Pharmacol Res. Aug;60(2) doi: /colourknot.info Epub Apr The endocannabinoid system: role in glucose and energy. PURPOSE OF REVIEW: Growing evidence suggests an important role in metabolic control of the endocannabinoid system, which is composed of cannabinoid. [The role of the endocannabinoid system in the regulation of endocrine function in the liver and adipose tissue as well as glucose metabolism in muscle cells.
Endocannabinoid Role Metabolism System’s The In
Endocannabinoids are cannabinoids that are naturally produced in the body by the brain. These endocannabinoids bind to cannabinoid receptors on target cells throughout the body, triggering a cellular response which is amplified or diminished as metabolic enzymes destroy or make more endocannabinoids. This activity produces diverse effects that range from anti-inflammatory responses to euphoria. These discoveries triggered an explosion of research exploring the endocannabinoid system.
The system has been implicated in multiple physiological functions and we now have valuable knowledge about the pharmacology, biochemistry, and clinical effects of endocannabinoids. It has been established that endocannabinoids have a role in the pathology of many disorders and it is believed that they also serve a "protective role" in many medical conditions. Diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson's disease, Huntington's disease, Alzheimer's disease and Tourette's syndrome could possibly be treated by drugs modulating endocannabinoid system.
There are at least two types of cannabinoid receptors. Many of the effects of cannabinoids and endocannabinoids are mediated by two G protein-coupled receptors GPCRs , CB1 and CB2, although there is new evidence that additional receptors may be involved. CB1 receptors are primarily found in several brain regions and the central nervous system. They are also found in the cerebellum and in both male and female reproductive systems.
These receptors mediate many of the psychoactive effects of cannabinoids. CB2 receptors are predominantly distributed in the immune system. They appear to be responsible for anti-inflammatory and other immune-related activity. The two primary endocannabinoids produced by the human body interact directly with these receptors. The cannabis plant happens contains phytocannabinoids - plant-based substances with an affinity for the cannabinoid receptors.
There is new evidence that suggests that the endocannabinoid system is more complex than first believed. Since , we have learned that cannabinoids were still able to affect blood pressure, pain, inflammation, and gastric motility in the absence of CB1 and CB2 receptors. This led to the discovery of at least eight other receptors to which cannabinoids bind. What is surprising is that the endocannabinoid system was discovered less than 30 years ago.
Peripheral expression of cannabinoid receptors led researchers to investigate the role of cannabinoids in the autonomic nervous system.
Research found that the CB 1 receptor is expressed presynaptically by motor neurons that innervate visceral organs. Cannabinoid-mediated inhibition of electric potentials results in a reduction in noradrenaline release from sympathetic nervous system nerves. Other studies have found similar effects in endocannabinoid regulation of intestinal motility, including the innervation of smooth muscles associated with the digestive, urinary, and reproductive systems.
At the spinal cord, cannabinoids suppress noxious-stimulus-evoked responses of neurons in the dorsal horn, possibly by modulating descending noradrenaline input from the brainstem. The endocannabinoid most researched in pain is palmitoylethanolamide. Palmitoylethanolamide is a fatty amine related to anandamide, but saturated and although initially it was thought that palmitoylethanolamide would bind to the CB1 and the CB2 receptor, later it was found that the most important receptors are the PPAR-alpha receptor , the TRPV receptor and the GPR55 receptor.
Palmitoylethanolamide has been evaluated for its analgesic actions in a great variety of pain indications  and found to be safe and effective. Basically these data are proof of concept for endocannabinoids and related fatty amines to be therapeutically useful analgesics; palmitoylethanolamide is available under the brand names Normast and PeaPure as nutraceuticals. Endocannabinoids are involved in placebo induced analgesia responses.
Increased endocannabinoid signaling within the central nervous system promotes sleep-inducing effects. Intercerebroventricular administration of anandamide in rats has been shown to decrease wakefulness and increase slow-wave sleep and REM sleep.
Anandamide is an endogenous cannabinoid neurotransmitter that binds to cannabinoid receptors. In mice it was demonstrated that certain features of a runner's high depend on cannabinoid receptors. Pharmacological or genetic disruption of cannabinoid signaling via cannabinoid receptors prevents the analgesic and anxiety-reducing effects of running. Neuroscientists often utilize transgenic CB 1 knockout mice to discern novel roles for the endocannabinoid system.
