Monthly Archives: January 2023

Delta-9 tetrahydrocannabinol (THC) effects on the cortisol stress response in bovine granulosa cells

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Toxicology in Vitro

“Maternal stress can result in changes in the hypothalamic-pituitary-adrenal (HPA) axis and lead to stress-related behaviours in offspring. Under physiological conditions, delta-9 tetrahydrocannabinol (THC) appears to be detrimental for fertility. However, cannabis is also commonly used for stress-relief. THC acts on the endocannabinoid receptors in granulosa cells (GCs), which affects oocyte competency. The objective of this study was to evaluate the effects of THC on in vitro bovine granulosa cell viability, apoptosis, and stress response pathway. GCs were cultured in vitro in the presence of clinically relevant therapeutic and recreational plasma doses of THC. Cortisol doses reflecting normal and elevated plasma levels were used to evaluate the effects of THC under induced stress in vitro. No effect of THC was observed on cell viability or apoptosis. High and low cortisol concentrations caused significant increases in 11β-HSD1 mRNA expression (n = 6, p < 0.0001). Interestingly, when combined with high [THC], there was a significant decrease in 11β-HSD1 expression compared to high and low cortisol treatments alone (p < 0.001, p < 0.05). GR expression was unaffected by cortisol treatments, and low [THC] treatment maintained increased expression in the presence of high and low cortisol treatments (n = 6, p < 0.01, p < 0.0001). Our findings represent a foundation to obtain useful data for evaluating THC potential therapeutic benefit.”

https://pubmed.ncbi.nlm.nih.gov/36596389/

“THC treatment does not affect granulosa cell viability or apoptosis.•

Cortisol treatments increase 11β-HSD1 gene expression.•

11β-HSD1 gene expression is reduced by THC treatment in combination with cortisol.•

Glucocorticoid receptor gene expression is increased in response to THC.”

https://www.sciencedirect.com/science/article/abs/pii/S0887233322002478?via%3Dihub


Cannabidiol Suppresses Cytokine Storm and Protects Against Cardiac and Renal Injury Associated with Sepsis

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“Background: Cytokine release syndrome, also termed “cytokine storm,” is the leading cause of morbidity and mortality among patients with various conditions such as sepsis. While cytokine storm is associated with multiple organ damage, acute cardiac and renal injury represents a hallmark of cytokine storm. Since recent reports have suggested that cannabidiol (CBD) may assist in the treatment of inflammatory diseases, our objective was to examine the effect of CBD on cytokine storm-induced cardiac and renal injury using the lipopolysaccharide (LPS)-induced sepsis mouse model. 

Materials and Methods: At 8 weeks of age, mice were randomly assigned to receive CBD (15 mg/kg) or vehicle one hour before a single injection of either phosphate-buffered saline or LPS (10 mg/kg) for an additional 24 h. 

Results: Our results show that CBD improves cardiac function and reduces renal injury in a mouse model of cytokine storm. Moreover, our data indicate that CBD significantly reduces systemic and renal inflammation to contribute to the improvements observed in a cytokine storm-model of cardiac and renal injury. 

Conclusions: Overall, the findings of this study suggest that CBD could be repurposed to reduce morbidity in patients with cytokine storm particularly in severe infections such as sepsis.”

https://pubmed.ncbi.nlm.nih.gov/36594988/

https://www.liebertpub.com/doi/10.1089/can.2022.0170


The effect of a long-term treatment with cannabidiol-rich hemp extract oil on the adenosinergic system of the zucker diabetic fatty (ZDF) rat atrium

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Frontiers - Crunchbase Company Profile & Funding

“Cannabidiol (CBD), the most extensively studied non-intoxicating phytocannabinoid, has been attracting a lot of interest worldwide owing to its numerous beneficial effects. The aim of this study was to explore the effect that CBD exerts on the adenosinergic system of paced left atria isolated from obese type Zucker Diabetic Fatty (ZDF) rats, maintained on diabetogenic rat chow, received 60 mg/kg/day CBD or vehicle via gavage for 4 weeks.

We found that N6-cyclopentyladenosine (CPA), a relatively stable and poorly transported A1 adenosine receptor agonist, elicited a significantly weaker response in the CBD-treated group than in the vehicle-treated one. In contrast, adenosine, a quickly metabolized and transported adenosine receptor agonist, evoked a significantly stronger response in the CBD-treated group than in the vehicle-treated counterpart (excepting its highest concentrations). These results can be explained only with the adenosine transport inhibitory property of CBD (and not with its adenosine receptor agonist activity).

