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Background: Prolonged alcohol consumption may lead to gastrointestinal tract dysfunction and cause abnormalities in the associated nervous system activity, thereby increasing the body's craving for alcohol. Lactobacillus casei is a probiotic that has been shown to reduce the incidence of alcohol-related diseases. However, it is unclear whether Lactobacillus casei can delay the development of alcohol dependence., Methods: The chronic intermittent active drinking method was used to establish a mouse alcohol dependence model. The mice were randomly divided into 4 treatment groups, as follows: (1) Control group: two bottles of distilled water alternately, 0.2 mL/d saline gavage. (2) Alcohol group: alternating water and alcohol, 0.2 mL/d saline gavage. (3) Low group: alternating water and alcohol, 0.2 mL/d 1 × 10 8 CFU of Lactobacillus casei by gavage. (4) High group: alternating water and alcohol, 0.2 mL/d 1 × 10 9 CFU of Lactobacillus casei by gavage. The daily water consumption (mL), alcohol consumption (mL) and body weight of each mouse were recorded. After that, pathological changes in the intestines, brain tissues and serum of the experimental animals were detected, while changes in the intestinal flora of the mice were analysed by 16S rRNA sequencing., Results: The Lactobacillus casei intervention did not produce a significant effect on body weight in alcohol-exposed mice (P>0.05), but significantly reduced alcohol preference in alcohol-exposed mice (P<0.05). Subsequent analyses showed that Lactobacillus casei significantly ameliorated intestinal, brain tissue, and systemic inflammatory responses in alcohol-exposed mice (P<0.05). 16S rRNA sequencing showed that alcohol-exposed mice treated with Lactobacillus casei exhibited a richer composition of intestinal microorganisms, such as f&#95;&#95;Rikenellaceae, g&#95;&#95;Alistipes&#95;A&#95;871400, and g&#95;&#95;Bacteroides&#95;H genera showed relative enrichment in the High group., Conclusion: By showing that Lactobacillus casei slows down alcohol preference and alleviates gut and brain tissue inflammation in alcohol-exposed mice, our findings provide a possible strategy: Lactobacillus casei may be able to serve as a potential target for the prevention and treatment of alcohol dependence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

One of the neurobiological correlates of alcohol use disorder (AUD) is the disruption of striatal dopaminergic function. Although regional differences in dopamine (DA) tone/function have been well studied, interregional relationships (represented as inter-subject covariance) have not been investigated and may offer a novel avenue for understanding DA tone. Positron emission tomography (PET) data with [ 11 C]raclopride in 22 social drinking controls and 17 AUD participants were used to generate group-level striatal covariance (partial Pearson correlation) networks, which were compared edgewise as well as on global network metrics and community structure. An exploratory analysis examined the impact of tobacco cigarette use status. Striatal covariance was validated in an independent publicly available [ 18 F]fallypride PET sample of healthy volunteers. Striatal covariance of control participants from both data sets showed a clear bipartition of the network into two distinct communities, one in the anterior and another in the posterior striatum. This organization was disrupted in the AUD participants' network, which showed significantly lower network metrics compared with the control participants' network. Stratification by cigarette use suggests differential consequences on group covariance networks. This work demonstrates that network neuroscience can quantify group differences in striatal DA and that its interregional interactions offer new insight into the consequences of AUD., (© 2024 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Alcohol use disorder (AUD) is frequently comorbid with anxiety disorders, yet whether alcohol abuse precedes or follows the expression of anxiety remains unclear. Rodents offer control over the first drink, an advantage when testing the causal link between anxiety and AUD. Here, we utilized a risk-avoidance task to determine anxiety-like behaviors before and after alcohol exposure. We found that alcohol's anxiolytic efficacy varied among inbred mice and mice with high risk-avoidance showed heightened alcohol relief. While dopamine D1 receptors in the striatum are required for alcohol's relief, their levels alone were not correlated with relief. Rather, the ratio between striatal D1 and D2 receptors was a determinant factor for risk-avoidance and alcohol relief. We show that increasing striatal D1 to D2 receptor ratio was sufficient to promote risk-avoidance and enhance alcohol relief, even at initial exposure. Mice with high D1 to D2 receptor ratio were more prone to continue drinking despite adverse effects, a hallmark of AUD. These findings suggest that an anxiety phenotype may be a predisposing factor for AUD., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Inflammation appears to be a critical mechanism in the development of alcohol use disorder (AUD) and a consequence of chronic alcohol use. The potential anti-inflammatory properties of cannabis may modulate the proinflammatory effects of alcohol. This study sought to extend previous work investigating the relationship between alcohol consumption, cannabis use and circulating interleukin (IL)-6 levels in a sample with AUD. One hundred and thirty-three individuals with an AUD provided blood samples to assess IL-6 and answered questions regarding alcohol and cannabis use. An ordinary least squares multiple regression analysis was conducted to assess the effect of alcohol and cannabis use on IL-6. A moderation analysis examined cannabis use as a potential moderator of the relationship between alcohol use and circulating IL-6 levels. Alcohol use was predictive of higher log IL-6 levels (standardized β = 0.16, p = 0.03), while cannabis use was not predictive of log IL-6 levels (p = 0.36). Days of cannabis use moderated the relationship between alcohol use and IL-6 levels, such that the relationship between alcohol use and IL-6 levels was only significant in individuals with AUD without recent cannabis use. This study extends previous work to a clinical sample with an AUD and underscores the importance of considering cannabis use in studies on alcohol use and inflammation. This study also indicates the need for in-depth analyses on cannabinoids and inflammation and the interaction between cannabinoids and alcohol use on inflammation., (© 2024 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Purpose: Exposure to alcohol-related cues is thought to elicit a conditional response characterized by increased craving in individuals with alcohol use disorder (AUD). In the context of AUD research, it is important to consider that not all individuals with an AUD are alcohol cue reactive. This study systematically examined subjective alcohol cue reactivity and its clinical and drinking correlates in individuals with an AUD enrolled in a human laboratory pharmacotherapy trial., Methods: Individuals with current moderate-to-severe AUD (N = 52) completed a standard alcohol cue exposure paradigm and individual difference assessments as part of a human laboratory pharmacotherapy trial (NCT04249882). We classified participants as cue reactive (CR+) and cue non-reactive (CR-), as indicated by self-reported, subjective alcohol urge, and examined group differences in baseline clinical characteristics and drinking outcomes over the course of the trial., Results: Twenty participants (38%) were identified as CR+, while 32 participants (62%) were identified as CR-. The CR+ and CR- groups did not differ in baseline drinking and AUD clinical characteristics, but the groups differed in race composition (p = 0.02) and smoking prevalence (p = 0.04) such that the CR+ group had lower prevalence of smokers. The CR+, compared with the CR-, group drank more during the trial titration period (p = 0.03). Both groups reduced drinking across the trial (p's < 0.001), but the CR+ group exhibited a smaller reduction in drinking, compared with the CR- group (time x group, p = 0.029; CR-, p < 0.0001; CR+: p = 0.01)., Conclusion: Results indicate that cue reactivity is a heterogenous construct. Recognizing this heterogeneity, and the clinical factors associated with it, is critical to advancing this paradigm as an early efficacy marker in AUD research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: The theory of aversive transmission posits that children of parents who have an alcohol use disorder (AUD) may abstain or limit their own alcohol use because they believe themselves to be at risk of developing problems with alcohol. The present study examined relationships among parental AUD, perceived parental AUD, perceived risk for AUD, addiction avoidance reasons for limiting alcohol use, and alcohol use using a random intercept cross-lagged panel model., Method: Participants ( N = 805; 48% female; 28% Latinx) were from a longitudinal study investigating intergenerational transmission of AUD. Parental AUD, perceived parental AUD, perceived risk for AUD, addiction avoidance reasons for limiting alcohol use, and alcohol use (quantity, frequency, and frequency of heavy drinking) were measured every 5 years from late adolescence ( M age = 20) to adulthood ( M age = 32). Random intercept cross-lagged panel models tested whether there were stable between-person relations or time-varying within-person relations among these variables., Results: At the between-person level, perceived parental AUD predicted greater addiction avoidance reasons for limiting alcohol use and greater perceived risk. Those with greater addiction avoidance reasons for limiting alcohol use were less likely to use any alcohol and drank less frequently. Parental AUD was associated with higher levels of alcohol use as well as perceived risk. No consistent cross-lagged paths were found at the within-person level., Conclusions: Study findings were at the between-person level rather than the within-person level. Future work on aversive transmission is needed to better understand this subgroup of children of parents with AUD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Alcohol use disorder (AUD) is a highly prevalent and often debilitating condition associated with high morbidity and mortality. Current AUD medications have limited efficacy and uptake. Alternative pharmacological options are needed., Methods: We constructed a mechanistic tree of all US Food and Drug Administration approved medications and used a tree-based scan statistic, TreeScan, to identify medications associated with greater than expected improvements in alcohol consumption. Our cohort included all United States (US) Department of Veterans Affairs (VA) patients with a diagnosis of AUD between 10/1/1999 and 9/30/2019 with multiple Alcohol Use Disorders Identification Test-Consumption Module scores within the VA electronic health record data., Results: Medications statistically associated with decreased alcohol consumption had, at large, minor effect sizes. Medications used in the treatment of chronic or life-threatening conditions like diabetes, chronic kidney disease, hepatitis C virus, or cancer produced larger effect sizes. Asenapine, an atypical antipsychotic, had a large effect with an observed to expected ratio of 1.78 (p = 0.003). Our findings were replicated in a propensity score matched population., Conclusion: Most medications significantly associated with decreased alcohol consumption in our analysis were either contraindicated with alcohol or likely attributable to patients abstaining from alcohol due to severe illness. However, the large effect of asenapine is notable, and a worthwhile candidate for more careful analysis., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Published by Elsevier Inc.)

