Category Archives: Endocannabinoid System

A biosynthetic pathway for anandamide

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“The endocannabinoid arachidonoyl ethanolamine (anandamide) is a lipid transmitter synthesized and released “on demand” by neurons in the brain. Anandamide is also generated by macrophages where its endotoxin (LPS)-induced synthesis has been implicated in the hypotension of septic shock and advanced liver cirrhosis. Anandamide can be generated from its membrane precursor, N-arachidonoyl phosphatidylethanolamine (NAPE) through cleavage by a phospholipase D (NAPE-PLD).

Here we document a biosynthetic pathway for anandamide in mouse brain…

Both PTPN22 and endocannabinoids have been implicated in autoimmune diseases, suggesting that the PLC/phosphatase pathway of anandamide synthesis may be a pharmacotherapeutic target.

The observed exclusive role of the PLC/phosphatase pathway in LPS-induced AEA synthesis may offer therapeutic targets for the treatment of these conditions.

Furthermore, cannabinoids have immunosuppressive effects in autoimmune models of multiple sclerosis and diabetes, and mice deficient in CB1 receptors show increased susceptibility to neuronal damage found in autoimmune encephalitis…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1557387/#!po=23.3333

The role of the endocannabinoid system in atherosclerosis.

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“Our current understanding of the pathophysiology of atherosclerosis suggests a prominent role for immune responses from its initiation through its complications. Given the increasing prevalence of cardiovascular risk factors worldwide, there is an urgent need to better understand the underlying mechanisms to improve current treatment protocols.

A growing body of evidence suggests that endocannabinoid signalling plays a critical role in the pathogenesis of atherogenesis and its clinical manifestations. Blocking CB(1) receptors has been shown to mediate not only weight reduction, but also several cardiometabolic effects in rodents and humans, indicating a potential relevance for the process of atherosclerosis.

Activation of CB(2) receptors with Delta(9)-tetrahydrocannabinol (THC) has been shown to inhibit atherosclerotic plaque progression in mice, mainly by inhibiting macrophage recruitment.

In conclusion, the precise role of the endocannabinoid system during atherosclerosis is not yet understood.”

http://www.ncbi.nlm.nih.gov/pubmed/18426500

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

Cannabinoid receptors in atherosclerosis.

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“…cannabinoid receptors are potential targets for the treatment of atherosclerosis…

Cannabinoids, such as Delta9-tetrahydrocannabinol, the major psychoactive compound of marijuana… was shown to inhibit disease progression through pleiotropic effects on inflammatory cells.

The development of novel cannabinoid receptor ligands that selectively target CB2 receptors or pharmacological modulation of the endocannabinoid system might offer novel therapeutic strategies in the treatment of atherosclerosis.

The immunomodulatory capacity of cannabinoids is now well established and suggests a broad therapeutic potential of cannabinoids for a variety of conditions, including atherosclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/16960500

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

Cannabinoid receptors in acute and chronic complications of atherosclerosis

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“Atherosclerosis is a chronic inflammatory disease that is the primary cause of myocardial infarction and stroke, which occur after sudden thrombotic occlusion of an artery.

A growing body of evidence suggests that cannabinoid signalling plays a fundamental role in atherosclerosis development and its clinical manifestations. Thus, CB2 receptors are protective in myocardial ischaemia/reperfusion and implicated in the modulation of chemotaxis, which is crucial for the recruitment of leukocytes during inflammation.

Delta-9-Tetrahydrocannabinol (THC)-mediated activation has been shown to inhibit atherosclerotic plaque progression in a CB2 dependent manner.

It is tempting to suggest that pharmacological modulation of the endocannabinoid system is a potential novel therapeutic strategy in the treatment of atherosclerosis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219535/

Peripheral and intra-dorsolateral striatum injections of the cannabinoid receptor agonist WIN 55,212-2 impair consolidation of stimulus-response memory.

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“The endocannabinoid system plays a major role in modulating memory. In the present study, we examined whether cannabinoid agonists influence the consolidation of stimulus-response/habit memory, a form of memory dependent upon the dorsolateral striatum (DLS)…

The results indicate that peripheral or intra-DLS administration of a cannabinoid receptor agonist impairs consolidation of DLS-dependent memory. The findings are discussed within the context of previous research encompassing cannabinoids and DLS-dependent learning and memory processes, and the possibility that cannabinoids may be used to treat some habit-like human psychopathologies (e.g. posttraumatic stress disorder) is considered.”

http://www.ncbi.nlm.nih.gov/pubmed/24838065

Prevention of Alzheimer’s Could Hinge on Marijuana Science

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Alzheimers Disease includes reduced brain activity and function (red areas above), the result of years of accumulated damage. Molecules in pot seem to prevent this damage.

“The British Journal of Pharmacologyhas published a paper that concludes that the ingredients in marijuana likely work to prevent the onset of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and age-related dementia.

