Tag Archives: cannabinoid receptors

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

Researchers Meet to Discuss Cannabinoid-Based Stroke Therapy

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Murikinati et al., 2010 shows that brain tissue is saved after a stroke with JWH-133

“The Cannabinoid Discussion Group at Temple University met for the second time this semester to review a recent scientific publication from a German Laboratory. The presenter was Zachary Reichenbach, an MD/Ph.D student at Temple, who is currently working in the laboratory of Dr.Ron Tuma. The Tuma lab is focused on studying cannabinoid based therapies for the treatment of cerebral ischemia resulting from stroke. Mr.Reichenbach led the discussion on a research paper which showed that the cannabinoid JWH-133 activates the cannabinoid type 2 receptor (CB2R), resulting a decrease in infarct size or brain damage duringreperfusion following an ischemic event.

Mr.Reichenbach provided background on stroke, stating that it is the 3rd cause of death in this country, and 85% of those strokes are of the ischemic variety. During an ischemic event there is a hyper-immune response resulting in the recruitment of immune cells that kill brain tissue. Cannabinoids have been shown to modulate the immune system, notably the Tuma lab has published data on the CB2 receptor’s anti-inflammatory effects. Activating the CB2 receptor decreases the migration of hyper-immune cells to the brain. The more brain you save, the more you save someone from disabilities or death.

When asked about the implications of these findings on a cannabinoid that could be a potential stroke therapy, Mr.Reichenbach replied that the results of his work and others is promising…

And just in case you were wondering, THC, the active ingredient in Cannabis, activates both the CB1 and CB2 receptor.”

http://www.examiner.com/article/researchers-meet-to-discuss-cannabinoid-based-stroke-therapy

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

Cannabinoids and Neuroprotection in Stroke

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“One of the most recently described neural signaling systems is that mediated by endogenous cannabinoids (endocannabinoids). Cannabinoids have recently been shown to attenuate neuronal injury induced by hypoxia and glucose deprivation in cell culture, as well as injury induced in rat brain following both global and focal cerebral ischemia in vivo.

Two endocannabinoids have been characterized in detail: N-arachidonylethanolamide and 2-arachidonylglycerol. Cannabinoid CB1 and CB2receptors have been cloned and an alternatively spliced CB1A isoform has been identified.

The development of metabolically stable, synthetic, enantiomeric cannabinoid receptor agonists and of CB1 and CB2 receptor antagonists has greatly aided the characterization of cannabinoid receptor-mediated processes, although certain aspects of cannabinoid signaling in some systems remain poorly understood.

Indirect evidence suggests that cannabinoids might serve as endogenous regulators of ischemic neuronal injury, but several recent reports provide more direct evidence bearing on such a role.

The author’s own findings provide evidence for CB1 receptor-mediated neuroprotection in vivo, but non-receptor-mediated protection in vitro.”

http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=3&p_RefId=129&p_IsPs=Y

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

Cannabinoids drug for inflammatory bowel

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Medindia

“Researchers from the University of Bath, UK has found that Cannabinoids derived from Cannabis has found to be effective in the treatment of inflammatory bowel diseases like Crohn’s disease and ulcerative colitis.

“The system that responds to cannabis in the brain is present and functioning in the lining of the gut,” lead researcher Dr. Karen Wright, of the University of Bath, explained to Reuters Health. “There is an increased presence of one component of this system during inflammatory bowel diseases,” she explained.

The report of the study was published in the Journal of Gastroenterology in which she has explained the location of CB1 and CB2 receptors in human colon tissue which binds to the Cannabinoid. She has used Human colon cell lines to establish the binding of the cannabinoid compounds and in her wound healing experiments.

Increased CB2 receptors are found in colonic tissue characteristic of inflammatory bowel disease. They found that the Cannabinoids helps in wound healing of the surface by CB1 related receptor mechanism.

“Cannabinoids, which we make ourselves, as well as synthetic Cannabinoids, can promote wound healing in the gut, which is extremely interesting given that inflammatory bowel disease involves damaged gut linings,” Wright said.”

http://www.medindia.net/news/view_news_main.asp?x=4578

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

Effects of the novel cannabinoid CB1 receptor antagonist PF 514273 on the acquisition and expression of ethanol conditioned place preference.

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“The centrally expressed cannabinoid receptor (CB1) has been considered a potential therapeutic target in treating alcoholism.

Though CB1 receptors have been shown to modulate primary and conditioned ethanol reward, much of this research employed animal models that require ethanol ingestion or oral routes of administration. This is problematic considering CB1 antagonist drugs have high anorectic liability and have been used clinically in the treatment of obesity. Therefore, the present study examined CB1 antagonism in DBA/2J mice using an unbiased ethanol-induced conditioned place preference (CPP) procedure, a paradigm that does not require ethanol ingestion…

Results from the present study appear inconsistent with other studies that have demonstrated a role for CB1 antagonism in ethanol reward using oral administration paradigms.

Our findings suggest that CB1 antagonism may have greater involvement in consummatory behavior than ethanol reward.”

http://www.ncbi.nlm.nih.gov/pubmed/24954022

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

The endocannabinoid system modulates stress, emotionality, and inflammation.

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“The physiological and behavioral effects of stress are well characterized.

Endocannabinoids are produced on demand and function to attenuate many of the physiological effects of the stress response.

The endocannabinoid system is made up of cannabinoid receptors, the fatty acid signaling molecules that bind to and activate these receptors, and the enzymes that synthesize and catabolize these endocannabinoid signaling molecules.

Cannabinoid research has recently grown substantially, due in no small part to the development of genetic research models as well as highly selective pharmaceutical tools.

The purpose of this minireview is to discuss a subset of the many parallels between cannabinoid and behavioral neuroimmunology research, with specific discussion of interactions between the endocannabinoid system and psychological stress, emotionality, and inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/24953427

THC Can Manage Sickle Cell Disease

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“Cannabinoids, the active ingredients in pot offer a new way to treat chronic and acute pain from sickle cell disease, ScienceDaily reports.

Currently the only treatment for the blood disease is opiods.

“Pain in SCD is described to be more intense than labor pain. The pain starts early in a patient’s life, often during infancy, and increases in severity with age.

[Cannibinoids are] effective in much lower amounts than opioids — the only currently approved treatment for this disease.”

http://www.eastbayexpress.com/LegalizationNation/archives/2010/07/23/daily-roundup-thc-can-manage-sickle-cell-disease-oakland-tweaks-medical-cannabis-taxes