Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis.

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“The endocannabinoid system was discovered in 1988 but has received little attention for its potential therapeutic possibilities.

That has started to change, and since 2000, a significant number of clinical trials of cannabinoids, principally for the control of spasticity in multiple sclerosis, have been undertaken. These studies have been difficult because of the nature of the disease and have involved patients for whom other therapies have failed or proved inadequate.

This paper outlines the background to the use of cannabinoids available and discusses the principles of practice associated with their safe use.

The focus has been on nabiximols, being the most studied and the only cannabinoid that has been both adequately researched for use in multiple sclerosis and granted a license by the regulators. However, what has emerged is that the effect for many patients can be much wider than just control of spasticity.

Within and outside of neurology there seems to be an expanding range of possibilities for the therapeutic use of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/26289248

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

Sativex® and clinical-neurophysiological measures of spasticity in progressive multiple sclerosis.

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“Despite the proven efficacy of Sativex® (9-delta-tetrahydrocannabinol plus cannabidiol) oromucosal spray in reducing spasticity symptoms in multiple sclerosis (MS), little is known about the neurophysiological correlates of such effects.

The aim of the study was to investigate the effects of Sativex on neurophysiological measures of spasticity (H/M ratio) and corticospinal excitability in patients with progressive MS.

This was a randomized, double-blind, placebo-controlled, crossover study…

Our findings confirm the clinical benefit of Sativex on MS spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/26289497

Cannabinoids and Glucocorticoids in the Basolateral Amygdala Modulate Hippocampal-Accumbens Plasticity after Stress.

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“Acute stress results in release of glucocorticoids which are potent modulators of learning and plasticity. This process is presumably mediated by the basolateral amygdala (BLA) where cannabinoids CB1 receptors play a key role in regulating the hypothalamic-pituitary-adrenal (HPA) axis.

Growing attention has been focused on nucleus accumbens (NAc) plasticity which regulates mood and motivation. The NAc integrates affective and context dependent input from the BLA and ventral subiculum (vSub), respectively.

Since our previous data suggest that the CB1/2 receptor agonist WIN55,212-2 (WIN) and glucocorticoid receptor (GR) antagonist RU-38486 (RU) can prevent the effects of stress on emotional memory, we examined whether intra-BLA WIN and RU can reverse the effects of acute stress on NAc plasticity…

The results suggest that glucocorticoid and cannabinoid systems in the BLA can restore normal function of the NAc and hence may play a central role in the treatment of a variety of stress-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26289146

Monoacylglycerol Lipase Regulates Fever Response.

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“Cyclooxygenase inhibitors such as ibuprofen have been used for decades to control fever through reducing the levels of the pyrogenic lipid transmitter prostaglandin E2 (PGE2). Historically, phospholipases have been considered to be the primary generator of the arachidonic acid (AA) precursor pool for generating PGE2 and other eicosanoids. However, recent studies have demonstrated that monoacyglycerol lipase (MAGL), through hydrolysis of the endocannabinoid 2-arachidonoylglycerol, provides a major source of AA for PGE2 synthesis in the mammalian brain under basal and neuroinflammatory states. We show here that either genetic or pharmacological ablation of MAGL leads to significantly reduced fever responses in both centrally or peripherally-administered lipopolysaccharide or interleukin-1β-induced fever models in mice. We also show that a cannabinoid CB1 receptor antagonist does not attenuate these anti-pyrogenic effects of MAGL inhibitors. Thus, much like traditional nonsteroidal anti-inflammatory drugs, MAGL inhibitors can control fever, but appear to do so through restricted control over prostaglandin production in the nervous system.”

http://www.ncbi.nlm.nih.gov/pubmed/26287872

[CANNABIS AND GLAUCOMA: AN ANCIENT LEGEND OR A NOVEL THERAPEUTIC HORIZON?].

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“Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure.

Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra-venous or by inhalation.

The main active ingredient of cannabis is THC (Tetra-Hydro-Cannabinol). One of THC’s reported effects is the reduction of intra-ocular pressure.

Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption.

Cannabis may be considered as a therapeutic option in glaucoma.”

http://www.ncbi.nlm.nih.gov/pubmed/26281086

Cannabinoids and Epilepsy.

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“Cannabis has been used for centuries to treat seizures.

Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies.

In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy.

These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures.

Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.”

http://www.ncbi.nlm.nih.gov/pubmed/26282273

Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release.

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“Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders.

Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties.

