International journal of methods in psychiatric researchŞükrü Alperen Korkmaz, Pınar Mutlu, Sibel Oymak, Gamze Çan
BACKGROUND/AIM: Risky alcohol use is common among university students and negatively impacts physical and psychosocial health. Current screening instruments focus only on behavioral indicators, neglecting psychosocial factors. This study aimed to develop an AI-supported, brief student-focused tool for assessing alcohol-related risk and to evaluate its preliminary reliability and validity among university students. MATERIALS AND METHODS: A total of 599 university students participated in this cross-sectional study. From a pool of 59 items covering behavioral, psychological, social, and academic questions related to alcohol use, a new risk model was created using 15 items selected with ChatGPT-supported AI algorithms (SARAS-15). Risk scores ranged from 0 to 27, categorizing participants into low, medium, and high-risk groups. The model's performance was evaluated using machine learning methods such as Random Forest, Logistic Regression, SVM, and KNN, along with cross-validation and ROC analysis. We also analyzed its internal consistency and its correlations with screening instruments (AUDIT, RAPS4-QF, CAGE). RESULTS: In machine learning analyses, the logistic regression model achieved the highest performance (93.5% accuracy, F1-score = 0.864, sensitivity = 0.826, specificity = 0.959). ROC analysis demonstrated excellent discrimination between low-risk (AUC = 0.96) and high-risk (AUC = 0.93) groups, with strong discrimination for the intermediate-risk group (AUC = 0.88). The Random Forest model achieved an overall accuracy of 87%, successfully differentiating between the low-risk group (F1 score = 0.91) and the high-risk group (F1 score = 1.00). The new model's Cronbach's alpha was 0.811, with strong convergent validity correlations with screening instruments (AUDIT, r = 0.861; RAPS4-QF, r = 0.793; CAGE, r = 0.631). CONCLUSION: The developed artificial intelligence-supported 15-item new risk score model is valid and reliable in assessing risky alcohol use among university students. This scale demonstrates a high level of agreement with traditional tests and can accurately detect three risk levels. Due to its multi-domain content structure, which addresses both behavioral and psychosocial effects, it serves as a complementary screening tool for early risk identification and intervention planning.
Family processBrian D Doss, Shayna Guttman, Maya Metser-Waldman, Nirvi Ajmera, Alex Dopp
Relationship distress is a prevalent issue with significant economic and societal consequences, including increased mental and physical health problems, decreased workplace productivity, and increased absences. Although couple therapy has been shown to improve relationship and individual well-being, its high costs limit accessibility. Digital relationship interventions provide a cost-effective alternative. However, limited research has assessed the cost-benefit of such programs using experimental designs. This study conducted a cost-benefit analysis of the OurRelationship program using data from two randomized controlled trials (RCTs). The Washington State Institute for Public Policy (WSIPP) cost-benefit model was applied to quantify economic benefits across four domains-depression, anxiety, alcohol misuse, and insomnia-relative to a waitlist control. Program costs were estimated at $280 per individual, and benefits were assessed in terms of healthcare savings, productivity gains, and labor market outcomes. The primary analysis found that, for every dollar spent on the OurRelationship program, $6.60 was saved in societal costs. Sensitivity analyses suggested benefit-cost ratios ranging from $1.88 to $22.06 depending on assumptions regarding the number of participants, duration of effects, and magnitude of program impact. Findings suggest that the OurRelationship program yields substantial economic benefits, making it a viable investment for policymakers, employers, and healthcare systems. The study supports broader implementation of efficacious digital relationship interventions and highlights the importance of economic evaluations in guiding funding decisions for relationship support programs. Further research should explore the long-term benefits and applicability across diverse populations.
