Tag Archives: CBD

Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy.

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International Journal of Medical Sciences“The inhibitor of DNA binding (Id) proteins are regulators of cell cycle and cell differentiation. Of all Id family proteins, Id1 is mostly linked to tumorigenesis, cellular senescence as well as cell proliferation and survival.

Overall, Id1 represent a promising target of anti-tumor therapeutics based on its potent promotion effect to cancer. Numerous drugs were found exerting their anti-tumor function through Id1-related signaling pathways, such as fucoidan, berberine, tetramethylpyrazine, crizotinib, cannabidiol and vinblastine.”

https://www.ncbi.nlm.nih.gov/pubmed/32410828

“Id1 is a promising target of anti-tumor treatment as many compounds exert anti-tumor properties by mediating Id1-related pathways.”

https://www.medsci.org/v17p0995.htm

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness. Moreover, reducing Id-1 expression with cannabinoids could also provide a therapeutic strategy for the treatment of additional aggressive cancers because Id-1 expression was found to be up-regulated during the progression of almost all types of solid tumors investigated.”

https://mct.aacrjournals.org/content/6/11/2921

A Phase 1, Randomised, Placebo-Controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Fed Healthy Volunteers.

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SpringerLink“There is increasing interest in the use of purified cannabidiol (CBD) as a treatment for a wide range of conditions due to its reported anti-inflammatory, anxiolytic, antiemetic and anticonvulsant properties.

OBJECTIVE:

The objective of this study was to assess the safety, tolerability and pharmacokinetics of a single ascending dose of a new lipid-based oral formulation of CBD in healthy volunteers after a high-fat meal.

RESULTS:

CBD was well tolerated in the healthy volunteers (mean age: 24.0 years) treated with a single oral dose of CBD. There were no safety concerns with increasing the dose and the safety profiles of the CBD-treated and placebo-treated subjects were similar. The most frequently reported treatment emergent adverse events (TEAEs) were headache (17%) and diarrhoea (8%). There were no reported serious adverse events (SAEs) and no clinical laboratory findings, vital signs, ECGs or physical examination findings that were reported as TEAEs or were of clinical significance during the study. After a high-fat meal, CBD was detected in plasma samples at 15 min postdose; the median time to maximum plasma concentration (Tmax) was 4 h across all three CBD dose cohorts. The CBD plasma exposure [maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC)] increased in a dose-proportional manner and declined to levels approaching the lower level of quantification by day 8. The terminal elimination half-life was approximately 70 h, suggesting that 2-3 weeks are needed to fully eliminate CBD.

CONCLUSIONS:

This new CBD formulation demonstrated a favourable safety and tolerability profile in healthy volunteers that was consistent with the profiles reported for other purified CBD products. No severe or serious AEs were observed in this study and there were no safety concerns.”

https://www.ncbi.nlm.nih.gov/pubmed/32409982

“Cannabidiol (CBD) is a major nonpsychoactive cannabinoid derived from the Cannabis plant that has attracted significant interest due to its anti-inflammatory, anxiolytic, antiemetic and anticonvulsant properties. The findings of this study contribute to the evolving knowledge of cannabidiol pharmacokinetics and indicate that this new oral lipid-based formulation of cannabidiol is generally safe and well tolerated at all doses studied. No severe or serious AEs were observed and there were no safety concerns.”

https://link.springer.com/article/10.1007%2Fs13318-020-00624-6

Cannabidiol on 5-FU-induced oral mucositis in mice.

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Oral Diseases

“The aim of this study was to evaluate the clinical, histological, hematological and oxidative stress effects of cannabidiol (CBD) in mice with induced oral mucositis.

RESULTS:

In the clinical evaluation, the groups treated with CBD showed less severity of oral lesions compared with the positive control at both experimental times. The intensity of the inflammatory response was also lower in the groups treated with this drug, but there was no statistically significant difference when compared with the positive control. With regard to erythrocyte, leukocyte and platelet counts and antioxidant enzyme activity, the groups treated with CBD showed better results, but only some of these variables showed statistically significant differences.

CONCLUSIONS:

CBD seems to exert an anti-inflammatory and antioxidant activity favoring a faster resolution of oral mucositis in this animal model.”

https://www.ncbi.nlm.nih.gov/pubmed/32400905

https://onlinelibrary.wiley.com/doi/abs/10.1111/odi.13413

PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment.

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pharmaceutics-logo“The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy.

Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells.

The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (-16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV-3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC50 values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher-although not statistically significant-tumour growth inhibition was observed with CBD-NPs compared to CBD in solution.

