Hydroxytyrosol Inhibits Cannabinoid CB1 Receptor Gene Expression in 3T3-L1 Preadipocyte Cell Line.

“The 3T3-L1 preadipocyte cell line is a well characterized cell model for studying the adipocyte status and the molecular mechanisms involved in differentiation of these cells. 3T3-L1 preadipocytes have the ability to synthesize and degrade endocannabinoid anandamide (AEA) and their differentiation into adipocytes increases the expression of cannabinoid (CB1) and PPAR-γ receptors.

Clinically, the blocking stimulation of the endocannabinoid pathway has been one of the first approaches proposed to counteract the obesity and obesity-associated diseases (such as diabetes, metabolic syndrome and cancer).

In this connection, here we studied in cultured 3T3-L1 pre-adipocytes the effects of n-3-PUFA, α-Linolenic acid (OM-3), n-6-PUFA, Linoleic acid (OM-6) and hydroxytyrosol (HT) on the expression of CB1 receptor gene and the adipogenesis-related genes PPAR-γ, Fatty Acid Synthase (FAS) and Lipoprotein Lipase (LPL).

HT was able to inhibit 3T3-L1 cell differentiation by down-regulating cell proliferation and CB1 receptor gene expression. HT exhibited anti-adipogenic effects, whereas OM-3 and OM-6 exerted an inhibitory action on cell proliferation associated with an induction of the preadipocytes differentiation and CB1 receptor gene expression.

Moreover, the expression of FAS and LPL genes resulted increased after treatment with both HT and OM-3 and OM-6.

The present study points out that the intake of molecules such as HT, contained in extra virgin olive oil, may be considered also in view of antiobesity and antineoplastic properties by acting directly on the adipose tissue and modulating CB1 receptor gene transcription.”

http://www.ncbi.nlm.nih.gov/pubmed/26189725

Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH).

“Diabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients…

Cannabis has been associated with reduced IR risk in some population-based surveys.

We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients…

Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients.

The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice.”

http://www.ncbi.nlm.nih.gov/pubmed/25778750

Brief Report: Cannabis Smoking and Diabetes Mellitus: Results from Meta-analysis with Eight Independent Replication Samples.

“Recently active cannabis smoking and diabetes mellitus are inversely associated…

…but there now is a more stable evidence base for new lines of clinical translational research on a possibly protective cannabis smoking-diabetes mellitus association suggested in prior research.”

http://www.ncbi.nlm.nih.gov/pubmed/25978795

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

 

Role of the Endocannabinoid System in Diabetes and Diabetic Complications.

“Increasing evidence suggests that an overactive endocannabinoid system (ECS) may contribute to the development of diabetes by promoting energy intake and storage, impairing both glucose and lipid metabolism, and by exerting pro-apoptotic effects in pancreatic β cells, and by facilitating inflammation in pancreatic islets.

Furthermore, hyperglycemia associated with diabetes has also been implicated in triggering perturbations of the ECS amplifying the above mentioned pathological processes, eventually culminating in a vicious circle.

Compelling evidence from preclinical studies indicates that the ECS also influences diabetes-induced oxidative stress, inflammation, fibrosis, and subsequent tissue injury in target organs for diabetic complications.

In this review, we provide an update on the contribution of the ECS to the pathogenesis of diabetes and diabetic microvascular (retinopathy, nephropathy, and neuropathy) and cardiovascular complications. The therapeutic potential of targeting the ECS is also discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/26076890#

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

Neuroprotective effects of cannabidiol in endotoxin-induced uveitis: critical role of p38 MAPK activation.

“Degenerative retinal diseases are characterized by inflammation and microglial activation.

The nonpsychoactive cannabinoid, cannabidiol (CBD), is an anti-inflammatory in models of diabetes and glaucoma.

We tested the hypothesis that retinal inflammation and microglia activation are initiated and sustained by oxidative stress and p38 mitogen-activated protein kinase (MAPK) activation, and that CBD reduces inflammation by blocking these processes…

Retinal inflammation and degeneration in uveitis are caused by oxidative stress.

CBD exerts anti-inflammatory and neuroprotective effects by a mechanism that involves blocking oxidative stress and activation of p38 MAPK and microglia.”

http://www.ncbi.nlm.nih.gov/pubmed/19052649

Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes.

“Cannabinoids are known to possess therapeutic properties including inhibition of oxidation, NMDA receptor-activation, and inflammation.

The present study evaluates the ability of CBD to reduce oxidative stress, preserve BRB function, and prevent neural cell death in experimental diabetes…

These results demonstrate that CBD treatment reduces neurotoxicity, inflammation, and BRB breakdown in diabetic animals through activities that may involve inhibition of p38 MAP kinase.

The nonpsychotropic CBD is a promising candidate for anti-inflammatory and neuroprotective therapeutics.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592672/

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

Cannabis Smoking and Diabetes Mellitus: Results from Meta-analysis with Eight Independent Replication Samples.

“Epidemiologic data, suggest an inverse cannabis smoking-diabetes mellitus association.

RESULTS:

Recently active cannabis smoking and diabetes mellitus are inversely associated. The meta-analytic summary odds ratio is 0.7 (95% confidence interval = 0.6, 0.8).

CONCLUSIONS:

Current evidence is too weak for causal inference, but there now is a more stable evidence base for new lines of clinical translational research on a possibly protective (or spurious) cannabis smoking-diabetes mellitus association suggested in prior research.”

http://www.ncbi.nlm.nih.gov/pubmed/25978795

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

Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain.

