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OBJECTIVE: Previous work has investigated parents' reports of motives for communicating with their young adults about alcohol. While parents' self-reported motives may predict intentions to communicate, young adults' perceptions of their parents' motives may be important for understanding young adults' responses to parent alcohol communication. The present study was conducted to explore college students' perceptions of their parents' motives for alcohol communication and to investigate whether perceptions of these motives predict changes in alcohol consumption and related consequences during the transition to college. METHOD: First-year college students (N = 306) participated in a longitudinal survey study. Baseline measures at pre-matriculation (T1) included assessments of student perceptions of their parents' motives for alcohol communication and covariates (e.g., perceived peer descriptive drinking norms, parental modeling and alcohol communication, and drinking and consequences). At a 1-month follow-up (T2), students reported on their alcohol use and consequences. RESULTS: Controlling for other predictors of college student drinking, results indicate that for each one-unit increase in perceived parental reactive communication motives, the incidence rate of typical weekly drinking increased by 9%, and heavy episodic drinking (HED) increased by 21%. Conversely, the incidence rate of HED decreased by 27% for each one-unit increase in perceived maternal family history communication motives. CONCLUSIONS: These findings suggest that college students' perceptions of their parents' motives for alcohol communication can significantly influence their drinking behavior during the transition to college.

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The American Indian Enculturation Scale (AIES) was developed for American Indian populations to measure connection to traditional culture, but it has not been evaluated in Alaska Native people. While American Indian and Alaska Native individuals are grouped together, significant differences exist between groups. As a part of a randomized controlled trial for contingency management to reduce alcohol use, 160 Alaska Native adults completed the AIES. The confirmatory factor analysis indicated that a one-factor, 15-item version of the AIES, removing items 1 and 2 and correlating items 8 and 10, was a reliable (15 items; α = 0.896) and valid measure in this sample (χ2 [89] = 155.788, p<.001; CFI = 0.903; TLI = 0.886; RMSEA = 0.068 [90% confidence interval {CI} 0.050-0.086]; p<.001; SRMR = 0.060). The study provides limited evidence of enculturation's structural validity, as measured by the AIES, for Alaska Native adults. Future confirmatory work and potential adaptation is needed to evaluate the empirical utility of the AIES for Alaska Native individuals seeking help to reduce alcohol use.

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Background: Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by alcohol seeking and consumption despite negative consequences. Despite the availability of multiple treatments, patients continue to exhibit high relapse rates. Thus, biomarkers that can identify patients at risk for heightened craving are urgently needed. Mounting preclinical and clinical evidence implicates perturbations in bioactive lipid signaling in the neurobiology of craving in AUD. We hypothesize that these lipids are potential biomarkers for predicting alcohol craving in patients with AUD. Methods: This study used archival deidentified clinical data and corresponding plasma specimens from 157 participants in 3 clinical studies of AUD. We evaluated plasma levels of 8 lipid species as predictors of craving in response to in vivo alcohol and affective cues during abstinence. Results: Participants were 109 men and 48 women who met DSM-5 criteria for severe AUD. We found that plasma levels of 12- and 15-HETE, 12/15-lipoxygenase-produced proinflammatory lipids, and palmitoylethanolamide, an anti-inflammatory fatty acid amide hydrolase-regulated lipid metabolite, were differentially correlated with alcohol craving during abstinence, predicting higher craving independent of demographics, alcohol use history, and multiple therapeutic treatments. Conclusions: Our findings highlight the promise of these lipid metabolites as biomarkers of heightened alcohol craving. The results open a novel opportunity for further research and clinical evaluation of these biomarkers to optimize existing treatments and develop new therapeutics for AUD.

Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by the compulsion to seek out and consume alcohol regardless of negative consequences. Despite the availability of multiple treatment options, patients continue to exhibit high relapse rates due in part to craving during abstinence. The current study evaluated the relationship between plasma lipids and alcohol craving during abstinence to determine whether we could predict vulnerable patients independent of treatment approach and history of alcohol use.

