Search Results (759)

Morphine is an opioid extracted from the poppy plant and highly effective for moderate to severe pain management. Development of techniques to measure the concentration of this highly addictive drug in various matrices is very important. This work was aimed at the development of a sensitive electrochemical method for detection of morphine in wastewater. Molecularly imprinted (MIP) electrodes were made by the electro-polymerization process using pyrrole as a monomer. Electro-polymerization was performed on glassy carbon electrodes in the presence of morphine before the extraction of the entrapped morphine molecules. Various techniques were employed to monitor the polymerization and response of the fabricated electrodes toward morphine. These techniques included Fourier transform infrared spectroscopy (FTIR), cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS). The morphine concentration was determined using SWV and CV by measuring the change in the redox peak current of [Fe(CN)₆]^−3/−4. These MIP electrode sensors were used to analyze morphine concentrations between 0 and 80.0 nM solution. The SWV showed a wider linear response region than CV. The detection limit using SWV was found to be 1.9 nM, while using CV, the detection limit was 2.75 nM. This MIP electrode sensor exhibited specificity when other closely related molecules were included and hence has potential as a cheap alternative technique for analysis of morphine. Full article

The investigation of the reward system is a fascinating domain with future applications for pain therapy and understanding addiction. We investigated interactions between tramadol use and the imidazoline system, through the modulatory effects of imidazoline receptor blockers, by behavior analysis and electroencephalography (EEG). Thirty-six male Wistar rats were placed within a conditioned place preference (CCP) setting using a three-compartment box apparatus. The transition of the six groups of subjects from one compartment to another was constantly monitored, related to preconditioning for one day, conditioning for eight days, and post-conditioning testing on day 10. During the conditioning phase, the groups received: a saline solution, efaroxan, idazoxan, tramadol, tramadol + efaroxan, and tramadol + idazoxan, respectively. The administration of efaroxan, idazoxan, or a saline solution in the non-preferred compartment did not alter the time spent by rats there. On the other hand, the administration of tramadol alone in the non-preferred compartment significantly increased the time spent by animals there (151.66 ± 11.69 s) post-conditioning as compared to preconditioning (34.5 ± 5.31 s) (p < 0.01), while the combination of efaroxan and tramadol significantly reduced its effect. After the combination with idazoxan, the effect of tramadol on increasing the time spent by the animal in the non-preferred compartment remained significantly higher than in the preconditioning phase. A significant increase in time spent in the non-preferred compartment demonstrates the existence of a CPP induction effect (by changing the preference). The effects of tramadol on the reward system can cause changes in the brain’s neuroplasticity, potentially leading to learned behaviors that promote drug seeking in previous non-preferred environments. Full article

Opioids are among the most effective drugs for treating moderate to severe pain. Unfortunately, opioid use, even short-term, can lead to addiction, tolerance, overdose, and respiratory depression. Therefore, efforts to design and develop novel compounds that would retain analgesic activity while reducing side effects continue unabated. The present study was designed to investigate the respiratory and cardiovascular effects of the hybrid peptide LENART01, which has evidenced potent antinociceptive and antimicrobial activity. This hybrid peptide, composed of N-terminally located dermorphin and C-terminal modified ranatensin pharmacophore, was tested in vivo in anesthetized rats. The main effect of LENART01 was apnea in 70% of examined animals, sighing, and a significant increase in blood pressure. Interestingly, the hybrid induced sighs less frequently than ranatensin, and apnea dependent on vagus nerve mu opioid receptor activation much less frequently and less intensely than dermorphin itself. This shows that LENART01 is a safer opioid system-related agent as compared to dermorphin for its prospective use in the treatment of pain. Full article

