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Hazardous alcohol consumption is highly prevalent for men who have sex with men (MSM). The 4 treatments currently approved by the Food and Drug Administration for alcohol use are reaching an alarmingly low percentage of people who would benefit from a reduction in their alcohol use. There is increasing interest in alternative methods of treatment, such as herbal supplements, to address hazardous drinking. However, research on the acceptability of alternative pharmacotherapies among MSM remains limited. We examined the prevalence and correlates of expressing interest in using herbal supplements for alcohol treatment among MSM with hazardous alcohol consumption. We conducted a secondary data analysis from a cross-sectional study of MSM who use alcohol, conducted from March 2015 to July 2017 in San Francisco, California, to assess the overall prevalence of interest in using herbal supplements to help reduce alcohol consumption. Associations between expressing interest in herbal supplements and demographic, social, and clinical characteristics were examined using bivariate and multivariable logistic regression models. One-third (66/200, 33%) of the participants expressed interest in an herbal supplement for reducing alcohol consumption. In the multivariable analyses, weekly binge drinking (adjusted odds ratio [aOR] 2.85, 95% CI 1.17-6.93), interest in abstaining from alcohol use (aOR 5.04, 95% CI 1.46-17.40), higher severity of alcohol dependence score (aOR 1.22, 95% CI 1.04-1.41), and interest in naltrexone (aOR 3.22, 95% CI 2.12-4.91) were independently associated with higher odds of being interested in using an herbal supplement to reduce alcohol consumption, adjusting for age, race or ethnicity, and education. We found that MSM who have hazardous drinking habits, more severe alcohol dependence, and interest in pharmacotherapy were more likely to express interest in using an herbal supplement for reducing alcohol consumption. To our knowledge, this is the first study that has evaluated correlates of interest in herbal supplements for alcohol use among MSM. As researchers implement novel alcohol treatment studies, they should focus on recruitment efforts among MSM with a motivation to reduce their alcohol use patterns.

INTRODUCTION: Opioid and alcohol use disorders are increasingly being addressed in primary care, yet how medications to treat these disorders are prescribed in rural regions is unknown. METHODS: We determined prevalence, types, and duration of medication prescription for opioid and/or alcohol use disorder among adult patients in rural primary clinics. The sample included 1874 adult patients who visited one of six rural primary care sites in the Northeastern and Northwestern United States at least once from October 2019 to January 2021 and had a diagnosis code for opioid use disorder (OUD), alcohol use disorder (AUD), or co-occurring opioid and alcohol use disorder (OUD + AUD) during that time. RESULTS: Patients with OUD + AUD were more likely to be prescribed medication for at least one of these disorders (85.3 %) than patients with OUD only (63.7 %) or AUD only (10.3 %). Further, the OUD + AUD group had the highest number of days on medication (M = 264.7), followed by OUD only (M = 220.5), then the AUD only group (M = 62.5). Only 8.8 % of patients with OUD + AUD were prescribed naltrexone or medication for OUD + AUD to treat both substance use disorders. CONCLUSIONS: Medications for treating AUD as well as OUD are available, but few patients with OUD + AUD and even fewer with AUD received pharmacological treatment for AUD. The current work highlights the need for rural clinicians to consider medications for AUD as an important treatment method for patients with AUD only or OUD + AUD.

RATIONALE: The alcohol cue exposure paradigm is a common method for evaluating new treatments for alcohol use disorder (AUD); however, it is unclear if medication-related reductions in cue-induced craving in the human laboratory can predict the clinical success of those medications in reducing alcohol consumption during clinical trials. OBJECTIVES: To use a novel meta-analytic approach to test whether medication effect sizes on cue-induced alcohol craving are associated with clinical efficacy in clinical trials. METHOD: We searched the literature for medications tested for AUD treatment using both the alcohol cue-reactivity paradigm and randomized clinical trials (RCTs). For alcohol cue-reactivity studies, we computed medication effect sizes for cue-induced alcohol craving (k = 36 studies, 15 medications). For RCTs, we calculated medication effect sizes for heavy drinking and abstinence (k = 139 studies, 19 medications). Using medication as the unit of analysis, we applied the Williamson-York bivariate weighted least squares estimation to account for errors in both independent and dependent variables. We also conducted leave-one-out cross validation simulations to examine the predictive utility of cue-craving medication effect sizes on RCT heavy drinking and abstinence endpoints. RESULTS: There was no significant relationship between medication effects on cue-induced alcohol craving in the human laboratory and medication effects on heavy drinking ( β ^ = 0.253, SE = 0.189, p = 0.090) and abstinence ( β ^ = 0.829, SE = 0.747, p = 0.133) in RCTs. CONCLUSIONS: The preliminary results of the current study challenge the assumption that alcohol cue-reactivity alone can be used as an early efficacy indicator for AUD pharmacotherapy development. These findings suggest that a wider range of early efficacy indicators and experimental paradigms be considered for Phase II testing of novel compounds.

BACKGROUND: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk. METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones. RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20). CONCLUSIONS: Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

The Addictions Neuroclinical Assessment (ANA) is a recently-developed framework offering a more holistic understanding of three neurofunctional and behavioral domains that reflect the neurobiological dysfunction seen in alcohol use disorder (AUD). While the ANA domains have been well-validated across independent laboratories, there is a critical need to identify neural markers that subserve the proposed neurofunctional domains. The current study involves secondary data analysis of a two-week experimental medication trial of ibudilast (50 mg BID). Forty-five non-treatment-seeking participants with AUD (17F / 28 M) completed a battery of validated behavioral assessments forming the basis of their incentive salience factor score, computed via factor analysis, as well as a functional neuroimaging (fMRI) task assessing their neural reactivity to visual alcohol cues after being on placebo or ibudilast for 7 days. General linear models were conducted to examine the relationship between incentive salience and neural alcohol cue-reactivity in the ventral and dorsal stratum. Whole-brain generalized linear model analyses were conducted to examine associations between neural alcohol cue-reactivity and incentive salience. Age, sex, medication, and smoking status were included as covariates. Incentive salience was not associated with cue-elicited activation in the dorsal or ventral striatum. Incentive salience was significantly positively correlated (p < 0.05) with alcohol cue-elicited brain activation in reward-learning and affective regions including the insula and posterior cingulate cortices, bilateral precuneus, and bilateral precentral gyri. The ANA incentive salience factor is reflected in brain circuitry important for reward learning and emotion processing. Identifying a sub-phenotype of AUD characterized by increased incentive salience to alcohol cues allows for precision medicine approaches, i.e. treatments specifically targeting craving and reward from alcohol use. This study serves as a preliminary bio-behavioral validation for the incentive salience factor of the ANA. Further studies validating the neural correlates of other ANA factors, as well as replication in larger samples, appear warranted.

Introduction: Visceral arterial aneurysms and pseudoaneurysms are rare but dangerous pathologies, with reported incidence of 0.01–0.2% of the worldwide population, as found on autopsy. Pancreaticoduodenal artery pathology accounts for approximately 2% of all visceral aneurysms; it is commonly caused by chronic inflammatory processes, such as pancreatitis or adjacent pseudocysts. Morbidity and mortality commonly result from rupture of the aneurysm itself, leading to life-threatening hemorrhage into the peritoneum or gastrointestinal tract.Case Report: Here we present the case of a 64-year-old male patient with previous history of alcohol use disorder leading to chronic pancreatitis and prior embolization of an inferior pancreaticoduodenal pseudoaneurysm, who presented to the emergency department (ED) with abdominal pain, nausea, and vomiting, and was found to have a large recurrent inferior pancreaticoduodenal pseudoaneurysm with associated obstructive cholangitis and pancreatitis via contrast-enhanced computed tomography (CT) of the abdomen and pelvis. The patient was managed emergently by interventional radiology angiography with embolic coiling and percutaneous biliary catheter placement, and he subsequently underwent biliary duct stenting with gastroenterology. The patient was successfully discharged after a brief hospitalization after resolution of his pancreatitis and associated hyperbilirubinemia.Conclusion: Pancreaticoduodenal artery aneurysms and pseudoaneurysms are rare and dangerous visceral pathologies. Patients can be diagnosed rapidly in the ED with CT imaging and needurgent endovascular management to prevent morbidity and mortality.

Alcohol Use Disorder (AUD) is a chronic relapsing disorder affecting an estimated 283 million individuals worldwide, with substantial health and economic consequences. Peroxisome proliferator-activated receptors (PPARs), particularly PPAR-α and PPAR-γ, have shown promise in preclinical studies as potential therapeutic targets for AUD. In this human laboratory study, we aimed to translate preclinical findings on the PPAR-α agonist fenofibrate to a human population with current AUD. We hypothesized that, relative to placebo, fenofibrate at the highest FDA-approved dose of 145 mg/d would attenuate responsiveness to in vivo alcohol cues in the lab and reduce drinking under natural conditions. However, the results did not show significant differences in craving and alcohol consumption between the fenofibrate and placebo groups. Reverse translational studies in rodent models confirmed the lack of fenofibrate effect at human-equivalent doses. These findings suggest that inadequate translation of drug dose from rodents to humans may account for the lack of fenofibrate effects on alcohol craving and consumption in humans with AUD. The results highlight the need for new brain-penetrant PPAR-α agonists to adequately test the therapeutic potential of PPAR-α agonists for AUD, and the importance of reverse translational approaches and selection of human-equivalent doses in drug development.

