qualitative research design employing semi-structured interviews was used, with a total of 20 interviews conducted (3 parents, 2 community leaders, 5 teachers, and 10 students, including dropouts). A thematic analysis procedure was employed for theme identification and analysis. There was evidence of a lack of community support in ensuring learners remain in school. Peer pressure was prevalent, given the influences and attachments students form with peers. This condition influences students to resort to drug abuse, teenage pregnancies, and early marriages as coping mechanisms for school dropouts. The overarching effect is a decline in academic comprehension, leading to school dropout rates. Parents and guardians play an active and collaborative role in discouraging practices that contribute to school dropout. Parent and community members must also be sensitised regarding the long-term negative effects of peer pressure and early marriage on education and future opportunities, especially for girls. Full article

Anti-inflammatory agents, antipyretics, and antibiotics are commonly used to manage fever and pain associated with infectious diseases in both adults and children. Despite their effectiveness, inappropriate and unnecessary prescriptions remain widespread, leading to adverse patient outcomes and, in the case of antibiotics, contributing to antimicrobial resistance. Addressing these issues requires effective stewardship programs focused on educating healthcare professionals and the public on evidence-based guidelines for optimal prescribing practices. This paper explores the five “A”s fundamental to infection management in pediatric and adult patients: appropriateness, abuse, antipyretics, anti-inflammatory agents, and antibiotics. Through a comprehensive literature review, expert perspectives, and clinical guidelines, the study evaluates the roles of anti-inflammatory agents (e.g., ibuprofen), antipyretics (e.g., paracetamol), and antibiotics in clinical practice, highlighting best practices for their use. Current guidelines emphasize that antipyretics should only be administered when fever is accompanied by significant discomfort or pain, as fever itself plays a role in the immune response. Based on the available literature, experts also suggest that paracetamol should be preferred as a first-line antipyretic due to its favorable safety profile, while ibuprofen should be used with caution, particularly during respiratory infections, varicella, and severe bacterial infections, due to its potential to exacerbate complications. According to experts, special consideration is also required for patients with renal or gastrointestinal comorbidities to prevent toxicity. Regarding antibiotics, prescriptions should be limited to clear evidence of bacterial infection to avoid unnecessary patient exposure and the development of antimicrobial resistance. Stewardship programs underscore the importance of selecting the right agent, optimizing dosing, and introducing shorter treatment regimens where supported by evidence, to improve therapeutic outcomes while minimizing resistance risks. Ultimately, this paper provides practical, evidence-based recommendations to support rational prescribing of antipyretics, anti-inflammatory drugs, and antibiotics, aiming to optimize patient outcomes, prevent unnecessary toxicity, and contribute to global efforts against antimicrobial resistance. Full article

Background and Objectives: One of the strongest early factors influencing later psychoactive substance use is adverse childhood experiences (ACEs). Studies investigate a variety of adverse experiences in relation to substance use, yet not all adverse childhood experiences are equal in intensity and harm. Our study aimed to address this gap by examining in detail the associations between individual ACEs, broader ACE categories, and different forms of psychoactive substance use. Materials and Methods: The study included 709 participants who completed self-report questionnaires. ACEs were measured using the MACE questionnaire. Marijuana use was measured using the CUDIT-R, alcohol use using the AUDIT, and heavy psychoactive substance use using the ASSIST. Linear regression analyses were used to predict associations. As expected, only a small part of the sample reported hard drug use; some analyses are limited to substantially fewer observations. Results: All regression models were statistically significant and predicted all three categories of psychoactive substances, but if we count the individual adverse experiences, the results become different. Although the results showed that ACE is a significant predictor of hard drug use and explains 25% of the variance, it is separately only emotional neglect that is associated with hard drug use. The regression analysis also explains 14% of the variance in marijuana use, but when considered separately, we found associations only with emotional neglect. The severity of alcohol use explains 13% of the variance, but only a few ACEs reach statistical significance: peer physical bullying, physical violence, and sexual abuse. Conclusions: The findings of our study suggest that adverse childhood experiences may not be qualitatively equivalent and therefore may not be evaluated only as a cumulative risk score. Separate ACE evaluations, instead of aggregate calculation of ACEs, may be useful to understand better which specific negative experiences have the greatest impact on subsequent use of psychoactive substances. The regression models explain only a small portion of the variance, which suggests that other factors may contribute to a larger share. Full article

