Abstract
There is a high co-occurrence of risky substance use among adults with traumatic brain injury (TBI), although it is unknown if the neurologic sequelae of TBI can promote this behavior. We propose that to conclude that TBI can cause risky substance use, it must be determined that TBI precedes risky substance use, that confounders with the potential to increase the likelihood of both TBI and risky substance use must be ruled out, and that there must be a plausible mechanism of action. In this review, we address these factors by providing an overview of key clinical and preclinical studies and list plausible mechanisms by which TBI could increase risky substance use. Human and animal studies have identified an association between TBI and risky substance use, although the strength of this association varies. Factors that may limit detection of this relationship include differential variability due to substance, sex, age of injury, and confounders that may influence the likelihood of both TBI and risky substance use. We propose possible mechanisms by which TBI could increase substance use that include damage-associated neuroplasticity, chronic changes in neuroimmune signaling, and TBI-associated alterations in brain networks.