AUTHOR=Juliano Vitor Augusto Laurino , Albernaz-Mariano Kairo Alan , Covre Luiza Helena Halas , Jucá Paloma Marinho , Pereira Robbert Mota , Shigeo-de-Almeida Amadeu , Sampaio Lucas Luzia , Duque Erica de Almeida , Munhoz Carolina Demarchi 

TITLE=Neurobiological intersections of stress and substance use disorders

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1548372

DOI=10.3389/fnins.2025.1548372

ISSN=1662-453X

ABSTRACT=Substance use has been intertwined with human history for millennia. Throughout the ages, people have consumed various substances for medicinal, spiritual, and recreational reasons, although occasional use differs significantly from substance use disorders (SUDs). Exposure to lifetime stressors constitutes a significant risk factor for both psychiatric disorders and SUD development and relapse. Indeed, hypothalamic–pituitary–adrenal (HPA) axis modulation, alterations in neuroanatomical and neurotransmitter systems, as well as neuroinflammation are common features of stress-related mood disorders and SUDs. In this mini-review, we will explore how stress exposure influences the SUDs' neurobiological basis on different scales—from large neural circuitries to specific molecular mechanisms—and discuss novel targets for potential treatments.