A global analysis of drug use disorders (DUDs) spanning 204 countries revealed that deaths more than doubled from 61,774 in 1990 to 137,278 in 2021, despite declining new case rates. Using Global Burden of Disease data, researchers found disability-adjusted life-years (DALYs) rose 75%, with the highest impact in high-income regions. North America saw an 11.2-fold rise in deaths, while East Asia recorded fewer new cases. Opioid-related DALYs increased 32%, and cocaine-related deaths more than doubled. Men aged 20–29 bore the greatest burden. Researchers warned that DUDs threaten global health goals by perpetuating disparities and straining public health systems.