Background/Objectives: Although therapeutic use of medicinal marijuana by patients in Poland became legal in 2017, there remains doubt among primary care physicians (PCPs) related to prescribing medicinal marijuana to their patients. In this study, we aimed to investigate the attitudes of family physicians and the systemic barriers that influence doctors’ therapeutic decisions with respect to prescribing medicinal marijuana. Methods: A 28-question survey was administered to a representative group of PCPs in the Lublin province of Poland. Statistical analysis of the answers of 293 (out of 301) respondents enabled us to determine the PCPs’ levels of knowledge about medicinal marijuana and their willingness to prescribe this type of therapy for their patients. Results: Only 32.3% of the surveyed PCPs had encountered patients who experienced symptoms associated with medicinal marijuana use. The two groups of symptoms most frequently reported by these PCPs were emotional agitation or playfulness (50.8%) and psychomotor retardation, drowsiness, and catatonia (25.4%). Only 41.0% of the surveyed PCPs perceived risks associated with prescribing medicinal marijuana to their patients, including the possibility of patients abusing medicinal marijuana, leading to addiction; sanctions from national regulatory bodies; trade in prescriptions (so-called “counterfeit prescriptions”); a lack of control over the resale of drugs by patients; and the absence of recommendations or guidelines for the use of medicinal marijuana. Our findings also demonstrate that only 5.2% of the surveyed PCPs had already prescribed medicinal marijuana in their professional practices. Conclusions: Limited willingness among PCPs to prescribe medicinal marijuana is primarily due to insufficient knowledge among physicians about the therapeutic effects of medicinal marijuana, its potential adverse effects, the legal framework for prescribing medications, and associated uncertainties. Full article

Trauma and substance use disorders commonly co-occur, are clinically complex, and are associated with poorer outcomes. This study applies mixture modeling methods in a co-occurring model to examine group membership patterns across trauma and substance use to identify differences in treatment outcomes. Using the constructs of trauma and substance use, a co-occurring model was conducted to examine group membership patterns at intake and identify differences in outcomes among court-mandated participants in a trauma-informed substance abuse treatment program. This approach uses a joint/cross-classification of two independent Latent Profile Analyses (LPAs) to examine patterns. Findings from the LPA identified three trauma and four substance use profiles. Classes from each LPA were regressed in the co-occurring model, resulting in 12 unique pattern combinations, which were then compared to examine the differences in graduate rates. The results demonstrated that those in the Minimal Trauma/Alcohol Use group were more likely to complete treatment than other higher drug-using populations. Given the complexity of the clinical treatment and the prevalence of co-occurring disorders, the application of this approach can provide a means to examine different grouping patterns across two diagnostic criteria that can guide and tailor treatment efforts. Full article

Fentanyl is a potent analgesic widely used in clinical practice. Fentanyl and its analogues are seriously abused and are emerging in the illegal drug market, leading to numerous intoxication cases. However, assessment of the potency of the pharmacological effect of these novel fentanyl analogues remains limited and inconsistent across studies. The development of novel analgesics has largely relied on the assessment of mu opioid receptor (MOR) binding affinity, with insufficient verification through the assessment of antinociceptive effects. This study evaluated the antinociceptive effects of 25 fentanyl analogues to investigate the relationship between chemical structure and antinociceptive effect. In this study, hot plate tests were conducted in mice to generate time–effect and dose–effect curves for the evaluation of the antinociceptive effect of fentanyl and its analogues. The results demonstrated that the antinociceptive effects of fentanyl analogues were dose- and time-dependent. The potency of the antinociceptive effect observed in this study generally aligned with the corresponding MOR binding affinities reported in the literature, although several analogues exhibited discrepancies. Structural modifications in different regions of the fentanyl scaffold affect the antinociceptive potency to different degrees, and the duration of action also varied across fentanyl analogues. Furthermore, opioid-induced hyperalgesia (OIH) was observed following administration of several fentanyl analogues, raising potential concerns regarding their abuse liability and development for analgesic purposes. Taken together, this study systematically evaluated and compared the antinociceptive effects of fentanyl analogues. The findings clarify the relationship between chemical structure and the antinociceptive effect, providing valuable insights for drug regulation and the development of novel analgesics. Full article

