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

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

Joseph P Allen  1 , Joshua S Danoff  2 , Meghan A Costello  2 , Gabrielle L Hunt  2 , Amanda F Hellwig  2 , Kathleen M Krol  2 , Simon G Gregory  3 , Stephanie N Giamberardino  3 , Karen Sugden  3 , Jessica J Connelly  2
Affiliations

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

Joseph P Allen et al. Drug Alcohol Depend. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest No conflict declared

Figures

Figure 1 -
Figure 1 -. Relation of Timing of Marijuana Use to Epigenetic Aging
Note: Standardized estimates above are after accounting for cell counts, chronological age, demographic factors, lifetime history of cigarette smoking (not shown) and other variables shown in model. Estimates in parentheses are from marijuana use at a given time point without considering/accounting for use at other time points.
Figure 2 –
Figure 2 –. Mediating Role of cg05575921 in link between Marijuana Use and Epigenetic Aging
Note: Standardized estimates above are after accounting for cell counts, chronological age, and demographic factors.
See this image and copyright information in PMC

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