Search Results (116)

Background/Objective: Fentanyl plays a pivotal role in the opioid epidemic, defined by four waves of overdose deaths. To analyse fentanyl research trends, examining its links to mental health, pharmaceutical development, healthcare, diseases, and pathophysiology within the broader social and health context of the time. Methods: To understand the evolution of scientific publications on fentanyl and its relationship to the opioid crisis, a search using Web of Science Core Collection and PubMed was conducted. A total of 53,670 documents were retrieved related to opioid scientific production, among which 1423 articles (3%) focused specifically on fentanyl. The 21,546 MeSH terms identified in these documents were analysed by publication year and specific fields: Psychiatry and Psychology, Chemicals and Drugs, Healthcare, Diseases, and Phenomena and Processes. R-statistical/FactoMineR libraries were used for the correspondence analysis. Results: In the first overdose death wave, research focused on improving therapies and reducing side effects. The second wave emphasised detoxification methods with naltrexone, methadone, and behavioural therapies. The third wave addressed psychological treatments and HIV-syringe-sharing prevention. The fourth wave prioritised less addictive analogues and understanding consumer profiles to combat the epidemic. Conclusions: Fentanyl research has evolved alongside real-world challenges, reinforcing the connection between patients’ needs, healthcare professionals’ roles, illicit users, policymakers, and the research community’s contributions to addressing both therapeutic use and its broader societal impact. These findings highlight the necessity for an interdisciplinary approach to scientific research integrating prevention, treatment, education, legal reform, and social support, emphasising the need for public health policies and collaborative research to mitigate its impact. Full article

Background and clinical significance: Acute reduction in vigilance is a frequent reason for emergency department admissions, especially among the elderly. While intracranial causes or infections with fluid depletion are often responsible, there remain cases where imaging, laboratory tests, and clinical examination fail to provide a clear diagnosis. Case presentation: A 91-year-old woman was presented to the emergency department with recurrent episodes of somnolence to deep coma. On admission, her vital signs were stable, and cerebral CT imaging revealed no intracranial pathology. Laboratory analyses, including blood gas measurements, were unremarkable. Empirical treatment for possible intoxications with benzodiazepines or opioids using flumazenil and naloxone had no effect. An Addison’s crisis was considered but excluded following methylprednisolone administration without improvement in consciousness. Eventually, an isolated elevation of serum ammonia was identified as the cause of the reduced vigilance. Further investigation linked the hyperammonemia to abnormal intestinal bacterial colonization, likely due to a prior ureteroenterostomy. There was no evidence of liver dysfunction, thus classifying the condition as non-hepatic hyperammonemia. Therapy was initiated with rifaximin, supported by aggressive laxative regimens. Ammonia levels and vital parameters were closely monitored. The patient’s condition improved gradually, with serum ammonia levels returning to normal and cognitive function fully restored. Conclusions: This case highlights an uncommon cause of coma due to non-hepatic hyperammonemia in the absence of liver disease, emphasizing the diagnostic challenge when standard evaluations are inconclusive. It underscores the need for broad differential thinking in emergency settings and the importance of considering rare metabolic disturbances as potential causes of altered mental status. Full article

Canada’s national surveillance shows an 11% year-over-year decline in deaths from opioid and other unregulated drug poisonings, and a 10% drop in related hospitalisations in 2024. In stark contrast, Québec, home to more than nine million residents, and Montréal, the country’s second-largest city, experienced a continued rise in suspected drug-poisoning mortality through 2024, with fentanyl or analogues detected in almost two-thirds of opioid deaths. We conducted a narrative synthesis of provincial coroner and public-health surveillance tables, Health Canada dashboards, and the 2022–2025 Québec Strategy on Psychoactive-Substance Overdose Prevention. Results indicate a 40% increase in opioid-related mortality since 2018, a parallel uptick in stimulant toxicity, and a five-fold rise in overdose reversals at Montréal supervised-consumption services during the COVID-19 pandemic recovery. We aim to summarise the key problems underlying this epidemic and offer province-specific public-health strategies while also sending a call to action for first-line clinicians and psychiatrists to integrate overdose-risk screening, take-home naloxone, and stimulant-use-disorder treatments into routine care. We further urge Québec healthcare professionals to deepen their knowledge of provincial services such as supervised-injection sites and stay up to date with the rapidly evolving substance-use-prevention literature. Québec’s divergent trajectory underscores the need for region-tailored harm-reduction investments and stronger policy-to-clinic feedback loops to reduce preventable deaths. Full article

