Abstract Research has shown a significant variation in neurobiological regulation in alcohol use or misuse and alcohol use disorder (AUD) influenced by environmental factors that constantly interact with biological underpinnings such as a person’s genetic background. These differences affect how individuals respond to treatment with pharmacological or behavioral therapies, including placebo responses. Here we discuss the dynamic nature of neurobiological dysregulation and highlight research conducted to identify specific genes whose expression alterations drive molecular level changes underlying placebo responses in AUD. Moreover, given that chronic pain and AUD are highly comorbid common conditions, we present similarities between the two conditions. A mechanistic understanding of the relationship between AUD and chronic pain is important for effective treatment and prevention of both conditions.