Growing evidence indicates that the glucagon-like peptide-1 (GLP-1) system is involved in the neurobiology of addictive behaviors, and GLP-1 analogues may be used for the treatment of alcohol use disorder (AUD). Here, we examined the effects of semaglutide, a long-acting GLP-1 analogue, on biobehavioral correlates of alcohol use in rodents. A drinking-in-the-dark procedure was used to test the effects of semaglutide on binge-like drinking in male and female mice. We also tested the effects of semaglutide on binge-like and dependence-induced alcohol drinking in male and female rats, as well as acute effects of semaglutide on spontaneous inhibitory postsynaptic currents (sIPSCs) from central amygdala (CeA) and infralimbic cortex (ILC) neurons. Semaglutide dose-dependently reduced binge-like alcohol drinking in mice; a similar effect was observed on the intake of other caloric/noncaloric solutions. Semaglutide also reduced binge-like and dependence-induced alcohol drinking in rats. Semaglutide increased sIPSC frequency in CeA and ILC neurons from alcohol-naive rats, suggesting enhanced GABA release, but had no overall effect on GABA transmission in alcohol-dependent rats. In conclusion, the GLP-1 analogue semaglutide decreased alcohol intake across different drinking models and species and modulated central GABA neurotransmission, providing support for clinical testing of semaglutide as a potentially novel pharmacotherapy for AUD.

According to the minorities’ diminished returns (MDR) theory, socioeconomic status (SES) indicators such as education attainment have smaller protective effects on health risk behaviors for racial and ethnic minority groups in comparison to the ‘dominant’ social group. However, most studies of MDR theory have been on comparison of Blacks versus Whites. Much less is known about diminished returns of SES in ethnic subpopulations (i.e., Hispanics versus non-Hispanic Whites). To test whether MDR also holds for the social patterning of problematic alcohol use among Hispanic and non-Hispanic Whites, this study investigated ethnic variations in the association between education attainment and alcohol binge drinking frequency in a population-based sample of adults. Los Angeles Family and Neighborhood Survey, 2001, included 907 non-Hispanic White and 2117 Hispanic White adults (≥18 years old). Hispanic ethnicity (moderator), education attainment (independent variable), alcohol binge drinking frequency (dependent variable), and gender, age, immigration status, employment status, self-rated health, and history of depression (confounders) were included in four linear regressions. In the overall sample that included both non-Hispanic and Hispanic Whites, higher education attainment was correlated with lower alcohol binge drinking frequency (b = −0.05, 95% CI = −0.09–−0.02), net of covariates. A significant interaction was found between ethnicity and education attainment (b = 0.09; 95% CI = 0.00–0.17), indicating a stronger protective effect of high education attainment against alcohol binge drinking frequency for non-Hispanic than Hispanic Whites. In ethnic-stratified models, higher level of education attainment was associated with lower binge drinking frequency among non-Hispanic Whites (b = −0.11, 95% CI = −0.19–−0.03), but not among Hispanic Whites (b = −0.01, 95% CI = −0.04–0.03). While, overall, higher education attainment is associated with lower frequency of alcohol binge drinking, this protective effect of education attainment seems to be weaker among Hispanic Whites compared to non-Hispanic Whites, a phenomenon consistent with the MDR theory.

Addiction is a chronic relapsing disease with high morbidity and mortality. Treatments for addiction include pharmacological and psychosocial interventions; however, currently available medications are limited in number and efficacy. The glucagon-like-peptide-1 (GLP-1) system is emerging as a potential novel pharmacotherapeutic target for alcohol and other substance use disorders (ASUDs). In this review, we summarize and discuss the wealth of available evidence from testing GLP-1 receptor (GLP-1R) agonist medications in preclinical models and humans with ASUDs, possible mechanisms underlying the impact of GLP-1R agonists on alcohol/substance use, gaps in knowledge, and future directions. Most of the research with GLP-1R agonists has been conducted in relation to alcohol use; psychostimulants, opioids, and nicotine have also been investigated. Preclinical evidence suggests that GLP-1R agonists reduce alcohol/substance use and other related outcomes. The main proposed mechanisms are related to reward processing, stress, and cognitive function, as well as broader mechanisms related to satiety, changes in gastric motility, and glucose homeostasis. More in-depth mechanistic studies are warranted. Clinical studies have been limited and their findings have been less conclusive; however, most support the safety and potential efficacy of GLP-1R agonists in ASUD treatment. Identifying preferred compounds, as well as possible subgroups who are most responsive to GLP-1R agonists are some of the key research questions to translate the promising preclinical data into clinical settings. Several clinical trials are underway to test GLP-1R agonists in people with ASUDs.