Pakistan journal of pharmaceutical sciencesIrfanullah Khan, Nazish Waris, Madiha Nizami, Uzma Ali, Aisha Iftikhar, Urooj Nazim, Asher Fawwad
BACKGROUND: Methamphetamine (MA) use induces oxidative stress and metabolic dysregulation. OBJECTIVES: This study is to compare and explore the association between oxidative stress markers and cardio metabolic risk factors in order to elucidate potential mechanisms linking MA use with metabolic and cardiovascular complications. METHODS: A comparative cross-sectional study was conducted and a total of 70 males aged 18 years and above were enrolled from Mamajee Welfare Trust: 35 healthy controls (Group A) and 35 MA users (Group B) confirmed via drug panel testing. Sociodemographic characteristics, substance use patterns, lifestyle behaviors and anthropometric indices were recorded through structured questionnaires. Fasting blood samples were analyzed for lipid profile, fasting plasma glucose, Troponin-I and antioxidant enzyme activities using standardized assays. Data analysis was performed using statistical packages for social sciences (SPSS) software (version 20). RESULTS: MA users reported significantly higher smoking, alcohol intake and physical inactivity. Body mass index (BMI) and systolic blood pressure were also significantly elevated (p<0.01). MA users exhibited pronounced dyslipidemia with increased lipid variables. Antioxidant enzyme activity was significantly lower in MA users, with higher catalase (5.31 ± 0.15 vs. 4.89 ± 0.32 ng/mL; p=0.047) and superoxide dismutase (SOD) levels (127 ± 43.1 vs. 109 ± 23.4 pg/mL; p=0.003) in healthy controls vs. MA users, respectively. In methamphetamine users, catalase correlated positively with BMI, cholesterol, triglycerides and low-density lipoprotein (LDL). While SOD in this group showed a significant positive association with blood pressure, lipid markers and very low density lipoprotein (VLDL), with a near-significant trend for Troponin-I. A significant interrelationship between catalase and SOD (r=0.381, p=0.003) in MA users was also observed. In multivariable analysis, MA use and antioxidant enzyme levels (catalase, SOD) were independently associated with BMI, blood pressure and lipid abnormalities. CONCLUSION: MA use is associated with considerable cardiometabolic disturbances and compromised antioxidant defenses, highlighting the need for early screening and preventive interventions.
Australian journal of primary healthWarren Jennings, Idin Panahi, Tim Piatkowski, Charlotte Wirtz, David Ting, Geoffrey Spurling
In Australia, opioid use disorder is a major public health concern, and opioid agonist treatment (OAT) is an effective and evidence-based approach for treating opioid use disorder, reducing morbidity, mortality and societal cost. In Australia, 60% of OAT prescribing occurs in general practice, but significant barriers exist. This scoping review aimed to find research describing the characteristics and evaluation of different models of primary care-based OAT in Australia. Following the PRISMA guidelines for scoping reviews, a systematic search was conducted of PubMed, Embase, Scopus and CINAHL, and several grey literature databases. We conducted a narrative synthesis, and derived study themes inductively from included studies. We identified 24 relevant articles over 34 years that reported primary research on general practice-based OAT. Seven studies evaluated general practice OAT; eight examined prescriber attitudes, behaviour and workforce; two described single-models of care; four investigated primary care OAT policy; and two studies examined consumer experiences. The studies showed primary care OAT was as effective as specialist care for retention in OAT; however, prescriber deficits exist, with lack of remuneration and stigma identified as common barriers. The multidisciplinary models of care all received external funding, with GPs well placed, but underfunded, to coordinate care. The limited research demonstrates research gaps in service delivery, models of care, funding and views of people who use drugs. Future research scope needs to be broadened to encompass improved national monitoring datasets, patient views, models of care, holistic support and coordination, and structural supports to recruit and retain active prescribers.
The lancet. PsychiatryPatrick Bach, Johan Franck, Jonas Hällgren, Härje Widing, Mika Gissler, Jeanette Westman
BACKGROUND: Evidence suggests that GLP-1 receptor agonists might reduce substance use across different substance use disorders. However, data on substance use-related outcomes after GLP-1 discontinuation are absent. This study aimed to investigate the risk of alcohol and substance use-related hospitalisations during and after exposure to GLP-1 receptor agonists. METHODS: This within-individual observational study used Swedish registers to identify residents of Stockholm County with a first registered diagnosis of type 2 diabetes between Jan 1, 2005, and Dec 31, 2024 who had received GLP-1 receptor agonists and, for comparison, DPP-4 inhibitors. Active follow‑up started on Jan 1, 2015, or on the date of the first registered diabetes diagnosis, whichever occurred later. Patients were followed up until the end of the observation period (Dec 31, 2024). The main outcomes were hospitalisations related to alcohol use disorder and substance use disorder (which included the alcohol use disorder-related events). Fixed-effects Poisson regression models were used to estimate rate ratios (RRs) of hospitalisations, comparing periods of GLP-1 receptor agonist or DPP-4 inhibitor exposure and two post-exposure windows (days 1-182 and 183-364) with unexposed periods in the same individuals. People with lived experience were not involved in the study. FINDINGS: 167 026 individuals with type 2 diabetes (mean age 63·98 years [SD 13·77]; median age 65·00 years [IQR 55·00-74·00]; 96 133 [57·6%] males and 70 893 [42·4%] females) were included in the study. Ethnicity data were unavailable. 