Food addiction (FA) is an emerging psychiatric condition that presents behavioral and neurobiological similarities with other addictions, and its early identification is essential to prevent the development of more severe disorders. The aim of the present study was to determine the ability of anthropometric measures, eating habits, symptoms related to eating disorders (ED), and lifestyle features to predict the symptoms of food addiction. Methodology: A cross-sectional study was conducted in a sample of 702 university students (77.3% women; age: 22 ± 6 years). The Food Frequency Questionnaire (FFQ), the Yale Food Addiction Scale 2.0 (YFAS 2.0), the Eating Attitudes Test (EAT-26), anthropometric measurements, and a set of self-report questions on substance use, physical activity level, and other questions were administered. A total of 6.4% of participants presented symptoms compatible with food addiction, and 8.1% were at risk for ED. Additionally, 26.5% reported daily smoking, 70.6% consumed alcohol, 2.9% used illicit drugs, and 29.4% took medication; 35.3% did not engage in physical activity. Individuals with food addiction had higher BMI (p = 0.010), waist circumference (p = 0.001), and body fat (p < 0.001) values, and a higher risk of eating disorders (p = 0.010) compared to those without this condition. In the multivariate logistic model, non-dairy beverage consumption (such as coffee or alcohol), vitamin D deficiency, and waist circumference predicted food addiction symptoms (R²_Nagelkerke = 0.349). Indeed, the machine learning approaches confirmed the influence of these variables. Conclusions: The prediction models allowed an accurate prediction of FA in the university students; moreover, the individualized approach improved the identification of people with FA, involving complex dimensions of eating behavior, body composition, and potential nutritional deficits not previously studied. Full article

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/Objectives: Muscle dysmorphia (MD), a subtype of body dysmorphic disorder, is prevalent among males who engage in the non-medical use of anabolic–androgenic steroids (AASs) and performance-enhancing drugs (PEDs). These individuals often experience severe psychopathology, including mood instability, compulsivity, and a distorted body image. Despite its clinical severity, no randomized controlled trials (RCTs) have evaluated structured psychological treatments in this subgroup. This study aimed to assess the efficacy of a manualized cognitive behavioral therapy (CBT) protocol in reducing MD symptoms and associated psychological distress among male steroid users. Results: Participants in the CBT group showed significant reductions in MD symptoms from the baseline to post-treatment (MDDI: p < 0.001, d = 1.12), with gains sustained at follow-up. Large effect sizes were also observed in secondary outcomes including depressive symptoms (PHQ-9: d = 0.98), psychological distress (K10: d = 0.93), disordered eating (EDE-Q: d = 0.74), and exercise addiction (EAI: d = 1.07). No significant changes were observed in the control group. Significant group × time interactions were found for all outcomes (all p < 0.01), indicating CBT’s specific efficacy. Discussion: This study provides the first RCT evidence that CBT significantly reduces both core MD symptoms and steroid-related psychopathology in men engaged in AAS/PED misuse. Improvements extended to mood, body image perception, and compulsive exercise behaviors. These findings support CBT’s transdiagnostic applicability in addressing both the cognitive–behavioral and affective dimensions of MD. Materials and Methods: In this parallel-group, open-label RCT, 59 male gym-goers with DSM-5-TR diagnoses of MD and a history of AAS/PED use were randomized to either a 12-week CBT intervention (n = 30) or a waitlist control group (n = 29). CBT sessions were delivered weekly online and targeted distorted muscularity beliefs, compulsive behaviors, and emotional dysregulation. Primary and secondary outcomes—Muscle Dysmorphic Disorder Inventory (MDDI), PHQ-9, K10, EDE-Q, EAI, and BIG—were assessed at the baseline, post-treatment, and 3-month follow-up. A repeated-measures ANOVA and paired t-tests were used to analyze time × group interactions. Conclusions: CBT offers an effective, scalable intervention for individuals with muscle dysmorphia complicated by anabolic steroid use. It promotes broad psychological improvement and may serve as a first-line treatment option in high-risk male fitness populations. Future studies should examine long-term outcomes and investigate implementation in diverse clinical and cultural contexts. Full article

Background/objectives: In 9/2020, the United States Food and Drug Administration )FDA( posted a black box warning for all benzodiazepines, addressing their association with serious risks of abuse, addiction, physical dependence, and withdrawal reactions. We evaluated changes in benzodiazepine dispensing rate trends after this warning. Methods: The dataset of Clalit Health Services (Israel’s largest insurer, with 5 million members) was used to identify and collect benzodiazepine dispensing data for all patients who were dispensed these drugs at least once during the study period (1/2017–12/2021). The dispensing rate (number of patients who were dispensed benzodiazepines per month divided by the number of patients alive during that month) was calculated for each month in the study period. Linear regression and change point regression were used to review the change in trend before and after the black box warning. New users of benzodiazepines after the black box warning were analyzed by age. Results: A total of 639,515 patients using benzodiazepines were reviewed. The mean benzodiazepine dispensing rate per month was 0.21 and ranged from 0.17 (in 2/2017) to 0.24 (in 3/2020). No significant change in trend was observed before vs. after the black box warning (slopes of 0.00675 percentage points per month and 0.00001 percentage points per month, respectively; p = 0.38). The change point regression analysis identified a change point in 4/2019, which is prior to the black box warning. New users were younger after the black box warning compared to before this warning. Conclusions: The FDA black box warning did not affect the dispensing rate of benzodiazepines. Full article

