Abstract
BACKGROUND: Global evidence on substance use disorders (SUDs) remains fragmented, and fewer analyses have benchmarked country-level burden against development gradients. We used Global Burden of Disease 2021 estimates to update long-term trends and inequalities in SUDs, including alcohol use disorder and drug use disorders (DUDs), from 1990 to 2021. METHODS: We analysed Global Burden of Disease 2021 estimates for SUDs, alcohol use disorder, and DUDs across 204 countries and territories. We report age-standardised prevalence rates (ASPR), incidence rates, and disability-adjusted life-years rates (age-standardised disability-adjusted life-years rate) per 100 000 population with 95% uncertainty intervals (UI). Analyses examined temporal trends, age-sex patterns, regional and national variation, socio-demographic index (SDI) - stratified gradients, and deviations of observed burden from SDI-based expected levels. RESULTS: In 2021, 162.86 million people had SUDs (95% UI = 145.95, 180.85). The global ASPR was 1982.13 per 100 000 (95% UI = 1773.57, 2206.29), declining by 16.9% (95% UI = -18.7, -14.9) since 1990; age-standardised incidence rate was 843.37 (95% UI = 736.21, 956.19), declining by 17.3% (95% UI = -19.7, -15.2); and ASDR was 393.36 (95% UI = 323.56, 469.04), declining by 9.1% (95% UI = -11.9, -5.7). Alcohol use disorder accounted for about 111.12 million cases (95% UI = 96.35, 127.90) (ASPR = 1335.43; 95% UI = 1153.65, 1539.75), and DUDs for about 53.12 million (95% UI = 46.99, 60.95) (ASPR = 663.80; 95% UI = 584.52, 766.14). Geographic heterogeneity was marked: high-income North America had the highest ASDR = 2193.48 (95% UI = 1861.45, 2529.02) and Western Sub-Saharan Africa the lowest ASDR = 136.22 (95% UI = 108.18, 170.26). Drug use disorder burden increased in several high-SDI settings in 2020-2021, while burden peaked in young adults (approximately 25-35 years) and was consistently higher among males. CONCLUSIONS: Despite declining global age standardised rates since 1990, SUDs remain a major source of health loss, with pronounced age-sex differences, substantial cross-country heterogeneity, and widening divergence by development level. Recent increases in drug-related burden in some high-SDI settings highlight the need for strengthened surveillance and context-specific prevention, treatment, and harm-reduction responses.