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Background Drug use disorders (DUDs) represent a significant global health burden with marked regional variations. This study compares DUDs burden, trends, and projections among China, India, and the United States (US)—three countries comprising approximately 40% of the world’s population and spanning a socio-demographic index (SDI) range from 0.61 to 0.88—to elucidate how developmental stages influence DUDs patterns and inform targeted interventions. Methods Data on the incidence, prevalence, deaths, and disability-adjusted life years (DALYs) of DUDs from 1990 to 2023 were extracted from the Global Burden of Disease Study 2023, stratified by sex, age group, and drug subtype. Temporal trends were analyzed via Joinpoint regression, and future burden to 2040 was projected using the Nordpred age-period-cohort model. Results In 2023, the US had the highest age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR), while India had the lowest. From 1990 to 2023, China showed declining trends across all age-standardized rate (ASR), in contrast to rising trends in the US; India showed mixed trends, with rises in ASIR, ASPR, and ASDR but a slight decrease in ASMR. The burden was concentrated in younger adults and men. Opioid use disorders contributed most to deaths and DALYs in all three countries. Projections from 2024 to 2040 indicate marked divergence: the US is expected to see growth across all indicators, with deaths nearly doubling (109.59%) and ASMR increasing by 90.76%; India is projected to experience rises in ASMR (30.40%) and ASDR (15.73%); while China shows modest increases across all ASR (4.61%–24.23%) despite a decline in incident cases (−7.45%). Conclusion DUDs burden and trends differ markedly among the three countries. Emerging trends underscore the need for sustained, targeted interventions focusing on high-risk populations and specific drug types to mitigate future impacts.