CB2 receptors are usually located in the immune cells of the peripheral nervous system. Once activated, they trigger an immune response to reduce inflammation, a role that is important in treating many chronic diseases.
Endocannabinoids are like the body’s natural THC. In fact, endocannabinoids got their name from cannabis. Plant cannabinoids were discovered first. Endo means within, and cannabinoid referring to a compound that fits into cannabinoid receptors.
Mast cells contain CB1 and CB2 receptors, which when activated inhibit mast cell release (R).
CBD products made from hemp potentially have several problems:
CB1 receptors are abundantly present in the brain and spinal cord. They are found in exceedingly high concentration in the parts of the brain that are associated with the behaviors they influence.
If you need a comprehensive overview MCAS, I encourage you to read my article: Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant.
MCAS is a type of mast cell activation disorder (MCAD) characterised by an abnormal activation of mast cells resulting in chronic multisystem polymorbidity of a general inflammatory nature, with or without an allergic nature. Mast cells are white blood cells that are concentrated at the entrances to body tissues (ears, ears, nose throat, skin, genitalia, rectum), and when activated, they release over 200 signalling chemicals (e.g. histamine, prostaglandins, leukotrienes, cytokines and chemokines). These chemical mediators trigger inflammation in response to the invasion of foreign toxins, infections or chemicals, resulting in a range of chronic symptoms. With MCAS, this function becomes upregulated and chronic, occurring at inappropriate times in response to substances that are not necessary a threat. This can lead to widespread symptoms in many different body organs and systems.
Disadvantages of Using Natural Treatments for Mast Cell Activation Syndrome
For a comprehensive resource on low-histamine foods, diets and recipes, I recommend my guide on the Low Histamine Diet as well as Healing Histamine.
Also, if you opt for natural treatments for MCAS and mast cell activation disorder, always be sure to disclose everything you are taking to your doctor so he or she has a clear idea of what is going on. It is also important that you make only one change at a time when attempting different combinations of treatment options.
There are many advantages of using natural treatments for MCAS, including:
Cannabidiol (CBD) is a natural non-psychotropic cannabinoid from marijuana (Cannabis sativa) with anti-epileptic and anti-inflammatory properties. Effect of CBD on naïve immune system is not precisely understood. In this study, we observed that administering CBD into naïve mice triggers robust induction of CD11b + Gr-1 + MDSC in the peritoneum, which expressed functional Arg1, and potently suppressed T cell proliferation ex vivo. Further, CBD-MDSC suppressed LPS-induced acute inflammatory response upon adoptive transfer in vivo. CBD-induced suppressor cells were comprised of CD11b + Ly6-G + Ly6-C + granulocytic and CD11b + Ly6-G − Ly6-C + monocytic subtypes, with monocytic MDSC exhibiting higher T cell suppressive function. Induction of MDSC by CBD was markedly attenuated in Kit-mutant (Kit W/W-v ) mast cell-deficient mice. MDSC response was reconstituted upon transfer of WT bone marrow-derived mast cells in Kit W/W-v mice suggesting the key role of cKit (CD117) as well as mast cells. Moreover, mast cell activator compound 48/80 induced significant levels of MDSC in vivo. CBD administration in mice induced G-CSF, CXCL1 and M-CSF, but not GM-CSF. G-CSF was found to play a key role in MDSC mobilization inasmuch as neutralizing G-CSF caused a significant decrease in MDSC. Lastly, CBD enhanced the transcriptional activity of PPARγ in luciferase reporter assay, and PPARγ selective antagonist completely inhibited MDSC induction in vivo suggesting its critical role. Together, the results suggest that CBD may induce activation of PPARγ in mast cells leading to secretion of G-CSF and consequent MDSC mobilization. CBD being a major component of Cannabis, our study indicates that marijuana may modulate or dysregulate the immune system by mobilizing MDSC.
Our experiments using c-Kit mutant Kit W/W-v that are also deficient in mast cells showed that induction of G-CSF and MDSC by CBD was significantly attenuated in these mice suggesting the crucial role of c-Kit. The restoration of response following adoptive transfer of mast cells indicated the likely role of mast cells and that mast cells might be the crucial responders in this pathway. This was further supported by the fact that a well known mast cell activator compound was able to induce MDSC cellular response in the peritoneum similar to CBD in vivo. Role of mast cells in the mobilization and function of MDSC has been previously demonstrated using in vivo tumor-models (60, 61). Nevertheless, given the fact that c-Kit is crucial for hematopoiesis and MDSC generation, and further reconstitution with BM-derived mast cells in these mice only replenishes mast cells on a c-kit-deficient background, the role of mast cells needs to be ultimately confirmed using new Cre transgenic model systems (62) devoid of defects in c-Kit or its ligand stem cell factor.
Mice were injected with CBD at different doses intraperitoneally. DMSO stock of CBD was diluted in sterile PBS and solubilized using a small amount of Tween-80. DMSO and Tween-80 similarly diluted in PBS at a ratio of 94:4:2 (PBS:DMSO:Tween-80) was used as the vehicle. The concentration of DMSO and Tween-80 in the vehicle was <3.2% and <2% respectively. Exudates cells in the peritoneal cavity were harvested after 12 or 24 h by performing peritoneal lavage with sterile, ice cold PBS (5mL×3), as described previously (28). Bone marrow cells were obtained by flushing tibia with ice cold PBS followed by RBC lysis. For in vivo blocking experiments, SR1, SR2 compounds, ZM 241385, BADGE, control IgG or anti-G-CSF Ab were injected i.p. at the indicated doses 1 h prior to injecting CBD. For thioglycolate (TG)-induced neutrophil response, 0.5 mL of 3% TG broth was injected intraperitoneally and cells were harvested 4 h or 16 h post-injection.
We analyzed G-CSF levels in peritoneal exudates of WT and c-Kit-mutant mast cell-deficient mice injected with CBD. Kit W/W-v mice produced significantly lower levels of G-CSF in the peritoneal exudates in response to CBD compared to control mice ( Fig. 7F ) suggesting that induction of G-CSF in vivo by CBD is c-Kit-dependent.
62%). After 24 hours of transfection, cells were treated with vehicle (control), CBD or a positive control PPARγ agonist, troglitazone. For in vitro assays the vehicle for CBD contained <0.1% DMSO at final concentrations. Luciferase assay was performed 24 hours following treatment using a commercially available Dual-Glo® luciferase assay system (Promega) and measured in a luminometer (Perkin Elmer). Values were expressed as normalized relative luciferase units and fold induction compared to control was calculated.