Role of the endocannabinoid system in management of patients with type 2 diabetes mellitus and cardiovascular risk factors.

“To review the role of the endogenous cannabinoid system (ECS) in the peripheral and central regulation of food intake, appetite, and energy storage and discuss the potential for the ECS to be an important target for lowering cardiovascular risk…

The ECS has been shown to have a key role in the regulation of energy balance, and modulation of this system may affect multiple cardiometabolic risk factors.

Clinical studies involving pharmacologic blockade of CB1 receptors in overweight patients with and without type 2 diabetes have demonstrated effective weight loss and improvements in several risk factors for cardiovascular disease.”

http://www.ncbi.nlm.nih.gov/pubmed/18194939

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

Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy.

“A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis.

In a cross-over design, each participant was exposed to a single dosing session of placebo, low (1% tetrahydrocannabinol, THC), medium (4% THC), or high (7% THC) doses of cannabis…

This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated a dose dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain.

This adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25843054

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

NEUROPROTECTIVE EFFECTS OF CANNABIS SATIVA ALCOHOLIC EXTRACT AGAINST SPINAL ALPHA MOTONEURONS DEGENERATION IN MALE TYPE II DIABETIC RATS

“Diabetic neourophaty is one of the long-term usual outcomes of diabetes.

According to anti-tumor, anti-diabetic and anti-oxidant effects of Cannabis sativa, the aim of this research was to investigate the effect of Cannabis sativa alcoholic extract on Alpha motoneurons degeneration after sciatic nerve compression in diabetic rats…

Conclusion: Using alcoholic extract of Cannabis sativa as a neuroprotective agent can prevent the progression of neural system disorders as a result of hyperglycemia.”

http://en.journals.sid.ir/ViewPaper.aspx?ID=278407

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

Cannabidiol improves vasorelaxation in Zucker Diabetic fatty rats through cyclooxygenase activation

“Cannabidiol (CBD) decreases insulitis, inflammation, neuropathic pain and myocardial dysfunction in preclinical models of diabetes.

We recently showed that CBD also improves vasorelaxation in the Zucker Diabetic fatty (ZDF) rat, and the objective of the present study was to establish the mechanisms underlying this effect…

CBD exposure enhances the ability of arteries to relax via enhanced production of vasodilator COX 1/2-derived products acting at EP4 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/25212218

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

Oxidative stress and cannabinoid receptor expression in type-2 diabetic rat pancreas following treatment with Δ9 -THC.

“We can suggest that Δ9 -THC may be an important agent for the treatment of oxidative damages induced by diabetes…

Furthermore, the present study for the first time emphasizes that Δ9 -THC may improve pancreatic cells via cannabinoid receptors in diabetes.

The aim of present study was to elucidate the effects of Δ9 -THC, a natural cannabinoid receptor agonist, on the expression and localization of cannabinoid receptors, and oxidative stress statue in type-2 diabetic rat pancreas.

Results demonstrate that the cannabinoid receptors are presented in both Langerhans islets and duct regions.

The curative effects of Δ9 -THC can be occurred via activation of cannabinoid receptors in diabetic rat pancreas.

Moreover, it may provide a protective effect against oxidative damage induced by diabetes.

Thus, it is suggested that Δ9 -THC can be a candidate for therapeutic alternatives of diabetes symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/25187240

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

Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression.

Fig. 1

“Cannabinoids are a group of compounds found in the marijuana plant (Cannabis sativaL.). Marijuana has been used both for recreational and medicinal purposes for several centuries.

Cannabinoids have been shown to be effective in the treatment of nausea and vomiting associated with cancer chemotherapy, anorexia and cachexia seen in HIV/AIDS patients, as well as neuropathic pain, and spasticity in multiple sclerosis.

More recently, the anti-inflammatory properties of cannabinoids are drawing significant attention. In the last 15 years, studies with marijuana cannabinoids led to the discovery of cannabinoid receptors (CB1 and CB2) and their endogenous ligands, which make up what is known as the endocannabinoid system.

Cannabinoids are a group of compounds present in Cannabis plant (Cannabis sativa L.). They mediate their physiological and behavioral effects by activating specific cannabinoid receptors. With the recent discovery of the cannabinoid receptors (CB1 and CB2) and the endocannabinoid system, research in this field has expanded exponentially.

Cannabinoids have been shown to act as potent immunosuppressive and anti-inflammatory agents and have been shown to mediate beneficial effects in a wide range of immune-mediated diseases such as multiple sclerosis, diabetes, septic shock, rheumatoid arthritis, and allergic asthma.

