The Role of Interleukin 6 in Substance Use Disorder Treatment Failure

Substance use disorders (SUDs) are often misunderstood as a reflection of an individual's lack of motivation or willpower or as a moral failing. SUDs are complex and require a biopsychosocial lens to understand the phenomenon, particularly treatment failure, which is described as a deficit in patients' willpower/self-regulation or dedication to managing their condition.Recent evidence has implicated inflammatory cytokines such as interleukin 6 (IL-6) in the action of substance use by impairing executive functioning, which is an essential aspect of self-regulatory control. Emerging research indicates that inflammation may also shape social behavior, including social withdrawal and approach, thus having potential implications on health-seeking and health-sustaining behaviors often interpreted as a dedication to managing health conditions.The aim of this two-part biobehavioral synthesis is to (a) examine the scientific evidence of the role of IL-6 in self-regulatory failure, (b) explore IL-6 as a common inflammatory mechanism across SUDs, and (c) investigate the role of IL-6 in social withdrawal and approach to gain an understanding of how this determinant may impact treatment failure.Overall, the evidence supports a new paradigm of treatment failure that stresses the influence of IL-6 on self-regulatory failure by way of dual cognitive processing and the role of IL-6 in shaping social behavior central to health-seeking and health-sustaining behaviors. This discovery will help to minimize stigma and blame. Understanding the role of IL-6 in treatment failure may elucidate novel targets for intervention, improve treatment outcomes, and break the social disconnection cycle often seen in SUDs.