Introduction: This study was conducted to determine whether specific emergency physician (EP) diagnoses and/or neurological signs/symptoms upon admission to the Emergency Department (ED) were associated with normal/non-informative emergency electroencephalogram (emEEG). Methods: Data from consecutive patients admitted to the ED of our tertiary hospital over a two-year period (1 January 2023–31 December 2024) were analyzed retrospectively. We evaluated the correlation between normal/non-specific emEEGs and EP admission diagnoses and neurological signs/symptoms on admission. Epileptic discharges and sharp waves with triphasic morphology were considered specific patterns. Results: A total of 2008 patients underwent emEEG recording during the study period. EmEEGs were considered non-informative in 100% of global amnesia diagnoses, 100% of cases of mild head trauma, 100% of cases of migraine with aura, 98.3% of transient ischemic attacks (TIAs), 95.6% of transient losses of consciousness (TLCs) when seizure was not the primary suspected diagnosis, and in 92.7% of falls of unknown dynamics. Epileptic patterns were detected in 4% of patients presenting with TLC and in 2.4% of those with falls of unknown dynamics, with approximately half of these patients having a pre-existing diagnosis of epilepsy. Triphasic waves were detected in 4.9% patients with falls of unknown dynamics, in 1.7% with TIA, and in 0.4% with TLC. All of these patients had fever/sepsis or metabolic/electrolyte disorders. Overall, across all clinical scenarios, emEEGs were considered non-informative in 385 (19.1%) tested patients. Conclusions: emEEGs are almost non-informative in the diagnostic pathway for patients with global amnesia, mild head trauma, and migraine with aura, and in patients with TIA, TLC, or falls of unknown dynamics. EPs can safely consider avoiding emEEGs in the absence of previous epilepsy diagnosis, fever/sepsis, metabolic/electrolyte disturbances, or drug abuse. Full article

Background/Objectives: Intoxication by psychoactive substances (PASs) in children, adolescents, and young adults is a growing public health concern, with evolving patterns of use and hospital presentation. This study aimed to analyze the trends in hospital admissions for PASs among children and youth aged 10 to 24 years in Slovenia during the 2013–2023 period. Methods: We performed a retrospective observational study on patients discharged after hospitalization due to poisoning by PASs, according to ICD 10 AM. We considered four groups: children (aged 10–14), adolescents (aged 15–19) and young adults (20–21 and 22–24 years old). Annual hospitalization rates were stratified by sex, age group, and PAS category. The joinpoint regression model was used to estimate the average annual percentage change (AAPC) and annual percentage change (APC) response time trend. Results: Of those hospitalized, 52% were male and 65% were adolescents, followed by children (13%). A statistically significant decrease in alcohol-related hospitalizations was observed in the 10–14 and 15–19 age groups for both sexes in the period 2013–2023, while a statistically significant increasing trend was observed for alcohol in 22–24-year-old males during the period 2019–2023, and in multiple drug/other/unspecified PASs in the 15–19 age group in the period 2015–2023. Conclusions: Slovenia has some peculiarities in the abuse of PASs. Sex reversal phenomena are present already among children (especially for alcohol), and there are shifting risks in polydrug use in adolescents and emerging threats, as well as an increase in sedative or hypnotic poisoning in female adolescents since 2017. Full article