The endocannabinoid system in obesity and type 2 diabetes.

“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/

Effects of Cannabinoids on T-cell Function and Resistance to Infection.

“This review examines the effects of cannabinoids on immune function, with a focus on effects on T-cells, as well as on resistance to infection. The paper considers the immune modulating capacity of marijuana, of ∆9-THC extracted from the marijuana plant, and synthetic cannabinoids…

The overall conclusion of the studies discussed in this review is that cannabinoids that bind to the CB2 receptor, including ∆9-THC and CB2 selective agonists are immunosuppressive.

The studies provide objective evidence for potentially beneficial effects of marijuana and ∆9-THC on the immune system in conditions where it is desirable to dampen immune responses.

An emerging area of investigation that is reviewed is evidence to support the conclusion that CB2 selective agonists are a new class of immunosuppressive and anti-inflammatory compounds that may have exceptional beneficial effects in a variety of conditions, such as autoimmune diseases and graft rejection, where it is desirable to dampen the immune response without psychoactive effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25876735

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

WIN 55,212-2, Agonist of Cannabinoid Receptors, Prevents Amyloid β1-42 Effects on Astrocytes in Primary Culture.

“Alzheimer´s disease (AD), a neurodegenerative illness involving synaptic dysfunction with extracellular accumulation of Aβ1-42 toxic peptide, glial activation, inflammatory response and oxidative stress, can lead to neuronal death.

Endogenous cannabinoid system is implicated in physiological and physiopathological events in central nervous system (CNS), and changes in this system are related to many human diseases, including AD…

In conclusion cannabinoid WIN 55,212-2 increases cell viability and anti-inflammatory response in cultured astrocytes. Moreover, WIN 55,212-2 increases expression of anti-oxidant Cu/Zn SOD and is able to prevent inflammation induced by Aβ1-42 in cultured astrocytes.

Further studies would be needed to assess the possible beneficial effects of cannabinoids in Alzheimer’s disease patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25874692

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

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 agonist rescues learning and memory after a traumatic brain injury.

“Traumatic brain injury (TBI) can cause persistent challenges including problems with learning and memory.

Previous studies suggest that the activation of the cannabinoid 1 receptor after a traumatic brain injury could be beneficial.

We tested the hypothesis that posttraumatic brain injury administration of a cannabinoid 1 receptor agonist can rescue deficits in learning and memory.

Young adult male rats were subjected to a moderately severe controlled cortical impact brain injury, with a subset given postinjury i.p. injections of a cannabinoid receptor agonist.

Utilizing novel object recognition and the morris water task, we found that the brain-injured animals treated with the agonist showed a marked recovery.”

http://www.ncbi.nlm.nih.gov/pubmed/25815355

“Taken together, this study shows that the administration of a CB1R agonist after a TBI rescues deficits in learning and memory.”  http://onlinelibrary.wiley.com/doi/10.1002/acn3.163/full

http://www.thctotalhealthcare.com/category/brain-trauma/

Role of endogenous cannabinoid system in the gut.

“The plant Cannabis has been used in clinic for centuries, and has been known to be beneficial in a variety of gastrointestinal diseases, such as emesis, diarrhea, inflammatory bowel disease and intestinal pain.

In this text, we’ll review the components of the endogenous cannabinoid system as well as its role in the regulation of gastrointestinal activities, thus providing relative information for further study.

Moreover, modulation of the endogenous cannabinoid system in gastrointestinal tract may provide a useful therapeutic target for gastrointestinal disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23963077

http://www.thctotalhealthcare.com/category/gastrointestinal-disorders/

Cannabinoid receptors as therapeutic targets for dialysis-induced peritoneal fibrosis.

“Long-term exposure to bioincompatible peritoneal dialysis solutions is frequently complicated with peritoneal fibrosis and ultrafiltration failure.

As cannabinoid receptor (CBR) ligands have been reported to be beneficial to ameliorate the process of liver fibrosis, we strove to investigate their therapeutic potential to prevent peritoneal fibrosis…

Intraperitoneal administration of CBR ligands (CB(1)R antagonist and CB(2)R agonist) offers a potential therapeutic strategy to reduce dialysis-induced peritoneal fibrosis and to prolong the peritoneal survival in peritoneal dialysis patients.”

http://www.ncbi.nlm.nih.gov/pubmed/23296044

Marijuana: A Time-Honored but Untested Treatment for Epilepsy.

Image result for marijuana

“The biology of the endocannabinoid system in the brain provides a possible basis for a beneficial pharmacological effect of marijuana on seizures.

However, evidence for efficacy of cannabis treatment of epilepsy is anecdotal because no acceptable randomized controlled trials have been done.

Proper dosage and means of administration remain unknown.

Cannabis is safer than other controlled substances, including tobacco or alcohol, and appears to be relatively safe compared with most pharmaceuticals used to treat epilepsy.”

 http://www.ncbi.nlm.nih.gov/pubmed/25715711

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

Are Cannabinoids Effective for Orofacial Pain States?

“…there is increasing attention being given in the media as well as in the biomedical sciences to the use as analgesic agents of the crude extracts of plants of the genus Cannabis (eg, marijuana) and their active ingredient delta 9-tetrahydrocannabinol (Δ9-THC).

These cannabinoid compounds have been reported in the biomedical literature to be beneficial in the treatment of some types of neuropathic pain and other pain states…

This review has found evidence indicating that they may be effective analgesic agents for neuropathic pain conditions refractory to other therapeutic approaches…

The clinical findings pointing to the usefulness of the cannabinoids for pain relief are supported by a growing body of evidence from basic science investigations addressing the possible efficacy and mechanisms of action of the cannabinoids in animal models of acute or chronic pain.

These preclinical findings add to the growing evidence that cannabinoid receptor agonists may be effective agents for the treatment of neuropathic pain and other types of pain.

They also point to their possible clinical utility in acute or chronic orofacial pain conditions, and thereby suggest an affirmative answer applies to the question posed in the title of this editorial.”

http://www.quintpub.com/journals/ofph/abstract.php?article_id=15025#.VPBsU033-iw

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

Cannabinoid signaling and liver therapeutics.

Journal of Hepatology Home

“Over the last decade, the endocannabinoid system has emerged as a pivotal mediator of acute and chronic liver injury, with the description of the role of CB1 and CB2 receptors and their endogenous lipidic ligands in various aspects of liver pathophysiology.

A large number of studies have demonstrated that CB1 receptor antagonists represent an important therapeutic target, owing to beneficial effects on lipid metabolism and in light of its antifibrogenic properties.

Unfortunately, the brain-penetrant CB1 antagonist rimonabant, initially approved for the management of overweight and related cardiometabolic risks, was withdrawn because of an alarming rate of mood adverse effects.

However, the efficacy of peripherally-restricted CB1 antagonists with limited brain penetrance has now been validated in preclinical models of NAFLD, and beneficial effects on fibrosis and its complications are anticipated.

CB2 receptor is currently considered as a promising anti-inflammatory and antifibrogenic target, although clinical development of CB2 agonists is still awaited.

In this review, we highlight the latest advances on the impact of the endocannabinoid system on the key steps of chronic liver disease progression and discuss the therapeutic potential of molecules targeting cannabinoid receptors…

Overwhelming evidence supports the therapeutic potential of peripherally-restricted CB1 antagonists and CB2 agonists in the management of chronic liver diseases.”

http://www.journal-of-hepatology.eu/article/S0168-8278(13)00212-2/fulltext

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