Shaboo is a street name commonly used in parts of Asia, particularly the Philippines and Thailand, to refer to methamphetamine, a powerful and highly addictive stimulant. Its long-term effects are related to chronic exposure to the drug effects, primarily neurotoxicity phenomena, which could lead to cognitive impairment, or psychiatric symptoms. We aim to present one case of problematic shaboo use in a patient referring to an addiction outpatient clinic in Northern Italy. This case highlights that the treatment of these patients involves careful multidisciplinary management. An accurate knowledge of the physical and psychological effects of New Psychoactive Substances is essential, as well as the implementation of a tailored psychological and social support program. Full article

Background/Objectives: Substance use disorders, particularly opioid addiction, continue to pose a major global health and toxicological challenge. Morphine dependence represents a significant problem in both clinical practice and preclinical research, particularly in modeling the pharmacodynamics of withdrawal. Rodent models remain indispensable for investigating the neurotoxicological effects of chronic opioid exposure and withdrawal. However, conventional behavioral assessments rely on manual observation, limiting objectivity, reproducibility, and scalability—critical constraints in modern drug toxicity evaluation. This study introduces MWB_Analyzer, an automated and high-throughput system designed to quantitatively and objectively assess morphine withdrawal behaviors in rats. The goal is to enhance toxicological assessments of CNS-active substances through robust, scalable behavioral phenotyping. Methods: MWB_Analyzer integrates optimized multi-angle video capture, real-time signal processing, and machine learning-driven behavioral classification. An improved YOLO-based architecture was developed for the accurate detection and categorization of withdrawal-associated behaviors in video frames, while a parallel pipeline processed audio signals. The system incorporates behavior-specific duration thresholds to isolate pharmacologically and toxicologically relevant behavioral events. Experimental animals were assigned to high-dose, low-dose, and control groups. Withdrawal was induced and monitored under standardized toxicological protocols. Results: MWB_Analyzer achieved over 95% reduction in redundant frame processing, markedly improving computational efficiency. It demonstrated high classification accuracy: >94% for video-based behaviors (93% on edge devices) and >92% for audio-based events. The use of behavioral thresholds enabled sensitive differentiation between dosage groups, revealing clear dose–response relationships and supporting its application in neuropharmacological and neurotoxicological profiling. Conclusions: MWB_Analyzer offers a robust, reproducible, and objective platform for the automated evaluation of opioid withdrawal syndromes in rodent models. It enhances throughput, precision, and standardization in addiction research. Importantly, this tool supports toxicological investigations of CNS drug effects, preclinical pharmacokinetic and pharmacodynamic evaluations, drug safety profiling, and regulatory assessment of novel opioid and CNS-active therapeutics. Full article

Background/Objectives: Contextual memory associated with methamphetamine (METH) use contributes to relapse and persistence of addiction. Angiotensin II type 1 receptor (AT1R) signaling has been implicated in drug reinforcement. LCZ696, a clinically used combination of sacubitril (a neprilysin inhibitor) and valsartan (an AT1R antagonist), may interfere with METH-associated memory through the modulation of dopaminergic pathways. Methods: Male C57BL/6J mice were tested in a conditioned place preference (CPP) paradigm to assess the effects of LCZ696, sacubitril (AHU377), and valsartan on METH-induced memory expression and reinstatement. Synaptic plasticity in the nucleus accumbens (NAc) was examined by assessing the levels of synaptophysin (Syp) and postsynaptic density protein 95 (Psd95), as well as dendritic spine density. Dopaminergic signaling in the ventral tegmental area (VTA) was evaluated via ELISA, Western blotting, and chromatin immunoprecipitation (ChIP), targeting cAMP response element-binding protein (Creb) binding to the tyrosine hydroxylase (Th) promoter. To further assess the role of Th, an adeno-associated virus (AAV9) carrying a CRISPR-Cas9-based sgRNA targeting Th (AAV9-Th-sgRNA) was microinjected into the VTA. Results: LCZ696 and valsartan significantly reduced METH-induced CPP and reinstatement. LCZ696 reversed METH-induced synaptic and dopaminergic alterations and suppressed Creb-mediated Th transcription. Th knockdown attenuated both CPP acquisition and relapse. Conclusions: LCZ696 disrupts METH-associated contextual memory by modulating dopaminergic signaling and Creb-dependent Th expression, supporting its potential as a treatment for METH use disorder. 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

