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

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.

Synergistic effects of cannabidiol and cytokine-induced killer cells via the modulation of TRPV2 channel and intracellular p-ERK 1/2 expression on non-small cell lung cancer cells

“…It is worth mentioning the therapeutic potential of CBD in combination with epigenetic and classical chemotherapy drugs are of importance [26], but the biological (unfavorable) effects of CBD itself on the epigenetic system cannot be excluded. There have been studies focusing on CBD-induced abnormal changes in DNA methylation [25,34,35], however, to our knowledge, the effect of CBD on long interspersed element 1 (LINE-1 or L1) remains elusive. In cancer cells, long interspersed element-1 (LINE-1 or L1) is a repetitive DNA retrotransposon that duplicates via a copy-and-paste genetic mechanism.…”

“…Limited evidence suggests that CBD may modulate epigenetic-related changes [25,26,27]. While the main focus of studies remains in genomic DNA methylation, any alterations in the repetitive genome (e.g.…”

Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders

“…While CB2 is mostly expressed in cells of the immune system, CB1 is highly common in the central nervous system (CNS) and is expressed mainly in the brain. 15 There is evidence that both endocannabinoid system neuromodulators 16 and CBD 17 can regulate epigenetic mechanisms. Interestingly, the epigenetic mechanism of DNA methylation in immune cells contributes to multiple sclerosis.…”

“…There is evidence that both endocannabinoid system neuromodulators 16 and CBD 17 can regulate epigenetic mechanisms. Interestingly, the epigenetic mechanism of DNA methylation in immune cells contributes to multiple sclerosis 18 .…”

Surprising Long Term Survival in Glioblastoma Patients Treated with Cannabidiol

“…The formation of GBM is a complex pathological process whereby, among other molecular modifications, a dysregulated methylation of DNA and histone modifications (e.g., methylation or acetylation/deacetylation) plays a role [4]. DNA methylation in GBM is characterised by the transfer of a methyl group donated by Sadenosylmethionine, mainly onto the C5 position of the cytosine to form 5-methylcytosine (5mC); it is a critical regulator of transcription, thus of tissue homeostasis and organ development [5]. If this happens in promoter ("regulatory") regions it is usually associated with gene silencing of transcription, while methylation in other, non-regulatory, transcriptional regions of the gene ("gene bodies") induces an increase or decrease of transcription.…”