“COVID-19 disease manifests itself in a wide range of signs and symptoms, beginning with mild symptoms, such as fever, cough, and dyspnea, progressing to acute respiratory distress syndrome (ARDS) and death in some cases. The cytokine storm, or an excess of cytokines released locally, is assumed to be the primary cause of ARDS and mortality in COVID-19 patients. To enhance the survival rate of COVID-19 patients, early management of the cytokine storm with immunomodulators is crucial. Although the effectiveness of some immunosuppressants, such as corticosteroids and tocilizumab, has been studied in clinical trials, the administration of these drugs should be exercised cautiously. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid from Cannabis sativa extracts with anti-inflammatory properties. This review is intended to discuss the possible utility of CBD for the management of COVID-19 patients, particularly those with ARDS.”
“Background: The underlying pathomechanism of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is the immune response to inflammation or infection within the pulmonary microcirculation. Systemic spread of pathogens, activated immune cells, and inflammatory mediators contributes significantly to mortality in patients with ARDS.
Objective: The endogenous cannabinoid system is a major modulator of the immune response during inflammation and infection. Phytocannabinoids, such as cannabidiol (CBD), have shown promising anti-inflammatory effects in several pathologies. The overall objective of this study was to evaluate the effects of CBD on local and systemic inflammation in endotoxin-induced ALI in mice.
Materials and Methods: ALI was induced by pulmonary endotoxin challenge. Four groups of male C57BL/6 mice were randomized in this study: control, ALI, ALI with CBD treatment, and control with CBD treatment. Analyses of local and systemic cytokine levels, lung histology, and leukocyte activation as visualized by intravital microscopy of the intestinal and pulmonary microcirculation were performed 6 h following intranasal endotoxin administration.
Results: Pulmonary endotoxin challenge induced significant inflammation evidenced by local and systemic cytokine and chemokine release, lung histopathology, and leukocyte adhesion. Intraperitoneal CBD treatment resulted in a significant decrease in systemic inflammation as shown by reduced leukocyte adhesion in the intestinal microcirculation and reduced plasma cytokine and chemokine levels. Pulmonary chemokine levels were decreased, while pulmonary cytokine levels were unchanged. Surprisingly, the ALI score was slightly increased by CBD treatment in a manner driven by enhanced neutrophil infiltration of the alveoli.
Conclusion: In this model of experimental ALI, CBD administration was associated with reduced systemic inflammation and heterogeneous effects on pulmonary inflammation. Future studies should explore the mechanisms involved as they relate to neutrophil infiltration and proinflammatory mediator production within the lungs.”
“Soluble epoxide hydrolase (sEH) is a therapeutic target for inflammation. In the present study, we isolated one new (1) and four known (2–5) compounds from the ethyl acetate fraction of hemp seed hulls. Their structures were elucidated as lignanamides via nuclear magnetic resonance and mass spectral analyses. All five compounds inhibited sEH activity, with half-maximal inhibitory concentrations of 2.7 ± 0.3 to 18.3 ± 1.0 μM. These lignanamides showed a competitive mechanism of inhibition via binding to sEH, with ki values below 10 μmol. Molecular simulations revealed that compounds 1–5 fit stably into the active site of sEH, and the key amino acid residues participating in their bonds were identified. It was confirmed that the potential inhibitors 4 and 5 continuously maintained a distance of 3.5 Å from one (Tyr383) and four amino (Asp335, Tyr383, Asn472, tyr516) residues, respectively. These findings provide a framework for the development of naturally derived sEH inhibitors.”
“Cannabis has shown promise in treating various neurological disorders, including Alzheimer’s disease (AD). AD is a devastating neurodegenerative disorder that affects millions of people worldwide. Current treatments for AD are limited and are not very effective.
This study investigated the enzyme-ligand relationship between nine active components of cannabis and human acetylcholinesterase (HuAChE) enzyme, which is significant in AD. Specifically, computational methods such as quantum mechanics, molecular docking, molecular dynamics, and free energy calculations were used to identify the cannabis phytochemicals with the highest HuAChE affinity and to understand the specific binding mechanisms involved.
Our results showed that cannabichromene and cannabigerol were the cannabis phytochemicals with the highest affinity for HuAChE, with cannabichromene exhibiting the greatest binding energy. However, both substances showed lower affinity than that of the pharmaceutical drug donepezil.
This study suggests that cannabichromene has a specific affinity for the peripheral anionic site (PAS) and acyl-binding pocket (ABP), while cannabigerol predominantly binds to PAS. Also, it was found that cannabichromene has a specific affinity for PAS and ABP, while cannabigerol predominantly binds to PAS.
Our findings suggest that cannabichromene and cannabigerol are potential therapeutic agents, but further research is needed to validate their effectiveness. The specific binding mechanisms identified may also provide helpful information for the design of more effective cannabis-based drugs.
