Tag Archives: CB2

The Expression Level of Cannabinoid Receptors Type 1 and 2 in the Different Types of Astrocytomas

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 SpringerLink“Astrocytomas, the most prevalent primary brain tumors, can be divided by histology and malignancy levels into four following types: pilocytic astrocytoma (grade I), diffuse fibrillary astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (grade IV). For high grade astrocytomas (grade III and grade IV), blood vessels formation is considered as the most important property.

The distribution of cannabinoid receptors type 1 (CB1) and cannabinoid receptor type 2 (CB2) in blood vessels and tumor tissue of astrocytoma is still controversial. Asrocytoma tissues were collected from 45 patients under the condition of tumor-related neurosurgical operation. The expression of CB1 and CB2 receptors was assessed using immunofluorescence, quantitative real-time RT-PCR and western blotting.

The results indicated an increased expression of CB1 receptors in tumor tissue. There was a significant difference in the mount of CB2 receptors in blood vessels. More was observed in the grade III and glioblastoma (grade IV) than astrocytoma of grade II and control.

This study suggested that, the expression increase of cannabinoid receptors is an index for astrocytoma malignancy and can be targeted as a therapeutic approach for the inhibition of astrocytoma growth among patients.”

https://pubmed.ncbi.nlm.nih.gov/32623617/

https://link.springer.com/article/10.1007%2Fs11033-020-05636-8

Administration of Δ9-Tetrahydrocannabinol (THC) Post-Staphylococcal Enterotoxin B Exposure Protects Mice From Acute Respiratory Distress Syndrome and Toxicity

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Frontiers in Pharmacology welcomes new Field Chief Editor ...“Acute Respiratory Distress Syndrome (ARDS) is a life-threatening complication that can ensue following Staphylococcus aureus infection. The enterotoxin produced by these bacteria (SEB) acts as a superantigen thereby activating a large proportion of T cells leading to cytokine storm and severe lung injury.

Δ9Tetrahydrocannabinol (THC), a psychoactive ingredient found in Cannabis sativa, has been shown to act as a potent anti-inflammatory agent. In the current study, we investigated the effect of THC treatment on SEB-induced ARDS in mice.

While exposure to SEB resulted in acute mortality, treatment with THC led to 100% survival of mice. THC treatment significantly suppressed the inflammatory cytokines, IFN-γ and TNF-α. Additionally, THC elevated the induction of regulatory T cells (Tregs) and their associated cytokines, IL-10 and TGF-β. Moreover, THC caused induction of Myeloid-Derived Suppressor Cells (MDSCs).

THC acted through CB2 receptor as pharmacological inhibitor of CB2 receptors blocked the anti-inflammatory effects. THC-treated mice showed significant alterations in the expression of miRNA (miRs) in the lung-infiltrated mononuclear cells (MNCs). Specifically, THC caused downregulation of let7a-5p which targeted SOCS1 and downregulation of miR-34-5p which caused increased expression of FoxP3, NOS1, and CSF1R.

Together, these data suggested that THC-mediated alterations in miR expression in the lungs may play a critical role in the induction of immunosuppressive Tregs and MDSCs as well as suppression of cytokine storm leading to attenuation of SEB-mediated lung injury.”

https://pubmed.ncbi.nlm.nih.gov/32612530/

“In summary, the current study suggests that treatment of mice with THC post-SEB challenge protects mice from SEB-mediated toxicity by inhibiting inflammation and ARDS through the modulation of miRs. Because SEB is a super antigen that drives cytokine storm, our studies suggest that THC is a potent anti-inflammatory agent that has the potential to be used as a therapeutic modality to treat SEB-induced ARDS.

It is of interest to note that a significant proportion of Coronavirus disease 2019 (COVID-19) patients come down with sepsis and ARDS accompanied by cytokine storm. ”

https://www.frontiersin.org/articles/10.3389/fphar.2020.00893/full

High Expression of Cannabinoid Receptor 2 on Cytokine-Induced Killer Cells and Multiple Myeloma Cells

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ijms-logo“Multiple myeloma (MM) is characterized by aberrant bone marrow plasma cell (PC) proliferation and is one of the most common hematological malignancies. The potential effect of cannabinoids on the immune system and hematological malignancies has been poorly characterized.

