An epigenome-wide study of over 1,000 adults found that both recent and cumulative marijuana use were associated with widespread DNA methylation changes, with affected genes enriched in pathways related to psychotic disorders, cell proliferation, and hormone signaling.
Genetics researchers, long-term cannabis users, anyone interested in biological mechanisms linking cannabis and mental health.
Marijuana-linked DNA changes enriched in schizophrenia and bipolar disorder pathways
What the researchers found
At examination year 15 (n = 1,023), 22 and 31 methylation markers were associated with recent and cumulative marijuana use. At year 20 (n = 883), 132 and 16 markers were found. Eight previously reported markers were replicated. The study identified 640 cis-meQTLs and 198 differentially methylated regions. Affected genes were overrepresented in pathways related to cellular proliferation, hormone signaling, and infections, as well as schizophrenia, bipolar disorder, and substance-related disorders.
Why it matters
This is one of the first studies to examine how cumulative, long-term marijuana use affects the epigenome in middle-aged adults. The enrichment of affected genes in psychiatric disorder pathways provides a potential biological mechanism linking chronic cannabis use to mental health outcomes.
The numbers in context
Year 15: 1,023 participants, 22 markers (recent use), 31 markers (cumulative). Year 20: 883 participants, 132 markers (recent), 16 markers (cumulative). 8 previously reported markers replicated. 640 cis-meQTLs. 198 differentially methylated regions.
How the study worked
Epigenome-wide association study within the CARDIA longitudinal cohort. Whole blood DNA methylation profiled at years 15 and 20 using the Illumina MethylationEPIC BeadChip. Recent and cumulative marijuana use assessed from year 0. FDR-corrected significance threshold.
What this study cannot tell us
Observational study cannot determine causation. Blood-based methylation may not reflect brain tissue changes. Self-reported marijuana use. Cannot rule out confounding by other lifestyle factors. Effect sizes of individual methylation changes were small.
How to read the evidence
Well-established longitudinal cohort (CARDIA) with validated epigenomic methods and replication of prior findings, though observational design limits causal inference.
When this study was published
Published 2023, using data from the CARDIA cohort (examinations at years 15 and 20).
The bigger picture
Epigenetic changes do not alter DNA sequence but can change gene expression. Finding that marijuana use is associated with methylation changes in genes linked to schizophrenia and bipolar disorder provides molecular-level evidence that may help explain the epidemiological associations between cannabis and psychotic disorders.
Questions still open
- Are these methylation changes reversible after cessation of marijuana use?
- Do the epigenetic changes precede or follow the development of psychiatric symptoms?
Common questions
Does marijuana change your DNA?
What conditions were the affected genes linked to?
Read the original research
Genome-wide DNA methylation association study of recent and cumulative marijuana use in middle aged adults.
Molecular psychiatry, 28(6), 2572-2582
Citation
Nannini, Drew R; Zheng, Yinan; Joyce, Brian T; Kim, Kyeezu; Gao, Tao; Wang, Jun; Jacobs, David R; Schreiner, Pamela J; Yaffe, Kristine; Greenland, Philip; Lloyd-Jones, Donald M; Hou, Lifang. (2023). Genome-wide DNA methylation association study of recent and cumulative marijuana use in middle aged adults.. Molecular psychiatry, 28(6), 2572-2582. https://doi.org/10.1038/s41380-023-02106-y
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