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Background: Patients with alcohol use disorder (AUD) and high-risk opioid use are at risk of serious complications. The purpose of this study was to estimate the prevalence of and factors associated with high-risk opioid use in patients with an alcohol use problem from 2005 to 2018. Methods: This repeated cross-sectional study analyzed data from first admissions for alcohol treatment (2005-2018) to the NYS Office of Addiction Services and Supports merged with Medicaid Claims Data. High-risk opioid use was defined as opioid dose ≥50 morphine mg equivalents (MME) per day; opioid prescriptions overlapping ≥7 days; opioids for chronic pain >90 days or opioids for acute pain >7 days. Results: Patients receiving ≥50 MME increased from 690 to 3226 from 2005 to 2010; then decreased to 2330 in 2018. From 2005-2011, patients with opioid prescriptions overlapping ≥7 days increased from 226 to 1594 then decreased to 892 in 2018. From 2005-2010, opioid use >7 days for acute pain increased from 133 to 970 and plateaued after 2010. From 2005-2018, patients who received opioids >90 days for chronic pain trended from 186 to 1655. White patients, females, age 36-55, patients with chronic and acute pain diagnoses had the highest rates of high-risk use. Conclusions: The prevalence of high-risk opioid use in patients with alcohol use problems increased from 2005 to 2011, and generally decreased after 2010. However, prevalence of opioids >90 days for chronic pain trended up from 2005 to 2018. High-risk opioid use among patients with AUD emphasizes the need to develop interventional strategies to improve patient care.

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Background: There are few efficient treatment options for alcohol addiction, which continues to be a serious public health concern. The possible contribution of gut microbiota to the onset and progression of alcohol addiction has been brought to light by recent studies. Probiotics have become a cutting-edge intervention in the treatment of alcohol consumption disorder because of its favorable effects on gut health. The purpose of this systematic review is to assess the body of research on the advantages of probiotics in treating alcoholism and associated neuroinflammatory conditions. Methods: To find pertinent research published from January 2012 to 2023, a thorough search of electronic databases, including PubMed, Scopus, Google Scholar and Web of Science, was carried out. Included were studies looking at how probiotics affect neuroinflammation, gut- brain axis regulation, alcohol addiction, and related behaviors. Findings: Several investigations have shown how beneficial probiotics are in reducing systemic inflammation and alcoholic liver disease (ALD). Probiotic treatments successfully corrected the imbalance of microbiota, decreased intestinal permeability, and stopped the passage of bacterial constituents such lipopolysaccharides (LPS) into the bloodstream. Additionally, probiotics helped to regulate neurotransmitter pathways, especially those connected to GABA, glutamate, and dopamine, which are intimately linked to behaviors related to addiction. Furthermore, it was shown that probiotics altered the expression of neurotransmitter signaling and dopamine receptors. Conclusion: There is strong evidence from this systematic study that probiotics have potential advantages in treating alcohol addiction. The potential of probiotic therapies is demonstrated by the way they modulate important neurotransmitter pathways implicated in addiction, decrease neuroinflammation, and restore the balance of gut flora. To fully investigate the therapeutic potential of probiotics in treating alcohol addiction and enhancing the general wellbeing of those afflicted by this condition, more research is necessary.

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Introduction: Depressive symptoms are linked with pain, anxiety, and substance use. Research estimating whether a reduction in depressive symptoms is linked to subsequent reductions in pain and anxiety symptoms and substance use is limited. Methods: Using data from the Veterans Aging Cohort Study, a multisite observational study of U.S. veterans, the authors used a target trial emulation framework to compare individuals with elevated depressive symptoms (Patient Health Questionnaire-9 score ≥ 10) who experienced reductions in depressive symptoms (Patient Health Questionnaire-9 score < 10) with those whose symptoms persisted (Patient Health Questionnaire-9 score ≥ 10) at the next follow-up visit (on average, 1 year later). Using inverse probability of treatment weighting, the authors estimated ORs and 95% CIs for associations between depressive symptom reduction status and improvement on the following: anxiety symptoms, pain symptoms, unhealthy alcohol use, and use of tobacco, cannabis, cocaine, and/or illicit opioids. Results: Reductions in depressive symptoms were associated with reductions in pain symptoms (OR=1.43, 95% CI=1.01, 2.02), anxiety symptoms (OR=2.50, 95% CI=1.63, 3.83), and illicit opioid use (OR=2.07, 95% CI=1.13, 3.81). Depressive symptom reductions were not associated with reductions in unhealthy alcohol use (OR=0.85, 95% CI=0.48, 1.52) or use of tobacco (OR=1.49, 95% CI=0.89, 2.48), cannabis (OR=1.07, 95% CI=0.63, 1.83), or cocaine (OR=1.28, 95% CI=0.73, 2.24). Conclusions: Reducing depressive symptoms may potentially reduce pain and anxiety symptoms and illicit opioid use. Future work should determine whether reductions achieved through antidepressant medications, behavioral therapy, or other means have comparable impact.

