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  • Cellular Function
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Role of marijuana components on the regenerative ability of stem cells

Please use this link to access this publication. Abstract Stem cell therapy promotes tissue regeneration and wound healing. Efforts have been made to prime stem cells to enhance their regenerative abilities. Certain marijuana components, namely the non-psychoactive cannabidiol (CBD) and psychoactive tetrahydrocannabinol (THC), are defined as immunomodulators.9 We test whether two sources of stem cells, primed with CBD or THC, would demonstrate improved regenerative abilities. Human adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMDSCs), not obtained from the same individual, were treated with low (300 nM) or high (3 μM) concentration CBD. Porcine ASCs and BMDSCs were isolated from a single pig, and...
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Cannabidiol Treatment Results in a Common Gene Expression Response Across Aggressive Cancer Cells from Various Origins

Please use this link to access this publication. Abstract Background: We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, downregulated the expression of the prometastatic gene inhibitor of DNA binding 1 (ID1) in cancer cells, leading to inhibition of tumor progression in vivo. While CBD is broadly used, including in the self-medication of cancer patients, and CBD-based therapies are undergoing clinical evaluation for cancer treatment, its mechanisms of action are still poorly understood. Methods: In this study, using microarray analysis and Western blot analysis for validation, we attempted to identify the full spectrum of genes regulated by CBD across various...
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Cannabidiol disrupts apoptosis, autophagy and invasion processes of placental trophoblasts

Please use this link to access this publication. Abstract Cannabidiol (CBD) is a constituent of Cannabis sativa without psychotropic activity, whose medical benefits have been recognised. However, little is known about the potential toxic effects of CBD on reproductive health. Placental development involves tightly controlled processes of cell proliferation, differentiation, apoptosis, autophagy and migration/invasion of trophoblast cells. Cannabis use by pregnant women has been increasing, mainly for the relief of nausea associated with the first trimester, which raises great concern. Regarding the crucial role of cytotrophoblast cells (CTs) and extravillous trophoblasts (EVTs) in placentation, the effects of CBD (1–10 µM) were studied, using in...
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Cannabidiol attenuates pulmonary arterial hypertension by improving vascular smooth muscle cells mitochondrial function

Abstract Rationale: Pulmonary arterial hypertension (PAH) is a chronic disease associated with enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional mitochondria, and the clinical therapeutic option for PAH is very limited. Recent studies showed that cannabidiol (CBD), a non-psychoactive constituent of cannabinoids, possessed antioxidant effect towards several cardiovascular diseases, whereas the mechanistic effect of CBD in PAH is unknown. Methods: In this study, the effects of CBD in PAH were determined by analyzing its preventive and therapeutic actions in PAH rodent models in vivo and PASMCs' proliferation test in vitro. Additionally, CBD's roles in mitochondrial function and oxidant stress were also...
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Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia

Abstract Cannabidiol (CBD) exhibits anti-inflammatory and neuroprotective properties and is suggested to be effective in the pre-clinical and clinical treatment of illnesses of the central nervous system (CNS). Two major types of CNS glial cells, astrocytes and microglia, play critical roles in the development and pathogenesis of CNS diseases. However, the mechanisms by which CBD plays an anti-inflammatory and neuroprotective role for these glial cells have not been fully elucidated. In this study, we examined the effects of CBD on the inflammatory response of mouse primary astrocytes and microglia. We also investigated whether the effect of CBD on cytokine release is mediated by the...
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Cannabidiol-Driven Alterations to Inflammatory Protein Landscape of Lipopolysaccharide-Activated Macrophages In Vitro May Be Mediated by Autophagy and Oxidative Stress

Abstract Background: The nonpsychotropic phytocannabinoid cannabidiol (CBD) presents itself as a potentially safe and effective anti-inflammatory treatment relative to clinical standards. In this present study, we compare the capacity of CBD to the corticosteroid dexamethasone (Dex) in altering the secreted protein landscape of activated macrophages and speculate upon the mechanism underpinning these alterations. Materials and Methods: Human THP-1 monocytes were differentiated into macrophages (THP-1 derived macrophages [tMACs]), activated with lipopolysaccharide (LPS), and then treated with 5, 10, 25, 50, or 100 μM CBD or 10 μM Dex for 24 h. Following treatment, cytotoxicity of CBD and protein expression levels from culture supernatants and from whole cell lysates...
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Cannabidiol Induces Apoptosis and Perturbs Mitochondrial Function in Human and Canine Glioma Cells

Abstract Cannabidiol (CBD), the major non-psychoactive compound found in cannabis, is frequently used both as a nutraceutical and therapeutic. Despite anecdotal evidence as an anticancer agent, little is known about the effect CBD has on cancer cells. Given the intractability and poor prognoses of brain cancers in human and veterinary medicine, we sought to characterize the in vitro cytotoxicity of CBD on human and canine gliomas. Glioma cells treated with CBD showed a range of cytotoxicity from 4.9 to 8.2 μg/ml; canine cells appeared to be more sensitive than human. Treatment with >5 μg/ml CBD invariably produced large cytosolic vesicles. The mode of cell...
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In Vitro Studies on Therapeutic Effects of Cannabidiol in Neural Cells: Neurons, Glia, and Neural Stem Cells

Abstract (‒)-Cannabidiol (CBD) is one of the major phytocannabinoids extracted from the Cannabis genus. Its non-psychoactiveness and therapeutic potential, partly along with some anecdotal—if not scientific or clinical—evidence on the prevention and treatment of neurological diseases, have led researchers to investigate the biochemical actions of CBD on neural cells. This review summarizes the previously reported mechanistic studies of the CBD actions on primary neural cells at the in vitro cell-culture level. The neural cells are classified into neurons, microglia, astrocytes, oligodendrocytes, and neural stem cells, and the CBD effects on each cell type are described. After brief introduction on CBD and in vitro studies...
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Regulatory Effects of Cannabidiol on Mitochondrial Functions: A Review

Abstract Cannabidiol (CBD) is part of a group of phytocannabinoids derived from Cannabis sativa. Initial work on CBD presumed the compound was inactive, but it was later found to exhibit antipsychotic, anti-depressive, anxiolytic, and antiepileptic effects. In recent decades, evidence has indicated a role for CBD in the modulation of mitochondrial processes, including respiration and bioenergetics, mitochondrial DNA epigenetics, intrinsic apoptosis, the regulation of mitochondrial and intracellular calcium concentrations, mitochondrial fission, fusion and biogenesis, and mitochondrial ferritin concentration and mitochondrial monoamine oxidase activity regulation. Despite these advances, current data demonstrate contradictory findings with regard to not only the magnitude of effects mediated by CBD, but also to...
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Cannabidiol modulation of oxidative stress and signalling

Abstract Cannabidiol (CBD), one of the primary non-euphoric components in the Cannabis sativa L. plant, has undergone clinical development over the last number of years as a therapeutic for patients with Lennox-Gastaut syndrome and Dravet syndromes. This phytocannabinoid demonstrates functional and pharmacological diversity, and research data indicate that CBD is a comparable antioxidant to common antioxidants. This review gathers the latest knowledge regarding the impact of CBD on oxidative signalling, with focus on the proclivity of CBD to regulate antioxidants and control the production of reactive oxygen species. CBD is considered an attractive therapeutic agent for neuroimmune disorders, and a body of literature indicates...
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