Category Archives: Endocannabinoid System

The Endocannabinoid System and Sex Steroid Hormone-Dependent Cancers.

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“The “endocannabinoid system (ECS)” comprises the endocannabinoids, the enzymes that regulate their synthesis and degradation, the prototypicalcannabinoid receptors (CB1 and CB2), some noncannabinoid receptors, and an, as yet, uncharacterised transport system.

Recent evidence suggests that both cannabinoid receptors are present in sex steroid hormone-dependent cancer tissues and potentially play an important role in those malignancies.

Sex steroid hormones regulate the endocannabinoid system and the endocannabinoids prevent tumour development through putative protective mechanisms that prevent cell growth and migration, suggesting an important role for endocannabinoids in the regulation of sex hormone-dependent tumours and metastasis.

Here, the role of the endocannabinoid system in sex steroid hormone-dependent cancers is described and the potential for novel therapies assessed.”

http://www.ncbi.nlm.nih.gov/pubmed/24369462

Involvement of cannabinoid receptors in peripheral and spinal morphine analgesia.

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“The interactions between the cannabinoid and opioid systems for pain modulation are reciprocal. However, the role and the importance of the cannabinoid system in the antinociceptive effects of opioids remain uncertain. We studied these interactions with the goal of highlighting the involvement of the cannabinoid system in morphine-induced analgesia.

In both phases of the formalin test, intra paw and intrathecal morphine produced similar antinociceptive effects in C57BL/6, cannabinoid type 1 and type 2 receptor wildtype (respectively cnr1WT and cnr2WT) mice. In cnr1 and cnr2 knockout (KO) mice, at the dose used the antinociceptive effect of intra paw morphine in the inflammatory phase of the formalin test was decreased by 87% and 76%, respectively. Similarly, the antinociceptive effect of 0.1 μg spinal morphine in the inflammatory phase was abolished in cnr1KO mice and decreased by 90% in cnr2KO mice. Interestingly, the antinociceptive effect of morphine in the acute phase of the formalin test was only reduced in cnr1KO mice. Notably, systemic morphine administration produced similar analgesia in all genotypes, in both the formalin and the hot water immersion tail flick tests.

Because the pattern of expression of the mu opioid receptor (MOP), its binding properties and its G protein coupling remained unchanged across genotypes, it is unlikely that the loss of morphine analgesia in the cnr1KO and cnr2KO mice is the consequence of MOP malfunction or downregulation due to the absence of its heterodimerization with either the CB1 or the CB2 receptors, at least at the level of the spinal cord.”

http://www.ncbi.nlm.nih.gov/pubmed/24365460

Endocannabinoid signalling in neuronal migration.

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“The endocannabinoid (eCB) system consists of several endogenous lipids, their target CB1 and CB2 receptors and enzymes responsible for their synthesis and degradation. The most abundant eCB in the central nervous system (CNS), 2-arachidonoyl glycerol (2-AG), triggers a broad range of signalling events by acting on CB1, the most abundant G protein-coupled receptor in the CNS. The eCB system regulates many physiological processes including neurogenesis, axon guidance and synaptic plasticity. Recent studies have highlighted an additional important role for eCB signalling in neuronal migration, which is crucial to achieve the complex architecture and efficient wiring of the CNS. Indeed, eCB signalling controls migration both pre- and post-natally, regulating interneuron positioning in the developing cortex and hippocampus and the polarized motility of stem cell-derived neuroblasts. While these effects may contribute to cognitive deficits associated with cannabis consumption, they also provide potential opportunities for endogenous stem cell-based neuroregenerative strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/24361301

The promise and dilemma of cannabinoid therapy: lessons from animal studies of bone disease.

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“The endocannabinoid system plays an important role in numerous physiological processes and represents a potential drug target for diseases ranging from brain disorders to cancer…

In the aging skeleton, CB1 deficiency causes accelerated osteoporosis characterized mainly by a significant reduction in bone formation coupled to enhanced adipocyte accumulation in the bone marrow.

A similar acceleration of bone loss was also reported in aging CB2-deficient mice but found to be associated with enhanced bone turnover.

This perspective describes the role of cannabinoid ligands and their receptors in bone metabolism and highlights the promise and dilemma of therapeutic exploitation of the endocannabinoid system for treatment of bone disorders.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868875/

The cytokine and endocannabinoid systems are co-regulated by NF-κB p65/RelA in cell culture and transgenic mouse models of Huntington’s disease and in striatal tissue from Huntington’s disease patients.

