Abstract
Substance use disorders (SUDs) are marked by heterogeneity in clinical symptomatology and high relapse rates following treatment. Here, we describe specific peripheral and central stress responses associated with the pathophysiology of SUDs. We outline potential stress response measures, including hypothalamus-pituitary-adrenal axis markers, autonomic responses, and central structural and functional brain alterations that could be exploited as putative biomarkers in SUDs. We posit that stress responses can be predictive of both the development of SUDs and their high relapsing nature. We examine their potential as candidate biomarkers, as well as the remaining challenges in developing and implementing their application for the prevention and treatment of SUDs.