Individuals with mental illness have a high incidence of comorbid substance use, with one of the most prevalent being alcohol use disorder (AUD). Naltrexone, FDA-approved for AUD, decreases reward associated with alcohol-related social cues. This study aimed to determine if a pharmacist-driven screening tool would increase the use of extended-release naltrexone (XR-NTX) in patients with AUD and a comorbid psychiatric condition. Pharmacists screened and recommended XR-NTX for adults admitted to the inpatient psychiatric unit, who had a DSM-5 diagnosis of AUD, a negative urine drug screen for opioids, and were hospitalized for at least 1 day. Endpoints evaluated included the number of XR-NTX doses administered during the screening period to the prescreening period, 30-day readmission rates, recommendation acceptance rates, and reasons for not administering XR-NTX. Pharmacists identified 66 of 641 screened patients who met the inclusion criteria and were candidates for XR-NTX. Compared to the preintervention period, more patients received XR-NTX for AUD (2 vs. 8). Readmission rates were similar between those with AUD who received XR-NTX and those who did not. Pharmacist-driven screening for AUD led to greater administration of XR-NTX when compared to the same 4-month period the year prior to initiating the study.

Varenicline has shown promise for treating alcohol use disorder (AUD); however, not everyone will respond to varenicline. Machine-learning methods are well suited to identify treatment responders. In the present study, we examined data from the National Institute on Alcohol Abuse and Alcoholism Clinical Intervention Group multisite clinical trial of varenicline using two machine-learning methods. Baseline characteristics taken from a randomized clinical trial of varenicline were examined as potential moderators of treatment response using qualitative interaction trees (N = 199) and group least absolute shrinkage and selection operator interaction nets (N = 200). Results align with prior research, highlighting smoking status, AUD severity, medication adherence, and drinking goal as predictors of treatment response. Novel findings included the interaction between age and cardiovascular health in predicting clinical response and stronger medication effects among individuals with lower craving. With increased integration of machine-learning methods, studies that effectively integrate methods and medication development have high potential to inform clinical practice.

Alcohol Use Disorder (AUD) is a significant public health issue in the United States. It affects millions of individuals and their families and contributes to substantial societal and economic burdens. Despite the availability of some pharmacological treatments, there is still a pressing need to develop more effective therapeutic strategies to address the diverse range of symptoms and challenges associated with AUD. Catechol-O-methyltransferase (COMT) inhibition recently emerged as a promising new approach to treating AUD due to its potential to improve cognitive effects commonly associated with AUD. Tolcapone, an FDA-approved COMT inhibitor, has shown some promise for treating AUD; however, its ability to decrease drinking in ethanol-dependent rats has not been well-established. In this study, we evaluated the effects of tolcapone on operant, oral ethanol self-administration in non-dependent and dependent rats, and in rats that self-administered oral saccharin. To induce dependence, rats underwent the chronic intermittent exposure to vapor model, and their drinking levels were assessed during acute withdrawal from ethanol. Our results demonstrated that tolcapone attenuated responding for ethanol in dependent rats only, without affecting self-administration in non-dependent rats or rats self-administering saccharin. Moreover, we found that tolcapone was differentially effective in different estrous phases in female rats. These findings suggest that COMT inhibition, specifically using tolcapone, may be a valuable pharmacotherapy for treating AUD, particularly in individuals who are physically dependent on alcohol. Further research is needed to elucidate the precise mechanisms underlying the observed effects and to assess the potential of COMT inhibitors in a broader population of individuals with AUD.

Fatigue is a multidimensional condition that may overlap with depression. Initial studies found that fatigue responds in only a limited way to standard monoaminergic antidepressants and mood stabilizers but does respond positively to intravenous (IV) racemic (R,S)-ketamine (ketamine). However, IV ketamine's use is limited by cost and access barriers. To date, no study has evaluated intranasal (IN) ketamine in individuals with fatigue. This study sought to evaluate the anti-fatigue effects of a single 50 mg dose of IN ketamine in individuals with major depressive disorder (MDD) or bipolar depression (BDep), both with and without comorbid alcohol use disorder (AUD). Twenty-eight individuals with primary diagnoses of MDD or BDep I/II currently experiencing a depressive episode with active suicidality were enrolled; approximately 60 % had comorbid AUD. Changes in the NIH-Brief Fatigue Inventory (NIH-BFI) were assessed at baseline and at 4, 24, and 48 h post-treatment. The group x time interaction for NIH-BFI score was significant (F = 3.44, p = 0.022), favoring IN ketamine over placebo. IN ketamine was well-tolerated with minimal adverse effects. Limitations include the limited sample size, short duration, and single, fixed dose. IN ketamine appears to induce rapid anti-fatigue effects in individuals with severe MDD and BDep both with and without comorbid AUD. This suggests that IN ketamine holds potential as an alternative, rapid-acting, anti-fatigue option for different medical conditions. • IN ketamine induced rapid anti-fatigue effects in patients with severe depression. • Consistent improvements were seen in both unipolar and bipolar depression. • Comorbid alcohol use disorder did not impact anti-fatigue response. [ABSTRACT FROM AUTHOR]

AbstractObjective: Co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) represents a prevalent and problematic comorbidity. Functional health literacy (FHL) may play a role in this comorbidity based on its previously documented role in hazardous drinking. The current study examined functional health literacy (FHL) regarding hazardous drinking among a sample with probable posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). Methods: The current study is a secondary analysis of data from a project studying the transdiagnostic risk and maintenance factors of PTSD and hazardous alcohol use among people with probable PTSD and AUD. Participants were 565 nationally recruited adults with probable PTSD and hazardous alcohol use (52.2% female, 68.8% non-Hispanic White, average age = 39.2 years ± 10.9 years). Linear regression models were conducted regressing hazardous alcohol use onto PTSD symptoms and FHL scores. An interaction term between FHL and PTSD symptoms was included in the regression models with age, biological sex, race, and income included as covariates. Results: Low FHL maintained a statistically significant role in predicting greater hazardous drinking (p < .001) even in the context of posttraumatic stress. High posttraumatic stress also emerged as a statistically significant predictor of hazardous alcohol use (p < .001). The interaction term between FHL and PTSD was not found to be a significant predictor of hazardous alcohol use (p = .222). Conclusion: FHL may be a relevant variable for better understand hazardous drinking among persons with comorbid PTSD and AUD. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications The limited effectiveness of current pharmacological treatments for alcohol use disorder (AUD) highlights the need for novel therapies. These may involve the glucagon‐like peptide‐1 receptor or the amylin receptor, as treatment with agonists targeting either of these receptors lowers alcohol intake. The complexity of the mechanisms underlying AUD indicates that combining agents could enhance treatment efficacy. While a combination of amylin receptor and GLP‐1 receptor agonists reduced food intake and body weight synergistic‐like, its influence on alcohol intake is unknown.Effects of a range of dose‐combinations of GLP‐1 receptor (dulaglutide) and amylin receptor (salmon calcitonin; sCT) agonists on alcohol intake were explored in male and female rats. We used dose combinations that either lowered alcohol intake as monotherapy (0.1 mg·kg−1 + 5 μg·kg−1), or that did not affect alcohol consumption per se (0.075 mg·kg−1 + 2 μg·kg−1).Acute administration of dulaglutide and sCT (0.1 mg·kg−1 + 5 μg·kg−1) reduced alcohol intake in males, but not in females. When higher doses were evaluated in female rats, a decrease in alcohol intake was observed. Furthermore, the low dose combination (0.075 mg·kg−1 + 2 μg·kg−1) decreased, in in a synergistic‐like manner, alcohol intake and prevented abstinence‐induced drinking without affecting kaolin intake in males. However, tolerance developed during sub‐chronic treatment.Collectively, these findings show that the combination of dulaglutide and sCT decreased, in in a synergistic‐like manner, alcohol consumption in male rats. Contrarily, higher doses are required for females. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is a psychiatric disorder that is widespread worldwide. Alcohol use is a significant contributor to the global burden of death, disability and disease. Modulation of the gut microbiota is a promising approach to improve the efficacy and minimize the adverse effects of colorectal cancer treatment. The relationship between the presence of microbes and AUD has been widely validated. However, few studies have examined this relationship using bibliometric methods. Therefore, this study analyzes the research hotspots and trends in human gut microbiology and AUD over the last two decades from a bibliometric perspective. This study aims at provide new directions for basic and clinical research in this field. Objective: A comprehensive discussion of the relationship between the current state of research and trends in AUD and intestinal flora. Methods: We collected publications from the Web of Science Core Collection database from 2003 to 2023 according to established inclusion criteria. We analyzed countries, institutions, authors, and research contributions using CiteSpace, VOSviewer, and Scimago Graphics to visualize research trends in the field. Results: A total of 2,102 publications were obtained, with a rapid increase in the number of publications since 2016. The United States and China are major contributors to the field and have established a network of partners in several countries. Five hundred ninety-five academic journals published articles on the topic. The author with the highest number of publications is Prof. Bernd Schnabl of the Department of Gastroenterology at the University of California, San Diego. In addition to "gut flora" and "AUD," high frequency words in the keyword co-occurrence network analysis included alcoholic liver disease, tryptophan metabolism, enterohepatic axis, and fecal microbial transplantation. Conclusion: The results of this study provide a bibliometric analysis and visualization of key research areas in the gut microbiota and AUD over the past 20 years. The results suggest that the role of the gut microbiota in AUD and its potential mechanisms, especially therapeutic targets, should be closely monitored and could become a hot topic in the field. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is associated with imbalanced bone turnover and psychological symptoms, but the relationship between bone and brain remains unclear. The study analyzed serum levels of a bone formation marker, procollagen type 1 N‐terminal propeptide (P1NP), and bone resorption marker, C‐terminal telopeptide of type I collagen (CTX‐1), in AUD patients before and after 2 weeks of alcohol withdrawal and investigated their correlation with psychological symptoms. Methods: Ninety patients with AUD and 117 healthy controls were recruited. P1NP and CTX‐1 levels were measured using Enzyme‐Linked Immunosorbent Assay. The Penn Alcohol Craving Scale (PACS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were assessed in the AUD group at baseline, week 1, and week 2 of withdrawal. Results: Baseline CTX‐1 levels, along with the CTX‐1/P1NP and P1NP/CTX‐1 ratio, were higher in the AUD group than controls. Over the 2‐week withdrawal, PACS, BDI, and BAI scores demonstrated significant reductions. P1NP (p < 0.001) and P1NP/CTX‐1 ratio increased (p < 0.001), while CTX‐1/P1NP ratio decreased (p < 0.001), indicating a propensity toward bone formation. Univariate analysis revealed that reductions in PACS, BDI, and BAI scores during withdrawal correlated with increased P1NP levels and decreased CTX‐1/P1NP ratios. However, multivariate analysis indicated that only PACS score reductions correlated with these changes. Conclusions: Bone metabolism shifted toward increased bone formation and decreased bone resorption during 2‐week alcohol withdrawal. The correlation between improvements in bone turnover markers and reduction in craving scores during withdrawal supports the concept of the bone‐brain axis. [ABSTRACT FROM AUTHOR]

