Endocannabidiod-System ECS – SYSTEM

ECS System

( ECS ) receptors (CB 1 and CB 2))

Historical studies suggest that the CBD increases or improves the production of its own endocannabinoids. (Endocannabinoid system)

This is because CBD chemically inhibits the production in our body of an enzyme that regulates and destroys our own excess endocannabinoids. This causes more of our own endocannabinoids to circulate in our body, which affects our physical condition.

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Recent studies also suggest that CBD can alter the effects of other natural chemicals in our bodies, including serotonin, which modulates mood and stress. Adenosine, which affects our sleep-wake cycle; and vanilloid, which helps to modulate pain.

homeostasis

The term homeostasis describes a process that serves to maintain a balance within dynamic systems. In the human body, homeostasis maintains the internal environment. CBD stands for cannabidiol and is a phytocannabinoid molecule that has no psychoactive properties in the hemp plant.

The endocannabinoid system, eating behaviour and energy homeostasis: The end or a new beginning?

The endocannabinoid system (ECS) consists of two receptors (CB 1 and CB 2)), several endogenous ligands (mainly anandamide and 2-AG) and over a dozen ligand-metabolising enzymes. ECS regulates many aspects of embryological development and homeostasis, including neuroprotection and neuronal plasticity, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory, and the focus of this review: hunger, feeding and metabolism. This brief review summarises the main findings that have supported the clinical use of CB1 antagonists / inverse agonists, the clinical concerns that have arisen and the possible future of cannabinoid-based therapy for obesity and related diseases. ECS controls energy balance and lipid metabolism centrally (in the hypothalamus and mesolimbic tracts) and peripherally (in adipocytes, liver, skeletal muscle and pancreatic isletal cells). Acts via numerous anorexic and orexigenic pathways. Overweight people appear to have an elevated endocannabinoid tone that drives CB1 receptor in feed-forward dysfunction. Several CB 1 antagonists / inverse agonists have been developed to treat obesity. Although these drugs were found to be effective in reducing food intake and abdominal obesity and cardiometabolic risk factors, they produced adverse psychiatric effects that limited their use and eventually led to the end of clinical use of systemic CB 1 ligands with significant inverse led agonist activity in complicated obesity. However, there are alternatives such as CB 1 partial agonists, neutral antagonists, peripherally restricted antagonists, allosteric modulators and other potential targets within the ECS suggest that cannabinoid-based therapy for obesity and associated cardiometabolic consequences should remain open.

understanding metabolic homeostasis and imbalance: What role does the endocannabinoid system play?

Endogenous endocannabinoids (ECs) (anandamide and 2-arachidonoylglycerol) are part of the leptin-regulated neural circuits involved in appetite regulation. One of the sites of the orexigenic action of ECs is the activation of cannabinoid-1 (CB 1 ) receptors in the lateral hypothalamus, from which neurons involved in the mediation of the food reward project into the limbic system. In animal models of obesity, pharmacological blockade or genetic ablation of CB 1 receptors leads to a temporary reduction in food intake, accompanied by sustained weight loss, reduced obesity and reversal of hormonal/metabolic changes, such as elevated levels of plasma leptin, insulin and glucose and triglyceride and reduced levels of plasma adiponectin (Acrp30). The beneficial effects of CB 1A blockade of weight and metabolism cannot be explained by appetite suppression alone. Animal studies suggest that CB 1- blockade has a direct peripheral as well as a central effect on fat metabolism. It has been shown that CB 1 receptor blockade with rimonabant not only reduces weight and obesity, but also directly modulates lipid metabolism at peripheral sites in skeletal muscle, adipose tissue and liver. Preclinical animal studies suggest that CB 1- blockade acts on adipocytes to increase Acrp30 expression, on hepatocytes to reduce de novo lipogenesis and increase fatty acid oxidation, and on skeletal muscle to lower blood glucose and insulin levels. Extrapolation from animal studies to clinical, CB 1 receptor blockade offers a promising strategy to not only reduce abdominal weight and obesity, but also to prevent and reverse the metabolic consequences.

The role of the endocannabinoid system in controlling energy homeostasis

The endocannabinoid system has recently been shown to be an important regulator of energy homeostasis, involved in both appetite control and peripheral fat metabolism. We briefly review the current understanding of the possible sites and cellular mechanisms involved in the central appetitive and peripheral metabolic effects of endocannabinoids. Studies in our laboratory using obese rodents with leptin deficiency and mice with CB1-cannabinoid (CB1) receptor deficiency have shown that endocannabinoids acting via CB1 are involved in the hunger-induced increase in food intake and are negatively regulated by leptin in the affected brain regions in appetite control, including hypothalamus, limbic forebrain and amygdala. CB1 – / – mice are lean and resistant to dietary obesity (DIO), although they consume similar amounts of energy as wild type mice with DIO, suggesting that CB1 regulation of body weight includes additional peripheral targets. Such targets appear to include both adipose tissue and the liver. CB1 expressed in adipocytes is involved in controlling adiponectin secretion and lipoprotein lipase activity. Recent results show that both endocannabinoids and CB1 are present in the liver and upregulated in DIO. CB1 stimulation increases de novoliver lipogenesis by activating the fatty acid biosynthesis pathway. Components of this pathway are also expressed in the hypothalamus, where they are involved in the regulation of appetite. The fatty acid biosynthetic pathway may therefore represent a common molecular target for the central appetitive and peripheral metabolic effects of endocannabinoids.

The endocannabinoid system acts as a regulator of immunohomeostasis in the intestine

Endogenous cannabinoids (endocannabinoids) are small molecules that are biosynthesised from membrane glycerophospholipid Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy levels by intervening in the enteric nervous system via cannabinoid receptors. Here we discover a role of AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the intestine and pancreas. This work shows an important immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect to AEA; CP acts by interfering with the vanilloid receptor TRPV1, causing local production of AEA which acts via CB2. We show that the involvement of cannabinoid / vanilloid receptors increases the number and immunosuppressive function of the regulatory CX3CR1 hi- macrophages (Mϕ), which express the highest levels of such receptors among intestinal immune cells. Additionally, TRPV1 – / – or CB2 – / – mice have less CX3CR1 hi Mϕ in the gut. Treatment of mice with CP also leads to differentiation of a regulatory subgroup of CD4 + cells, the Tr1 cells, in IL-27-dependent manner in vitro and in vivo. In a functional demonstration, the tolerance induced by TRPV1 intervention can be transferred by transferring CD4 + to naïve mice with non-obese diabetes (NOD) [model of type 1 diabetes (T1D)] T cells. In addition, oral administration of AEA to NOD mice provides protection against T1D. Our study reveals a role of the endocannabinoid system in maintaining immunohomeostasis in the gut/pancreas, and shows a conversation between the nervous and immune systems using different receptors.

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The crucial role of the endocannabinoid system in emotional homeostasis: avoiding excess and deficiencies

The endocannabinoid system is crucial for regulating emotional and stress reactivity. Despite the promising therapeutic value of its pharmacological modulation, deficient and excessive endocannabinoid signal transduction should be avoided. This brief review provides a current review on this topic and emphasizes the relevance of a normative endocannabinoid system for emotional homeostasis.

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