Search Results (933)

According to the World Drug Report, there are nearly 300 million drug users globally. Drug addiction is a chronic, relapsing brain disease that leads to medical, psychological, and social complications. This neuropsychiatric disorder is characterized by a compulsive drug-seeking behavior, continued use despite harmful consequence, and long-lasting changes in the brain. The reward system, which involves dopaminergic circuits, plays a key role in addiction. Dopamine levels have been described to fluctuate throughout the day, in a circadian fashion, and the effects of drugs have been shown to depend on the time when they are used. Hence, due to its important role in the control of circadian rhythms, the orexinergic system seems to have a role in the regulation of addiction. This system is composed by the orexin receptors 1 and 2 (OX₁R and OX₂R), the ligands orexin A (OXA) and orexin B (OXB) and their respective enzymes for degradation or synthesis. Here, we explore how orexin receptors and orexin peptides are involved in addiction. For instance, OX₁R has been shown to be strongly involved in specific behaviors such as drug-seeking for stimulants, alcohol and other addiction problems, whereas OX₂R appears to be linked with arousal and stress responses. We also investigate how the orexinergic system may regulate drug-seeking behavior by interaction with other brain systems such as the dopaminergic, cannabinoid or opioid systems. Finally, the potential of receptor complexes as new therapeutic targets to treat drug addiction is explored. Full article

The increasing consumption of artificially sweetened beverages among young people, coupled with prevalent digital technology use, presents growing public health concerns regarding potential effects on health and behavior. This study aimed to determine the concentrations of three commonly used artificial sweeteners—acesulfame K, saccharin, and aspartame—in soft drinks available on the market in Osijek, Croatia, to assess their compliance with European Union regulations, and to investigate the consumption patterns and possible associations with internet addiction among university students. Laboratory analysis of 43 beverages was performed using high-performance liquid chromatography with diode array detection, while a cross-sectional survey of 792 students collected data on sociodemographic characteristics, beverage consumption, and internet use. Acesulfame K was the most frequently detected sweetener, followed by aspartame and saccharin, with mean concentrations of 50.1 mg/L, 22.7 mg/L, and 19.76 mg/L, respectively. Overall, 85.7% of the students stated that they consumed artificially sweetened drinks, with an average consumption of 0.2 L/day. Internet addiction was found in 39.8% of the participants, but no significant correlation was found between beverage consumption and internet addiction (p = 0.177). All measured concentrations of sweeteners were below the legal limits. These results suggest that while exposure to artificial sweeteners in beverages is within safe limits, further research is needed to assess cumulative intake and its potential impact on behavioral health in young adults. Full article

Gacha games, particularly those using Free-to-Play (F2P) models, have become increasingly popular yet controversial due to their addictive mechanics, often likened to gambling. This study investigates the inherent addictive mechanisms of Gacha games, focusing on Genshin Impact, a leading title in the genre. We analyze the interplay between reward frequency, game attractiveness, and player addiction using the Game Refinement theory and the Motion in Mind framework. Our analysis identifies a critical threshold at approximately 55 pulls per rare item ($N\approx 55$), with a corresponding gravity-in-mind value of 7.4. Beyond this point, the system exhibits gambling-like dynamics, as indicated by Game Refinement and Motion in Mind metrics. This threshold was measured using empirical gacha data collected from Genshin Impact players and analyzed through theoretical models. While not claiming direct causal evidence of player behavior change, the results highlight a measurable boundary where structural design risks fostering addiction-like compulsion. The study contributes theoretical insights with ethical implications for game design, by identifying critical thresholds in reward frequency and game dynamics that mark the shift toward gambling-like reinforcement. The methodologies, including quantitative analysis and empirical data, ensure robust results contributing to responsible digital entertainment discourse. Full article