Background: This study shows the first evidence for pannexin 1 channels as a new target to develop medications for alcohol use disorder (AUD). Due to its history of long‐term safe clinical use and preclinical evidence of reducing excessive alcohol intake in rodents, probenecid has clinical potential for AUD. Methods: We conducted a Phase I/IIa randomized, double‐blind, placebo‐controlled, crossover trial investigating the safety, tolerability, and efficacy of an oral dose of probenecid (2 g) when administered with alcohol (0.08 g/dL) in individuals who regularly consume alcohol to the 0.08 g/dL level (N = 35) and in individuals with mild to severe AUD. Alcohol pharmacokinetics and subjective responses were evaluated to assess potential interactions between probenecid and alcohol. Alcohol craving, inflammatory biomarkers, cognitive assessments, and hemodynamics were assessed as additional alcohol research domains. All outcomes were assessed both in the ascending and descending limb of alcohol intoxication using Generalized Estimating Equation. Results: Probenecid did not exert any significant effect on alcohol pharmacokinetics and did not affect alcohol stimulation or sedation. Probenecid, compared to placebo, significantly decreased alcohol craving during the alcohol ascending limb. Inflammatory biomarkers, cognitive performance following alcohol ingestion, and hemodynamics were likewise not affected by probenecid administration. Analysis of sex as a biological variable revealed no differences of probenecid compared to placebo. Conclusions: Taken together, our data support the potential of probenecid for treatment of AUD and suggest that pannexin 1 channels represent a novel emerging therapeutic target for the development of new pharmacotherapies for treating AUD. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) affects 5% of the global population. Despite its high prevalence, the pathophysiology of AUD remains enigmatic, hindering the development of novel therapeutics. Interestingly, the liver hormone fibroblast growth factor 21 (FGF21), which is currently in late-stage clinical trials for the treatment of non-alcoholic steatohepatitis, has been implicated by recent genome-wide association studies as a regulator of alcohol consumption. This study aimed to evaluate plasma responses of FGF21 to an alcohol challenge in three groups: 15 males with AUD, 15 healthy males with a father with AUD (Predisposed), and 15 healthy males without any predisposition to AUD (Controls). All participants were investigated after an overnight fast. Assessments, including blood sampling and visual analog scale-assessed desire for alcohol intake, were performed before and for 10 h after ingesting 0.5 g alcohol per kg body weight over 10 min. The three groups were age and body-mass index-matched and had normal plasma concentrations of transaminases and FibroScan®-assessed elastography. Baseline FGF21 concentrations did not differ between groups, but individuals with AUD exhibited greater FGF21 responses to alcohol (area under the curve (AUC 0–600 min): 954 ± 665 ng/ml × min (mean (standard deviation)) compared to Controls (AUC 0–600 min : 453 ± 333 ng/ml × min, P = 0.03) but not Predisposed (AUC 0–600 min : 556 ± 429 ng/ml × min, P = 0.11). In conclusion, we demonstrate greater alcohol-induced FGF21 responses in individuals with AUD compared to healthy individuals without paternal predisposition to AUD, suggesting a role for FGF21 in AUD pathophysiology. • Fibroblast growth factor 21 (FGF21) is secreted after acute alcohol intake in men. • We show greater alcohol-induced FGF21 responses in individuals with alcohol use disorder compared to healthy individuals. • Healthy men predisposed to AUD had a stronger desire for alcohol just after intake compared to a control group. [ABSTRACT FROM AUTHOR]

Alcohol Use Disorder (AUD) is a growing problem worldwide, causing an incredible burden on health and the economy. Though AUD impacts people of all backgrounds and demographics, increasing evidence has suggested robust sex differences in alcohol drinking patterns and AUD-induced negative emotionality or hyperkatifeia. Rates of problematic drinking have significantly risen among women, and women face more severe negative emotional consequences in abstinence such as increased risk of comorbidity with an anxiety or mood disorder and more severe symptoms of depression. As such, a bevy of preclinical literature using contingent methods of alcohol (ethanol) consumption has amassed in recent years to better understand sex as a biological variable in alcohol drinking and abstinence-induced negative emotionality. Mice are widely used to model alcohol drinking, as they are conducive to genetic manipulation strategies, and many strains will voluntarily consume alcohol. Sex-specific results from these mouse studies, however, have been inconsistent. Therefore, this review aims to summarize the current knowledge on sex differences in AUD-related contingent ethanol drinking and abstinence-induced negative emotionality in mice. Various contingent mouse drinking models and negative emotional-based behavioral paradigms are introduced and subsequently discussed in the context of sex differences to show increasing indications of sex specificity in mouse preclinical studies of AUD. With this review, we hope to inform future research on potential sex differences in preclinical mouse models of AUD and provide mounting evidence supporting the need for more widespread inclusion of preclinical female subjects in future studies. • Sex differences in AUD are evident, with increasingly severe outcomes in women. • Voluntary ethanol drinking models show clinically relevant sex differences. • Preclinical models of negative emotional behavior reflect unique sex differences. • Further research using females is crucial for sex specific understanding of AUD. [ABSTRACT FROM AUTHOR]

