The Limbic System in Co-Occurring Substance Use and Anxiety Disorders: A Narrative Review Using the RDoC Framework

Substance use disorders (SUDs) and anxiety disorders (ADs) are highly comorbid, a co-occurrence linked to worse clinical outcomes than either condition alone. While the neurobiological mechanisms involved in SUDs and anxiety disorders are intensively studied separately, the mechanisms underlying their comorbidity remain an emerging area of interest. This narrative review explores the neurobiological processes underlying this comorbidity, using the Research Domain Criteria (RDoC) framework to map disruptions in positive valence, negative valence, and cognitive systems across the three stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Anxiety and substance use play a reciprocal role at each stage of addiction, marked by significant psychosocial impairment and dysregulation in the brain. A more thorough understanding of the neural underpinnings involved in comorbid SUDs and anxiety disorders will contribute to more tailored and effective therapeutic interventions and assessments.