Objectives: This study aimed to evaluate the validity of World Health Organization (WHO) risk drinking level reductions as meaningful endpoints for clinical practice and research. This study examined whether such reductions were associated with a lower likelihood of a current alcohol use disorder (AUD) diagnosis and fewer AUD criteria., Methods: We conducted a secondary data analysis to address these objectives using data from a multisite randomized controlled trial of gabapentin enacarbil extended release in treating moderate to severe AUD among adults (N = 346). Participants received gabapentin enacarbil extended release or placebo for 6 months. The timeline follow-back was used to assess WHO risk drinking level reductions, and the Mini-International Neuropsychiatric Interview was used to assess Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria at baseline (past year) and end of treatment (past month)., Results: Most participants (80.1%) achieved at least a 1-level reduction in the WHO risk drinking levels from baseline to end of treatment, and nearly half of participants (49.8%) achieved at least a 2-level reduction. At least a 1-level reduction or at least a 2-level reduction in WHO risk drinking level predicted lower odds of an active AUD diagnosis (1-level: odds ratio, 0.74 [95% confidence interval (CI), 0.66-0.84]; 2-level: odds ratio, 0.71 [95% CI, 0.64-0.79]) and fewer AUD criteria (1-level: B , -1.66 [95% CI, -2.35 to -0.98]; 2-level: B , -1.76 [95% CI, -2.31 to -1.21]) at end of treatment., Conclusions: World Health Organization risk drinking level reductions correlate with Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria, providing further evidence for their use as endpoints in alcohol intervention trials, which has potential implications for broadening the base of AUD treatment., (Copyright © 2024 American Society of Addiction Medicine.)

Background: This study assesses the psychometric properties of DSM-5 criteria of AUD in older Swedish adolescents using item response theory models, focusing specifically on the precision of the scale at the cut-offs for mild, moderate, and severe AUD., Methods: Data from the second wave of Futura01 was used. Futura01 is a nationally representative cohort study of Swedish people born 2001 and data for the second wave was collected when participants were 17/18 years old. This study included only participants who had consumed alcohol during the past 12 months (n = 2648). AUD was measured with 11 binary items. A 2-parameter logistic item response theory model (2PL) estimated the items' difficulty and discrimination parameters., Results: 31.8% of the participants met criteria for AUD. Among these, 75.6% had mild AUD, 18.3% had moderate, and 6.1% had severe AUD. A unidimensional AUD model had a good fit and 2PL models showed that the scale measured AUD over all three cut-offs for AUD severity. Although discrimination parameters ranged from moderate (1.24) to very high (2.38), the more commonly endorsed items discriminated less well than the more difficult items, as also reflected in less precision of the estimates at lower levels of AUD severity. The diagnostic uncertainty was pronounced at the cut-off for mild AUD., Conclusion: DSM-5 criteria measure AUD with better precision at higher levels of AUD severity than at lower levels. As most older adolescents who fulfil an AUD diagnosis are in the mild category, notable uncertainties are involved when an AUD diagnosis is set in this group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Alcohol-related harm, a major cause of disease burden globally, affects people along a spectrum of use. When a harmful pattern of drinking is present in the absence of significant behavioral pathology, low-intensity brief interventions that provide information about health consequences of continued use provide large health benefits. At the other end of the spectrum, profound behavioral pathology, including continued use despite knowledge of potentially fatal consequences, warrants a medical diagnosis, and treatment is strongly indicated. Available behavioral and pharmacological treatments are supported by scientific evidence but are vastly underutilized. Discovery of additional medications, with a favorable balance of efficacy versus safety and tolerability can improve clinical uptake of treatment, allow personalized treatment, and improve outcomes. Here, we delineate the clinical conditions when pharmacotherapy should be considered in relation to the main diagnostic systems in use and discuss clinical endpoints that represent meaningful clinical benefits. We then review specific developments in three categories of targets that show promise for expanding the treatment toolkit. GPCRs remain the largest category of successful drug targets across contemporary medicine, and several GPCR targets are currently pursued for alcohol-related indications. Endocrine systems are another established category, and several promising targets have emerged for alcohol indications. Finally, immune modulators have revolutionized treatment of multiple medical conditions, and they may also hold potential to produce benefits in patients with alcohol problems.