Background: Borderline Personality Disorder (BPD) often emerges during adolescence and young adulthood, a period marked by heightened vulnerability to impulsivity and affective dysregulation. While impulsivity is a core feature of BPD, its multidimensional expression in this age group remains insufficiently documented. This study examined impulsivity traits in young adults with BPD, their associations with depressive and anxiety symptoms, and their links to risk behaviors. Methods: A total of 160 participants aged 16–25 were recruited in Belgium between 2021 and 2023: 44 with BPD from inpatient and outpatient psychiatric services and 116 healthy controls from schools and universities. Assessments included the short UPPS-P, Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI-T), and the Diagnostic Interview for Borderlines–Revised (DIB-R). Logistic regressions with robust errors and Kendall’s tau-b correlations were used. Results: Compared with controls, individuals with BPD scored higher on all UPPS-p subscales except Sensation Seeking (e.g., Negative Urgency: 14 vs. 10, p < 0.001). Logistic regression identified Negative Urgency (OR = 5.31, 95% CI: 2.07–13.62, p = 0.001) and Positive Urgency (OR = 3.26, 95% CI: 1.37–7.75, p = 0.007) as independent predictors of BPD. Within the BPD group, depressive and anxiety symptoms correlated with several UPPS-P dimensions, notably Negative Urgency and Lack of Perseverance. Suicide attempts were associated with the DIB-R total score, BDI-II, and STAI-T, while substance use was linked to the DIB-R impulsivity subscale and STAI-T. Conclusions: Emotional impulsivity—particularly Negative Urgency—emerges as a central feature of BPD in emerging adulthood. Its interplay with depressive and anxiety symptoms, and its associations with suicidal and addictive behaviors, support a dual-level conceptualization of impulsivity as both a dispositional trait and a state-dependent clinical risk factor. Full article

Smartphone addiction has emerged as a significant public health concern, particularly among adolescents and young adults. This narrative review, conducted in line with the ANDJ checklist, synthesizes evidence from 25 systematic reviews and meta-analyses, complemented by randomized controlled trials and clinical studies, to provide a structured overview of the field. The study selection flow and publication trends reveal a rapidly expanding research landscape, with most evidence produced in the last decade, reflecting both the ubiquity of smartphones and increasing awareness of their health impacts. The synthesis highlights converging findings across reviews: excessive smartphone use is consistently associated with psychosocial, behavioral, and academic challenges, alongside sleep disturbances and mental health symptoms. Common messages include the recognition of smartphone addiction as a multidimensional phenomenon, while emerging themes point to heterogeneity in definitions, tools, and methodological approaches. Comparative analysis of reviews underscores both shared risk factors—such as emotional dysregulation and social isolation—and differences in study designs and target populations. Importantly, this review identifies critical gaps, including the lack of standardized definitions, limited longitudinal evidence, and scarce cross-cultural validation. At the same time, promising opportunities are noted, from lifestyle-based interventions (e.g., physical activity) to educational and policy-level strategies fostering digital literacy and self-regulation. The post-pandemic context further emphasizes the need for sustained monitoring and adaptive responses. Overall, this review calls for youth-centered, multi-sector interventions aligned with WHO recommendations, supporting coordinated, evidence-based action across health, education, and policy domains. Full article

Background: Problematic internet use among adolescents is linked to poorer mental health, academic performance, and social functioning, yet evidence from Eastern Europe remains limited. Methods: We conducted a school-based cross-sectional study at a Romanian high school (Arad County) including 308 students aged 15–18 years (154 males, 154 females). Students completed a demographic/behavioral questionnaire and the 20-item Internet Addiction Test (IAT), a widely used measure of problematic internet use. The prespecified primary analysis was a multivariable linear regression of IAT score on sex, age group, residence, daily screen time, prior attempts to reduce use, and main internet purpose; supporting analyses included t-tests, ANOVA, and Pearson correlation (α = 0.05). Results: In bivariable comparisons, males, older adolescents (17–18 years), and urban residents reported higher IAT scores; screen time correlated with IAT (r = 0.460, p < 0.001), and prior reduction attempts were associated with higher scores (Cohen’s d = 0.80). In the adjusted model, male sex (β = 4.97), older age (β = 5.36), greater daily screen time (β = 1.67 per hour), prior attempts to reduce use (β = 4.13), and primarily using the internet for gaming (β = 5.71) remained significant predictors (all p ≤ 0.045); urban residence was not retained (p = 0.218). The model explained 43% of IAT variance (R² = 0.43). Conclusions: Demographic and behavioral factors independently predict adolescent problematic internet use, highlighting high-risk profiles (older males, heavy screen time, gaming focus, prior reduction attempts). These findings support school-based screening and targeted digital-health interventions in underrepresented contexts. Full article

Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose intravenous (IV) administration in a mice model of depression. Low-intensity focused ultrasound (LIFU) was employed to induce transcranial, region-specific drug release in the lateral habenula (LHb). Methods: Ket-NDs were synthesized using a thin-film hydration method with sonication and emulsification, incorporating perfluoropentane as the core material. Characterization was performed using light microscopy, cryogenic scanning electron microscopy (cryo-SEM), transmission electron microscopy, and dynamic light scattering (DLS). Drug EE and loading efficiency (LE) were quantified by reversed-phase high-performance liquid chromatography. A chronic restraint stress model was established, and Ket-NDs were administered intravenously followed by LIFU targeting the LHb. Antidepressant efficacy and biosafety were systematically evaluated. Results: (1) Ket-NDs exhibited uniform spherical morphology and a narrow size distribution, as confirmed by DLS (particle size: 139.75 ± 9.43 nm; Polydispersity index: 0.225 ± 0.025) and cryo-SEM analysis (number-average diameter: 109.5 ± 10.4 nm). The zeta potential was −15.93 ± 5.906 mV, and the formulation remained stable under 4 °C storage. (2) Ket-NDs demonstrated high EE (78.25 ± 16.13%) and LE (15.55 ± 4.49%). (3) In depressive mice, IV administration of Ket-NDs followed by LIFU targeting the LHb significantly improved behavioral outcomes: increased locomotor activity in the open field test, elevated sucrose preference index, and reduced immobility time in the tail suspension test. (4) Safety assessments revealed no significant organ toxicity or brain tissue damage in ultrasound-exposed regions. Conclusions: In summary, this study developed stable Ket-NDs. When combined with LIFU, they enable precise regional drug delivery to the brain, showcasing a promising treatment strategy for depression with reduced systemic side effects. Full article

Background/Objectives: Alcohol use disorder (AUD) is a major public health issue with rising global occurrence and metabolic consequences. Modeling the addictive behaviors associated with AUD remains inadequate and elusive. Even more so, models that are representative of AUD in concert with excessive caloric intake are limited. Some consequences of chronic alcohol use overlap with the metabolic phenotype of hypercaloric diets. Recently characterized metabolic dysfunction-associated steatotic liver disease with increased alcohol intake (MetALD) helps to differentiate these conditions. This study aims to investigate metabolic phenotypes and gene expression alterations in MetALD mice that are grouped by alcohol preference based on blood phosphatidylethanol levels and alcohol consumption. Methods: Mice were fed high-fat and chow diets, with water and 10% EtOH, for 13 weeks. mRNA sequencing was performed across multiple tissues including brain, liver, skeletal muscle, ileum, and white adipose tissue, and gut microbiome diversity was evaluated via 16S sequencing. Results: Key findings included reduced glucagon in alcohol-preferring mice with no significant differences in dyslipidemia and hepatic steatosis. Additionally, we observed reduced gut microbiome diversity and Wnt signaling with elevated acute-phase response genes in ileum tissue. Reduced Wnt and Hippo signaling in the brain and liver, respectively, was also revealed. Other gene ontologies discovered included increased neural inflammation and adipose mitochondrial translation. Nek3, Ntf3, Cux1, and Irf6 expression changes were shared across at least three tissues and may be potential biomarkers of alcohol addiction. Conclusions: This novel model assists future intervention research in the characterization of MetALD and identifies potential biomarkers of alcohol preference. Full article

Purpose: Adolescence is a period of increased vulnerability to addictive behaviors, and Primary Health Care (PHC) plays a crucial role in prevention and intervention (e.g., through Screening, Brief Intervention, and Referral to Treatment), but professionals often face barriers, such as inadequate training and systemic challenges, particularly within the Greek context. Given the lack of data on their needs, this study aimed to investigate the levels of self-perceived knowledge/skills, attitudes regarding communication and readiness, perceived barriers, and educational expectations among PHC professionals in Greece. Method: A cross-sectional descriptive survey was conducted using an anonymous questionnaire with a convenience sample of 331 PHC professionals from 5 Health Regions. Results: Professionals recognized the high importance of effective communication (M = 4.31/5) but reported low preparedness (M = 2.65/5) and moderate confidence in knowledge, especially in screening tools/motivational interviewing (M = 2.25/5). Lack of training was the main barrier (87.6%). A strong positive correlation was found between knowledge and preparedness (rho = 0.68, p < 0.001), but not between age/experience and readiness (p > 0.05). Discussion: The study highlights a significant readiness gap and a substantial need for specialized training for PHC professionals in Greece, regardless of experience. Targeted interventions are required to enhance skills (especially in SBIRT/MI) and self-efficacy, alongside action to address systemic barriers. Full article

