“Cannabinoids inhibit tumor neovascularisation as part of their tumorregressive action.
However, the underlying mechanism is still under debate. In the present study the impact of cannabinoids on potential tumor-to-endothelial cell communication conferring anti-angiogenesis was studied…
Collectively, our data suggest a pivotal role of the anti-angiogenic factor TIMP-1 inintercellular tumor-endothelial cell communication resulting in anti-angiogenic features of endothelial cells.”
“In the last years, cannabinoids have emerged as promising neuroprotective agents in several animal paradigms of acute and degenerative brain damage. Most neuroprotective effects of cannabinoids result from the activation of cannabinoid Type 1 (CB1R) and Type 2 (CB2R) receptors in neural and immune cells.
Besides, the stimulating effect of cannabinoids on proliferation, survival, and differentiation of neural progenitor cells provides interesting prospects for long-term neural repair after acute brain damage.
The endocannabinoid system has been involved in the modulation of neural stem cells proliferation, survival and differentiation as well as in the generation of new oligodendrocyte progenitors in the postnatal brain. The present work aims to test the effect of the synthetic Type 1 and Type 2 cannabinoid receptor agonist WIN55212-2 on these processes in the context of neonatal rat brain hypoxia–ischemia (HI)…
Our results suggest that the activation of the endocannabinoid system promotes white and gray matter recovery after neonatal HI injury…
In conclusion, we have demonstrated that the synthetic cannabinoid WIN55212-2 enhances SVZ cell proliferation, oligodendrogenesis, white matter remyelination, and neuroblast generation after neonatal HI.
These findings, summed to the previously described neuroprotective properties of cannabinoids after acute brain damage, may possess therapeutic repercussions in the long-term management of neonatal HI encephalopathy, a prevalent and devastating condition for which no pharmacological treatments are yet available.”
http://stroke.ahajournals.org/content/41/12/2956.full
“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.”
“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
“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.”
“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
“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.”
“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…
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.”
“The impact of the endogenous cannabinoids (AEA, 2-AG, PEA, and virodamine) on the immune cell expressed cannabinoid receptors (CB1, CB2, TRPV-1, and GPR55) and consequent regulation of immune function is an exciting area of research with potential implications in the prevention and treatment of inflammatory and autoimmune diseases.
Despite significant advances in understanding the mechanisms through which cannabinoids regulate immune functions, not much is known about the role of endocannabinoids in the pathogenesis or prevention of autoimmune diseases.
Inasmuch as CB2 expression on immune cells and its role has been widely reported, the importance of CB1 in immunological disorders has often been overlooked especially because it is not highly expressed on naive immune cells.
Therefore, the current review aims at delineating the effect of endocannabinoids on CB1 receptors in T cell driven autoimmune diseases. This review will also highlight some autoimmune diseases in which there is evidence indicating a role for endocannabinoids in the regulation of autoimmune pathogenesis.
Overall, based on the evidence presented using the endocannabinoids, specifically AEA, we propose that the peripheral CB1 receptor is involved in the regulation and amelioration of inflammation associated with autoimmune diseases.”
“The cannabinoids are a group of terpenophenolic compounds present in the marijuana plant, Cannabis sativa. At present, three general types of cannabinoids have been identified: phytocannabinoids present uniquely in the cannabis plant, endogenous cannabinoids produced in humans and animals, and synthetic cannabinoids generated in a laboratory. It is worth noting that Cannabis sativa produces over 80 cannabinoids…
An accumulating body of evidence suggests that endocannabinoids and cannabinoid receptors type 1 and 2 (CB(1), CB(2)) play a significant role in physiologic and pathologic processes, including cognitive and immune functions.
…there is growing appreciation of the therapeutic potential of cannabinoids in multiple pathologic conditions involving chronic inflammation (inflammatory bowel disease, arthritis, autoimmune disorders, multiple sclerosis, HIV-1 infection, stroke, Alzheimer’sdisease to name a few), mainly mediated by CB(2) activation.
This review attempts to summarize recent advances in studies of CB(2) activation in the setting of neuroinflammation, immunomodulation and HIV-1 infection.
The full potential of CB2 agonists as therapeutic agents remains to be realized.
Despite some inadequacies of preclinical models to predict clinical efficacy in humans and differences between the signaling of human and rodent CB2 receptors, the development of selective CB2 agonists may open new avenues in therapeutic intervention.
Such interventions would aim at reducing the release of pro-inflammatory mediators particularly in chronic neuropathologic conditions such as HAND or MS.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663904/