Excessive alcohol consumption results in gastrointestinal (GI) tract dysfunction, including disruption of the intestinal barrier and exposure of the liver to microbes and gut-derived pathogen-associated molecular patterns (PAMPs). The upper GI tract is exposed to the highest amount of alcohol, but little is known about alcohol's impact on GI inflammation. This study aimed to evaluate the initial effects of alcohol binges on GI inflammation.
A murine model of binge drinking was established with daily oral gavages of alcohol (3.5 g/kg) for 3 days in C57BL/6J female mice. The proximal small intestine (PSI), distal small intestine (DSI), and colon were evaluated for inflammation at 3 and 24 h after the last binge. To determine whether reactive oxygen species (ROS) contribute to intestinal inflammation, a subset of mice were given 500 mg/kg N-acetyl-cysteine (NAC) with alcohol via gavage. To assess the role of neutrophil extracellular traps (NETs), mice were treated 1 h before the alcohol binges with 5 mg/kg of DNase, a nonspecific inhibitor of NETs.
Alcohol binges induced a PSI enteropathy with neutrophil recruitment, activation, NETs, and increased serum endotoxin without significant changes in PSI pro-inflammatory cytokines. Neutrophil recruitment and serum endotoxin normalized 24 h after the last binge with persistent PSI villous blunting. While alcohol generated ROS, administration of the antioxidant, NAC, failed to prevent the PSI enteropathy, neutrophil activation, or increased serum endotoxin. DNase treatment improved the PSI enteropathy and reduced serum endotoxin, neutrophil recruitment, and neutrophil activation. We found robust upregulation of Gal-3 and CXCL10 in the PSI after alcohol binges is associated with neutrophil recruitment and activation.
Alcohol binges result in a PSI enteropathy, transient infiltration of neutrophils, and NETs that are independent of ROS production. Treatment with DNase, a nonspecific inhibitor of NETs, mitigates alcohol-induced PSI enteropathy, neutrophil recruitment and bacterial translocation.
Unhealthy alcohol use (UAU) describes a continuum of drinking behaviors ranging from risky consumption to severe alcohol use disorder (AUD). Despite its high prevalence, most individuals across this spectrum remain untreated. Contingency management (CM), a behavioral intervention utilizing reward-based incentives, effectively promotes behavior change in various substance use disorders but remains insufficiently studied across the full UAU spectrum. This systematic review and meta-analysis assesses the efficacy and clinical utility of CM for reducing alcohol use among individuals with UAU.
We comprehensively searched MEDLINE, EMBASE, PsycINFO, Scopus, and Cochrane Central through February 2025 for randomized and non-randomized trials comparing CM to treatment-as-usual or non-contingent rewards in adults with UAU. Eligible studies reported at least one objective measure of alcohol use. The primary outcome was a reduction in alcohol consumption. Meta-analyses were performed using the Generic Inverse Variance method (RevMan 5.4), with statistical significance set at p < 0.05. Heterogeneity was evaluated using Cochran's Q and I2 statistics, and the risk of bias was assessed with Cochrane Risk of Bias 2 and ROBINS-I tools.
Twenty-nine studies (21 randomized controlled trials and 8 non-randomized studies; n = 2615; mean age = 41.0 years; 30.3% female) were included. CM significantly increased alcohol-negative samples (OR = 3.07, 95% CI: 2.43–3.87) and alcohol-free days (OR = 3.97, 95% CI: 1.74–9.08). CM was also effective in reducing self-reported alcohol consumption and concurrent nicotine and stimulant use. However, it did not significantly improve continuous abstinence duration (SMD = 0.88, 95% CI: −0.34 to 2.10).
This systematic review and meta-analysis demonstrates that CM effectively reduces alcohol use among adults with UAU. Given its adaptability and scalability, CM represents a promising intervention, addressing an important gap in evidence-based approaches for early intervention, harm reduction, and broader treatment of alcohol-related problems.
Alcohol analgesia (AA) is a well-established phenomenon and important motivator of pain self-medication with alcohol. Alcohol intoxication produces widespread alterations in many brain areas involved in pain processing. Sex and family history (FH) of problematic alcohol use both influence AA. Investigation of neural response to experimental pain during alcohol intoxication, and potential interactive effects of sex and FH, may clarify important pathways of risk for pain chronicity and alcohol use disorder.