Suzetrigine represents a groundbreaking advancement in acute pain management as the first FDA-approved selective Na_v1.8 inhibitor. This comprehensive review synthesizes data from clinical trials, pharmacological studies, and prescribing information to evaluate its mechanism, efficacy, safety, and clinical implications. With demonstrated superiority over placebo in pivotal trials (SPID48: 29.3–48.4; p < 0.0001) and a favorable safety profile devoid of opioid-like addiction risks, suzetrigine offers a much-needed alternative in the opioid crisis era. However, its modest effect size compared to full-dose opioids, CYP3A-mediated drug interactions, and limited long-term data warrant judicious use. This article provides a balanced perspective on suzetrigine’s role in modern pain management protocols. Full article

Background/Objectives: In the current opioid crisis, medical hypnosis has been proposed as an alternative to opioids to control acute and chronic pain. The aim of this study was to use a meta-analysis to conduct an objective assessment of the value of medical hypnosis for the management of acute and chronic pain and opioid consumption. Methods: An initial PubMed search showed 111 relevant studies out of 1115. Twelve randomized controlled studies (RCTs) were identified, published from January 2014 to December 2024, focusing on acute and chronic pain. These RCTs were analyzed to compare the effects of medical hypnosis vs. standard care. Results: The use of medical hypnosis for acute pain was found to decrease pain by 0.54 standard deviations (SD) compared to the standard care, and the effect was medium and statistically significant (95% CI [0.19–0.90]; p = 0.0024). Oral morphine equivalents (OME) in the hypnosis group were 1.5 SD lower than in the placebo group, which was statistically significant (95% CI [0.12, 2.88]; p = 0.03). Unlike the effectiveness of hypnosis for acute pain treatment, hypnosis was not found to have any impact on the treatment of chronic pain. The mean pain value difference in the hypnosis group had little effect and showed a statistically insignificant result—a Hedges’ g score of 0.07 (95% CI [−0.14–0.27]; p = 0.518). Conclusions: The use of medical hypnosis was associated with a statistically significant decrease in acute pain scores and OME, suggesting it is a potential alternative to opioids, but our analysis indicates that hypnosis does not reduce chronic pain. Full article

The opioid drug overdose death rate remains a significant public health crisis in the U.S., where an opioid epidemic has led to a dramatic rise in overdose deaths over the past two decades. Since 1999, opioids have been implicated in approximately 75% of the nearly one million drug-related deaths. Research indicates that the epidemic is caused by both over-prescribing and social and psychological determinants such as economic stability, hopelessness, and social isolation. Impeding this research is the lack of measurements of these social and psychological constructs at fine-grained spatial and temporal resolution. To address this issue, we sourced data from Reddit, where people share self-reported experiences with opioid substances, specifically using opioid drugs through different routes of administration. To achieve this objective, an opioid overdose dataset is created and manually annotated in binary and multi-classification, along with detailed annotation guidelines. In traditional manual investigations, the route of administration is determined solely through biological laboratory testing. This study investigates the efficacy of an automated tool leveraging natural language processing and transformer model, such as RoBERTa, to analyze patterns of substance use. By systematically examining these patterns, the model contributes to public health surveillance efforts, facilitating the identification of at-risk populations and informing the development of targeted interventions. This approach ultimately aims to enhance prevention and treatment strategies for opioid misuse through data-driven insights. The findings show that our proposed methodology achieved the highest cross-validation score of 93% for binary classification and 91% for multi-class classification, demonstrating performance improvements of 9.41% and 10.98%, respectively, over the baseline model (XGB, 85% in binary class and 81% in multi-class). Full article

Background: Screening for substance use disorder (SUD) is a critical step to address the ongoing opioid crisis in the U.S., but fewer than 10% of people at risk screen. Technology may play a role in substantially increasing screening by making screening accessible through artificially intelligent (AI) chatbots. Methods: This was a single-arm mixed-methods pilot study to establish the system usability of an AI chatbot delivering information about substances, substance use disorder, and treatment options, and implementing self-screening for anxiety, depression, and substance use disorder. Participants were asked to engage with the AI chatbot for seven days and could self-select to screen. Results: Of the 92 participants enrolled, 91 engaged with the system at least once, and 29 (32%) completed at least one screener. Those who screened were given a referral if they exhibited moderate or severe anxiety, depression, and/or SUD. Over three-quarters (83%) of those screened received a referral for treatment, and 50% of those referred made an appointment for care. Users indicated that they found the system helpful and informative, and they felt comfortable screening. Conclusions: While other AI systems that share information about mental health and substance use exist, we know of no other AI chatbot that is being deployed specifically to facilitate SUD screening and referral. The system we describe here shows potential to support self-screening. Users generally find the system acceptable to use. AI technology may allow for improved access to SUD screening and treatment referrals, a critical step in responding to the opioid crisis. Full article

