Alcohol (Hanover, York County, Pa.)最新文献

Medication development for alcohol use disorder (AUD) represents a challenging, costly, and time-consuming process. A typical development trajectory involves testing compounds in animal models, human laboratory studies, and randomized clinical trials (RCTs). This paper reviews a series of data-driven studies seeking to evaluate best practices in medication development for AUD at each of the three levels of analysis. First, we evaluate the role of behavioral pharmacology paradigms in early efficacy testing and highlight the importance of preclinical and human laboratory evidence in making critical “go/no-go” decisions throughout the development process. Second, we discuss a recent translational meta-analytic approach that integrates preclinical, human laboratory, and RCT data to inform AUD medication development. This narrative review synthesizes findings from systematic reviews, meta-regression analyses, and integrated data across stages of medication testing. Findings from this work suggest that factors such as sample characteristics and study design influence the detection of medication effects on AUD outcomes, emphasizing the need for standardized methodologies. Furthermore, findings suggest that early efficacy signals in animal models and human laboratory studies can predict specific clinical trial outcomes, offering valuable insights for data-informed decision making in medication development. Together, these studies bridge the gap between the preclinical and clinical stages, facilitating more efficient medication development for AUD.

Alcohol intake is widely accepted in diverse cultures around the world, although heavy and prolonged consumption can be harmful. Alcohol influences multiple organs through interorgan and intercellular signaling cascades. The common health conditions associated with alcohol use disorder (AUD) are pancreatitis, liver cirrhosis, neuropathies, cardiomyopathies, and dementia. By virtue of its anatomical orientation and function, the lung continually encounters microbes, and this can be exacerbated by excessive alcohol consumption. Alcohol abuse is a well-known risk factor for bacterial infection in the lung. Increased susceptibility to bacterial pneumonia is caused by impaired immune responses in individuals with AUD. The key cells to defend against pulmonary infections are innate immune cells, including alveolar macrophages, neutrophils, and adaptive immune cells, such as T and B cells. This review highlights recent advances illuminating the roles of innate immune responses in bacterial pneumonia and the effects of alcohol in bacterial pneumonia. Understanding the molecular mechanisms associated with innate immunity in the lung is essential for developing effective strategies to control pneumonia and alcohol-mediated immunosuppression.

The alcohol cue-exposure paradigm has a long and rich history in alcohol use disorder (AUD) research, contributing to the identification of risk factors, the recognition of craving as a core symptom, the understanding of AUD neurobiology, and the development of both pharmacological and behavioral treatments. The goal of this review was to evaluate the utility of the alcohol cue-exposure paradigm as a screening tool for AUD medication development and to provide recommendations for refinement of the paradigm. First, we review evidence supporting the predictive validity and clinical applicability of the alcohol cue-exposure paradigm. Second, we examine current practices in implementing the paradigm in AUD pharmacotherapy studies. Third, we highlight several areas for refinement and offer recommendations for the implementation of this paradigm. Finally, we outline key conclusions and actionable future directions. In summary, while the alcohol cue-exposure paradigm has an established foundation in the study of AUD pharmacotherapies, its future success hinges on a concerted effort to refine and standardize protocols and validate outcome measures in large-scale studies. Addressing these priorities could accelerate the development and regulatory approval of novel treatments for AUD.