Alcohol consumption continues to be prevalent and is on the rise in many countries, posing a grave risk for the health and wellbeing of millions and creating a strain on health services worldwide. A hopeful trend has emerged, however, as consumers' growing preference for healthier, sustainable lifestyles has led traditional alcoholic brands to innovate, launching reduced or non-alcoholic (NoLo) options. This aligns with the SDGs and is reflected in NoLo spirits representing four of Spain's top ten disruptive innovations of 2022. This paper uses a mixed methodology in a qualitative-quantitative sequential approach to gain insight into this phenomenon. The study involved 13 in-depth interviews with HoReCa (an acronym for Hotels, Restaurants, and Caterings) professionals and four focus groups among consumers. Second, behavioral reasoning theory (BRT) was used in a quantitative study aiming to explore motivations for and against consuming NoLo spirits. Data from a survey of 620 participants was conducted and analyzed using SEM-PLS to measure the antecedents of consumer's behavioral intention towards NoLo spirits and to gauge the potential for marketing opportunities. The research reveals that the purchase intention of NoLo spirits is strongly related to health consciousness, while enjoying the effects of alcohol for fun and entertainment, and the social pressure to drink hinders its consumption. In addition, it was found that "reasons for" are more substantial than "reasons against" the consumption of those beverages, differing significantly by age group. Results offer implications for theory and practice, including recommendations for practitioners and regulators willing to improve sustainability in the industry. Further, this paper helps augment the innovation adoption literature by using BRT in the paradoxical context of consumers' increasing alcohol abuse despite their professed attempts to adopt healthier lifestyles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Alcohol use disorder is associated with overvaluation of alcohol relative to other rewards, in part due to dynamic increases in value in response to alcohol-related cues. In a neuroeconomic framework, alcohol cues increase behavioral economic demand for alcohol, but the neural correlates these cue effects are unknown. This functional magnetic resonance imaging study combined a neuroeconomic alcohol purchase task with an alcohol cue exposure in 72 heavy drinkers with established sensitivity to alcohol cues (51 % female; mean age=33.74). Participants reported how many drinks they would consume from $0-$80/drink following exposure to neutral and alcohol images in a fixed order. Participants purchased significantly more drinks in the alcohol compared to the neutral condition, which was also evident for demand indices (i.e., intensity, breakpoint, Omax, elasticity; ps<0.001; ds=0.46-0.92). Alcohol purchase decisions were associated with activation in rostral middle and medial frontal gyri, anterior insula, posterior parietal cortex, and dorsal striatum, among other regions. Activation was lower across regions in the alcohol relative to neutral cue condition, potentially due to greater automaticity of choices in the presence of alcohol cues or attenuation of responses due to fixed cue order. These results contribute to growing literature using neuroeconomics to understand alcohol misuse and provide a foundation for future research investigating decision-making effects of environmental alcohol triggers., Competing Interests: Declaration of competing interest J.M. is a Principal and Senior Scientist with Beam Diagnostics, Inc. and a Consultant to Clairvoyant Therapeutics, Inc. Neither organization had any role in the current research. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss the diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry., Prim Care Companion CNS Disord 2024;26(3):23f03644 ., Author affiliations are listed at the end of this article., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Background and Aims: Relapse is common in alcohol dependence (AD) and alcohol use disorder (AUD), so alcohol reduction therapy should be measured over as long a period as possible; however, existing reviews do not consider the duration of treatment and therefore alcohol reduction therapy may not have been appropriately evaluated. This review evaluated the efficacy and safety of alcohol reduction pharmacotherapy in patients with AD or AUD according to the duration of treatment., Methods: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) that assessed 15 pharmacological agents. MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov and the International Clinical Trials Registry Platform were searched for eligible trials through to May 2021. Outcomes were heavy drinking days (HDD), total alcohol consumption (TAC), any adverse event and days without drinking., Results: Fifty-five RCTs (n = 8891) were included. Nalmefene was superior to placebo for reducing HDD (standard mean difference [SMD] -0.28, 95% confidence interval [CI] -0.37, -0.18) and TAC (SMD -0.25, 95% CI -0.35, -0.16) in the long-term, but not in the short-term. Topiramate was superior to placebo for reducing HDD (SMD -0.35, 95% CI -0.59, -0.12) and days without drinking (SMD 0.46, 95% CI 0.11, 0.82), and baclofen was superior for reducing TAC (SMD -0.70, 95% CI -1.29, -0.11), in the short-term. The frequency of adverse events was higher with nalmefene and topiramate than with placebo., Conclusion: Nalmefene, topiramate and baclofen may be effective as alcohol reduction pharmacotherapy; however, only nalmefene has demonstrated long-term efficacy, and nalmefene and topiramate have a significantly higher frequency of adverse events compared with placebo., (© 2024 Society for the Study of Addiction.)

Competing Interests: SR-E is supported by the National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre (NIHR203310). AD has received a NIHR Liver Disease Research Partnership Grant (Chief Investigator) on alcohol-related liver disease, with payments made to his institution. WR has received royalties or licenses from Siemens Healthineers, as the inventor of the Enhanced Liver Fibrosis test used in diagnosis and assessment of alcohol-related liver disease, and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, and educational events from Siemens Healthineers. JRM receives salary support from University of Nottingham and Medical Research Council UK. All other authors declared no competing interests.