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BACKGROUND: Increasing evidence suggests that GLP-1 receptor agonists (GLP-1RA) have a potential use in addiction treatment. Few studies have assessed the impact of GLP-1RA on substance use disorder (SUD), particularly in humans. The study aimed to do systematic review of clinical trials to assess GLP-1RA's effect on reducing SUD in patients. METHODS: The scientific literature was reviewed using the MEDLINE, Scopus and Cochrane Library databases, following PRISMA guidelines. Studies including patients with a diagnosis of SU who were treated with GLP-1RA were selected. The primary outcome was GLP-1RA's therapeutic effect on SUD, and the secondary outcomes were therapeutic effects of GLP-1RA on weight, BMI and HbA1c. RESULTS: 1218 studies were retrieved, resulting in 507 papers after title and abstract screening. Following full-text review, only 5 articles met inclusion criteria. We incorporated a total of 630 participants utilizing Exenatide (n=3) and Dulaglutide (n=2) as GLP-1RAs. Therapeutic effect of GLP-1RA on SUD was assessed in 5 studies, with 3 demonstrating a significant decrease in SUD (alcohol and nicotine). GLP-1RA's impact on body weight, BMI, and HbA1c, was reported in 3 studies. These revealed a notable reduction in these parameters among the GLP-1RA treated group. CONCLUSION: This review will give an overview of current new findings in human studies; we suggest that the effects of GLP-1RA in SUD is a possible new option of therapy in addiction medicine.

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BACKGROUND: According to data from the Federal Statistical Office, the diagnosis of alcohol use disorder (AUD) (F 10) is the second most common main diagnosis for hospital treatment. Those affected by this disorder are often repeatedly hospitalized at short intervals due to relapses; however, little is known about the factors that influence readmission rates after initial treatment. AIM OF THE STUDY: The aim of this retrospective analysis is to analyze the effects of treatment type (qualified withdrawal treatment (QE) versus physical detoxification) and discharge mode on the probability of readmission in alcohol-dependent patients after inpatient treatment. MATERIAL AND METHODS: Data from 981 male and female alcohol-dependent patients who completed either qualified withdrawal treatment (QE) (68% men; mean age 47.6 years) or inpatient detoxification (74% men; mean age 48.0 years) were analyzed. Predictors of regular discharge were determined separately for both types of treatment using stepwise logistic regression. RESULTS: Patients who had completed a qualified withdrawal treatment were significantly more likely to be regularly discharged. Regular completion of the qualified withdrawal treatment (QE) led to a relative reduction in the readmission rate of 25.64% within 1 year compared to a physical detoxification. CONCLUSION: In order to prevent readmission and chronic courses of alcohol use disorder (AUD), qualified withdrawal treatment should always be recommended to affected patients instead of physical detoxification. Aktuelle Daten des Statistischen Bundesamtes für das Jahr 2022 zeigen, dass die Diagnose "Psychische und Verhaltensstörungen durch Alkohol (F 10.X)" die zweithäufigste Hauptdiagnose bei Krankenhausbehandlungen darstellt [13]. Im Gesundheitssystem entstehen durch dieses Erkrankungsbild und seine somatischen und psychischen Folgeerkrankungen jährlich ca. 10 Mrd. € direkte Kosten [13]. Dieser Sachverhalt wird dadurch kontrastiert, dass die Krankenkassen die qualifizierte Entzugsbehandlung (QE) als leitliniengerechte Goldstandardtherapie [4] wiederholt infrage stellen [10].