Cannabidiol (CBD) may be used to treat various diseases. CBD is known to exert immunomodulatory effects through the activation of cannabinoid receptor 2 (CB2), which is expressed in high levels in the hematopoietic system.

Cytokine-induced killer (CIK) cells are a heterogeneous population of polyclonal T lymphocytes obtained via ex vivo sequential incubation of peripheral blood mononuclear cells (PBMCs) with interferon-γ (IFN-γ), anti CD3 monoclonal antibody, and IL-2. They are characterized by the expression of CD3+ and CD56+, which are surface markers common to T lymphocytes and natural killer (NK) cells. CIK cells are mainly used in hematological patients who suffer relapse after allogeneic transplantation.

Here, we investigated their antitumor effect in combination with pure cannabidiol in KMS-12 MM cells by lactate dehydrogenase LDH cytotoxicity assay, CCK-8 assay, and flow cytometry analysis. The surface and intracellular CB2 expressions on CIK cells and on KMS-12 and U-266 MM cell lines were also detected by flow cytometry.

Our findings confirm that the CB2 receptor is highly expressed on CIK cells as well as on MM cells. CBD was able to decrease the viability of tumor cells and can have a protective role for CIK cells. It also inhibits the cytotoxic activity of CIKs against MM at high concentrations, so in view of a clinical perspective, it has to be considered that the lower concentration of 1 µM can be used in combination with CIK cells. Further studies will be required to address the mechanism of CBD modulation of CIK cells in more detail.”

https://pubmed.ncbi.nlm.nih.gov/32471216/

https://www.mdpi.com/1422-0067/21/11/3800

Cannabinoid Receptor Type 2: A Possible Target in SARS-CoV-2 (CoV-19) Infection?

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ijms-logo“In late December 2019, a novel coronavirus (SARS-CoV-2 or CoV-19) appeared in Wuhan, China, causing a global pandemic. SARS-CoV-2 causes mild to severe respiratory tract inflammation, often developing into lung fibrosis with thrombosis in pulmonary small vessels and causing even death. COronaVIrus Disease (COVID-19) patients manifest exacerbated inflammatory and immune responses, cytokine storm, prevalence of pro-inflammatory M1 macrophages and increased levels of resident and circulating immune cells. Men show higher susceptibility to SARS-CoV-2 infection than women, likely due to estrogens production. The protective role of estrogens, as well as an immune-suppressive activity that limits the excessive inflammation, can be mediated by cannabinoid receptor type 2 (CB2). The role of this receptor in modulating inflammation and immune response is well documented in fact in several settings. The stimulation of CB2 receptors is known to limit the release of pro-inflammatory cytokines, shift the macrophage phenotype towards the anti-inflammatory M2 type and enhance the immune-modulating properties of mesenchymal stromal cells. For these reasons, we hypothesize that CB2 receptor can be a therapeutic target in COVID-19 pandemic emergency.”

https://pubmed.ncbi.nlm.nih.gov/32471272/

https://www.mdpi.com/1422-0067/21/11/3809

Targeting Cannabinoid Receptor 2 on Peripheral Leukocytes to Attenuate Inflammatory Mechanisms Implicated in HIV-Associated Neurocognitive Disorder.

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 SpringerLink“HIV infection affects an estimated 38 million people. Approximately 50% of HIV patients exhibit neurocognitive dysfunction termed HIV-Associated Neurocognitive Disorder (HAND). HAND is a consequence of chronic low-level neuroinflammation due to HIV entry into the brain. Initially, monocytes become activated in circulation and traffic to the brain. Monocytes, when activated, become susceptible to infection by HIV and can then carry the virus across the blood brain barrier. Once in the brain, activated monocytes secrete chemokines, which recruit virus-specific CD8+ T cells into the brain to further promote neuroinflammation. HAND is closely linked to systemic inflammation driven, in part, by HIV but is also due to persistent translocation of microorganisms across the GI tract. Persistent anti-viral responses in the GI tract compromise microbial barrier integrity. Indeed, HIV patients can exhibit remarkably high levels of activated (CD16+) monocytes in circulation.

