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Objective: The COVID-19 pandemic may have interfered with individuals' access to alcohol use disorder (AUD) treatment, but limited research has documented the impact of treatment interference on drinking behavior. This study's purpose was to examine the associations of AUD treatment interference with problematic alcohol use, and the moderating roles of perceived stress and resilience., Method: A cross-sectional survey design was employed. Data were drawn from the baseline assessment of the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol Study. Between June 2020 and March 2021, 288 participants (48.6% female, 51.4% male) responded to key measures of interest by phone and/or through an online survey. Study hypotheses were tested using multiple linear regression models adjusted for demographic characteristics (age, sex, race, ethnicity, years of education, household income, marital status), study enrollment phase, and history of AUD., Results: Self-reported AUD treatment interference was positively associated with problematic alcohol use as measured by the Alcohol Use Disorders Identification Test ( b = 2.05, p < 0.001). Significant moderation effects indicated the association between AUD treatment interference and problematic alcohol use was stronger at a high level of perceived stress ( b = 3.08, p < 0.001) and was attenuated at a high level of resilience ( b = -0.13, p = 0.874)., Conclusions: Self-reported AUD treatment interference may indicate interruption to individuals' support systems and highlight the need for continued access to treatment. Fostering positive coping strategies and resilience may help individuals mitigate risks of problematic drinking amidst a public health crisis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vergeer, Luk, Stangl, McCabe, Ziausyte, Schwandt, Goldman, Ramchandani and Diazgranados.)

Background: Alcohol and nicotine interact with the nicotinic acetylcholine receptor system to alter reward-related responses, thereby contributing to the co-use and misuse of these drugs. A missense polymorphism rs16969968 (G>A) in the CHRNA5 gene has shown a strong association with nicotine-related phenotypes. However, less is known about the impact of this variant on alcohol-related phenotypes., Methods: We assessed the main and interactive effect of smoking and rs16969968 polymorphism on alcohol consumption using the Alcohol Use Disorders Identification Test (AUDIT), Timeline Follow Back (TLFB), and Lifetime Drinking History (LDH) in 980 healthy adults without alcohol use disorder. We further examined the effect of the rs16969968 polymorphism on acute alcohol consumption using a free-access i.v. alcohol self-administration (IV-ASA) human laboratory paradigm in a subset of 153 nonsmoking participants. Subjective alcohol responses, alcohol sensitivity, and expectancy measures were compared between genotype groups (GG; AA/AG)., Results: We observed a significant association of smoking with AUDIT, TLFB, and LDH measures across genotype groups, with smokers showing higher scores compared with nonsmokers. Additionally, we found an association between genotype and TLFB-total drinks in the IV-ASA subset, with the GG group showing higher scores than AA/AG group. Relatedly, the alcohol negative expectancy score was significantly lower in the GG group than the AA/AG group., Conclusions: Our findings underscore the association of smoking with alcohol measures. We found preliminary evidence for the protective effect of the functional CHRNA5 polymorphism on alcohol consumption and its association with increased negative alcohol expectancies, which highlights the substantial heterogeneity in alcohol responses., (Published by Oxford University Press on behalf of CINP 2024.)

Objective: Individuals with a history of suicidality may be especially vulnerable to the adverse impact of COVID-related stressors, but this vulnerability has not been demonstrated. This study examined the longitudinal effects of suicidality history (ideation only or attempt vs. none) and interactions with COVID-related stressors (e.g., work interruptions, childcare challenges, and financial stress) on anxiety symptoms, depressive symptoms, and problematic drinking., Methods: Longitudinal data from 517 participants were drawn from the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol and COVID-19 Pandemic Impact on Alcohol Study. Lifetime history of suicidality was assessed using the clinician administered Columbia-Suicide Severity Rating Scale. Multiple regressions tested the interaction between suicidality history and COVID-related stressors on clinical outcomes., Results: Compared to individuals without any history of suicidality (79.9%; n  = 413), individuals with a history of suicide ideation only (14.5%; n  = 75) and suicide attempt (5.6%; n  = 29) had higher anxiety symptoms, depressive symptoms, and problematic drinking during the pandemic. Significant interaction effects showed the associations between COVID-related stressors and mental disorder symptoms were stronger among individuals with suicide attempt history than individuals without suicidality history., Conclusions: History of suicide attempt in combination with high COVID-related stressors put individuals at the greatest risk for pandemic mental disorder symptoms. Individuals with suicide attempt history may have lower coping resources to handle COVID-related stressors. Suicide risk assessment and intervention to increase cognitive flexibility and emotional regulation skills may help these individuals manage emotional distress experienced during the COVID-19 pandemic and beyond., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC on behalf of American Psychiatric Association.)

