Lifetime marijuana use and epigenetic age acceleration: A 17-year prospective examination

Drug Alcohol Depend. 2022 Apr 1:233:109363. doi: 10.1016/j.drugalcdep.2022.109363. Epub 2022 Feb 17.


Aims: This study was designed to assess links between lifetime levels of marijuana use and accelerated epigenetic aging.

Design: Prospective longitudinal study, following participants annually from age 13 to age 30.

Setting and participants: A community sample of 154 participants recruited from a small city in the Southeastern United States.

Measurements: Participants completed annual assessments of marijuana use from age 13 to age 29 and provided blood samples that yielded two indices of epigenetic aging (DNAmGrimAge and DunedinPoAm) at age 30. Additional covariates examined included history of cigarette smoking, anxiety and depressive symptoms, childhood illness, gender, adolescent-era family income, and racial/ethnic minority status.

Findings: Lifetime marijuana use predicted accelerated epigenetic aging, with effects remaining even after covarying cell counts, demographic factors and chronological age (β's = 0.32 & 0.27, p's < 0.001, 95% CI's = 0.21-0.43 & 0.16-0.39 for DNAmGrimAge and DunedinPoAm, respectively). Predictions remained after accounting for cigarette smoking (β's = 0.25 & 0.21, respectively, p's < 0.001, 95% CI's = 0.14-0.37 & 0.09-0.32 for DNAmGrimAge and DunedinPoAm, respectively). A dose-response effect was observed and there was also evidence that effects were dependent upon recency of use. Effects of marijuana use appeared to be fully mediated by hypomethylation of a site linked to effects of hydrocarbon inhalation (cg05575921).

Conclusions: Marijuana use predicted epigenetic changes linked to accelerated aging, with evidence suggesting that effects may be primarily due to hydrocarbon inhalation among marijuana smokers. Further research is warranted to explore mechanisms underlying this linkage.

Keywords: Dosage effects; Epigenetic aging; Lifetime cannabis exposure; Prospective longitudinal assessment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acceleration
  • Adolescent
  • Adult
  • Child
  • Epigenesis, Genetic
  • Ethnicity
  • Humans
  • Longitudinal Studies
  • Marijuana Smoking* / epidemiology
  • Marijuana Smoking* / genetics
  • Marijuana Use* / epidemiology
  • Minority Groups
  • Prospective Studies