A meta-analysis of 9,436 participants across seven cohorts and two ancestries identified four DNA methylation sites significantly associated with lifetime cannabis use after accounting for cigarette smoking effects.
Epigenetics and genomics researchers; biomarker scientists developing objective measures of cannabis exposure.
4 cannabis-specific DNA methylation sites identified across 9,436 participants
What the researchers found
Four CpG sites were significantly associated with lifetime cannabis use independent of smoking: cg22572071 (near ADGRF1), cg15280358 (in ADAM12), cg00813162 (in ACTN1), and cg01101459 (near LINC01132). In never-smokers, an additional site was found (cg14237301 in APOBR). A methylation score from these sites explained 3.79% of the variance in lifetime cannabis use.
Why it matters
Separating cannabis-specific epigenetic effects from smoking effects has been a major challenge. This large multi-ethnic study identifies methylation changes attributable to cannabis itself, which could serve as biomarkers and starting points for understanding how cannabis affects health at the molecular level.
The numbers in context
9,436 participants (7,795 European, 1,641 African ancestry). 4 significant CpG sites after FDR correction (p < 5.85 x 10^-7). 1 additional site in never-smokers. Methylation score explained 3.79% of variance in lifetime cannabis use.
How the study worked
Trans-ancestry epigenome-wide association study (EWAS) meta-analysis across seven cohorts including 7,795 European and 1,641 African ancestry participants. Analyses controlled for cigarette smoking effects. Leave-one-out approach for methylation score validation.
What this study cannot tell us
Peripheral blood methylation may not reflect brain or lung tissue changes. Binary outcome (ever vs never use) does not capture dose or frequency. Cross-sectional design cannot determine whether methylation changes are cause or consequence of use. 3.79% variance explained is modest.
How to read the evidence
Large multi-cohort meta-analysis with trans-ancestry replication and careful smoking adjustment. Strong methodology for epigenetic research.
When this study was published
2024 study
The bigger picture
These cannabis-specific DNA methylation changes could serve as objective biomarkers for cannabis exposure in research settings and may help explain biological pathways through which cannabis affects health outcomes differently from tobacco.
Questions still open
- What biological functions do the identified genes (ADGRF1, ADAM12, ACTN1) serve, and could their methylation changes explain specific health outcomes? Do these methylation changes reverse after stopping cannabis use?
Common questions
What does DNA methylation mean for health?
Could this be used as a drug test?
Read the original research
Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use.
Molecular psychiatry, 29(1), 124-133
Citation
Fang, Fang; Quach, Bryan; Lawrence, Kaitlyn G; van Dongen, Jenny; Marks, Jesse A; Lundgren, Sara; Lin, Mingkuan; Odintsova, Veronika V; Costeira, Ricardo; Xu, Zongli; Zhou, Linran; Mandal, Meisha; Xia, Yujing; Vink, Jacqueline M; Bierut, Laura J; Ollikainen, Miina; Taylor, Jack A; Bell, Jordana T; Kaprio, Jaakko; Boomsma, Dorret I; Xu, Ke; Sandler, Dale P; Hancock, Dana B; Johnson, Eric O. (2024). Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use.. Molecular psychiatry, 29(1), 124-133. https://doi.org/10.1038/s41380-023-02310-w
Explore the wider topic
- Cannabis and Your Cardiovascular System: Heart Risk, Stroke, and What the Research Shows
- Cannabis and Your Heart: What the Cardiovascular Research Shows
- Coughing Up Black Stuff After Quitting Weed: What It Means
- Lung Recovery After Quitting Weed: The Complete Timeline
- Weed and Your Lungs: Recovery Timeline After Quitting
- Quitting Weed as a Woman: Hormones, Cycles, and Recovery
- Cannabis, Weight, and Diet: What Quitting Does to Your Appetite
- Sex After Quitting Weed: What Changes and What Doesn't
- Cannabis and Driving: DUI Laws, Impairment Science, and What You Need to Know
- Weed and Acne: Can Quitting Cannabis Clear Your Skin?
- Weed and Fertility: What Couples Should Know
- Weed and Your Gut: How Cannabis Affects Digestion
- Weed and Your Heart: Cardiovascular Effects and Recovery
- Weed, Testosterone, and Male Health: What the Research Actually Shows