Much attention has been paid to the public health crisis that has resulted from the opioid epidemic. Given the high number of opioid users that are of childbearing age, the impact of utero exposure is a serious concern. Unfortunately, there is little knowledge regarding the consequences of opioid exposure during early development. While neurobehavioral effects of opioid exposure are well-documented, effects of exposure on embryogenesis remain largely unexplored. To address this gap in knowledge, we investigated the effects of oxycodone and fentanyl exposure on gene expression in zebrafish (Danio rerio) embryos using whole embryo RNA sequencing. Embryos were exposed to environmentally relevant (oxycodone HCl 10.6 ng/L and fentanyl citrate 0.629 ng/L) and therapeutically relevant doses (oxycodone HCl 35.14 μg/L and fentanyl citrate 3.14 μg/L) from 2 to 24 h post-fertilization (hpf), followed by another 24 h of opioid-free development. mRNA profiling at 48 hpf revealed dose- and drug-specific gene expression changes. Lower doses of oxycodone and fentanyl both induced more differentially expressed transcripts (DETs) than higher doses, potentially indicative of opioid receptor desensitization occurring at higher concentrations. In total, 892 DETs (corresponding to 866 genes) were identified across all conditions suggesting continued differential gene expression well after cessation of opioid exposure. Gene ontology analysis revealed changes in gene expression relating to extracellular matrix (ECM) organization, cell adhesion, and visual and nervous system formation. Key pathways include those involved in axon guidance, synapse formation, and ECM biosynthesis/remodeling, all of which have potential implications on neural connectivity and sensory development. These findings demonstrate that very early developmental exposure to opioids induces persistent transcriptomic changes which may have lasting implications for vertebrate cellular functions. Overall, these data provide insights into the molecular mechanisms of opioid-induced alterations during development. Full article

Concerns sparked by the US opioid epidemic have led to increased attempts to reduce England’s overall opioid consumption. Variations in health literacy across the country have led to differing prescribing practices, with increased chronic conditions appearing in areas of increased socioeconomic deprivation. This review investigated the relationship between increased opioid utilization and increased socioeconomic deprivation, aiming to highlight areas of England which have the highest opioid consumption. The review has investigated a range of socioeconomic factors, such as unemployment and fuel poverty, which have consequently influenced the higher frequency of opioid prescribing in areas where these factors were highest. Opioid abuse was most prevalent in areas with higher levels of deprivation. Geographically, areas with the highest levels of deprivation, and consequent opioid consumption, were situated in the North of England, with cities like London having a significantly lower consumption rate in comparison. These trends are a good starting point when designing future opioid epidemic-prevention strategies, as specific areas can be targeted to propel a reduction in opioid prescribing and addiction and thus decrease the likelihood of an opioid crisis forming. Although a longitudinal study would have strengthened the findings of this review, it was not feasible due to practical constraints. Full article

Chronic low back pain (CLBP) significantly impacts individuals’ quality of life and functional abilities. In non-oncological settings, CLBP is often treated for long periods using pharmacotherapy. This paper provides a comprehensive overview of pharmacological treatments for CLBP, detailing their mechanisms of action, adverse effects, and evidence supporting their use. We discuss various medication classes, including NSAIDs, acetaminophen, antidepressants, gabapentinoids, tramadol, major opioids, corticosteroids, antispasticity drugs, benzodiazepines, and antibiotics. Special emphasis is given to the opioid crisis, examining its history, the pathophysiology of opioid tolerance and dependence, the need for cautious opioid use, the key challenges in treatment and emerging medications for CLBP. We also share insights from our experiences with polypharmacy, commonly seen in CLBP patients, at a specialized pain centre in Belgium. Full article

Objectives: The United States has been greatly impacted by the opioid overdose epidemic, and fentanyl has largely contributed to the rise in overdose deaths in the past decade. We have analyzed trends in fentanyl-related mortality amongst adolescents and young adults (AYAs) to further describe emerging trends by ethnicity, gender, and age. Methods: We used mortality data from the U.S. Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) Multiple Cause of Death file from 2009 to 2022. Drug overdose mortalities were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes. Joinpoint regression was used to examine mortality rates involving fentanyl by ethnicity (Hispanic and non-Hispanic), gender, and age category. Results: The Average Annual Percent Change (AAPC) for fentanyl-involved mortality increased for all adolescents and young adults within the United States from 2009 to 2022. The greatest AAPCs for fentanyl-related mortalities occurred amongst, Hispanic AYAs, Male AYAs, and 13–18-year-olds. Conclusions: Significant increases in fentanyl-related mortalities have occurred in AYAs from 2009 to 2022. Disparities by ethnicity and emerging trends in gender and age category highlight the need for targeted approaches to help aid in reducing fentanyl-involved mortality amongst AYAs. There is an urgent need for harm reduction and public health efforts to address this escalating crisis. 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