Objective: To identify latent classes of positive coping behaviors during the COVID-19 pandemic and examine associations with alcohol-related and mental health outcomes across participants with and without a history of alcohol use disorder (AUD)., Methods: Baseline data from 463 participants who were enrolled in the NIAAA COVID-19 Pandemic Impact on Alcohol (C19-PIA) Study were analyzed. Latent class analysis (LCA) was applied to five positive coping behaviors during COVID-19: taking media breaks, taking care of their body, engaging in healthy behaviors, making time to relax, and connecting with others. Latent class differences and the moderating role of history of AUD on six alcohol-related and mental health outcomes were examined using multiple regression models., Results: LCA revealed two latent classes: 83.4% High Positive Coping and 16.6% Low Positive Coping. Low Positive Coping was associated with higher levels of perceived stress, anxiety symptoms, and loneliness. A history of AUD was consistently associated with higher levels of alcohol-related and mental health outcomes. Significant interactions between Coping Latent Classes and history of AUD indicated that the associations of Low Positive Coping with problematic alcohol use, depressive symptoms, and drinking to cope motives were either stronger or only significant among individuals with a history of AUD., Conclusions: Individuals with a history of AUD may be particularly vulnerable to depressive symptoms and alcohol-related outcomes, especially when they do not utilize positive coping strategies. The promotion of positive coping strategies is a promising avenue to address alcohol-related and mental health problems during a public health crisis and warrants future research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Fear of COVID-19 is a risk factor for anxiety and depressive symptoms. During the COVID-19 pandemic, drinking to cope with psychological distress has been proposed as a key mechanism leading to problematic drinking. The goal of this study was to test social media addiction as a mediator linking fear of COVID-19 to mental health symptoms and problematic alcohol use., Methods: In between April 6 and July 2 of 2022, 250 participants completed an online survey as part of the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol Study. Path analyses were conducted to test the mediational pathways., Results: Using the polythetic classification scheme, 13.2% ( n  = 33) of participants were classified as having social media addiction. Compared with participants without social media addiction, participants with social media addiction spent significantly more time on social media platforms and on digital communications with a family member or friend. They also reported greater fear of COVID-19, higher anxiety symptoms, and higher depressive symptoms. Path analyses indicated that social media addiction mediated the associations of fear of COVID-19 with anxiety and depressive symptoms. Furthermore, there were indirect pathways linking fear of COVID-19 to problematic alcohol use through higher social media addiction and higher anxiety and depressive symptoms., Conclusion: Social media addiction may be a maladaptive coping mechanism that individuals with high fear of COVID-19 utilized to deal with uncertainty and perceived risks during the pandemic. Findings underscore the need to examine cognitions related to fear of COVID-19 and address excessive social media use in the context of mental health and alcohol interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luk, Geda, Stangl, Cheng, Schwandt, Goldman, Diazgranados and Ramchandani.)

