Search Results (114)

The use of opioids for cancer-related pain is essential but poses significant challenges due to the risk of misuse and the development of opioid use disorder (OUD). This review takes a multidisciplinary perspective based on the current scientific literature to analyze the pharmacological mechanisms, classification, and therapeutic roles of opioids in oncology. Key risk factors for opioid misuse—including psychiatric comorbidities, prior substance use, and insufficient clinical monitoring—are discussed in conjunction with validated tools for pain assessment and international guidelines. The review emphasizes the importance of integrating toxicological, pharmacological, physiological, and public health perspectives to promote rational opioid use. Pharmacogenetic variability is explored as a determinant of treatment response and addiction risk, underscoring the value of personalized medicine. Evidence-based strategies such as early screening, psychosocial interventions, and the use of buprenorphine-naloxone are presented as effective measures for managing OUD in cancer patients. Ultimately, this work advocates for safe, patient-centered opioid prescribing practices that ensure effective pain relief without compromising safety or quality of life. Full article

The gender gap in drug use is narrowing in regions where access to criminalized substances, such as opioids, is increasing. While research shows that substance use is gendered, less is known about the cultural norms and values shaping women’s drug use, as most studies focus on men. Cross-national comparisons of cultural models of addiction are needed to better understand how addiction is perceived and to inform culturally responsive treatment approaches for women. This study examined cultural models of addiction among reproductive-aged women receiving treatment for substance misuse in London, Toronto, and Delhi. Participants completed a semi-structured questionnaire with open-ended and free-list prompts. Findings revealed shared cultural models attributing drug use to psychological factors, such as self-medicating to manage negative emotions or enhance positive ones, as well as relational, developmental, and biological influences. In conclusion, the study highlights the importance of incorporating cultural models into research and treatment. By using an inductive approach to explore meanings surrounding drug use among people in recovery, researchers can better understand how interventions are received and interpreted through existing internal frameworks. 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: Pain is a prevalent issue among breast cancer patients and survivors, with a significant proportion receiving hydrocodone for pain management. However, the rescheduling of hydrocodone from Schedule III to Schedule II by the U.S. Drug Enforcement Administration (DEA) in October 2014 raised concerns about potential barriers to opioid access for cancer patients, particularly among vulnerable populations such as dually eligible Medicare–Medicaid beneficiaries and racial/ethnic minorities. Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data including 52,306 early-stage breast cancer patients from 2011 to 2019. We employed multivariable logistic regression models with model specification tests to stratify the subgroups and evaluate the differential effects of the policy change by Medicaid dual eligibility and race–ethnicity, while adjusting for other patient demographics, clinical characteristics, and cancer treatments. Results: The rescheduling of hydrocodone was associated with significantly different effects on prescription opioid use across subgroups, with the most pronounced reduction in hydrocodone prescription observed among dual-eligible racial/ethnic minority patients (adjusted odds ratio [AOR] = 0.57; 95% confidence interval [CI]: 0.44–0.74; p < 0.001). Non-dual-eligible patients experienced a smaller reduction in hydrocodone use (AOR = 0.84; 95% CI: 0.78–0.90; p < 0.001). Concurrently, non-hydrocodone opioid use significantly increased among non-dual-eligible non-Hispanic White patients (AOR = 1.29; 95% CI: 1.19–1.40; p < 0.001), suggesting a substitution effect, while smaller non-significant increases were observed among other subgroups. Conclusions: Hydrocodone rescheduling led to the greatest reduction in hydrocodone use among dual-eligible racial–ethnic minority patients. The corresponding increase in non-hydrocodone opioid use was limited to non-dual-eligible non-Hispanic White patients. These findings highlight the need for opioid policies that balance misuse prevention with equitable access to pain relief, particularly among underserved populations. Full article

Background/Objectives: In 2022, 2.2 million adolescents were diagnosed with substance use disorders, including 265,000 with opioid use disorder. The National Survey on Drug Use and Health revealed that 130,000 adolescents misused prescription pain medications, often obtaining them from friends or relatives. This age group perceives weekly heroin use as less risky than those younger or older. Methods: A questionnaire was developed for 7th to 12th graders in a rural Texas school district as part of a fentanyl awareness curriculum. The questionnaire included Likert scale, multiple choice, and yes/no questions. The participants were categorized into younger (grades 7th and 8th) and older students (grades 9th through 12th), and associations were explored between demographic characteristics, responses, and grade groups using chi-square tests. To assess confidence, behavior, and the impact of education, we used chi-square and Fisher’s exact tests. Results: The participants (n = 94; 85.11%) identified as Hispanic or Latino, with a smaller percentage identifying as White or more than one race. An association was found between feeling more in control of actions related to substances and fentanyl (p-value = 0.04) after receiving education. No association was found between education and confidence in identifying fentanyl. Conclusions: This study aligns with a surge in fentanyl-related overdose deaths in a high-intensity drug trafficking region. Recent fentanyl overdoses among school-age children prompted legislative changes in 2023, making this study valuable for understanding the epidemic within the geographical context. These results suggest that school-based education may play a role in strengthening adolescents’ behavioral intentions to fentanyl exposure, though additional efforts are needed to improve risk identification. 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

