Perturbation of 3D nuclear architecture, epigenomic dysregulation and aging, and cannabinoid synaptopathy reconfigures conceptualization of cannabinoid pathophysiology: part 1–aging and epigenomics DOI Creative Commons
Albert Stuart Reece, Gary Kenneth Hulse

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 5, 2023

Much recent attention has been directed toward the spatial organization of cell nucleus and manner in which three-dimensional topologically associated domains transcription factories are epigenetically coordinated to precisely bring enhancers into close proximity with promoters control gene expression. Twenty lines evidence robustly implicate cannabinoid exposure accelerated organismal cellular aging. Aging recently shown be caused by increased DNA breaks. These breaks rearrange maldistribute epigenomic machinery weaken reverse differentiation, cause genome-wide demethylation, reduce transcription, lead inhibition developmental pathways, contribute progressive loss function chronic immune stimulation that characterize Both lineage-defining superenhancers superanchors them weakened. Cannabis phenocopies elements this process reproduces chromatin breakages, reduces DNA, RNA protein histone synthesis, interferes controlling both modifications, induces general hypomethylation, epigenomically disrupts critical boundary cohesin motors create loops. This pattern widespread interference programs relative dedifferentiation (which is pro-oncogenic) reinforced impairment intermediate metabolism locks stem cell-like hyper-replicative state) perpetuates increases aging senescence programs, damage, genomic instability, oncogenesis), together account for diverse teratologic carcinogenic outcomes reported large epidemiologic studies Europe, USA, elsewhere. It also accounts prominent phenotype observed clinically long-term cannabis use disorder 20 characteristics it manifests. Increasing daily use, increasing pregnancy, exponential dose-response effects heighten clinical urgency these findings. Together, findings indicate genotoxicity epigenotoxicity features dependence strongly multiomics investigations genome-epigenome-transcriptome-metabolome, conformation, 3D nuclear architecture. Considering well-established relationships, diversity cannabinoids, multigenerational nature implications, great caution warranted community penetration.

Language: Английский

Exploring the therapeutic potential of cannabinoids in cancer by modulating signaling pathways and addressing clinical challenges DOI Creative Commons

Manal Bint Faiz,

Faiza Naeem,

Muhammad Irfan

et al.

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 27, 2024

Language: Английский

Citations

4
Microglial cannabinoid receptor 2 and epigenetic regulation: implications for the treatment of depression DOI Creative Commons
Priyanka Sharma,

Rajni Daksh,

Saumya Khanna

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177422 - 177422

Published: Feb. 1, 2025

Language: Английский

Citations

0
Regulatory Roles and Therapeutic Potential of miR-122-5p in Hypoxic-Ischemic Brain Injury: Comprehensive Review DOI

Abdulaziz S. Bamahel,

Xun Sun,

Wei Wu

et al.

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

Citations

0
Unraveling the Mechanisms of Cannabidiol’s Pharmacological Actions: A Comprehensive Research Overview DOI

Iqra Kalsoom,

Kiran Shehzadi,

Hansheng Li

et al.

Topics in Current Chemistry, Journal Year: 2024, Volume and Issue: 382(2)

Published: June 3, 2024

Language: Английский

Citations

3
Modeling the Effect of Cannabinoid Exposure During Human Neurodevelopment Using Bidimensional and Tridimensional Cultures DOI Creative Commons
Enrique Estudillo, Jorge Iván Castillo-Arellano,

Emilio G. Martínez

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 70 - 70

Published: Jan. 7, 2025

Our knowledge about the consumption of cannabinoids during pregnancy lacks consistent evidence to determine whether it compromises neurodevelopment. Addressing this task is challenging and complex since pregnant women display multiple confounding factors that make difficult identify real effect cannabinoids' consumption. Recent studies shed light on issue by using pluripotent stem cells human origin, which can recapitulate These revolutionary platforms allow studying how exogenous could alter neurodevelopment without ethical concerns factors. Here, we review information date clinical impact cannabinoid brain development nervous system in humans cultured as 2D 3D development.

Language: Английский

Citations

0
Cannabinoids Transmogrify Cancer Metabolic Phenotype via Epigenetic Reprogramming and a Novel CBD Biased G Protein-Coupled Receptor Signaling Platform DOI Open Access
David A. Bunsick, Jenna Matsukubo, Myron R. Szewczuk

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1030 - 1030

Published: Feb. 6, 2023

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

Language: Английский

Citations

6
Unveiling the Potential of Phytocannabinoids: Exploring Marijuana’s Lesser-Known Constituents for Neurological Disorders DOI Creative Commons
Balapal S. Basavarajappa, Shivakumar Subbanna

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1296 - 1296

Published: Oct. 13, 2024

Cannabis sativa is known for producing over 120 distinct phytocannabinoids, with Δ

Language: Английский

Citations

2
Geospatiotemporal and Causal Inferential Study of European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Orofacial Anomalies DOI Creative Commons
Albert Stuart Reece, Gary Kenneth Hulse

Journal of Xenobiotics, Journal Year: 2023, Volume and Issue: 13(1), P. 42 - 74

Published: Feb. 1, 2023

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

Language: Английский

Citations

5
Exploring the therapeutic potential of natural compounds modulating the endocannabinoid system in various diseases and disorders: review DOI
Gidion Wilson, Lingling Yang, Xiaojuan Su

et al.

Pharmacological Reports, Journal Year: 2023, Volume and Issue: 75(6), P. 1410 - 1444

Published: Oct. 31, 2023

Language: Английский

Citations

4
Prenatal cannabinoid exposure: why expecting individuals should take a pregnancy pause from using cannabinoid products DOI Creative Commons

Alexis Lin,

Gelonia Dent,

Suzy Davies

et al.

Frontiers in Pediatrics, Journal Year: 2023, Volume and Issue: 11

Published: Oct. 11, 2023

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

Language: Английский

Citations

3