Category Archives: Endocannabinoid System

Endocannabinoids, Related Compounds and Their Metabolic Routes.

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“Endocannabinoids are lipid mediators able to bind to and activate cannabinoid receptors, the primary molecular targets responsible for the pharmacological effects of the Δ9-tetrahydrocannabinol.

These bioactive lipids belong mainly to two classes of compounds: N-acylethanolamines and acylesters, being N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, their main representatives.

During the last twenty years, an ever growing number of fatty acid derivatives (endocannabinoids and endocannabinoid-like compounds) have been discovered and their activities biological is the subject of intense investigations.

Here, the most recent advances, from a therapeutic point of view, on endocannabinoids, related compounds, and their metabolic routes will be reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/25347455

Evaluation of the tolerability and efficacy of Sativex in multiple sclerosis.

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“Refractory spasticity, central neuropathic pain and bladder dysfunction are common clinical problems in patients with multiple sclerosis (MS). None of the currently available oral medications has proven to be reliably effective and can be limited by toxicity.

Cannabinoids have shown therapeutic effects on those MS-associated symptoms.

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) Sativex (nabiximols) is an oromucosal spray formulation that contains THC and CBD in an approximate 1:1 ratio and is described as an endocannabinoid system modulator.

The efficacy of THC/CBD on MS-associated spasticity, pain and bladder dysfunction has been studied in clinical trials as well as in clinical practice studies. Adverse effects are usually mild or moderate and the low rate of drug discontinuation provides good evidence of long-term tolerability. This article focuses on the pharmacological properties, clinical efficacy and tolerability of THC/CBD in MS patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25331416

Cannabis, cannabidiol, and epilepsy – From receptors to clinical response.

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“The use of cannabis for medicinal purposes is becoming more prevalent.

For this purpose, various preparations of cannabis of varying strengths and content are being used.

The recent changes in the legal environment have improved the availability of products with high cannabidiol (CBD) and low tetrahydrocannabinol (THC) concentrations.

There is some anecdotal evidence of their potential efficacy, but the mechanisms of such action are not entirely clear.

Some suspect an existence of synergy or “entourage effect” between CBD and THC.

There is strong evidence that THC acts via the cannabinoid receptor CB1.

The mechanism of action of CBD is less clear but is likely polypharmacological.

The scientific data support the role of the endocannabinoid system in seizure generation, maintenance, and control in animal models of epilepsy.

There are clear data for the negative effects of cannabis on the developing and mature brain though these effects appear to be relatively mild in most cases.

Further data from well-designed studies are needed regarding short- and long-term efficacy and side effects of CBD or high-CBD/low-THC products for the treatment of seizures and epilepsy in children and adults.”

http://www.ncbi.nlm.nih.gov/pubmed/25282526

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

Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity nervous pathways.

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“Involvement of the endocannabinoid system in pathophysiological mechanisms responsible for spasticity has been demonstrated in animal models of MS…

Evidence indicates that the antispasticity effects of THC:CBD oromucosal spray (Sativex®) are associated with enhanced cortical long-term potentiation.

CB1 receptors, which are associated with movement, postural control, and pain and sensory perception, influence glutamatergic pathways.

THC:CBD oromucosal spray was shown to reverse motor cortex plasticity from long-term depression through long-term potentiation of synaptic transmission, thereby restoring, at least in part, effective corticospinal inputs to spinal circuits.”

http://www.ncbi.nlm.nih.gov/pubmed/25278116

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabinoids Alleviate Experimentally Induced Intestinal Inflammation by Acting at Central and Peripheral Receptors.

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“… an attempt to further investigate the role of cannabinoid (CB) system in the pathogenesis of inflammatory bowel diseases…

CONCLUSIONS:

This is the first evidence that central and peripheral CB receptors are responsible for the protective and therapeutic action of cannabinoids in mouse models of colitis.

Our observations provide new insight to CB pharmacology and validate the use of novel ligands AM841 and CB13 as potent tools in CB-related research.”

http://www.ncbi.nlm.nih.gov/pubmed/25275313

Tapping into the endocannabinoid system to ameliorate acute inflammatory flares and associated pain in mouse knee joints.

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“During the progression of rheumatoid arthritis (RA), there are frequent but intermittent flares in which the joint becomes acutely inflamed and painful.

Although a number of drug therapies are currently used to treat RA, their effectiveness is variable and side effects are common.

Endocannabinoids have the potential to ameliorate joint pain and inflammation, but these beneficial effects are limited by their rapid degradation.

One enzyme responsible for endocannabinoid break down is fatty acid amide hydrolase (FAAH). The present study examined whether URB597, a potent and selective FAAH inhibitor, could alter inflammation and pain in a mouse model of acute synovitis.

Conclusions: These results suggest that the endocannabinoid system of the joint can be harnessed to decrease acute inflammatory reactions and the concomitant pain associated with these episodes.”

http://www.ncbi.nlm.nih.gov/pubmed/25260980

http://www.thctotalhealthcare.com/category/rheumatoid-arthritis-2/

Cannabinoid receptor type 2 activation in atherosclerosis and acute cardiovascular diseases.

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“In the last decades, the cannabinoid system (comprising synthetic and endogenous cannabinoid agonists and antagonists, their receptors and degrading enzymes) has been shown to induce potent immunomodulatory activities in atherogenesis and acute ischemic complications.

Differently from the other cannabinoid receptors in which controversial results are reported, the selective activation of the cannabinoid receptor type 2 (CB2) has been shown to play anti-inflammatory and protective actions within atherosclerotic vessels and downstream ischemic peripheral organs.

CB2 is a transmembrane receptor that triggers protective intracellular pathways in cardiac, immune and vascular cells in both in human and animal models of atherosclerosis…

medications activating CB2 function in the circulation or peripheral target organs might be a promising approach against atherogenesis.

This review updates evidence from preclinical studies on different CB2-triggered pathways in atherosclerosis and acute ischemic events.”

http://www.ncbi.nlm.nih.gov/pubmed/25245379

Effects of cannabidiol in the treatment of patients with Parkinson’s disease: An exploratory double-blind trial.

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“Parkinson’s disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons.

… the endocannabinoid system has emerged as a promising target.

…Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities…”

http://www.ncbi.nlm.nih.gov/pubmed/25237116

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

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury.

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“One of the most important causes of brain injury in the neonatal period is a perinatal hypoxic-ischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death.

Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes.

Among them, the endocannabinoid system emerges as a natural system of neuroprotection.

The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant.

The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.”

http://www.ncbi.nlm.nih.gov/pubmed/25206720

The endocannabinoid system as a potential therapeutic target for pain modulation.

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“Although cannabis has been used for pain management for millennia, very few approved cannabinoids are indicated for the treatment of pain and other medical symptoms.

Cannabinoid therapy re-gained attention only after the discovery of endocannabinoids and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the enzymes playing a role in endocannabinoid metabolism.

Nowadays, research has focused on the inhibition of these degradative enzymes and the elevation of endocannabinoid tonus locally; special emphasis is given on multi-target analgesia compounds, where one of the targets is the endocannabinoid degrading enzyme.

In this review, I provide an overview of the current understanding about the processes accounting for the biosynthesis, transport and metabolism of endocannabinoids, and pharmacological approaches and potential therapeutic applications in this area, regarding the use of drugs elevating endocannabinoid levels in pain conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/25207181

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