Category Archives: Endocannabinoid System

Cannabinoid receptor 2 attenuates microglial accumulation and brain injury following germinal matrix hemorrhage via ERK dephosphorylation in vivo and in vitro.

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“Microglia accumulation plays detrimental roles in the pathology of germinal matrix hemorrhage (GMH) in the immature preterm brain.

Here, we investigated the effects of a cannabinoid receptor 2 (CB2R) agonist on microglia proliferation and the possible involvement of the mitogen-activated protein kinase (MAPK) family pathway in a collagenase-induced GMH rat model and in thrombin-induced rat microglia cells.

Overall, these findings suggest that activation of the endocannabinoid system might attenuate inflammation-induced secondary brain injury after GMH in rats by reducing microglia accumulation through a mechanism involving ERK dephosphorylation.

Enhancing CB2R activation is a potential treatment to slow down the course of GMH in preterm newborns.”

http://www.ncbi.nlm.nih.gov/pubmed/25963415

http://www.thctotalhealthcare.com/category/brain-trauma/

 

The evolving role of the endocannabinoid system in gynaecological cancer.

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“The ‘endocannabinoid system’ (ECS), comprising endogenous ligands (endocannabinoids) and their regulating enzymes, together with the cannabinoid receptors, has attracted a great deal of attention because it affects not only all facets of human reproduction, from gametogenesis through to parturition and beyond, but also targets key mechanisms affecting some hallmarks of cancer.

Recent evidence showing that cannabinoid receptors play a very important role in the development of malignancies outside of the reproductive organs suggests a similar role for the ECS in the establishment or continued development of gynaecological malignancy.

More than 2100 sources were obtained from which only 112 were specifically important to the topic. Analysis of those articles supports a role of the ECS in gynaecological cancers but leaves many gaps in our knowledge that need to be filled.

 

How some of the relevant receptors are activated and cause changes in cell phenotypes that progress to malignancy remains undiscovered and an area for future research. Increasing evidence suggests that malignant transformation within the female genital tract could be accompanied by deregulation of components of the ECS, acting through rather complex cannabinoid receptor-dependent and receptor-independent mechanisms.

 

The paucity of studies in this area suggests that research using animal models is needed to evaluate endocannabinoid signalling in cancer networks. Future randomized clinical studies should reveal whether endocannabinoids or their derivatives prove to be useful therapeutic targets for gynaecological and other cancers.”

http://www.ncbi.nlm.nih.gov/pubmed/25958409

Lipopolysaccharide-induced murine embryonic resorption involves changes in endocannabinoid profiling and alters progesterone secretion and inflammatory response by a CB1-mediated fashion.

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“Genital tract infections are a common complication of human pregnancy that can result in miscarriage. We have previously shown that a lipopolysaccharide (LPS) induces embryonic resorption in a murine model of inflammatory miscarriage. This is accompanied by a dramatic decrease in systemic progesterone levels associated with a robust pro-inflammatory response that results in embryo resoprtion.

Here, we tested the hypothesis that the endogenous cannabinoid system (eCS), through cannabinoid receptor 1 (CB1), plays a role in regulating progesterone levels and, therefore, the pro-inflammatory response.

We show that LPS treatment in pregnant mice causes significant changes in the eCS ligands, which are reversed by progesterone treatment. We further show the CB1-KO mice maintain higher plasma progesterone levels after LPS treatment, which is associated with a feebler uterine inflammatory response and a significant drop in embryo resorption.

These data suggest that manipulation of CB1 receptors and/or ligands is a potential therapeutic avenue to decrease infection-induced miscarriage.”

http://www.ncbi.nlm.nih.gov/pubmed/25958042

Downstream effects of endocannabinoid on blood cells: implications for health and disease.

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“Endocannabinoids (eCBs), among which N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are the most biologically active members, are polyunsaturated lipids able to bind cannabinoid, vanilloid and peroxisome proliferator-activated receptors. Depending on the target engaged, these bioactive mediators can regulate different signalling pathways, at both central and peripheral levels.

The biological action of eCBs is tightly controlled by a plethora of metabolic enzymes which, together with the molecular targets of these substances, form the so-called “endocannabinoid system”.

The ability of eCBs to control manifold peripheral functions has received a great deal of attention, especially in the light of their widespread distribution in the body.

In particular, eCBs are important regulators in blood, where they modulate haematopoiesis, platelet aggregation and apoptosis, as well as chemokine release and migration of immunocompetent cells.

Here, we shall review the current knowledge on the pathophysiological roles of eCBs in blood. We shall also discuss the involvement of eCBs in those disorders affecting the haematological system, including cancer and inflammation.

Knowledge gained to date underlines a fundamental role of the eCB system in blood, thus suggesting that it may represent a therapeutic promise for a broad range of diseases involving impaired hematopoietic cell functions.”

http://www.ncbi.nlm.nih.gov/pubmed/25957591

The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain.

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“The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressedcannabinoid receptor 2 (CB₂).

…the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.

Cannabis preparations, which have been used since thousands of years for the treatment of pain have recently come again into the focus as potential therapeutics for inflammatory and neuropathic pain conditions. Currently, cannabis extracts and synthetic preparations of the psychoactive cannabis compound Δ9-tetrahydrocannabinol (THC) have been approved in many countries for clinical pain management at doses and formulations that show on only minor central side effects…

A natural selective agonist for CB2 receptors is the plant volatile BCP, which represents a dietary phytocannabinoid. BCP is found in large amounts in the essential oils of many common spices and food plants… Several health effects have been attributed to BCP or medicinal plants containing BCP, including anti-inflammatory, local anesthetic, anti-carcinogenic, anti-fibrotic and anxiolytic-like activity.

