medRxiv - Addiction Medicine最新文献

{"title":"Altered brain glucose metabolism in nicotine use but not in hazardous alcohol consumption or problem gambling of healthy middle-aged adults","authors":"Seunghyeon Shin, Keunyoung Kim, Jihyun Kim, Hyun-Yeol Nam, Ju Won Seok, Kyoungjune Pak","doi":"10.1101/2024.04.29.24306507","DOIUrl":"https://doi.org/10.1101/2024.04.29.24306507","url":null,"abstract":"<strong>Objectives</strong> We aimed to determine whether chronic nicotine use, alcohol consumption, and gambling alters brain glucose metabolism.","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140884230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum cytokine and inflammatory markers in individuals with heroin use disorder: potential biomarkers for diagnosis and disease severity","authors":"Eduardo R. Butelman, Yuefeng Huang, Flurin Cathomas, Pierre-Olivier Gaudreault, Panos Roussos, Scott J. Russo, Rita Z. Goldstein, Nelly Alia-Klein","doi":"10.1101/2024.04.29.24306559","DOIUrl":"https://doi.org/10.1101/2024.04.29.24306559","url":null,"abstract":"Opioid use disorders cause major morbidity and mortality, and there is a pressing need for novel mechanistic targets and biomarkers for diagnosis and prognosis. Exposure to mu-opioid receptor (MOR) agonists causes changes in cytokine and inflammatory protein networks in peripheral blood, and also in brain glia and neurons. Individuals with heroin use disorder (iHUD) show dysregulated levels of several cytokines in blood. However, there is limited data on a comprehensive panel of such markers in iHUD versus healthy controls (HC), especially as a multi-target biomarker. We used a validated proximity extension assay for relative quantification of 92 cytokines and inflammatory proteins in serum of iHUD on medication assisted therapy (MAT; n=21), versus HC (n=24). Twenty-nine targets showed significant group differences (primarily iHUD&gt;HC), surviving multiple comparison correction (p=0.05). This included 19 members of canonical cytokine families, including specific chemokines, interleukins, growth factors, and tumor necrosis factor (TNF)-related proteins. For dimensionality reduction, data from these 19 cytokines were entered into a principal component (PC) analysis, and PC1 scores were iHUD&gt;HC (p&lt;0.0001). A receiver-operating characteristic (ROC) curve analysis yielded an AUROC=91.7% (p&lt;0.0001). This PC1 score remained a positive predictor of being in the HUD group in a multivariable logistic regression, which included demographic/clinical variables. Overall, this study shows a panel of cytokines that differ significantly between iHUD and HC, and provides a multi-target “cytokine biomarker score” for potential diagnostic purposes, and examination of disease severity.","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140884326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of year-long cannabis use for medical symptoms on brain activation during cognitive processes","authors":"Debbie Burdinski, Alisha Kodibagkar, Kevin Potter, Randi Schuster, A. Eden Evins, Satrajit Ghosh, Jodi Gilman","doi":"10.1101/2024.04.29.24306516","DOIUrl":"https://doi.org/10.1101/2024.04.29.24306516","url":null,"abstract":"<strong>Importance:</strong> Cannabis is increasingly being used to treat medical symptoms, but the effects of cannabis use on brain function in those using cannabis for these symptoms is not known.","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140884445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline gut microbiome and metabolites are correlated with alcohol consumption in a zonisamide clinical trial of heavy drinking alcoholic civilians","authors":"Liv R. Dedon, Hanshu Yuan, Jinhua Chi, Haiwei Gu, Albert J. Arias, Jonathan M. Covault, Yanjiao Zhou","doi":"10.1101/2024.04.02.24305199","DOIUrl":"https://doi.org/10.1101/2024.04.02.24305199","url":null,"abstract":"Development and severity of alcohol use disorder (AUD) has been linked to variations in gut microbiota and their associated metabolites in both animal and human studies. However, the involvement of the gut microbiome in alcohol consumption of individuals with AUD undergoing treatment remains unclear. To address this, stool samples (n=48) were collected at screening (baseline) and trial completion from a single site of a multi-site double-blind, placebo-controlled trial of Zonisamide in individuals with AUD. Alcohol consumption, gamma-glutamyl transferase (GGT), and phosphatidylethanol (PEth)levels were measured both at baseline and endpoint of 16-week trial period. Fecal microbiome was analyzed <em>via</em> 16S rRNA sequencing and metabolome <em>via</em> untargeted LC-MS. Both sex (p = 0.003) and psychotropic medication usage (p = 0.025) are associated with baseline microbiome composition. The relative abundance of 12 genera at baseline was correlated with percent drinking reduction, baseline and endpoint alcohol consumption, and changes in GGT and