Subjects (N = 97, Mean age = 26.23, SD = 4.97, 52.26% female, 41.23% FH +) completed two laboratory sessions in which they consumed alcohol (breath alcohol concentration, BrAC = 0.08 g/dL) or placebo (BrAC = 0.00 g/dL) beverages and completed functional magnetic resonance imaging (fMRI) scanning while experiencing painful, thermal sensations. Blood-oxygenation-level-dependent (BOLD) activation during painful stimuli was assessed with a general linear model (GLM; factors: condition, sex, FH). Generalized psychophysical interaction (gPPI) investigated alterations in functional connectivity during heat pain with seed regions with altered BOLD activation in GLM analyses. Potential alcohol-induced cerebrovascular effects were examined using arterial spin labeling.
Subjective report of pain during scanning was not found to differ between beverage conditions. No effects of alcohol on cerebral blood flow were detected. Across conditions, we noted widespread activation during noxious stimuli within regions canonically associated with pain processing. Male subjects exhibited significantly less BOLD activation during the alcohol than placebo session in the right dorsolateral prefrontal cortex. No FH effects were identified. Pain-related connectivity with this region was altered with aspects of the frontal, occipital, insular, and supramarginal gyri.
Alcohol may subtly influence neural processes involved in pain perception, particularly among regions involved in top-down pain modulation uniquely between sexes. These effects may be more visible in interregional indices of brain function. Future investigations of multidimensional neural metrics and at various alcohol doses are needed to further explore mechanisms of AA.
Fetal alcohol spectrum disorder (FASD) is associated with a range of developmental, behavioral, and physical impairments. While much research to date has focused on developmental and behavioral aspects of FASD, there is growing evidence that children with FASD may experience alterations in renal and cardiovascular function. By also comparing eating behaviors between children with FASD and typically developing children, this may provide some clues to the underlying causes of these physiological changes.
In this study, we recruited children and adolescents with (n = 34) and without (n = 22) a diagnosis of FASD. We measured several cardiovascular and renal outcomes and analyzed potential associations with eating behaviors related to food approach and avoidance, assessed from caregiver report using the Children's Eating Behavior Questionnaire (CEBQ).
Children with FASD had significantly elevated urinary sodium-to-potassium (Na+/K+) ratio, a trend for increasing urine sodium (Na+), and a reduction in the normal age-associated rise in urine creatinine compared to typically developing controls. The FASD group also exhibited significantly elevated resting heart rate. Additionally, those with a diagnosis of FASD had higher scores for subscales of food approach (food responsiveness, emotional overeating, desire to drink) and a trend toward a higher food avoidance score on the CEBQ. A subset of these behavioral scores was associated with cardiovascular but not renal outcomes.
Together, these findings suggest that renal and cardiovascular function may be altered in children and adolescents with FASD, which may be linked to abnormal food-related behaviors and/or other clinical or demographic factors. While the mechanisms underlying these early-life physiological changes are not fully understood, it is likely they contribute to poorer long-term health outcomes. Further research is needed to validate these preliminary findings in larger cohorts, explore the underlying mechanisms and investigate potential long-term implications of these findings.
Several facets of substance use self-stigma have been identified, and these constructs may be important within the specific context of alcohol use disorder (AUD) treatment. Gaining a better understanding of self-stigma among individuals who are seeking treatment for AUD may help inform treatment approaches and ultimately could improve treatment to help reduce AUD-related self-stigma.
We recruited 121 participants (52.9% women, 46.3% men) who were primarily White (84.2%) and not Hispanic identifying (90.0%), with a mean age of 44.4 years (SD = 10.3) from a telehealth AUD treatment program. Participants completed an online survey and self-reported demographic information, family history of drinking problems, AUD severity, drinking goals (coded as abstinent or non-abstinent), and three facets of self-stigma (self-devaluation, fear of enacted stigma, and stigma avoidance). Bivariate associations between gender and self-stigma facets were examined via t-tests. Preliminary predictors of each facet of self-stigma were examined using regression analyses. Given mixed prior findings on the association between gender and self-stigma, we also examine interactions of gender with significant predictors of self-stigma.
Women reported higher levels of self-devaluation (p = 0.02) and stigma avoidance (p = 0.02) compared to men. Ordinal logistic regression analyses with Holm correction showed that higher levels of AUD severity predicted greater stigma avoidance (OR = 1.80 [95% CI: 1.23, 2.63], Holm p = 0.021). No other variables were predictive of stigma following correction. Gender did not interact with AUD severity in predicting stigma.
Findings suggest that higher AUD severity is associated with greater stigma avoidance. Consequently, to effectively address self-stigma, telehealth interventions should be tailored to the specific experiences and needs of people with higher AUD severity.
