Regulation of DNA Methylation by Cannabidiol and Its Implications for Psychiatry: New Insights from In Vivo and In Silico Models

Genes (Basel). 2022 Nov 20;13(11):2165. doi: 10.3390/genes13112165.

Abstract

Cannabidiol (CBD) is a non-psychotomimetic compound present in cannabis sativa. Many recent studies have indicated that CBD has a promising therapeutic profile for stress-related psychiatric disorders, such as anxiety, schizophrenia and depression. Such a diverse profile has been associated with its complex pharmacology, since CBD can target different neurotransmitter receptors, enzymes, transporters and ion channels. However, the precise contribution of each of those mechanisms for CBD effects is still not yet completely understood. Considering that epigenetic changes make the bridge between gene expression and environment interactions, we review and discuss herein how CBD affects one of the main epigenetic mechanisms associated with the development of stress-related psychiatric disorders: DNA methylation (DNAm). Evidence from in vivo and in silico studies indicate that CBD can regulate the activity of the enzymes responsible for DNAm, due to directly binding to the enzymes and/or by indirectly regulating their activities as a consequence of neurotransmitter-mediated signaling. The implications of this new potential pharmacological target for CBD are discussed in light of its therapeutic and neurodevelopmental effects.

Keywords: DNA methylation; DNMT; anxiety; cannabidiol; depression; stress.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cannabidiol* / pharmacology
  • Cannabidiol* / therapeutic use
  • Cannabis*
  • Computer Simulation
  • DNA Methylation / genetics
  • Humans
  • Psychiatry*

Substances

  • Cannabidiol

Grants and funding

This research was funded by Aarhus University Research Foundation (AUFF-E-2020-7-1 9), Lundbeck Foundation (R366-2021-255/R346-2020-1465) and Sao Paulo State Research Foundation (FAPESP 2017/24304-0).