PeTH over the course of treatment (p.adj &lt; 0.05). Overall microbiome community structure at baseline differed between high and low responders (67-100% and 0-33% drinking reduction, respectively; p = 0.03). A positive relationship between baseline fecal GABA levels and percent drinking reduction (R=0.43, p &lt; 0.05) was identified by microbiome function prediction and confirmed by ELISA and metabolomics. Predicted microbiome function and metabolomics analysis have found that tryptophan metabolic pathways are over-represented in low responders. These findings highlight importance of baseline microbiome and metabolites in alcohol consumption in AUD patients undergoing zonisamide treatment.","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140596246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fentanyl initiation rate following the requirement for specialist approval","authors":"Oren Miron, Yael Wolff Sagy, Mark Levin, Esti Lubich, Jordan Lewinski, Maya Shpunt, Wiessam Abu Ahmad, Ilya Borochov, Doron Netzer, Gil Lavie","doi":"10.1101/2024.03.13.24304188","DOIUrl":"https://doi.org/10.1101/2024.03.13.24304188","url":null,"abstract":"Importance Healthcare organizations are exploring tools to address unwarranted fentanyl use which often leads to increased risk of addiction and overdose. Objective To assess the impact of a requirement for a specialist's approval on fentanyl initiation for non-oncological pain.\u0000Design, Settings and Participants Retrospective cohort examination of fentanyl initiations and opioid dispensations for 4.4 million members of Clalit Health Services following a requirement for specialist's approval for fentanyl initiation on July 2022, which was expanded 6 months later for continued use.\u0000Main Outcomes and Measures We analyzed the change in initiations of fentanyl in the year before and after the implementation and 95% confidence interval, with a sub-group analysis by age group. We also compared total opioid dispensation, fentanyl, and non-fentanyl in the 6th and 12th month after the implementation with the predicted rate based on pre-implementation rates. Results The fentanyl initiation rate in the year before the requirement was 711/1,000,000 capita, which decreased following the requirement by -81% (95% confidence interval:-77%; -85%). The decrease attenuated with age: at ages 0-17 years -100% (16%; -216%), at ages 18-39 years -88% (-78%; -97%), at ages 40-64 years -89% (-83%; -95%) and at ages 65 years and above -73% (-68%; -79%). In the 6th month after the requirement was implemented the morphine milligram equivalent from dispensation of total opioids and fentanyl was lower than predicted by 7% and 12% respectively, while non-fentanyl opioids dispensation was 3% higher than predicted. In the 12th month after the initiation requirement, the dispensation of total opioids and fentanyl was lower than predicted by 26% and 39% respectively, while in non-fentanyl opioids it was 4% higher than predicted.\u0000Conclusions and Relevance Our results indicate that requiring specialist approval for fentanyl initiation for non-oncological chronic pain was associated with a decrease in fentanyl prescription initiations, especially among non-elderly patients. A decrease also occurred gradually in total opioid dispensations, further decreasing following the extension of the requirement to continuous fentanyl. These findings suggest that requiring specialist approval for non-oncological fentanyl initiations is likely an effective strategy to be considered by other healthcare providers.","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140147894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic liability for anxiety associates with treatment response to the monoamine stabilizer OSU6162 in alcohol dependence","authors":"Mun-Gwan Hong, Lotfi Khemiri, Joar Guterstam, Johan Franck, Nitya Jayaram-Lindstrom, Philippe A. Melas","doi":"10.1101/2024.03.11.24304098","DOIUrl":"https://doi.org/10.1101/2024.03.11.24304098","url":null,"abstract":"OSU6162, a monoamine stabilizer, has demonstrated efficacy in reducing alcohol and anxiety-related behaviors in preclinical settings. In a previous randomized, double-blind, placebo-controlled trial involving patients with alcohol dependence (AD), we found that OSU6162 significantly reduced craving for alcohol, but did not alter drinking behaviors. In the present study, we explored the hypothesis that genetic predispositions related to AD or associated traits, might influence the response to OSU6162 treatment in original trial participants (N=56). To investigate this, we calculated polygenic risk scores (PRSs) over several statistical significance thresholds from genome-wide association studies on (i) alcohol use disorder and alcohol consumption (N=200-202k), (ii) problematic alcohol use (N=435k), (iii) drinks per week (N=666k), (iv) major depression (N=500k), and (v) anxiety (using both case-control comparisons and