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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Existing literature suggests the co-occurrence of post-traumatic stress disorder (PTSD) and psychosis among young adults is related to hazardous drinking. However, the influencing mechanisms among these co-occurrences are inconclusive. Thus, this study aimed to investigate the symptomatic associations between PTSD, psychosis, and hazardous drinking., Methods: This study included 96,218 young Chinese adults, divided into three groups (PTSD, Psychosis, and co-occurring PTSD-Psychosis). PTSD, psychosis, and hazardous drinking were measured by the ten-item Trauma Screening Questionnaire, the seven-item Psychosis Screener Scale, and the four-item Alcohol Use Disorders Identification Test, respectively. Network analysis was utilized to explore and compare the symptomatic correlation between PTSD, psychosis, and hazardous drinking., Results: In this study, the most crucial symptom (both central and bridge) was "delusion of control" among the three networks. Hazardous drinking was another main bridge symptom. Compared to the Psychosis group and the co-occurring PTSD-Psychosis group, "Delusion of reference or persecution" to "Grandiose delusion" was the strongest edge in "the network structure of the PTSD group"., Limitations: The cross-sectional study cannot determine the causal relationship. Applying self-reporting questionnaires may cause inherent bias. Young adult participants limited the generalization of the results to other groups., Conclusions: Among the three network structures, delusion of control was the most crucial symptom, and hazardous drinking was another bridge symptom; the edge of delusion of reference or persecution and grandiose delusion was strongest in the PTSD group's network. Efforts should be taken to develop diverse targeted interventions for these core symptoms to relieve PTSD, psychosis, and hazardous drinking in young adults., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Children whose parents have alcohol use problems are at an increased risk of several negative consequences, such as poor school performance, an earlier onset of substance use, and poor mental health. Many would benefit from support programs, but the figures reveal that only a small proportion is reached by existing support. Digital interventions can provide readily accessible support and potentially reach a large number of children. Research on digital interventions aimed at this target group is scarce. We have developed a novel digital therapist-assisted self-management intervention targeting adolescents whose parents had alcohol use problems. This program aims to strengthen coping behaviors, improve mental health, and decrease alcohol consumption in adolescents., Objective: This study aims to examine the effectiveness of a novel web-based therapist-assisted self-management intervention for adolescents whose parents have alcohol use problems., Methods: Participants were recruited on the internet from social media and websites containing health-related information about adolescents. Possible participants were screened using the short version of the Children of Alcoholics Screening Test-6. Eligible participants were randomly allocated to either the intervention group (n=101) or the waitlist control group (n=103), and they were unblinded to the condition. The assessments, all self-assessed, consisted of a baseline and 2 follow-ups after 2 and 6 months. The primary outcome was the Coping With Parents Abuse Questionnaire (CPAQ), and secondary outcomes were the Center for Epidemiological Studies Depression Scale, Alcohol Use Disorders Identification Test (AUDIT-C), and Ladder of Life (LoL)., Results: For the primary outcome, CPAQ, a small but inconclusive treatment effect was observed (Cohen d=-0.05 at both follow-up time points). The intervention group scored 38% and 46% lower than the control group on the continuous part of the AUDIT-C at the 2- and 6-month follow-up, respectively. All other between-group comparisons were inconclusive at either follow-up time point. Adherence was low, as only 24% (24/101) of the participants in the intervention group completed the intervention., Conclusions: The findings were inconclusive for the primary outcome but demonstrate that a digital therapist-assisted self-management intervention may contribute to a reduction in alcohol consumption. These results highlight the potential for digital interventions to reach a vulnerable, hard-to-reach group of adolescents but underscore the need to develop more engaging support interventions to increase adherence., Trial Registration: ISRCTN Registry ISRCTN41545712; https://www.isrctn.com/ISRCTN41545712?q=ISRCTN41545712., International Registered Report Identifier (irrid): RR2-10.1186/1471-2458-12-35., (©Håkan Wall, Helena Hansson, Ulla Zetterlind, Pia Kvillemo, Tobias H Elgán. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 10.04.2024.)

Excessive and uncontrolled consumption of alcohol can cause alcohol use disorder (AUD), but its pharmacological mechanisms are not fully understood. Inhibiting the reverse mode activity of the sodium-calcium exchanger (NCX) can reduce the risk of alcohol withdrawal seizures, suggesting that NCX could play a role in controlling alcohol consumption. Here, we investigated how two potent inhibitors of NCX reverse mode activity, SN-6 (NCX1) and KB-R7943 (NCX3), affect voluntary alcohol consumption in adult male and female rats using the intermittent alcohol access two-bottle choice paradigm. Initially, animals were trained to drink 7.5% ethanol and water for four weeks before administering SN-6 and KB-R7934. Afterward, their alcohol intake, preference, and water intake were recorded 2 and 24 h after exposure to water and 7.5% ethanol. SN-6 significantly reduced alcohol consumption by 48% in male and 36% in female rats without affecting their water intake. Additionally, SN-6 significantly reduced alcohol preference in females by 27%. However, KB-R7943 reduced alcohol consumption by 42% in female rats and did not affect alcohol preference or water intake. These findings suggest that alcohol exposure increased NCX reverse activity, and targeting NCX1 could be an effective strategy for reducing alcohol consumption in subjects susceptible to withdrawal seizures.

Ethanol is one of the psychoactive substances most used by young individuals, usually in an intermittent and episodic manner, also called binge drinking. In the adolescent period, brain structures undergo neuromaturation, which increases the vulnerability to psychotropic substances. Our previous studies have revealed that ethanol binge drinking during adolescence elicits neurobehavioral alterations associated with brain damage. Thus, we explored the persistence of motor function impairment and cerebellum damage in the context of ethanol withdrawal periods (emerging adulthood and adult life) in adolescent female rats. Female Wistar rats (35 days old) received orally 4 cycles of ethanol (3.0 g/kg/day) or distilled water in 3 days on-4 days off paradigm (35th until 58th day of life). Motor behavioral tests (open field, grip strength, beam walking, and rotarod tests) and histological assays (Purkinje's cell density and NeuN-positive cells) were assessed on the 1-, 30-, and 60-days of binge alcohol exposure withdrawal. Our findings demonstrate that the adolescent binge drinking exposure paradigm induced cerebellar cell loss in all stages evaluated, measured through the reduction of Purkinje's cell density and granular layer neurons. The cerebellar tissue alterations were accompanied by behavioral impairments. In the early withdrawal, the reduction of spontaneous movement, incoordination, and unbalance was seen. However, the grip strength reduction was found at long-term withdrawal (60 days of abstinence). The cerebellum morphological changes and the motor alterations persisted until adulthood. These data suggest that binge drinking exposure during adolescence causes motor function impairment associated with cerebellum damage, even following a prolonged withdrawal, in adult life., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Studies indicate that bariatric surgery is associated with an increased risk of alcohol use disorder (AUD). It is considered some patients develop the disorder after surgery, without having antecedents of preoperative alcohol problems. This qualitative study aimed to explore the experiences of people who developed AUD postoperatively and understand how they make sense of the onset of this disorder. A semi-directed interview was carried out with eight adults who had undergone bariatric surgery and developed AUD de novo postoperatively. Data were analysed using interpretative phenomenological analysis. Four superordinate themes emerged: (1) 'losing control over drinking and self after surgery'; (2) 'feelings of guilt, shame and loss contrasted with perceptions of still being lucky'; (3) 'trying to make sense of the onset of AUD'; and (4) 'retrospective evaluation of bariatric surgery and preoperative information'. These themes indicated loss of control was a central aspect of participant's experiences of postoperative alcohol consumption. AUD was associated with negative emotions and cognitions, but several participants still considered themselves lucky. All tried to make sense of this disorder's onset; many felt they would not have developed AUD if they had not undergone surgery. The onset of AUD influenced their current perceptions and feelings about surgery and the preoperative information regarding AUD risks. Taken together, these results provide insight into the subjective experience of suffering from new-onset AUD post-surgery. However, more studies are necessary to gain a better understanding of the physical and psychological implications of postoperative AUD., (© 2023 World Obesity Federation.)

