Subacute CBD exposure altered DNA methylation at over 3,300 sites in the mouse hippocampus, with changes concentrated in genes related to cell adhesion, neural development, and conditions like autism and schizophrenia.
Epigenetics researchers, neuroscientists studying CBD mechanisms, and clinicians interested in long-term effects of CBD use.
3,323 DNA methylation sites altered by 14 days of CBD
What the researchers found
CBD-treated mice had 3,323 differentially methylated loci with a slight skew toward global hypomethylation. Enrichment analysis found affected genes were involved in cell adhesion, dendritic spine development, and excitatory postsynaptic potential. Disease ontology showed overrepresentation in gene sets associated with autism spectrum disorder and schizophrenia.
Why it matters
If CBD changes DNA methylation patterns in the brain, this could be a mechanism underlying its behavioral effects and could have implications for long-term use, including potential risks and benefits that persist after CBD is discontinued.
The numbers in context
3,323 differentially methylated loci. Slight skew toward hypomethylation. 20 mg/kg CBD daily for 14 days. Enrichment in gene sets for autism, schizophrenia, and neural development.
How the study worked
12-week-old male mice received 20 mg/kg CBD or vehicle daily by oral administration for 14 days. Hippocampal tissue was analyzed using reduced-representation bisulfite sequencing (RRBS) to map genome-wide DNA methylation changes.
What this study cannot tell us
Animal study with only 14 days of exposure. Only male mice studied. Hippocampus was the only brain region examined. The biological significance of the methylation changes (whether they alter gene expression or behavior) was not tested.
How to read the evidence
Genome-wide epigenetic analysis with robust methodology, but single brain region, one sex, and no functional validation.
When this study was published
2020 animal study. First genome-wide DNA methylation analysis of CBD exposure in adult brain.
The bigger picture
Epigenetic changes can persist long after the initial exposure. Understanding how CBD alters the epigenome could help explain its therapeutic effects and also raise questions about unintended consequences of chronic use.
Questions still open
- Do these methylation changes persist after CBD discontinuation? Do they translate into functional gene expression changes? Would human hippocampal tissue show similar epigenetic responses to CBD? Could these changes contribute to CBD's therapeutic or adverse effects?
Common questions
What is DNA methylation?
Does this mean CBD changes genes permanently?
Read the original research
Subacute cannabidiol alters genome-wide DNA methylation in adult mouse hippocampus.
Environmental and molecular mutagenesis, 61(9), 890-900
Citation
Wanner, Nicole M; Colwell, Mathia; Drown, Chelsea; Faulk, Christopher. (2020). Subacute cannabidiol alters genome-wide DNA methylation in adult mouse hippocampus.. Environmental and molecular mutagenesis, 61(9), 890-900. https://doi.org/10.1002/em.22396
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