Category Archives: Diabetes

Δ9-tetrahydrocannabinol treatment improved endothelium-dependent relaxation on streptozotocin/nicotinamide-induced diabetic rat aorta.

Posted on by
Reply

Publication Cover

“In this study, we investigated the possible effect of Δ(9)-tetrahydrocannabinol (THC), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, on metabolic control and vascular complications of diabetes in streptozotocin/nicotinamide (STZ/NIC) induced type 2 diabetes mellitus.

These results suggested that THC improved endothelium-dependent relaxation in STZ/NIC induced diabetic rat aorta and that these effects were mediated at least in part, by control of hyperglycemia and enhanced endothelial nitric oxide bioavailability.”

Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes.

Posted on by
Reply

“Type 2 diabetes, a chronic disease, affects about 150 million people world wide.

It is characterized by insulin resistance of peripheral tissues such as liver, skeletal muscle, and fat. Insulin resistance is associated with elevated levels of tumor necrosis factor alpha (TNF-alpha), which in turn inhibits insulin receptor tyrosine kinase autophosphorylation.

It has been reported that cannabis is used in the treatment of diabetes.

A few reports indicate that smoking cannabis can lower blood glucose in diabetics.

Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis.”

http://www.ncbi.nlm.nih.gov/pubmed/19345076

Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III

Posted on by
Reply

Logo of bmjo

“To determine the association between diabetes mellitus (DM) and marijuana use.

We hypothesised that the prevalence of DM would be reduced in marijuana users due to the presence of one or more cannabinoids because of their immunomodulatory and anti-inflammatory properties.

Our analyses of adults aged 20–59 years in the NHANES III database showed that participants who used marijuana had lower prevalence of DM and had lower odds of DM relative to non-marijuana users.

We did not find an association between the use of marijuana and other chronic diseases, such as hypertension, stroke, myocardial infarction and heart failure.

Marijuana use was independently associated with a lower prevalence of DM.

In conclusion, marijuana use was associated with a decreased prevalence of DM.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289985/

The effect of spinally administered WIN 55,212-2, a cannabinoid agonist, on thermal pain sensitivity in diabetic rats.

Posted on by
Reply

“These data show that cannabinoids have potent antinociceptive effects through direct actions in the spinal dorsal horn of nociceptive pathway. This suggests that intrathecally administered cannabinoids may offer hopeful strategies for the treatment of diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/27279983

[MEDICAL CANNABIS – A SOURCE FOR A NEW TREATMENT FOR AUTOIMMUNE DISEASE?].

Posted on by
Reply

“Medical uses of Cannabis sativa have been known for over 6,000 years. Nowadays, cannabis is mostly known for its psychotropic effects and its ability to relieve pain, even though there is evidence of cannabis use for autoimmune diseases like rheumatoid arthritis centuries ago. The pharmacological therapy in autoimmune diseases is mainly based on immunosuppression of different axes of the immune system while many of the drugs have major side effects. In this review we set out to examine the rule of Cannabis sativa as an immunomodulator and its potential as a new treatment option. In order to examine this subject we will focus on some major autoimmune diseases such as diabetes type I and rheumatoid arthritis.”

http://www.ncbi.nlm.nih.gov/pubmed/27215114

Modulation of cellular redox homeostasis by the endocannabinoid system

Posted on by
Reply

“The endocannabinoid system (ECS) and reactive oxygen species (ROS) constitute two key cellular signalling systems that participate in the modulation of diverse cellular functions.

Importantly, growing evidence suggests that cross-talk between these two prominent signalling systems acts to modulate functionality of the ECS as well as redox homeostasis in different cell types…

To conclude, there is growing appreciation that the ECS may play an important role in the regulation of cellular redox homeostasis…

Indeed, the studies highlighted in this review show that ECS function can impact upon free radical production in a number of different ways.

Crucially, given the importance of redox status in the development of numerous pathologies, these findings identify ECS components as potential therapeutic targets for the treatment of oxidative stress-related neurological, cardiovascular and metabolic disorders.”

http://rsob.royalsocietypublishing.org/content/6/4/150276

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Posted on by
Reply

Image result for Curr Clin Pharmacol.

“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

The role of carbon monoxide on the anti-nociceptive effects and expression of cannabinoid 2 receptors during painful diabetic neuropathy in mice.

Posted on by
Reply

“The activation of cannabinoid 2 receptors (CB2R) attenuates chronic pain, but the role played by carbon monoxide synthesized by the inducible heme oxygenase 1 (HO-1) on the anti-nociceptive effects produced by a selective CB2R agonist, JWH-015, during painful diabetic neuropathy remains unknown.

The activation of HO-1 enhanced the anti-nociceptive effects of JWH-015 in diabetic mice, suggesting that coadministration of JWH-015 with CORM-2 or CoPP might be an interesting approach for the treatment of painful diabetic neuropathy in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/27020787

Cannabinoids inhibit insulin receptor signaling in pancreatic β-cells.

Posted on by
Reply

“Optimal glucose homeostasis requires exquisitely precise adaptation of the number of insulin-secreting β-cells in the islets of Langerhans. Insulin itself positively regulates β-cell proliferation in an autocrine manner through the insulin receptor (IR) signaling pathway.

It is now coming to light that cannabinoid 1 receptor (CB1R) agonism/antagonism influences insulin action in insulin-sensitive tissues. However, the cells on which the CB1Rs are expressed and their function in islets have not been firmly established. We undertook the current study to investigate if intraislet endogenous cannabinoids (ECs) regulate β-cell proliferation and if they influence insulin action.

These findings provide direct evidence for a functional interaction between CB1R and IR signaling involved in the regulation of β-cell proliferation and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and proliferation in diabetes.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064093/

Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.

Posted on by
Reply

“Recent reports have shown that cannabinoid 1 receptors (CB1Rs) are expressed in pancreatic β cells, where they induce cell death and cell cycle arrest by directly inhibiting insulin receptor activation. Here, we report that CB1Rs regulate the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulator cyclin D2 in pancreatic β cells. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist, WIN55,212-2, led to a decrease in the expression of Bcl-2 and cyclin D2, in turn inducing cell cycle arrest in G0/G1 phase and caspase-3-dependent apoptosis. Additionally, genetic deletion and pharmacological blockade of CB1Rs after injury in mice led to increased levels of Bcl-2 and cyclin D2 in pancreatic β cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of β-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes.”

http://www.ncbi.nlm.nih.gov/pubmed/26967640