The increase in alcohol consumption in society has not only led to a number of medical issues but has also become a matter of considerable legal importance. Thus, there is both scientific interest and the necessity to diagnose alcohol abuse in the application of the provisions of the law through laboratory tests that ensure maximum objectivity. The purpose of this work is to study and compare the diagnostic performance of two of the main markers of alcohol abuse, serum carbohydrate-deficient transferrin (CDT) and Ethyl glucuronide (EtG) in a group of 336 driving under the influence (DUI) of alcohol offenders. Thus, it is possible to establish the best marker of alcohol consumption in order to assess the fitness to drive of DUI subjects.EtG was detected in 55 hair samples, while CDT was detected in 5 blood samples. Of the EtG-positive subjects 96,4% had CDT values below the cut-off. While CDT refers to an alcohol consumption of approximately the previous 10 days, EtG allows to detect an excessive alcohol consumption of the last few months. Because of these two different time-windows, EtG proves to be more reliable, since it is more difficult for subjects to change their drinking practice to test negative to toxicological analysis. The determination of Ethyl glucuronide on hair matrix is a valuable tool for the diagnosis of alcohol abuse, with high sensitivity and specificity and certainly greater reliability than traditional markers such as CDT, being a direct marker of alcohol consumption., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Estimating occupational disparity in heavy drinking jointly for weekdays and the weekend may be misleading for prevention purposes, because reasons for disparity in both periods may differ. The main objective was to assess occupational disparity in heavy average drinking (HAD) by week period and sex. 42,108 employees aged 16-64 were recruited from national surveys in Spain between 2011 and 2020. The outcome was HAD, defined as daily alcohol intake over 20 g (men) or 10 g (women). Occupation was classified in 15 categories. HAD adjusted prevalence ratios (HAD-aPRs) taking all occupations as reference, and relative adjusted excess prevalences (HAD-aEPs) comparing the weekend to weekdays in each occupation, were estimated using Poisson regression models with robust variance adjusted for sociodemographic and health covariates. The HAD-aPRs comparing each occupation with all occupations ranged 0.63-1.92 on weekdays and 0.65-1.45 on the weekend, with the highest aPRs on weekdays in construction, hospitality and primary-sector workers (1.92-1.62). The weekend-weekdays HAD-aEPs by occupation ranged 2.60-8.33, with the highest values in technicians/administrators, other professionals, teachers and health professionals (8.33-6.44). The global aEP was higher in women (6.04) than in men (3.92), especially in occupations just mentioned (8.70-11.73 in women vs. 3.64-6.32 in men). There was a considerable relative disparity in HAD risk between occupations on weekdays, with the highest risks in certain low-skilled occupations. Such disparity decreased on the weekend. The relative weekend increase in HAD risk was greater in women and in certain high-skilled occupations. This should be considered when designing prevention interventions on harmful drinking., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Wrist-worn alcohol biosensors continuously and discreetly record transdermal alcohol concentration (TAC) and may allow alcohol researchers to monitor alcohol consumption in participants' natural environments. However, the field lacks established methods for signal processing and detecting alcohol events using these devices. We developed software that streamlines analysis of raw data (TAC, temperature, and motion) from a wrist-worn alcohol biosensor (BACtrack Skyn) through a signal processing and machine learning pipeline: biologically implausible skin surface temperature readings (< 28°C) were screened for potential device removal and TAC artifacts were corrected, features that describe TAC (e.g., rise duration) were calculated and used to train models (random forest and logistic regression) that predict self-reported alcohol consumption, and model performances were measured and summarized in autogenerated reports. The software was tested using 60 Skyn data sets recorded during 30 alcohol drinking episodes and 30 nonalcohol drinking episodes. Participants ( N = 36; 13 with alcohol use disorder) wore the Skyn during one alcohol drinking episode and one nonalcohol drinking episode in their natural environment. In terms of distinguishing alcohol from nonalcohol drinking, correcting artifacts in the data resulted in 10% improvement in model accuracy relative to using raw data. Random forest and logistic regression models were both accurate, correctly predicting 97% (58/60; AUC-ROCs = 0.98, 0.96) of episodes. Area under TAC curve, rise duration of TAC curve, and peak TAC were the most important features for predictive accuracy. With promising model performance, this protocol will enhance the efficiency and reliability of TAC sensors for future alcohol monitoring research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Harmful alcohol consumption is a major socioeconomic burden to the health system, as it can be the cause of mortality of heavy alcohol drinkers. The dopaminergic (DAergic) system is thought to play an important role in the pathogenesis of alcohol drinking behaviour; however, its exact role remains elusive. Fibroblast growth factor 2 (FGF-2), a neurotrophic factor, associated with both the DAergic system and alcohol consumption, may play an important role in DAergic neuroadaptations during alcohol abuse. Within this study, we aimed to clarify the role of endogenous FGF-2 on the DAergic system and whether there is a possible link to alcohol consumption. We found that lack of FGF-2 reduces the alcohol intake of mice. Transcriptome analysis of DAergic neurons revealed that FGF-2 knockout (FGF-2 KO) shifts the molecular fingerprint of midbrain dopaminergic (mDA) neurons to DA subtypes of the ventral tegmental area (VTA). In line with this, proteomic changes predominantly appear also in the VTA. Interestingly, these changes led to an altered regulation of the FGF-2 signalling cascades and DAergic pathways in a region-specific manner, which was only marginally affected by voluntary alcohol consumption. Thus, lack of FGF-2 not only affects the gene expression but also the proteome of specific brain regions of mDA neurons. Our study provides new insights into the neuroadaptations of the DAergic system during alcohol abuse and, therefore, comprises novel targets for future pharmacological interventions., (© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic-assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4-12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5-MeO-DMT. Primarily, 5-MeO-DMT is able to induce mystical experiences and ego-dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood-related comorbidities consistent with the negative reinforcement and self-medication paradigms. In addition, preliminary evidence indicates that 5-MeO-DMT modulates neural oscillations that might subserve ego-dissolution (increases in gamma), psychological flexibility and mindfulness (increases in theta), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5-MeO-DMT is characterized by neuroplasticity, anti-inflammation, 5-HT 2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood-related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action., (© 2024 The Author. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Social cognition impairments are a common feature of alcohol use disorders (AUD). However, it remains unclear whether these impairments are solely the consequence of chronic alcohol consumption or whether they could be a marker of vulnerability., Methods: The present study implemented a family history approach to address this question for a key process of social cognition: theory of mind (ToM). Thirty healthy adults with a family history of AUD (FH+) and 30 healthy adults with a negative family history of AUD (FH-), matched for age, sex, and education level, underwent an fMRI cartoon-vignette paradigm assessing cognitive and affective ToM. Participants also completed questionnaires evaluating anxiety, depressive symptoms, childhood trauma, and alexithymia., Results: Results indicated that FH+ individuals differed from FH- individuals on affective but not cognitive ToM processing, at both the behavioral and neural levels. At the behavioral level, the FH+ group had lower response accuracy for affective ToM compared with the FH- group. At the neural level, the FH+ group had higher brain activations in the left insula and inferior frontal cortex during affective ToM processing. These activations remained significant when controlling for depressive symptoms, anxiety, and childhood trauma., Conclusions: These findings highlight difficulties during affective ToM processing among first-degree relatives of AUD patients, supporting the idea that some of the impairments exhibited by these patients may already be present before the onset of AUD and may be considered a marker of vulnerability.