Chronic alcohol-related myopathy presents with proximal muscle weakness. We studied the effect of vitamin D supplementation on muscle weakness in adults with alcohol use disorder. The study was a randomized controlled trial. Participants were community-dwelling adults with alcohol use disorder. Participants allocated to VIDIO, vitamin D intensive outreach, received bimonthly oral doses of 50,000–100,000 IU cholecalciferol for 12 months. Participants allocated to CAU, care as usual, received prescriptions of once-a-day tablets containing 800 IU cholecalciferol and 500 mg calcium carbonate. Data included demographic variables, laboratory tests, alcohol use, and rating scales of help-seeking and support. Main outcomes were the participants' quadriceps maximum voluntary contractions (qMVC) and serum-25(OH)vitamin D concentrations, 25(OH)D. In 66 participants, sex ratio 50/16, mean age 51 years, alcohol use was a median of 52 [IQR 24–95] drinks per week. Baseline qMVC values were 77% (SD 29%) of reference values. Laboratory tests were available in 44/66 participants: baseline 25(OH)D concentrations were 39.4 (SD 23.7) nmol/L. Thirty-one participants with 25(OH)D concentrations <50 nmol/L received either VIDIO or CAU and improved in qMVC, respectively, with a mean of 51 (p < 0.05) and 62 N (no p value because of loss of follow-up) after one year of treatment. Vitamin D status increased with a mean of +56.1 and + 37.4 nmol/L, respectively, in VIDIO and CAU. The qMVC values improved during vitamin supplementation in adults with vitamin D deficiency and alcohol use disorder. Despite higher 25(OH)D concentrations in VIDIO, in terms of muscle health no advice could be given in favor of one vitamin strategy over the other. • In alcohol use disorder, vitamin D deficiency is common. • Chronic alcoholic myopathy commonly presents with proximal muscle weakness. • Muscle strength has improved during vitamin D supplementation. • Muscle weakness was less prominent in persons living in sheltered care facilities. • Although many drinks were reported, CDT test results were low. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) poses a significant public health challenge. Individuals with AUD engage in chronic and excessive alcohol consumption, leading to cycles of intoxication, withdrawal, and craving behaviors. This review explores the involvement of the cortical amygdala (CoA), a cortical brain region that has primarily been examined in relation to olfactory behavior, in the expression of alcohol dependence and excessive alcohol drinking. While extensive research has identified the involvement of numerous brain regions in AUD, the CoA has emerged as a relatively understudied yet promising candidate for future study. The CoA plays a vital role in rewarding and aversive signaling and olfactory-related behaviors and has recently been shown to be involved in alcohol-dependent drinking in mice. The CoA projects directly to brain regions that are critically important for AUD, such as the central amygdala, bed nucleus of the stria terminalis, and basolateral amygdala. These projections may convey key modulatory signaling that drives excessive alcohol drinking in alcohol-dependent subjects. This review summarizes existing knowledge on the structure and connectivity of the CoA and its potential involvement in AUD. Understanding the contribution of this region to excessive drinking behavior could offer novel insights into the etiology of AUD and potential therapeutic targets. • The cortical amygdala is involved in alcohol-dependent drinking. • The cortical amygdala connects to key brain regions involved in alcohol use disorder. Increased the cortical amygdala activity during alcohol withdrawal in dependent subjects may enhance glutamatergic signaling to the central amygdala, bed nucleus of the stria terminalis and basolateral amygdala. [ABSTRACT FROM AUTHOR]

This study investigates the impact of race, gender, and ethnicity on the progression from diagnosis to cirrhosis and subsequent survival in patients with alcohol use disorder, with a specific focus on identifying potential disparities in health outcomes. Employing a STROBE-compliant, retrospective cohort design, we analyzed data from patients diagnosed with alcohol use disorder from January 2000 to December 2022, using the University of California Health Data Warehouse. We estimated survival functions using the Kaplan–Meier method and assessed demographic associations using both bivariate and multivariate Cox proportional hazards models. The analysis highlighted a significant association between Hispanic ethnicity and an accelerated timeline for both the diagnosis of alcohol-related cirrhosis following diagnosis of alcohol use disorder and mortality post-cirrhosis diagnosis. The former was evident only in bivariate analysis, but the latter association persisted in multivariate analysis. Gender did not demonstrate a significant correlation with the time to these outcomes, though multiracial identification emerged as a protective factor. The study reveals critical health disparities in the progression and outcomes of cirrhosis, particularly between Hispanic and non-Hispanic patients. These findings underscore the urgent need for targeted healthcare interventions and policies that address these disparities. Future research should delve deeper into the multifaceted factors influencing these outcomes, facilitating the development of more nuanced and effective prevention and treatment strategies for alcohol use disorder and its severe complications. • This study utilizes a STROBE-compliant, retrospective analysis of a large, diverse patient population. • Hispanic ethnicity is a key risk factor for faster progression to cirrhosis in patients with alcohol use disorder. • Following cirrhosis diagnosis, Hispanic patients had significantly shorter survival than non-Hispanic patients. • This study underscores the need for targeted healthcare strategies to address ethnic disparities in alcohol use disorder. [ABSTRACT FROM AUTHOR]

Introduction Persons with behavioral health conditions are disproportionally burdened by their tobacco use. Research is limited on how often this patient population is offered tobacco cessation interventions at healthcare visits. This study examines if cessation treatment offered at healthcare visits differs based on the clinical condition. Aims and Methods Using data from the 2015 to 2018 National Ambulatory Medical Care Survey, we examined tobacco cessation counseling and medications (bupropion, nicotine replacement therapies, and varenicline) from 4590 visits by patients with current tobacco use. Separate multivariate logistic regressions were used to assess whether the odds of receiving tobacco cessation treatment varied by three groups of clinical conditions: (1) substance use disorder and/or alcohol use disorder, (2) depression, and (3) physical conditions. Results The odds of being offered smoking cessation counseling are 4.02 times greater for visits by patients with substance use disorder and/or alcohol use disorder compared to visits by patients with depression (p  < .001), while the odds of receiving smoking cessation medication are 2.36 times greater for visits by patients with depression compared to visits by patients with substance use disorder and/or alcohol use disorder (p  < .01). Visits by patients with substance use disorder and/or alcohol use disorder have 2.36 times the odds of receiving any combination of tobacco cessation treatment compared to visits by patients with depression (p  < .001). Conclusions Providers are offering cessation treatment at visits by patients with behavioral health conditions at either higher or comparable rates to those without; however, tobacco cessation treatment continues to be underutilized by providers during office visits. Implications The results of our study have implications for increasing educational opportunities for healthcare providers to improve their confidence in offering tobacco cessation treatment to patients with behavioral health conditions. These patients are motivated to quit smoking, yet cessation treatment is underutilized in this population despite having a greater health effect than most other clinical interventions. Incorporating tobacco cessation education in medical school curricula and post-graduate training can help eliminate barriers for physicians to routinely provide cessation assistance. Collaboration between clinicians and behavioral health providers can also enhance tobacco treatment support and improve cessation rates. [ABSTRACT FROM AUTHOR]

Aims: To investigate the factors associated with interoception in patients with alcohol use disorder and determine whether treatment causes changes in their interoception. Methods: The Body Perception Questionnaire‐Body Awareness ultra‐short version Japanese version (BPQ‐BAVSF‐J) was used to measure interoception in 50 alcohol‐dependent participants (27 in the inpatient group and 23 in the outpatient group). The BPQ‐BAVSF‐J was administered and data on aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma‐glutamyl transpeptidase (γ‐GTP), mean corpuscular volume, platelet count, and Fib‐4 index were extracted at admission and immediately before discharge for the inpatient group and at the first outpatient visit and approximately 3 months after the visit for the outpatient group. Results: The mean age of the 50 participants was 51.0 ± 12.3 years. Significant associations were found between the BPQ‐BAVSF‐J and Fib‐4 index and AST. The BPQ‐BAVSF‐J score significantly decreased at discharge in the inpatient group. AST, ALT, γ‐GTP, and Fib‐4 index of liver function were also significantly lower at discharge. In contrast, in the outpatient group, there were no significant changes in the BPQ‐BAVSF‐J score, AST level, ALT level, γ‐GTP level, and Fib‐4 index between at the first outpatient visit and approximately 3 months after the visit. Conclusions: Interoception in patients with alcohol use disorder increased with worsening liver function and decreased with improvement in liver function owing to treatment. This suggests that the BPQ‐BAVSF‐J score, an easily accessible scale, may be used to detect early deterioration of liver function through regular administration. [ABSTRACT FROM AUTHOR]

The glymphatic system, a physiological pathway recently identified, has attracted considerable attention for its potential role in the pathophysiology of neurological disorders. Despite significant research efforts, the exact contribution of the glymphatic system to alcohol use disorder (AUD) remains largely elusive. This study was a secondary analysis by analyzing a subset of the original data to examine changes in the ALPS index and determine its association with cognitive abilities in individuals with AUD. We recruited 40 individuals with AUD and 40 healthy controls (HC). All subjects underwent MRI scans and clinical cognitive scale assessments. Diffusion tensor imaging along the perivascular space (DTI-ALPS) index was used to estimate the differences in glymphatic activity between both groups, and linear regression analysis was used to examine the association between ALPS index and cognitive performance measures. A statistically significant difference in the ALPS index was observed between both groups (p < 0.001), with the AUD group showing statistically lower ALPS index compared with the HC group (p < 0.001). Additionally, a positive correlation was identified between the ALPS index and MoCA/MMSE scores, indicating that higher ALPS index is indicative of better cognitive performance in individuals with AUD. The findings of this study provide evidence of ALPS index in individuals with AUD and establish a link between the ALPS index and the cognitive impairments observed in AUD patients. These findings might suggest the importance of glymphatic activity in the emergence of cognitive deficits among those impacted by AUD, but a stronger link between ALPS index and glymphatic system is needed to better understand the relationship between glymphatic function and healthy outcomes. [ABSTRACT FROM AUTHOR]

Objective: The impact of cannabis use disorder (CUD) on education functioning and GPA was examined within the context of co-occurring alcohol use disorder (AUD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Participants: Undergraduates (N = 210) who reported using cannabis within the past six months were recruited. Methods: Hierarchical multiple regression analyses were used to determine whether CUD symptom severity and presence of probable CUD diagnosis predicted educational impairment and current GPA, over and above other mental health conditions. Results: CUD symptom severity, but not probable CUD, significantly predicted greater educational impairment, over and above probable PTSD and MDD, which were also significant predictors. CUD symptom severity, but not probable CUD, significantly predicted lower GPA. Conclusion: In addition to other common mental health conditions, CUD may be an important area of assessment and intervention for university counseling centers to foster student academic success. [ABSTRACT FROM AUTHOR]

