Molecular Insights into Epigenetics and Cannabinoid Receptors

Basavarajappa, Balapal S.; Subbanna, Shivakumar

doi:10.3390/biom12111560

Cited by 12 publications

(5 citation statements)

References 168 publications

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“…There is increasing recent concern at the epigenetic impacts and, therefore, transgenerational effects of many cannabinoids [ 54 , 95 , 96 ]. Recent serial whole epigenome screening has identified many sets of functional annotations identified in the Ingenuity Pathway Analysis of human sperm, including particularly the following, which are of relevance to the morphogenesis of facial structures [ 8 ]: Head development (47 genes, page 304, p = 0.00012).…”

Section: Discussionmentioning

confidence: 99%

Geospatiotemporal and Causal Inferential Study of European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Orofacial Anomalies

Reece

Hulse

2023

JoX

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Introduction. Since high rates of congenital anomalies (CAs), including facial CAs (FCAs), causally attributed to antenatal and community cannabis use have been reported in several recent series, it was of interest to examine this subject in detail in Europe. Methods. CA data were taken from the EUROCAT database. Drug exposure data were downloaded from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Income was taken from the World Bank’s online sources. Results. On the bivariate maps of both orofacial clefts and holoprosencephaly against resin, the Δ9-tetrahydrocannabinol concentration rates of both covariates increased together in France, Bulgaria, and the Netherlands. In the bivariate analysis, the anomalies could be ranked by the minimum E-value (mEV) as congenital glaucoma > congenital cataract > choanal atresia > cleft lip ± cleft palate > holoprosencephaly > orofacial clefts > ear, face, and neck anomalies. When nations with increasing daily use were compared to those without, the former had generally higher rates of FCAs (p = 0.0281). In the inverse probability weighted panel regression, the sequence of anomalies—orofacial clefts, anotia, congenital cataract, and holoprosencephaly—had positive and significant cannabis coefficients of p = 2.65 × 10−5, 1.04 × 10−8, 5.88 × 10−16, and 3.21 × 10−13, respectively. In the geospatial regression, the same series of FCAs had positive and significant regression terms for cannabis of p = 8.86 × 10−9, 0.0011, 3.36 × 10−8, and 0.0015, respectively. Some 25/28 (89.3%) E-value estimates and 14/28 (50%) mEVs were >9 (considered to be in the high range), and 100% of both were >1.25 (understood to be in the causal range). Conclusion. Rising cannabis use is associated with all the FCAs and fulfils the epidemiological criteria for causality. The data indicate particular concerns relating to brain development and exponential genotoxic dose-responses, urging caution with regard to community cannabinoid penetration.

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Section: Discussionmentioning

confidence: 99%

Geospatiotemporal and Causal Inferential Study of European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Orofacial Anomalies

Reece

Hulse

2023

JoX

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“…Current research has only begun to uncover the pathways involved in cannabisinduced changes in DNA methylation, histone modifications, and miRNA expression [59]. Of the existing research, evidence supports the hypothesis that cannabis can alter the activity of histone and DNA-modifying enzymes [58].…”

Section: Molecular Insights Into Cannabis-induced Epigenetic Effectsmentioning

confidence: 99%

Cannabinoids Transmogrify Cancer Metabolic Phenotype via Epigenetic Reprogramming and a Novel CBD Biased G Protein-Coupled Receptor Signaling Platform

Bunsick

Matsukubo

Szewczuk

2023

Cancers

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The concept of epigenetic reprogramming predicts long-term functional health effects. This reprogramming can be activated by exogenous or endogenous insults, leading to altered healthy and different disease states. The exogenous or endogenous changes that involve developing a roadmap of epigenetic networking, such as drug components on epigenetic imprinting and restoring epigenome patterns laid down during embryonic development, are paramount to establishing youthful cell type and health. This epigenetic landscape is considered one of the hallmarks of cancer. The initiation and progression of cancer are considered to involve epigenetic abnormalities and genetic alterations. Cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer development, including DNA methylation, histone modifications, nucleosome positioning, non-coding RNAs, and microRNA expression. Endocannabinoids are natural lipid molecules whose levels are regulated by specific biosynthetic and degradative enzymes. They bind to and activate two primary cannabinoid receptors, type 1 (CB1) and type 2 (CB2), and together with their metabolizing enzymes, form the endocannabinoid system. This review focuses on the role of cannabinoid receptors CB1 and CB2 signaling in activating numerous receptor tyrosine kinases and Toll-like receptors in the induction of epigenetic landscape alterations in cancer cells, which might transmogrify cancer metabolism and epigenetic reprogramming to a metastatic phenotype. Strategies applied from conception could represent an innovative epigenetic target for preventing and treating human cancer. Here, we describe novel cannabinoid-biased G protein-coupled receptor signaling platforms (GPCR), highlighting putative future perspectives in this field.

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“…In a review by Basavarajappa et al, several studies highlight the importance of further evaluation of CB receptor regulation by epigenetic modifications ( 13 , 44 ). Di Marzo et al .…”

Section: Epigenetics and Exogenous Cannabinoidsmentioning

confidence: 99%

“…In a review by Basavarajappa et al, several studies highlight the importance of further evaluation of CB receptor regulation by epigenetic modifications (13,44). Di Marzo et al eloquently describes the discovery of an expanded eCB, the endocannabinoidome (eCBome), an elaborate signaling system that participates in neuronal development and synaptic plasticity in most brain areas (13,(45)(46)(47) and is subsequently involved in the onset, progression, and symptomology of major neuropsychiatric disorders, providing a potential target for the development of novel therapeutics against these disorders [see Figure 2 (11)(12)(13)].…”

Section: Epigenetics and Exogenous Cannabinoidsmentioning

confidence: 99%

Prenatal cannabinoid exposure: why expecting individuals should take a pregnancy pause from using cannabinoid products

Lin,

Dent,

Davies

et al. 2023

Front. Pediatr.

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Cannabinoid use in all populations is increasing as legalization across the United States continues. Concerningly, there is a lack of caution provided by medical providers to pregnant individuals as to the impact the use of cannabinoids could have on the developing fetus. Research continues in both the preclinical and clinical areas, and is severely needed, as the potency of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, has increased dramatically since the initial studies were completed. Thus far, clinical studies raise compelling evidence for short term memory deficits, impulse control issues, and attention deficiencies following prenatal cannabinoid exposure (PCE). These changes may be mediated through epigenetic modifications that not only impact the current offspring but could carry forward to future generations. While additional studies are needed, a pregnancy pause from cannabinoid products should be strongly recommended by providers to ensure the optimal health and well-being of our future generations.

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Molecular Insights into Epigenetics and Cannabinoid Receptors

Cited by 12 publications

References 168 publications

Geospatiotemporal and Causal Inferential Study of European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Orofacial Anomalies

Geospatiotemporal and Causal Inferential Study of European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Orofacial Anomalies

Cannabinoids Transmogrify Cancer Metabolic Phenotype via Epigenetic Reprogramming and a Novel CBD Biased G Protein-Coupled Receptor Signaling Platform

Prenatal cannabinoid exposure: why expecting individuals should take a pregnancy pause from using cannabinoid products

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