1559 (0·9%) individuals had at least one alcohol use disorder-related hospitalisation and 2008 (1·2%) had at least one substance use disorder-related hospitalisation. 41 109 (24·6%) individuals received GLP-1 receptor agonists during the study period, and 23 666 (14·2%) received DPP-4 inhibitors. 308 (0·7%) of those receiving GLP-1 receptor agonists had at least one alcohol-related hospitalisation during the observational period, and 444 (1·1%) had at least one substance use-related hospitalisation; 957 (66·1%) of the 1447 substance use disorder-related hospitalisations recorded in these 444 individuals were attributed to alcohol use disorder. GLP-1 exposure was associated with lower rates of hospitalisations related to alcohol use disorder (RR 0·55, 95% CI 0·43-0·70) and substance use disorder (0·61, 0·50-0·74) compared with unexposed periods for the same individuals. For individuals with alcohol use disorder, the association with hospitalisation rate reduction persisted during days 1-182 after discontinuation of GLP-1 receptor agonists (0·70, 0·50-0·98) but was no longer evident during days 183-364 after discontinuation (1·07, 0·71-1·63); for substance use disorder, there were no statistically significant associations with reduction after discontinuation of GLP-1 receptor agonists (days 1-182: 0·79, 0·61-1·02; days 183-364: 0·89, 0·63-1·26). DPP-4 inhibitors were not associated with consistent rate reductions. INTERPRETATION: GLP-1 receptor agonist treatment was associated with lower rates of hospitalisation in individuals with alcohol use disorder and substance use disorder. This association extended into the first 182 days after discontinuation for alcohol use disorder but not for substance use disorder. Findings support clinical monitoring of substance use when GLP-1 receptor agonist treatment is stopped. FUNDING: Forte, Karolinska Institutet, and Region Stockholm.
This study integrated UPLC-QE Orbitrap-MS/MS, network pharmacology, and experimental validation to investigate the chemical profile and therapeutic mechanisms of the Yueju pill (YJP) in the treatment of alcoholic liver disease (ALD). Chemical analysis identified 91 compounds in the YJP. After SwissADME screening, 45 active ingredients were predicted as potential bioactive compounds. By overlapping the targets of these compounds with ALD-related targets, a "component-target-disease" network was constructed, revealing 183 common targets. Enrichment analysis indicated that YJP exerts its therapeutic effects through multiple pathways, including the HIF-1 signaling pathway. In animal experiments, an ALD mouse model was established using the Lieber-DeCarli ethanol liquid diet. YJP intervention significantly reduced serum TG, AST, and ALT levels, alleviated hepatic lipid deposition and collagen deposition, improved liver mitochondrial homeostasis, and decreased hepatic HIF-1α expression. Moreover, the YJP improved intestinal barrier integrity and upregulated intestinal HIF-1α and occludin expression, reflecting a therapeutic mechanism involving coordinated regulation of the gut-liver axis.
Journal of viral hepatitisMeredith A Barranco, Sarah Shufelt, Colleen Flanigan, Larissa Wilberschied, Tomoko Udo
Hepatitis C virus (HCV) infection disproportionately impacts people who inject drugs (PWID). Understanding the prevalence and correlates of current and lifetime HCV infection is necessary to inform prevention, testing and treatment efforts among PWID to reduce HCV burden and achieve HCV elimination targets in this population From June 2021-December 2023, 751 PWID were recruited from syringe service harm reduction programs (SSP) and by referral from communities around New York State (NYS). Participants completed web-based surveys on risk factors and social determinants of health and were tested for HCV antibody and RNA to assess their current and lifetime HCV status (never infected, previously infected, or currently infected). Controlling for recruitment site as a fixed effect, a multivariate mixed logistic regression model was built to assess factors significantly associated with HCV status. Among PWID, 58% had a lifetime history of infection, and 29% were currently infected (50% among those with a lifetime history of infection). Daily/almost-daily injection, opioid injection, homelessness, and experience of abscess (all past-year) were significantly associated with current infection, as was younger age. Past-year SSP utilization was associated with a lifetime history of infection. PWID are a priority population to achieve HCV elimination in NYS. Our findings show that HCV burden is high among PWID utilizing SSPs. Expanding access to HCV care and treatment in harm reduction service settings while also providing services to address social determinants of health may be an effective strategy to progress towards reducing the burden of HCV among PWID.