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BACKGROUND: Sexual behaviors, particularly risky sexual behavior, has become a serious public health concern among adolescents worldwide, presenting a substantial obstacle to the prevention of sexually transmitted infections, including human immunodeficiency virus (HIV). However, there is limited research using consistent and standardized methodology to examine associations between tobacco and alcohol use frequency and both total and risky sexual behaviors among adolescents. We aimed to examine the association between tobacco and/or alcohol use with both total and risky sexual behaviors among adolescents worldwide. METHODS: Data were collected from the Global School-based Student Health Survey, which comprised 211,847 adolescents aged 12-17 years from 59 countries. The frequency of tobacco or alcohol use during the past 30 days was categorized as 0, 1-2, 3-5, 6-9, or ≥ 10 days. Tobacco and alcohol use were also categorized as non-use, tobacco use alone, alcohol use alone, and combined use. Multi-variable logistic regression analysis was used to examine both the independent and combined associations of tobacco and alcohol use with total and risky sexual behaviors. RESULTS: Compared with no tobacco use, the odds ratio of engaging in sexual intercourse increased with the frequency of tobacco use from 1 to 2 days to ≥ 10 days (total: 2.03 [95% confidence interval 1.47-2.81] to 3.98[2.63-6.03]; risky: 2.43[1.75-3.38] to 4.21[3.26-5.42]), as well as with the frequency of alcohol use. Overall, combined users had greater likelihood of both total and risky sexual behaviors than tobacco users alone, alcohol users alone, and non-users. Similarly, the association between risky sexual behaviors and tobacco use alone was more pronounced among adolescent girls (vs. adolescent boys), as were those of risky sexual behaviors with alcohol use alone among younger adolescents aged 12-14 years (vs. aged 15-17 years) and with tobacco and/or alcohol use among adolescents in the Western Pacific region (vs. Regions of Africa and Americas). CONCLUSIONS: Our findings suggest independent and combined associations between tobacco and/or alcohol use with sexual behaviors among adolescents, with variations across age, sex, and WHO region.

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Background: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) commonly co-occur and are associated with more severe symptomatology than either disorder alone, increased risk of suicide, and poorer response to existing treatments. A promising therapeutic intervention is the integration of 3,4-methylenedioxymethamphetamine (MDMA) and psychotherapy. The Food and Drug Administration (FDA) designated MDMA- assisted therapy (MDMA-AT) as a Breakthrough Therapy for PTSD based on results from six Phase 2 clinical trials. Case data from the first study evaluating MDMA-AT study for AUD found the treatment was well tolerated and alcohol use was significantly reduced post treatment. Methods: This manuscript reports the premise, design, and methodology of the first open-label trial of MDMA-AT for military veterans (N = 12) with PTSD and AUD. Neuroimaging and biomarker data are included to evaluate brain changes, and neuroinflammation, pre-post treatment. Conclusions: The clinical component (comorbidity) and the regulatory processes (Schedule I drug) for setting up this clinical trial are long and complex. The research community will benefit from this work to establish common clinical trial outcomes, standardized protocols, and risk assessments for FDA approval. Clinicaltrialsgov: NCT05943665.

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Background & Aims: People who drink alcohol excessively are at increased risk of developing metabolic dysfunction and alcohol-related liver disease (MetALD) or the more severe form alcohol-related liver disease (ALD). One of the most significant challenges concerns the early detection of MetALD/ALD. Previously, we have demonstrated that the lysosomal enzyme cathepsin D (CTSD) is an early marker for metabolic dysfunction-associated steatohepatitis (MASH). Here, we hypothesized that plasma CTSD can also serve as an early indicator of MetALD/ALD. Methods: We included 303 persistent heavy drinkers classified as having MetALD or ALD (n = 152) and abstinent patients with a history of excessive drinking (n = 151). Plasma CTSD levels of patients with MetALD/ALD without decompensation were compared with 40 healthy controls. Subsequently, the relationship between plasma CTSD levels and hepatic histological scores was established. Receiver-operating characteristic curves were generated to assess the precision of plasma CTSD levels in detecting MetALD/ALD. Lastly, plasma CTSD levels were compared between abstainers and drinkers. Results: Plasma CTSD levels were higher in patients with MetALD/ALD compared to healthy controls. While hepatic disease parameters (AST/ALT ratio, liver stiffness measurement) were higher at advanced histopathological stages (assessed by liver biopsy), plasma CTSD levels were already elevated at early histopathological stages. Furthermore, combining plasma CTSD levels with liver stiffness measurement and AST/ALT ratio yielded enhanced diagnostic precision (AUC 0.872) in detecting MetALD/ALD in contrast to the utilization of CTSD alone (AUC 0.804). Plasma CTSD levels remained elevated in abstainers. Conclusion: Elevated levels of CTSD in the circulation can serve as an early indicator of MetALD/ALD. Impact and implications: Alcohol-related liver disease is the leading cause of liver disease-related morbidity and mortality worldwide. However, the currently available non-invasive methods to diagnose MetALD/ALD are only able to detect advanced stages of MetALD/ALD. Here, we demonstrate that plasma levels of the lysosomal enzyme cathepsin D are already elevated at early stages of MetALD/ALD. Moreover, cathepsin D levels outperformed the currently available non-invasive methods to detect MetALD/ALD. Plasma levels of cathepsin D could therefore be a useful non-invasive marker for detection of MetALD/ALD.