Background: Dentophobia, a significant barrier to dental healthcare, may be influenced by an increased dependency on digital technology and internet addiction, particularly among younger populations. This study aimed to assess the effectiveness of Virtual Reality Exposure Therapy (VRET) compared to traditional methods in managing dentophobia, particularly among individuals exhibiting high levels of internet dependency. Methods: A comparative study involving two groups, each consisting of 50 young adults aged 18–30 years, diagnosed with dentophobia, was conducted. Group A participants, who exhibited high familiarity and borderline addictive behavior towards digital technologies, received VRET using VR-BOX glasses across four specific dental scenarios: dental chair positioning, oral examination, anesthesia administration, and dental drilling procedures. Group B received traditional “tell–show–do” management without VR assistance. Anxiety levels were evaluated using the Modified Dental Anxiety Scale (MDAS) before and after interventions and at follow-up intervals of one week, three months, and six months. Results: Both groups showed significant reductions in anxiety scores across all follow-up periods. Mild to phobic anxiety scores demonstrated no significant differences between VRET and traditional method groups. The average MDAS scores post-intervention were similar, indicating comparable effectiveness between both treatment modalities. Conclusions: Virtual Reality Exposure Therapy effectively reduces dentophobia among young adults, particularly those with significant internet dependency. Although VRET’s effectiveness was similar to conventional methods, it holds considerable promise for improving treatment adherence and comfort among digitally dependent individuals. Full article

Impulsivity and compulsivity are key transdiagnostic constructs implicated in addictive and criminal behaviors, often overlapping under the broader concept of behavioral dysregulation. While impulsivity has been widely assessed using experimental tasks and self-report measures, few tools specifically target compulsivity in forensic populations. This study aimed to adapt and validate the Spanish version of the Impulsive-Compulsive Behaviours Checklist (ICB) in a prison sample. The ICB was administered to 700 incarcerated men (mean age = 37.33 years) following a rigorous translation and back-translation procedure, along with pilot testing for clarity. Exploratory and confirmatory factor analyses revealed a stable two-factor structure consistent with theoretical expectations. Internal consistency was satisfactory (McDonald’s omega and Cronbach’s alpha = 0.79–0.80), and convergent validity was supported by significant correlations with the UPPS-P Impulsive Behavior Scale, the Obsessive Beliefs Questionnaire (OBQ-44), the European Addiction Severity Index (EuropASI), and the Symptom Checklist-90-Revised (SCL-90-R). These findings support the Spanish ICB as a valid and reliable tool for assessing impulsive and compulsive traits in forensic contexts. Its use may enhance the identification of differentiated clinical profiles and inform targeted interventions for mental health and reintegration in prison populations. Full article

Background: Tobacco use remains a major public health concern among young adults and is often complicated by co-occurring addictive behaviors. Objective: This study analyzed motivation for change, assessed with the decisional balance framework, in relation to multiple addictions among young smokers seeking treatment. Methods: Ninety-eight participants from the University of Granada enrolled in either an app-based cognitive–behavioral therapy (CBT) program (n = 35) or a traditional face-to-face CBT program (n = 63). Recruitment relied on self-identification and voluntary participation. Standardized instruments were applied to measure nicotine dependence (FTND), behavioral and substance-related addictions (MULTICAGE CAD-4), cannabis dependence (SDS), and motivation for change (DBQ). Logistic and stepwise regression analyses were conducted to identify predictors of treatment choice and motivational outcomes. Results: Younger participants and students were more likely to choose the app-based program. Compulsive buying was linked to perceiving more disadvantages of smoking, whereas sex addiction, cannabis dependence, and other substance addictions were associated with perceiving fewer disadvantages. Conclusions: Treatment preferences and motivational profiles differ according to age, academic status, and co-occurring addictions. These findings highlight the need to tailor smoking cessation strategies to individual profiles and support the role of mobile health tools in engaging digitally oriented populations. Full article

