Enhancement of endocannabinoid signalling protects against cocaine-induced neurotoxicity.

Posted on May 3, 2015 by David

“Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited.

Evidence suggest that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication…

In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signalling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity.”

http://www.ncbi.nlm.nih.gov/pubmed/25933444

http://www.thctotalhealthcare.com/category/addiction/

Endocannabinoids regulate the activity of astrocytic hemichannels and the microglial response against an injury: In vivo studies.

Posted on April 29, 2015 by David

“Anandamide (AEA) is an endocannabinoid (EC) that modulates multiple functions in the CNS and that is released in areas of injury, exerting putative neuroprotective actions.

In the present study, we have used intravital microscopy to analyze the role of the EC system in the glial response against an acute insult…

In summary, these findings demonstrate that AEA modifies glial functions by promoting an enhanced pro-inflammatory glial response in the brain.”

http://www.ncbi.nlm.nih.gov/pubmed/25917763

Distinct roles of the endocannabinoids anandamide and 2-arachidonoylglycerol in social behavior and emotionality at different developmental ages in rats.

Posted on April 29, 2015 by David

“To date, our understanding of the relative contribution and potential overlapping roles of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the regulation of brain function and behavior is still limited. To address this issue, we investigated the effects of systemic administration of JZL195, that simultaneously increases AEA and 2-AG signaling by inhibiting their hydrolysis, in the regulation of socio-emotional behavior in adolescent and adult rats.

These findings provide the first evidence for a role of 2-AG in social behavior, highlight the different contributions of AEA and 2-AG in the modulation of emotionality at different developmental ages and suggest that pharmacological inhibition of AEA and 2-AG hydrolysis is a useful approach to investigate the role of these endocannabinoids in neurobehavioral processes.”

http://www.ncbi.nlm.nih.gov/pubmed/25914159

[The role of endocannabinoid system in physiological and pathological processes in the eye].

Posted on April 28, 2015 by David

“Plant of Cannabis sativa/ marihuana except for its psychotropic effects possesses a range of pharmacological properties, that has been utilized for medical purposes over a period of millenia.

Investigations concerning biochemical mechanism of action of the main and most active pharmacological compound of Cannabis sativa, cannabinoid 9-THC, contributed to the discovery of cannabinoid receptors both in the central nervous system (CNS) and peripheral tissues, that mediated actions of this substance.

The discovery made possible identification of a new, endogenous signaling system referred to as the endocannabinoid system.

Besides cannabinoid receptors CB1 and CB2, the system includes it’s endogenic ligands (endocannabinoids) and compounds that participate in their biosynthesis and inactivation. Structure and functioning of the endocannabinoid system is conservative in all vertebrates.

It’s activation with plant, synthetic and endogenous cannabinoids has an influence on multiple physiological and pathological processes within the eye.”

http://www.ncbi.nlm.nih.gov/pubmed/19195174

The endocannabinoid system as a target for the treatment of neurodegenerative disease.

Posted on April 27, 2015 by David

“The Cannabis sativa plant has been exploited for medicinal, agricultural and spiritual purposes in diverse cultures over thousands of years.

Cannabis has been used recreationally for its psychotropic properties, while effects such as stimulation of appetite, analgesia and anti-emesis have lead to the medicinal application of cannabis.

Indeed, reports of medicinal efficacy of cannabis can been traced back as far as 2700 BC, and even at that time reports also suggested a neuroprotective effect of the cultivar.

…alterations in the endocannabinoid system have been extensively investigated in a range of neurodegenerative disorders.

In this review we examine the evidence implicating the endocannabinoid system in the cause, symptomatology or treatment of neurodegenerative disease. We examine data from human patients and compare and contrast this with evidence from animal models of these diseases. On the basis of this evidence we discuss the likely efficacy of endocannabinoid-based therapies in each disease context.

There has been anecdotal and preliminary scientific evidence of cannabis affording symptomatic relief in diverse neurodegenerative disorders. These include multiple sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases, and amyotrophic lateral sclerosis.

This evidence implied that hypofunction or dysregulation of the endocannabinoid system may be responsible for some of the symptomatology of these diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931550/

Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice.

Posted on April 26, 2015 by David

“There is evidence to suggest that a dysregulation of endocannabinoid signaling may contribute to the etiology and pathophysiology of migraine.

Thus, patients suffering from chronic migraine or medication overuse headache showed alterations in the activity of the arachidonoylethanolamide (AEA) degrading enzyme fatty acid amide hydrolase (FAAH) and a specific AEA membrane transporter, alongside with changes in AEA levels.

The precise role of different endocannabinoid system components is, however, not clear. We have therefore investigated mice with a genetic deletion of the two main cannabinoid receptors CB1 and CB2, or the main endocannabinoid degrading enzymes, FAAH and monoacylglycerol lipase (MAGL), which degrades 2-arachidonoylglycerol (2-AG), in a nitroglycerine-induced animal model of migraine.

