Category Archives: Diabetes

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

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“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/

 

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

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“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/

The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications.

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“Oxidative stress and inflammation play critical roles in the development of diabetes and its complications.

Recent studies provided compelling evidence that the newly discovered lipid signaling system (ie, the endocannabinoid system) may significantly influence reactive oxygen species production, inflammation, and subsequent tissue injury, in addition to its well-known metabolic effects and functions.

The modulation of the activity of this system holds tremendous therapeutic potential in a wide range of diseases, ranging from cancer, pain, neurodegenerative, and cardiovascular diseases to obesity and metabolic syndrome, diabetes, and diabetic complications.

This review focuses on the role of the endocannabinoid system in primary diabetes and its effects on various diabetic complications, such as diabetic cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy, particularly highlighting the mechanisms beyond the metabolic consequences of the activation of the endocannabinoid system.

The therapeutic potential of targeting the endocannabinoid system and certain plant-derived cannabinoids, such as cannabidiol and Δ9-tetrahydrocannabivarin, which are devoid of psychotropic effects and possess potent anti-inflammatory and/or antioxidant properties, in diabetes and diabetic complications is also discussed.

Although there is much controversy in the field of EC research, experimental evidence and clinical trials have clearly shown that ECS plays a key role in the development of primary diabetes and various diabetic complications. Although inhibition of CB1 receptors has proven to be effective in clinical trials of obesity and metabolic syndrome, this approach has ultimately failed because of increasing patient anxiety. However, recent preclinical studies clearly showed that peripherally restricted CB1 antagonists may represent a viable therapeutic strategy to avoid the previously mentioned adverse effects.

Importantly, CB1 inhibition, as discussed in this review, may also directly attenuate inflammatory responses and ROS and reactive nitrogen species generation in endothelial, immune, and other cell types, as well as in target tissues of diabetic complications, far beyond its known beneficial metabolic consequences. The main effects of CB1 receptor activation on the development of diabetes and diabetic complications are summarized in Figure 1. CB2 agonists may exert beneficial effects on diabetes and diabetic complications by attenuating inflammatory response and ensuing oxidative stress (Figure 2).

Natural cannabinoids, such as CBD and THCV, also have tremendous therapeutic potential.

CBD is a potent antioxidant and anti-inflammatory agent that does not appear to exert its beneficial effects through conventional CB receptors and is already approved for human use.

THCV and its derivatives, which may combine the beneficial effects of simultaneous CB1 inhibition and CB2 stimulation, are still under intense preclinical investigation. It will be interesting to see how newly developed, peripherally restricted CB1 receptor antagonists and/or CB2 receptor agonists and certain natural cannabinoids, such as CBD and THCV, will influence the clinical outcomes of diabetic patients.

We hope that some of these new approaches will be useful in clinical practice in the near future to aid patients with diabetes.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349875/

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

The endocannabinoid system in obesity and type 2 diabetes.

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“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.

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“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.”

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

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“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.

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“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

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“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

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“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.

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“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/