Bipolar disordersGi Jung Shin, Jesse D Hinckley, Amanda E Guyer, Manpreet K Singh
BACKGROUND: Aberrant thalamic structure has been documented in youth with bipolar disorder (BD) and linked with cannabis use, which commonly co-occurs with BD. However, the timeline of when these associations evolve remains unclear. This study aimed to longitudinally compare thalamic volume among youth with and without first episode mania who do or do not use cannabis and other substances. METHODS: Demographic and magnetic resonance imaging (MRI) data from youth (13-18 years old) with BD (n = 22) were compared to similarly aged healthy youth (n = 23) at baseline and 12-month follow-up. Clinical group status, including BD and substance misuse and dependence, was evaluated using semistructured interviews. Multivariate analyses accounting for total brain volume and baseline age were conducted to evaluate baseline and longitudinal group differences in thalamic volume. RESULTS: At 12 months, BD youth had significantly smaller left thalamus volumes compared to healthy youth (p = 0.009). Lifetime cannabis use was associated with smaller left thalamus volumes for all youth (p < 0.001) and for youth with BD compared to healthy controls (p < 0.001) across time. Among BD youth, co-occurring lifetime substance use was associated with significant volumetric reductions in the left thalamus from baseline to follow-up (p = 0.004), but not among healthy youth (p = 0.517). No significant group differences or changes were observed in the right thalamus. CONCLUSIONS: BD is associated with smaller left thalamic volume after the first manic episode. Cannabis use may compound thalamic volume reductions in youth with BD. Investigations with larger sample sizes are needed to replicate these findings and examine clinical correlates of cannabis use alongside long-term thalamic trajectories.
Bipolar disordersManuel Gurpegui, Luis Gutiérrez-Rojas, José M Martínez-Ortega, Jesús García-Jiménez, Sara Jiménez-Fernández, Pablo J González-Domenech, Lucía Pérez-Costillas
INTRODUCTION: The prevalence of tobacco smoking and high nicotine dependence (ND) in bipolar disorder (BD) is higher than in the general population but lower than in schizophrenia. This study aims to analyse the relationship of smoking behaviours, including age at onset of daily smoking (AODS), with age at onset of BD and course-of-illness variables -particularly recurrent suicide attempt- in a community sample of BD patients, also compared in their smoking behaviour variables with a sample of non-psychiatric adults. METHODS: Samples of 108 patients with BD and 290 non-psychiatric adults were compared in their smoking habit. High ND was defined by a score of ≥ 6 on the Fagerström Test for Nicotine Dependence. Logistic regression analyses were employed to identify factors associated with daily smoking and high ND. Hazard curves were used to compare AODS between patients and controls and, among patients, age of BD onset between smokers and non-smokers. Within-subject survival times -AODS and the age at onset of BD symptoms- were compared with a multi-state illness-death model. RESULTS: Compared with controls, BD patients showed higher prevalences of current daily smoking (44% vs. 34%) and high ND (25% vs. 9%); and lower smoking cessation rates (23% vs. 38%). Among BD patients, recurrent suicide attempt showed a strong independent association with both daily smoking and high ND. AODS was later in BD patients than the control group. Among patients, illness onset was earlier in smokers and AODS was earlier than illness onset. CONCLUSION: Addressing tobacco consumption should be an integral component of BD prevention and treatment strategies.
International journal of psychology : Journal international de psychologieWojciech Kulesza, Paweł Muniak, Dariusz Dolinski, Oliwia Marciszewska, Joanna Siemianowska
Tobacco addiction, a major cause of preventable death, requires an understanding of how it develops and is maintained. This paper examines mimicry as a 'social glue' in smokers' social interactions and its influence on the development and maintenance of smoking behaviour. A first laboratory experiment showed that nonverbal mimicry (physical actions, hand and arm movements and body posture) increases cigarette consumption due to increased liking for the mimicker, proving that mimicry not only binds (smokers) but first and foremost reduces chances for quitting smoking. The second experiment, conducted in a natural setting, showed that mimicry of smoking behaviour reduced the desire to quit smoking. This suggests that whilst mimicry acts as a strong 'social glue' amongst smokers, it also impedes efforts to quit. Thus, it seems that mimicry maintains smoking addiction and overcoming tobacco addiction might require severing the social bonds created by mimicry (e.g., smoking in solitary).