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Background: Understanding the interplay between psychopathology of alcohol withdrawal syndrome (AWS) in alcohol use disorder (AUD) patients may improve the effectiveness of relapse interventions for AUD. Network theory of mental disorders assumes that mental disorders persist not of a common functional disorder, but from a sustained feedback loop between symptoms, thereby explaining the persistence of AWS and the high relapse rate of AUD. The current study aims to establish a network of AWS, identify its core symptoms and find the bridges between the symptoms which are intervention target to relieve the AWS and break the self-maintaining cycle of AUD. Methods: Graphical lasso network were constructed using psychological symptoms of 553 AUD patients. Global network structure, centrality indices, cluster coefficient, and bridge symptom were used to identify the core symptoms of the AWS network and the transmission pathways between different symptom clusters. Results: The results revealed that: (1) AWS constitutes a stable symptom network with a stability coefficient (CS) of 0.21-0.75. (2) Anger (Strength = 1.52) and hostility (Strength = 0.84) emerged as the core symptom in the AWS network with the highest centrality and low clustering coefficient. (3) Hostility mediates aggression and anxiety; anger mediates aggression and impulsivity in AWS network respectively. Conclusions: Anger and hostility may be considered the best intervention targets for researching and treating AWS. Hostility and anxiety, anger and impulsiveness are independent but related dimensions, suggesting that different neurobiological bases may be involved in withdrawal symptoms, which play a similar role in withdrawal syndrome.

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BACKGROUND: Hazardous alcohol use and alcohol use disorder (AUD) are highly prevalent among clients in mental health services, yet significant gaps remain in the adequate assessment of alcohol use and provision of appropriate alcohol interventions. The aim of this study was to conduct an exploration of (i) alcohol intervention elements used in mental health services and (ii) professionals' reported barriers and facilitators in identifying and intervening with hazardous alcohol use and AUD. METHODS: Qualitative data were obtained by conducting semi-structured interviews among a purposive sample of 18 professionals from 13 different Dutch mental health services organizations (i.e., five integrated mental health organizations with addiction services, five mental health organizations without addiction services, and three addiction services organizations without mental health services). Transcripts were qualitatively analyzed using inductive thematic analysis. RESULTS: Identified alcohol intervention elements included conducting assessments, brief interventions, treatment, referrals of clients, collaborations with other parties, and providing information to professionals. Professionals mentioned nine barriers and facilitators in the identification and intervention with hazardous alcohol use and AUD, including three aspects of professionals' behavior (i.e., professionals' agenda setting, knowledge and skills, and attitudes), actions related to identification and intervening, client contact, collaboration with other parties, and three factors in a wider context (i.e., organizational characteristics, organizational resources, and governmental aspects). CONCLUSIONS: Although diverse alcohol intervention elements are available in Dutch mental health services, it remains unclear to what extent these are routinely implemented. To better address hazardous alcohol use and AUD in mental health services, efforts should focus on enhancing alcohol training, improving collaboration with addiction services, providing appropriate tools, and facilitating support through organizational and governmental measures.