Background: Heavy alcohol consumption-associated chemosensory dysfunction is understudied, and early detection can help predict disease-associated comorbidities, especially those related to four quality of life (QOL) domains (physical, psychological, social and environment). We examined self-reports of chemosensory ability of individuals with different alcohol drinking behaviors and their association with changes in QOL domains., Methods: Participants (n = 466) were recruited between June 2020 and September 2021 into the NIAAA COVID-19 Pandemic Impact on Alcohol study. Group-based trajectory modeling was used to categorize participants without any known COVID-19 infection into three groups (non-drinkers, moderate drinkers and heavy drinkers) based on their Alcohol Use Disorders Identification Test consumption scores at four different time points (at enrollment, week 4, week 8 and week 12). Linear mixed models were used to examine chemosensory differences between these groups. The associations between chemosensory abilities and QOL were determined in each group., Results: We observed significant impairment in self-reported smell ability of heavy drinking individuals compared to non-drinkers. In contrast, taste ability showed marginal impairment between these groups. There were no significant differences in smell and taste abilities between the moderate and non-drinking groups. Heavy drinkers' impairment in smell and taste abilities was significantly associated with deterioration in their physical, psychological, social and environmental QOL., Conclusion: Persistent heavy drinking was associated with lower chemosensory ability. Heavy drinkers' reduced smell and taste function and association with poorer QOL indicate that early assessment of chemosensory changes may be crucial in identifying poorer well-being outcomes in heavy drinkers at risk for alcohol use disorder., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Roughly half of patients with alcohol use disorder prefer non-abstinence based approaches to treatment. However, only individuals who can limit their alcohol use after low-risk consumption are most likely to benefit from these approaches. This pilot study developed a laboratory-based intravenous alcohol self-administration paradigm to determine the characteristics of individuals who could successfully resist consuming alcohol after an initial exposure., Methods: Seventeen non-treatment seeking heavy drinkers completed two versions of an intravenous alcohol self-administration paradigm designed to assess impaired control over alcohol use. In the paradigm, participants received a priming dose of alcohol and then entered a 120-min resist phase, in which they received monetary rewards if they resisted self-administering alcohol. We used Cox proportional hazards regression to determine the impact of craving and Impaired Control Scale scores on rate of lapse., Results: 64.7% of participants across both versions of the paradigm were unable to resist alcohol for the duration of the session. Craving at baseline (HR = 1.07, 95% CI 1.01-1.13, p = 0.02) and following priming (HR = 1.08, 95% CI 1.02-1.15, p = 0.01) were associated with rate of lapse. Individuals who lapsed endorsed greater attempts to control their drinking over the prior six months compared to individuals who resisted., Conclusions: This study provides preliminary evidence that craving may be predictive of risk of lapse in individuals who are trying to limit alcohol intake after consuming a small initial amount of alcohol. Future studies should test this paradigm in a larger and more diverse sample., Competing Interests: The authors declare that there is no conflict of interest., (© 2022 The Authors. Published by Elsevier B.V.)

Objective: Interindividual variation in responses to alcohol is substantial, posing challenges for medical management and for understanding the biological underpinnings of alcohol use disorders (AUD). It is important to understand whether diverse alcohol responses such as sedation, which is predictive of risk and partly heritable, occur concurrently or independently from responses such as blackouts and withdrawal. We hypothesized that latent factors accounting for sources of variance in diverse alcohol response phenotypes could be identified in a large, deeply phenotyped sample of patients with AUD., Methods: We factor analyzed 17 alcohol response related items from the Alcohol Dependence Scale (ADS) in 938 individuals diagnosed with AUD via structured clinical interviews. Demographic, genetic, and clinical characteristics were tested as predictors of the latent factors by multiple indicators, multiple causes analysis., Results: The final factor solution included three alcohol response factors: Physical Symptoms, Perceptual Disturbances, and Neurobiological Effects. Both gender and genetic ancestry were identified as variables influencing alcohol response. Major depressive disorder positively predicted physical symptoms and aggression negatively predicted physical symptoms. Barratt's Impulsivity Scale total score predicted the Physical and Perceptual domains. Family history, average drinks per drinking day, and negative urgency (an impulsivity measure) predicted all three domains., Conclusions: Diverse items from the ADS concurrently load onto three correlated alcohol response factors rather than loading independently. Genetic ancestry and clinical characteristics predicted the severity of items that define the alcohol response factors even after accounting for degree of alcohol consumption. Co-occurring phenotypes point towards an underlying shared physiology of diverse alcohol responses., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC. on behalf of the American Psychiatric Association.)

