Cannabinoid CB2 receptor (CB2R) stimulation delays rubrospinal mitochondrial-dependent degeneration and improves functional recovery after spinal cord hemisection by ERK1/2 inactivation.

Posted on September 5, 2014 by David

“Spinal cord injury (SCI) is a devastating condition… Modulation of the endocannabinoid system (ECS) counteracts neurodegeneration, and pharmacological modulation of type-2 cannabinoid receptor (CB2R) is a promising therapeutic target for several CNS pathologies, including SCI…

These findings implicate the ECS, particularly CB2R, as part of the endogenous neuroprotective response that is triggered after SCI.

Thus, CB2R modulation might represent a promising therapeutic target that lacks psychotropic effects and can be used to exploit ECS-based approaches to counteract neuronal degeneration.”

http://www.ncbi.nlm.nih.gov/pubmed/25188514

http://www.thctotalhealthcare.com/category/spinal-cord-injury/

Cannabinoids for Neuropathic Pain.

Posted on August 28, 2014 by David

“Treatment options for neuropathic pain have limited efficacy and use is fraught with dose-limiting adverse effects.

The endocannabinoid system has been elucidated over the last several years, demonstrating a significant interface with pain homeostasis.

Exogenous cannabinoids have been demonstrated to be effective in a range of experimental neuropathic pain models, and there is mounting evidence for therapeutic use in human neuropathic pain conditions.

This article reviews the history, pharmacologic development, clinical trials results, and the future potential of nonsmoked, orally bioavailable, nonpsychoactive cannabinoids in the management of neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25160710

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

Neuropathic orofacial pain: cannabinoids as a therapeutic avenue.

Posted on August 26, 2014 by David

“Neuropathic orofacial pain (NOP) exists in several forms including pathologies such as burning mouth syndrome (BMS), persistent idiopathic facial pain (PIFP), trigeminal neuralgia (TN) and postherpetic neuralgia (PHN).

The pathophysiology of some of these conditions is still unclear and hence treatment options tend to vary and include a wide variety of treatments including cognitive behavior therapy, anti-depressants, anti-convulsants and opioids; however such treatments often have limited efficacy with a great amount of inter-patient variability and poorly tolerated side effects.

Analgesia is one the principal therapeutic targets of the cannabinoid system and many studies have demonstrated the efficacy of cannabinoid compounds in the treatment of neuropathic pain.

This review will investigate the potential use of cannabinoids in the treatment of symptoms associated with NOP.”

http://www.ncbi.nlm.nih.gov/pubmed/25150831

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

The Role of Endocannabinoid Signaling in the Molecular Mechanisms of Neurodegeneration in Alzheimer’s Disease.

Posted on August 26, 2014 by David

“Alzheimer’s disease (AD) is the most common form of progressive neurodegenerative disease characterized by cognitive impairment and mental disorders… AD is multifaceted in nature and is linked to different multiple mechanisms in the brain…

The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway.

Recently, the endocannabinoid system emerged as novel potential therapeutic target to treat AD.

In fact, exogenous and endogenous cannabinoids seem to be able to modulate multiple processes in AD, although the mechanisms that are involved are not fully elucidated.

This review provides an update of this area. In this review, we recapitulate the role of endocannabinoid signaling in AD and the probable mechanisms through which modulators of the endocannabinoid system provide their effects, thus highlighting how this target might provide more advantages over other therapeutic targets.”

http://www.ncbi.nlm.nih.gov/pubmed/25147120

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

Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease.

Posted on August 18, 2014 by David

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“Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders… Cannabinoids may also offer neuroprotection in Huntington’s disease (HD)…

Here, we examined this hypothesis in a rat model ofHuntington’s disease (HD)…

Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed…

…neuroprotection was attained exclusively with antioxidant cannabinoids like Δ9-tetrahydrocannabinol (Δ9-THC; or cannabidiol (CBD)…

In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be upregulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-alpha.

Altogether, our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706932/

http://www.thctotalhealthcare.com/category/huntingtons/

Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity.

Posted on August 18, 2014 by David

Brain

“Cannabinoid-derived drugs are promising agents for the development of novel neuroprotective strategies.

…in Huntington’s disease there is a very early downregulation of CB₁ receptors in striatal neurons that, together with the undesirable psychoactive effects triggered by CB₁ receptor activation, foster the search for alternative pharmacological treatments.

These findings support a pivotal role for CB₂ receptors in attenuating microglial activation and preventing neurodegeneration that may pave the way to new therapeutic strategies for neuroprotection in Huntington’s disease as well as in other neurodegenerative disorders with a significant excitotoxic component.

