Please use this link to access this publication. Abstract Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear transcription factors, with three characterized subtypes: PPARα, PPARβ/δ, and PPARγ. The biological correlation between the two PPAR subtypes PPARα and γ and carcinogenesis is well-characterized; however, substantially less is known about the biological functions of PPARβ/δ. PPARβ/δ has been reported to repress transcription when PPARβ/δ and PPARα or PPARγ are simultaneously expressed in some cells, and MDA-MB-231 cells express functional levels of PPARβ/δ. We have previously reported that Δ9-tetrahydrocannabinol (Δ9-THC), a major cannabinoid component of the drug-type cannabis plant, can stimulate the expression of fatty acid 2-hydroxylase (FA2H) via upregulation of PPARα expression in human breast...

Please use this link to access this publication. Abstract The effect of cannabidiol (CBD), a high-affinity agonist of the transient receptor potential vanilloid-2 (TRPV2) channel, has been poorly investigated in human brain microvessel endothelial cells (BMEC) forming the blood–brain barrier (BBB). TRPV2 expression and its role on Ca2+ cellular dynamics, trans-endothelial electrical resistance (TEER), cell viability and growth, migration, and tubulogenesis were evaluated in human primary cultures of BMEC (hPBMEC) or in the human cerebral microvessel endothelial hCMEC/D3 cell line. Abundant TRPV2 expression was measured in hCMEC/D3 and hPBMEC by qRT-PCR, Western blotting, nontargeted proteomics, and cellular immunofluorescence studies. Intracellular Ca2+ levels were increased by heat and...

Please use this link to access this publication. Abstract Introduction Cannabidiol (CBD) containing products are available in a plethora of flavors in oral, sublingual, and inhalable forms. Immunotoxicological effects of CBD containing liquids were assessed by hypothesizing that CBD regulates oxidative stress and lipopolysaccharide (LPS) induced inflammatory responses in macrophages, epithelial cells, and fibroblasts. Methods Epithelial cells (BEAS-2B and NHBE), macrophages (U937), and lung fibroblast cells (HFL-1) were treated with varying CBD concentrations or exposed to CBD aerosols. Generated reactive oxygen species (ROS) and inflammatory mediators were measured. Furthermore, monocytes and epithelial cells were stimulated with LPS in combination with CBD or dexamethasone to understand the anti-inflammatory effects of CBD. Results CBD showed differential effects...

Abstract Cannabis use is frequent in HIV-infected individuals for its appetite stimulation and anti-inflammatory effects. To identify the underlying molecular mechanisms associated with these effects, we simultaneously profiled micro-RNA (miRNA) and mRNA expression in the colon of chronically simian immunodeficiency virus (SIV)-infected rhesus macaques administered either vehicle (VEH/SIV; n = 9) or Δ9-tetrahydrocannabinol (Δ9-THC; THC/SIV; n = 8). Pro-inflammatory miR-130a, miR-222, and miR-29b, lipopolysaccharide-responsive miR-146b-5p and SIV-induced miR-190b were significantly upregulated in VEH/SIV rhesus macaques. Compared to VEH/SIV rhesus macaques, 10 miRNAs were significantly upregulated in THC/SIV rhesus macaques, among which miR-204 was confirmed to directly target MMP8, an extracellular matrix-degrading collagenase that was significantly downregulated in THC/SIV...

Abstract Currently we are faced with an ever-growing use of Δ9-tetrahydrocannabinol (THC) preparations, often used as supportive therapies for various malignancies and neurological disorders. As some of illegally distributed forms of such preparations, like cannabis oils and butane hash oil, might contain over 80% of THC, their consumers can become intoxicated or experience various detrimental effects. This fact motivated us for the assessments of THC toxicity in vivo on a Wistar rat model, at a daily oral dose of 7 mg/kg which is comparable to those found in illicit preparations. The main objective of the present study was to establish the magnitude and dynamics...

Abstract Cannabinoids, the biologically active constituents of Cannabis, have potent neuronal and immunological effects. However, the basic and medical research dedicated to medical cannabis and cannabinoids is limited. The influence of these treatments on hematologic reconstitution and on the development of graft versus host disease (GVHD) after bone marrow transplantation (BMT) is largely unknown. In this research, we compared the influence of D9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on lymphocyte activation in vitro and in murine BMT models. Our in vitro results demonstrate that these treatments decrease activated lymphocyte proliferation and affect cytokine secretion. We also discovered that CBD and THC utilize different receptors...

Please use this link to access this publication. Abstract Cannabidiol (CBD) is a natural compound with psychoactive therapeutic properties well described. Conversely, the immunological effects of CBD are still poorly explored. In this study, the potential anti-inflammatory effects and underlying mechanisms of CBD and its analog Dimethyl-Heptyl-Cannabidiol (DMH-CBD) were investigated using RAW 264.7 macrophages. CBD and DMH-CBD suppressed LPS-induced TNF production and NF-kB activity in a concentration-dependent manner. Both compounds reduced the NF-kB activity in a μM concentration range: CBD (IC50 = 15 μM) and DMH-CBD (IC50 = 38 μM). However, the concentrations of CBD that mediated NF-kB inhibition were similar to those that cause cytotoxicity (LC50 = 58 μM). Differently, DMH-CBD inhibited the NF-kB activation without cytotoxic...

Abstract Background: The aim of this study was to evaluate cytotoxic, mutagenic and genotoxic effects on buccal mucosa and peripheral blood cells from marijuana and tobacco smokers. Methods: For this purpose, a total of 45 volunteers were distributed into four groups: CTRL group (control): individuals who did not smoke marijuana or tobacco (n = 11); Group M: Marijuana smokers (n = 13); Group T: Tobacco smokers (n = 13); Group M + T: Smokers of both marijuana and tobacco (n = 08). Results: Smokers of both marijuana and tobacco led an increase of micronucleated cells on buccal mucosa when compared to control group. The...

Abstract Cannabidiol (CBD), a non-psychoactive cannabinoid, has been reported to mediate antioxidant, anti-inflammatory, and anti-angiogenic effects in endothelial cells. This study investigated the influence of CBD on the expression of heme oxygenase-1 (HO-1) and its functional role in regulating metabolic, autophagic, and apoptotic processes of human umbilical vein endothelial cells (HUVEC). Concentrations up to 10 µM CBD showed a concentration-dependent increase of HO-1 mRNA and protein and an increase of the HO-1-regulating transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). CBD-induced HO-1 expression was not decreased by antagonists of cannabinoid-activated receptors (CB1, CB2, transient receptor potential vanilloid 1), but by the reactive oxygen...

Please use this link to access this publication. Abstract Aims Cannabinoids are the chemical compounds with a high affinity for cannabinoid receptors affecting the central nervous system through the release of neurotransmitters. However, the current knowledge related to the role of such compounds in the regulation of cellular aging is limited. This study aimed to investigate the effect of cannabidiol and tetrahydrocannabinol on the function of aged pancreatic islets. Main methods The expression of p53, p38, p21, p16, and Glut2 genes and β-galactosidase activity were measured as hallmarks of cell aging applying real-time PCR, ELISA, and immunocytochemistry techniques. Pdx1 protein expression, insulin release, and oxidative stress markers were compared between young...