Xylazine, commonly called “tranq” or “sleep cut”, is a strong α2-adrenergic agonist used in veterinary practice as a sedative, analgesic, and muscle-relaxing agent. It has never been approved by the Food and Drug Administration for human use, but its use by people is on the rise. In the last decades, due to its low cost and ease of availability, it has often been illicitly used due to its abuse potential as a drug for attempted sexual assault and intended poisoning. In addition, xylazine’s presence in the human body has also been related to domestic accidental events. Generally, it is combined with multiple other drugs, typically by intravenous injection, potentiating the doping effects. Xylazine’s mechanism of action is different from that of other illicit opioids, such as heroin and fentanyl, and it has no known antidote approved for use in humans. The combination with fentanyl prolongs the euphoric sensation and may heighten the risk of fatal overdose. Furthermore, it may cause adverse effects, including central nervous system (CNS) and respiratory depression, bradycardia, hypotension, and even death. Recent reports of xylazine misuse have risen alarmingly and describe people who become “zombies” because of the drug’s harmful effects on the human body, including serious wound formation that could even lead to limb amputation. This paper is an extensive review of the existing literature about xylazine and specifically deals with the chemistry, pharmacokinetics, pharmacodynamic, and toxicological aspects of this compound, highlighting the most recent studies. Full article

Firefighters are vulnerable to opioid misuse given the adverse effects their occupation has on mental and physical health. Yet there are limited data on opioid misuse within this population. This study examined the prevalence of illicit prescription opioid use among a nationally representative sample of U.S. firefighters and factors related to opioid misuse. Data were collected through reliable questionnaires from 617 firefighters prior to participating in an intervention designed to mitigate the negative impacts of trauma. The lifetime prevalence of illicit prescription opioid use was 14% compared to 13% in the general U.S. population. The most commonly misused opioids were hydrocodones with trade names Vicodin, Lortab, and Lorcet (72% of those illicitly using opioids). Illicit prescriptions opioid use was not significantly correlated with any demographics examined. However, firefighters who engaged in illicit opioid use exhibited poorer mental health, more alcohol-related problems, and an increased likelihood of misusing other prescription medications. In a regression analysis, alcohol consumption issues, Post-Traumatic Stress Disorder (PTSD), and the illicit use of sedatives and tranquilizers emerged as significant predictors of illicit prescription opioid use. Illicit prescription opioid use by firefighters is a potential problem especially when considered along with other factors such as mental health. Longitudinal studies are needed to further deepen our knowledge about this issue. 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

The search for effective pain management solutions remains a critical challenge, especially amidst growing concerns over the use of conventional opioids. In the US, opioid-related mortality rates have surged to as many as 80 deaths per 100,000 people in some states, with an estimated economic burden of USD 1.5 trillion annually—exceeding the gross domestic product (GDP) of most US industrial sectors. A remarkable breakthrough lies in the discovery that indole and oxindole alkaloids, produced by several genera within the plant Tribe Naucleeae, act on opioid receptors without activating the beta-arrestin-2 pathway, the primary driver of respiratory depression and overdose deaths. This systematic review explores the pharmacological properties, mechanisms of action, dosing considerations, interactions, and long-term effects of mitragynine and corynoxeine, alkaloids from the Southeast Asian plant Mitragyna speciosa (kratom) and others in the Tribe Naucleeae. Mitragynine, a partial opioid receptor agonist, and corynoxeine, known for its anti-inflammatory and neuroprotective effects, demonstrate significant therapeutic potential for managing diverse pain types—including neuropathic, inflammatory, nociceptive, visceral, and central pain syndromes—with a focus on cancer pain. Unlike traditional opioids, these compounds do not recruit beta-arrestin-2, avoiding key adverse effects such as respiratory depression, severe constipation, and rapid tolerance development. Their distinct pharmacological profiles make them innovative candidates for safer, non-lethal pain relief. However, challenges persist, including the unregulated nature of kratom products, inconsistencies in potency due to crude extract variability, potential for misuse, and adverse drug interactions. Addressing these issues requires establishing standardized quality control protocols, such as Good Manufacturing Practices (GMP), to ensure consistent potency and purity. Clear labeling requirements with dosage guidelines and warnings should be mandated to ensure safe use and prevent misuse. Furthermore, the implementation of regulatory oversight to monitor product quality and enforce compliance is essential. This review emphasizes the urgency of focused research to optimize dosing regimens, characterize the pharmacodynamic profiles of these alkaloids, and evaluate long-term safety. By addressing these gaps, the mitragynine- and corynoxeine-related drug classes can transition from promising plant-derived molecules to validated pharmacotherapeutic agents, potentially revolutionizing the field of pain management. 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

