The endocannabinoid system in obesity and type 2 diabetes.

“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.

“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.

“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/

Modulation of HIVGP120 Antigen-Specific Immune Responses In Vivo by Δ9-Tetrahydrocannabinol.

“Approximately 25 % of HIV patients use marijuana for its putative therapeutic benefit…

Previously, a surrogate in vitro mouse model was established, which induced CD8+ T cell proliferation and gp120-specific IFNγ production. ∆9-Tetrahydrocannabinol (THC), the predominant psychoactive compound in marijuana, suppressed or enhanced the responses depending on the magnitude of cellular activation.

The purpose of the current study was to investigate whether THC produced similar effects in vivo and therefore a mouse model to induce HIVgp120-specific immune responses was established…

Collectively, our findings demonstrate that under certain conditions, THC enhances HIV antigen-specific immune responses, which occurs through CB1/CB2-dependent and -independent mechanisms.”

http://www.ncbi.nlm.nih.gov/pubmed/25900076

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

A Basal Tone of 2-Arachidonoylglycerol Contributes to Early Oligodendrocyte Progenitor Proliferation by Activating Phosphatidylinositol 3-Kinase (PI3K)/AKT and the Mammalian Target of Rapamycin (MTOR) Pathways.

“A basal tone of the endocannabinoid 2-arachidonoylglycerol (2-AG) enhances late oligodendrocyte progenitor cell (OPC) differentiation. Here, we investigated whether endogenous 2-AG may also promote OPC proliferation in earlier stages…

Our data suggest that proliferation of early OPCs stimulated by PDGF-AA and bFGF depends on the tonic activation of cannabinoid receptors by endogenous 2-AG and provide further evidence on the role of endocannabinoids in oligodendrocyte development, being important for the maintenance and self-renewal of the OPCs.

The results highlight the therapeutic potential of the endocannabinoid signaling in the emerging field of brain repair.”

http://www.ncbi.nlm.nih.gov/pubmed/25900077

Medicinal Marijuana May Help Cure Children With Severe Epilepsy

A marijuana plant

“Recent research found that a liquid form of therapeutic marijuana can provide cure to children with treatment-resistant epilepsy.

The said study will be presented at the American Academy of Neurology’s 67th Annual Meeting in Washington, DC in late April.”

http://au.ibtimes.com/medicinal-marijuana-may-help-cure-children-severe-epilepsy-1440398

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

Intrathecal Injection of JWH-015 Attenuates Bone Cancer Pain Via Time-Dependent Modification of Pro-inflammatory Cytokines Expression and Astrocytes Activity in Spinal Cord.

“Cannabinoid receptor type 2 (CB2) agonists display potential analgesic effects in acute and neuropathic pain.

Overall, our results provided evidences for the persistent participation of inflammation reaction in the progression of bone cancer pain, and demonstrated that JWH-015 reduced the expression of IL-1β, IL-6, IL-18, and TNF-α and inhibited astrocytes activation in a time-dependent manner, thereby displaying an analgesic effect.”

Differential upregulation of the cannabinoid CB2 receptor in neurotoxic and inflammation-driven rat models of Parkinson’s disease.

“The cannabinoid CB2 receptor has recently emerged as a potential anti-inflammatory target to break the self-sustaining cycle of neuroinflammation and neurodegeneration that is associated with neurodegenerative diseases.

…the aim of this study was to investigate and compare the changes that occur in the endocannabinoid system in neurotoxic and inflammation-driven models of Parkinson’s disease.

…this study has shown that the endocannabinoid system is dysregulated in animal models of Parkinson’s disease, and has also revealed significant differences in the level of dysregulation between the models themselves.

This study indicates that targeting the CB2 receptor may represent a viable target for anti-inflammatory disease modification in Parkinson’s disease.”

 http://www.ncbi.nlm.nih.gov/pubmed/25895887

http://www.thctotalhealthcare.com/category/parkinsons-disease/

Differential Pharmacological Regulation of Sensorimotor-Gating Deficit in CB1 Knockout Mice and Associated Neurochemical and Histological Alterations.

“The endocannabinoid system has been widely involved in the pathophysiology of sensorimotor gating deficits. The present study is aimed to evaluate the pharmacological modulation of the sensorimotor gating impairment induced by cannabinoid CB1 receptor (CB1r) deletion…

These data further support the important role of CB1r in sensorimotor gating regulation and the therapeutic usefulness of methylphenidate for the treatment of psychiatric disorders with associated pre-attentional deficits.”

http://www.ncbi.nlm.nih.gov/pubmed/25895455

Attenuation of morphine antinociceptive tolerance by cannabinoid CB1 and CB2 receptor antagonists.

“Cannabinoid CB1 and CB2 receptor antagonists may be useful for their potential to increase or prolong opioid analgesia while attenuating the development of opioid tolerance.

The aim of this study was to investigate the effects of AM251 (a selective CB1 antagonist) and JTE907 (a selective CB2 antagonist) on morphine analgesia and tolerance in rats…

In conclusion, we observed that co-injection of AM251 and JTE907 with morphine attenuated expression of tolerance to morphine analgesic effects and decreased the morphine analgesia.”

http://www.ncbi.nlm.nih.gov/pubmed/25894754