Sexual violence is associated with posttraumatic stress disorder (PTSD), but relatively less research has explored whether it is associated with hazardous drinking. PTSD symptoms may indirectly influence the association between sexual violence and hazardous alcohol use. This association may be moderated by gender. The aim of the current study was to cross-sectionally test whether sexual violence is indirectly associated with hazardous drinking through PTSD symptoms and explore whether gender moderates this association. Hypotheses were tested among 631 adults (M age = 38, 56% men, 78.6% White) with probable PTSD and hazardous drinking who completed online self-report surveys. Results indicated sexual violence, compared with other trauma types, was associated with more severe hazardous drinking. There was a significant indirect effect of PTSD symptoms in this association. There was no evidence of a moderating effect of gender. PTSD symptoms may drive hazardous drinking among sexual violence survivors. Results also underscore associations between sexual violence and alcohol use, regardless of gender. Future work should continue to investigate these associations prospectively. [ABSTRACT FROM AUTHOR]

Background and aims: Alcohol use disorder (AUD) is characterized by low levels of engagement with effective treatments. Enhancing awareness of AUD treatments and how to navigate the treatment system is crucial. Many individuals use online sources (e.g. search engines) for answers to health‐related questions; web‐based results include a mix of high‐ and low‐quality information. Artificial intelligence may improve access to quality health information by providing concise, high‐quality responses to complex health‐related questions. This study evaluated the quality of ChatGPT‐4 responses to AUD‐related queries. Method: A comprehensive list of 64 AUD‐related questions was developed through a combination of Google Trends analysis and expert consultation. ChatGPT‐4 was prompted with each question, followed by a request to provide 3–5 peer‐reviewed scientific citations supporting each response. Responses were evaluated for whether they were evidence‐based, provided a referral and provided supporting documentation. Results: ChatGPT‐4 responded to all AUD‐related queries, with 92.2% (59/64) of responses being fully evidence‐based. Although only 12.5% (8/64) of responses included referrals to external resources, all responses (100%; 5/5) to location‐specific ('near me') queries directed individuals to appropriate resources like the NIAAA Treatment Navigator. Most (85.9%; 55/64) responses to the follow‐up question provided supporting documentation. Conclusions: ChatGPT‐4 responds to alcohol use disorder‐related questions with evidence‐based information and supporting documentation. ChatGPT‐4 could be promoted as a reasonable resource for those looking online for alcohol use disorder‐related information. [ABSTRACT FROM AUTHOR]

We sought to determine the utility of the Alcohol Use Disorder Identification Test (AUDIT) in screening for alcohol use disorder (AUD) among 688 users of antiretroviral therapy (ART). We used the receiver operating characteristic (ROC) curve analysis to assess whether the AUDIT reliably detected AUD against the Structured Clinical Interview for the DSM (SCID). Of the samples, 22.09% (CI: 19.05% to 25.38%) of participants met the diagnostic criteria for AUD. Among men (n = 135) and women (n = 553), the prevalence estimates were 31.9% and 19.7%, respectively. For men, a cut-off score of 6 predicted AUD with 88.36% (95%CI: 74.92-96.11) sensitivity and 88.04% (95%CI: 79.61-93.88) specificity. For women, a cut-off score of 4 on the AUDIT yielded an optimal sensitivity of 92.66% (95% CI: 86.05%-96.78%) and a specificity of 93.24% (95% CI: 90.49-95.40%). For men, the AUDIT yielded a positive predictive value (PPV) of 75.55% (95% CI: 66.26%-85.87%) and a negative predictive value (NPV) of 91.49% (95% CI: 87.63-97.37%); for women the PPV and NPV were 77.09% (70.34%-82.68%) and 98.11% (96.37%-99.02%), respectively. The instrument's good sensitivity and specificity indicate it is likely to be useful for screening and referral of ART users who are probably cases of AUD. [ABSTRACT FROM AUTHOR]

Objective: Young Latinas and Black women drink less than women of other racial/ethnic groups but experience more alcohol-related problems in midlife. This study aims to identify modifiable factors to prevent adult onset of alcohol use disorder (AUD) in this population. Methods: Data were collected at six time points as part of the Harlem Longitudinal Development Study from 365 Latinas (47%) and Black (53%) women (mean age at time 1 = 14, standard deviation 1.3). Structural equation modeling was used to test hypothesized pathways from childhood physical and sexual abuse to AUD via depressive mood, anxiety disorders, and somatic complaints in the 20s. We also tested the moderation effect of the high school academic environment by including in the structural equation model two latent variable interaction terms between the school environment and each of the abuse variables. Results: Childhood physical and sexual abuse was positively associated with depressive mood, anxiety disorders, and somatic complaints when participants were in the 20s. Depressive mood mediated childhood abuse and AUD when women were in the 30s. The high school academic environment attenuated the effect of physical, but not sexual abuse, on depressive mood (β = −0.59, B = −9.38, 95% CI [−14.00, −4.76]), anxiety symptoms (β = −0.61, B = −14.19, 95% CI [−21.76, −6.61]), appetite loss (β = −0.41, B = −10.52, 95% CI [−15.61, −5.42]), and sleeplessness (β = −0.50, B = −9.56, 95% CI [−13.95, −5.17]) in the early 20s. Conclusions: Our findings underscore the need to invest in early violence prevention interventions and in education to ensure equitable access to quality, academically oriented, and safe schools. [ABSTRACT FROM AUTHOR]

Objective: How people define recovery may affect their recovery goals, service use, and ultimately their outcomes. We examined recovery definitions among adults in recovery from an alcohol use disorder (AUD) who had different service use histories. Method: We analyzed online survey data from 1,492 adults with resolved lifetime AUD in "treated recovery" (any use of specialty services, such as inpatient or outpatient rehabilitation; n = 375), "assisted recovery" (any use of lay services, such as mutual-help groups, and no use of specialty services; n = 174), or "independent recovery" (no use of specialty or lay services; n = 943). Surveys assessed recovery definitions using the 39-item What Is Recovery? (WIR) scale. We compared endorsement of WIR domains and individual recovery elements across groups using survey-weighted chi-square tests and logistic regression. Results: Endorsement of WIR scale domains was significantly lower among the independent than treated and assisted groups, but few differences emerged between the treated and assisted groups. Two recovery elements were endorsed by approximately equivalent majorities of all groups: "being honest with myself" (92.7%–94.8%) and "taking care of my physical health" (87.4%–90.9%). Five additional elements were similarly endorsed by large majorities (≥85%) in each group, albeit at lower levels in the independent group. Conclusions: People who have experienced AUD and have not obtained alcohol services may have a narrower definition of recovery compared to those accessing treatment or attending mutual-help groups. This suggests a need to broaden alcohol services to better match varied recovery definitions; however, some highly endorsed elements suggest commonalities across recovery pathways. Public Health Significance Statement: How people with alcohol problems define recovery may affect their decisions and behaviors (e.g., substance use goals and help-seeking patterns) and related outcomes (e.g., substance use and well-being). The present study concluded that those in independent recovery from an alcohol problem may have a narrower definition of recovery than those who have accessed treatment or attended mutual-help groups. The different conceptions of recovery among those in independent recovery may contribute to their avoidance of alcohol services, suggesting that broadening such services to better serve those with varied recovery definitions could result in greater services uptake and ultimately better outcomes. [ABSTRACT FROM AUTHOR]

Objective: Understanding the causal mechanisms through which telephone and mobile health continuing care approaches reduce alcohol use can help develop more efficient interventions that effectively target these mechanisms. Self-efficacy for successfully coping with high-risk alcohol relapse situations is a theoretically and empirically supported mediator of alcohol treatment. This secondary analysis aims to examine self-efficacy as a mechanism through which remote-delivered continuing care interventions reduce alcohol use. Method: The study included 262 adults (Mage = 46.9, SD = 7.4) who had completed 3 weeks of an intensive outpatient alcohol treatment program. The sample was predominantly male (71%), African American (82%), and completed a high school education (71%). The four-arm randomized clinical trial compared three active continuing care interventions (telephone monitoring and counseling [TMC], addiction comprehensive health enhancement support system [ACHESS], and combined delivery of TMC and ACHESS) to usual care and assessed longitudinal measures of alcohol use and self-efficacy. Analyses employed the potential outcomes framework and sensitivity analyses to address threats to causal inference resulting from an observed mediator variable. Results: Relative to usual care, the two intervention conditions that included TMC reduced alcohol use through improvements to self-efficacy. There was no evidence that self-efficacy mediated the effect of ACHESS on alcohol use. Conclusions: Based on our findings, self-efficacy is an important mechanism through which telephone continuing care interventions affect alcohol use. Future research to identify which components of TMC influence self-efficacy and factors that mediate ACHESS effects could enhance the effectiveness of remote delivery of continuing care. Public Health Significance Statement: This study found that telephone monitoring and counseling, alone and in combination with the smartphone-delivered addiction comprehensive health enhancement support system, appears to be effective at reducing alcohol use over 12 months through improvements to an individual's belief that they can abstain from drinking in high-risk scenarios. [ABSTRACT FROM AUTHOR]