Background/Objectives: As long-term prescription opioid use is associated with increased morbidity and mortality, timely dose reduction of prescription opioids should be considered. However, most research has been conducted on patients using heroin. Given the differences between prescription and illicit opioid use, the aim of this review was to provide an overview of pharmacological strategies to reduce prescription opioid use or improve clinical outcomes for people who experience long-term prescription opioid use, including those with opioid use disorder. Methods: We conducted a systematic database search of PubMed, Embase, CINAHL, and the Cochrane Library. Outcomes included dose reduction, treatment dropout, pain, addiction, and outcomes relating to quality of life (depression, functioning, quality of life). Results: We identified thirteen studies (eight randomized controlled trials and five observational studies). Pharmacological strategies were categorized into two categories: (1) deprescribing (tapering) opioids or (2) opioid agonist treatment (OAT) with long-acting opioids. Tapering strategies decreased opioid dosage and had mixed effects on pain and addiction. OAT with buprenorphine or methadone led to improvements in pain relief and quality of life, with a slight (non-significant) preference for methadone in terms of treatment retention (RR = 1.10 [CI: 0.89–1.37]) but not for other outcomes. Most studies had high dropout rates and a serious risk of bias. Conclusions: Tapering reduced prescription opioid doses had mixed effects on pain. OAT improved clinical outcomes without dose reduction. Based on our review findings, there is no clear preference for either tapering or OAT. Tapering may be considered first as it reduces dependency, tolerance, and side effects, but is associated with adverse events and not always feasible. OAT can be a suitable alternative. Non-pharmacological interventions may facilitate tapering. Further research is needed to identify novel pharmacological strategies to facilitate opioid tapering. Registration: PROSPERO 2022 CRD42022323468. Full article

 Background: Substance use disorder in the United States represents a complex and growing public health crisis, marked by increasing rates of overdose deaths and the misuse of prescription medications. There is a critical need for furthering the understanding of the molecular and genetic mechanisms that can lead to substance use disorder. Identifying significant variants in the kynurenine pathway could help identify therapeutic targets for intervention. Methods: The All of Us cohort builder evaluated the frequency of variants of four genes, TDO2, IDO1, IDO2, and KMO, encoding enzymes in the kynurenine pathway. The samples were broken into six cohorts: alcohol, cannabis, cocaine, opioid, other use disorder, and control. Using Chi-square analysis, the frequency of at least one copy of a variant allele was calculated. Results: Chi-square analysis showed a significant variation in genetic frequency (p-value < 0.005) in 14 of 18 polymorphisms analyzed. The cocaine cohort had the most significant variants (13), cannabis had 11, opioids had 3, other use disorders had 2, and alcohol had 1 significant variant. Conclusions: This study found associations of polymorphisms in the TDO2, IDO1, IDO2, and KMO genes of individuals with a substance use disorder. These results provide evidence of potential predictors of increased susceptibility to substance use disorder.  Full article

Introduction: Evidence suggests an increasing misuse of veterinary medicines by humans. This study aims to analyse Adverse Events (AEs) associated with selected veterinary products using the Food and Drug Administration Adverse Events Reporting System (FAERS). Methods: A descriptive pharmacovigilance analysis was conducted on AEs related to 21 drugs approved for human and/or animal use. Results: A total of 38,756 AEs, including 9566 fatalities, were identified. The United States reported the highest number of cases (13,532), followed by Canada (2869) and the United Kingdom (1400). Among the eight drugs licenced exclusively for animals, levamisole, pentobarbital, and xylazine were most frequently reported. Reports predominantly involved males (57%) from the 18–64 age group, with incidents related mainly to overdose, dependence, and multi-agent toxicities. Unmasking techniques revealed ‘intentional overdose’ as the primary reaction. Polysubstance use was evident in 90% of the drugs, with benzodiazepines/Z-drugs and opioids as common co-used classes. Conclusions: Veterinary medications are increasingly infiltrating the illicit drug market due to their pharmacological properties. This trend highlights the need for heightened vigilance and awareness to prevent further public health risks associated with the adulteration of illicit substances with veterinary products like xylazine and pentobarbital. Full article

Anxiety-based cognitive distortions pertaining to somatic perception (ABCD-SPs)—primarily catastrophizing, fear avoidance, and kinesiophobia—have been repeatedly linked to worsening chronic, non-cancer pain (CNCP) outcomes of increased disability, amplified pain, ineffective opioid use, and opioid misuse. Several studies have suggested that treating ABCD-SPs can improve pain outcomes, yet identification and targeting of ABCD-SPs are not part of the standard medical pain assessment and treatment plan. Utilizing a narrative review of proposed mechanisms, published patient perspectives, and study correlations connecting these cognitive distortions with CNCP outcomes, an approach for better practice in the delivery of standard medical CNCP care can be deduced and formulated into a Belief and Behavior Action Plan (BBAP) for medical clinicians treating CNCP to implement into initial and maintenance care planning. These recommendations require relatively few resources to implement and have the potential to disseminate more effective CNCP treatment on a large scale now and in the future with the new frontier of cognitive computing in medicine. Full article