If all the effects of CBD are attributed to the interstitial adenosine accumulation caused by CBD in the myocardium, then a significantly increased adenosinergic activation can be assumed during the long-term oral CBD treatment, suggesting a considerably enhanced adenosinergic protection in the heart.

Considering that our results may have been influenced by A1 adenosine receptor downregulation due to the chronic interstitial adenosine accumulation, an adenosinergic activation smaller than it seemed cannot be excluded, but it was above the CBD-naïve level in every case. Additionally, this is the first study offering functional evidence about the adenosine transport inhibitory action of CBD in the myocardium.”

https://pubmed.ncbi.nlm.nih.gov/36588715/

https://www.frontiersin.org/articles/10.3389/fphar.2022.1043275/full

Treatment of Ovarian Hyperstimulation Syndrome in a Mouse Model by Cannabidiol, an Angiogenesis Pathway Inhibitor

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“Studies suggest that ovarian hyperstimulation syndrome (OHSS) can be treated by reducing the level of vascular endothelial growth factor (VEGF). However, due to the side effects of commercially available VEGF-reducing drugs, they can be ruled out as a suitable treatment for OHSS; therefore, researchers are looking for new medications to treat OHSS.

This study is aimed at investigating the effects of cannabidiol (CBD) in an OHSS model and to evaluate its efficacy in modulating the angiogenesis pathway and VEGF gene expression.

For this purpose, 32 female mice were randomly divided into four groups (eight mice per group): control group, group 2 with OHSS induction, group 3 receiving 32 nmol of dimethyl sulfoxide after OHSS induction, and group 4 receiving 30 mg/kg of CBD after OHSS induction. The animals’ body weight, ovarian weight, vascular permeability (VP), and ovarian follicle count were measured, and the levels of VEGF gene and protein expression in the peritoneal fluid were assessed.

Based on the results, CBD decreased the body and ovarian weights, VP, and corpus luteum number compared to the OHSS group (p < 0.05). The peritoneal VEGF gene and protein expression levels reduced in the CBD group compared to the OHSS group (p < 0.05). Also, CBD caused OHSS alleviation by suppressing VEGF expression and VP. Overall, CBD downregulated VEGF gene expression and improved VP in OHSS.”

https://pubmed.ncbi.nlm.nih.gov/36588534/

“Based on the present findings, CBD exerts potent antiangiogenic effects by influencing many associated pathways. It led to the alleviation of OHSS by suppressing VEGF gene expression and VP. Also, CBD downregulated VEGF expression and improved VP in OHSS. It is hoped that the current results can help reduce the symptoms and complications of OHSS and prevent the cancellation of IVF cycles.”

https://www.hindawi.com/journals/bmri/2022/1111777/

Comparative changes in breast cancer cell proliferation and signalling following somatostatin and cannabidiol treatment

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Biochemical and Biophysical Research Communications

“Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer-related death among women worldwide. Somatostatin (SST) and Cannabinoids have an anti-proliferative and pro-apoptotic effect, but the mechanisms of their actions remain elusive.

In the present study, we have evaluated the effects of SST, Cannabidiol (CBD) alone or in combination on receptor expression, cell proliferation and apoptosis and related downstream signalling pathways in MDA-MB-231 and MCF-7 breast cancer cells.

The results presented here demonstrate the cell type and agonist-dependent changes in receptor expression at the cell membrane, inhibition of cell proliferation and increased apoptosis following treatment with SST and CBD alone and in combination. In comparison to MDA-MB-231 cells, MCF-7 cells treated with SST alone and in combination with CBD exhibited inhibition of phosphorylated Protein Kinase B (pAKT) and phosphorylated-Phosphoinositide 3-Kinase (pPI3K) expression. Importantly, inhibition of PI3K/AKT activation was accompanied by enhanced PTEN expression in MCF-7 cells.

These results highlight the possible interaction between SSTR and CBR subtypes with the implication in the modulation of receptor expression, cell viability and signal transduction pathways in a breast cancer cell type-dependent manner.”

https://pubmed.ncbi.nlm.nih.gov/36586156/

“Marijuana (or cannabis) is a source of large numbers of compounds known as phytocannabinoids, such as delta-9-tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD) that have therapeutic implications in cancer, pain, inflammation and neurological diseases.”

https://www.sciencedirect.com/science/article/abs/pii/S0006291X22017442?via%3Dihub