Recent studies, including our own, show that HIV patients using medical marijuana exhibit lower levels of circulating CD16+ monocytes than non-cannabis using HIV patients. Cannabis is a known immune modulator, including anti-inflammatory properties, mediated, in part, by ∆9-tetrahydrocannabinol (THC), as well as less characterized minor cannabinoids, such as cannabidiol (CBD), terpenes and presumably other cannabis constituents. The immune modulating activity of THC is largely mediated through cannabinoid receptors (CB) 1 and 2, with CB1 also responsible for the psychotropic properties of cannabis.

Here we discuss the anti-inflammatory properties of cannabinoids in the context of HIV and propose CB2 as a putative therapeutic target for the treatment of neuroinflammation. Graphical Abstract HIV-associated neurocognitive disorder is a systemic inflammatory disease leading to activation of plasmacytoid dendritic cells, monocytes and T cells. Monocyte and CD8 T cell migration across the BBB and interaction with astrocytes promotes neurotoxic inflammatory mediators release. CB2 ligands are proposed as therapeutics capable of suppressing systemic and localized inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/32409991

https://link.springer.com/article/10.1007%2Fs11481-020-09918-7

Beneficial effects of the phytocannabinoid Δ9-THCV in L-DOPA-induced dyskinesia in Parkinson’s disease.

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Neurobiology of Disease“The antioxidant and CB2 receptor agonist properties of Δ9-tetrahydrocannabivarin (Δ9-THCV) afforded neuroprotection in experimental Parkinson’s disease (PD), whereas its CB1 receptor antagonist profile at doses lower than 5 mg/kg caused anti-hypokinetic effects.

In the present study, we investigated the anti-dyskinetic potential of Δ9-THCV (administered i.p. at 2 mg/kg for two weeks), which had not been investigated before.

In summary, our data support the anti-dyskinetic potential of Δ9-THCV, both to delay the occurrence and to attenuate the magnitude of dyskinetic signs. Although further studies are clearly required to determine the clinical significance of these data in humans, the results nevertheless situate Δ9-THCV in a promising position for developing a cannabinoid-based therapy for patients with PD.”

https://www.ncbi.nlm.nih.gov/pubmed/32387338

“Δ9-THCV exhibited anti-dyskinetic properties in L-DOPA-treated Pitx3ak mutant mice. It delayed the onset of dyskinetic signs and reduced their neurochemical changes. It also reduced their intensity when given once dyskinesia was already present. This potential adds to other properties of Δ9-THCV as antiparkinsonian therapy.

In summary, our data support the anti-dyskinetic potential of Δ9-THCV to ameliorate adverse effects caused by L-DOPA, in particular delaying the occurrence and attenuating the magnitude of dyskinetic signs. This adds to its promising symptom-alleviating and neuroprotective properties described previously. Although further studies are clearly required to determine the clinical significance of these data in humans, the results nevertheless situate Δ9-THCV in a promising position for developing a cannabinoid-based therapy for PD patients.”

https://www.sciencedirect.com/science/article/pii/S0969996120301674?via%3Dihub

Cannabinoid type 2 receptor agonist JWH133 decreases blood pressure of spontaneously hypertensive rats through relieving inflammation in the rostral ventrolateral medulla of the brain.

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Journal of Hypertension | The International Society of Hypertension“Neuroinflammation in the rostral ventrolateral medulla (RVLM) has been reported to be associated with hypertension. The upregulation and activation of the cannabinoid type 2 (CB2) receptor may be part of the active process of limiting or downregulating the inflammatory process.