Objective: Exercise is increasingly used as adjunct treatment for alcohol use disorder (AUD). Evidence suggests that moderate-to-high-intensity exercise can ameliorate cravings. We explored the potential mediating effects of changes in mood states in the relationship between exercise intensity and alcohol cravings. Method: Secondary analyses of a nested single-arm trial within a randomized controlled trial (FitForChange). In total, 117 sedentary adults (68.4% female, M = 52 ± 12 years) with clinician diagnosed (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) AUD and indications of craving (Desire for Alcohol Questionnaire) completed a 12-min submaximal cardiorespiratory fitness test on a cycle ergometer. Assessments of craving, mood states (POMS), and state anxiety (STAI-Y1) were taken immediately before, after, and 30 min after exercise. Ratings of perceived exertion (RPE) were included as indirect measures of exercise intensity. The med4way command in Stata was used to explore mediating and interaction effects of improvements in total mood disturbance (TMD) and state anxiety. Results: Improvements in mood and anxiety did not mediate the effect of higher exercise intensity on reductions in alcohol craving. A significant reference interaction was found between "hard" (or greater) exertion and anxiety improvements (β = −1.06, 95% CI [−1.50, −0.61]). Participants whose anxiety reduced during exercise had two times higher odds of reduced cravings when exercising at a higher intensity than participants whose anxiety worsened (OR = 2.04, 95% CI [1.12, 3.72]). Conclusions: Reductions in anxiety may partly explain the positive effect of higher exercise intensity on alcohol cravings. The findings are preliminary and require replication in future studies. Public Health Significance Statement: Alcohol use disorder (AUD) is prevalent and associated with poor somatic and psychiatric health. Exercise interventions are shown to reduce cravings for alcohol in those with AUD, but the underlying mechanisms are unclear. This study found that decreases in state anxiety in those reporting higher exercise intensity were associated with reductions in postexercise alcohol cravings. Findings can inform future exercise-based interventions for AUD. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) is abundant in the Cannabis sativa plant and exhibits complex immunomodulatory, anxiolytic, antioxidant, and antiepileptic properties. Several studies suggest that CBD could be used for different purposes in alcohol use disorder (AUD) and alcohol-related injuries to the brain and the liver. In this study, we focused on analyzing transcriptional alterations in human dermal fibroblasts (HDFs) cell line challenged simultaneously with ethanol and CBD as an ethanol-protective agent. We aimed to expose the genes and pathways responsible for at least some of the CBD effects in those cells that can be related to the AUD. Transcriptome analysis was performed using HDFs cell line that expresses both cannabinoid receptors and can metabolize ethanol through alcohol dehydrogenase activity. Fibroblasts are also responsible for the progression of liver fibrosis, a common comorbidity in AUD. With the use of a cellular test, we found that CBD at the lowest applied concentration (0.75 μM) was able to stimulate depressed metabolism and reduce the level of apoptosis of cells treated with different concentrations of ethanol to the level observed in the control cells. Similar observations were made at the transcriptome level, in which cells treated with ethanol and CBD had similar expression profiles to the control cells. CBD also affects several genes connected with extracellular matrix formation (especially its collagen constituent), which can have potential implications for, e.g., fibrosis process. [ABSTRACT FROM AUTHOR]

Background: There is a high prevalence of generalized anxiety disorder among immigrants in South Korea. The effect on health behavior is a major concern. However, epidemiological studies suggest that African asylum seekers with generalized anxiety disorders most often manifest co-occurring alcohol use disorder attributes. This study aimed to examine the mediating and moderating effect of emotional intelligence and coping strategies on the generalized anxiety disorder and alcohol use disorder of African asylum seekers in South Korea. Methods: Using the SPSS PROCESS macro, a cross-sectional quantitative survey design, self-reported questionnaires were distributed to 302 African asylum seekers living in South Korea. The data was performed with descriptive statistics and moderated mediation analysis using ordinary least squares path analysis to investigate all research problems. Results: The study path model showed a good fit and supported the hypothesis that generalized anxiety disorder has a detrimental effect on alcohol use disorder and a negative effect on emotional intelligence. Emotional intelligence was proven to be a mediator, and coping strategies moderated the relationship between generalized anxiety disorder and alcohol use disorder. Conclusions: Emotional intelligence and coping strategies are critical constructs to help control African asylum seekers' anxiety disorders and desire for alcohol consumption. [ABSTRACT FROM AUTHOR]

Knowledge of the association between wellbeing and substance use disorder (SUD) treatment outcomes can guide recovery definitions, measurement strategies, and intervention development. This study recruited individuals in treatment for SUD (N = 81, M = 39 years old, 53% female, 26% BIPOC). Wellbeing indicators included positive affect, serenity, flourishing, satisfaction with life, gratitude, quality of life, commitment to sobriety, and confidence staying sober. Outcomes included abstinence during treatment and treatment retention. After adjusting for urges to use, recruitment site, previous treatment episodes, legal issues, and days of sobriety in logistic regression analyses, only happiness with recovery remained significantly associated with either outcome (and was significantly associated with both outcomes: OR = 1.8 and 1.5, respectively, p < .05). Assessed via a single item (‘In general, I am happy with my recovery’), this construct shows promise as a novel, simple indicator of wellbeing in recovery and a potential target for intervention. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption is a significant public health concern among young people worldwide. While alcohol use is culturally embedded in many Nepalese communities, evidence regarding the prevalence of problematic drinking and its associated factors remains scarce among youths. This study aims to assess the prevalence of alcohol consumption and problematic drinking and their associated factors among management undergraduate students of Bhaktapur, Nepal. Method: A cross-sectional study was conducted among 304 undergraduate students in Bhaktapur, Nepal. The Alcohol Use Disorders Identification Test (AUDIT) was used to assess problematic drinking. Pearson's chi-square test and multivariable logistic regression analysis were performed to determine factors associated with alcohol consumption and problematic drinking, at the 5% level of significance. Results: The prevalence of alcohol consumption was 58.2% (95% CI:52.0-63.6%), with 26.6% (95% CI: 19.2–33.1%) exhibiting problematic drinking. Being male (aOR: 2.05, 95% CI:1.11–3.76), dissatisfaction with academic performance (aOR: 2.43, 95% CI:1.35–4.38), and alcohol preparation at home (aOR: 2.54, 95% CI: 1.20–5.40) were associated with alcohol consumption. Problematic drinking was linked to male gender (aOR: 4.03, 95% CI: 1.71–9.46), living in a joint family (aOR: 2.40, 95% CI: 1.09–5.29), poor perceived emotional support from family (aOR: 4.94, 95% CI: 1.50-16.26), and traumatic experience (aOR: 2.68, 95% CI: 1.19–6.02). Conclusion: This study revealed the concerning prevalence of alcohol consumption and dependency among Nepali undergraduate students. These findings highlight the need for comprehensive interventions targeting gender, the family environment, and academic factors to address alcohol misuse among Nepali youth. [ABSTRACT FROM AUTHOR]

IntroductionMethodResultsConclusionsPatients with alcohol use disorder (AUD) may have distortions in time perception. This study investigated subjective time dilation (the tendency to perceive a time interval longer than it is) and its association with craving and impulsivity in AUD.Thirty abstinent male inpatients with AUD (age 29–60 years) and thirty sex-, age-, and education-matched healthy controls completed a temporal generalization task, which assessed the preference (point of subjective equality, PSE) and sensitivity of time perception in the second range. Craving for alcohol was assessed using the Alcohol Urge Questionnaire. Impulsivity was assessed using a delay discounting task and the Barratt Impulsiveness Scale-11. A comprehensive battery of neuropsychological tests was used to measure executive function (flanker task, symbol digit modalities test, trail-making test-A/B), negative emotionality (Beck Depression Inventory-II, Self-rating Anxiety Scale), and incentive salience (monetary incentive delay task) following the Addictions Neuroclinical Assessment (ANA) framework.AUD patients exhibited a smaller PSE than healthy controls, perceiving a time interval 8% longer than it was. AUD patients with a smaller PSE showed a greater craving for alcohol but not greater impulsivity. Exploratory factor analysis incorporating the PSE and ANA measures revealed four latent factors. The PSE loaded highly onto a factor reflecting time perception but not three other factors reflecting executive function, negative emotionality, and incentive salience.AUD patients exhibit a pathological form of subjective time dilation, which is associated with a greater craving for alcohol. Time perception may be an independent functional dimension for understanding addictive behaviors in AUD. [ABSTRACT FROM AUTHOR]