Students with fetal alcohol spectrum disorders (FASD) are at risk of poor academic performance and school disruption given teachers' limited opportunity to learn about how to support them. The Families Moving Forward (FMF) Program and its derivative mobile health intervention, FMF Connect, provide an ideal framework to inform a scalable intervention for teachers. The current study aimed to develop and test the FMF Connect Teacher Companion website using the ADAPT-ITT framework, including teacher input.
With teacher input, materials from the FMF Program and FMF Connect were adapted to be relevant to teachers' needs and the classroom setting. Next, 37 teachers participated in a fully remote, nonblinded, randomized two-group parallel design pilot trial of the website. Eligible teachers had direct contact with a student with FASD aged 5–12 in an educational setting. The pilot trial was preregistered and publicly available on ClinicalTrials.gov (study no.: NCT05986565) prior to recruitment commencement. Descriptive statistical analysis aimed to understand technological functionality and study design acceptability.
Findings of both website (n = 21) and control (n = 16) groups demonstrated the website was satisfactory and functional. Participants had positive impressions of all content but reported some negative impressions around aesthetics and the large amount of information.
The FMF Connect Teacher Companion website is a feasible, acceptable FASD-informed resource for teachers.
Tobacco use disorder (TUD) and alcohol use disorder (AUD) frequently co-occur and together are associated with worse prognoses. There are few options for treating both disorders concurrently. This study examined whether the antiepileptic drug topiramate would be effective for treating adults with both AUD and TUD.
Participants (n = 236) from three sites were randomly assigned to receive treatment adherence counseling and either placebo, low-dose topiramate (up to 125 mg/day), or high-dose topiramate (up to 250 mg/day) for up to 18 weeks, with a 5-week titration period. The primary outcomes were the mean percentage of heavy drinking days (PHDD) and the smoking continuous abstinence rate with biochemical verification during the last 4 weeks of treatment. Secondary outcomes included quality of life and craving for alcohol and cigarettes. We also conducted post hoc exploratory repeated measures analyses to maximize the use of available data.
None of the prespecified primary or secondary outcomes differed across medication groups. However, the exploratory analyses indicated that participants treated with the 250 mg dose had lower mean PHDD and drinks per day than those taking the lower dose or placebo. Additionally, participants in both the 125 and 250 mg groups smoked fewer cigarettes per day and reported greater cigarette abstinence than those in the placebo group.
While the primary analyses did not find evidence that topiramate decreases drinking and smoking behavior, likely influenced by a high attrition rate and poor medication adherence, exploratory repeated measures analyses suggest that topiramate 250 mg reduces drinking behavior and that both the 125 mg and 250 mg doses reduce smoking behavior. Future studies that maximize treatment adherence are needed to more definitively determine whether topiramate is an effective treatment for AUD and TUD.
Alcohol-associated liver disease (ALD) is increasingly affecting young adults, but comprehensive analyses of hospitalization patterns in this demographic remain limited. We aimed to evaluate trends in hospitalization rates, disease severity, and healthcare costs for ALD among adults aged 20–49 years compared with older adults.
We conducted a retrospective analysis using the National Inpatient Sample (2016–2022) to evaluate ALD-related hospitalizations in adults ≥20 years. Using ICD-10 codes, we identified hospitalization of ALD, alcohol-associated cirrhosis and alcohol-associated hepatitis, analyzing hospitalization rates, decompensation rates, and inflation-adjusted costs. Temporal trends were assessed using joinpoint regression analysis with results expressed as mean annual percentage change and Cochrane–Armitage test.
Among 1,159,959 hospitalizations in young adults with ALD, rates increased more steeply compared to older adults (annual increase: 4.48% vs. 1.78%), rising from 106.5 to 144.7 per 100,000 persons versus 269.5 to 295.0 per 100,000 persons, respectively. By 2020, alcohol-associated hepatitis hospitalization rates in young adults surpassed older adults (65.6 vs. 61.3 per 100,000). The 30–39 age group represented the largest increase (31% to 37.5%) among young adults. Decompensated alcohol-associated cirrhosis increased across all age groups, most prominently in ages 20–29 (31.3% to 36.4%). National costs doubled from $1.69 billion to $3.45 billion.
Young adults demonstrated accelerated increases in ALD-related hospitalizations and disease severity compared to older adults, with a particularly pronounced trend during the pandemic period. These findings suggest a need for age-specific preventive and therapeutic interventions.
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