quantitative anxiety factor scores, N=17-18k). Linear regression analyses assessing the interaction effects between PRSs and treatment type (OSU6162 or placebo) identified significant associations when considering anxiety factor scores (FDR&lt;0.05). Specifically, in OSU6162-treated AD individuals, there was a negative correlation between anxiety factor PRS (at the genome-wide significance threshold that included one genetic variant) and several drinking outcomes, including number of drinks consumed, percentage of heavy drinking days, and changes in blood phosphatidylethanol (PEth) levels. These correlations were absent in the placebo group. While preliminary, these findings suggest the potential utility of anxiety PRS in predicting response to OSU6162 treatment in AD. Further research using larger cohorts and more comprehensive genetic data is necessary to confirm these results and to advance personalized medicine approaches in alcohol use disorder.","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140147971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol, smoking, and illicit substance use in Cameroon: unveiling related risk factors among university students in Yaounde","authors":"Fabrice Zobel Lekeumo Cheuyem, Michel Franck Edzamba, Adidja Amani, Tatiana Mossus","doi":"10.1101/2024.03.10.24304034","DOIUrl":"https://doi.org/10.1101/2024.03.10.24304034","url":null,"abstract":"Background: Substance use, including alcohol, tobacco and illicit drugs, is a growing public health problem worldwide. There is a rapid increase in substance use among young adults in many sub-Saharan African countries. This study aimed to assess the factors associated with the use of different psychoactive substances among university students in Yaounde.\u0000Methods: A cross-sectional and analytical study was conducted from September to October 2023 at Yaounde 1 University in Cameroon. All eligible students aged 18 years and older who gave written informed consent were included. A convenience nonprobability sampling method was used to recruit consenting students. The data collectors were medical students who were trained for 2 days and given appropriate instructions before the survey. The data collected were reviewed and checked for completeness before being entered. The data were analyzed using Statistics 4.3.1.\u0000Results: A total of 191 university students were enrolled in the study. Age (p-value=0.002), level of study (p-value=0.048), and smoking status (p-value=0.005) of the participants were significant factors associated with alcohol on univariate analysis. Multivariate logistic regression showed that students aged 20-25 years were significantly 2.9 times more likely to drink alcohol than those aged less than 20 years (p-value=0.003). Students who smoke were 2.7 times more likely to drink alcohol than those who do not smoke (p-value=0.008). Living situation (p=0.013) and drug use status (p-value&lt;0.0001) were significant factors associated with smoking on univariate analysis. On multivariate analysis, drug users were 3.2 times more likely to smoke than drug non-users (p-value&lt;0.0001). Drug use was significantly associated with district of residence of consumer on univariate analysis (p-value=0.024). Living situation (p-value=0.016), faculty/school(p-value=0.04), and district of residence (p-value=0.037) were significantly associated with polysubstance use. Students living in shared accommodation were 3.8 times more likely to be polysubstance users than those living with their families (p-value=0.023). Almost all smokers (95.1%) reported being aware the of the psychosocial, mental and health consequences of substance use (p-value=0.021).\u0000Conclusion: Several factors have been associated with substance use among college students. These sociodemographic factors can help to strategize and implement tailored interventions to reduce the risk of subsequent substance dependence and other harmful consequences.","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140106873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroanatomical variability associated with early substance use initiation: Results from the ABCD Study","authors":"Alex P Miller, David AA Baranger, Sarah E Paul, Hugh Garavan, Scott Mackey, Susan F Tapert, Kimberly H LeBlanc, Arpana Agrawal, Ryan Bogdan","doi":"10.1101/2024.03.06.24303876","DOIUrl":"https://doi.org/10.1101/2024.03.06.24303876","url":null,"abstract":"The extent to which neuroanatomical variability associated with substance involvement reflects pre-existing risk and/or consequences of substance exposure remains poorly understood. In the Adolescent Brain Cognitive Development^SM (ABCD®) Study, we identify associations between global and regional differences in brain structure and early substance use initiation (i.e., occurring &lt;15 years of age; ns_analytic=6,556-9,804), with evidence that associations precede initiation. Neurodevelopmental variability in