β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice.

“…high-fat diet (HFD) feeding stimulated solid tumor growth and lymph node (LN) metastasis… β-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in many essential oils and has been shown to exert anti-inflammatory activities….

BCP inhibits HFD-induced melanoma progression…

β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice.” http://www.ncbi.nlm.nih.gov/pubmed/26025912

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

http://www.thctotalhealthcare.com/category/melanoma/

CB2 receptor activation prevents glial-derived neurotoxic mediator production, BBB leakage and peripheral immune cell infiltration and rescues dopamine neurons in the MPTP model of Parkinson’s disease

“Parkinson’s disease (PD) is characterized by the degeneration of nigrostriatal dopamine neurons.

The endocannabinoid system consists of cannabinoid receptors, their ligands and enzymes for the synthesis and degradation of cannabinoids.

Our results suggest that targeting the cannabinoid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with glial activation, BBB disruption and peripheral immune cell infiltration.

In summary, we demonstrated that activation of the CB2 receptor inhibits BBB damage, the expression of iNOS and proinflammatory cytokines/chemokines in activated microglia, the infiltration of T cells and astroglial expression of MPO, resulting in the survival of dopamine neurons in vivo in the MPTP mouse model of PD.

Therefore, it is likely that targeting the CB2 receptor may have therapeutic value in the treatment of aspects of PD related to neuroinflammation.”

http://www.nature.com/emm/journal/v48/n1/full/emm2015100a.html

Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving cannabinoid receptor CB2.

“Chronic pain is commonly and closely correlated with inflammation.

Both cannabinoid signaling and mesenchymal stem cells (MSCs) have been demonstrated to reduce inflammatory pain.

Although cannabinoid signaling is essential for mesenchymal stem cell survival and differentiation, little is known about its role in modulatory effect of MSCs on inflammation and pain sensitivity. Here we showed that mouse bone-marrow derived MSCs (BM-MSCs) expressed both cannabinoid receptor type 1 and 2 (CB1 and CB2). CB2 expression level in BM-MSCs increased with their maturation.

In addition, we found that tetrahydrocannabinol (THC) activated CB2 receptor and ERK signaling, consequently enhancing the modulation of MSCs on inflammation-associated cytokine release from lipopolysaccharides-stimulated microglia.

Consistent with in vitro data, THC pretreatment enhanced the immunomodulatory effects of BM-MSC on thermal hyperalgesia and mechanical allodynia in chronic constriction injury model, by decreasing the release of pro-inflammation cytokines.

Our study revealed the crucial role of THC in promoting the immunomodulatory effects of MSCs and proposed a new strategy to alleviate pain based on stem cells therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/26824325

Characterization of a novel adult murine immortalized microglial cell line and its activation by amyloid-beta.

“Alzheimer’s disease is associated with amyloid-beta (Aβ)-induced microglia activation.

This pro-inflammatory response promotes neuronal damage, and therapies are sought to limit microglial activation.

The objective of this study was to characterize Aβ-induced activation of IMG cells, and here, we demonstrate the ability of cannabinoids to significantly reduce this inflammatory response.

Aβ-induced activation of IMG cells was suppressed by delta-9-tetrahydrocannabinol and the CB2-selective agonist JWH-015 in a time- and concentration-dependent manner.

IMG cells recapitulate key features of microglial cell activation. As an example of their potential pharmacological use, cannabinoids were shown to reduce activation of Aβ-induced iNOS gene expression.”

http://www.ncbi.nlm.nih.gov/pubmed/26819091

Clinical/Therapeutic Approaches for Cannabinoid Ligands in Central and Peripheral Nervous System Diseases: Mini Review.

“Cannabinoids, the components of Cannabis sativa Linnaeus, interact with CB1 and CB2 receptors, which are located both in the central nervous system and in the periphery and thus may exert a widespread biological activity in the body.

