“The aim of this study was to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models…
CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.”
“The sepsis syndrome represents an improper immune response to pathogens and is associated with an unacceptably high rate of mortality. Although supportive care is of benefit to the septic patient, there are no viable therapeutics available that target the immune system suitable for the whole septic population. Recently, using a physiologically relevant murine mouse model, the cannabiniod 2 receptor has been shown to play a critical role in the host response to sepsis. Here, the structure, expression, signaling, and function of the CB2 receptor on leukocytes will be reviewed. Further, the effects mediated by the CB2 receptor during sepsis will be reviewed. Altogether, alterations in inflammation and the host response during sepsis by the CB2 receptor support its use as a possible therapeutic agent.”
“Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics.
The present study explored the effect of modulating the CB2 receptor pathway in an acute sepsis mouse model.
Using various compounds we have shown different mechanisms of activating CB2 receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis.”
http://www.jpp.krakow.pl/journal/archive/04_14/pdf/171_04_14_article.pdf
http://www.jpp.krakow.pl/journal/archive/04_14/pdf/183_04_14_article.pdf
“The endogenous cannabinoid system—named for the plant that led to its discovery—is one of the most important physiologic systems involved in establishing and maintaining human health.
Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells. With its complex actions in our immune system, nervous system, and virtually all of the body’s organs, the endocannabinoids are literally a bridge between body and mind.
By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease.
…either stimulating or inhibiting the endocannabinoid system could have beneficial effects.
The most direct route of THC administration is by smoking marijuana or other forms of cannabis. Yet purified, FDA-approved medicinal preparations of THC are available in pill form… Why not just take a pill? There are several reasons that some patients prefer puffing over swallowing. One quantitatively minor factor is potential lethality.
It is possible to get a fatal overdose by swallowing too many THC pills at once, whereas documented evidence of death simply from smoking too much cannabis does not seem to exist.”
“Abnormalities in social behavior are found in almost all psychiatric disorders, such as anxiety, depression, autism, and schizophrenia. Thus, comprehension of the neurobiological basis of social interaction is important for a better understanding of numerous pathologies and improved treatments.
Several findings have suggested that an alteration of cannabinoid receptor type 1 (CB1) receptor function could be involved in the pathophysiology of such disorders…
In conclusion, we provide evidence that CB1 receptors specifically modulate the social investigation of female mice in a neuronal subtype-specific manner.”
“Interleukin (IL)-17 is a proinflammatory and fibrogenic cytokine mainly produced by T-helper (Th)17 lymphocytes, together with the hepatoprotective and antifibrogenic cytokine, IL-22.
Cannabinoid receptor 2 (CB2) is predominantly expressed in immune cells and displays anti-inflammatory and antifibrogenic effects.
In the present study, we further investigated the mechanism underlying antifibrogenic properties of CB2 receptor and explored its effect on the profibrogenic properties of IL-17.
These data demonstrate that CB2 receptor activation decreases liver fibrosis by selectively reducing IL-17 production by Th17 lymphocytes via a STAT5-dependent pathway, and by blunting the proinflammatory effects of IL-17 on its target cells, while preserving IL-22 production.”
“Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions..
Cannabinoids are compounds derived from the Cannabis sativa plant and exert many effects on the immune system. Cannabinoids have potential as therapeutic agents in several different disease conditions, including experimental autoimmune hepatitis, Multiple Sclerosis, and Graft vs. Host Disease…
This report suggested a role of the endogenous cannabinoid system in regulation of allergic inflammation.
These studies also suggest that endogenous cannabinoid system is one of the homeostatic mechanisms that the body employs to down-regulate immune response to foreign antigens as well as combat autoimmunity.
Targeting of this system could yield valuable therapeutics in the future.”
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0093954
“For centuries Cannabis sativa and cannabis extracts have been used in natural medicine.
Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis.
In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma.
Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications.
The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.”
“Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism, is caused by the silencing of the FMR1 gene, leading to the loss of fragile X mental retardation protein (FMRP), a synaptically expressed RNA-binding protein regulating translation.
The endocannabinoid system (ECS) is a key modulator of synaptic plasticity, cognitive performance, anxiety, nociception and seizure susceptibility, all of which are affected in FXS. The cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) are activated by phospholipid-derived endocannabinoids, and CB1R-driven long-term regulation of synaptic strength, as a consequence of mGluR5 activation, is altered in several brain areas of Fmr1 knockout mice.
We found that CB1R blockade in male Fmr1 knockout (Fmr1(-/y)) mice through pharmacological and genetic approaches normalized cognitive impairment, nociceptive desensitization, susceptibility to audiogenic seizures, overactivated mTOR signaling and altered spine morphology, whereas pharmacological blockade of CB2R normalized anxiolytic-like behavior. Some of these traits were also reversed by pharmacological inhibition of mTOR or mGluR5.
Thus, blockade of ECS is a potential therapeutic approach to normalize specific alterations in FXS.”