“Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. It is the most common cause of death among critically ill patients in non-coronary intensive care units and the incidence continues to rise. Although advanced management was applied, the prognosis of sepsis patients remains poor. As a G-protein coupled receptor, cannabinoid receptor 2 (CB2R) was implicated in a wide variety of diseases. In this study, we aimed to investigate the role of CB2R in sepsis.
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The use of cannabis in supportive care and treatment of brain tumor
“Anticancer Effects of Cannabinoids may be able to Prolong Life.
Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC. Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive. Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients. THC, a partial CB1, CB2 agonist, has the stigma of psychotropic effects that are mediated by CB1 stimulation. However, CB1 stimulation is necessary for improving mood and appetite and many other effects. At present, it is hard to imagine a better approach than adjusting THC doses individually to balance wanted versus unwanted effects. Generally, higher doses are needed to achieve analgesic and antiemetic effects. Even much higher, supraphysiologic oral doses would be needed to combat tumors. Combinations were synergistic under many circumstances such as in pain and antitumor studies. Cannabinoids differ in their antitumor activities and probably in their mechanisms and targets, which is a rationale for combinations. However, for many pharmacological effects (except against tumors) roughly 10-times higher daily doses are needed for CBD compared to THC. In summary, the endocannabinoid system is likely playing a crucial role in palliative care. The future will show whether an optimized treatment strategy with cannabinoids can also prolong life of brain tumor patients by their virtue to combat cancer cells.”https://academic.oup.com/nop/article/4/3/151/2918616
“Cannabinoid Drug Prolongs the Life of Brain Tumor Patients in Phase II Trials” https://labiotech.eu/gw-pharmaceuticals-brain-tumor/
]]>“Funded by the National Institutes of Health to find evidence that marijuana damages the immune system, the study found instead that THC slowed the growth of 3 kinds of cancer in mice—lung and breast cancer, and a virus-induced leukemia. The US Drug Enforcement Agency quickly shut down the Virginia study and all further cannabis/tumor research even though the researchers demonstrated remarkable antitumor effects.”
Cannabinoids in health and disease: pharmacological potential in metabolic syndrome and neuroinflammation.
“The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena.
In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving.
Moreover, cannabinoid agonists are able to reduce inflammatory response.
In this review a brief history of cannabinoids and the protagonists of the endocannabinoidergic system, i.e. synthesis and degradation enzymes and main receptors, will be described. Furthermore, the pharmacological effects of cannabinoids will be outlined. An overview of the involvement of the endocannabinoidergic system in neuroinflammatory and metabolic pathologies will be made.
Finally, particular attention will also be given to the new pharmacological entities acting on the two main receptors, cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), with particular focus on the neuroinflammatory and metabolic mechanisms involved.”
Inhibition of fatty acid amide hydrolase by PF-3845 alleviates the nitrergic and proinflammatory response in rat hippocampus following acute stress.
“Long term exposure to stress has been demonstrated to cause neuroinflammation through a sustained overproduction of free radicals, including nitric oxide, via an increased inducible nitric oxide synthase (iNOS) activity.
Similar to nitric oxide, endocannabinoids are synthesised on demand, with preclinical observations suggesting that cannabinoid receptor agonists and endocannabinoid enhancers inhibit nitrergic activity.
RESULTS:
The results demonstrate that pre-treatment with PF-3845 rapidly ameliorates plasma corticosterone release at 60 minutes of stress. An increase in endocannabinoid signalling also induces an overall attenuation in iNOS, tumor necrosis factor-alpha convertase, interleukin-6, cyclooxygenase-2, peroxisome proliferator-activated receptor gamma mRNA, and the transactivation potential of NF-κB in the hippocampus.
CONCLUSIONS:
These results suggest that enhanced endocannabinoid levels in the dorsal hippocampus have an overall anti-nitrosative and anti-inflammatory effect following acute stress exposure.”“Inhibition of fatty acid amide hydrolase (FAAH) potentiates endocannabinoid activity and is hypothesized to have therapeutic potential for mood and anxiety disorders and pain” https://www.ncbi.nlm.nih.gov/pubmed/29575526
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“Studies show that cancer cell invasion or metastasis is the primary cause of death in malignancies including breast cancer.
The existence of cancer stem cells (CSCs) in breast cancer may account for tumor initiation, progression, and metastasis.
Recent studies have reported different effects of 
“Activating the endocannabinoid system has become a major focus in the search for novel therapeutics for anxiety and deficits in fear extinction, two defining features of PTSD. We examined whether chronic treatment with the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.2, 0.3, 0.4 mg/kg, i.p.) or the CB1/2 receptor agonist WIN55,212-2 (0.25, 0.5 mg/kg, i.p.) injected for 3 weeks to rats exposed to the shock and reminders model of PTSD would attenuate post-stress symptoms and affect basolateral amygdala (BLA) and CA1 CB1 receptors.
Exposure to shock and reminders enhanced acoustic startle response and impaired extinction. Rats exposed to shock and reminders and chronically treated with URB597 demonstrated normalized startle response and intact extinction kinetics. WIN55,212-2 only affected the startle response. The therapeutic effects of URB597 and WIN55,212-2 were found to be CB1 receptor dependent, as these effects were blocked when a low dose of the CB1 receptor antagonist AM251 (0.3 mg/kg, i.p. for 3 weeks) was co-administered. Moreover, URB597, but not WIN55,212-2, normalized the shock/reminders-induced upregulation in CB1 receptor levels in the BLA and CA1. One hour after the shock, N-arachidonoylethanolamine (AEA) was increased in the BLA and decreased in the CA1. Circulating 2-arachidonoylglycerol (2-AG) concentrations were decreased in shocked rats, with no significant effect in the BLA or CA1. FAAH activity was increased in the CA1 of shocked rats.
Chronic cannabinoid treatment with URB597 can ameliorate PTSD-like symptoms suggesting FAAH inhibitors as a potentially effective therapeutic strategy for the treatment of disorders associated with inefficient fear coping.”
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