To sum up, poly-lactic-co-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/32397428

https://www.mdpi.com/1999-4923/12/5/439

Activation of CB1R Promotes Lipopolysaccharide-Induced IL-10 Secretion by Monocytic Myeloid-Derived Suppressive Cells and Reduces Acute Inflammation and Organ Injury.

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The Journal of Immunology: 204 (10)“Cannabis sativa and its principal components, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol, are increasingly being used to treat a variety of medical problems, including inflammatory conditions.

Although studies suggest that the endocannabinoid system has immunomodulatory properties, there remains a paucity of information on the effects of cannabinoids on immunity and on outcomes of infection and injury.

We investigated the effects and mechanism(s) of action of cannabinoid receptor agonists, including Δ9-THC, on inflammation and organ injury in endotoxemic mice.

Administration of Δ9-THC caused a dramatic early upregulation of plasma IL-10 levels, reduced plasma IL-6 and CCL-2 levels, led to better clinical status, and attenuated organ injury in endotoxemic mice. The anti-inflammatory effects of Δ9-THC in endotoxemic mice were reversed by a cannabinoid receptor type 1 (CB1R) inverse agonist (SR141716), and by clodronate-induced myeloid-cell depletion, but not by genetic invalidation or blockade of other putative Δ9-THC receptors, including cannabinoid receptor type 2, TRPV1, GPR18, GPR55, and GPR119. Although Δ9-THC administration reduced the activation of several spleen immune cell subsets, the anti-inflammatory effects of Δ9-THC were preserved in splenectomized endotoxemic mice. Finally, using IL-10-GFP reporter mice, we showed that blood monocytic myeloid-derived suppressive cells mediate the Δ9-THC-induced early rise in circulating IL-10.

These results indicate that Δ9-THC potently induces IL-10, while reducing proinflammatory cytokines, chemokines, and related organ injury in endotoxemic mice via the activation of CB1R. These data have implications for acute and chronic conditions that are driven by dysregulated inflammation, such as sepsis, and raise the possibility that CB1R-signaling may constitute a novel target for inflammatory disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/32385136

https://www.jimmunol.org/content/early/2020/05/07/jimmunol.2000213

Inhibitory Effect of Cannabidiol on the Activation of NLRP3 Inflammasome Is Associated with Its Modulation of the P2X7 Receptor in Human Monocytes.

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 Go to Volume 0, Issue 0“Cannabidiol (CBD), a phytocannabinoid, has been reported to have anti-inflammatory effects associated with NLRP3 inflammasome activation, but its mechanism of anti-inflammasome action remains unclear.

Herein, we report CBD’s effect on NLRP3 inflammasome activation and its modulation of P2X7, an inflammasome activation-related receptor, in human THP-1 monocytes.

Overall, the observed CBD suppressive effect on NLRP3 inflammasome activation in THP-1 monocytes was associated with decreased potassium efflux, as well as in silico prediction of P2X7 receptor binding.

CBD inhibitory effects on the NLRP3 inflammasome may contribute to the overall anti-inflammatory effects reported for this phytocannabinoid.”

https://www.ncbi.nlm.nih.gov/pubmed/32374168

https://pubs.acs.org/doi/10.1021/acs.jnatprod.0c00138

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Two-weeks treatment with cannabidiol improves biophysical and behavioral deficits associated with experimental type-1 diabetes.

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Neuroscience Letters“The prevalence rates of depression and anxiety are at least two times higher in diabetic patients, increasing morbidity and mortality.

Cannabidiol (CBD) has been identified as a therapeutic agent viable to treat diverse psychiatric disorders. Thus, this study aimed to investigate the effect of CBD treatment (once a day for 14 days starting two weeks after diabetes induction; at doses of 0, 3, 10 or 30 mg/kg, i.p.) on depression- and anxiety-like behaviors associated with experimental diabetes induced by streptozotocin (60 mg/kg; i.p.) in rats.

Levels of plasma insulin, blood glucose, and weight gain were evaluated in all experimental groups, including a positive control group treated with imipramine. The rats were tested in the modified forced swimming test (mFST) and elevated plus maze (EPM) test. Besides, the levels of serotonin (5-HT), noradrenaline (NA) and dopamine (DA) in two emotion-related brain regions, the prefrontal cortex (PFC) and hippocampus (HIP) were evaluated using high-pressure liquid chromatography.

