Tag Archives: CB2

Cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of Huntington’s disease.

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“Here, we show that the genetic deletion of CB2 receptors in a slowly progressing HD mouse model accelerates the onset of motor deficits and increases their severity.

Treatment of mice with a CB2 receptor agonist extends life span and suppresses motor deficits, synapse loss, and CNS inflammation…

CB2 receptor signaling in peripheral immune cells suppresses neurodegeneration in HD mouse models

The development of peripherally restricted CB2 receptor agonists holds promise for treating HD and other neurodegenerative diseases.

In summary, our results suggest CB2 receptor signaling in peripheral immune cells has an important role in HD and other neurodegeneration disorders. Further elucidation of the molecular mechanisms that underlie these effects may lead to novel therapeutic strategies to treat these disorders.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753072/

http://www.thctotalhealthcare.com/category/huntingtons/

Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling.

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Figure 1.

“To further investigate the role of the cannabinoid system in pilosebaceous unit biology, we have explored in the current study whether and how endocannabinoids have an impact on human sebaceous gland biology…

Here, we provide the first evidence that SZ95 sebocytes express CB2 but not CB1…

…our results collectively suggest that human sebocytes utilize a paracrine-autocrine, endogenously active, CB2-mediated endocannabinoid signaling system for positively regulating lipid production and cell death.

CB2 antagonists or agonists therefore deserve to be explored in the management of skin disorders characterized by sebaceous gland dysfunctions (e.g., acne vulgaris, seborrhea, dry skin).”

http://www.fasebj.org/content/22/10/3685.long

Mechanisms of control of neuron survival by the endocannabinoid system.

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“Endocannabinoids act as retrograde messengers that, by inhibiting neurotransmitter release via presynaptic CB(1) cannabinoid receptors, regulate the functionality of many synapses. In addition, the endocannabinoid system participates in the control of neuron survival.

Thus, CB(1) receptor activation has been shown to protect neurons from acute brain injury as well as in neuroinflammatory conditions and neurodegenerative diseases.

Cannabinoid neuroprotective activity relies on the inhibition of glutamatergic neurotransmission and on other various mechanisms, and is supported by the observation that the brain overproduces endocannabinoids upon damage.

Besides promoting neuroprotection, a role for the endocannabinoid system in the control of neurogenesis from neural progenitors has been put forward. In addition, activation of CB(2) cannabinoid receptors on glial cells may also participate in neuroprotection by limiting the extent of neuroinflammation.

Altogether, these findings support that endocannabinoids constitute a new family of lipid mediators that act as instructive signals in the control of neuron survival.”

http://www.ncbi.nlm.nih.gov/pubmed/18781978

Cannabinoid receptor CB2 is expressed on vascular cells, but not astroglial cells in the post-mortem human Huntington’s disease brain.

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“Huntington’s disease (HD) is an inherited neurological disease with motor, cognitive and psychiatric symptoms. Characterised by neuronal degeneration, HD pathology is initially apparent in the striatum and cortex.

Considerable research has recently suggested that the neurological immune response apparent in brain injury and disease may provide a valuable therapeutic target.

Cannabinoid CB2 receptors are localised and up-regulated on a number of peripheral immune cell types following inflammation and injury.

…our observation that CB2 is present on blood vessel cells, with increased CD31 co-localisation in HD may represent a new context for CB2 therapeutic approaches to neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/24978314

http://www.thctotalhealthcare.com/category/huntingtons/

Activation of cannabinoid 2 receptors protects against cerebral ischemia by inhibiting neutrophil recruitment

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Figure 1.

“THE CONSEQUENCES OF ISCHEMIC INJURY in liver, heart, and brain can be ameliorated by cannabinoids, a group of diverse compounds that include constituents of the plant Cannabis sativa (phytocannabinoids), endogenous lipids (endocannabinoids), and synthetic substances. Most of the effects of cannabinoids are mediated by the G-protein-coupled receptors cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2)… 

Cannabinoids protect against ischemic stroke…

Activation of the cannabinoid 2 receptor (CB2) reduces ischemic injury in several organs…

In conclusion, our data demonstrate that by activating p38 in neutrophils, CB2 agonists inhibit neutrophil recruitment to the brain and protect against ischemic brain injury.”

http://www.fasebj.org/content/24/3/788.long

Cannabis gives stroke patients hope

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“New research by University of Otago scientists suggests some mechanisms in the brain targeted by cannabis could become drugs targets to counter brain cell damage after a stroke.

Researchers from the Medical School’s Department of Pharmacology and Toxicology have been the first in the world to show the cannabinoid CB2 receptor appears in the rat brain following a stroke. Their findings were published recently in the journal Neuroscience Letters.

Dr John Ashton says the CB2 receptor is a protein produced as part of the body’s immune response system.

“This response is triggered by stroke and causes the inflammation that leads to damage in the area of the brain around where the stroke has occurred.