\nIntroduction: Beyond the memory deficits classically observed in individuals with alcohol use disorder (IwAUD), research has recently focused on the study of autobiographical memory (AM) processes in IwAUD by analysing the content of AM narratives, and the implications for self-conception have been discussed. However, little is known about how IwAUD subjectively experience autobiographical recall. Methods: Thirty-seven IwAUD and 37 control participants were invited to perform an AM task that involved recalling memories for 4 life periods (2 important memories per period). Then, they assessed their subjective experience during AM recall using 6 phenomenological scales evaluating emotional valence, emotional intensity, sensory details, distancing, sharing, and vividness. Anxiety and depression symptoms, interoceptive sensibility, and difficulties in emotion regulation were also measured. Results: The IwAUD experienced greater distancing during AM recall, except during childhood AM recall, indicating that IwAUD are more prone to feeling that the person they are today is different from the person in their retrieved AMs. Very few intergroup differences were observed for AMs from childhood, adolescence-young adulthood, and adulthood, and a greater number of differences were observed for AMs from the last year: the IwAUD experienced AMs with a more negative valence, greater emotional intensity, fewer sensory details, greater distancing, and less sharing. A positive correlation was observed between distancing and interoceptive sensibility in the IwAUD group. Conclusion: Although these results suggest good preservation of autonoetic consciousness in IwAUD, except for more recent AMs, it is insufficient for IwAUD to experience a sense of self-continuity. This difficulty in maintaining a continuous sense of self may constitute a risk for AUD relapse. Beyond the memory deficits classically observed in individuals with alcohol use disorder (IwAUD), research has recently focused on the study of autobiographical memory (AM), which is the memory of personal experiences and facts about the self. By analysing the content of AM narratives in IwAUD, recent studies have reported a degradation of AMs content that may impact the self-conception of IwAUD. However, little is known about how IwAUD subjectively experience autobiographical recall. Thirty-seven IwAUD and 37 control participants were invited to perform an AM task that involved recalling memories for 4 life periods (2 important memories per period) and to assess their subjective experience during AM recall using 6 phenomenological scales. Anxiety and depression symptoms, interoceptive sensibility, and difficulties in emotion regulation were also measured. The IwAUD were more likely to feel that the person they are today is different from the person in their retrieved AMs (greater distancing), except during childhood AM recall. Very few intergroup differences were observed for AMs from childhood, adolescence-young adulthood, and adulthood, and a greater number of differences were observed for AMs from the last year: the IwAUD experienced AMs with a more negative valence, greater emotional intensity, fewer sensory details, greater distancing, and less sharing. A positive correlation was observed between distancing and interoceptive sensibility in the IwAUD group, indicating that the greater their interoceptive sensibility was, the more the IwAUD felt that they were a different person from the person in their AMs. [ABSTRACT FROM AUTHOR]

Alcohol is the most consumed and abused psychoactive drug globally, but the molecular mechanisms driving alcohol action and its associated behaviors in the brain remain enigmatic. Here, we have discovered a transmembrane protein TMEM132B that is a GABA A receptor (GABA A R) auxiliary subunit. Functionally, TMEM132B promotes GABA A R expression at the cell surface, slows receptor deactivation, and enhances the allosteric effects of alcohol on the receptor. In TMEM132B knockout (KO) mice or TMEM132B I499A knockin (KI) mice in which the TMEM132B-GABA A R interaction is specifically abolished, GABAergic transmission is decreased and alcohol-induced potentiation of GABA A R-mediated currents is diminished in hippocampal neurons. Behaviorally, the anxiolytic and sedative/hypnotic effects of alcohol are markedly reduced, and compulsive, binge-like alcohol consumption is significantly increased. Taken together, these data reveal a GABA A R auxiliary subunit, identify the TMEM132B-GABA A R complex as a major alcohol target in the brain, and provide mechanistic insights into alcohol-related behaviors. [Display omitted] • Single-pass transmembrane protein TMEM132B is a GABA A R auxiliary subunit • TMEM132B promotes GABA A R expression at the cell surface and slows receptor deactivation • TMEM132B enhances the allosteric effects of alcohol on various GABA A Rs • Genetic inactivation of TMEM132B in mice alters alcohol-related behaviors Identification of TMEM132B as a GABA A R auxiliary subunit that modulates alcohol action in the brain at both the molecular and behavioral levels. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests muscarinic acetylcholine receptors represent novel targets to treat alcohol use disorder. In this review, we draw from literature across medicinal chemistry, molecular biology, addiction and learning/cognition fields to interrogate the proposition for muscarinic receptor ligands in treating various aspects of alcohol use disorder, including cognitive dysfunction, motivation to consume alcohol and relapse. In support of this proposition, we describe cholinergic dysfunction in the pathophysiology of alcohol use disorder at a network level, including alcohol‐induced adaptations present in both human post‐mortem brains and reverse‐translated rodent models. Preclinical behavioural pharmacology implicates specific muscarinic receptors, in particular, M4 and M5 receptors, as potential therapeutic targets worthy of further interrogation. We detail how these receptors can be selectively targeted in vivo by the use of subtype‐selective allosteric modulators, a strategy that overcomes the issue of targeting a highly conserved orthosteric site bound by acetylcholine. Finally, we highlight the intense pharma interest in allosteric modulators of muscarinic receptors for other indications that provide an opportunity for repurposing into the alcohol use disorder space and provide some currently unanswered questions as a roadmap for future investigation. [ABSTRACT FROM AUTHOR]

Introduction: Substance Use Disorder (SUD) screening tools used in current practice are designed to identify SUD once patients have begun regular dangerous drug use. While these screening tools are valuable, prevention and avoidance of SUD would save countless lives. The climbing number of deaths due to drug overdose make screening for and prevention of SUD imperative. This study addresses this care gap. The aim was to develop a simple screening tool for patients who may be prone to develop Alcohol Use Disorder (AUD) and/or SUD prior to addiction. It was hypothesized that participants with initially positive emotional experiences would be correlated with a future SUD diagnosis. Methods: The study involved a self-administered survey using a cross-sectional design and was carried out over one-month in the spring of 2021. Those patients who presented to the MAT clinic (SUD group) were seen in a separate area than the patients presenting for urgent care (Comparison group). Participants (N = 259) were voluntarily recruited from MAT and Urgent care: Patients receiving acute care were assigned to the Comparison (N = 126, 50.8% female, 5.7% non-white, 27.2% age < 34) and those receiving treatment for SUD were assigned to the MAT group (N =133, 40.8% female, 4.8% non-white, 36.8% ≤34). The survey questioned demographics (4 items), risk factors for AUD/SUD (6 items), information about first alcohol/opioid experiences (16 items), and factors for seeking AUD/SUD treatment and recovery (2 items). Feelings were categorized as positive (e.g., euphoria, happiness, self-confident), neutral (e.g., nothing, normal), or negative (e.g., depressed, sad, sick). Results: The MAT group felt more positive feelings with first usage of alcohol and opioids compared to the comparison group (p<.001). With first usage of opioids specifically, MAT (0.13 ± 0.04) and comparison (0.29 ± 0.07) groups differed (p <.001). Over half (55.3%), of the MAT participants reported feeling self-confident with first use of alcohol while only 29.7% of the comparison reported this (p<.001). Over three-fifths (63.7%) of the MAT group reported feeling of euphoria with the first usage of opioids compared to one-tenth (9.8%) in the comparison group (p<.001). Discussion: This retrospective cross-sectional report shows the first affective responses to substances may predict risk for future SUD and could be a prevention screening tool. Asking patients about positive feelings with first usage of alcohol/opioids could be a simple screening tool employed for prevention. [ABSTRACT FROM AUTHOR]

Background: Alcohol dependence is associated with several neuropsychological abnormalities, such as increased impulsivity or attentional bias towards drug-related stimuli. However, it is debated whether these abnormalities are on the decline after long-term abstinence from alcohol. Inpatient rehabilitation treatment enables the longitudinal investigation of such variables during a long, largely secured, period of abstinence. Methods: This study involved alcohol-dependent patients consecutively admitted for a duration of 14–26 weeks to an inpatient rehabilitation treatment center located in a hospital specializing in substance use disorders. Craving and impulsivity were assessed with the means of two questionnaires (e.g., OCDS-G and BIS-11); conversely, attentional bias and problems with inhibition were measured with the help of two computer-based experiments (e.g., dot–probe task and stop–signal–reaction task). Investigations were conducted at entry, after 6 weeks, and during the last two weeks of the inpatient treatment. Results: A total of 130 patients with alcohol dependence (mean age 43.3 years; 78.5% male) completed the first, N = 102 the second, and N = 83 the final assessment. Over the whole period of inpatient treatment, there was a significant decrease in patients' scores for both craving (t(83) = 7.8, p < 0.001) and impulsivity (t(82) = −3.75, p < 0.001, t(82) = 4.4, p < 0.001). However, there were no significant changes regarding attentional bias (t(82) = 0.16, p = 0.494) and inhibitory control (t(76) = 0.04, p = 0.482) scores. Conclusions: Neuropsychological abnormalities associated with alcohol dependence might persist even after a long abstinence period. The decrease in both craving and impulsivity levels may be explained by the protected, alcohol-free, hospital environment; however, patients' risk of post-discharge relapse may remain high, as the basic neurobiological mechanisms of alcohol dependence may persist for long periods, and possibly for more than 3–6 months. [ABSTRACT FROM AUTHOR]