Its effects against cocaine neurotoxicity, however, has remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms.

In conclusion, CBD protects against seizures in a model of cocaine intoxication.

CBD should be further investigated as a strategy for alleviating psychostimulant toxicity.”

http://www.ncbi.nlm.nih.gov/pubmed/26283212

A 4-Week Pilot Study With the Cannabinoid Receptor Agonist Dronabinol and Its Effect on Metabolic Parameters in a Randomized Trial.

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“Dronabinol (synthetic Δ9- tetrahydrocannabinol) is used in patients with nausea and vomiting from chemotherapy and in AIDS patients for appetite stimulation.

Recently, dronabinol was used to successfully treat visceral hypersensitivity causing noncardiac chest pain. With widening uses of this medication, we aim to explore its effects on metabolic parameters in long-term dosing and hypothesize that it will not affect major metabolic parameters.

A double-blind, placebo-controlled, 28-day trial was performed with patients 18 to 75 years old without cardiac disease…

Dronabinol administration does not significantly affect basic metabolic components after a period of 28 days.

The implications of these findings are important because dronabinol may be able to be used in patients with metabolic disorders. The favorable trends observed here warrant further exploration into its long-term effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26283236

The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases.

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“Endocannabinoids (eCBs) are endogenous lipid ligands that bind to cannabinoid receptors that also mediate the effects of marijuana.

The eCB system is comprised of eCBs, anandamide, and 2-arachidonoyl glycerol, their cannabinoid-1 and cannabinoid-2 receptors (CB1 and CB2, respectively), and the enzymes involved in their biosynthesis and degradation.

It is present in both the central nervous system and peripheral organs including the kidney.

The current review focuses on the role of the eCB system in normal kidney function and various diseases, such as diabetes and obesity, that directly contributes to the development of renal pathologies.

Normally, activation of the CB1 receptor regulates renal vascular hemodynamics and stimulates the transport of ions and proteins in different nephron compartments. In various mouse and rat models of obesity and type 1 and 2 diabetes mellitus, eCBs generated in various renal cells activate CB1 receptors and contribute to the development of oxidative stress, inflammation, and renal fibrosis.

These effects can be chronically ameliorated by CB1 receptor blockers.

In contrast, activation of the renal CB2 receptors reduces the deleterious effects of these chronic diseases.

Because the therapeutic potential of globally acting CB1 receptor antagonists in these conditions is limited due to their neuropsychiatric adverse effects, the recent development of peripherally restricted CB1 receptor antagonists may represent a novel pharmacological approach in treating renal diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26280171

[The endocannabinoid system role in the pathogenesis of obesity and depression].

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“Excessive consumption and obesity do not always have to be strictly pathological. The adjustment of food intake as well as the pleasure of eating are the results of the circulation of neurotransmitters, hormones and glucocorticoids which have an ability to regulate the activity of many receptors connected with G protein, including endocannabinoid receptors.

The key role of endocannabinoids in pathogenesis of obesity is their overproduction by adipose cells.

Endocannabinoids (eCBs) affect CB1 receptors and increase hunger, willingness to intake food, decrease peristalsis and delay stomach emptying.

In obese people increased levels of both central and peripheral endocannabinoids are observed. It may be connected with higher availability of endocannabinoid precursors to synthesis from adipose tissue and lipids.

Raised concentration of eCBs in the body may be the consequence of their catabolism dysfunction. There is a positive correlation between amount the number of receptors in the peripheral tissues and obesity increase.

It is thought that expression of CB1 receptors in mesolimbic system is connected with motivation to consume food in response to rewarding factor.

The appetite increase after cannabinoids use is probably caused by rewarding action of the consumed food and it results from excessive dopaminergic transmission in award system.

The pharmacological inhibition of endocannabinoids activity leads to weight loss, but may also have negative consequences such as decreased mood, reduced tolerance of pain, intensified anxiety, anhedonia, depressive symptoms, even suicidal thoughts.

In post mortem examinations a decrease in CB1 receptor density in grey matter of glial cells in patients with major depression was identified. The pleiotropic and extensive activity of endocannabinoid system can influence a range of neurotransmitters thereby modulating the psychiatric life phenomena, simultaneously being involved in metabolism control and energetic system of human body.

Hence it is a link between metabolic disorders and depression and anxiety disorders. Therefore, in obese people depressive comorbidity is higher and it significantly worsens prognosis and decreases life quality.”

http://www.ncbi.nlm.nih.gov/pubmed/26277182