Gut microbesIzabella Sall, Randi Foxall, Lindsey Felth, Anirudh Gaur, Jennifer L Whistler, Cheryl A Whistler
Although opioids are effective analgesics, they can lead to problematic drug use behaviors that underlie opioid use disorder (OUD). Opioids also cause gut microbiota dysbiosis, which is linked to altered opioid responses. We used a longitudinal paradigm of voluntary oral morphine self-administration to capture multiple facets of drug seeking and preserve both individual behavioral responses and individual gut microbiota variation to investigate the role of the gut microbiota in a mouse model of OUD. Although all the mice consumed morphine, only a subset of the mice that transitioned to a state we defined statistically as compulsive. In compulsive mice, morphine constricted natural variability and fragmented the microbiota community networks, which convergently reorganized to form robust novel connections post-morphine. In contrast, the more variable communities of non-compulsive mice were highly interconnected during morphine disturbance and displayed more continuity post-morphine, suggesting greater flexibility and adaptability. Compulsive mice displayed a greater loss of functional diversity and a shift in favor of potential pathobionts, whereas non-compulsive mice better preserved genera associated with gut health and broader functional diversity. These findings highlight the potential role of persistent and stable opioid-induced microbiota dysbiosis in long-term behavioral changes underlying OUD and contributing to vulnerability to relapse.
European journal of psychotraumatologyAustin M Hahn, Sudie E Back, Daryl R Hesse, Carla Kmett Danielson, Katherine L Mills, Emma L Barrett, Therese K Killeen, Michaela Buckhannon, Rachel L Tomko, M…
Background: Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) frequently co-occur during adolescence and are associated with substantial functional impairment and elevated risk for chronic comorbidity. Despite strong evidence supporting integrated, trauma-focused treatments for adults with PTSD + SUD, the adolescent treatment literature remains limited.Objective: This review synthesizes current evidence on the integrated treatments for co-occurring PTSD + SUD problems among adolescents and youth, with emphasis on evaluating the strength of the evidence and identifying key directions for future research.Method: Targeted searches identified randomized controlled trials, open trials, pilot studies, and feasibility studies evaluating treatments for adolescents with PTSD + SUD problems. Studies were included if they reported PTSD and/or substance use outcomes. Findings from the adult PTSD + SUD literature were reviewed to inform developmentally appropriate adaptation for youth.Results: The adolescent evidence base is sparse. Risk Reduction Through Family Therapy (RRFT) is the only integrated treatment supported by multiple randomized controlled trials, demonstrating durable improvements in PTSD symptoms and substance use. Preliminary evidence also supports Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure for Adolescents (COPE-A). Across studies, trauma-focused treatment was not associated with increased substance use and was generally acceptable to adolescents. However, conclusions are constrained by small samples, heterogeneous interventions, and limited long-term and implementation data.Conclusions: Integrated, trauma-focused psychotherapies appear safe and promising for adolescents with co-occurring PTSD + SUD problems. Larger trials, mechanistic research, and implementation-focused studies are needed to inform best practices and expand access to effective care.
Gut microbesFernanda Raya Tonetti, Hui Han, Marcos F Fondevila, Wenchao Wei, Burcin Özdirik, Jasmohan S Bajaj, Mitchell L Schubert, Masoumeh Sikaroodi, Patrick M Gillevet,…
Gastric acid-suppressive medications, particularly proton pump inhibitors (PPIs), are commonly used in patients with alcohol-associated liver disease (ALD) to prevent and manage upper gastrointestinal bleeding, gastroesophageal reflux disease, and non-steroidal anti-inflammatory/aspirin-induced gastroesophageal damage. By inhibiting the gastric H⁺/K⁺-ATPase, PPIs suppress acid secretion and impair bacterial killing, thereby promoting gut dysbiosis that disrupts barrier integrity and enhances bacterial translocation, ultimately exacerbating liver injury. PPIs are frequently co-administered with antibiotics for indications such as gastrointestinal bleeding, Spontaneous Bacterial Peritonitis (SBP), other infections, or hepatic encephalopathy prophylaxis, but the consequences of this combined therapy on gut microbial ecology and disease outcomes remain unclear. Our study addresses this gap by showing how PPI use, alone or with antibiotics, reshapes the gut microbiome and aggravates liver disease progression. In previous studies, we showed that PPIs promote dysbiosis and ALD progression in mice and humans by facilitating intestinal expansion and hepatic translocation of Gram-positive Enterococcus. Fecal cytolysin, an Enterococcus faecalis exotoxin that induces hepatocyte death, predicts mortality in patients with alcohol-associated hepatitis (AH). In this study, we have examined the mechanism by which PPIs alone and in combination with non-absorbable antibiotics targeting Gram-positive bacteria influence ALD, as well as the disease mechanisms associated with cytolytic Enterococcus faecalis and the development of therapeutic strategies. In mice, alcohol administration during gastric acid suppression promoted expansion of Gram-positive taxa, including cytolysin-producing Enterococcus. Similarly, PPI use in patients with AH was associated with increased fecal Enterococcus and higher 30-d mortality, underscoring the translational relevance of our findings. Unexpectedly, treatment of acid-suppressed mice with non-absorbable antibiotics designed to suppress Gram-positive bacteria worsened ethanol-induced steatohepatitis: while Enterococcus abundance decreased, Streptococcus and other potentially pathogenic taxa expanded, leading to increased bacterial translocation and aggravated liver injury. In patients with cirrhosis or metabolic dysfunction-associated steatotic liver disease (MASLD), PPIs did not promote Enterococcus expansion, indicating etiology-dependent microbiome responses. Finally, we identified dipalmitoylphosphatidylcholine and Caspase-1 inhibitor as in vitro and in vivo modulators of cytolysin activity, highlighting potential therapeutic avenues. Collectively, our study demonstrates how PPIs and non-absorbable antibiotics targeting Gram-positive bacteria interact with the gut microbiome to drive ALD, underscoring the need for careful therapeutic management.
