Emma L Winterlind, Samantha G Malone, Michael R Setzer, Mikela A Murphy, David Saunders, Joshua C Gray
N-acetylcysteine (NAC) may serve as a novel pharmacotherapy for substance use and substance craving in individuals with substance use disorders (SUDs), possibly through its potential to regulate glutamate. Though prior meta-analyses generally support NAC's efficacy in reducing symptoms of craving, individual trials have found mixed results. The aims of this updated meta-analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with SUD and (2) explore subgroup differences, risk of bias and publication bias across trials. Database searches of PubMed, Cochrane Library and ClinicalTrials.gov were conducted in June and July of 2023 to identify relevant randomized control trials (RCTs). The meta-analysis consisted of 9 trials which analysed data from a total of 623 participants. The most targeted substance in the clinical trials was alcohol (3/9; 33.3%), followed by tobacco (2/9; 22.2%) and multiple substances (2/9; 22.2%). Meta-analysis, subgroup analyses and leave-one-out analyses were conducted to examine the treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests and funnel plot tests were conducted to examine the risk of bias and publication bias. NAC did not significantly outperform placebo in reducing symptoms of craving in the meta-analysis (SMD = 0.189, 95% CI = -0.015-0.393). Heterogeneity was very high in the meta-analysis (99.26%), indicating that findings may have been influenced by clinical or methodological differences in the study protocols. Additionally, results indicate that there may be publication bias present. Overall, our findings are contrary to those of prior meta-analyses, suggesting a limited impact of NAC on substance craving. However, the high heterogeneity and presence of publication bias identified warrants cautious interpretation of the meta-analytic outcomes.
{"title":"N-acetylcysteine as a treatment for substance use cravings: A meta-analysis.","authors":"Emma L Winterlind, Samantha G Malone, Michael R Setzer, Mikela A Murphy, David Saunders, Joshua C Gray","doi":"10.1111/adb.70001","DOIUrl":"10.1111/adb.70001","url":null,"abstract":"<p><p>N-acetylcysteine (NAC) may serve as a novel pharmacotherapy for substance use and substance craving in individuals with substance use disorders (SUDs), possibly through its potential to regulate glutamate. Though prior meta-analyses generally support NAC's efficacy in reducing symptoms of craving, individual trials have found mixed results. The aims of this updated meta-analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with SUD and (2) explore subgroup differences, risk of bias and publication bias across trials. Database searches of PubMed, Cochrane Library and ClinicalTrials.gov were conducted in June and July of 2023 to identify relevant randomized control trials (RCTs). The meta-analysis consisted of 9 trials which analysed data from a total of 623 participants. The most targeted substance in the clinical trials was alcohol (3/9; 33.3%), followed by tobacco (2/9; 22.2%) and multiple substances (2/9; 22.2%). Meta-analysis, subgroup analyses and leave-one-out analyses were conducted to examine the treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests and funnel plot tests were conducted to examine the risk of bias and publication bias. NAC did not significantly outperform placebo in reducing symptoms of craving in the meta-analysis (SMD = 0.189, 95% CI = -0.015-0.393). Heterogeneity was very high in the meta-analysis (99.26%), indicating that findings may have been influenced by clinical or methodological differences in the study protocols. Additionally, results indicate that there may be publication bias present. Overall, our findings are contrary to those of prior meta-analyses, suggesting a limited impact of NAC on substance craving. However, the high heterogeneity and presence of publication bias identified warrants cautious interpretation of the meta-analytic outcomes.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"29 11","pages":"e70001"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S R Aggarwal, C H Griffiths, K O Lindros, T N Palmer
Ethanol has profound acute effects on hepatic metabolism. While many of these effects are mediated via the redox imbalance that accompanies hepatic ethanol oxidation via the alcohol dehydrogenase (ADH) pathway, there is increasing evidence that ethanol also perturbs hepatic metabolism via its modulation of cyclic AMP-mediated signalling pathways. This paper examines the effects of ethanol on glucagon-stimulated protein phosphorylation using SDS-PAGE to analyse the 32P-labelling of cytosolic peptides in isolated rat hepatocytes pre-equilibrated with 32PO4(3-). We show that ethanol has biphasic effects on glucagon-stimulated protein phosphorylation. At a low concentration (50 mM), ethanol decreased the phosphorylation of certain peptides, whereas at higher concentrations (100-200 mM) it increased the 32P-labelling of all of the eleven glucagon-stimulated cytosolic peptides. The non-metabolizable alcohol 2-methylpyrazole-2-ol had no effects on glucagon-stimulated protein phosphorylation. The ADH inhibitor 4-methylpyrazole at 150 mM ethanol concentration abolished the potentiating effect of ethanol on the glucagon-stimulated phosphorylation of most peptides. In conclusion, the results indicate that ethanol alters glucagon-receptor-dependent protein phosphorylation in isolated hepatocytes via a complex mechanism that is partially dependent on ethanol oxidation via ADH.
{"title":"Effects of ethanol on glucagon-stimulated protein phosphorylation in isolated hepatocytes.","authors":"S R Aggarwal, C H Griffiths, K O Lindros, T N Palmer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Ethanol has profound acute effects on hepatic metabolism. While many of these effects are mediated via the redox imbalance that accompanies hepatic ethanol oxidation via the alcohol dehydrogenase (ADH) pathway, there is increasing evidence that ethanol also perturbs hepatic metabolism via its modulation of cyclic AMP-mediated signalling pathways. This paper examines the effects of ethanol on glucagon-stimulated protein phosphorylation using SDS-PAGE to analyse the 32P-labelling of cytosolic peptides in isolated rat hepatocytes pre-equilibrated with 32PO4(3-). We show that ethanol has biphasic effects on glucagon-stimulated protein phosphorylation. At a low concentration (50 mM), ethanol decreased the phosphorylation of certain peptides, whereas at higher concentrations (100-200 mM) it increased the 32P-labelling of all of the eleven glucagon-stimulated cytosolic peptides. The non-metabolizable alcohol 2-methylpyrazole-2-ol had no effects on glucagon-stimulated protein phosphorylation. The ADH inhibitor 4-methylpyrazole at 150 mM ethanol concentration abolished the potentiating effect of ethanol on the glucagon-stimulated phosphorylation of most peptides. In conclusion, the results indicate that ethanol alters glucagon-receptor-dependent protein phosphorylation in isolated hepatocytes via a complex mechanism that is partially dependent on ethanol oxidation via ADH.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"1 4","pages":"415-25"},"PeriodicalIF":3.4,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24102761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号