The effects of the genetic deletion of pharmacological blockade of FAAH are mediated by CB1 receptors, because they were completely disrupted with the CB1 antagonist rimonabant.

These results identify FAAH as a target for migraine pharmacotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25910421

http://www.thctotalhealthcare.com/category/headachemigraine/

The complex modulation of lysosomal degradation pathways by cannabinoid receptor 1 and 2.

Posted on April 25, 2015 by David

“The two main receptors of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and 2 (CB2R) were described in the early 1990s. Since then, different physiological functions have been revealed that are linked to the activity of these two G-protein-coupled receptors.

CB1R and CB2R activity influences signal Cascades, which are known to play a role in the regulation of the cellular “self-digestion” process called autophagy. A variety of these signaling pathways are integrated by the mammalian target of rapamycin complex 1 (mTORC1) that acts as an inhibitor of autophagy. Others, like AMP-activated protein kinase dependent signaling pathway, are able to bypass mTORC1 to modulate the autophagic activity directly.

In the recent years, several scientific reports demonstrate an involvement of CB1R and CB2R signaling in the control of the autophagic activity in different paradigms.

In this review, we summarize the recent literature on this topic, which is in part contradictory and therefore, it is of great importance to illuminate the results of the single reports in the physiological context of the model systems used in these studies.

Utilizing CB1R and CB2R as pharmacological targets to modulate the autophagic activity is a promising treatment strategy for the treatment of different patho-physiological conditions and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25908257

CB1 Knockout Mice Unveil Sustained CB2-Mediated Anti-Allodynic Effects of the Mixed CB1/CB2 Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain.

Posted on April 24, 2015 by David

“Cannabinoids suppress neuropathic pain through activation of cannabinoid CB1 and/or CB2 receptors. However, unwanted CB1-mediated cannabimimetic effects limit clinical use…

Our results using the mixed CB1/CB2 agonist document that CB1 and CB2 receptor activations produce mechanistically distinct suppression of neuropathic pain.

Our study highlights the therapeutic potential of targeting cannabinoid CB2 receptors to bypass unwanted central effects associated with CB1receptor activation.”

http://www.ncbi.nlm.nih.gov/pubmed/25904556

http://www.thctotalhealthcare.com/category/neuropathic-pain/

The endocannabinoid system in obesity and type 2 diabetes.

Posted on April 23, 2015 by David

“Endocannabinoids (ECs) are defined as endogenous agonists of cannabinoid receptors type 1 and 2 (CB1 and CB2). ECs, EC anabolic and catabolic enzymes and cannabinoid receptors constitute the EC signalling system. This system participates in the control of lipid and glucose metabolism at several levels, with the possible endpoint of the accumulation of energy as fat.

Following unbalanced energy intake, however, the EC system becomes dysregulated, and in most cases overactive, in several organs participating in energy homeostasis, particularly, in intra-abdominal adipose tissue. This dysregulation might contribute to excessive visceral fat accumulation and reduced adiponectin release from this tissue, and to the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes.

This phenomenon might form the basis of the mechanism of action of CB1 antagonists/inverse agonists, recently developed by several pharmaceutical companies as adjuvants to lifestyle modification for weight reduction, glycaemic control and dyslipidaemia in obese and type 2 diabetes patients.

It also helps to explain why some of the beneficial actions of these new therapeutics appear to be partly independent from weight loss.”

http://www.ncbi.nlm.nih.gov/pubmed/18563385

http://www.thctotalhealthcare.com/category/obesity-2/

http://www.thctotalhealthcare.com/category/diabetes/

The endocannabinoid system: a promising target for the management of type 2 diabetes.

Posted on April 23, 2015 by David

“Type 2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a high incidence of cardiovascular complications.

Several animal and human observations suggest that the endocannabinoid (EC) system is overactivated in presence of abdominal obesity and/or diabetes, and contributes to disturbances of energy balance and metabolism.

Not only it regulates the intake of nutrients through central mechanisms located within the hypothalamus and limbic area, but it also intervenes in transport, metabolism and deposit of the nutrients in the digestive tract, liver, adipose tissue, skeletal muscle, and possibly pancreas.

Activation of both central and peripheral CB1 receptors promotes weight gain and associated metabolic changes. Conversely, rimonabant, the first selective CB(1) receptor antagonist in clinical use, has been shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and to increase HDL cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients.

Rimonabant was generally well-tolerated, but with a slightly higher incidence of depressed mood disorders, anxiety, nausea and dizziness compared to placebo. New trials are supposed to confirm the potential role of rimonabant (and other CB1 neutral antagonists or inverse agonists) in overweight/obese patients with type 2 diabetes and high risk cardiovascular disease.”

http://www.ncbi.nlm.nih.gov/pubmed/19275673

http://www.thctotalhealthcare.com/category/diabetes/