European journal of psychotraumatologyAmanda M Bunting, Hunter Molloy, Brittany Griffin, Ana Ventuneac, Tanya Renn
Background: Polysubstance use of stimulants and opioids is prevalent among patients receiving methadone in opioid treatment programmes (OTPs) and has been linked with complex clinical profiles and poor outcomes, including psychiatric comorbidity, overdose death, and early attrition from treatment.Objective: The study goal was to adapt the evidence-based intervention Skills Training in Affective and Interpersonal Regulation with Narrative Therapy (STAIR-NT) for polysubstance populations informed by the ADAPT-ITT framework to gain preliminary information regarding intervention acceptability and implementation barriers.Method: To obtain feedback on adapting the intervention and approaches to integrate it, focus groups with key stakeholders (i.e. counsellors, clinical leadership) were conducted, as well as individual interviews with patients receiving treatment at OTPs in New York City, USA. Following decisions regarding intervention adaption, two protocol versions were tested using an open pilot.Results: Patients and key stakeholders were enthusiastic about the intervention and its potential to meet patient treatment needs, bridge gaps in mental health care, and improve outcomes. Specific strategies were identified to adapt the intervention related to session length, treatment delivery format, and choice of interventionist. This qualitative work informed the creation of a 6-week protocol that was tested in an open pilot. Patients were randomized to receive four STAIR sessions with two 90-minute NT sessions (one session per week) or four STAIR sessions with four 60-minute NT sessions delivered in a massed schedule over two weeks. Participants who completed treatment generally preferred the four-session NT format; however, substantial implementation barriers impacted retention. Barriers related to scheduling and patients' complex vulnerabilities, including housing instability and illness.Conclusions: Adapting and testing the STAIR-NT intervention within the OTP setting provided an opportunity to align the therapeutic format, content, and implementation with lived experiences and clinical needs of patients. The selected protocol will be tested in a pilot randomized controlled trial.
METHODS: A hospital-based cross-sectional study was conducted among hypertensive outpatients at the University of Gondar Comprehensive and Specialized Hospital from January 30 to May 30, 2024. Participants were selected using simple random sampling. Alcohol use disorder was assessed using the Alcohol Use Disorders Identification Test (AUDIT) and medication adherence was evaluated over a three-month period. Bivariable and multivariable logistic regression analyses identifed factors associated with AUD and non-adherence to antihypertensive therapy. Statistical significance was set at p < 0.05. RESULTS: A total of 400 participants were included (response rate: 100%), with a mean age of 44.9 ± 12.5 years. The prevalence of AUD was 12.2%, comprising hazardous drinking (8.0%), harmful use (2.5%), and alcohol dependence (1.7%). Male sex (AOR = 3.60; 95% CI: 1.30-9.94), cigarette smoking (AOR = 8.56; 95% CI: 3.89-18.82), and comorbidities (AOR = 3.87; 95% CI: 1.75-8.56) were independently associated with AUD. Overall, 42.2% of participants were non-adherent to antihypertensive therapy. Alcohol dependence was associated with nearly fourfold higher odds of poor adherence compared with social drinking. CONCLUSION: AUD is common among hypertensive patients and is significantly associated with poor adherence to antihypertensive therapy. Integrating alcohol use screening and intervention into routine hypertension care may improve medication adherence and treatment outcomes.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VTiandian Wang, Anuj A Biswas, Feng Zhang, Rongjin Sun, Ming Hu
With annual overdose deaths in the United States over 1 million, medication-assisted treatment with buprenorphine (BUP) remains the first-line, gold-standard therapy for opioid use disorder (OUD). Because OUD is a chronic, relapsing condition that requires long-term pharmacotherapy, long acting injectables (LAI) and implantable formulations offer important advantages over daily formulations for maintenance treatment. By comparing transmucosal BUP and LAI formulations' systemic exposure profiles and μ-opioid receptor (MOR) occupancy, converging data demonstrate that higher and more sustained BUP exposure with low variability is required to fully suppress withdrawal, cravings, and illicit opioid use. These findings indicated that currently marketed formulations may not adequately address the clinical challenges associated in the fentanyl/polysubstance era. Accordingly, this rationale-based review proposes a mechanistic framework supporting the development of next-generation BUP-PLGA solid biodegradable implants to maintain