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“Transcriptional dysregulation is a major pathological feature of Huntington’s disease (HD). The goal of this study was to understand how p65/RelA co-regulated genes, specifically those of the cytokine and endocannabinoid systems, were affected in HD. p65/RelA levels were lower in human HD tissue and R6/2 HD mice, as were the levels of the type 1 cannabinoid receptor (CB1), IL-1β, IL-8, CCL5, GM-CSF, MIP-1β, and TNFα, all of which may be regulated by p65/RelA. Activation of p65/RelA restored CB1 and CCL5 expression in STHdh cell models of HD. Therefore, p65/RelA activation may normalize the expression of some genes in HD.”

http://www.ncbi.nlm.nih.gov/pubmed/24360910

Cannabinoid System of the Lateral Septum in the Modulation of Anxiety-like Behaviors in Rats.

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“A large body of evidence suggests that the cannabinoid CB1 receptor plays a key role in the regulation of emotional behaviors. The present study was designed to evaluate the effects of CB1 agonist and antagonist on anxiety-like behaviors in the lateral septum (LS) region of the rat brain using elevated plus maze test…

The results suggest that the cannabinoid system of the lateral septum modulates anxiety-like behavior through CB1 receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/24329144

Cannabidiol as a potential treatment for psychosis.

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“…the cannabis constituent cannabidiol (CBD) may have antipsychotic properties.

This review concisely describes the role of the endocannabinoid system in the development of psychosis and provides an overview of currently available animal, human experimental, imaging, epidemiological and clinical studies that investigated the antipsychotic properties of CBD…

Evidence from several research domains suggests that CBD shows potential for antipsychotic treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/24309088

The cannabinoid receptor type 2 as mediator of mesenchymal stromal cell immunosuppressive properties.

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“Recently, the presence of the endocannabinoid system in hematopoietic and neural stem cells has been demonstrated…

In the present study, we have investigated, through a multidisciplinary approach, the involvement of the endocannabinoids in migration, viability and cytokine release of human mesenchymal stromal cells.

We show, for the first time, that cultures of human mesenchymal stromal cells express all of the components of the endocannabinoid system, suggesting a potential role for the cannabinoid CB2 receptor as a mediator of anti-inflammatory properties of human mesenchymal stromal cells, as well as of their survival pathways and their capability to home and migrate towards endocannabinoid sources.”

http://www.ncbi.nlm.nih.gov/pubmed/24312195

Cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction.

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“AIMS: To review knowledge on cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction.

 

RESULTS AND DISCUSSION:

Components of the endocannabinoid system-cannabinoid (CB) receptor types 1 and 2, anandamide, and fatty acid amide hydrolase (FAAH), which degrades anandamide and related fatty-acid amides-have been located to lower urinary tract tissues of mice, rats, monkeys, and humans. Studies have located CB receptors in urothelium and sensory nerves and FAAH in the urothelium. CB receptor- and FAAH-related activities have also been reported in the lumbosacral spinal cord. Data on supraspinal CB functions in relation to micturition are lacking. Cannabinoids are reported to reduce sensory activity of isolated tissues, cause antihyperalgesia in animal studies of bladder inflammation, affect urodynamics parameters reflecting sensory functions in animals models, and appear to have effects on storage symptoms in humans. FAAH inhibitors have affected sensory bladder functions and reduced bladder overactivity in rat models. Cannabinoids may modify nerve-mediated functions of isolated lower urinary tract tissues.

CONCLUSIONS:

Evidence suggests components of the endocannabinoid system are involved in regulation of bladder function, possibly at several levels of the micturition pathway. It is unclear if either CB receptor has a dominant role in modification of sensory signals or if differences exist at peripheral and central nervous sites. Amplification of endocannabinoid activity by FAAH inhibitors may be an attractive drug target in specific pathways involved in LUTS.”

http://www.ncbi.nlm.nih.gov/pubmed/24285567

Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress.

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“Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues.

Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice.

Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells.

This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.” http://www.ncbi.nlm.nih.gov/pubmed/24281104

“The therapy of gliomas, the most frequent class of malignant primary brain tumors and one of the most aggressive forms of cancer characterized by high invasiveness, a high proliferation rate and rich neovascularization, could benefit from the use of cannabinoids, the active compounds of Cannabis sativa, and their synthetic derivatives. They have been shown to mimic the endogenous substances named “endocannabinoids” that activate specific cannabinoid receptors (CB1 and CB2).

Cannabinoids have been proven to inhibit glioma tumor growth in either in vitro or in vivo models through several cellular pathways such as elevating ceramide levels, modulating PI3K/Akt, MAPK kinases, inducing autophagy and oxidative stress state in glioma cells, thus arresting cell proliferation and inducing apoptosis. Since cannabinoids kill tumor cells without toxicity on their non transformed counterparts, probably modulating the cell survival/cell death pathways differently, they can represent a class of new potential anticancer drugs.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835116/

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