DNA Methylation Profiles of Long-Term Cannabis Users in Midlife: An Evaluation of Published Markers

TL;DR

This study finds that long-term cannabis use is linked to specific DNA methylation changes, some of which are also seen in tobacco users and may be reversible after quitting.

Contribution

The study identifies nine DNA methylation markers robustly associated with long-term cannabis use after adjusting for tobacco and other factors.

Findings

Long-term cannabis use is associated with hypomethylation of nine DNA methylation markers.

Six of these markers are linked to gene expression, indicating biological relevance.

Cannabis cessation is associated with less extreme DNA methylation changes compared to ongoing users.

Abstract

Long-term cannabis use has been linked to a number of health problems, including respiratory problems, cardiovascular diseases, cognitive decline, and mental illness. Epigenetic responses to cannabis use could underlie cannabis-related health problems. We examined the DNA-methylation profiles of long-term cannabis users in midlife, re-evaluating a set of 246 previously published cannabis-associated methylation markers. Data were from the Dunedin Study, a five-decade longitudinal study of a birth cohort (analytic n = 787). Peripheral whole blood was drawn when the cohort was age 45, and DNA methylation was assayed using the EPIC 850K BeadChip. Analyses compared long-term cannabis users with non-users and, for a benchmark comparison, with long-term tobacco users. Results showed that long-term cannabis use was associated with sixteen of the previously published 246 cannabis-related methylation markers. All cannabis-related methylation markers were also associated with long-term tobacco use. Nonetheless, after adjusting for long-term tobacco use and other covariates, including childhood SES, family history of substance dependence, and long-term alcohol use, long-term cannabis use was robustly associated with hypomethylation of nine markers: cg05575921, cg21566642, cg03636183, cg21161138, cg01940273, cg17739917, cg05086879, cg02978227, cg23079012. Six of the nine cannabis-related markers were associated with gene expression levels, suggesting meaningful biological associations. Cannabis quitters showed less extreme DNA hypomethylation than long-term cannabis users. Long-term cannabis use could affect the epigenome similarly to tobacco use, possibly though smoke inhalation. Cannabis cessation, like tobacco cessation, may reverse altered DNA methylation.