“The blood-brain barrier (BBB) disruption and the following development of brain edema, is the most life-threatening secondary injury after intracerebral hemorrhage (ICH). This study is to investigate a potential role and mechanism of JWH133, a selected cannabinoid receptor type2 (CB2R) agonist, on protecting blood-brain barrier integrity after ICH.
Category Archives: Endocannabinoid System
The relationship of endocannabinoidome lipid mediators with pain and psychological stress in women with fibromyalgia – a case control study.
“Characterized by chronic widespread pain, generalized hyperalgesia, and psychological stress fibromyalgia (FM) is difficult to diagnose and lacks effective treatments. The endocannabinoids – arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), and the related oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) – are endogenous lipid mediators with analgesic and anti-inflammatory characteristics, in company with psychological modulating properties (e.g., stress and anxiety), and are included in a new emerging “ome”, the endocannabinoidome. This case -control study compared the concentration differences of AEA, OEA, PEA, SEA, and 2-AG in 104 women with FM and 116 healthy controls (CON). All participants OEArated their pain, anxiety, depression, and current health status. The relationships between the lipid concentrations and the clinical assessments were investigated using powerful multivariate data analysis and traditional bivariate statistics. The concentrations of OEA, PEA, SEA, and 2-AG were significantly higher in FM than in CON; significance remained for OEA and SEA after controlling for BMI and age. 2-AG correlated positively with FM duration and BMI, and to some extent negatively with pain, anxiety, depression, and health status. In FM, AEA correlated positively with depression ratings. The elevated circulating levels of endocannabinoidome lipids suggest that these lipids play a role in the complex pathophysiology of FM and might be signs of ongoing low-grade inflammation in FM. Although the investigated lipids are significantly altered in FM their biological roles are uncertain with respect to the clinical manifestations of FM. Thus, plasma lipids alone are not good biomarkers for FM.
PERSPECTIVE:
This study reports about elevated plasma levels of endocannabinoidome lipid mediators in FM. The lipids suitability to work as biomarkers for FM in the clinic were low, however their altered levels indicate that a metabolic asymmetry is ongoing in FM, which could serve as basis during explorative FM pain management.” https://www.ncbi.nlm.nih.gov/pubmed/29885369 https://www.jpain.org/article/S1526-5900(18)30197-4/fulltext]]>Cannabinoid receptor type 1 in the brain regulates the affective component of visceral pain in mice.
“Endocannabinoids acting through cannabinoid receptor type 1 (CB1) are major modulators of peripheral somatic and visceral nociception. Although only partially studied, some evidence suggests a particular role of CB1 within the brain in nociceptive processes.
As the endocannabinoid system regulates affect and emotional behaviors, we hypothesized that cerebral CB1 influences affective processing of visceral pain-related behaviors in laboratory animals.
To study nocifensive responses modulated by supraspinal CB1, we used conditional knock-out mice lacking CB1 either in cortical glutamatergic neurons (Glu-CB1-KO), or in forebrain GABAergic neurons (GABA-CB1-KO), or in principle neurons of the forebrain (CaMK-CB1-KO). These mutant mice and mice treated with the CB1 antagonist SR141716 were tested for different pain-related behaviors. In an acetic acid-induced abdominal constriction test, supraspinal CB1 deletions did not affect nocifensive responses. In the cerulein-model of acute pancreatitis, mechanical allodynia or hyperalgesia were not changed, but Glu-CB1- and CaMK-CB1-KO mice showed significantly increased facial grimacing scores indicating increased affective responses to this noxious visceral stimulus. Similarly, these brain-specific CB1 KO mice also showed significantly changed thermal nociception in a hot-plate test.
These results reveal a novel, and important role of CB1 expressed by cortical glutamatergic neurons in the affective component of visceral nociception.”
https://www.ncbi.nlm.nih.gov/pubmed/29885522
Sub-chronic treatment with cannabidiol but not with URB597 induced a mild antidepressant-like effect in diabetic rats.
“Depression associated with diabetes has been described as a highly debilitating comorbidity. Due to its complex and multifactorial mechanisms, the treatment of depression associated with diabetes represents a clinical challenge.
Cannabidiol (CBD), the non-psychotomimetic compound derived from Cannabis sativa, has been pointed out as a promising compound for the treatment of several psychiatric disorders.
Here, we evaluated the potential antidepressant-like effect of acute or sub-chronic treatment with CBD in diabetic rats using the modified forced swimming test (mFST).
Also, to better understand the functionality of the endocannabinoid system in diabetic animals we also evaluated the effect of URB597, a fatty acid amide hydrolase inhibitor.
Acute treatment with either CBD or URB induced an antidepressant-like effect in NGL rats, but not in DBT rats. However, sub-chronic treatment with CBD (only at a dose of 30 mg/kg), but not with URB597, induced a mild antidepressant-like effect in DBT animals. Neither body weight nor blood glucose levels were altered by treatments.
Considering the importance of the endocannabinoid system to the mechanism of action of many antidepressant drugs, the mild antidepressant-like effect of the sub-chronic treatment with CBD, but not with URB597 does not invalidate the importance of deepening the studies involving the endocannabinoid system particularly in DBT animals.”
https://www.ncbi.nlm.nih.gov/pubmed/29885450
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“The endocannabinoid system (ECS) is composed of cannabinoid receptors, their endogenous ligands, and the enzymes involved in endocannabinoid turnover.
Modulating the activity of the ECS may influence a variety of physiological and pathophysiological processes.
A growing body of evidence indicates that activation of cannabinoid receptors by endogenous, plant-derived, or synthetic cannabinoids may exert beneficial effects on gastrointestinal inflammation and visceral pain.
The present ex vivo study aimed to investigate immunohistochemically the distribution of cannabinoid receptors CB1, CB2, G protein-coupled receptor 55 (GPR55), and peroxisome proliferation activation receptor alpha (PPARα) in the canine gastrointestinal tract.
Cannabinoid receptors showed a wide distribution in the gastrointestinal tract of the dog.
Since cannabinoid receptors have a protective role in inflammatory bowel disease, the present research provides an anatomical basis supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders and visceral hypersensitivity in canine acute or chronic enteropathies.”
“Currently available antidepressants have a substantial time lag to induce therapeutic response and a relatively low efficacy. The development of drugs that addresses these limitations is critical to improving public health.
Cannabidiol (CBD), a non-psychotomimetic component of