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/

Pharmacologic effects of cannabidiol on acute reperfused myocardial infarction in rabbits: evaluated with 3.0T cardiac magnetic resonance imaging and histopathology.

“Cannabidiol (CBD) has anti-inflammatory effects.

We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform…

Compared to controls, CBD treatment improved systolic wall thickening, significantly increased blood flow in the AAR, significantly decreased microvascular obstruction, increased the PDR by 1.7-fold, lowered the AMI-core/AAR ratio, and increased the MSI.

These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis.

Thus, CBD therapy reduced AMI size and facilitated restoration of LV function.

We demonstrated that this experimental platform has potential theragnostic utility.”

http://www.ncbi.nlm.nih.gov/pubmed/26065843

In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe.

“Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases…

Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care.

The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe…

The combined evidence indicates that NIR760-mbc94 is a promising inflammation imaging probe. Moreover, in vivo CB2R-targeted fluorescence imaging may have potential in the study of inflammation-related diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26069858

Involvement of cannabinoid receptors in infrasonic noise-induced neuronal impairment.

“Excessive exposure to infrasound, a kind of low-frequency but high-intensity sound noise generated by heavy transportations and machineries, can cause vibroacoustic disease which is a progressive and systemic disease, and finally results in the dysfunction of central nervous system.

Our previous studies have demonstrated that glial cell-mediated inflammation may contribute to infrasound-induced neuronal impairment, but the underlying mechanisms are not fully understood.

Here, we show that cannabinoid (CB) receptors may be involved in infrasound-induced neuronal injury.

…our results provide the first evidence that CB receptors may be involved in infrasound-induced neuronal impairment possibly by affecting the release of proinflammatory cytokines.”

http://www.ncbi.nlm.nih.gov/pubmed/26058582

The effect of phytocannabinoids on airway hyper-responsiveness, airway inflammation, and cough.

“Cannabis has been demonstrated to have bronchodilator, anti-inflammatory, and antitussive activity in the airways…

We compared the effects of Δ(9)-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, cannabidiolic acid, and tetrahydrocannabivarin on contractions of the guinea pig-isolated trachea and bronchoconstriction induced by nerve stimulation or methacholine in anesthetized guinea pigs following exposure to saline or the proinflammatory cytokine, tumor necrosis factor α (TNF-α)…

Only Δ(9)-tetrahydrocannabinol inhibited TNF-α-enhanced vagal-induced bronchoconstriction, neutrophil recruitment to the airways, and citric acid-induced cough responses…

The other cannabinoids did not influence cholinergic transmission, and only Δ(9)-THC demonstrated effects on airway hyper-responsiveness, anti-inflammatory activity, and antitussive activity in the airways.”

http://www.ncbi.nlm.nih.gov/pubmed/25655949

Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2.

“Here, we show a novel pharmacology for inhibition of human neutrophil migration by endocannabinoids, phytocannabinoids, and related compounds.

This study reveals that certain endogenous lipids, phytocannabinoids, and related ligands are potent inhibitors of human neutrophil migration, and it implicates a novel pharmacological target distinct from cannabinoid CB(1) and CB(2) receptors; this target is antagonized by the endogenous compound N-arachidonoyl l-serine.

Furthermore, our findings have implications for the potential pharmacological manipulation of elements of the endocannabinoid system for the treatment of various inflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/17965195

A Cannabinoid CB1 Receptor Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with no Psychoactive Effects.

“The CB1 receptor represents a promising target for the treatment of several disorders including pain-related disease states.

However, therapeutic applications of Δ9-tetrahydrocannabinol (THC) and other CB1 orthosteric receptor agonists remain limited because of psychoactive side effects. Positive allosteric modulators (PAMs) offer an alternative approach to enhance CB1 receptor function for therapeutic gain with the promise of reduced side effects…

These data suggest that ZCZ011 acts as a CB1 PAM and provide the first proof of principle that CB1 PAMs offer a promising strategy to treat neuropathic and inflammatory pain with minimal or no cannabimimetic side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26052038

Targeting cannabinoid receptors as a novel approach in the treatment of graft-versus-host disease: evidence from an experimental murine model.

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“Allogeneic hematopoietic cell transplantation (HCT) is widely used to treat patients with life-threatening malignant and nonmalignant hematological diseases. However, allogeneic HCT often is accompanied by severe and lethal complications from graft-versus-host disease (GVHD)…

Cannabinoids, the active ingredients found in Cannabis sativa, have been shown to exhibit a wide range of pharmacological properties. Studies from our laboratory and elsewhere have suggested that cannabinoids exhibit potent anti-inflammatory properties and therefore can be used to treat autoimmune and inflammatory diseases.

Cannabinoids have been shown to inhibit tumor cell growth and angiogenesis, suggesting their potential use in the treatment of gliomas, prostate and breast cancers, and malignancies of immune origin.

Δ9-Tetrahydrocannabinol (THC) is one of the most extensively investigated ingredients found in cannabis. THC activates both CB1 and CB2, thereby mediating both psychotropic and anti-inflammatory properties.

Inasmuch as our previous studies suggested that THC exhibits anti-inflammatory and immunosuppressive properties, we tested the possibility of its use in treating GVHD in a parent → F1 model. We hereby demonstrate for the first time that administration of THC during allogeneic transplantation can significantly suppress GVHD…

Our results demonstrate for the first time that targeting cannabinoid receptors may constitute a novel treatment modality against acute GVHD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164345/

Cannabidiol for the Prevention of Graft-Versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

“Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT).

Cannabidiol (CBD), a non-psychotropic ingredient of Cannabis sativa possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT…

The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double blind controlled study is warranted.”

http://www.ncbi.nlm.nih.gov/pubmed/26033282

A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.

“We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size…

We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia…”

http://www.ncbi.nlm.nih.gov/pubmed/26032254

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