Cannabis users had specific gene variants and altered DNA methylation patterns compared to non-users | Research

The takeaway

A study comparing 40 cannabis users to 96 controls found a significant association between a cannabinoid receptor 1 gene variant and cannabis use, higher DNA methylation at dopamine-related genes in users, and a protective effect of higher education.

Read this if you are interested in the genetics and epigenetics of cannabis use and why some people may be more predisposed than others.

CB1 receptor gene variant significantly associated with cannabis use (p=0.01)

What the researchers found

Researchers compared genetic variants and DNA methylation patterns between 40 cannabis users and 96 control subjects.

A variant in the CNR1 gene (which codes for the CB1 cannabinoid receptor) was significantly associated with cannabis use (p=0.01). A trend was also observed for a variant in the CNR2 gene (CB2 receptor, p=0.058).

Cannabis users showed significantly higher DNA methylation at two specific locations: exon 8 of the DRD2 gene (dopamine D2 receptor, p=0.034) and a CpG-rich region of the NCAM1 gene (neural cell adhesion molecule, p=0.0004). Higher methylation typically means reduced gene expression.

Higher education level appeared to decrease the risk of cannabis use, and females were less likely to use cannabis than males.

The researchers noted that the altered methylation could be either a pre-existing marker that predisposes to cannabis use or a consequence of long-term cannabis exposure.

Why it matters

This study connects three levels of biology: genetic variants (DNA sequence), epigenetics (DNA methylation), and behavior (cannabis use). The finding that dopamine receptor gene methylation differs in cannabis users provides a potential biological mechanism for how cannabis use might alter brain reward circuitry.

The numbers in context

40 cannabis users vs. 96 controls. CNR1 rs1049353 significantly associated (p=0.01). DRD2 exon 8 hypermethylated in users (p=0.034). NCAM1 CpG region hypermethylated (p=0.0004). Females less likely to use. Higher education protective.

How the study worked

Case-control candidate gene association study with 40 cannabis users and 96 controls. Examined variants in ANKK1, NCAM1, CNR1, and CNR2 genes. DNA methylation analyzed using MeDIP-qPCR at candidate regions in dopaminergic and endocannabinoid pathway genes.

What this study cannot tell us

Small sample size (40 users) limits statistical power and increases risk of false positives. Cross-sectional design cannot determine whether methylation differences preceded or followed cannabis use. Candidate gene approach examines only pre-selected genes, missing genome-wide effects. Confounders like tobacco and alcohol use were not fully detailed.

How to read the evidence

Small case-control study with candidate gene approach provides preliminary evidence of genetic and epigenetic associations, requiring replication in larger samples.

When this study was published

Published in 2018. Genetic and epigenetic research in cannabis use has expanded with larger genome-wide studies since.

The bigger picture

Epigenetic changes like DNA methylation represent a bridge between genetic predisposition and environmental exposure. If cannabis use causes methylation changes at dopamine receptor genes, this could explain some of the lasting effects on reward processing that persist after cessation.

Questions still open

Do the methylation changes at DRD2 and NCAM1 reverse after cannabis cessation? Could CNR1 gene variants be used to identify individuals at higher genetic risk for cannabis use? Does the protective effect of education operate through biological or social pathways?

Common questions

Is there a gene for cannabis use?

Not a single gene, but this study found a variant in the CNR1 gene (CB1 cannabinoid receptor) significantly associated with cannabis use. Genetic predisposition likely involves many genes, each contributing a small effect.

Does cannabis change your DNA?

Not your DNA sequence, but potentially your DNA methylation, which affects how genes are expressed. Cannabis users had higher methylation at dopamine receptor (DRD2) and neural adhesion (NCAM1) genes, though it is unclear whether this preceded or resulted from use.

Read the original research

Gene variants and educational attainment in cannabis use: mediating role of DNA methylation.

Translational psychiatry, 8(1), 23

View on PubMed ↗Publisher’s paper ↗

Citation

Gerra, Maria Carla; Jayanthi, Subramaniam; Manfredini, Matteo; Walther, Donna; Schroeder, Jennifer; Phillips, Karran A; Cadet, Jean Lud; Donnini, Claudia. (2018). Gene variants and educational attainment in cannabis use: mediating role of DNA methylation.. Translational psychiatry, 8(1), 23. https://doi.org/10.1038/s41398-017-0087-1