“The objective of this study was to explore the potential role of G-protein-coupled receptor kinase 2 (GRK2) in the progression of cannabinoid 2 receptor (CB2) agonist-induced analgesic effects of bone cancer pain.
The results affirmed CB2 receptor agonists might serve as new treatment targets for bone cancer pain.
Moreover, spinal GRK2 was an important regulator of CB2 receptor agonist-analgesia pathway.”
“Previous studies have shown that cannabinoidergic system is involved in anxiety.
The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat.
It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system.
It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior.”
“In the present study, we tested the hypothesis that cannabinoids have both acute and chronic modulatory effects on nerve-mediated contractions in NGF-induced airway inflammation.
This study shows that stimulation of cannabinoid CB1 receptors modifies the increase of neuronal activity and density in NGF-induced airway inflammation and directly inhibits cholinergic contractions in the airways by a presynaptic mechanism.
These findings indicate a protective role of CB1 receptors in airway inflammation.”
“Anti-inflammatory and immunological properties of cannabinoids have been reported in several tissues.
Also, cannabinoid receptors type 2 (CB2) were reported to be expressed in osteoblast and osteoclast, suggesting a key role in bone metabolism.
The aim of the present study was to assess the effect of the treatment with the cannabinoid-2 receptor agonist HU-308 in the oral health of rats subjected to lipopolysaccharide (LPS)-induced periodontitis.
This study demonstrates the anti-inflammatory, osteoprotective and pro-homeostatic effects of HU-308 in oral tissues of rats with LPS-induced periodontitis.”
“Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation.
Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation.
Our results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis.”
“Different types of insults to the CNS lead to axon demyelination. Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells.
With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an in vitro model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination.
“Endocannabinoid system plays an important role in the regulation of diverse physiological functions.
Although cannabinoid type 2 receptors (CB2) are involved in the modulation of immune system in peripheral tissues, recent findings demonstrated that they are also expressed in the central nervous system and could constitute a new target for the treatment of neurodegenerative disorders.”
“The G-protein-coupled chemokine receptor, CXCR4, generates signals that lead to cell migration, cell proliferation, and other survival mechanisms which result in the metastatic spread of primary tumor cells to distal organs.
Numerous studies have demonstrated that CXCR4 can form homodimers, or can heterodimerize with other GPCRs to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor.
Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells.
Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2, and ultimately, reduced cancer cell functions such as calcium mobilization and cellular chemotaxis.
Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells, as well as CXCR4-mediated migration of immune cells, it is therefore plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4.
Taken together, the data illustrates a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function, and perhaps, tumor progression.”
“Previous studies have shown that modulation of the receptor-mediated endocannabinoid system during ischemia injury can induce potent neuroprotective effects.
However, little is known about whether cannabinoid-2 (CB2) receptor agonist would produce a protective effect on blood-spinal cord barrier (BSCB) during ischemia.
Taken together, all of these results suggested that JWH-015 might regulate the BSCB permeability and this effect could be related to paracellular and transcellular pathway.
And pharmacological CB2R ligands offer a new strategy for BSCB protection during ischemic injury.”
“Endocannabinoids are arachidonic acid derivatives and part of a novel bioactive lipid signaling system, along with their G-coupled cannabinoid receptors (CB₁ and CB₂) and the enzymes involved in their biosynthesis and degradation.
However, their roles in hematopoiesis and hematopoietic stem and progenitor cell (HSPC) functions are not well characterized. Here, we show that bone marrow stromal cells express endocannabinoids (anandamide and 2-arachidonylglycerol), whereas CB₂ receptors are expressed in human and murine HSPCs.
On ligand stimulation with CB₂ agonists, CB₂ receptors induced chemotaxis, migration, and enhanced colony formation of bone marrow cells, which were mediated via ERK, PI3-kinase, and Gαi-Rac1 pathways.
Taken together, these results demonstrate that the endocannabinoid system is involved in hematopoiesis and that CB₂/CB₂ agonist axis mediates repopulation of hematopoiesis and mobilization of HSPCs.
Thus, CB₂ agonists may be therapeutically applied in clinical conditions, such as bone marrow transplantation.”