A restricted population of CB1 cannabinoid receptors with neuroprotective activity.

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“The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain…

The data unequivocally identify the restricted population of CB1 receptors located on glutamatergic terminals as an indispensable player in the neuroprotective activity of (endo)cannabinoids, therefore suggesting that this precise receptor pool constitutes a promising target for neuroprotective therapeutic strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/24843137

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

Cannabinoids in pain management: CB1, CB2 and non-classic receptor ligands.

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“The available commercial cannabinoids have a narrow therapeutic index. Recently developed peripherally restricted cannabinoids, regionally administered cannabinoids, bifunctional cannabinoid ligands and cannabinoid enzyme inhibitors, endocannabinoids, which do not interact with classic cannabinoid receptors (CB1r and CB2r), cannabinoid receptor antagonists and selective CB1r agonists hold promise as analgesics…

Expert opinion: Regional and peripherally restricted cannabinoids will reduce cannabinomimetic side effects. Spinal cannabinoids may increase the therapeutic index by limiting the dose necessary for response and minimize drugs exposure to supraspinal sites where cannabinomimetic side effects originate. Cannabinoid bifunctional ligands should be further explored. The combination of a CB2r agonist with a transient receptor potential vanilloid (TRPV-1) antagonist may improve the therapeutic index of the CB2r agonist. Enzyme inhibitors plus TRPV-1 blockers should be further explored. The development of analgesic tolerance with enzyme inhibitors and the pronociceptive effects of prostamides limit the benefits to cannabinoid hydrolyzing enzyme inhibitors.

Most clinically productive development of cannabinoids over the next 5 years will be in the area of selective CB2r agonists. These agents will be tested in various inflammatory, osteoarthritis and neuropathic pains.”

http://www.ncbi.nlm.nih.gov/pubmed/24836296

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

Cannabis Proves Effective In Treating Crohn’s Disease According To New Study

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cannibis crohn's disease drug

“A new clinical study published in the journal Pharmacology and by the National Institute of Health has found that cannabis is effective in treating Crohn’s disease, which is a form of inflammatory bowel disease (IBD)…

The study, entitled: “Cannabis Finds Its Way into Treatment of Crohn’s Disease”  is co-authored by Rudolf Schicho, PhD and M. Storr, both of the Institute of Experimental and Clinical Pharmacology, Medical University of Graz in Graz, Austria.

In the study abstract, Schicho and Storr note that In ancient medicine, cannabis was widely used to treat and cure bowel disturbances and inflammation, and a recent clinical study now shows that the medicinal herb Cannabis sativa lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases.”

http://bionews-tx.com/news/2014/01/29/cannabis-proves-effective-treating-crohns-disease-according-new-study/

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

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/

Towards a personalized treatment in depression: endocannabinoids, inflammation and stress response.

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“The complex nature of depression is mirrored by difficulties in tailoring its treatment. Key underlying mechanisms of this mental disorder include elevated inflammation and a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. More recently, the endocannabinoid system has been proposed as another important component in the pathogenesis of depression, and strong evidence suggests that all three systems communicate with each other. A growing number of genetic studies have investigated polymorphisms in depression in each of these systems separately. However, no study to date has looked at these genes in conjunction. In this article we will review the crosstalk between the endocannabinoid system, immune system and HPA axis; and discuss the evidence of gene polymorphisms and their relation to the risk of depression and its treatment. We propose future directions where genes of these three systems are considered from a joint perspective to improve prediction of treatment response, taking into account potentially overlooked genetic variations.”

http://www.ncbi.nlm.nih.gov/pubmed/24798725

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