DNA methylation profiles of long-term cannabis users in midlife: a comprehensive evaluation of published cannabis-associated methylation markers in a representative cohort.

Epigenetic responses to cannabis use could link cannabis use to health problems. We examined the DNA-methylation profiles of long-term cannabis users in midlife, re-evaluating a set of 246 cannabis-associated methylation markers that were previously identified in other studies. 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 850 K BeadChip. Analyses compared long-term cannabis users with non-users and, for a benchmark comparison, long-term tobacco users. Results showed that long-term cannabis use was associated with sixteen of the previously published 246 cannabis-related methylation markers. Methylation markers that were associated with long-term cannabis use were also associated with long-term tobacco use. However, after adjusting for long-term tobacco use and other covariates, long-term cannabis use was robustly associated with hypomethylation of nine markers: cg05575921, cg21566642, cg03636183, cg21161138, cg01940273, cg17739917, cg05086879, cg02978227, cg23079012. Cannabis-related hypomethylation was associated with higher gene expression in the Dunedin Cohort, suggesting meaningful biological associations. A comparison of long-term cannabis users with cannabis quitters revealed that quitters showed less extreme DNA hypomethylation. Long-term cannabis use could affect the epigenome similarly to tobacco use, possibly at least partly though smoke inhalation. Cannabis cessation, like tobacco cessation, may reverse altered DNA methylation.

Duke Scholars

Author Terrie E. Moffitt Psychology & Neuroscience

Author Avshalom Caspi Psychology & Neuroscience

Author Kyle Bourassa