Cannabidiol prevents disruptions in sensorimotor gating induced by psychotomimetic drugs that last for 24-h with probable involvement of epigenetic changes in the ventral striatum

Pedrazzi, João Francisco Cordeiro; Sales, Amanda J.; Guimarães, Francisco Silveira; Joca, Sâmia Regiane Lourenço; Crippa, José Alexandre S; Del‐Bel, Elaine

doi:10.1016/j.pnpbp.2021.110352

Cited by 13 publications

(8 citation statements)

References 84 publications

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“…Our study is the first to determine that adolescent CBD does not affect sensorimotor gating in Nrg1 TM HET mice. Effects of CBD in adult animals appear dependent on treatment duration, as acute CBD robustly reverses PPI deficits of mice after acute MK-801 or amphetamine challenge ( Long et al, 2006 ; Pedrazzi et al, 2015 , 2021 ), but chronic CBD is less effective and only reverses PPI deficits at one prepulse intensity in a chronic MK-801 mouse model ( Gomes et al, 2015 ). Interestingly, PPI was elevated in Nrg1 mutant mice in the first PPI test (i.e., baseline), but not the second PPI test (i.e., during the THC battery).…”

Section: Discussionmentioning

confidence: 99%

The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia

Visini

Brown

Weston–Green

et al. 2022

Front. Cell. Neurosci.

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Cannabidiol (CBD) is a non-intoxicating cannabinoid with antipsychotic-like properties, however it’s potential to prevent schizophrenia development has not been thoroughly investigated. Brain maturation during adolescence creates a window where CBD could potentially limit the development of schizophrenia. The neuregulin 1 transmembrane domain heterozygous (Nrg1 TM HET) mutant mouse shows face, predictive, and construct validity for schizophrenia. Here we sought to determine if CBD given in adolescence could prevent the development of the schizophrenia-relevant phenotype, as well as susceptibility to the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) in Nrg1 TM HET mice. Adolescent male Nrg1 mutants and wild type-like (WT) animals were administered 30 mg/kg CBD i.p. daily for seven weeks, and were tested for locomotion, social behavior, sensorimotor gating and cognition, and sensitivity to acute THC-induced behaviors. GAD67, GluA1, and NMDAR1 protein levels were measured in the hippocampus, striatum, and prefrontal cortex. Chronic adolescent CBD increased locomotion in animals regardless of genotype, was anxiolytic, and increased social behavior when animals were tested for their acute THC response. CBD did not alleviate the schizophrenia-relevant hyperlocomotive phenotype of Nrg1 mutants, nor deficits in social behaviors. Nrg1 mutant mice treated with CBD and THC showed no habituation to a startle pulse, suggesting CBD increased vulnerability to the startle habituation-reducing effects of THC in mutant mice. CBD increased levels of GluA1, but reduced levels of GAD67 in the hippocampus of Nrg1 mutants. These results suggest adolescent CBD is not effective as a preventative of schizophrenia-relevant behavioral deficits in mutants and may actually contribute to pathological changes in the brain that increase sensitivity to THC in particular behavioral domains.

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Section: Discussionmentioning

confidence: 99%

The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia

Visini

Brown

Weston–Green

et al. 2022

Front. Cell. Neurosci.

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“…Corroborating those findings, acute CBD administration (60 or 30 mg/kg) attenuated the dysfunctions in the sensorimotor gating induced by psychomimetic drugs in adult Wistar rats associated with changes in global DNAm in two brain regions [ 107 ]. However, CBD effects in the corresponding DNAm changes were rather complex, both increasing or decreasing global DNAm depending on the brain region analyzed (prefrontal cortex vs. ventral striatum) and the drug used as the psychomimetic (amphetamine or MK-801) [ 101 ].…”

Section: Regulation Of Dnam By Cbdmentioning

confidence: 94%

“…Altogether, these studies suggest that the antipsychotic effect of CBD might involve dynamic and tissue-specific regulation of DNAm in schizophrenia, but the methods used in such studies do not allow for further conclusions regarding the precise mechanisms involved in CBD effects. The dual regulation of DNAm described in the study of Pedrazzi and colleagues [ 107 ] suggests indirect mechanisms due to CBD affecting different neurotransmitter systems involved in schizophrenia (e.g., D2 and 5-HT1A), as it seems to be the case for antipsychotic drugs [ 114 ]. Therefore, future studies should consider the analysis of DNAm of individual genes through more advanced techniques, such as Whole-Genome Bisulfite Sequencing (WGBS), to evaluate CBD effects compared with known antipsychotic drugs.…”

Section: Regulation Of Dnam By Cbdmentioning

confidence: 99%

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

Domingos

Silva

Filho

et al. 2022

Genes

Self Cite

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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.

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“…In a study on the effects of CBG in skin conditions, CBG demonstrated inhibitory action on keratinocyte proliferation in a CB1/CB2 receptor-independent manner, being a good candidate for the treatment of psoriasis [130]. Additionally, CBG acted as a transcriptional repressor controlling cell proliferation and differentiation through a mechanism that involved increasing DNA methylation on the keratin-10 gene, making CBG a good candidate for the development of novel therapeutics for skin disease [131].…”

Section: Cannabigerol (Cbg)-type Compoundsmentioning

confidence: 99%

Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

et al. 2021

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The most important discoveries in pharmacology, such as certain classes of analgesics or chemotherapeutics, started from natural extracts which have been found to have effects in traditional medicine. Cannabis, traditionally used in Asia for the treatment of pain, nausea, spasms, sleep, depression, and low appetite, is still a good candidate for the development of new compounds. If initially all attention was directed to the endocannabinoid system, recent studies suggest that many of the clinically proven effects are based on an intrinsic chain of mechanisms that do not necessarily involve only cannabinoid receptors. Recent research has shown that major phytocannabinoids and their derivatives also interact with non-cannabinoid receptors such as vanilloid receptor 1, transient receptor ankyrin 1 potential, peroxisome proliferator-activated receptor-gamma or glitazone receptor, G55 protein-coupled receptor, and nuclear receptor, producing pharmacological effects in diseases such as Alzheimer’s, epilepsy, depression, neuropathic pain, cancer, and diabetes. Nonetheless, further studies are needed to elucidate the precise mechanisms of these compounds. Structure modulation of phytocannabinoids, in order to improve pharmacological effects, should not be limited to the exploration of cannabinoid receptors, and it should target other courses of action discovered through recent research.

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Cannabidiol prevents disruptions in sensorimotor gating induced by psychotomimetic drugs that last for 24-h with probable involvement of epigenetic changes in the ventral striatum

Cited by 13 publications

References 84 publications

The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia

The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia

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

Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

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