This chapter traces the historical evolution of America’s relationship with psychoactive substances, from nineteenth century medical use of opium to the racially coded policies of the twentieth century and the shifting narratives of the opioid crisis in the twenty-first century. It highlights how race, gender, class, and shifting media narratives have shaped both public perceptions and drug policy responses over time. Drawing on key legislation such as the Harrison Narcotics Tax ActHarrison Narcotics Tax Act and the role of figures like Harry Anslinger, the chapter demonstrates how addiction was redefined from a medical condition to a legal and moral offense, disproportionately targeting marginalized communities. Through detailed historical analysis, it exposes how media framing contributed to synthetic panicsSynthetic panic and moral crusades, pathologizing Black and Latino drug users while eliciting empathy for white opioid usersWhite opioid users in recent decades. The chapter concludes by linking historical patterns to contemporary policy debates, emphasizing the need for equitable, evidence-based responses to addiction that resist punitive reflexes and racialized narratives.