Objective: Although numerous reports document college students' risk-taking behaviors, few examine these behaviors in a developmental context. The purpose of this study was to examine female freshmen college students' pre-college experiences and parenting influences on first semester experiences with alcohol misuse, sexual risk-taking, and adverse outcomes, including violence., Methods: We surveyed 229 female freshman residential college students at the end of their first semester in college., Results: Participants who drank frequently in high school were more likely to binge drink in college and regret doing something while drinking. Mother-daughter closeness and parental discussions of sexual risks, personal safety and danger avoidance were associated with a reduced likelihood of regretting doing something while drinking, experiencing sexual violence, and having sex without a condom. Parental provision of alcohol was associated with alcohol misuse., Conclusion: These findings provide a life course perspective on the development of risk behaviors and adverse outcomes during emerging adulthood.

Aims: The aim of the study was to disentangle the contributions of alcohol and alcohol-related liver disease (ALD) towards dementia by independently measuring the association between alcohol use disorder (AUD) alone and ALD with dementia., Design: This was a nation-wide cohort study., Setting: The study was conducted in Sweden from 1987 to 2020., Participants: DELIVER (DEcoding the epidemiology of LIVER disease in Sweden) cohort, containing administrative codes on patients with chronic liver disease from the National Patient Register and other registers between 1987 and 2020., Measurements: International Classification of Disease 9th (ICD-9) and 10th (ICD-10) version codes were used to define the presence of AUD, ALD and dementia. The associations of AUD alone and ALD with incident dementia were estimated using Cox regression models adjusting for potential confounders. Cumulative incidences were also calculated accounting for competing risks of death., Findings: A total of 128 884 individuals with AUD alone, 17 754 with ALD and 2 479 049 controls were identified. During a median follow-up of 8.9 years, 13 395 (10.4%), 2187 (12.3%) and 138 925 (5.6%) dementia cases were identified in these groups, respectively. Dementia rates were increased in AUD alone [adjusted hazard ratio (aHR) = 4.6, 95% confidence interval (CI) = 4.5-4.6] and in ALD (aHR = 8.6, 95% CI = 8.3-9.0) compared with controls. AUD alone was also associated with increased rates of vascular dementia (aHR = 2.3, 95% CI = 2.2-2.5) and Alzheimer's disease (aHR = 1.4, 95% CI = 1.3-1.4), while ALD was only associated with vascular dementia (aHR = 2.7, 95% CI = 2.3-3.2). The median age at dementia diagnosis was 67 years [interquartile range (IQR) = 56-76] in AUD alone and 63 years (IQR = 56-71) in ALD compared with 85 years (IQR = 79-89) in controls., Conclusion: In Sweden, patients with alcohol use disorder (AUD) appear to have increased rates of dementia and diagnosis at a younger age, compared with patients without AUD. Concurrent alcohol-related liver disease appears to increase the diagnosis rate and lower the median age further., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Brain damage related to alcohol consumption is associated with impairments in cognitive functions, among which memory and verbal learning stand out. The main objective is to evaluate memory and verbal learning in a sample of 111 patients with alcohol use disorder (AUD) versus 78 with major depressive disorder (MDD) and 100 healthy controls. The evaluation included sociodemographic and clinical variables, the Hamilton Depression Scale (HDRS) and the California Verbal Learning Test (CVLT). One-way ANOVA was used for comparisons between the 3 groups and two-way ANCOVAS including different covariates. The one-way ANOVA shows that patients with AUD and MDD had scores similar to each other and lower than those of the control group (p < 0.001), with the exception of the Cued CVLT (worse scores in MDD vs AUD, p < 0.001). After including age, sex and years of completed studies as covariates, the differences between the AUD and MDD groups persisted compared to the control group (p ≤ 0.003) in all indices except for the Immediate Free CVLT and the Cued CVLT (worse performance in MDD vs AUD, p = 0.022 and p = 0.035, respectively). In the second ANCOVA, after controlling for depression severity, differences were only detected between AUD patients and healthy controls (p ≤ 0.007). Patients with AUD present a significant impairment in learning and verbal memory when compared with patients with MDD and with healthy people.

This article traces the origin of various charts and tables delineating the stages of alcohol influence in relation to the clinical signs and symptoms of drunkenness and a person's blood-alcohol concentration (BAC). In forensic science and legal medicine, the most widely used such table was created by Professor Kurt M. Dubowski (University of Oklahoma). The first version of the Dubowski alcohol table was published in 1957, and minor modifications appeared in various articles and book chapters until the final version was published in 2012. Seven stages of alcohol influence were identified including subclinical (sobriety), euphoria, excitement, confusion, stupor, alcoholic coma and death. The BAC causing death was initially reported as 0.45+ g%, although the latest version cited a mean and median BAC of 0.36 g% with a 90% range from 0.21 g% to 0.50 g%. An important feature of the Dubowski alcohol table was the overlapping ranges of BAC for each of the stages of alcohol influence. This was done to reflect variations in the physiological effects of ethanol on the nervous system between different individuals. Information gleaned from the Dubowski table is not intended to apply to any specific individual but more generally for a population of social drinkers, not regular heavy drinkers or alcoholics. Under real-world conditions, much will depend on a person's age, race, gender, pattern of drinking, habituation to alcohol and the development of central nervous tolerance. The impairment effects of ethanol also depend to some extent on whether observations are made on the rising or declining phase of the blood-alcohol curve (Mellanby effect). There will always be some individuals who do not exhibit the expected behavioral impairment effects of ethanol, such as regular heavy drinkers and those suffering from an alcohol use disorder., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alcohol consumption causes both physical and psychological harm and is a leading risk factor for noncommunicable diseases. Digital alcohol interventions have been found to support those looking for help by giving them tools for change. However, whether digital interventions can help tackle the long-term societal consequences of harmful alcohol consumption in a cost-effective manner has not been adequately evaluated. In this Viewpoint, we propose that studies of digital alcohol interventions rarely evaluate the consequences of wider dissemination of the intervention under study, and that when they do, they do not take advantage of modeling techniques that allow for appropriately studying consequences over a longer time horizon than the study period when the intervention is tested. We argue that to help decision-makers to prioritize resources for research and dissemination, it is important to model long-term costs and health outcomes. Further, this type of modeling gives important insights into the context in which interventions are studied and highlights where more research is required and where sufficient evidence is available. The viewpoint therefore invites the researcher not only to reflect on which interventions to study but also how to evaluate their long-term consequences., (©Katarina Ulfsdotter Gunnarsson, Martin Henriksson, Marcus Bendtsen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 27.03.2024.)