Overall, this study provides valuable insights into the potential of cannabis-based drugs for treating neurological diseases.”
“The difficulty of detection at an early stage and the ease of developing resistance to chemotherapy render ovarian cancer (OVC) difficult to cure. Although several novel cancer therapies have been developed recently, drug resistance remains a concern since chemotherapy remains as the most commonly used treatment for cancer patients. Therefore, there is an urgent need to reclaim potential combination treatments for OVC.
So far, there have been several research targeting the endocannabinoid system (ECS) in cancer. Among the various cannabinoid-based drugs, endocannabinoids, which are lipid molecules generated in the body, have been reported to produce many anti-tumor effects; however, research investigating the anti-chemoresistance effect of endocannabinoids in OVC remains unclear.
In this study, we aimed to combine endocannabinoids, anandamide (AEA), and 2-arachidonoylglycerol (2-AG) with chemotherapeutic drugs as a combination approach to treat OVC.
Our results showed that OVC cells expressed both cannabinoid receptors (CBR), CB1 and CB2, suggesting the possibility of endocannabinoid system (ECS) as a target. We found that the anti-chemoresistance effect mediated by endocannabinoids was caused by upregulation of ceramide levels, leading to severe endoplasmic reticulum (ER) stress and increased autophagy in chemoresistant cancer cells. Therefore, chemoresistant cancer cell growth was inhibited, and cell apoptosis was induced under combined treatments. Based on our results, endocannabinoids overcomed chemoresistance of OVC cells in vitro.
Our findings suggest that drugs targeting ECS may have the potential to be adjuvants for chemotherapy by increasing the efficacy of chemotherapeutic drugs and decreasing their side effects.”
“Cancer is one of the most difficult diseases to treat and cure.”
“Cannabinol (CBN), one of the active ingredients from the cannabis plant, is the breakdown molecule of Δ9-tetrahydrocannabinol (Δ9-THC) which is the most abundant psychoactive cannabinoid.”
“Cannabinol (CBN) is a weak-psychoactive cannabinoid and has been shown to exert several bio-logical activities. At the same time, not much is known about the anti-cancer activities of CBN. In this report, we characterized the anti-tumor effects of CBN on the glioma A172, liver cancer HepG2 and breast cancer HCC1806 cell lines.
We found that CBN reduces the proliferation of the analyzed cancer cells and modulates the level of cannabinoid receptors, including GPR18, CB2 and GPR55. Furthermore, CBN inhibits the ERK1/2 pathway in A172 and HepG2 cells, while suppressing the AKT pathway in HCC1086 cells. Moreover, CBN may cause apoptosis through downregulation of p21 and p27 as well as a cell cycle arrest at G1 or S-phase via decreasing the CDK1, CDK2, and cyclin E1 levels.
Taken together, these results offer new insights into the anti-cancer properties of CBN.”
“CBN, one of the weak-psychoactive cannabinoids, have demonstrated various medicinal properties, including anti-inflammatory, antibacterial, analgesic and even anti-tumor.”
“In this study, we revealed the antitumor activity of CBN in three different tumor cell lines, glioma A172, liver cancer HepG2 and breast cancer HCC1806 cell lines. We report that cannabinol inhibits proliferation of several cancer cell lines by regulation of the signaling pathways involving ERK and AKT as well as by altering the expression of cannabinoid receptors. Moreover, we also found that CBN induces apoptosis and cell cycle arrest and partially uncovered underlying molecular mechanisms. Our findings provide novel information about the anti-cancer properties of CBN and justify further research to investigate the role of CBN as cancer therapeutic.”
“Postnatal neurogenesis has been shown to rely on the endocannabinoid system. Here we aimed at unravelling the role of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, with high affinity for the non-classical cannabinoid receptor TRPV1, on subventricular zone (SVZ) postnatal neurogenesis.
Using the neurosphere assay, SVZ-derived neural stem/progenitor cells (NSPCs) were incubated with CBDV and/or 5′-Iodoresinferotoxin (TRPV1 antagonist), and their role on cell viability, proliferation, and differentiation were dissected. CBDV was able to promote, through a TRPV1-dependent mechanism, cell survival, cell proliferation and neuronal differentiation. Furthermore, pulse-chase experiments revealed that CBDV-induced neuronal differentiation was a result of cell cycle exit of NSPCs. Regarding oligodendrocyte differentiation, CBDV inhibited oligodendrocyte differentiation and maturation. Since our data suggested that the CBDV-induced modulation of NSPCs acted via TRPV1, a sodium-calcium channel, and that intracellular calcium levels are known regulators of NSPCs fate and neuronal maturation, single cell calcium imaging was performed to evaluate the functional response of SVZ-derived cells. We observed that CBDV-responsive cells displayed a two-phase calcium influx profile, being the initial phase dependent on TRPV1 activation.
