“Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear.
In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome.
We conclude that activation of CB2R ameliorates DSS-induced colitis through enhancing autophagy that may inhibit NLRP3 inflammasome activation in macrophages.”
“We provide evidence for the presence of cannabinoid CB2 receptors in some cellular types of the cochlea of the adult albino rat. Cannabinoids and their receptors are increasingly being studied because of their high potential for clinical use. As a hyperspecialized portion of the peripheral nervous system, study of the expression and function of cannabinoid receptors in the hearing organ is of high interest. Stria vascularis and inner hair cells express CB2 receptor, as well as neurites and cell bodies of the spiral ganglion. Cellular types such as supporting cells and outer hair cells, in which the expression of other types of functional receptors has been reported, do not significantly express CB2 receptors in this study. An up-regulation of CB2 gene expression was detected after an ototoxic event such as cisplatin treatment, probably due to pro-inflammatory events triggered by the drug. That fact suggests promising potential of CB2receptor as a therapeutic target for new treatments to palliate cisplatin-induced hearing loss and other ototoxic events which triggers inflammatory pathways.” http://www.ncbi.nlm.nih.gov/pubmed/27564061
“In conclusion, evidence for the presence of cannabinoid CB2 receptor by immunohystochemistry and by RT-qPCR was provided. An immunolabeling of CB2 antibodies in four structures of the adult rat cochlea was found. That was, stria vascularis, inner hair cells, auditory afferent nerves and cell bodies of the spiral ganglion. Up-regulation of CB2 gene expression in animals exposed to CDDP treatment was also detected, when compared with healthy animals. This fact was partially supported by the higher immunofluorescence observed in the stria vascularis of CDDP-treated animals if compared with the healthy ones. These results suggest a considerable promising potential of CB2 receptor as a target of new treatments against CDDP-induced ototoxicity, and probably against other inflammatory diseases in the inner ear. Further research is needed to determine the functionality of CB2receptors in the organ of Corti and the potential therapeutic role of agonists and antagonists of these receptors.” http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161954
“Study: Cannabinoids a Potential Treatment Option for Chemotherapy-Induced Hearing Loss” http://www.theweedblog.com/study-cannabinoids-potential-treatment-option-chemotherapy-induced-hearing-loss/
“Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders.
We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory.
In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA).
These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor-dependent manner.”
“Endocannabinoids and cannabinoid receptors are expressed in various central pain modulation regions. They maintain in dynamic changes in the expression level and distribution under different pathological and physiological conditions. These changes possess advantage as well as disadvantage. Exogenous administration of endocannabinoids exerts analgesic effect in different pain models, which is mainly mediated by the cannabinoid CB1 and CB2 receptors. Inhibition of enzymes for degrading endocannabinoids in different pain models also shows analgesic effect due to the increased local levels of endocannabinoids.”
“Vascular dementia is the second most common cause of cognitive decline in aged people but the effectual therapeutic target is still missing.
Chronic cerebral hypoperfusion (CCH) has been widely found in vascular dementia (VaD) patients. CCH is thought to link with neurodegenerative disorders and their subsequent cognitive impairment.
The present study has been framed to investigate the role of selective agonist of CB2 receptor (1-phenylisatin) in CCH induced VaD.
These results indicate that 2VO induced CCH in rats, which was attenuated with the treatment of 1-phenylisatin.
Hence, it may be suggested that modulation in cannabinoid receptor may provide benefits in CCH as cognitive impairment and VaD.
Therefore, pharmacological positive modulation of CB2 receptors may be a potential research target for alleviation of VaD.”
“Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents.
Abundant evidence indicates that cannabinoids modulate immune responses.
An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors.
Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells.
Cannabinoids suppress Toll-like receptor-mediated inflammatory responses.
Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids.
Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses.
Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases.
This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them.”
“G protein coupled receptors (GPCR’s) exert their effects through multiprotein signaling complexes. The cannabinoid receptor type 1 (CB1) is among the most abundant GPCR’s in the mammalian brain and involved in a plethora of physiological functions. We used a combination of viral-mediated cell type-specific expression of a tagged CB1 fusion protein (CB1-SF), tandem affinity purification (TAP) and proteomics on hippocampal mouse tissue to analyze the composition and differences of CB1 protein complexes in glutamatergic neurons and in GABAergic interneurons. Purified proteins underwent tryptic digestion and were identified using deep-coverage data-independent acquisition with ion mobility separation-enhanced mass spectroscopy, leading to the identification of 951 proteins specifically enriched in glutamatergic and GABAergic CB1-SF TAP samples as compared to controls. Gene Ontology and protein network analyses showed an enrichment of single proteins and functional clusters of proteins involved in already well described domains of CB1 functions. Supported by this consistent dataset we could confirm already known CB1 interactors, reveal new potentially interacting proteins and differences in cell type-specific signaling properties of CB1, thereby providing the foundation for further functional studies on differential CB1 signaling.”
“2-Arachidonylglycerol (2-AG) inhibits the production in vitro of tumor necrosis factor-alpha (TNF-alpha) by mouse macrophages, as well as in mice. It has no effect on the production of nitric oxide (NO). The effect on TNF-alpha is enhanced when 2-AG is administered together with 2-linoleylglycerol (2-Lino-G) and 2-palmitylglycerol (2-PalmG), an ‘entourage effect’ previously noted in several behavioral and binding assays. 2-AG also suppresses the formation of radical oxygen intermediates.”
“The cannabinoid receptor type 1 (CB1) is highly expressed in the dorsal portion of hippocampus – a brain region that has been involved in the control of conditioned emotional response (CER) in the contextual fear conditioning (CFC) model.
These responses are characterized by increased freezing behavior and autonomic parameters. Moreover, CB1 receptors activation negatively modulate the release of several neurotransmitters, including glutamate and GABA, which also have been related to modulation of CER. Therefore, our aim was to investigate the involvement of CB1 receptors in the dorsal hippocampus on CER expression.
Our results suggest that increased CER evoked by CB1 blockade in the dorsal hippocampus depends on NMDA receptor activation and NO formation. Moreover, a fine-tune control promoted by GABAergic and glutamatergic mechanisms in this brain area modulate the CER after CB1 blockade.”
“The relationship between cannabinoid receptor signaling and psychosis vulnerability requires further exploration.
The endocannabinoid signaling system is extensive, with receptors exerting regulatory functions in both immune and central nervous systems.
In the brain, cannabinoid receptors (CBR) directly modulate neurotransmitter systems.
In the peripheral lymphocyte, CBRs mediate cytokine release, with dysregulated cytokine levels demonstrated in schizophrenia.
These results continue to support dysregulation of particular aspects of the endocannabinoid signaling system in participants with schizophrenia selected for the self-reported absence of marijuana abuse/dependence.”
http://www.ncbi.nlm.nih.gov/pubmed/27591408