Long-Term Marijuana Use Was Linked to DNA Changes in Genes Related to Schizophrenia, Bipolar Disorder, and Cell Growth
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?Are these methylation changes reversible after cessation of marijuana use?
- ?Do the epigenetic changes precede or follow the development of psychiatric symptoms?
Trust & Context
- Key Stat:
- Marijuana-linked DNA changes enriched in schizophrenia and bipolar disorder pathways
- Evidence Grade:
- Well-established longitudinal cohort (CARDIA) with validated epigenomic methods and replication of prior findings, though observational design limits causal inference.
- Study Age:
- Published 2023, using data from the CARDIA cohort (examinations at years 15 and 20).
- Original Title:
- Genome-wide DNA methylation association study of recent and cumulative marijuana use in middle aged adults.
- Published In:
- Molecular psychiatry, 28(6), 2572-2582 (2023)
- Authors:
- 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
- Database ID:
- RTHC-04809
Evidence Hierarchy
Follows a group of people over time to track how outcomes develop.
What do these levels mean? →Frequently Asked Questions
Does marijuana change your DNA?
Not the DNA sequence itself, but this study found marijuana use was associated with changes in DNA methylation, which affects how genes are turned on or off. These epigenetic changes were found in genes linked to psychiatric disorders.
What conditions were the affected genes linked to?
The genes with methylation changes were overrepresented in pathways related to schizophrenia, bipolar disorder, substance-related disorders, cell proliferation, and hormone signaling.
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Cite This Study
https://rethinkthc.com/research/RTHC-04809APA
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
MLA
Nannini, Drew R, et al. "Genome-wide DNA methylation association study of recent and cumulative marijuana use in middle aged adults.." Molecular psychiatry, 2023. https://doi.org/10.1038/s41380-023-02106-y
RethinkTHC
RethinkTHC Research Database. "Genome-wide DNA methylation association study of recent and ..." RTHC-04809. Retrieved from https://rethinkthc.com/research/nannini-2023-genomewide-dna-methylation-association
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.