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

https://doi.org/10.1016/j.drugalcdep.2022.109363Get rights and content

Highlights

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    Lifetime levels of marijuana use predicted accelerated epigenetic aging.

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    Predictions remained even after accounting for cigarette smoking and a wide range of potential confounding variables.

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    Dose-response and recency of use effects were both observed.

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.

Section snippets

. Introduction

Over the past fifteen years, debates around the status of marijuana (Cannabis sativa) have increased significantly in the United States and elsewhere as the movement to legalize its possession and use has gained steam (Caulkins et al., 2016). As marijuana use becomes legal in more places and its use becomes more common (SAMSHA, 2020), increasing our understanding of its potential long-term physical effects becomes critical. Evidence to date regarding negative physical health effects of

Participants

This report is drawn from a larger longitudinal investigation of the long-term outcomes of adolescent social development in familial and peer contexts. The final sample of participants for analyses included 154 participants of 184 originally assessed at age 13 and for whom epigenetic data was obtained at age 30 (M = 29.70, SD = 2.16; 84% retention). Adolescents were recruited from the 7th and 8th grades of a public middle school drawing from suburban and urban populations in the Southeastern

Preliminary analyses

Means and standard deviations for all primary variables used in the study are presented in Table 1. Marijuana use and epigenetic aging scores were examined for distributional properties and skewness and kurtosis and were both within acceptable levels (i.e., less than 2). DNAmGrimAge and DunedinPoAm were correlated at r = 0.72; both measures were correlated with methylation at site cg05575921 (r’s = − 0.75 and − 0.65 for DNAmGrimage and DunedinPoAm, respectively; all p’s < 0.001).

Primary analyses

Hypothesis 1

Lifetime

Discussion

This study found a substantial link between lifetime levels of marijuana use and two different measures of epigenetic aging, assessed at age 30. This link remained even after accounting for the effects of lifetime cigarette smoking history. Further, the predictive link from lifetime marijuana use to epigenetic age acceleration was of similar magnitude to the observed effect of cigarette smoking. Follow-up analyses suggest these links are likely to be mediated by the epigenetic effects of smoke

Role of Funding Source

This study was supported by grants from the National Institute of Child Health and Human Development and the National Institute of Mental Health (5R37HD058305-23, R01HD058305-16A1, R01-MH58066). We thank the Duke Molecular Physiology Institute Molecular Genomics Core for processing Illumina DNA methylation arrays.

CRediT authorship contribution statement

All authors made substantial contributions to this manuscript. Drs. Allen and Connelly designed the study and directed its implementation, including quality assurance and control. Mr. Danoff and Ms. Krol provided content expertise on epigenetic analyses and input to analytic strategy. Ms. Costello, Ms. Hunt and Ms. Hellwig, Ms. Krol provided expertise on the design of the study and the analytic strategy. Drs. Gregory, Giamberardino oversaw primary epigenetic data processing. Dr. Sugden provided

Conflict of Interest

No conflict declared.

Acknowledgements

This study was supported by grants from the National Institute of Child Health and Human Development and the National Institute of Mental Health (5R37HD058305-23, R01HD058305-16A1, R01-MH58066). We thank the Duke Molecular Physiology Institute Molecular Genomics Core for processing Illumina DNA methylation arrays. Correspondence can be addressed to either Joseph Allen or Jessica Connelly at Department of Psychology, University of Virginia, PO Box 400400, Charlottesville, VA 22904-4400. Email: //[email protected]

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