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

TY - JOUR

T1 - Regulation of DNA Methylation by Cannabidiol and Its Implications for Psychiatry

T2 - New Insights from In Vivo and In Silico Models

AU - Domingos, Luana B

AU - Silva, Nicole R

AU - Chaves Filho, Adriano J M

AU - Sales, Amanda J

AU - Starnawska, Anna

AU - Joca, Sâmia

PY - 2022/11

Y1 - 2022/11

N2 - 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.

AB - 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.

KW - Cannabidiol/pharmacology

KW - Cannabis

KW - Computer Simulation

KW - DNA Methylation/genetics

KW - Humans

KW - Psychiatry

UR - http://www.scopus.com/inward/record.url?scp=85153401508&partnerID=8YFLogxK

U2 - 10.3390/genes13112165

DO - 10.3390/genes13112165

M3 - Review

C2 - 36421839

SN - 2073-4425

VL - 13

JO - Genes

JF - Genes

IS - 11

M1 - 2165

ER -