Smoking, vaping, or eating the pot molecules THC and CBD directly effects nerve cell function, resulting in reduced chronic brain inflammation, reduced oxidative stress, and reduced cellular dysfunction — all the while promoting stability of the human body’s internal environment (homeostasis) and healthy brain cells (neurotrophic support)…

Pot likely prevents Alzheimer’s and other neurodegenerative diseases at the individual cell level. Molecules in pot like THC and CBD (called cannabinoids) plug into a primal, chemical signaling system in cells called “the endocannabinoid system.” Cannabinoids dampen inflammation, protect cells from oxidative damage, and promote cell health on a number of levels, the paper shows.

Manipulating the endocannabinoid system will likely be a key to preventing or curing a bunch of neurodegenerative disorders, the paper concludes.”

http://www.eastbayexpress.com/LegalizationNation/archives/2014/05/13/prevention-of-alzheimers-could-hinge-on-marijuana-science

“Prevention of Alzheimer’s Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation”  http://www.jneurosci.org/content/25/8/1904.long

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

The influence of cannabinoids on generic traits of neurodegeneration

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“In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay the progression of these diseases but there is currently no cure.

Modulation of the endogenous cannabinoid system is emerging as a potentially viable option in the treatment of neurodegeneration. Endocannabinoid signalling has been found to be altered in many neurodegenerative disorders. To this end, pharmacological manipulation of the endogenous cannabinoid system, as well as application of phytocannabinoids and synthetic cannabinoids have been investigated. Signalling from the CB1 and CB2 receptors are known to be involved in the regulation of Ca2+ homeostasis, mitochondrial function, trophic support and inflammatory status, respectively, while other receptors gated by cannabinoids such as PPARγ, are gaining interest in their anti-inflammatory properties.

Through multiple lines of evidence, this evolutionarily conserved neurosignalling system has shown neuroprotective capabilities and is therefore a potential target for neurodegenerative disorders. This review details the mechanisms of neurodegeneration and highlights the beneficial effects of cannabinoid treatment.”

http://onlinelibrary.wiley.com/doi/10.1111/bph.12492/full

Endocannabinoid signaling in Alzheimer’s disease: current knowledge and future directions.

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“The importance of the endocannabinoid system (ECS) in the modulation functions of the central nervous system has been extensively investigated during the last few years. In particular, accumulated evidence has implicated ECS in the pathophysiology of Alzheimer’s disease (AD), that is a progressive, degenerative, and irreversible disorder characterized by the accumulation in the brain of beta-amyloid fragments forming insoluble plaques, and of intracellular neurofibrillary tangles (NTFs) associated with synaptic and neuronal loss. In all the processes involved in the formation of both plaques and NFTs, the key-role played by the ECS has been documented. Here, we review current knowledge and future directions of ECS modulation both in animal models of AD and in human tissues, underlying the role of endocannabinoid signaling in the development of AD hallmarks. Overall, the available data suggest that next generation therapeutics might target distinct ECS elements, for instance CB2 receptor or fatty acid amide hydrolase, as a promising approach to halt or at least to slow down disease progression.”

http://www.ncbi.nlm.nih.gov/pubmed/24813316

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

[Importance of the endocannabinoid system in the regulation of energy homeostasis].

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“The endocannabinoid system is an endogenous signaling system that plays a role in the regulation of energy homeostasis and lipid and glucose metabolism-all of which can influence cardiometabolic risk. The endocannabinoid system appears to be a promising novel mechanistic pathway that modulates important aspects afcardiovascular and metabolic function. The endocannabinoid system is normally a silent physiologic system that becomes transiently activated, that is, only when needed. Evidence suggests that the endocannabinoid system is tonically overactive in human obesity and in animal models of genetic and diet-induced obesity. However, there is evidence in studies that the ECS is tonically overactivated in obesity, although it remains unclear whether overactivation of the ECS precedes or is consequent to expression of the obese phenotype. Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce smoking, body weight and improve and improves the profile of several metabolic risk factors in high-risk patients.”

http://www.ncbi.nlm.nih.gov/pubmed/23687711

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

Mitochondria: A Possible Nexus for the Regulation of Energy Homeostasis by the Endocannabinoid System?

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“The endocannabinoid system (ECS) regulates numerous cellular and physiological processes through the activation of receptors targeted by endogenously produced ligands called endocannabinoids. Importantly, this signalling system is known to play an important role in modulating energy balance and glucose homeostasis. For example, current evidence indicates that the ECS becomes overactive during obesity whereby its central and peripheral stimulation drives metabolic processes that mimic the metabolic syndrome. Herein, we examine the role of the ECS in modulating the function of mitochondria which play a pivotal role in maintaining cellular and systemic energy homeostasis, in large part due to their ability to tightly coordinate glucose and lipid utilisation. Because of this, mitochondrial dysfunction is often associated with peripheral insulin resistance and glucose intolerance, as well as the manifestation of excess lipid accumulation in the obese state. This review aims to highlight the different ways through which the ECS may impact upon mitochondrial abundance and/or oxidative capacity, and where possible, relate these findings to obesity-induced perturbations in metabolic function. Furthermore, we explore the potential implications of these findings in terms of the pathogenesis of metabolic disorders and how these may be used to strategically develop therapies targeting the ECS.”

http://www.ncbi.nlm.nih.gov/pubmed/24801388

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