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Current treatments for alcohol use disorders (AUD) have limited efficacy. Recently, Cannabidiol (CBD) has been examined in a multitude of clinical settings. Preclinical and clinical results suggest that CBD might be particularly well suited for the treatment of AUD and may reduce alcohol cue and stress-induced craving and alcohol seeking. This study aims to investigate this new pharmacotherapy with a particular focus on neurobiological and physiological indicators of craving. Methods: In this double-blind, within-subject, randomised, placebo-controlled, cross-over study, non-treatment seekers will be randomly allocated to three days of four 200 mg CBD gel capsules (800 mg/day) or placebo, with an 18-day washout period. Cognitive, clinical, and neuroimaging assessments will be completed during these three days. The CBD and placebo assessments will be compared. The primary outcomes are i) BOLD signal as a proxy for regional activity during a cue reactivity and a fear response task measured with functional magnetic resonance imaging (fMRI), ii) heart rate variability and skin conductance levels as a proxy for psychophysiological responses to alcohol stimuli. The secondary outcomes are: i) neurometabolite levels (γ-Aminobutyric acid, ethanol, glutathione, and glutamate + glutamine (combined signal)) using magnetic resonance spectroscopy (MRS); ii) functional connectivity using resting state fMRI (rsfMRI); iii) executive functioning task results; iv) clinical outcomes such as craving, anxiety, and sleep. Discussion: This study will improve the understanding of the mechanisms of action of CBD and provide early signals of efficacy regarding the therapeutic potential of CBD in the treatment of alcohol use disorder. ClinicalTrials.gov Identifier: NCT05387148.

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Background: This study aimed to provide an up-to-date evaluation of the burden of alcohol use disorder and its consequences in Iran from 1990 to 2019. Methods: We assessed the burden of alcohol use disorder and its three subsequent disorders, including cirrhosis and other chronic liver diseases, liver cancer, and cardiomyopathy using Global Burden of Disease (GBD) data. We retrieved data on incidence, prevalence, death, Years of Life Lost from mortality (YLL), Years of healthy life Lost due to Disability (YLD), and Disability-Adjusted Life Year (DALY), which is calculated by summing YLL and YLD values, indices, as well as sociodemographic index (SDI) values. Results: Age-standardized DALY rate of alcohol use disorder reduced from 55.5 in 1990 to 41.8 per 100,000 in 2019 (-24.1 %). Similarly, age-standardized DALY rates of cirrhosis due to alcohol use (-28.7 %), liver cancer due to alcohol use (-20.9 %), and alcoholic cardiomyopathy (-36.3 %) decreased in Iran from 1990 to 2019. In 2019, alcohol use disorder had the highest DALY rate among individuals younger than 55 years, while cirrhosis due to alcohol use imposed the greatest burden on those older than 55. After adjusting for the year, SDI was negatively associated with the age-standardized DALY rate of liver cancer due to alcohol use (p < 0.001), positively associated with that of alcoholic cardiomyopathy (p = 0.002), and not significantly associated with the burden of other conditions (p > 0.05). Conclusions: Despite reductions in the age-standardized DALY rate of alcohol use disorders and related consequences among Iranians, they remain a serious public health concern in Iran.

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Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically. Objective: To examine the association between substance use and clinical and neuropathological endpoints of CTE. Methods: Our sample included 429 deceased male football players. CTE was neuropathologically diagnosed. Informant interviews assessed features of substance use and history of treatment for substance use to define indicators: history of substance use treatment (yes vs no, primary variable), alcohol severity, and drug severity. Outcomes included scales that were completed by informants to assess cognition (Cognitive Difficulties Scale, BRIEF-A Metacognition Index), mood (Geriatric Depression Scale-15), behavioral regulation (BRIEF-A Behavioral Regulation Index, Barratt Impulsiveness Scale-11), functional ability (Functional Activities Questionnaire), as well as CTE status and cumulative p-tau burden. Regression models tested associations between substance use indicators and outcomes. Results: Of the 429 football players (mean age = 62.07), 313 (73%) had autopsy confirmed CTE and 100 (23%) had substance use treatment history. Substance use treatment and alcohol/drug severity were associated with measures of behavioral regulation (FDR-p-values<0.05, ΔR2 = 0.04-0.18) and depression (FDR-p-values<0.05, ΔR2 = 0.02-0.05). Substance use indicators had minimal associations with cognitive scales, whereas p-tau burden was associated with all cognitive scales (p-values <0.05). Substance use treatment had no associations with neuropathological endpoints (FDR-p-values>0.05). Conclusions: Among deceased football players, substance use was common and associated with clinical symptoms.