Logo of molpain

“Despite the frequency of diabetes mellitus and its relationship to diabetic peripheral neuropathy (DPN) and neuropathic pain (NeP), our understanding of underlying mechanisms leading to chronic pain in diabetes remains poor.

Recent evidence has demonstated a prominent role of microglial cells in neuropathic pain states.

One potential therapeutic option gaining clinical acceptance is the cannabinoids, for which cannabinoidreceptors (CB) are expressed on neurons and microglia. We studied the accumulation and activation of spinal and thalamic microglia in streptozotocin (STZ)-diabetic CD1 mice and the impact of cannabinoid receptor agonism/antagonism during the development of a chronic NeP state.

The prevention of microglial accumulation and activation in the dorsal spinal cord was associated with limited development of a neuropathic pain state.

Cannabinoids demonstrated antinociceptive effects in this mouse model of DPN.

These results suggest that such interventions may also benefit humans with DPN, and their early introduction may also modify the development of the NeP state.”  http://www.ncbi.nlm.nih.gov/pubmed/20236533

“Tetrahydrocannabinol (THC), a component in marijuana, acts at both CB1 and CB2 receptors, but other forms of cannabinoids such as cannabinol and cannabidiol act predominantly at CB2 receptors. Such CB2 agonists may be potential anti-inflammatory therapies, antagonizing the 2-AG-induced recruitment of microglia and impacting upon development of an inflammatory state. Such properties may permit the cannabinoids to act in the prevention of microglial activation, perhaps limiting the development of neuropathic pain.

The present data confirm the efficacy of cannabinoid agonists, both for the CB1 and CB2 receptor, in modulation of acute thermal and tactile hypersensitivity as features of neuropathic pain. Furthermore, CB1 agonism from the onset of the offending stimulus (diabetes) normally leading to neuropathic pain ameliorated the development of a neuropathic pain state.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845559/

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

 

Israeli-American Team Hopes to Cure Diabetes With Cannabis

israel diabetes

“An American-Israeli biotech team is taking cannabis research to the next level by developing novel therapies using cannabis extract to treat diabetes, inflammatory conditions, chronic pain and cardiovascular disease.

ISA Scientific just signed a deal with Yissum, the technology-transfer company of the Hebrew University of Jerusalem, Hadasit, the technology-transfer company of the Hadassah Medical Organization in Jerusalem, and the Kennedy Trust for Rheumatology Research (KIR) in the United Kingdom to help bring the drugs to market.

All the credit for the idea, however, goes to a Hebrew University researcher who has worked on idea for years.

“Raphael Mechoulam deserves all the credit for this,” fellow researcher Chaim Lotan of Hadassah University Medical Center said.

Mechoulam discovered that cannabidiol (CBD) receptors existed not only in the brain but in other tissues found throughout the body.

Knowing this, he then went to work finding a way to alter cannabinoids to work on certain areas of the body.

“He synthesized a whole ‘family’ of cannabinoids, and therefore with some changes in molecular structure you can tailor cannabinoids to different receptors,” Lotan said.

Lotan, a cardiologist, helped work on making a drug for the heart.

“My role was only the cardiac part,” he explained “but we may see effects in other organs as well since we found so many receptors.”

The team is now ready for Phase 2 trials of the drug for diabetes and chronic pain and is hopeful that the drug, which has now psychoactive properties at all, will ultimately provide a solution that may not only manage diabetes but perhaps even cure the widespread disease.

“Unlike insulin and other existing medications for diabetes, CBD may actually suppress, reverse and perhaps cure the disease,” ISA Scientific Chief Executive Officer Mark J. Rosenfeld said. “So, the therapeutic alternatives offered by cannabis chemistry could go far in helping to resolve conditions responsible for a huge public health crisis in China and elsewhere.””

http://www.jspacenews.com/israeli-american-team-hopes-cure-diabetes-cannabis/

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

Inhaled cannabis reduces pain in diabetic peripheral neuropathy patients, study suggests

“A small study finds that inhaling cannabis could demonstrate a dose-dependent pain reduction in patients with diabetic peripheral neuropathy.

Researchers at the University of California, United States conducted a study in which 16 patients with painful diabetic peripheral neuropathy were given placebo, or single doses of cannabis.

These doses were either low (one per cent tetrahydrocannibinol, THC), medium (four per cent THC) or high (seven per cent THC).

Tests were first performed on baseline spontaneous pain, evoked pain and cognitive function. Subsequently, participants either inhaled the cannabis or placebo, with measurements of pain intensity and cognitive function assessed over a three-hour period.

The higher the content of THC participants inhaled, the less pain they felt. The high dose of THC had a significant effect when researchers evoked pain using foam brush and von Frey.

These are tools used to test neuropathic pain in patients – von Frey are a set of filaments that test the pain of a patients by pushing against the skin to assess when the sensation becomes painful.

Patients on the high dose of THC showed impaired performance on the neuropsychological tests, but researchers concluded the pain reduction of patients adds further evidence on the efficacy of cannabis in treating diabetic peripheral neuropathy.

The results of this study were published in the Journal of Pain and Palliative Care Pharmacology.

Earlier this month, the CBD compound in cannabis was reported by researchers as a potential treatment for diabetes.”

http://www.diabetes.co.uk/news/2015/apr/inhaled-cannabis-reduces-pain-in-diabetic-peripheral-neuropathy-patients,-study-suggests-95680845.html

“Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy.”  http://www.ncbi.nlm.nih.gov/pubmed/25843054

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