Potential of the cannabinoid CB2 receptor as a pharmacological target against inflammation in Parkinson’s disease.

“Inflammation is an important pathogenic factor in Parkinson’s disease (PD), so that it can contribute to kill dopaminergic neurons of the substantia nigra and to enhance the dopaminergic denervation of the striatum.

The cannabinoid type-2 (CB2) receptor has been investigated as a potential anti-inflammatory and neuroprotective target in different neurodegenerative disorders, but still limited evidence has been collected in PD.

Here, we show for the first time that CB2 receptors are elevated in microglial cells recruited and activated at lesioned sites in the substantia nigra of PD patients compared to control subjects.

Using this experimental model, we recently described a much more intense deterioration of tyrosine hydroxylase (TH)-containing nigral neurons in CB2 receptor-deficient mice compared to wild-type animals, supporting a potential neuroprotective role for this receptor. In the present study, we further explored this issue…

In conclusion, we have provided the first evidence on the up-regulation of CB2receptors in glial elements in postmortem tissues of PD patients, which has been confirmed in an inflammatory model of this disease. In addition, we have provided evidence on the benefits derived from their activation in relation with the activation of microglial cells, the infiltration of macrophages and also certain capability of these cells to generate proinflammatory factors.”

http://www.ncbi.nlm.nih.gov/pubmed/25863279

http://www.thctotalhealthcare.com/category/parkinsons-disease/

Cannabinoids receptor type 2, CB2, expression correlates with human colon cancer progression and predicts patient survival.

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/25859556

http://www.thctotalhealthcare.com/category/colon-cancer/

Role of Cannabinoid Receptor CB2 in HER2 Pro-oncogenic Signaling in Breast Cancer.

“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.”

[Protective effect of paeoniflorin on the hippocampus in rats with cerebral ischemia-reperfusion through activating cannabinoid receptor 2].

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=Paeoniflorin

http://www.ncbi.nlm.nih.gov/pubmed/?term=Paeonia+lactiflora

http://en.wikipedia.org/wiki/Paeonia_lactiflora

 

 

Activation of Cannabinoid CB2 receptors Reduces Hyperalgesia in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis.

“Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis…

Our results suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of the spinal cord, to suppress the hypersensitivity associated with experimental autoimmune encephalomyelitis.

These are the first pre-clinical studies to directly promote CB2 as a promising target for the treatment of central pain in an animal model of multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/25849525

Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

“Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae.

Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity…

Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.”

Renal Effects of Chronic Pharmacological Manipulation of CB2 in Rats with Diet Induced Obesity.

“In diabetic nephropathy CB2 agonism reduces albuminuria and podocyte loss; however the role of CB2 in obesity-related nephropathy is unknown. The aim of this study was to determine the role of CB2 in a model of diet-induced obesity (DIO)…

This study demonstrates that while agonism of CB2 with AM1241 treatment for six weeks does not reduce weight gain in obese rats, it leads to improvements in obesity related renal dysfunction.”

http://www.ncbi.nlm.nih.gov/pubmed/25537025

Alexandros Makriyannis is a professor in the Department of Medicinal Chemistry at Northeastern University, where his research group has synthesized many new compounds with cannabinoid activity.

Interaction of cannabinoid receptor 2 and social environment modulates chronic alcohol consumption.

“Genetic and environmental factors contribute nearly with equal power to the development of alcoholism. Environmental factors, like negative life events or emotionally disruptive conditions initiate and promote alcohol drinking and relapse.

The endocannabinoid system is involved in hedonic control and modulates stress reactivity. Furthermore, chronic alcohol drinking alters endocannabinoid signalling, which in turn influences the stress reactivity.

Recently it has been shown that CB2 receptor activity influences stress sensitivity and alcohol drinking. We hypothesised that CB2 receptors influence the impact of environmental risk factors on alcohol preference and consumption. Therefore, in this study we investigated the alcohol-drinking pattern of wild type and CB2 deficient animals under single and group housing conditions using different alcohol drinking models, like forced drinking, intermittent forced drinking and two-bottle choice paradigms.

Our data showed that CB2 receptor modulates alcohol consumption and reward.

Interestingly, we detected that lack of CB2 receptors led to increased alcohol drinking in the intermittent forced drinking paradigm under group housing conditions.

Furthermore, we found that CB2 knockout mice consumed more food and that their body weight gain was modulated by social environment.

On the base of these data, we conclude that social environment critically affects the modulatory function of CB2 receptors especially in alcohol intake.

These findings suggest that a treatment strategy targeting CB2 receptors may have a beneficial effect on pathologic drinking particularly in situations of social stress and discomfort.”

Cannabinoid receptor type 2 is time-dependently expressed during skin wound healing in mice.

“Dynamic localization of CB2R and quantitative analysis of CB2R mRNA during skin wound healing in mice were performed…

In conclusion, dynamic distribution and expression of CB2R suggest that CB2R is involved in modulating macrophages and myofibroblasts in response to inflammatory event and repair process in mouse skin wound healing, and CB2R is available as a marker for wound age determination.”

http://www.ncbi.nlm.nih.gov/pubmed/22814434

The cannabinoid receptor type 2 is time-dependently expressed during skeletal muscle wound healing in rats.

“The expression of the cannabinoid receptor type 2 (CB2R) was investigated by immunohistochemistry, Western blotting, and RT-PCR during wound healing of contused skeletal muscle in rats with attempt of its applicability to skeletal muscle wound age estimation…

In conclusion, dynamic distribution and expression of CB2R suggest that CB2R be involved in modulating macrophages in response to inflammatory event in rat skeletal muscle wound healing and CB2R be available as a marker for wound age determination.”