Cannabis: old medicine with new promise for neurological disorders.

Posted on February 20, 2017 by David

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“Marijuana is a complex substance containing over 60 different forms of cannabinoids, the active ingredients. Cannabinoids are now known to have the capacity for neuromodulation, via direct, receptor-based mechanisms at numerous levels within the nervoussystem. These have therapeutic properties that may be applicable to the treatment of neurological disorders; including anti-oxidative, neuroprotective, analgesic and anti-inflammatory actions; immunomodulation, modulation of glial cells and tumor growth regulation. This article reviews the emerging research on the physiological mechanisms of endogenous and exogenous cannabinoids in the context of neurological disease.” https://www.ncbi.nlm.nih.gov/pubmed/12054093

“Cannabinoids in the Treatment of Neurological Disorders” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604187/

Cannabinoid Receptor 2 Signaling in Neurodegenerative Disorders: From Pathogenesis to a Promising Therapeutic Target.

Posted on February 19, 2017 by David

“As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically.

Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis.

In particular, the up-regulation of type-2 cannabinoid (CB2) receptors has been found in a number of neurodegenerative disorders. Thus, the modulation of CB2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neuronal degeneration.

For these reasons this review will focus on the CB2 receptor as a promising pharmacological target in a number of neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/28210207

“Targeting Cannabinoid CB2 Receptors in the Central Nervous System. Medicinal Chemistry Approaches with Focus on Neurodegenerative Disorders” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020102/

“The influence of cannabinoids on generic traits of neurodegeneration. 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. 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.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954477/

Monoglyceride lipase as a drug target: At the crossroads of arachidonic acid metabolism and endocannabinoid signaling.

Posted on February 19, 2017 by David

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“Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoylglycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body. Importantly, recent observations demonstrate that 2-AG represents a quantitatively important source for arachidonic acid, the precursor of prostaglandins and other inflammatory mediators. Accordingly, MGL-mediated 2-AG degradation affects lipid signaling by cannabinoid receptor-dependent and independent mechanisms. Recent genetic and pharmacological studies gave important insights into MGL’s role in (patho-)physiological processes, and the enzyme is now considered as a promising drug target for a number of disorders including cancer, neurodegenerative and inflammatory diseases. This review summarizes the basics of MG (2-AG) metabolism and provides an overview on the therapeutic potential of MGL.”

https://www.ncbi.nlm.nih.gov/pubmed/28213089

Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?

Posted on February 16, 2017 by David

“Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/28197175

“The endocannabinoid system in amyotrophic lateral sclerosis. There is increasing evidence that cannabinoids and manipulation of the endocannabinoid system may have therapeutic value in ALS. Cannabinoids exert anti-glutamatergic and anti-inflammatory actions through activation of the CB(1) and CB(2) receptors. The ability of cannabinoids to target multiple neurotoxic pathways in different cell populations may increase their therapeutic potential in the treatment of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/18781981

“Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis (ALS). Our data suggest that cannabinoid CB1 receptors might be potential therapeutic targets for this dramatic disease.” http://www.ncbi.nlm.nih.gov/pubmed/19452308

“Cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis. Cannabinoid CB2 receptor-selective compounds may be the basis for developing new drugs for the treatment of ALS and other chronic neurodegenerative diseases.” http://www.ncbi.nlm.nih.gov/pubmed/16781706

“Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. The cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/15204022

“Δ9-Tetrahydrocannabinol (Δ9-THC) is the main psychoactive constituent in the plant Cannabis sativa (marijuana) and produces its effects by activation of cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) cannabinoid receptors. Administration of the non-selective partial cannabinoid agonists Δ9-THC or cannabinol are successful in delaying motor impairment and prolonging survival in mice after the onset of symptoms. Collectively, these studies suggest that cannabinoid receptors might serve as novel therapeutic targets for ALS drug development. CB2 agonists may slow motor neuron degeneration and preserve motor function, and represent a novel therapeutic modality for treatment of ALS.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819701/

“Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS)” http://www.ncbi.nlm.nih.gov/pubmed/22594565

“Therapeutic options for amyotrophic lateral sclerosis (ALS) remain limited. Evidence suggests that cannabinoids, the bioactive ingredients of marijuana (Cannabis sativa) might have some therapeutic benefit in this disease. We found that this treatment significantly delays disease onset. Cannabinoids might be useful in ameliorating symptoms in ALS.” http://www.ncbi.nlm.nih.gov/pubmed/16183560

“Marijuana is a substance with many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). These include analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. In addition, marijuana has now been shown to have strong antioxidative and neuroprotective effects. Marijuana should be considered in the pharmacological management of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/11467101

“Ideally, a multidrug regimen would be required to comprehensively address the known pathophysiology of ALS. REMARKABLY, cannabis appears to have activity in all of those areas. Cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. Cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.” http://www.ncbi.nlm.nih.gov/pubmed/20439484

“In light of the above findings, there is a valid rationale to propose the use of cannabinoid compounds in the pharmacological management of ALS patients. Cannabinoids indeed are able to delay ALS progression and prolong survival.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270417/

http://www.thctotalhealthcare.com/category/amyotrophic-lateral-sclerosis-als-lou-gehrigs-disease/

GPR55: a new promising target for metabolism?

Posted on February 16, 2017 by David

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“GPR55 is a G-protein coupled receptor (GPCR) that has been identified as a new cannabinoid receptor. Given the wide localization of GPR55 in brain and peripheral tissues, this receptor has emerged as a regulator of multiple biological actions. Lysophosphatidylinositol (LPI) is generally accepted as the endogenous ligand of GPR55. In this review, we will focus on the role of GPR55 in energy balance and glucose metabolism. We will summarize its actions on feeding, nutrient partitioning, gastrointestinal motility and insulin secretion in preclinical models and the scarce data available in humans. The potential of GPR55 to become a new pharmaceutical target to treat obesity and type 2 diabetes, as well as the foreseeing difficulties are also discussed.” https://www.ncbi.nlm.nih.gov/pubmed/28196832

“GPR55 – a putative “type 3” cannabinoid receptor in inflammation.” https://www.ncbi.nlm.nih.gov/pubmed/26669245

http://www.thctotalhealthcare.com/tag/gpr55/

Cannabidiol: an alternative therapeutic agent for oral mucositis?

Posted on February 14, 2017 by David

“Chemo- and radiotherapy are therapeutic modalities often used in patients with malignant neoplasms. They kill tumour cells but act on healthy tissues as well, resulting in adverse effects. Oral mucositis is especially of concern, due to the morbidity that it causes.

We reviewed the literature on the etiopathogenesis of oral mucositis and the activity of cannabidiol, to consider the possibility of its use for the prevention and treatment of oral mucositis.

The control of oxidative stress may prevent and alleviate oral mucositis. Studies have demonstrated that cannabidiol is safe to use and possesses antioxidant, anti-inflammatory and analgesic properties.

The literature on the use of cannabidiol in dentistry is still scarce. Studies investigating the use of cannabidiol in oral mucositis and other oxidative stress-mediated side effects of chemotherapy and radiotherapy on the oral mucosa should be encouraged.”

https://www.ncbi.nlm.nih.gov/pubmed/28191662

“Review: cannabidiol may be beneficial for oral mucositis. The researchers found evidence that oxidative stress control could prevent and relieve oral mucositis. Cannabidiol was found to be safe to use and demonstrated antioxidant, anti-inflammatory, and analgesic properties,” https://medicalxpress.com/news/2017-02-cannabidiol-beneficial-oral-mucositis.html

“Cannabidiol could be beneficial for the treatment of oral mucositis, according to a review published online Feb. 12 in the Journal of Clinical Pharmacy and Therapeutics.” http://www.bioportfolio.com/news/article/3029295/Review-cannabidiol-may-be-beneficial-for-oral-mucositis.html

Modulation of Human Peripheral Blood Mononuclear Cell Signaling by Medicinal Cannabinoids.

