Activation of Cannabinoid Type Two Receptors (CB2) Diminish Inflammatory Responses in Macrophages and Brain Endothelium.

“Chronic neuroinflammatory disorders (such as HIV associated neurodegeneration) require treatment that decreases production of inflammatory factors by activated microglia and macrophages and protection of blood brain barrier (BBB) injury secondary to activation of brain endothelium.

Cannabioid type 2 receptor (CB2) is highly expressed on macrophages and brain microvasular enndothelial cells (BMVEC) and is upregulated in inflammation and HIV infection. It has been shown that CB2 activation dampened inflammatory responses in macrophages and BMVEC.

In this study, we assessed by PCR array the expression of a wide range of genes increased in macrophages and BMVEC in inflammation. TNFα treatment upregulated 33 genes in primary human BMVEC, and two highly selective CB2 agonists diminished expression of 31 and 32 genes.

These results were confirmed by functional assays (BBB protection after inflammatory insult and decreased migration of monocytes across BMVEC monolayers after CB2stimulation). Similarly, CB2 stimulation in primary human macrophages led to the suppression of 35 genes out of the 50 genes upregulated by LPS. Such changes in gene expression paralleled diminished secretion of proinflammatory factors.

These results indicate the potential utility of CB2agonists for the treatment of neuroinflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/25666933

Antidepressant-like effects of the cannabinoid receptor ligands in the forced swimming test in mice: Mechanism of action and possible interactions with cholinergic system.

“The purpose of the experiments was to explore the role of the endocannabinoid system, through cannabinoid (CB) receptor ligands, nicotine and scopolamine, in the depression-related responses using the forced swimming test (FST) in mice…

Our results provide clear evidence that the endocannabinoid system participates in the depression-related behavior and through interactions with cholinergic system modulate these kind of responses.”

http://www.ncbi.nlm.nih.gov/pubmed/25660201

http://www.thctotalhealthcare.com/category/depression-2/

Cannabinoid Receptor CB2 Is Involved in Tetrahydrocannabinol-Induced Anti-Inflammation against Lipopolysaccharide in MG-63 Cells.

“Cannabinoid Δ9-tetrahydrocannabinol (THC) is effective in treating osteoarthritis (OA)…

Activation of cannabinoid receptor CB2 reduces inflammation; whether the activation CB2 is involved in THC-induced therapeutic action for OA is still unknown.

We hypothesized that the activation of CB2 is involved in THC-induced anti-inflammation in the MG-63 cells exposed to LPS, and the anti-inflammation is mediated by cofilin-1…

We found that THC suppressed the release of proinflammatory factors, including tumor necrosis factor α (TNF-α), interleukin- (IL-) 1β, IL-6, and IL-8, decreased nuclear factor-κB (NF-κB) expression, and inhibited the upregulation of cofilin-1 protein in the LPS-stimulated MG-63 cells.

These results suggested that CB2 is involved in the THC-induced anti-inflammation in LPS-stimulated MG-63 cells, and the anti-inflammation may be mediated by cofilin-1.”

http://www.ncbi.nlm.nih.gov/pubmed/25653478

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310496/

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

Cannabinoid CB2 receptor stimulation attenuates brain edema and neurological deficits in a germinal matrix hemorrhage rat model.

“Germinal matrix hemorrhage (GMH) is one of the most common and devastating cerebrovascular events that affect premature infants, resulting in a significant socioeconomic burden. However, GMH has been largely unpreventable, and clinical treatments are mostly inadequate.

In the present study, we tested the hypothesis that a selective CB2 receptor agonist, could attenuate brain injury and neurological deficits…

This current study suggests a potential clinical utility for CB2R agonists as a potential therapy to reduce neurological injury and improve patient outcomes after GMH.”

http://www.ncbi.nlm.nih.gov/pubmed/25625355

Cannabinoid receptor 1 controls nerve growth in ectopic cyst in a rat endometriosis model.