In the present study, we investigated the analgesic effects of BCP in formalin-induced inflammation model and in a model of neuropathic pain, which involves the partial ligation of the sciatic nerve… BCP is the first natural CB2 receptor agonist, which could orally reduce inflammatory responses in different animal models of pain.

Thus, it is likely that BCP belongs to a group of common plant natural products with major potential impact on human health.

The oral intake of this dietary cannabinoid with vegetable food could be advantageous in the daily routine clinical practice over synthetic cannabinoid agonists.”

http://www.europeanneuropsychopharmacology.com/article/S0924-977X(13)00302-7/fulltext

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

Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain.

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“Despite the frequency of diabetes mellitus and its relationship to diabetic peripheral neuropathy (DPN) and neuropathic pain (NeP), our understanding of underlying mechanisms leading to chronic pain in diabetes remains poor.

Recent evidence has demonstated a prominent role of microglial cells in neuropathic pain states.

One potential therapeutic option gaining clinical acceptance is the cannabinoids, for which cannabinoidreceptors (CB) are expressed on neurons and microglia. We studied the accumulation and activation of spinal and thalamic microglia in streptozotocin (STZ)-diabetic CD1 mice and the impact of cannabinoid receptor agonism/antagonism during the development of a chronic NeP state.

The prevention of microglial accumulation and activation in the dorsal spinal cord was associated with limited development of a neuropathic pain state.

Cannabinoids demonstrated antinociceptive effects in this mouse model of DPN.

These results suggest that such interventions may also benefit humans with DPN, and their early introduction may also modify the development of the NeP state.”  http://www.ncbi.nlm.nih.gov/pubmed/20236533

“Tetrahydrocannabinol (THC), a component in marijuana, acts at both CB1 and CB2 receptors, but other forms of cannabinoids such as cannabinol and cannabidiol act predominantly at CB2 receptors. Such CB2 agonists may be potential anti-inflammatory therapies, antagonizing the 2-AG-induced recruitment of microglia and impacting upon development of an inflammatory state. Such properties may permit the cannabinoids to act in the prevention of microglial activation, perhaps limiting the development of neuropathic pain.

The present data confirm the efficacy of cannabinoid agonists, both for the CB1 and CB2 receptor, in modulation of acute thermal and tactile hypersensitivity as features of neuropathic pain. Furthermore, CB1 agonism from the onset of the offending stimulus (diabetes) normally leading to neuropathic pain ameliorated the development of a neuropathic pain state.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845559/

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

 

The role of cannabinoids in adult neurogenesis.

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“Cannabinoids are a unique class of chemical compounds incorporating plant-derived cannabinoids (the active components of Cannabis sativa), the endogenous cannabinoids and synthetic cannabinoid ligands, and these compounds are becoming increasingly recognized for their roles in neural developmental processes.

Indeed, cannabinoids have clear modulatory roles in adult neurogenesis, likely through activation of both CB1 and CB2receptors.

In recent years a large body of literature has deciphered the signalling networks involved in cannabinoid-mediated regulation of neurogenesis. This timely review summarises the evidence that the cannabinoid system is intricately associated with neuronal differentiation and maturation of NPCs, and highlights intrinsic/extrinsic signalling mechanisms that are cannabinoid targets.

Overall these findings identify the central role of the cannabinoid system in adult neurogenesis in the hippocampus and the lateral ventricles, and hence provide insight into the processes underlying post-developmental neurogenesis in the mammalian brain.”

Arachidonylethanolamide induces apoptosis of human glioma cells through vanilloid receptor-1.

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“The anti-tumor properties of cannabinoids have recently been evidenced, mainly with delta9-tetrahydrocannabinol (THC).

Here we investigated whether the most potent endogenous cannabinoid, arachidonylethanolamide (AEA), could be a candidate.

We observed that AEA induced apoptosis in long-term and recently established glioma cell lines via aberrantly expressed vanilloid receptor-1 (VR1).

In contrast with their role in THC-mediated death, both CB1 and CB2 partially protected glioma against AEA-induced apoptosis.

These data show that the selective targeting of VR1 by AEA or more stable analogues is an attractive research area for the treatment of glioma.”

http://www.ncbi.nlm.nih.gov/pubmed/15453094

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

Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1.

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“Delta(9)-Tetrahydrocannabinol, the active agent of Cannabis sativa, exhibits well-documented antitumor properties, but little is known about the possible effects mediated by endogenous cannabinoids on human tumors. In the present study, we analyzed the effect of arachidonyl ethanolamide (AEA) on cervical carcinoma (CxCa) cell lines.

The major finding was that AEA induced apoptosis of CxCa cell lines via aberrantly expressed vanilloid receptor-1, whereas AEA binding to the classical CB1 and CB2 cannabinoid receptors mediated a protective effect…

Overall, these data suggest that the specific targeting of VR1 by endogenous cannabinoids or synthetic molecules offers attractive opportunities for the development of novel potent anticancer drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/15047233

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

Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine.

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“Drugs that facilitate dopaminergic neurotransmission such as amphetamine induce PPI disruption in human and rodents.

Clinical and neurobiological findings suggest that the endocannabinoid system and cannabinoids may be implicated in the pathophysiology and treatment of schizophrenia.

Cannabidiol (CBD), a non-psychotomimetic constituent of the Cannabis sativa plant, has also been reported to have potential as an antipsychotic.

Our aim was to investigate if CBD pretreatment was able to prevent PPI disruption induced by amphetamine…

Pretreatment with CBD attenuated the amphetamine-disruptive effects…

These results corroborate findings indicating that CBD induces antipsychotic-like effects.

In addition, they pointed to the nucleus accumbens as a possible site of these effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25943166

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