“This Commenatry highlights the article by Rom et al which shows that selective cannabinoid receptor 2 activation in leukocytes decreases key steps in monocyte-blood brain barrier engagement suppressing inflammatory leukocyte responses and preventing neuroinflammation.”
Tag Archives: cannabinoid receptors
Selective Activation of Cannabinoid Receptor 2 in Leukocytes Suppresses Their Engagement of the Brain Endothelium and Protects the Blood-Brain Barrier.
“Cannabinoid receptor 2 (CB2) is highly expressed in immune cells and stimulation decreases inflammatory responses. We tested the idea that selective CB2 activation in human monocytes suppresses their ability to engage the brain endothelium and migrate across the blood-brain barrier (BBB), preventing consequent injury…
These results indicate that selective CB2 activation in leukocytes decreases key steps in monocyte-BBB engagement, thus suppressing inflammatory leukocyte responses and preventing neuroinflammation.”
The role of androgen receptor in transcriptional modulation of cannabinoid receptor type 1 gene in rat trigeminal ganglia.
“We have previously shown that anti-hyperalgesic effects of cannabinoid agonists under inflammatory condition are much greater in male than female, and that inflammatory cytokines upregulate cannabinoid receptor type 1 (CB1) expression in male, but not female, trigeminal ganglia (TG) in a testosterone-dependent manner. In this study, we investigated the mechanisms underlying the testosterone-mediated regulation of peripheral CB1 expression…
These experiments provided compelling evidence that testosterone regulates CB1 gene transcription in TG through AR following cytokine stimulation.
These results should provide mechanistic bases for understanding cytokine-hormone-neuron interactions in peripheral cannabinoid systems, and have important clinical implications for pain patients in whom testosterone level is naturally low, gradually declining or pharmacologically compromised.”
Bladder function in a cannabinoid receptor type 1 knock-out mouse.
“OBJECTIVE: To evaluate bladder function in an established cannabinoid type 1 (CB1) receptor knock-out mouse model via organ bath (in vitro) and urodynamic (cystometric; in vivo) experiments.
CONCLUSIONS: In vitro, bladder strips from CB1 KO mice responded to muscarinic receptor stimulation similar to WT controls, but were less responsive to electrical stimulation of nerves. In vivo, CB1 KO mice had a higher micturition frequency and more spontaneous activity than WT animals.
The present findings suggest that CB1 receptors are involved in peripheral and central nervous control of micturition.”
http://www.ncbi.nlm.nih.gov/pubmed/24053792
“Cannabinoid receptor 1 also plays a role in healthy bladder.” http://www.ncbi.nlm.nih.gov/pubmed/24053739
Structure-Activity Relationship Study of Indole-2-carboxamides Identifies a Potent Allosteric Modulator for the Cannabinoid Receptor 1 (CB1).
“The cannabinoid CB1 receptor is involved in complex physiological functions. The discovery of CB1 allosteric modulators generates new opportunities for drug discovery targeting the pharmacologically important CB1 receptor…”
Therapeutic Potential of a Novel Cannabinoid Agent CB52 in the Mouse Model ofExperimental Autoimmune Encephalomyelitis.
“The endocannabinoid system has recently emerged as a promising therapeutic target for MS. The protective mechanisms of cannabinoids are thought to be mediated by activation of cannabinoid receptor 1 (CB1) and 2 (CB2)…
activation of CB1 receptors contributes significantly to the anti-inflammatory and neuroprotective effects of cannabinoids on MS.”
Treatment of spasticity in multiple sclerosis: new perspectives regarding the use of cannabinoids.
“Spasticity remains a prevalent symptom in multiple sclerosis, with a significant associated disability and quality of life impairment… Cannabinoids provide a new way for therapy.
A delta-9-tetrahydrocannabinol plus cannabidiol (1:1) association, administered through an oromucosal route, has been approved in several countries including Spain; it causes a specific effect on CB(1) and CB(2) receptors, with traditional psychotropic cannabis actions being minimized.
Randomized, placebo-controlled trials, as well as longer-term open-label extensions, have shown a clear-cut efficacy to reduce spasticity and their associated symptoms in those patients refractory to other therapies, with a good tolerability/safety profile.
No tolerance, abuse or addictive issues have been found…”
The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway.
“Delta9-tetrahydrocannabinol and other cannabinoids exert pro-apoptotic actions in tumor cells via the CB2 cannabinoid receptor…
Here we used the human leukemia cell line Jurkat-that expresses CB2 as the unique CB receptor-to investigate…
In summary, results presented here show that CB2 receptor activation signals apoptosis via a ceramide-dependent stimulation of the mitochondrial intrinsic pathway.”
Cannabinoid receptors expression in bone marrow trephine biopsy of chronic lymphocytic leukaemia patients treated with purine analogues.
“Cannabinoid receptors CB1 and CB2 are part the endocannabinoid system that plays an important role in the process of proliferation and apoptosis of different neoplastic cells. B-cell chronic lymphocytic leukaemia is one of the diseases in which these processes are altered… The aim of our study was the assessment of cannabinoid receptor expression on the B-lymphocytes in bone marrow trephine biopsy from leukaemic patients at diagnosis and after purine analogue treatment….
CONCLUSION:
The study provides original evidence for the existence of cannabinoid receptors on B-lymphocytes in chronic lymphocytic leukaemia patients. The receptors are thought to be a new structure that can modify the course of the disease and may be considered as a new target in leukaemia treatment.”
Cannabidiol-Induced Apoptosis in Human Leukemia Cells: A Novel Role of Cannabidiol in the Regulation of p22phox and Nox4 Expression
“Marijuana has been suggested as a potent therapeutic agent alleviating such complications as intraocular pressure in glaucoma and cachexia, nausea, and pain in AIDS and cancer patients. A number of recent studies now suggest the possible use of these compounds for the treatment of cannabinoid receptor-expressing tumors…
In the current study, we examined the effects of the nonpsychoactive cannabinoid, cannabidiol, on the induction of apoptosis in leukemia cells. Exposure of leukemia cells to cannabidiol led to cannabinoid receptor 2 (CB2)-mediated reduction in cell viability and induction in apoptosis. Furthermore, cannabidiol treatment led to a significant decrease in tumor burden and an increase in apoptotic tumors in vivo…
Together, the results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22phox expression, may be a novel and highly selective treatment for leukemia…
In summary, the current study demonstrates that CBD-induced apoptosis may constitute a novel approach to treat malignancies of the immune system…”
Full text: http://molpharm.aspetjournals.org/content/70/3/897.long