This study was designed to determine the role of the CB2 receptor in blood pressure (BP) through relieving neuroinflammation in the RVLM in spontaneously hypertensive rats (SHRs).

CONCLUSION:

Taken together, our results suggest that exciting the CB2 receptor relieves proinflammatory cytokine levels in the RVLM to decrease the BP, HR and RSNA in SHRs.”

https://www.ncbi.nlm.nih.gov/pubmed/32238784

https://journals.lww.com/jhypertension/Abstract/2020/05000/Cannabinoid_type_2_receptor_agonist_JWH133.15.aspx

Cannabinoid receptor 2 agonist promotes parameters implicated in mucosal healing in patients with inflammatory bowel disease.

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Issues“Cannabis benefits patients with inflammatory bowel disease (IBD).

Cannabinoid receptors are expressed in gut immune cells and in epithelial cells of inflamed guts.

Mucosal healing (MH) requires epithelial layer restoration.

CONCLUSION:

Using ex vivo and in vitro human models, we demonstrated that manipulating the cannabinoid system affects colon cells and secretome characteristics that facilitate MH in IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/32213014

“Experimental studies and recent clinical trials suggest that treatment with cannabis benefits patients with IBD.”

https://journals.sagepub.com/doi/10.1177/2050640619889773

Endocannabinoid Modulation of Microglial Phenotypes in Neuropathology.

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Image result for frontiers in neurology“Microglia, the resident immune cells of the central nervous system, mediate brain homeostasis by controlling neuronal proliferation/differentiation and synaptic activity. In response to external signals from neuropathological conditions, homeostatic (M0) microglia can adopt one of two activation states: the classical (M1) activation state, which secretes mediators of the proinflammatory response, and the alternative (M2) activation state, which presumably mediates the resolution of neuroinflammation and tissue repair/remodeling.

Since chronic inflammatory activation of microglia is correlated with several neurodegenerative diseases, functional modulation of microglial phenotypes has been considered as a potential therapeutic strategy.

The endocannabinoid (eCB) system, composed of cannabinoid receptors and ligands and their metabolic/biosynthetic enzymes, has been shown to activate anti-inflammatory signaling pathways that modulate immune cell functions. Growing evidence has demonstrated that endogenous, synthetic, and plant-derived eCB agonists possess therapeutic effects on several neuropathologies; however, the molecular mechanisms that mediate the anti-inflammatory effects have not yet been identified.

Over the last decade, it has been revealed that the eCB system modulates microglial activation and population. In this review, we thoroughly examine recent studies on microglial phenotype modulation by eCB in neuroinflammatory and neurodegenerative disease conditions.

We hypothesize that cannabinoid 2 receptor (CB2R) signaling shifts the balance of expression between neuroinflammatory (M1-type) genes, neuroprotective (M2-type) genes, and homeostatic (M0-type) genes toward the latter two gene expressions, by which microglia acquire therapeutic functionality.”

https://www.ncbi.nlm.nih.gov/pubmed/32117037

https://www.frontiersin.org/articles/10.3389/fneur.2020.00087/full

Cannabinoid receptor 2 activation alleviates septic lung injury by promoting autophagy via inhibition of inflammatory mediator release.

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Cellular Signalling“Septic lung injury is one of main causes of high mortality in severe patients. Inhibition of excessive inflammatory response is considered as an effective strategy for septic lung injury.

Previous studies have shown that cannabinoid receptor 2 (CB2), a G protein-coupled receptor, play an important role in immunosuppression.

Whether CB2 can be used as a therapeutic target for septic lung injury is unclear. The aim of this study is to explore the role of CB2 in sepsis and its potential mechanism.

These results suggest that CB2 serves as a protective target for septic lung injury by decreasing inflammatory factors, which is associated with the enhancement of autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/32027949

“Activation of cannabinoid receptor 2 can alleviate sepsis-induced lung injury.”

https://www.sciencedirect.com/science/article/abs/pii/S0898656820300334?via%3Dihub