Initial Drug Sensitivity and Vulnerability to Substance Use Disorders: A Review of Individual Influences

Individual differences in the sensitivity and response to drugs of abuse are reliably associated with later patterns of substance use and, for some, progression to a substance use disorder diagnosis. This review synthesizes human drug challenge, longitudinal, and translational animal evidence to characterize how early or initial sensitivity to drugs, shaped by heritable and developmental factors, may relate to subsequent risk. These initial responses, through associative learning, may influence how drug-paired cues acquire motivational significance over time. Ample evidence suggests that early response variability is a biologically grounded and measurable correlate of SUD vulnerability, detectable well before chronic neuroadaptation, with potential utility for targeted prevention and intervention efforts.