Background/Objectives: The opioid crisis has disproportionately impacted U.S. military veterans, who face heightened risks of opioid use disorder and overdose due to chronic pain and mental health conditions. The pharmaceutical industry’s role in misrepresenting opioid risks—leading to over USD 50 billion in legal settlements—has included targeted marketing to vulnerable populations. This study examines Janssen Pharmaceuticals’ “Imagine the Possibilities Pain Coalition” (IPPC), which aimed to increase opioid use among veterans with chronic non-cancer pain. Insights from this public health industry document analysis offer guidance for military medicine and healthcare policymaking. Methods: Using the Opioid Industry Document Archive (OIDA), housed at Johns Hopkins University and the University of California, San Francisco, researchers conducted retrospective content analysis. Documents referencing veterans were identified through keyword searches on Johns Hopkins’ SciServer portal and reviewed using CoCounsel, an AI-based legal document platform using a human-in-the-loop approach. Relevant documents were examined by the authors to extract material aligned with the research focus. Results: The IPPC employed strategies to influence opioid prescribing for veterans. These included educational materials that minimized addiction risks and exaggerated long-term benefits and empathy-driven narratives prioritizing immediate pain relief over potential harms. Ghostwriting ensured favorable perspectives on opioids in scientific literature, aligning with broader industry strategies to promote opioids for chronic pain. Conclusions: The targeted marketing of opioids to veterans has exacerbated the opioid crisis, as documented in government reports and litigation. Rigorous oversight of industry-funded coalitions and evidence-based practices are critical to insulating military healthcare from corporate influence and addressing the opioid crisis among veterans. Full article

Fentanyl is a synthetic opioid widely used for its potent analgesic effects in chronic pain management and intraoperative anesthesia. However, its high potency, low cost, and accessibility have also made it a significant drug of abuse, contributing to the global opioid epidemic. This review aims to provide an in-depth analysis of fentanyl’s medical applications, pharmacokinetics, metabolism, and pharmacogenetics while examining its adverse effects and forensic implications. Special attention is given to its misuse, polydrug interactions, and the challenges in determining the cause of death in fentanyl-related fatalities. Fentanyl misuse has escalated dramatically, driven by its substitution for heroin and its availability through online platforms, including the dark web. Polydrug use, where fentanyl is combined with substances like xylazine, alcohol, benzodiazepines, or cocaine, exacerbates its toxicity and increases the risk of fatal outcomes. Fentanyl undergoes rapid distribution, metabolism by CYP3A4 into inactive metabolites, and renal excretion. Genetic polymorphisms in CYP3A4, OPRM1, and ABCB1 significantly influence individual responses to fentanyl, affecting its efficacy and potential for toxicity. Fentanyl’s side effects include respiratory depression, cardiac arrhythmias, gastrointestinal dysfunction, and neurocognitive impairments. Chronic misuse disrupts brain function, contributes to mental health disorders, and poses risks for younger and older populations alike. Fentanyl-related deaths require comprehensive forensic investigations, including judicial inspections, autopsies, and toxicological analyses. Additionally, the co-administration of xylazine presents distinct challenges for the scientific community. Histological and immunohistochemical studies are essential for understanding organ-specific damage, while pharmacogenetic testing can identify individual susceptibilities. The growing prevalence of fentanyl abuse highlights the need for robust forensic protocols, advanced research into its pharmacogenetic variability, and strategies to mitigate its misuse. International collaboration, public education, and harm reduction measures are critical for addressing the fentanyl crisis effectively. Full article

The complexity of our life experiences and the rapid progress in science and technology clearly necessitate reflections from the humanities. The ever-growing intersection between science and society fosters the emergence of novel interdisciplinary fields of research. During the past decade, Medical Humanities arose to meet the need to unravel hidden information beyond technology-driven and fact-based medicine. In the present paper, we put forward the hypothesis that there is a similar requirement to develop Pharmaceutical Humanities as an academic discipline within pharmacy and pharmaceutical biology. Based on Thomas Kuhn’s epistemological theory on the structure of scientific revolutions, one may argue that a paradigm change for Pharmaceutical Humanities might open new levels of insight. Many complex diseases (e.g., cancer, neurological diseases, and mental disorders) remain uncurable for many patients by current pharmacotherapies, and the old beaten paths in our therapeutic thinking may at least partly have to be left behind. By taking examples from Pharmaceutical Biology, we attempt to illustrate that the transdisciplinary dialogue with the humanities is fertile ground not only for enlarging our understanding of disease-related conditions but also for exploring new ways of combatting diseases. In this context, we discuss aspects related to traditional herbal medicine, fair access and benefit sharing of indigenous knowledge about medicinal plants, post-traumatic stress syndrome, the opioid crisis, stress myocardiopathy (broken heart syndrome), and global environmental pollution with microplastics. We also explore possibilities for a narrative turn in pharmacy. The urgent need for inter- and transdisciplinary solutions to pressing health-related problems in our society may create a scholarly atmosphere for the establishment of Pharmaceutical Humanities as a fruitful terrain to respond to the current demands of both science and society. Full article