Cannabinoid receptor 1 (CB1) is mainly expressed on the cells of the central nervous system as well as in the periphery. In contrast, cannabinoid receptor 2 (CB2) is predominantly expressed on immune cells. The precise mechanisms through which cannabinoids mediate immunosuppression is only now beginning to be understood…

In this review, we will focus on apoptotic mechanisms of immunosuppression mediated by cannabinoids on different immune cell populations and discuss how activation of CB2 provides a novel therapeutic modality against inflammatory and autoimmune diseases as well as malignancies of the immune system, without exerting the untoward psychotropic effects…

…cannabinoids do induce apoptosis in immune cells, alleviating inflammatory responses and protecting the host from acute and chronic inflammation.

The cumulative effect of cannabinoids on all cell populations of the immune system can be beneficial, when there is a need for immune suppression.

For example, in patients with autoimmune diseases such as multiple sclerosis, arthritis and lupus, or in those with septic shock, where the disease is caused by activated immune cells, targeting the immune cells via CB2 agonists may trigger apoptosis and act as anti-inflammatory therapy.

CB2 select agonists are not psychoactive and because CB2 is expressed primarily in immune cells, use of CB2 agonists could provide a novel therapeutic modality against autoimmune and inflammatory diseases.

In addition to the use of exogenous cannabinoids, in vivo manipulation of endocannabinoids may also offer novel treatment opportunities against cancer and autoimmune diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005548/

Protective role of cannabinoid receptor type 2 in a mouse model of diabetic nephropathy.

“The cannabinoid receptor type 2 (CB2) has protective effects in chronic degenerative diseases. Our aim was to assess the potential relevance of the CB2 receptor in both human and experimental diabetic nephropathy (DN)…

The CB2 receptor is expressed by podocytes, and in experimental diabetes, CB2 beneficialactivation ameliorates both albuminuria and podocyte protein loss, suggesting a protective effect of signaling through CB2 in DN.

In conclusion, our findings may have important implications for DN. The beneficial effect… makes CB2 agonism an attractive new strategy for the treatment of DN. CB2 activation may also positively affect other diabetes-related complications as CB2 agonists may, under certain conditions, delay progression of atherosclerotic lesions and ameliorate diabetes-induced neuropathic pain…

Our study may thus pave the way for future clinical trials on CB2 agonists in humans.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161308/

Cannabinoid receptor 2 expression in human proximal tubule cells is regulated by albumin independent of ERK1/2 signaling.

“The cannabinoid receptor type 2 (CB2) is reduced in podocytes of animals and humans with Type 2 Diabetes Mellitus (T2DM), with activation of CB2 ameliorating albuminuria in animals. As albuminuria also is due to proximal tubule dysfunction, the aim of this study is to investigate tubular expression of CB2 under diabetic conditions in addition to the cell signaling pathways that underlie these changes…

We have demonstrated that internalization of albumin is required to reduce CB2 mRNA and protein expression in proximal tubules in vitro. Consequently, altered expression of CB2 in both the podocytes and tubules may contribute to the albuminuria observed in T2DM.”

http://www.ncbi.nlm.nih.gov/pubmed/24280624

Common polymorphism in the cannabinoid type 1 receptor gene (CNR1) is associated with microvascular complications in type 2 diabetes.

“Endocannabinoids exert their biological effects via interaction with G-protein coupled cannabinoid receptors CB1 and CB2. Polymorphisms in the CNR1 gene (encoding CB1 receptor) were previously found to be associated with dyslipidemia and cardiovascular diseases. We investigated a role of the polymorphism in CNR1 gene in type 2 diabetes and its complications…

The novel finding of our study is the association of the G1359A polymorphism with diabetic nephropathy and diabetic retinopathy in patients with T2DM. This polymorphism was also associated with cardiovascular disease in the patient group.”

http://www.ncbi.nlm.nih.gov/pubmed/24075694

CB1 cannabinoid receptors couple to focal adhesion kinase to control insulin release.

“Endocannabinoid signaling has been implicated in modulating insulin release from β cells of the endocrine pancreas. β Cells express CB1cannabinoid receptors (CB1Rs), and the enzymatic machinery regulating anandamide and 2-arachidonoylglycerol bioavailability…

We conclude that FAK downstream from CB1Rs mediates endocannabinoid-induced insulin release by allowing cytoskeletal reorganization that is required for the exocytosis of secretory vesicles.

These findings suggest a mechanistic link between increased circulating and tissue endocannabinoid levels and hyperinsulinemia in type 2 diabetes.”

http://www.ncbi.nlm.nih.gov/pubmed/24089517