Category Archives: Endocannabinoid System

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

Posted on by

“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 by

“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/

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

Posted on by

“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/

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

Posted on by

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/

Chronic cannabinoid receptor stimulation selectively prevents motor impairments in a mouse model of Huntington’s disease.

Posted on by

“Huntington’s disease (HD) is a devastating neurodegenerative disease…

The endocannabinoid system (ECS) is a relevant candidate to participate in the etiopathology of HD as it is a key modulator of brain function, especially in areas primarily affected by HD…

… improving ECS function may constitute a useful strategy to eliminate or at least delay the appearance of HD symptoms…

…chronic administration was able to prevent the appearance of motor deficits, to increase the number of striatal huntingtin inclusions and to prevent the loss of striatal medium-sized spiny neurons, without affecting the social or cognitive alterations.

These findings suggest that prolonged administration of cannabinoid receptor agonists could be an appropriate strategy for selectively improving motor symptoms and stimulating neuroprotective processes in HD patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25123645

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

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

Posted on by

“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.”

Endocannabinoid signaling and epidermal differentiation.

Posted on by

“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

[A role for the endocannabinoid system in hepatic steatosis].

Posted on by

“The endocannabinoid system (SEC) is an important modulator of several metabolic functions.

This system is composed by cannabinoid receptors type 1 and 2 (RCB1 and RCB2), their endogenous ligands, known as endocannabinoids, and the enzymes involved in their synthesis and degradation. A deregulated SEC originates metabolic alterations in several tissues, resulting in the typical manifestations of the metabolic syndrome…

In this review we discuss the proposed mechanisms by which SEC is involved in the etiology of hepatic steatosis, as well as the therapeutic possibilities involving peripheral RCB1/RCB2 antagonism/agonism, for the treatment of this condition.”

http://www.ncbi.nlm.nih.gov/pubmed/25052273

http://www.thctotalhealthcare.com/category/hepatic-steatosis/

Mechanisms of control of neuron survival by the endocannabinoid system.

Posted on by

“Endocannabinoids act as retrograde messengers that, by inhibiting neurotransmitter release via presynaptic CB(1) cannabinoid receptors, regulate the functionality of many synapses. In addition, the endocannabinoid system participates in the control of neuron survival.

Thus, CB(1) receptor activation has been shown to protect neurons from acute brain injury as well as in neuroinflammatory conditions and neurodegenerative diseases.

Cannabinoid neuroprotective activity relies on the inhibition of glutamatergic neurotransmission and on other various mechanisms, and is supported by the observation that the brain overproduces endocannabinoids upon damage.

Besides promoting neuroprotection, a role for the endocannabinoid system in the control of neurogenesis from neural progenitors has been put forward. In addition, activation of CB(2) cannabinoid receptors on glial cells may also participate in neuroprotection by limiting the extent of neuroinflammation.

Altogether, these findings support that endocannabinoids constitute a new family of lipid mediators that act as instructive signals in the control of neuron survival.”

http://www.ncbi.nlm.nih.gov/pubmed/18781978

Defective Adult Neurogenesis in CB1 Cannabinoid Receptor Knockout Mice

Posted on by

Fig. 1.

“…endogenous cannabinoid signaling mechanisms may represent a key component of cell-survival programs mobilized in the injured brain.

In addition to their neuroprotective effects, cannabinergic systems may also have an important role in brain development…

…expression of endocannabinoids and cannabinoid receptors in brain…

Neurogenesis, or the birth of new neurons, continues to occur beyond development and into adulthood, and several lines of evidence suggest that cannabinoid signaling may be involved in this process as well…

In addition to the well known effects of growth factors, a variety of drugs has been shown to influence adult neurogenesis. These include excitatory amino acid receptor antagonists, antidepressants, lithium, nitric oxide donors, phosphodiesterase inhibitors, and statins.

Together with the finding that neurogenesis can be regulated by cannabinoids, these observations imply that a broad range of pharmacological approaches may exist through which to modify neurogenesis for therapeutic purposes.”

http://molpharm.aspetjournals.org/content/66/2/204.full