Lifetime marijuana use and epigenetic age acceleration: A 17-year prospective examination
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]
References (38)
- et al.
The international personality item pool and the future of public-domain personality measures
J. Res. Personal.
(2006) - et al.
Associations between cigarette smoking and cannabis dependence: a longitudinal study of young cannabis users in the United Kingdom
Drug Alcohol. Depend.
(2015) - et al.
Psychotherapeutic, licit, and illicit use of drugs among adolescents: an epidemiological perspective
J. Adolesc. Health Care
(1987) - et al.
Psychosocial stress and epigenetic aging
Int. Rev. Neurobiol.
(2020) - et al.
Epigenetic effects of cannabis exposure
Biol. Psychiatry
(2016) - et al.
Epigenome‐wide association study for all‐cause mortality in a cardiovascular cohort identifies differential methylation in castor zinc finger 1 (CASZ 1)
J. Am. Heart Assoc.
(2019) - et al.
Running with the pack: teen peer-relationship qualities as predictors of adult physical health
Psychol. Sci.
(2015) - et al.
DNA methylation differentiates smoking from vaping and non-combustible tobacco use
Epigenetics
(2021) - et al.
Accuracy and utility of an epigenetic biomarker for smoking in populations with varying rates of false self-report
Am. J. Med. Genet. B Neuropsychiatr. Genet.
(2017) - et al.
Chronic adolescent marijuana use as a risk factor for physical and mental health problems in young adult men
Psychol. Addict. Behav.
(2015)
Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm
Elife
Lung disease induced by drug addiction
Thorax
Developmental trajectories of marijuana use from adolescence to adulthood: Personal predictors
Arch. Pediatr. Adolesc. Med.
Marijuana Legalization: What Everyone Needs to Know®
General and oral health implications of cannabis use
Aust. Dent. J.
Epigenetic aging in major depressive disorder
Am. J. Psychiatry
DNA methylation age of human tissues and cell types
Genome Biol.
HIV-1 infection accelerates age according to the epigenetic clock
J. Infect. Dis.
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