Grip strength is considered one of the simplest and reliable indices of general health. Although motor ability and strength are commonly affected in people with alcohol use disorder (AUD), factors predictive of grip strength decline in AUD have not been investigated. Here, we employed a data‐driven analysis predicting grip strength from measurements in 53 controls and 110 AUD participants, 53 of whom were comorbid with HIV infection. Controls and AUD were matched on sex, age, and body mass index. Measurements included commonly available metrics of brain structure, neuropsychological functioning, behavioural status, haematological and health status, and demographics. Based on 5‐fold stratified cross‐validation, a machine learning approach predicted grip strength separately for each cohort. The strongest (top 10%) predictors of grip were then tested against grip strength with correlational analysis. Leading grip strength predictors for both cohorts were cerebellar volume and mean corpuscular haemoglobin concentration. Predictors specific to controls were Backwards Digit Span, precentral gyrus volume, diastolic blood pressure, and mean platelet volume, which together significantly predicted grip strength (R2 = 0.255, p = 0.001). Unique predictors for AUD were comorbidity for HIV infection, social functioning, insular volume, and platelet count, which together significantly predicted grip strength (R2 = 0.162, p = 0.002). These cohort‐specific predictors were doubly dissociated. Salient predictors of grip strength differed by diagnosis with only modest overlap. The constellation of cohort‐specific predictive measurements of compromised grip strength provides insight into brain, behavioural, and physiological factors that may signal subtly affected yet treatable processes of physical decline and frailty. [ABSTRACT FROM AUTHOR]

Aim: To investigate the long-term effect of Screening, Brief Intervention, and Referral to Treatment (SBIRT) on alcohol treatment utilization among general hospital inpatients. Methods: This 36-month follow-up of a randomized controlled trial included general hospital inpatients who were screened using the Alcohol Use Disorder Identification Test (AUDIT). Patients with an AUDIT score of 8+ were included. Patients were randomized to either SBIRT (Relay) or treatment as-usual (TAU). Outcome was attendance at a specialized outpatient treatment institution or prescription of pharmacological alcohol treatment in general practice. Using the Danish Civil Registration System, patients were followed in the Danish National Patient Registry, Danish National Alcohol Treatment Register, and the Danish National Prescription Registry. Data was collected up to 36 months after discharge. Results: The study population consisted of 258 patients in the Relay group and 303 patients in the TAU group. In the Relay group, 36 (14.0%) patients received treatment versus 23 (7.6%) in the TAU group. Patients in the Relay group had higher odds for receiving treatment compared to the TAU group (OR: 1.97, 95% CI: 1.1–3.4, p = 0.01). Significantly more patients in the Relay group scored 16+ on the AUDIT and had already tried to change their alcohol consumption (both p < 0.01). Adjusted for potential confounders, the effect of the Relay intervention was reduced (OR: 1.37, 95%CI: 0.7–2.5, p = 0.31). Conclusions: This study did not find evidence that SBIRT is better than TAU at sustaining significant long-term alcohol treatment utilization after discharge among inpatients from general hospital. [ABSTRACT FROM AUTHOR]

We updated systematic reviews for mindfulness and acceptance and commitment therapy for problematic alcohol use and disorders. We found growing evidence mindfulness was associated with reduced alcohol consumption and/or other therapeutic effects and was superior to other treatments under certain conditions. Mindfulness may be valuable for treating comorbidity and offer an alternative to traditional psychosocial interventions. [ABSTRACT FROM AUTHOR]

Background Despite conflicting findings on the association between socioeconomic status and drinking, little is known about the impact of deprivation as a measure of inequality on alcohol use disorders (AUDs). Methods We used the Korea Welfare Panel Study, a longitudinal survey conducted from 2012 to 2022, and included 1569 Korean adult participants. Deprivation (at least one including food, housing, medical, educational, and credit deprivation) was measured by self-report and divided into four categories according to the change in deprivation experience from the previous year to the following year. AUD was measured using the Korean version of the Alcohol Use Disorders Identification Test scale. Multivariable logistic regression was used to estimate odds ratios and 95% confidence intervals and adjusted for confounders. Results Among 1569 participants, worsened deprivation and consistent deprivation were positively associated with AUD compared to non-deprivation. In particular, worsened deprivation was more likely to be associated with AUD in participants with low household income, high school education level, and economic activity. Conclusion We found that worsened deprivation and consistent deprivation were associated with AUD. Deprivation should be considered as a health policy intervention to improve drinking problems. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol use disorder (AUD) is a significant cause of morbidity and mortality globally. However, uptake of AUD pharmacotherapies among clinicians has remained low. There exists a research gap regarding clinician attitudes and the diffusion of AUD pharmacotherapies among Indian clinicians. We conducted a survey to assess the same. Methods: An online survey was sent to clinicians nationwide from February and April 2023 to assess attitudes and practices regarding various AUD medications. Logistic and ordinal regression models evaluate the clinician and caseload factors determining medication diffusion and attitudes. Results: A total of 387 clinicians responded to our survey. Most of them were males (61.7%) and trained psychiatrists (56.3%). The diffusion for acamprosate, naltrexone, and disulfiram was 69.8%, 81.4%, and 58.2%, respectively. Baclofen had the highest diffusion. Female respondents had significantly lower perceived efficacy, acceptability, and safety for disulfiram. Independent practitioners were more likely to prescribe all pharmacotherapies except baclofen. Discussion: Diffusion for alcohol pharmacotherapies was incomplete. Baclofen had the highest diffusion, probably reflecting its cost and safety profile. Despite its perceived efficacy, safety concerns impacted the diffusion of disulfiram. Female clinicians had lower perceived attitudes toward disulfiram. Specific training for AUD pharmacotherapies is warranted for female clinicians and nonpsychiatrists. [ABSTRACT FROM AUTHOR]

Objective: Alcohol consumption patterns during the COVID-19 pandemic have varied notably. Participants: We examined the acute impact of the pandemic on alcohol use disorder (AUD) in a generalizable sample of college students who were surveyed pre-pandemic and re-surveyed in May 2020. Method: Items assessed pre-pandemic included DSM-5 AUD and mental health symptoms. A COVID-19 impacts questionnaire was administered, and alcohol and mental health items re-assessed. Results: AUD symptoms decreased from pre-pandemic to during the pandemic, demonstrating a change in trajectory compared to prior cohorts. Students with persistent AUD reported greater concurrent symptoms of PTSD, depression, and alcohol consumption than those with remitted AUD (ps ≤.02), but not increased COVID-19 impact. Persistent AUD status was predicted by higher sensation seeking and alcohol consumption. Conclusions: Students with concurrent mental health problems are at continued risk for persistent AUD. Findings highlight the impact of the college environment and social context for drinking on AUD. [ABSTRACT FROM AUTHOR]

Objectives: Food and Alcohol Disturbance (FAD) is the phenomenon in which individuals exhibit co-occurring hazardous alcohol and eating behaviors to either negate caloric intake associated with alcohol and/or maximize intoxication. While the Compensatory Eating and Behaviors in Response to Alcohol Scale (CEBRACS) is the most widely used measure to assess FAD to date, its factor-structure has yet to be confirmed. Methods: The current study utilized confirmatory factor analysis (CFA) to examine the CEBRACS' four factor subscales as well as recently proposed alternative scoring structures. Participants: Participants (N = 582) were American college students from seven universities (18–24 years; 67% cisgender women; 70% non-Hispanic White). Results: The CFA failed to provide optimal fit for all models tested. Results of invariance testing found no measurement variance by sex, suggesting the failure of the four-factor solution was not due to noninvariance. Conclusions: Overall, findings do not support continued use of the original 21-item CEBRACS. [ABSTRACT FROM AUTHOR]

Background: Unhealthy alcohol use is prevalent among people living with HIV/AIDS (PLWH) and contributes to impaired functioning, diminished quality of life, and poorer HIV outcomes. Common cooccurring conditions such as chronic pain may be associated with negative outcomes both directly and through its influence on unhealthy drinking itself. However, there is relatively little known about how pain influences unhealthy drinking among PLWH over time. The current study examined whether pain was associated with indices of unhealthy alcohol use, namely heavy drinking and alcohol use disorder (AUD) assessed 12 months later. Methods: The study sample (n = 207) was from the Boston Alcohol Research Collaboration on HIV/AIDS (ARCH) Cohort, a prospective cohort of PLWH with a history of illicit substance or unhealthy alcohol use. We conducted logistic regression analyses to examine the associations between pain and both heavy drinking and AUD status (DSM‐5 criteria) (yes/no) over time. In secondary analyses, we examined whether pain was associated with greater AUD severity and whether pain interference was associated with heavy drinking and AUD outcomes. Results: We found that pain at baseline was associated with greater odds of AUD [aOR = 2.29 (95% CI: 1.13, 4.64), p = 0.02] but not heavy drinking [aOR = 0.91 (95% CI: 0.44, 1.88), p = 0.79] at 12 months. Pain was also associated with more severe AUD. Analyses of pain interference showed similar results. Conclusions: Pain is prospectively associated with higher odds of AUD among PLWH with a substance/unhealthy alcohol use history. Providers should routinely address pain among PLWH to improve AUD outcomes. [ABSTRACT FROM AUTHOR]