Purpose of review: To provide an update on medication development efforts for alcohol use disorder (AUD) by reviewing recently published (past two years) human studies that evaluated medications' effects on alcohol-related outcomes. Recent findings: Forty-five publications were found suitable for this review. A variety of compounds have been tested in the past two years as potential pharmacological options for AUD, including medications that act on multiple targets (topiramate, aripiprazole, quetiapine), calcium channels (gabapentin), GABA receptors (baclofen, diazepam), glutamate receptors (ifenprodil, memantine, glycine), nicotinic acetylcholine receptors (varenicline, mecamylamine), α1 adrenergic receptors (prazosin, doxazosin), neuroendocrine pathways (oxytocin, a vasopressin receptor 1b antagonist, a ghrelin receptor inverse agonist), and others (samidorphan, ibudilast, Nacetylcysteine, citoline). Important findings and limitations regarding the effects of these medications on alcohol-related outcomes are discussed. Summary: There is a critical need to increase the armamentarium of medications for AUD. Human laboratory studies may help screen and prioritize promising targets and compounds before running large clinical trials. Given the complexity of AUD and the heterogeneity of afflicted patients, future studies should also investigate potential moderators and predictors of response to each pharmacological intervention.

Growing evidence suggests that the glucagon‐like peptide‐1 (GLP‐1) system modulates alcohol seeking and consumption, and GLP‐1 analogues may represent novel pharmacotherapies for alcohol use disorder (AUD). Accordingly, it is important to understand the potential effects of alcohol on the endogenous GLP‐1 system. In a series of secondary analyses of previous human laboratory experiments, we first examined the effects of alcohol administration, with different doses and routes of administration, on peripheral active GLP‐1 concentrations in heavy‐drinking individuals with AUD enrolled in placebo‐controlled pharmacological studies (only placebo conditions were analysed here). Alcohol administration resulted in a significant reduction of GLP‐1 levels across the four experiments (oral alcohol, variable dose: F3,28 = 6.52, p = 0.002; oral alcohol, fixed dose: F7,75.94 = 5.08, p < 0.001; intravenous alcohol, variable dose: F4,37.03 = 20.72, p < 0.001; intravenous alcohol, fixed dose: F4,13.92 = 10.44, p < 0.001). Next, central expression of the GLP‐1 receptor (GLP‐1R) in post‐mortem brain tissues (amygdala, ventral tegmental area, nucleus accumbens, hippocampus and prefrontal cortex) was compared between individuals with AUD and controls. Fold change of GLP‐1R mRNA in the hippocampus was significantly higher in individuals with AUD, compared to controls (F1,21 = 6.80, p = 0.01). A trend‐level effect with the same direction was also found in the prefrontal cortex (F1,20 = 3.07, p = 0.09). Exploratory analyses showed that GLP‐1R gene expression levels were correlated with behavioural measures of alcohol drinking (hippocampus) and cigarette smoking (hippocampus and prefrontal cortex). Collectively, these data provide novel information on the crosstalk between alcohol and GLP‐1 in a clinically relevant sample. Further studies are needed to understand the underlying mechanisms of this link.

Background: The gastrointestinal tract has been speculated to serve as a reservoir for Acinetobacter, however little is known about the ecological fitness of Acinetobacter strains in the gut. Likewise, not much is known about the ability of Acinetobacter to consume dietary, or host derived nutrients or their capacity to modulate host gene expression. Given the increasing prevalence of Acinetobacter in the clinical setting, we sought to characterize how A. calcoaceticus responds to gut-related stressors and identify potential microbe-host interactions.Materials and Methods: To accomplish these aims, we grew clinical isolates and commercially available strains of A. calcoaceticus in minimal media with different levels of pH, osmolarity, ethanol and hydrogen peroxide. Utilization of nutrients was examined using Biolog phenotypic microarrays. To examine the interactions of A. calcoaceticus with the host, inverted murine organoids where the apical membrane is exposed to bacteria, were incubated with live A. calcoaceticus, and gene expression was examined by qPCR.Results: All strains grew modestly at pH 6, 5 and 4; indicating that these strains could tolerate passage through the gastrointestinal tract. All strains had robust growth in 0.1 and 0.5 M NaCl concentrations which mirror the small intestine, but differences were observed between strains in response to 1 M NaCl. Additionally, all strains tolerated up to 5% ethanol and 0.1% hydrogen peroxide. Biolog phenotypic microarrays revealed that A. calcoaceticus strains could use a range of nutrient sources, including monosaccharides, disaccharides, polymers, glycosides, acids, and amino acids. Interestingly, the commercially available A. calcoaceticus strains and one clinical isolate stimulated the pro-inflammatory cytokines Tnf, Kc, and Mcp-1 while all strains suppressed Muc13 and Muc2.Conclusion: Collectively, these data demonstrate that A. calcoaceticus is well adapted to dealing with environmental stressors of the gastrointestinal system. This data also points to the potential for Acinetobacter to influence the gut epithelium.