Global marijuana use has risen markedly in recent decades. Although prior research suggests that marijuana use is associated with epigenetic alterations, its relationship with biological aging remains unclear. This study aimed to examine the association between marijuana use and accelerated aging and explore the mediating role of metal exposure.

Using data from 12,806 U.S. adults (NHANES 2005–2018), biological age (BA) was calculated using two validated algorithms, phenotypic age (PhenoAge) and Klemera–Doubal biological age (KD-BioAge), with aging acceleration defined as the residuals from linear regression of BA on chronological age (CA). Marijuana use status was ascertained via standardized interviews. Analyses included survey-weighted multivariable linear regression, stratified subgroup analyses, joint exposure assessments, and mediation analyses.

Current marijuana users exhibited significantly accelerated aging versus never users: PhenoAge acceleration (β = 0.72, 95% CI: 0.41–1.02, P   <  0.001) and KD-BioAge acceleration (β = 0.36, 95% CI: 0.14–0.59, P  = 0.002), after full adjustment. Subgroup and joint exposure analyses showed consistent associations, with evidence of additive associations among dual users of marijuana and tobacco. Mediation analyses identified blood cadmium as a partial mediator, explaining 15.6% and 8.3% of aging acceleration for PhenoAge and KD-BioAge, respectively.

This study provides robust epidemiological evidence linking marijuana use to accelerated biological aging, with blood cadmium identified as a potential mechanistic link. These findings highlight the public health importance of understanding the long-term physiological correlates of marijuana use.