While CB 1 knockout mice are healthy and live into adulthood, there are significant differences between CB 1 knockout and wild-type mice. When subjected to a high-fat diet, CB 1 knockout mice tend to be about sixty percent leaner and slightly less hungry than wildtype. The endocannabinoid system is by molecular phylogenetic distribution of apparently ancient lipids in the plant kingdom, indicative of biosynthetic plasticity and potential physiological roles of endocannabinoid-like lipids in plants,  and detection of arachidonic acid AA indicates chemotaxonomic connections between monophyletic groups with common ancestor dates to around million years ago silurian ; devonian.
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The traditional view that PA engages the monoaminergic and endorphinergic systems has been challenged by the discovery of the endocannabinoid system ECS , composed of endogenous lipids, their target receptors, and metabolic enzymes.
Indeed, direct and indirect evidence suggests that the ECS might mediate some of the PA-triggered effects throughout the body. To our knowledge, the first experimental study aimed at investigating the influence of PA on ECS in humans was carried out in by Sparling and coworkers , who showed increased plasma AEA content after 45 min of moderate intensity exercise on a treadmill or cycle ergometer.
Since then, other human studies have shown increased blood concentrations of AEA A dependence of the increase of AEA concentration on exercise intensity has also been documented. Several experimental data support the hypothesis that ECS might, at least in part, explain PA effects on brain functions, because: Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the 'runner's high', which may function to encourage habitual aerobic exercise.
Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes.
How mobility and movement are at the center of human evolution. Issues, News, and Reviews Cell Death and Differentiation. British Journal of Pharmacology. Int J Obes Lond. Indeed, a fold increase in the potency of hypocretin-1 to activate the ERK signaling was observed when CB1 and HcrtR1 were co-expressed These data provide unambiguous identification of CB1-HcrtR1 heteromerization, which has a substantial functional impact.
The existence of a cross-talk between the hypocretinergic and endocannabinoid systems is strongly supported by their partially overlapping anatomical distribution and common role in several physiological and pathological processes.
However, little is known about the mechanisms underlying this interaction. CB1 is present in neurons of the enteric nervous system and in sensory terminals of vagal and spinal neurons in the gastrointestinal tract Massa et al. Activation of CB1 is shown to modulate nutrient processing, such as gastric secretion, gastric emptying, and intestinal motility.
CB1 is shown to co-localize with the food intake inhibiting neuropeptide, corticotrophin-releasing hormone, in the paraventricular nucleus of the hypothalamus, and with the two orexigenic peptides, melanin-concentrating hormone in the lateral hypothalamus and with pre-pro-orexin in the ventromedial hypothalamus Inui, ; Horvath, The ECS works through many anorexigenic and orexigenic pathways where ghrelin, leptin, adiponectin, endogenous opioids, and corticotropin-releasing hormones are involved Viveros et al.
OX1—CB1 dimerization was suggested to strongly potentiate orexin receptor signaling, but a likely explanation for the signal potentiation is, instead, offered by the ability of OX1 receptor signaling to produce 2-arachidonoyl glycerol, a CB1 receptor ligand, and a subsequent co-signaling of the receptors Haj-Dahmane and Shen, ; Turunen et al.
However, this does not preclude dimerization. Orexin receptor subtypes readily formed homo- and hetero di mers, as suggested by significant BRET signals. CB1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. However, it is unclear whether this affects their signaling.
As orexin receptors efficiently signal via endocannabinoid production to CB1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations available for cannabinoid receptors. Activation of central CB1R The Open Pain Journal. From Bench to Bedside 1st ed. A popular belief has been that endogenous endorphins mediate these beneficial effects. Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running.
We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner's high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models. An update to the review in Annals of Botany". Recreational and medical applications rights Industrial applications. Autoflowering cannabis Cannabis indica ruderalis sativa Difference between C. Medical cannabis History Timeline Religious and spiritual use Chalice.
Cannabis in pregnancy Dependence Effects of cannabis Long-term Endocannabinoid system Impaired driving. Adult lifetime use by country Annual use by country. Return to class B Uruguay: Decriminalization of non-medical use Rescheduling per the Controlled Substances Act. Cannabis political parties List of British politicians who have acknowledged cannabis use List of American politicians who have acknowledged cannabis use.
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The endocannabinoid system and energy metabolism. actions have been attributed to endocannabinoids, and their involvement in several pathophysiological. The endocannabinoid system (ECS) has emerged as one of the most relevant regulators of energy balance. The ECS acts through two. Interestingly, the endocannabinoid system was recently shown to control several metabolic functions by acting on peripheral tissues such as.