Our results showed that CBD treatment (only at the higher dose of 30 mg/kg) reduced the exaggerated depressive- and anxiogenic-like behaviors of diabetic (DBT) rats, which may be associated with altered 5-HT, NA and/or DA levels observed in the PFC and HIP. Treatment with CBD (higher dose) also induced a significant increase in weight gain and the insulin levels (and consequently reduced glycemia) in DBT rats. The long-term CBD effects gave rise to novel therapeutic strategies to limit the physiological and neurobehavioral deficits in DBT rats.

This approach provided evidence that CBD can be useful for treating psychiatry comorbidities in diabetic patients.”

https://www.ncbi.nlm.nih.gov/pubmed/32360935

“Treatment of diabetic rats with cannabidiol induced antidepressant- and anxiolytic-like behaviors.”

https://www.sciencedirect.com/science/article/abs/pii/S0304394020302901?via%3Dihub

Altered dopamine D3 receptor gene expression in MAM model of schizophrenia is reversed by peripubertal cannabidiol treatment.

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Biochemical Pharmacology“Gestational methylazoxymethanol acetate (MAM) treatment produces offspring with adult phenotype relevant to schizophrenia, including positive- and negative-like symptoms, cognitive deficits, dopaminergic dysfunction, structural and functional abnormalities.

Here we show that adult rats prenatally treated with MAM at gestational day 17 display significant increase in dopamine D3 receptor (D3) mRNA expression in prefrontal cortex (PFC), hippocampus and nucleus accumbens, accompanied by increased expression of dopamine D2 receptor (D2) mRNA exclusively in the PFC. Furthermore, a significant change in the blood perfusion at the level of the circle of Willis and hippocampus, paralleled by the enlargement of lateral ventricles, was also detected by magnetic resonance imaging (MRI) techniques.

Peripubertal treatment with the non-euphoric phytocannabinoid cannabidiol (30 mg/kg) from postnatal day (PND) 19 to PND 39 was able to reverse in MAM exposed rats: i) the up-regulation of the dopamine D3 receptor mRNA (only partially prevented by haloperidol 0.6 mg/kg/day); and ii) the regional blood flow changes in MAM exposed rats. Molecular modelling predicted that cannabidiol could bind preferentially to dopamine D3 receptor, where it may act as a partial agonist according to conformation of ionic-lock, which is higly conserved in GPCRs.

In summary, our results demonstrate that the mRNA expression of both dopamine D2 and D3 receptors is altered in the MAM model; however only the transcript levels of D3 are affected by cannabidiol treatment, likely suggesting that this gene might not only contribute to the schizophrenia symptoms but also represent an unexplored target for the antipsychotic activity of cannabidiol.”

https://www.ncbi.nlm.nih.gov/pubmed/32360362

https://www.sciencedirect.com/science/article/abs/pii/S000629522030232X?via%3Dihub

Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?

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ijms-logo“Cannabis sativa is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes.

Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ9-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol.

The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions.

Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions.

Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract.

With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.”

https://www.ncbi.nlm.nih.gov/pubmed/32357565

https://www.mdpi.com/1422-0067/21/9/3067

Targeting the Endocannabinoid System in Borderline Personality Disorder.

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“Borderline Personality Disorder (BPD) is a chronic debilitating psychiatric disorder characterized mainly by emotional instability, chaotic interpersonal relationships, cognitive disturbance (e.g. dissociation and suicidal thoughts) and maladaptive behaviors. BPD has a high rate of comorbidity with other mental disorders and high burden on society.

In this review, we focus on two compromised brain regions in BPD – the hypothalamus and the corticolimbic system, emphasizing the involvement and potential contribution of the endocannabinoid system (ECS) to improvement in symptoms and coping.

The hypothalamus-regulated endocrine axes (hypothalamic pituitary – gonadal, thyroid & adrenal) have been found to be dysregulated in BPD. There is also substantial evidence for limbic system structural and functional changes in BPD, especially in amygdala and hippocampus, including cortical regions within the corticolimbic system.

Extensive expression of CB1 and CB2 receptors of the ECS has been found in limbic regions and the hypothalamus. This opens new windows of opportunity for treatment with cannabinoids such as cannabidiol (CBD) as no other pharmacological treatment has shown long-lasting improvement in the BPD population to date.

This review aims to show the potential role of the ECS in BPD patients through their most affected brain regions, the hypothalamus and the corticolimbic system. The literature reviewed does not allow for general indications of treatment with CBD in BPD. However, there is enough knowledge to indicate a treatment ratio of high level of CBD to low level of THC.

A randomized controlled trial investigating the efficacy of cannabinoid based treatments in BPD is warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/32351183

http://www.eurekaselect.com/181504/article