Alcohol hangover is a combination of mental, sympathetic, and physical symptoms experienced the day after a single period of heavy drinking, starting when blood alcohol concentration approaches zero. How individual measures/domains of hangover symptomology might differ with moderate to heavy alcohol consumption and how these symptoms correlate with the drinking markers is unclear. We investigated the amount/patterns of drinking and hangover symptomology by the categories of alcohol drinking. We studied males and females in three groups: 12 heavy drinkers (HD; >15 drinks/week, 34-63 years old (y.o.)); 17 moderate drinkers (MD; 5-14 drinks/week, 21-30 y.o.); and 12 healthy controls (social/light drinkers, SD; <5 drinks/week, 25-54 y.o.). Demographics, drinking measures (Timeline followback past 90 days (TLFB90), Alcohol Use Disorders Identification Test (AUDIT)), and alcohol hangover scale (AHS) were analyzed. Average drinks/day was 5.1-times greater in HD compared to MD. Average AHS score showed moderate incapacity, and individual measures and domains of the AHS were significantly elevated in HD compared to MD. Symptoms of three domains of the AHS (mental, gastrointestinal, and sympathetic) showed domain-specific significant increase in HD. A domain-specific relation was present between AUDIT and specific measures of AHS scores in HD, specifically with the dependence symptoms. Exacerbation in hangover symptomology could be a marker of more severe alcohol use disorder.

Preclinical evidence suggests that ghrelin, a peptide synthesized by endocrine cells of the stomach and a key component of the gut-brain axis, is involved in alcohol seeking as it modulates both central reward and stress pathways. However, whether and how ghrelin administration may impact alcohol intake in humans is not clear. For, we believe, the first time, this was investigated in the present randomized, crossover, double-blind, placebo-controlled, human laboratory study. Participants were non-treatment-seeking alcohol-dependent heavy-drinking individuals. A 10-min loading dose of intravenous ghrelin/placebo (3 mcg kg -1 ) followed by a continuous ghrelin/placebo infusion (16.9 ng/kg/min) was administered. During a progressive-ratio alcohol self-administration experiment, participants could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System. In another experiment, brain functional magnetic resonance imaging was conducted while participants performed a task to gain points for alcohol, food or no reward. Results showed that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered (percent change: 24.97±10.65, P=0.04, Cohen's d=0.74). Participants were also significantly faster to initiate alcohol self-administration when they received ghrelin, compared to placebo (P=0.03). The relationships between breath alcohol concentration and subjective effects of alcohol were also moderated by ghrelin administration. Neuroimaging data showed that ghrelin increased the alcohol-related signal in the amygdala (P=0.01) and modulated the food-related signal in the medial orbitofrontal cortex (P=0.01) and nucleus accumbens (P=0.08). These data indicate that ghrelin signaling affects alcohol seeking in humans and should be further investigated as a promising target for developing novel medications for alcohol use disorder.

The endogenous opioid system may be involved in the development and maintenance of alcohol use disorder (AUD) and is a target for existing AUD pharmacotherapies. A functional polymorphism of the mu-opioid receptor gene (OPRM1 A118G, rs1799971) may alter the risk of developing AUD. Human laboratory studies have demonstrated that minor allele carriers self-administer more alcohol, show greater sensitivity to alcohol's effects, and exhibit increased alcohol-induced dopamine release. On the other hand, large genome-wide association studies and meta-analyses of candidate gene studies have not found an association between this genotype and alcohol dependence diagnosis. Given this discrepancy, the present study sought to verify whether OPRM1 A118G was associated with alcohol self-administration, subjective response to alcohol, and craving in a sample of 106 social drinkers of European ancestry who completed an intravenous alcohol self-administration session. We found no relationship between OPRM1 rs1799971 genotype and subjective response to alcohol or craving. OPRM1 genotype was not associated with total alcohol exposure or likelihood of attaining a binge-level exposure (80 mg%) during the intravenous alcohol self-administration session. Analysis of 90-day Timeline Followback interview data in a larger sample of 965 participants of European ancestry found no relationship between OPRM1 genotype and alcohol consumption in either alcohol dependent or non-dependent participants. These findings suggest that there may not be an association between OPRM1 rs1799971 genotype and alcohol consumption or sensitivity in individuals of European ancestry.