Taken together, this work unveiled a novel and untapped neurogenic potential of CBDV via TRPV1 modulation. These findings pave the way to future neural stem cell biological studies and repair strategies by repurposing this non-psychoactive cannabinoid as a valuable therapeutic target.”
“Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has been discussed for its safety and efficacy in cancer treatments. For this reason, we have inquired into its use on triple-negative human breast cancer. Analyzing the biological effects of CBD on MDA-MB-231, we have demonstrated that both CBD dosage and serum concentrations in the culture medium influence its outcomes; furthermore, light scattering studies demonstrated that serum impacts the CBD aggregation state by acting as a surfactant agent. Pharmacological studies on CBD in combination with chemotherapeutic agents reveal that CBD possesses a protective action against the cytotoxic effect exerted by cisplatin on MDA-MB-231 grown in standard conditions. Furthermore, in a low serum condition (0.5%), starting from a threshold concentration (5 µM), CBD forms aggregates, exerts cytostatic antiproliferative outcomes, and promotes cell cycle arrest activating autophagy. At doses above the threshold, CBD exerts a highly cytotoxic effect inducing bubbling cell death. Finally, IGF-1 and EGF antagonize the antiproliferative effect of CBD protecting cells from harmful consequences of CBD aggregates. In conclusion, CBD effect is strongly associated with the physical state and concentration that reaches the treated cells, parameters not taken into account in most of the research papers.”
“Among the various biological properties of phytocannabinoids, their ability to induce antiproliferative effects in different human cancer cells raises the scientific interest in their therapeutic potential in the field of oncology.”
“Prostate cancer is the second most frequent cancer diagnosed in men in the world today. Almost all prostate cancers are adenocarcinomas and develop from gland cells. We used the PC3 prostate cancer cell line, which is well studied and derived from a bone metastasis of a grade IV prostatic adenocarcinoma.
Cannabidiol (CBD), a major non-psychoactive constituent of cannabis, is a cannabinoid with anti-tumor properties but its effects on prostate cancer cells are not studied in detail.
Here, we found cannabidiol decreased prostate cancer cell (PC3) viability up to 37.25% and induced apoptotic cell death in a time and dose-dependent manner. We found that CBD activated the caspases 3/7 pathways and increased DNA fragmentation. Furthermore, we observed an increase of pro-apoptotic genes Bax, an increased level of reactive oxygen species, lower reduced glutathione level, and altered mitochondrial potential in response to CBD treatment leading to lower cellular ATP.
Overall, our results suggest that CBD may be effective against prostate cancer cells.”
“In summary, we have demonstrated CBD as a potential therapeutic molecule in the treatment of prostate cancer based on its properties of anti-proliferative effect on PC3 cancer cells by promoting intrinsic apoptotic pathway via mitochondrial and NFkB activation followed by intracellular ROS generation and reducing cellular redox status of glutathione.”
“Introduction: The effects of cannabidiol (CBD) on cognition has been investigated in recent years to determine the therapeutic potential of this cannabinoid for a broad gamut of medical conditions, including neuropsychiatric disorders. The aim of the present study was to perform a systematic review of studies that analyzed the effects of the acute and chronic administration of CBD on cognition in humans and animals both to assess the cognitive safety of CBD and to determine a beneficial potential of CBD on cognition.
Methods: The PubMed, Web of Science, PsycINFO, and Scopus databases were searched in December of 2022 for relevant articles using the following combinations of keywords: (“cannabidiol” OR “CBD”) AND (“cognition” OR “processing cognitive” OR “memory” OR “language” OR “attention” OR “executive function” OR “social cognition” OR “perceptual motor ability” OR “processing speed”).
Results: Fifty-nine articles were included in the present review (36 preclinical and 23 clinical trials). CBD seems not to have any negative effect on cognitive processing in rats. The clinical trials confirmed these findings in humans. One study found that repeated dosing with CBD may improve cognitive in people who use cannabis heavily but not individuals with neuropsychiatric disorders. Considering the context of neuropsychiatric disorders in animal models, CBD seems to reverse the harm caused by the experimental paradigms, such that the performance of these animals becomes similar to that of control animals.
Conclusions: The results demonstrate that the chronic and acute administration of CBD seems not to impair cognition in humans without neuropsychiatric disorders. In addition, preclinical studies report promising results regarding the effects of CBD on the cognitive processing of animals. Future double-blind, placebo-controlled, randomized clinical trials with larger, less selective samples, with standardized tests, and using different doses of CBD in outpatients are of particular interest to elucidate the cognitive effects of CBD.”