Alcohol use disorder (AUD) is the most prevalent substance use disorder worldwide. Acamprosate and naltrexone are anti-craving drugs used in AUD pharmacotherapy. However, molecular mechanisms underlying their anti-craving effect remain unclear. This study utilized a patient-derived induced pluripotent stem cell (iPSC)-based model system and anti-craving drugs that are used to treat AUD as "molecular probes" to identify possible mechanisms associated with alcohol craving. We examined the pathophysiology of craving and anti-craving drugs by performing functional genomics studies using iPSC-derived astrocytes and next-generation sequencing. Specifically, RNA sequencing performed using peripheral blood mononuclear cells from AUD patients with extreme values for alcohol craving intensity prior to treatment showed that inflammation-related pathways were highly associated with alcohol cravings. We then performed a genome-wide assessment of chromatin accessibility and gene expression profiles of induced iPSC-derived astrocytes in response to ethanol or anti-craving drugs. Those experiments identified drug-dependent epigenomic signatures, with IRF3 as the most significantly enriched motif in chromatin accessible regions. Furthermore, the activation of IRF3 was associated with ethanol-induced endoplasmic reticulum (ER) stress which could be attenuated by anti-craving drugs, suggesting that ER stress attenuation might be a target for anti-craving agents. In conclusion, we found that craving intensity was associated with alcohol consumption and treatment outcomes. Our functional genomic studies suggest possible relationships among craving, ER stress, IRF3 and the actions of anti-craving drugs., (© 2024. The Author(s).)

Background: Alcohol use disorder (AUD) is a major clinical problem in Uganda. Explanatory models (EMs) of illness are important as they have consequences for treatment. Clinicians´ knowledge about patients´ EMs can improve understanding of the latter´s perspectives and adapting treatments. There is a lack of African studies about EMs of AUD. The aim of this study was to explore EMs for AUD among hospitalized patients and their relatives at the alcohol and drug unit (ADU) at Butabika hospital in Uganda., Methods: An adapted version of the Explanatory Model Interview Catalogue (EMIC) was used for interviews with ten patients and five relatives to investigate how both hospitalized patients with AUD and their relatives understand the disease. Data were analysed for themes with a qualitative content analysis and support of the software program, OpenCode 4.03., Results: Five major themes were identified from the patient interviews: "Context promotes AUD"; "Alcohol is part of culture"; "Spiritual causes of AUD in the community"; "Help through Western medicine and religious sources is preferred" and "Social problems and stigmatization". Six major themes identified from the interviews with relatives were: "Numerous causes of drinking alcohol"; "Devastating consequences of drinking alcohol"; "Exploiting persons with AUD"; "Others' suffering"; "Relatives struggling for help" and "Suggested solutions"., Conclusions: Patients' EMs of AUD included social and spiritual explanations. Alcohol is seen as an important part of the Ugandan culture among both patients and their relatives. The results indicate it is important in clinical contexts to investigate the EMs of the patients and relatives to individually tailor treatment interventions., (© 2024. The Author(s).)

Competing Interests: Intérêts concurrents:: Evan Wood est médecin; il travaille à l’Autorité de la santé du littoral de Vancouver pour la prise en charge du sevrage et entreprend des travaux sur la médecine des toxicomanies en milieu professionnel. Le Dr Wood est également professeur de médecine à l’Université de la Colombie-Britannique, un poste appuyé par une chaire de recherche du Canada de niveau 1 des Instituts de recherche en santé du Canada (IRSC) et il a reçu une subvention pour un projet R01 de l’Institut national des États-Unis sur l’abus de drogues, versée à l’Université de la Colombie-Britannique. Le laboratoire de recherche du Dr Wood est en outre appuyé par des subventions des IRSC versées à l’Initiative canadienne de recherche sur l’abus de substances. Il a également entrepris des travaux de consultation sur les enjeux juridiques liés aux troubles d’utilisation des substances et pour une société qui se consacre à la santé mentale appelée Numinus Wellness, dont il a été médecin-chef. Le Dr Wood a aussi reçu une rémunération sous forme d’actions ordinaires de Numinus. Il déclare avoir reçu des honoraires pour des conférences et des présentations non liées à l’industrie (p. ex., conférences universitaires ou éducatives), y compris une allocution pour la Société médicale canadienne sur l’addiction (SMCA), rémunérée à même le budget de la conférence de la SMCA; une série de séances scientifiques à l’Université Dalhousie (payée par l’université); et une conférence pour la plateforme éducative des équipes soignantes, des liens avec les services administratifs (indépendamment des travaux soumis et sans liens financiers avec l’industrie pharmaceutique). Le Dr Wood a aussi reçu une rémunération pour des rapports et témoignages d’expert sur des questions juridiques ayant trait au trouble d’utilisation des substances psychoactives, y compris de l’Association canadienne de protection médicale et de syndicats représentant des travailleurs souffrant de possibles troubles d’utilisation des substances. Il a reçu des bourses de déplacement des IRSC. Jessica Bright, Nirupa Goel et Josey Ross déclarent avoir reçu des bourses salariales du Centre sur la toxicomanie de la Colombie-Britannique, en appui à l’élaboration du présent manuscrit. Katelyn Halpape déclare avoir reçu des subventions du Programme sur l’usage et les dépendances aux substances de Santé Canada et du ministère canadien des Services aux Autochtones pour la Clinique de la douleur chronique de l’Université de la Saskatchewan. La Dre Halpape déclare aussi avoir reçu des honoraires en tant que rédactrice d’un chapitre du manuel intitulé The Clinical Handbook of Psychotropic Drugs. Aucun autre intérêt concurrent n’a été déclaré.

Competing Interests: Intérêts concurrents:: Nikki Bozinoff déclare avoir reçu des bourses de recherche de l’Academic Health Sciences Alternate Funding Program (Programme de financement alternatif de l’Académie des sciences de la santé), des Instituts de recherche en santé du Canada et de la communauté philanthropique womenmind (indépendamment du manuscrit soumis). La Dre Bozinoff a reçu une subvention du National Institute on Drug Abuse (Institut national sur la toxicomanie) (R25-DA037756), en appui du présent manuscrit, ainsi que des honoraires du Collège des médecins de famille de l’Ontario pour des activités éducatives et un paiement du Centre de toxicomanie et de santé mentale pour l’élaboration de matériel de perfectionnement professionnel continu indépendamment du présent manuscrit. Aucun autre intérêt concurrent n’a été déclaré.

