Methamphetamine and Cocaine Overdose Deaths in the United States, 1999-2023.

The ongoing "fourth wave" of the U.S. overdose epidemic has been marked by rising deaths co-involving fentanyl with stimulants such as methamphetamine and cocaine. Using data obtained from the CDC WONDER Multiple Cause of Death database, this serial cross-sectional study analyzed stimulant overdose mortality trends between 1999 and 2023. We stratified crude mortality rates by sex, race and ethnicity, and opioid co-involvement. We used Joinpoint regression to examine temporal trends and estimate annual percentage changes (APC) within time segments. From 1999 to 2023, methamphetamine-involved overdose deaths increased from 547 to 34,855, with mortality rates rising from 0.20 (95% CI, 0.18-0.21) to 10.41 (95% CI, 10.30-10.52) per 100,000 (AAPC: 18.49% [95% CI, 17.67-20.17]; p < 0.001). Cocaine-involved overdose deaths increased from 3,822 to 29,449, with mortality rates rising from 1.37 (95% CI, 1.33-1.41) to 8.79 (95% CI, 8.69-8.89) per 100,000 (AAPC: 8.80% [95% CI, 8.18-9.95]; p < 0.001). Stimulants were involved in 7.95% and 10.28% of fentanyl overdoses in 1999 and 2011, respectively, but dramatically rose to 56.67% by 2023. Methamphetamine-involved overdose deaths were highest among American Indian/Alaska Native individuals, accounting for 44.50% of overdose deaths, while cocaine-involved overdose deaths were highest among Black individuals, comprising 48.47% of overdose deaths. Rising stimulant mortality, particularly in racial and ethnic minoritized populations, underscores the need for expanding access to harm reduction resources, greater funding for stimulant use disorder research, and targeted public health interventions.