a conservative therapeutic benchmark (e.g. Css ≥ 5 ng/mL) for extended durations (e.g. 3-6 months) with low variability (e.g. no large burst release, major lag phase or phase inversion). However, progress in implant development has been hindered by limited mechanistic understanding of drug release. In PLGA-BUP systems, poor IVIVC is largely driven by the low and pH-dependent solubility of BUP, which can make dissolution rate-limiting in vivo and interact with the evolving PLGA acidic microenvironment (acidification, porosity formation, and autocatalytic degradation). Future research should be prioritized to determine directly whether polymer erosion coincides with drug release in PLGA depots, or whether residual, poorly soluble BUP persists locally and releases under dissolution-limited kinetics. Clarifying these mechanisms is not only essential to fulfill the regulatory and translational expectations of the FDA and NIDA, but also to deepen mechanistic understanding and accelerate the rational development of LAI formulations for poorly soluble drug.
Gut microbesSusana Delgado Ocaña, Guadalupe Herrera, Daniel Guzmán, David W Self, Santiago Cuesta
Addiction is a chronic and relapsing disorder that affects millions of people worldwide; nonetheless, currently available FDA-approved treatments are limited in number and effectiveness. In past years, the gut-brain axis has emerged as a key modulatory factor associated with different psychiatric disorders, including addiction. Working in mice, we have shown that cocaine exposure alters the composition of the gut microbiome, increasing the abundance of Proteobacteria. This microbial shift, in turn, leads to a depletion in host glycine levels, altering cocaine-induced transcriptional changes in the Nucleus Accumbens (NAc) and facilitating the development of behavioral sensitization and conditioned place preference. Among the behavioral models to study psychostimulant use disorders, cocaine self-administration (SA) remains the most translational. Therefore, here we investigated whether Proteobacteria-induced glycine depletion can affect cocaine SA in mice. Using the human Escherichia coli HS and the glycine-uptake-deficient mutant E. coli HS ΔCycA, we build upon our previous findings and demonstrate that the ability of gut Proteobacteria to use glycine during cocaine SA shapes the trajectory and long-term neurobehavioral plasticity induced by the drug. Furthermore, we show that this bacterial-induced glycine depletion impacts the NAc proteome, altering its vulnerability to undergo molecular adaptations across different stages of the SA paradigm. Altogether, our findings show that the gut microbiome, and particularly the Proteobacteria phylum, is a crucial factor influencing short and long-term adaptation underlying motivation and cocaine-seeking behaviors.
Sleep medicineRodolfo Espinoza-Abad, María Del Carmen Gogeascoechea-Trejo, Fabio García-García
OBJECTIVE: To examine the associations of chronotype and sleep quality with psychoactive substance use among adolescents attending schools with different schedules and patterns associated with chronotype-school schedule combinations. METHODS: A cross-sectional study was conducted in 1311 adolescents aged 11-19 years from public and private schools. Chronotype was assessed using the Children's Morningness-Eveningness Questionnaire, sleep quality using the Pittsburgh Sleep Quality Index, and psychoactive substance use through structured questionnaires. Logistic regression models examined the independent and joint associations of chronotype and sleep quality with psychoactive substance use. Formal Chronotype × School Schedule interactions were also tested. RESULTS: Most adolescents reported insufficient sleep (65 % slept <8 h/night) and regular or poor sleep quality (80 %). Morning-shift students reported shorter sleep duration than evening-shift students. In separate adjusted models, evening chronotype and poor sleep quality were associated with higher odds of alcohol, tobacco, and cannabis use. In fully adjusted models, sleep quality remained the most consistent predictor across substance categories, whereas chronotype associations were substantially attenuated. Formal Chronotype × School Schedule interactions were not statistically significant for alcohol, tobacco, or cannabis use. However, analyses using a combined chronotype-school schedule variable identified significant differences in alcohol, tobacco, and cannabis use patterns across chronotype-school schedule groups. CONCLUSIONS: Sleep quality showed the most consistent associations with psychoactive substance use across multiple substance categories. Although the school schedule did not significantly modify chronotype-related associations, chronotype-school schedule combinations were associated with distinct substance-use patterns. These findings highlight sleep health as a potential target for adolescent substance-use prevention.