Addiction remains a persistent public health crisis, marked by poor treatment retention and limited pharmacotherapy options. Emerging treatments, such as psychedelic-assisted psychotherapy and neuromodulation, offer promising avenues for circuit-level interventions in behavioral addictions. This narrative review synthesizes the current landscape of psychedelic compounds and neuromodulation techniques with a focus on their mechanisms of action, applications in specific behavioral addictions, and translational potential. By targeting disrupted reward, executive control, and stress regulation networks, these interventions may facilitate meaningful recovery and long-term remission in otherwise treatment refractory cases. We highlight key findings, current research limitations, and future directions in integrating these novel therapies into the treatment of gambling disorder; internet gaming disorder/gaming disorder, predominantly online; internet use disorder; and compulsive sexual behavior disorder. Full article

Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated genes in human cancer, including non-small cell lung carcinoma (NSCLC). Sustained expression of KRAS is required for survival in KRAS-dependent tumors. KRAS tumors can become independent upon bypassing this addiction. Tissue inhibitor of metalloproteinase-1 (TIMP-1) exhibits a range of novel functions in addition to its initially recognized activity as a physiological inhibitor of matrix metalloproteinases (MMPs). It has repeatedly been associated with cancer progression and poor prognosis in multiple cancers. This study investigates the relationship between TIMP-1 modulation and KRAS dependency in NSCLC. We found an inverse expression of KRAS and TIMP-1 in NSCLC lines. Modulating TIMP-1 levels altered KRAS expression and affected KRAS-dependency features. Overexpression of TIMP-1 decreases the KRAS levels in dependent cells and knocking-down TIMP-1 increases KRAS levels in independent cells with concomitant change in RAS-GTP levels. TIMP-1 modulation influenced apoptosis upon KRAS ablation, with TIMP-1 overexpression decreasing apoptosis in dependent cells and TIMP-1 knockdown increasing it in independent cells. Bioinformatic analysis depicted variant-specific perturbations between KRAS and TIMP-1 expression. Furthermore, EMT marker expression was altered upon TIMP-1 modulation, suggesting the role of TIMP-1 in EMT induction in KRAS-independent cells. These findings emphasize the intricate relationship between TIMP-1 and KRAS in NSCLC, shedding light on potential mechanisms underlying tumor behavior and response to therapy. Full article

Background/Objectives: Use of social media among college students is ubiquitous. Excessive use of social media has been linked to distractions, reduced academic focus, and poor mental health outcomes such as anxiety and depression. The determinants of social media use among college students are not well understood. Hence, the purpose of this study was to conduct a scoping review on the behavioral, demographic, and psychosocial determinants, explore theoretical frameworks, and suggest evidence-based recommendations. Methods: This scoping review was conducted between January 2024 and May 2025 following PRISMA-ScR guidelines, using MEDLINE (PubMed), CINAHL, and ERIC databases. Peer-reviewed studies were included if they focused on college students (ages 18–30), investigated determinants of social media use, and met predefined inclusion criteria. Results: A total of 22 studies met the inclusion criteria. Studies were conducted in Bangladesh, Canada, China, Egypt, India, Nigeria, Pakistan, Saudi Arabia, Turkey, and the United States, and the majority used cross-sectional designs (n = 20). A consistent finding across the reviewed studies was the strong association between social media overuse and symptoms of depression, anxiety, stress, and emotional dysregulation. Very few theoretical frameworks for understanding the determinants of social media were used. According to the reviewed studies, factors such as fear of missing out, sleep quality, and prolonged social media use consistently emerged as significant predictors of adverse mental health outcomes (p < 0.05). Conclusions: In this study, problematic social media use (PSMU) was linked to increased mental health issues, suggesting that students frequently engage in social comparison and experience feelings of missing out (FoMO), which exacerbate emotional distress. There is a need for integrated approaches in addressing PSMU within educational environments, particularly in fostering healthier digital habits among students. There is a need to conduct more concerted research using longitudinal designs and contemporary theoretical frameworks in this area. Full article