“To investigate whether cannabinoid receptor 1 (CB1R) is involved in nerve growth in endometriosis-associated ectopic cyst…

CONCLUSIONS:

CB1R was involved in the nerve growth of ectopic cyst associated with endometriosis.”

http://www.ncbi.nlm.nih.gov/pubmed/25623980

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

Regulation of inflammation and proliferation of human bladder carcinoma cells by type-1 and type-2 cannabinoid receptors.

“Pro-inflammatory cytokines, growth and angiogenic factors released by leukocytes are involved in carcinogenesis and cancer progression, but they are also crucial for fighting tumour growth and spreading.

We have previously demonstrated that endocannabinoids modulate cell-to-cell crosstalk during inflammation. Here, we investigated the inflammatory and tumourigenic properties of endocannabinoids in a human urinary bladdercarcinoma cell line…

Collectively, these findings suggest that CB receptors may play distinct roles in cancer biology, depending on the specific ligand employed.

CONCLUSIONS:

The in vivo assessment of the role of CB receptors in inflammation and cancer might be instrumental in broadening the understanding about bladder cancer biology.”

http://www.ncbi.nlm.nih.gov/pubmed/25445433

http://www.thctotalhealthcare.com/category/bladder-cancer/

The effects of Δ9-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis

“Cannabis is taken as self-medication by patients with inflammatory bowel disease for symptomatic relief.

Cannabinoid receptor agonists decrease inflammation in animal models of colitis, but their effects on the disturbed motility is not known. (-)-Cannabidiol (CBD) has been shown to interact with Δ9-tetrahydrocannabinol (THC) in behavioural studies, but it remains to be established if these cannabinoids interact in vivo in inflammatory disorders.

Therefore the effects of CBD and THC alone and in combination were investigated in a model of colitis…

In this model of colitis, THC and CBD not only reduced inflammation but also lowered the occurrence of functional disturbances. Moreover the combination of CBD and THC could be beneficial therapeutically, via additive or potentiating effects.

As the two phytocannabinoids modulate the immune system and differ in their pharmacological profile, their combination could be more beneficial than either drug alone. Additionally CBD could not only potentiate the therapeutic effects of THC, but also attenuate some of its undesirable effects…”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931570/

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

Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis.

“Recent studies have suggested immunomodulatory and anti-inflammatory effects of cannabinoid receptor 2 (CB2R) activation, which is devoid of psychoactivity. We have demonstrated the expression of CB2R in synovial tissue from patients with rheumatoid arthritis (RA), and its specific activation shows inhibitory effects on fibroblast-like synoviocytes. However, it is still unclear whether selective activation of CB2R inhibits joint inflammation or protects joint damage in RA.

CONCLUSIONS:

Activation of CB2R by HU-308 has therapeutic potential for RA to suppress synovitis and alleviate joint destruction by inhibiting the production of autoantibodies and proinflammatory cytokines.”

http://www.ncbi.nlm.nih.gov/pubmed/25601571

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

Endocannabinoids and acute pain after total knee arthroplasty.

“Osteoarthritis (OA) of the knee is a progressive disease that is associated with inflammation of the joints and lower extremity pain. Total knee arthroplasty (TKA) is a surgical procedure that aims to reduce pain and restore motor function in patients suffering from OA. The immediate postoperative period can be intensely painful leading to extended recovery times including persistent pain.

The endocannabinoid system regulates nociception, and the activation of cannabinoid receptors produces antinociceptive effects in preclinical models of OA…

Taken together, our results are the first to reveal associations between central and peripheral endocannabinoid levels and postoperative pain. This suggests that endocannabinoid metabolism may serve as a target for the development of novel analgesics both for systemic or local delivery into the joint.”

http://www.ncbi.nlm.nih.gov/pubmed/25599456

Proapoptotic effect of endocannabinoids in prostate cancer cells.

“Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies.

The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs…

Based on these results, we suggest that endocannabinoids may be a beneficial option for the treatment of prostate cancer that has become nonresponsive to common therapies.”

http://www.ncbi.nlm.nih.gov/pubmed/25606819

http://www.thctotalhealthcare.com/category/prostate-cancer/