Overall, the reduction of neuronal CB₁ receptors and the upregulation of microglial CB₂ receptors support a crucial role for the ECB system in the pathogenesis of Huntington’s disease.

The use of drugs targeting the ECB system via CB₁ receptors aimed at restoring neurochemical alterations and palliating symptoms might constitute an interesting strategy for the management of Huntington’s disease and other neurodegenerative disorders with a significant excitotoxicity component.”

http://brain.oxfordjournals.org/content/132/11/3152.long

http://www.thctotalhealthcare.com/category/huntingtons/

Cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of Huntington’s disease.

Posted on August 18, 2014 by David

“Here, we show that the genetic deletion of CB2 receptors in a slowly progressing HD mouse model accelerates the onset of motor deficits and increases their severity.

Treatment of mice with a CB2 receptor agonist extends life span and suppresses motor deficits, synapse loss, and CNS inflammation…

CB2 receptor signaling in peripheral immune cells suppresses neurodegeneration in HD mouse models

The development of peripherally restricted CB2 receptor agonists holds promise for treating HD and other neurodegenerative diseases.

In summary, our results suggest CB2 receptor signaling in peripheral immune cells has an important role in HD and other neurodegeneration disorders. Further elucidation of the molecular mechanisms that underlie these effects may lead to novel therapeutic strategies to treat these disorders.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753072/

http://www.thctotalhealthcare.com/category/huntingtons/

Cannabis-Based Medicine Reduces Multiple Pathological Processes in AβPP/PS1 Mice.

Posted on August 16, 2014 by David

“Several recent findings suggest that targeting the endogenous cannabinoid system can be considered as a potential therapeutic approach to treat Alzheimer’s disease (AD).

The present study supports this hypothesis demonstrating that delta-9-tetrahydrocannabinol (THC) or cannabidiol (CBD) botanical extracts, as well as the combination of both natural cannabinoids, which are the components of an already approved cannabis-based medicine, preserved memory in AβPP/PS1 transgenic mice when chronically administered during the early symptomatic stage.

Moreover, THC + CBD reduced learning impairment in AβPP/PS1 mice.

…suggesting a cannabinoid-induced reduction in the harmful effect of the most toxic form of the Aβ peptide.

Among the mechanisms related with these positive cognitive effects, the anti-inflammatory properties of cannabinoids may also play a relevant role…

In summary, the present findings show that the combination of THC and CBD exhibits a better therapeutic profile than each cannabis component alone and support the consideration of a cannabis-based medicine as potential therapy against AD.”

http://www.ncbi.nlm.nih.gov/pubmed/25125475

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

Cannabinoids as therapeutic agents in cancer: current status and future implications

Posted on August 15, 2014 by David

“Cannabinoids… active compounds of the Cannabis sativa plant… cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents.

They have been shown to possess anti-proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models…” http://www.ncbi.nlm.nih.gov/pubmed/25115386

“Cannabinoids… the active compounds of the Cannabis sativa plant… anti-cancer agents… anti-proliferative… anti-angiogenic… anti-migratory and anti-invasive… The administration of single cannabinoids might produce limited relief compared to the administration of crude extract of plant containing multiple cannabinoids, terpenes and flavanoids.” Full-text: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B0%5D=2233&path%5B1%5D=3664

http://www.thctotalhealthcare.com/category/cancer/

Endocannabinoid signaling and epidermal differentiation.

Posted on July 27, 2014 by David

“Endocannabinoids represent a class of endogenous lipid mediators, that are involved in various biological processes, both centrally and peripherally. The prototype member of this group of compounds, anandamide, regulates cell growth, differentiation and death; this holds true also in the skin, that is the largest organ of the body constantly exposed to physical, chemical, bacterial and fungal challenges.

The epidermis is a keratinized multistratified epithelium that functions as a barrier to protect the organism from dehydration, mechanical trauma, and microbial insults, and epidermal differentiation represents one of the best characterized mechanisms of cell specialization.

In this review, we shall summarize current knowledge about the main members of the so-called “endocannabinoid system (ECS)”, in order to put in a better perspective the manifold roles that they play in skin pathophysiology.

In particular, we shall discuss some aspects of the molecular regulation by endocannabinoids of proliferation and terminal differentiation (“cornification”) of mammalian epidermis, showing that ECS is finely regulated by, and can interfere with, the differentiation program.

In addition, we shall review evidence demonstrating that disruption of this fine regulation might cause different skin diseases, such as acne, seborrhoea, allergic dermatitis, itch, psoriasis and hair follicle regression (catagen), making of ECS an attractive target for therapeutic intervention.”

http://www.ncbi.nlm.nih.gov/pubmed/21628127