In recent years, methamphetamine (METH) misuse in the US has been rapidly increasing, and there is no FDA-approved pharmacotherapy for METH use disorder (MUD). We previously determined that ubiquitin-protein ligase parkin is involved in the regulation of METH addictive behaviors in rat models of MUD. Parkin is not yet a “druggable” drug target; therefore, this study aimed to determine which biological processes, pathways, and proteins downstream of parkin are likely drug targets against MUD. Employing young adult Long Evans male rats with parkin deficit or excess in the nucleus accumbens (NAc), label-free proteomics, and molecular biology, we determined that the pathways downstream of parkin that are candidates for regulating METH addictive behaviors in young adult male rats are mitochondrial respiration, oxidative stress, AMPA receptor trafficking, GABAergic neurotransmission, and actin cytoskeleton dynamics. 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

Exposure to chronic stress creates vulnerability to drug misuse and presents a barrier to sustained recovery for many individuals experiencing substance use disorders (SUDs). Preclinical literature demonstrates that stress modulates psychostimulant intake and seeking, yet there are wide gaps in our understanding of the specific mechanisms by which stress promotes brain changes that may govern addiction-related behaviors. Recent data suggest that microglia, innate immune cells in the central nervous system, are highly responsive to chronic stressors, and several mechanistic links have been explored highlighting the critical role microglia play in stress-related brain adaptation. Importantly, psychostimulants may engage similar microglial machinery, which opens the door for investigation into how microglia may be involved in shaping motivation for psychostimulants, especially in the context of stress exposure. The aims of this review are threefold: 1. Offer a brief overview of microglial biology in the adult brain. 2. Review current methods of interrogating microglial function with a focus on morphometric analyses. 3. Highlight preclinical research describing how microglia contribute to brain changes following chronic stress and/or psychostimulant exposure. Ultimately, this review serves to prime investigators studying the intersection of stress and SUDs to consider the relevant impacts of microglial actions. Full article

Epidermal growth factor receptor (EGFR) mutations occur in approximately 10–20% of Caucasian and up to 50% of Asian patients with oncogene-addicted non-small cell lung cancer (NSCLC). Most frequently, alterations include exon 19 deletions and exon 21 L858R mutations, which confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs). In the last decade, the third-generation EGFR-TKI osimertinib has represented the first-line standard of care for EGFR-mutant NSCLC. However, the development of acquired mechanisms of resistance significantly impacts long-term outcomes and represents a major therapeutic challenge. The mesenchymal–epithelial transition (MET) gene amplification and MET protein overexpression have emerged as prominent EGFR-independent (off-target) resistance mechanisms, detected in approximately 25% of osimertinib-resistant NSCLC. Noteworthy, variability in diagnostic thresholds, which differ between fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) platforms, complicates its interpretation and clinical applicability. To address MET-driven resistance, several therapeutic strategies have been explored, including MET-TKIs, antibody–drug conjugates (ADCs), and bispecific monoclonal antibodies, and dual EGFR/MET inhibition has emerged as the most promising strategy. In this context, the bispecific EGFR/MET antibody amivantamab has demonstrated encouraging efficacy, regardless of MET alterations. Furthermore, the combination of the ADC telisotuzumab vedotin and osimertinib has been associated with activity in EGFR-mutant, c-MET protein-overexpressing, osimertinib-resistant NSCLC. Of note, several novel agents and combinations are currently under clinical development. The success of these targeted approaches relies on tissue re-biopsy at progression and accurate molecular profiling. Yet, tumor heterogeneity and procedural limitations may challenge the feasibility of re-biopsy, making biomarker-agnostic strategies viable alternatives. Full article