Table 1. Epigenetic alterations related to the effects of cannabinoids in different organisms and biological systems.
Asterisks indicate the examples where cannabinoids have been shown to affect epigenetic regulation in brain or neurons.
| Cannabinoid | Epigenetic alteration | Biological target | Associated effect or consequence | References |
|---|---|---|---|---|
| Cannabis | Increased CpG DNA methylation at promoter | Human peripheral blood cells | Negative correlation between CB1R methylation and mRNA levels in schizophrenic cannabis users | (57) |
| Cannabis | Met/Met COMT gene genotype and promoter CpG DNA methylation | Human adolescent peripheral blood cells | Less likely cannabis dependence and decreased risk of psychosis | (61) |
| * THC | H3K4me3, H3K9me2; Promoter, gene body | Adult rat brain (NAc) | Decreased Drd2 gene mRNA levels in response to in utero THC exposure | (30) |
| * THC | H3K9me2, H3K9me3; Promoter, gene body | Adult rat brain (NAc shell) | Increased Penk gene mRNA levels in response to adolescent THC exposure | (31) |
| * THC | CpG DNA methylation at promoters, intergenic regions, especially in gene bodies | Adult rat NAc with parental THC exposure | Altered methylation enriched in genes implicated in synaptic plasticity | (15) |
| THC | H3K4me3, H3K9me3, H3K27me3, H3K36me3; Promoters, intergenic regions, gene bodies | Differentiating mouse lymph node cells | Genome-wide alterations in histone modifications associated with dysregulated genes and non-coding RNAs | (32) |
| THC | Increased HDAC3 expression | Human trophoblast cell line BeWo | Gene dysregulation during placental development | (70) |
| * THC | DNA methylation at CpG islands; miRNAs | Cerebellum and peripheral T cells of simian immunodeficiency virus-infected macaques | Altered DNA methylation, mRNA and miRNA expression profiles | (37) |
| THC | miRNAs | Mouse myeloid-derived suppressor cells | Altered mRNA, miRNA, and differentiation profile | (35) |
| THC | miRNAs | Intestine of simian immunodeficiency virus-infected macaques | Altered miRNA profile and intestinal epithelial cell composition | (34) |
| Exogenous anandamide | Increased global DNA methylation | Spontaneously immortalized human keratinocytes (HaCaT cell line) | Decreased expression of differentiation-related genes and altered cell differentiation | (51) |
| Exogenous anandamide | miRNAs | Mouse lymph node cells | Altered interleukin production and inflammatory response | (36) |
| HU-210, JWH-133 cannabinoid agonists | H3K9me3; Global levels | CB1R and CB2R-expressing human glioma stem-like cells (U87MG and U373MG lines) | Induction of differentiation, inhibition of gliomagenesis | (29) |
| * HU-210 cannabinoid agonist | miRNAs | Adolescent rat brain (entorhinal cortex) | Altered miRNA profile | (78) |