Alcohol use disorder (AUD) remains a major public health concern. The dynorphin (DYN)/κ-opioid receptor (KOP) system is involved in actions of alcohol, particularly its withdrawal-associated negative affective states. This study tested the ability of LY2444296, a selective, short-acting, KOP antagonist, to decrease alcohol self-administration in dependent male and female Wistar rats at 8 h abstinence. Animals were trained to orally self-administer 10% alcohol (30 min/day for 21 sessions) and were made dependent via chronic intermittent alcohol vapor exposure for 6 weeks or exposed to air (nondependent). After 6 weeks, the effect of LY2444296 (0, 3, and 10 mg/kg, p.o.) was tested on alcohol self-administration at 8 h of abstinence. A separate cohort of rats was prepared in parallel, and their somatic withdrawal signs and alcohol self-administration were measured after LY2444296 administration at 8 h, 2 weeks, and 4 weeks abstinence. LY2444296 at 3 and 10 mg/kg significantly reduced physical signs of withdrawal in dependent rats at 8 h abstinence, only. Furthermore, 3 and 10 mg/kg selectively decreased alcohol self-administration in dependent rats at only 8 h abstinence. These results highlight the DYN/KOP system in actions of alcohol during acute abstinence, suggesting KOP antagonism could be beneficial for mitigating acute withdrawal signs and, in turn, significantly reduce excessive alcohol consumption associated with AUD., (© 2024. The Author(s).)

Aim: Alcohol use disorder (AUD) is the most prevalent form of addiction, with a great burden on society and limited treatment options. A recent clinical trial reported significant clinical benefits of deep transcranial magnetic stimulations (Deep TMS) targeting midline frontocortical areas. However, the underlying biological substrate remained elusive. Here, we report the effect of Deep TMS on the microstructure of white matter., Methods: A total of 37 (14 females) AUD treatment-seeking patients were randomized to sham or active Deep TMS. Twenty (six females) age-matched healthy controls were included. White matter integrity was evaluated by fractional anisotropy (FA). Secondary measures included brain functional connectivity and self-reports of craving and drinking units in the 3 months of follow-up period., Results: White matter integrity was compromised in patients with AUD relative to healthy controls, as reflected by the widespread reduction in FA. This alteration progressed during early abstinence (3 weeks) in the absence of Deep TMS. However, stimulation of midline frontocortical areas arrested the progression of FA changes in association with decreased craving and relapse scores. Reconstruction of axonal tracts from white-matter regions showing preserved FA values identified cortical regions in the posterior cingulate and dorsomedial prefrontal cortices where functional connectivity was persistently modulated. These effects were absent in the sham-stimulated group., Conclusions: By integrating brain structure and function to characterize the alcohol-dependent brain, this study provides mechanistic insights into the TMS effect, pointing to myelin plasticity as a possible mediator., (© 2023 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Alcohol-related liver disease is the most common indication for liver transplantation. It is essential for providers in transplantation to be informed of the state of the science in evaluation of alcohol use disorder (AUD). This review examines the broad range of approaches to the evaluation of AUD ranging from traditional interview approaches to recent literature on artificial intelligence models. The empirical support for methods of evaluation is examined. The authors discuss the use of each method in the context of patients seeking a liver transplant for alcohol-related liver disease. This review emphasizes the importance of using objective assessments so that transplant centers make evidence-based decisions and reduce cognitive bias. The review concludes with a proposed assessment battery for evaluation and bridges to future directions in the field of AUD assessment in liver transplantation., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Neurofilament light chain (NFL), as a measure of neuroaxonal injury, has recently gained attention in alcohol dependence (AD). Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme which metabolizes the alcohol breakdown product acetaldehyde. An ALDH2 single nucleotide polymorphism (rs671) is associated with less ALDH2 enzyme activity and increased neurotoxicity. We examined the blood NFL levels in 147 patients with AD and 114 healthy controls using enzyme-linked immunosorbent assay and genotyped rs671. We also followed NFL level, alcohol craving and psychological symptoms in patients with AD after 1 and 2 weeks of detoxification. We found the baseline NFL level was significantly higher in patients with AD than in controls (mean  ±  SD: 264.2  ±  261.8 vs. 72.1 ± 35.6 pg/mL, p < 0.001). The receiver operating characteristic curve revealed that NFL concentration could discriminate patients with AD from controls (area under the curve: 0.85; p < 0.001). The NFL levels were significantly reduced following 1 and 2 weeks of detoxification, with the extent of reduction correlated with the improvement of craving, depression, and anxiety (p < 0.001). Carriers with the rs671 GA genotype, which is associated with less ALDH2 activity, had higher NLF levels either at baseline or after detoxification compared with GG carriers. In conclusion, plasma NFL level was increased in patients with AD and reduced after early abstinence. Reduction in NFL level corroborated well with the improvement of clinical symptoms. The ALDH2 rs671 polymorphism may play a role in modulating the extent of neuroaxonal injury and its recovery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Problem alcohol drinking continues to be a substantial cost and burden. In addition, alcohol consumption in women has increased in recent decades, and women can have greater alcohol problems and comorbidities. Thus, there is a significant need for novel therapeutics to enhance sex-specific, individualized treatment. Heart rate (HR) and HR variability (HRV) are of broad interest because they may be both biomarkers for and drivers of pathological states. HRV reflects the dynamic balance between sympathetic (SNS, 'fight or flight') and parasympathetic (PNS, 'rest and digest') systems. Evidence from human studies suggest PNS predominance in women and SNS in men during autonomic regulation, indicating the possibility of sex differences in risk factors and physiological drivers of problem drinking. To better understand the association between HRV sex differences and alcohol drinking, we examined whether alcohol consumption levels correlated with time domain HRV measures (SDNN and rMSSD) at baseline, at alcohol drinking onset, and across 10 min of drinking, in adult female and male Wistar rats. In particular, we compared both HRV and HR measures under alcohol-only and compulsion-like conditions (alcohol + 10 mg/L quinine), because compulsion can often be a significant barrier to treatment of alcohol misuse. Importantly, previous work supports the possibility that different HRV measures could be interpreted to reflect PNS versus SNS influences. Here, we show that females with higher putative PNS indicators at baseline and at drinking onset had greater alcohol consumption. In contrast, male intake levels related to increased potential SNS measures at drinking onset. Once alcohol was consumed, HR predicted intake level in females, perhaps a pharmacological effect of alcohol. However, HRV changes were greater during compulsion-like intake versus alcohol-only, suggesting HRV changes (reduced SNS in females, reduced PNS and increased HR in males) specifically related to aversion-resistant intake. We find novel and likely clinically relevant autonomic differences associated with biological sex and alcohol drinking, suggesting that different autonomic mechanisms may promote differing aspects of female and male alcohol consumption., (© 2024 Society for the Study of Addiction.)