Posted on February 9, 2017 by David

“Medical marijuana is increasingly prescribed as an analgesic for a growing number of indications, amongst which terminal cancer and multiple sclerosis.

In this study we aimed to investigate the immune-cell modulatory properties of medical cannabis.

Healthy volunteers were asked to ingest medical cannabis, and kinome profiling was used to generate comprehensive descriptions of the cannabis challenge on inflammatory signal transduction in the peripheral blood of these volunteers.

Results were related to both short term and long term effects in patients experimentally treated with a medical marijuana preparation for suffering from abdominal pain as a result of chronic pancreatitis or other causes.

The results reveal an immunosuppressive effect of cannabinoid preparations via deactivation of signaling through the pro-inflammatory p38 MAP kinase and mTOR pathways and a concomitant deactivation of the pro-mitogenic ERK pathway. However, long term cannabis exposure in two patients resulted in reversal of this effect.

While these data provide a powerful mechanistic rationale for the clinical use of medical marijuana in inflammatory and oncological disease, caution may be advised with sustained use of such preparations.”

https://www.ncbi.nlm.nih.gov/pubmed/28174520

http://journal.frontiersin.org/article/10.3389/fnmol.2017.00014/full

Cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance.

Posted on February 6, 2017 by David

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“Cannabinoid receptors are fundamentally involved in all aspects of intestinal physiology, such as motility, secretion, and epithelial barrier function. They are part of a broader entity, the so-called endocannabinoid system which also includes their endocannabinoid ligands and the ligands’ synthesizing/degrading enzymes.

The system has a strong impact on the pathophysiology of the gastrointestinal tract and is believed to maintain homeostasis in the gut by controlling hypercontractility and by promoting regeneration after injury.

For instance, genetic knockout of cannabinoid receptor 1 leads to inflammation and cancer of the intestines. Derivatives of Δ⁹-tetrahydrocannabinol, such as nabilone and dronabinol, activate cannabinoid receptors and have been introduced into the clinic to treat chemotherapy-induced emesis and loss of appetite; however, they may cause many psychotropic side effects.

New drugs that interfere with endocannabinoid degradation to raise endocannabinoid levels circumvent this obstacle and could be used in the future to treat emesis, intestinal inflammation, and functional disorders associated with visceral hyperalgesia.”

https://www.ncbi.nlm.nih.gov/pubmed/28161834

A selective CB2R agonist (JWH133) restores neuronal circuit after Germinal Matrix Hemorrhage in the preterm via CX3CR1+ microglia.

Posted on February 6, 2017 by David

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“Microglia play dual roles after germinal matrix hemorrhage, and the neurotrophic phenotype maybe neuroprotective.

We raise the hypothesis that a cannabinoid receptor2 agonist (JWH133) accelerates the CX3CR1⁺ microglia secreting neurotrophic factors and restores damaged neuronal circuit.

Overall, this study provides evidence that JWH133 promoted a neurotrophic phenotype of microglia (CX3CR1⁺ microglia), beyond merely alleviating microglial proliferation and inflammation.

Moreover, JWH133 restored impaired neuronal circuit, which represent a novel therapeutic strategy following GMH in clinic.”

https://www.ncbi.nlm.nih.gov/pubmed/28153531

Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation.

Posted on January 26, 2017 by David

“Microglial cells are important mediators of the immune response in the CNS. The phytocannabinoid, cannabidiol (CBD), has been shown to have central anti-inflammatory properties, and the purpose of the present study was to investigate the effects of CBD and other phytocannabinoids on microglial phagocytosis.

CONCLUSIONS AND IMPLICATIONS:

The TRPV-dependent phagocytosis-enhancing effect of CBD suggests that pharmacological modification of TRPV channel activity could be a rational approach to treating neuroinflammatory disorders involving changes in microglial function and that CBD is a potential starting point for future development of novel therapeutics acting on the TRPV receptor family.”

https://www.ncbi.nlm.nih.gov/pubmed/24641282