Journal of affective disordersS Stanislaus, C F Thirstrup, H L Kjærstad, K S O Sletved, M Faurholt-Jepsen, K Munkholm, K W Miskowiak, M Vinberg, K Coello, L V Kessing
BACKGROUND: Comorbid substance use is common in patients with bipolar disorder (BD) and associated with a more severe illness course and higher mortality rates. We aimed to investigate 1) the prevalence of lifetime comorbid substance misuse in patients with newly diagnosed BD compared with healthy controls (HC), and 2) differences in illness characteristics between patients with and without comorbid substance misuse. METHODS: We included 376 patients with newly diagnosed BD and 200 HC. Lifetime substance misuse (including alcohol and drug use) was identified through baseline interview and through systematic review of electronic health records. RESULTS: The prevalence of lifetime substance misuse was higher for patients with newly diagnosed BD (43%). Patients with BD had a high prevalence of lifetime comorbid drug misuse (38%) than alcohol misuse (19%). Among patients, lifetime substance misuse was associated with male sex (OR = 2.86 [1.82; 4.55] p < 0.001), childhood trauma (β = 5.33 [2.68; 7.99], p = 0.003), BD type I (OR = 1.71 [1.09; 2.68], p = 0.042), presence of suicide attempts (OR = 2.26 [1.36; 3.75], p = 0.005) and more sick days the preceding year (β = 41.43 [16.90; 65.96], p = 0.012). LIMITATIONS: Information regarding substance use was partly gathered retrospectively using electronic health records. HC were recruited among blood donors and may not be representative of the general population. CONCLUSION: We found a high prevalence of lifetime comorbid substance misuse, particularly drug misuse in patients with newly diagnosed BD. Lower clinical focus on drug use than alcohol may have contributed to higher observed prevalence of drug use. This highlights the need for early clinical assessment and integrated treatment.
PsychoneuroendocrinologyVítor Hugo Santos, Yannis Paloyelis, Manuel Morgado, Joana Ramos Rodrigues, Ricardo Tjeng, Manuela Fraga, Paula Carriço, Lia Fernandes, Daniel Martins
BACKGROUND: Intranasal oxytocin (OT) has been proposed as a promising adjunctive treatment for Alcohol Use Disorder (AUD), yet randomized controlled trials (RCTs) have yielded mixed and inconclusive findings. To clarify its therapeutic potential, we conducted a comprehensive meta-analysis using frequentist, Bayesian, and variability-based approaches. METHODS: We performed a multilevel random-effects meta-analysis of six eligible RCTs comparing intranasal OT with placebo for alcohol-related outcomes. Hedges' g values were calculated and winsorised at |g| = 3 to limit leverage from extreme small-sample effects. Moderator analyses assessed outcome domain, OT dose, treatment duration, year of publication, administration frequency, and clinical setting. Publication bias was evaluated using multilevel PET-PEESE with cluster-robust correction, Egger's test, trim-and-fill, and limit meta-analysis. Bayesian multilevel models examined average treatment effects and outcome variability. RESULTS: The overall pooled effect was not statistically significant (Hedges' g = 0.34, 95% CI -0.48-1.17, p = 0.47), with substantial between-study heterogeneity (Q(48) = 504.40, p < .001). Cook's distance identified Pedersen et al. (2013) as statistically influential; moderator and publication bias analyses were conducted on the remaining five studies. No significant moderation was observed by outcome domain, dose, duration, frequency, or setting. Year of publication showed a nominally significant positive association with effect size in the restricted sample (β = 0.184, p = .042). Multiple publication bias diagnostics converged on the absence of a systematic adjusted effect. Bayesian multilevel analysis confirmed the absence of a credible treatment effect (posterior mean μ = -0.005, 95% CrI -0.53-0.52). Robust Bayesian meta-analysis provided moderate support for the null hypothesis (BF₀₁ = 4.74). Variability analyses found no evidence that OT increased outcome dispersion relative to placebo (lnVR = -0.146, p = .153 after robust correction), providing no support for latent responder subgroups. CONCLUSIONS: Contrary to early expectations, intranasal OT does not confer a consistent therapeutic benefit across alcohol-related outcomes. The lack of evidence for publication bias or increased outcome variability argues against latent differential responsiveness driving effects. Nonetheless, context-sensitive signals - particularly in domains related to social-cognitive processing - underscore the need for mechanistically informed trials. Future research should prioritise precision frameworks to clarify when, for whom, and under what conditions OT may yield meaningful clinical benefit.