Cannabidiol Inhibits SARS-CoV-2 Replication through Induction of the Host ER Stress and Innate Immune Responses
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ABSTRACT: The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1a RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time.
Project description:In the current study, we aimed at exploring the effects of the major non-psychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland functions. We found that CBD behaved as a highly effective anti-acne agent, targeting all the three key, sebocyte-specific steps of the pathogenesis (i.e. without compromising viability or basal sebaceous lipid production, CBD normalized pro-acne agents-induced excessive lipid synthesis, reduced proliferation and exerted anti-inflammatory actions). The goal of the present microarray analyses was to identify signaling pathways and target genes being involved in mediating the above beneficial effects of CBD. Microarray analyses were performed by using three independent sets of control (vehicle-treated) and CBD-treated (10 M-NM-<M, 24-hr) human, immortalized SZ95 sebocytes. The first two sets of the samples were analyzed by two-color microarrays (M-bM-^@M-^\rep1M-bM-^@M-^] and M-bM-^@M-^\rep2M-bM-^@M-^]). Later on, the RNA from the second sample set was used for the M-bM-^@M-^\rep2-1M-bM-^@M-^] hybridization (techical repeat). Finally, we analyzed the third (biological) sample set by using one-color microarray (M-bM-^@M-^\rep3M-bM-^@M-^]).
Project description:Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS) to activate BV-2 microglial cells, we examined how Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and cannabidiol (CBD) the non-psychoactive component, modulate the inflammatory response. Microarray analysis of genome-wide mRNA levels was performed using Illumina platform and the resulting expression patterns analyzed using the Ingenuity Pathway Analysis to identify functional subsets of genes, and the Ingenuity System Database to denote the gene networks regulated by CBD and THC.
Project description:Cannabidiol (CBD) oral spray on murine oral ulcer significantly inhibited inflammation, relieved pain and accelerated healing process. To gain insight into transcriptional regulation of CBD on cells related to healing progress of oral ulcer, we performed RNA-Seq on the immortalized human oral keratinocyte HOK-16B cell lines stimulated with LPS and ATP, after 10μM CBD or vehicle excipient pretreatment.
Project description:In the current study, we aimed at exploring the effects of the major non-psychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland functions. We found that CBD behaved as a highly effective anti-acne agent, targeting all the three key, sebocyte-specific steps of the pathogenesis (i.e. without compromising viability or basal sebaceous lipid production, CBD normalized pro-acne agents-induced excessive lipid synthesis, reduced proliferation and exerted anti-inflammatory actions). The goal of the present microarray analyses was to identify signaling pathways and target genes being involved in mediating the above beneficial effects of CBD.
Project description:Cannabis has been used throughout history for medicinal and recreational purposes. The most notable cannabinoids derived from these plants are cannabidiol (CBD) and tetrahydrocannabinol (THC). Although well studied for their therapeutic effects, and highly debated concerning their recreational use, the underlying mechanisms of their biological effects are poorly defined. Here we used isobaric tag-based sample multiplexed proteome profiling to investigate protein abundance differences in the human neuroblastoma SH-SY5Y cell line treated with CBD and THC. We highlighted significantly regulated proteins by each treatment and performed pathway classification and associated protein-protein interaction analysis. Our data suggest that these treatments may result in mitochondrial dysfunction and induce endoplasmic reticulum stress. This dataset can be mined further to investigate the potential role of CBD and THC in various biological and disease contexts and thus provide a foundation for future studies.
Project description:The non-psychotomimetic phytocannabinoid cannabidiol (CBD) has shown anticonvulsant effects in several seizure models in rats and mice. However, the mechanisms by which CBD exerts its antiepileptic effects are not fully elucidated. MicroRNAs (miRNA) are short non-coding RNAs which regulate protein expression. Dysregulation of miRNAs can contribute to the pathology of various diseases, including epilepsy. This could indicate that the modulation of miRNAs is a potential mechanism of action for the therapeutic effects of CBD. Therefore, we sequenced hippocampal samples from CBD or vehicle treated naive mice to see the effects of CBD on miRNA expression.
Project description:Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS) to activate BV-2 microglial cells, we examined how Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and cannabidiol (CBD) the non-psychoactive component, modulate the inflammatory response.
Project description:Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS) to activate BV-2 microglial cells, we examined how Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and cannabidiol (CBD) the non-psychoactive component, modulate the inflammatory response through miRNA expression
Project description:Cannabidiol (CBD) showed antiproliferative activity and induction of apoptosis in chronic myelogenous leukaemia cancer cells (K562 cells). A consolidated DARTS (Drug Affinity Response Target Stability) and t-LIP-MRM (targeted- Limited Proteolysis-Multiple Reaction Monitoring Mass spectrometry) platform was applied to unveil the interactome of CBD and to shed light on its mechanism of action. Both approaches point to the identification of DNA topoisomerase 2-alpha (TOP2A) as a major CBD target in K562 cells.
Project description:Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on Hepatocellular carcinoma cells (HCC) remains unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of Integrative Stress Response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4-IGFBP1-Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively, these observations indicate that CBD could be considered as a potential compound for HCC therapy.