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AIMS: We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone. METHODS: Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [n = 8]), naltrexone plus placebo (NAL-PLAC [n = 7]), prazosin plus placebo (PRAZ-PLAC [n = 7]), or placebo plus placebo (PLAC-PLAC [n = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD). RESULTS: In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial. CONCLUSION: These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial.

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AIM: The purpose of this study was to explore Muslim's perceptions and views of raising awareness on safe alcohol use and counterfeit alcohol harms in Islamic countries. SUBJECT AND METHODS: Qualitative semi-structured interviews with a purposive sample from the Gulf Council Cooperation (GCC) countries. The data were analysed using a reflexive thematic analysis method. RESULTS: Twenty-three participants took part in this study. We have identified five themes from the data, including perceptions on alcohol use in the GCC, community's openness to alcohol discussions, approaches to raising awareness on alcohol use, all forbidden is desirable, and legalisation is the solution. All participants acknowledged the existence of alcohol use in GCC communities and advocated for the need to raise public awareness about the harms of alcohol use. Opinions on approaches to raising awareness varied. Some participants suggested focusing awareness on the religious messages prohibiting alcohol use, emphasising that alcohol is harmful in any quantity. For some, raising awareness of safe alcohol consumption was viewed as accepting and encouraging alcohol use, which goes against Islamic religious beliefs. Some participants attributed alcohol misuse and the consumption of counterfeit alcohol to the ban on alcohol products in some GCC countries. CONCLUSIONS: Muslims acknowledge the existence of alcohol use in Muslim communities, yet there is a hesitancy in raising awareness of safe alcohol use. Although challenging, there is a need to combine the public health perspective on safe alcohol use while providing messages that acknowledge the religious aspect.

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Background: Few studies have previously evaluated the long-term impact of initiating the combined use of alcohol and cocaine early-in-life during adolescence. Our preclinical study characterized changes in affective-like behavior and/or voluntary ethanol consumption emerging later on in adulthood induced by a prior adolescent drug exposure, as well as tested therapeutical interventions (i.e., cannabidiol or ketamine) to prevent the observed effects. Methods: We performed three independent studies with male and female Sprague-Dawley rats, treated in adolescence (postnatal days, PND 29-38) with non-contingent paradigms of ethanol, cocaine, their combination or vehicle. Later on, adult rats were (1) scored for their affective-like state (forced-swim, elevated-plus maze, novelty-suppressed feeding, sucrose preference), (2) allowed to freely drink ethanol for 6 weeks (two-bottle choice), or (3) treated with cannabidiol or ketamine before given access to ethanol in adulthood. Results: No signs of increased negative affect were observed in adulthood following the adolescent treatments. However, adolescent ethanol exposure was a risk-factor for later developing an increased voluntary ethanol consumption in adulthood, both for male and female rats. This risk was similar when ethanol was combined with adolescent cocaine exposure, since cocaine alone showed no effects on later ethanol intake. Finally, rats exposed to adolescent ethanol and pretreated in adulthood with cannabidiol (and/or ketamine, but just for females) reduced their ethanol voluntary consumption. Conclusion: Our data provided two therapeutical options capable of preventing the impact of an early drug initiation during adolescence by decreasing voluntary ethanol consumption in adult rats.

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BACKGROUND: Alcohol use disorder is associated with a variety of complications, including alcohol withdrawal syndrome (AWS), which may occur in those who decrease or stop alcohol consumption suddenly. AWS is associated with a range of signs and symptoms, which are most commonly treated with GABAergic medications. CLINICAL QUESTION: Is phenobarbital an effective treatment for AWS? EVIDENCE REVIEW: Studies retrieved included two prospective, randomized, double-blind studies and three systematic reviews. These studies provided estimates of the effectiveness and safety of phenobarbital for treatment of AWS. CONCLUSIONS: Based on the available literature, phenobarbital is reasonable to consider for treatment of AWS. Clinicians must consider the individual patient, clinical situation, and comorbidities when selecting a medication for treatment of AWS.