“Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis.
The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study…
Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context.”
“Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects…
The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain.”
“The adipocyte-derived, anorectic hormone, leptin, was recently shown to owe part of its regulatory effects on appetite-regulating hypothalamic neuropeptides to the elevation of ROS levels in arcuate nucleus (ARC) neurons.
Leptin is also known to exert a negative regulation on hypothalamic endocannabinoid levels and hence on cannabinoid CB1 receptor activity.
Here we investigated the possibility of a negative regulation by CB1 receptor of leptin-mediated ROS formation in the ARC…
We conclude that CB1 activation reverses leptin-induced ROS formation, and hence possibly some of the ROS-mediated effects of the hormone, by preventing PPAR-γ inhibition by leptin, with subsequent increase of catalase activity.
This mechanism might underlie in part CB1 orexigenic actions under physiopathological conditions accompanied by elevated hypothalamic endocannabinoid levels.”
The effects of cannabinoids have been known for centuries and over the past several decades two G-protein coupled receptors, CB1 and CB2, have been identified that are responsible for their activity.
Endogenous lipid-derived cannabinergic agents have been found, biosynthetic and catabolic machinery characterized, and synthetic agents have been designed to modulate these receptors.
Selective agents including agonists, antagonists, inverse agonists and novel allosteric modulators targeting either CB1 or CB2 have been developed to inhibit or augment their basal tone.
As a result, the role these receptors play in human physiology and their potential therapeutic applications in disease states are being elucidated.
The CB1 receptor while ubiquitous is densely expressed in the brain and CB2 is largely found on cells of immune origin.
This minireview highlights the role of CB1 in excitotoxic assaults in the brain and its potential to limit addiction liability.
In addition, it will examine the relationship between receptor activity and stimulation of insulin release from pancreatic β-cells, insulin resistance and feeding behavior leading toward obesity.
The role of CB2 in the neuropathology of amyotrophic lateral sclerosis and in the central manifestations of chronic HIV infection potentially converges at inflammatory cell activation thereby providing an opportunity for intervention.
Lastly, CB2 modulation is discussed in the context of an experimental model of post-menopausal osteoporosis.
Achieving exquisite receptor selectivity and elucidating the mechanisms underlying receptor inhibition and activation will be essential for the development of the next generation of cannabinergic-based therapeutic agents.”
“Patients suffering from chronic pain are often also diagnosed with a psychiatric condition, in particular generalized anxiety and major depression. The underlying pathomechanisms contributing to this comorbidity, however, are not entirely clear.
In this manuscript we have focussed on the potential role of the cannabinoid receptor CB1, because it is known to modulate neuronal circuits contributing to chronic pain states and affective behaviours.
For this purpose we analysed the consequences of a partial sciatic nerve ligation on anxiety- and depression related behaviours in mice lacking CB1 receptors.
Our results show that the development of mechanical hypersensitivity was similar in CB1 deficient mice and wild type controls. However, CB1 knockouts showed much more pronounced behavioural manifestations of anxiety-related behaviors in the light-dark and zero-maze tests, sucrose anhedonia, and disturbed home-cage activity.
These results indicate that the endocannabinoid system affects chronic pain-induced mood changes through CB1 receptors.”
“The endocannabinoids (eCBs), N-arachidonoylethanolamine (anandamide, AEA) and 2-ararchidonylglycerol (2-AG) have been identified as main endogenous ligands for cannabinoid receptors.
Developing a sensitive and robust method to determine AEA and 2-AG has been shown to be essential to understand their effects in stress regulation and the pathogenesis of affective disorders.
Detection was performed in multiple reaction monitoring (MRM) mode with an electrospray ionization source operated in positive ion mode. The method was applied to assess plasma and brain eCBs in tumor-bearing mice.”
“Several lines of evidence have shown that the endogenous cannabinoids are implicated in several neuropsychiatric diseases. Notably, preclinical and human clinical studies have shown a pivotal role of the cannabinoid system in nicotine addiction.
The CB1 receptor inverse agonist/antagonist rimonabant (also known as SR141716) was effective to decrease nicotine-taking and nicotine-seeking in rodents, as well as the elevation of dopamine induced by nicotine in brain reward area. Rimonabant has been shown to improve the ability of smokers to quit smoking in randomized clinical trials. However, rimonabant was removed from the market due to increased risk of psychiatric side-effects observed in humans.
Recently, other components of the endogenous cannabinoid system have been explored. Here, we present the recent advances on the understanding of the role of the different components of the cannabinoid system on nicotine’s effects.
Those recent findings suggest possible alternative ways of modulating the cannabinoid system that could have implication for nicotine dependence treatment.”
“Many studies have demonstrated that the endocannabinoid system (ECS) is altered in different tumor types, including colon cancer.
However, little is known about the role of the ECS in tumor progression.
Here we report the correlation between CB 2 expression and pathological data in a series of 175 colorectal cancer patients, as well as the response of the HT29 colon cancer-derived cell line upon CB 2 activation…
These results raise the question whether the activation of CB 2 should be considered as anti-tumoral therapy.”
“Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. However, the biological role of these receptors in tumor physio-pathology is still unknown…
Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and they suggest that CB2 may be a biomarker with prognostic value in these tumors.”
Objective:
To investigate the protective effect of paeoniflorin on hippocampal neurons in rats subjected to cerebral ischemia and reperfusion through activating cannabinoid receptor 2 (CBR2).
Conclusion:
CBR2 may participate in the protective effect of paeoniflorin on hippocampal neurons of cerebral ischemia-reperfusion rat models.”
http://www.ncbi.nlm.nih.gov/pubmed/25854559
http://www.ncbi.nlm.nih.gov/pubmed/?term=Paeonia+lactiflora
http://en.wikipedia.org/wiki/Paeonia_lactiflora
