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  • ∆9-tetrahydrocannabinol (THC), Cannabidiol (CBD)
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THC and CBD affect metabolic syndrome parameters including microbiome in mice fed high fat-cholesterol diet

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut microbiome in NAFLD. While cannabis and its phytocannabinoids may potentially be benefcial for treating metabolic disorders such as NAFLD, their efects on liver diseases and gut microbiota profle have yet to be addressed. In this study, we evaluated the therapeutic efects of the two major cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on NAFLD progression. Methods: NAFLD was induced by feeding mice a high fat-cholesterol diet (HFCD) for 6 weeks. During this period,...
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Effects of phytocannabinoids on heart rate variability and blood pressure variability in female post-concussion syndrome patients: case series

Please use this link to access this publication Abstract Cannabidiol (CBD) can exert neuroprotective effects without being intoxicating, and in combination with Δ9-tetrahydrocannabinol (THC) CBD has shown to protect against THC psychosis. Acute concussion and post-concussion syndrome (PCS) can result in autonomic dysfunction in heart rate variability (HRV), but less information is available on blood pressure variability (BPV). Furthermore, the effects of phytocannabinoids on HRV and BPV in PCS are unknown. The purpose of this study was to observe the influence of daily administration of CBD or a combination of CBD and THC on HRV and BPV parameters in four female PCS participants. Participants...
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A Low Dose of Pure Cannabidiol Is Sufficient to Stimulate the Cytotoxic Function of CIK Cells without Exerting the Downstream Mediators in Pancreatic Cancer Cells

Abstract Despite numerous studies conducted over the past decade, the exact role of the cannabinoid system in cancer development remains unclear. Though research has focused on two cannabinoid receptors (CB1, CB2) activated by most cannabinoids, CB2 holds greater attention due to its expression in cells of the immune system. In particular, cytokine-induced killer cells (CIKs), which are pivotal cytotoxic immunological effector cells, express a high-level of CB2 receptors. Herein, we sought to investigate whether inducing CIK cells with cannabidiol can enhance their cytotoxicity and if there are any possible counter effects in its downstream cascade of phosphorylated p38 and CREB using a pancreatic ductal...
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Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation

Please use this link to access this publication Abstract Chronic stress impairs radial neural stem cell (rNSC) differentiation and adult hippocampal neurogenesis (AHN), whereas promoting AHN can increase stress resilience against depression. Therefore, investigating the mechanism of neural differentiation and AHN is of great importance for developing antidepressant drugs. The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against depression. However, whether CBD can modulate rNSC differentiation and hippocampal neurogenesis is unknown. Here, by using the chronic restraint stress (CRS) mouse model, we showed that hippocampal rNSCs mostly differentiated into astrocytes under stress conditions. Moreover, transcriptome analysis revealed that the FoxO signaling...
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Medicinal cannabis for the treatment of anxiety disorders

Please use this link to access publication Abstract Background: Anxiety is second most common reason for medicinal cannabis prescription in Australia and is being treated with both Delta9-tetrahydrocannabinol (THC)-containing and cannabidiol (CBD)-dominant products. Objective: The aim of this article is to summarise recent advances in the understanding of medicinal cannabis in treating anxiety and recent trends in prescribing. Discussion: Clinical trials and laboratory studies provide evidence of anxiolytic effects of CBD in healthy volunteers and clinical populations, although current evidence is insufficient to support CBD as a first-line treatment. The evidence regarding the use of THC-dominant products for anxiety is ambiguous, with exacerbation of...
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Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling

Abstract Cannabis sativa L. is increasingly emerging for its protective role in modulating neuroinflammation, a complex process orchestrated among others by microglia, the resident immune cells of the central nervous system. Phytocannabinoids, especially cannabidiol (CBD), terpenes, and other constituents trigger several upstream and downstream microglial intracellular pathways. Here, we investigated the molecular mechanisms of a CBD- and terpenes-enriched C. sativa extract (CSE) in an in vitro model of neuroinflammation. We evaluated the effect of CSE on the inflammatory response induced by exposure to lipopolysaccharide (LPS) in BV-2 microglial cells, compared with CBD and β-caryophyllene (CAR), CB2 receptors (CB2r) inverse and full agonist, respectively. The LPS-induced upregulation of the...
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Botanically-Derived Δ9-Tetrahydrocannabinol and Cannabidiol, and Their 1:1 Combination, Modulate Toll-like Receptor 3 and 4 Signalling in Immune Cells from People with Multiple Sclerosis

Abstract The innate immune response to bacterial and viral molecules involves the coordinated production of cytokines, chemokines, and type I interferons (IFNs), which is orchestrated by toll-like receptors (TLRs). TLRs, and their intracellular signalling intermediates, are closely associated with multiple sclerosis (MS) pathogenesis. Recent data from our laboratory reported that the plant-derived cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), regulate viral and bacterial inflammatory signalling pathways controlled by TLR3 and TLR4 in macrophages. The aim of this study was to assess the impact of THC and CBD, when delivered in isolation and in combination (1:1), on TLR3- and TLR4-dependent signalling in peripheral blood mononuclear cells...
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Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts

Abstract In light of the increased popularity of phytocannabinoids (pCBs) and their appearance in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of pCBs in skin rejuvenation. Utilizing healthy and stress-induced premature senescent (SIPS) CCD-1064Sk skin fibroblasts, the effects of pCBs on cellular viability, functional activity, metabolic function, and nuclear architecture were tested. Both delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) within the range of 0.5 µM to 2.0 µM increased cell growth in a dose-dependent manner while significantly decreasing senescence as measured by beta-galactosidase activity. Utilizing a scratch assay, both THC and CBD (2.0 µM) significantly improved...
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Cannabidiol-Treated Ovariectomized Mice Show Improved Glucose, Energy, and Bone Metabolism With a Bloom in Lactobacillus

Abstract Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammation, and increased risk of cardiometabolic disease and osteoporosis. The risk-benefit profile of hormone replacement therapy is not favorable in postmenopausal women therefore better treatment options are needed. Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice. We evaluated the efficacy of cannabidiol (25 mg/kg) administered perorally to OVX and sham surgery mice for 18 weeks. Compared to VEH-treated OVX mice, CBD-treated OVX mice had improved oral glucose tolerance, increased energy expenditure, improved whole body...
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Long-term use of cannabidiol-enriched medical cannabis in a prospective cohort of children with drug-resistant developmental and epileptic encephalopathy

Abstract Objective We report our findings regarding effectiveness, safety, and tolerability of cannabidiol (CBD)-enriched medical cannabis as add-on therapy in children with drug-resistant epileptic encephalopathies (DEEs) after a median follow-up of 20 months. Methods A prospective cohort study was conducted to assess effectiveness, safety, and tolerability of CBD-enriched medical cannabis oil added to standard antiseizure medications in children with drug-resistant DEE seen at a single center. Results Between October 2018 and March 2020, 59 patients were enrolled. Mean age at enrollment was 10.5 years (range, 2–17 years). Median treatment duration was 20 months (range, 12–32). Median age at first seizure was 8 months (range,...
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