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

Abstract

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.

Article type: Research Article

Keywords: Genetics, Molecular biology

Authors: Madeline H. Meier ⚬, Karen Sugden, Terrie E. Moffitt, Benjamin S. Williams, Kyle J. Bourassa ⚬, Renate Houts, Sandhya Ramrakha, Reremoana Theodore, Avshalom Caspi ⚬

Affiliations: https://ror.org/03efmqc40grid.215654.10000 0001 2151 2636Department of Psychology, Arizona State University, Tempe, AZ USA; https://ror.org/00py81415grid.26009.3d0000 0004 1936 7961Department of Psychology & Neuroscience, Duke University, Durham, NC USA; https://ror.org/00py81415grid.26009.3d0000 0004 1936 7961Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC USA; https://ror.org/00py81415grid.26009.3d0000 0004 1936 7961Center for Genomic and Computational Biology, Duke University, Durham, NC USA; https://ror.org/0220mzb33grid.13097.3c0000 0001 2322 6764Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, England; https://ror.org/01xtthb56grid.5510.10000 0004 1936 8921PROMENTA Research Center, University of Oslo, Oslo, Norway; https://ror.org/02d29d188grid.512153.1Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham VA Health Care System, Durham, NC USA; https://ror.org/05vzafd60grid.213910.80000 0001 1955 1644Department of Psychology, Georgetown University, Washington, DC USA; https://ror.org/03njmea73grid.414179.e0000 0001 2232 0951Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC USA; https://ror.org/01jmxt844grid.29980.3a0000 0004 1936 7830Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand

License: © The Author(s) 2025, corrected publication 2025 CC BY 4.0 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Article links: DOI: 10.1038/s41380-025-03042-9  |  PubMed: 40579423  |  PMC: PMC12436150

Relevance: Moderate: mentioned 3+ times in text

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