brain structure may confer risk for substance involvement.","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140076299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applying Multi-Theory Model (MTM) in Determining Intentions to Smoking Cessation among male Health Worker Smokers in Kabul, Afghanistan","authors":"Farkhondeh Amin Shokravi, Mousa Bashir, Anoshiravan Kazemnezhad","doi":"10.1101/2024.02.22.24303218","DOIUrl":"https://doi.org/10.1101/2024.02.22.24303218","url":null,"abstract":"Introduction: Globally, smoking causes lung cancer and a wide range of acute and chronic diseases. A fourth-generation behavioral framework, the multi-theory model (MTM) of health behavior change was used to predict the initiation and maintenance of smoking cessation among health worker smokers.\u0000Methods: By visiting different Health Centers, a convenience sample of male health worker smokers from west part of Kabul city, was invited to participate in this cross-sectional study. A valid and reliable 37-item MTM-based survey instrument was administered to the male participants who smoked. To explain smoking cessation behavior, stepwise multiple regressions were conducted. The entire value of the Cronbach alpha coefficient (α) of the subscales and the scale for the initiation of MTM variables was 0.80 and for the sustenance of MTM variables was 0.79. Results: The study was completed by 170 participants. Participants were averaging 29.33 years of age (SD = 6.21). The average number of years smokers reported (SD = 4.7), was 5.6. Smoking cigarettes was the median (SD = 5.21), with 5.64 cigarettes consumed per day. Changes in the physical environment (+0.2225, P = 0.029) and behavioral confidence (+0.441, P = 0.014) were significant predictors of smoking cessation initiation. The intention to sustain smoking cessation behavior was significantly influenced by emotional transformation (β = 0.222, P = 0.017) and practicing for change (β = 0.217, P = 0.015).\u0000Conclusions: There was moderate variance in smoking cessation behavior among health worker smokers in Kabul's western part explained by two MTM constructs ( behavioral confidence, physical environment) for initiation and two MTM constructs (emotional transformation ,practicing for change) for maintenance. Smoking cessation behavior can be assessed using MTM both at the initiation and maintenance stages. It is important to develop future interventions using MTM constructs aiming to change smokers' behavior in regard to quitting smoking.\u0000Keywords: smoking cessation, multi-theory model, initiation, sustenance, health workers","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139951216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the association between the FTO gene and neuroticism reveals indirect effects on subjective well-being and problematic alcohol use","authors":"Wenjie Cai, Yvonne Forsell, Catharina Lavebratt, Philippe A. Melas","doi":"10.1101/2024.02.20.24303076","DOIUrl":"https://doi.org/10.1101/2024.02.20.24303076","url":null,"abstract":"Associations between the fat mass and obesity-associated (FTO) gene and obesity are well-established. However, recent studies have linked FTO to addiction phenotypes and dopaminergic signaling, thus suggesting broader psychiatric implications. We explored this assumption by conducting a phenome-wide association study (PheWAS) across 4,756 genome-wide association studies (GWASs), identifying 26 psychiatric traits associated with FTO at the multiple-corrected significance level. These traits clustered into four categories: substance use, chronotype/sleep, well-being, and neuroticism. To validate these findings, we analyzed a functionally suggestive FTO variant (rs1421085) in a separate cohort, examining its impact on (i) alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), (ii) subjective well-being based on the WHO (Ten) Well-Being Index, and (iii) neuroticism based on Schafer's Five Factor Model (FFM) or the Karolinska Scales of Personality (KSP). Our results confirmed a direct association between rs1421085 and neuroticism that was independent of age, sex, alcohol use, body mass index (BMI), and childhood adversities. Interestingly, while no direct association with alcohol intake was observed, both cross-sectional and lagged longitudinal mediation analyses uncovered indirect relationships between rs1421085 and problematic alcohol use (AUDIT-P), with increased neuroticism acting as the intermediary. Mediation analyses also supported an indirect effect of rs1421085 on lower well-being through the pathways of increased neuroticism and BMI. Our study is the first to validate a direct association between FTO and neuroticism. However, additional studies are warranted to affirm the causal pathways linking FTO to well-being and alcohol use through neuroticism.","PeriodicalId":501282,"journal":{"name":"medRxiv - Addiction Medicine","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}