“If the inflammation can be stopped or reduced then it offers the hope of reducing the extent of the damage caused by stroke – and CB2 offers a potential target for such a drug.””

http://www.sciencealert.com.au/news/20071404-15007.html

“Cerebral hypoxia-ischemia and middle cerebral artery occlusion induce expression of the cannabinoid CB2 receptor in the brain. The presence of CB2-positive cells in the brain following stroke may provide a novel strategy for cannabinoid-mediated intervention into stroke induced neurodegeneration without the psychoactive effects of CB1 receptor stimulation.” https://www.ncbi.nlm.nih.gov/pubmed/17123706

Cannabis Counter Brain Cell Damage After a Stroke

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“New research by University of Otago scientists suggests some mechanisms in the brain targeted by cannabis could become drugs targets to counter brain cell damage after a stroke.

Researchers from the Medical School’s Department of Pharmacology and Toxicology have been the first in the world to show the cannabinoid CB2 receptor appears in the rat brain following a stroke.

Their findings were published recently in the journal Neuroscience Letters.

Dr John Ashton says the CB2 receptor is a protein produced as part of the body’s immune response system.

“This response is triggered by stroke and causes the inflammation that leads to damage in the area of the brain around where the stroke has occurred.

“If the inflammation can be stopped or reduced then it offers the hope of reducing the extent of the damage caused by stroke – and CB2 offers a potential target for such a drug.”

Dr Ashton says cannabis targets both the CB2 and the related CB1 receptors.

“THC, the major active ingredient of cannabis, acts mainly on CB1 but it also affects CB2. While THC is known to have some positive effects in terms of pain management its use is severely limited because of the way it triggers the psychoactive CB1 receptors in the brain,” he says.

“The aim would be to develop a drug that targets the CB2 receptor without affecting CB1.”

Dr Ashton says the relationship between cannabis and cannabinoid drugs has similarities to the relationship between heroin and codeine.

“Heroin and codeine share common targets, but by designing codeine in such a way that it eliminated the psychoactive side-effects seen with heroin, a therapeutically useful drug was developed. There is the potential to do the same with cannabinoids.”

Drugs targeting CB2 could also have potential therapeutic use in other conditions involving inflammatory damage to the brain, such as Huntington’s Disease and Alzheimer’s Disease. There may also be scope to use them in pain management.

“CB2 cells are also found in the spinal cord. They regulate pain signals making them a potential target for new pain killing drugs.””

http://www.hightimes.com/read/cannabis-counter-brain-cell-damage-after-stroke

Long-term cannabinoid type 2 receptor agonist therapy decreases Bacterial Translocation In Rats with cirrhosis and ascites.

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“Intestinal hyper-permeability, impaired peritoneal macrophages (PMs) phagocytosis, and, bacterial translocation (BT) resulting in increased systemic and local infection/inflammation such as spontaneous bacterial peritonitis (SBP), together with increased tumor necrosis factor-α (TNFα) levels, are all implicated in the pathogenesis of cirrhosis-related complications.

Manipulation of cannabinoid receptors (CB1R and CB2R), which are expressed on the gut mucosa and PMs, has been reported to modulate intestinal inflammation and systemic inflammatory cytokines release. Our study aims to explore the effects of chronic CB1R/CB2R agonist/antagonist treatments on relevant abnormalities in cirrhotic ascitic rats…

CONCLUSIONS:

Our study suggests that CB2R agonist have the potential to treat BT and various relevant abnormalities through the inhibition of systemic/intestinal oxidative stress, inflammatory cytokines and TNFα releases in cirrhosis. Overall, chronic CB2R agonist treatment affects multiple approach mechanisms, and the direct effect on hyperdynamic circulation is only minor.”

http://www.ncbi.nlm.nih.gov/pubmed/24953022

Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling.

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“The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. As a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells.

Here, we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo.

These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology.”

http://www.ncbi.nlm.nih.gov/pubmed/24942731

http://www.thctotalhealthcare.com/category/cancer/

Cannabinoid CB2 Receptor as a New Phototherapy Target for the Inhibition of Tumor Growth.

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“The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB2 receptor (CB2R) as a new target and used a CB2R-targeted photosensitizer, IR700DX-mbc94, for phototherapy treatment…

Taken together, IR700DX-mbc94 is a promising phototherapy agent with high target-specificity. Moreover, CB2R appears to have great potential as a phototherapeutic target for cancer treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/24779700

“Target-selective phototherapy using a ligand-based photosensitizer for type 2 cannabinoid receptor. Phototherapy is a powerful, noninvasive approach for cancer treatment, with several agents currently in clinical use… We show that our CB2R-targeted phototherapy agent, IR700DX-mbc94, is specific for CB2R and effective only when bound to the target receptor. Overall, this opens up the opportunity for development of an alternative treatment option for CB2R-positive cancers.”  http://www.ncbi.nlm.nih.gov/pubmed/24583052