The main medicinal properties of cannabinoids include analgesic, anti-inflammatory, antitumor, appetite stimulation, antiemesis, and muscle relaxation effects.

This mini review aims to explore existing clinical trials that investigated the use of cannabinoids in diseases affecting the nervous system.

There is evidence that cannabinoid-based drugs may effectively control some symptoms associated with nervous system dysfunction, especially various types of pain and neurologic disorders, although studies are limited.

The efficacy of cannabinoid drugs in the treatment of nervous system diseases should be verified in future large-scale randomized clinical trials.”

http://www.ncbi.nlm.nih.gov/pubmed/26818043

RGS proteins as targets in the treatment of intestinal inflammation and visceral pain: New insights and future perspectives.

“Regulators of G protein signaling (RGS) proteins provide timely termination of G protein-coupled receptor (GPCR) responses. Serving as a central control point in GPCR signaling cascades, RGS proteins are promising targets for drug development. In this review, we discuss the involvement of RGS proteins in the pathophysiology of the gastrointestinal inflammation and their potential to become a target for anti-inflammatory drugs. Specifically, we evaluate the emerging evidence for modulation of selected receptor families: opioid, cannabinoid and serotonin by RGS proteins. We discuss how the regulation of RGS protein level and activity may modulate immunological pathways involved in the development of intestinal inflammation. Finally, we propose that RGS proteins may serve as a prognostic factor for survival rate in colorectal cancer. The ideas introduced in this review set a novel conceptual framework for the utilization of RGS proteins in the treatment of gastrointestinal inflammation, a growing major concern worldwide.”

http://www.ncbi.nlm.nih.gov/pubmed/26817719

The endocannabinoid system and NGF are involved in the mechanism of action of resveratrol: a multi-target nutraceutical with therapeutic potential in neuropsychiatric disorders.

“Resveratrol is a polyphenolic compound with antioxidant, anti-inflammatory, and neuroprotective effects. It has also shown antidepressant-like effects in the behavioral studies; however, its mechanism(s) of action merit further evaluation.

Resveratrol like the classical antidepressant, amitriptyline, affects brain NGF and eCB signaling under the regulatory drive of CB1receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/26780936

Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

“Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen.

Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis.

Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors.

Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease.

CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme.

Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD…

CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.”

http://www.ncbi.nlm.nih.gov/pubmed/26772776

Evaluation of the role of the cannabidiol system in an animal model of ischemia/reperfusion kidney injury.

“This work aimed to investigate the effects of the administration of cannabidiol in a kidney ischemia/reperfusion animal model…

The cannabidiol treatment had a protective effect against inflammation and oxidative damage in the kidney ischemia/reperfusion model.

These effects seemed to be independent of CB1/CB2 receptor activation.”

http://www.ncbi.nlm.nih.gov/pubmed/26761477

“In conclusion, the present study suggests that cannabidiol treatment has a protective effect against inflammation and oxidative damage in the utilized kidney ischemia/reperfusion model.” http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0103-507X2015000400383&lng=en&nrm=iso&tlng=en

Purified Cannabidiol, the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis.

“Multiple Sclerosis (MS) is a global concern disease leading to a progressive, chronic and demyelinating condition, affecting the central nervous system (CNS).

The pathology has an inflammatory/autoimmune origin; nevertheless, neuronal cell death mechanisms are not to be underestimated.

The present study was designed to test the effects of intraperitoneal administration of cannabidiol (CBD), the main non-psychotropiccannabinoid of Cannabis sativa (CS), in an experimental model of MS. The aim is to evaluate the capability of CBD administration to thwart the cascade of mediators involved in MS-induced apoptosis.

We have demonstrated that, alone, purified CBD possesses an anti-apoptotic power against the neurodegenerative processes underlying MS development. This represents an interesting new profile of CBD that could lead to its introduction in the clinical management of MS.”

http://www.ncbi.nlm.nih.gov/pubmed/26744883

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/