The role of stress in drug addiction. An integrative review

Background: The high prevalence and burden to society of drug abuse and addiction is undisputed. However, its conceptualisation as a brain disease is controversial, and available interventions insufficient. Research on the role of stress in drug addiction may bridge positions and develop more effective interventions. Aim: The aim of this paper is to integrate the most influential literature to date on the role of stress in drug addiction. Methods: A literature search was conducted of the core collections of Web of Science and Semantic Scholar on the topic of stress and addiction from a neurobiological perspective in humans. The most frequently cited articles and related references published in the last decade were finally redrafted into a narrative review based on 130 full-text articles. Results and discussion: First, a brief overview of the neurobiology of stress and drug addiction is provided. Then, the role of stress in drug addiction is described. Stress is conceptualised as a major source of allostatic load, which result in progressive long-term changes in the brain, leading to a drug-prone state characterized by craving and increased risk of relapse. The effects of stress on drug addiction are mainly mediated by the action of corticotropin-releasing factor and other stress hormones, which weaken the hippocampus and prefrontal cortex and strengthen the amygdala, leading to a negative emotional state, craving and lack of executive control, increasing the risk of relapse. Both, drugs and stress result in an allostatic overload responsible for neuroadaptations involved in most of the key features of addiction: reward anticipation/craving, negative affect, and impaired executive functions, involved in three stages of addiction and relapse. Conclusion: This review elucidates the crucial role of stress in drug addiction and highlights the need to incorporate the social context where brain-behaviour relationships unfold into the current model of addition.