This chapter analyses the historical transformation from ritualistic and therapeutic use of mind-altering substances to their global regulation and criminalisation. Focusing on the colonial and industrial eras, it highlights how opium, coca, and alcohol were recontextualised as economic commodities and instruments of empire. The chapter tracks the emergence of international drug control regimes, moral panics, and racialised legislation — particularly the British Opium Wars, US Harrison Narcotics Act, and global treaties. The intersection of state regulation, corporate profit, and public health is critically examined through case studies including the US opioid crisis. In parallel, sugar and caffeine are discussed as ‘soft’ stimulants that escaped moral scrutiny despite their neurochemical effects. The chapter concludes with a comparative look at regulation and commodification, showing how different substances became entangled in legal, moral, and economic narratives.