Aims: The orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol., Method: Association analysis was performed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample, comprising AUD individuals and controls (N = 1127). Then, a post-hoc analysis using data from a human laboratory study of intravenous alcohol self-administration (IV-ASA, N = 144) was performed to investigate the association of this SNP with subjective responses following a fixed dose of alcohol (priming phase) and alcohol self-administration (ad libitum phase)., Results: The case-control study revealed a trend association (N = 1127, OR = 0.665, CI = 0.44-1.01, P = 0.056) between AUD diagnosis and Leu72Met. In AUD subjects, the SNP was associated with significantly lower average drinks per day (n = 567, β = -2.49, 95% CI = -4.34 to -0.64, P = 0.008) and significantly fewer heavy drinking days (n = 567, β = -12.00, 95% CI = -19.10 to -4.89, P < 0.001). The IV-ASA study further revealed that 72Met carriers had greater subjective responses to alcohol (P < 0.05) when compared to Leu72Leu both at priming and during ad lib self-administration., Conclusion: Although preliminary, these findings suggest that the Leu72Leu genotype may lead to increased risk of AUD possibly via mechanisms involving a lower response to alcohol resulting in excessive alcohol consumption. Further investigations are warranted., Short Summary: We investigated whether a Leu72Met missense polymorphism in the prepro-ghrelin gene, is associated with alcohol use disorder, alcohol consumption and subjective responses to alcohol. Although preliminary, results suggest that the Leu72Leu genotype may lead to increased risk of alcohol use disorder possibly via mechanisms involving a lower response to alcohol., (Medical Council on Alcohol and Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Self-administration is a hallmark of all addictive drugs, including alcohol. Human laboratory models of alcohol self-administration have characterized alcohol-seeking behavior and served as surrogate measures of the effectiveness of pharmacotherapies for alcohol use disorders. Intravenous alcohol self-administration is a novel method that assesses alcohol exposure driven primarily by the pharmacological response to alcohol and may have utility in characterizing unique behavioral and personality correlates of alcohol-seeking and consumption., Methods: This study examined exposure-response relationships for i.v. alcohol self-administration, and the influence of impulsivity and alcohol expectancy, in healthy, nondependent drinkers (n=112). Participants underwent a 2.5-hour free-access i.v. alcohol self-administration session using the Computerized Alcohol Infusion System. Serial subjective response measures included the Drug Effects Questionnaire and Alcohol Urge Questionnaire. To characterize the motivational aspects of alcohol consumption prior to potential acute adaptation, the number of self-infusions in the first 30 minutes of the free-access session was used to classify participants as low- and high-responders., Results: High-responders showed greater subjective responses during i.v. alcohol self-administration compared with low responders, reflecting robust exposure-driven hedonic responses to alcohol. High-responders also reported heavier drinking patterns and lower scores for negative alcohol expectancies on the Alcohol Effects Questionnaire. High-responders also showed higher measures of impulsivity on a delayed discounting task, supporting previous work associating impulsivity with greater alcohol use and problems., Conclusions: These findings indicate that early-phase measures of free-access i.v. alcohol self-administration are particularly sensitive to the rewarding and motivational properties of alcohol and may provide a unique phenotypic marker of alcohol-seeking behavior., (Published by Oxford University Press on behalf of CINP 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD). Case-control analysis (N = 908) was performed on a sample of individuals enrolled in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) intramural research program. The Study of Addiction: Genetics and Environment (SAGE) sample (N = 3803) was used for confirmation purposes. Post hoc analyses were carried out on data from a human laboratory study of intravenous alcohol self-administration (IV-ASA; N = 81) in social drinkers and from a functional magnetic resonance imaging study in alcohol-dependent individuals (N = 22) subjected to a Monetary Incentive Delay task. In the preclinical study, a GLP-1R agonist was evaluated in a mouse model of alcohol dependence to demonstrate the role of GLP-1R for alcohol consumption. The previously reported functional allele 168Ser (rs6923761) was nominally associated with AUD (P = 0.004) in the NIAAA sample, which was partially replicated in males of the SAGE sample (P = 0.033). The 168 Ser/Ser genotype was further associated with increased alcohol administration and breath alcohol measures in the IV-ASA experiment and with higher BOLD response in the right globus pallidus when receiving notification of outcome for high monetary reward. Finally, GLP-1R agonism significantly reduced alcohol consumption in a mouse model of alcohol dependence. These convergent findings suggest that the GLP-1R may be an attractive target for personalized pharmacotherapy treatment of AUD.