Tag Archives: cannabinoid receptors

Endocannabinoid-mediated improvement on a test of aversive memory in a mouse model of fragile X syndrome.

Posted on by

“Silencing the gene FMR1 in fragile X syndrome (FXS) with consequent loss of its protein product, FMRP, results in intellectual disability, hyperactivity, anxiety, seizure disorders, and autism-like behavior. In a mouse model (Fmr1 knockout (KO)) of FXS, a deficit in performance on the passive avoidance test of learning and memory is a robust phenotype.

We report that drugs acting on the endocannabinoid (eCB) system can improve performance on this test.

Our results indicate that the eCB system is involved in FXS and suggest that the eCB system is a promising target for treatment of FXS.”

http://www.ncbi.nlm.nih.gov/pubmed/25979787

http://www.thctotalhealthcare.com/category/fragile-x-syndrome-fxs/

Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite.

Posted on by

“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.

In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Delta9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation.

These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.

“Cannabinoid components of marijuana, such as (−)Δ9-tetrahydrocannabinol (THC), or the synthetic cannabinoid WIN55,212-2, have been shown to prevent glutamate- or NMDA-induced neurotoxicity in isolated neurons or in the brain via activation of the cannabinoid receptor subtype CB1.

…the nonpsychotropic component of marijuana, cannabidiol (CBD), and the synthetic nonpsychotropic cannabinoid, HU-211, as well as THC have been demonstrated as potent antioxidants and/or NMDA receptor antagonists that protect neuron cultures from glutamate-induced death or from oxidative stress.

… we demonstrated that THC and CBD are neuroprotective against NMDA-induced retinal injury and that their protective actions are in part because of an effect in reducing formation of lipid peroxides, nitrite/nitrate, and nitrotyrosine.

In addition to possessing neuroprotective or retinal neuroprotective activity as demonstrated here and elsewhere, cannabinoids such as THC, WIN55,212-2, endogenous cannabinoid 2-arachidonoylglycerol, as well as nonpsychotropic HU-211 have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models.

 This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.

In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.

The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892413/

http://www.thctotalhealthcare.com/category/glaucoma-2/

Neuroprotective effects of cannabidiol in endotoxin-induced uveitis: critical role of p38 MAPK activation.

Posted on by

“Degenerative retinal diseases are characterized by inflammation and microglial activation.

The nonpsychoactive cannabinoid, cannabidiol (CBD), is an anti-inflammatory in models of diabetes and glaucoma.

We tested the hypothesis that retinal inflammation and microglia activation are initiated and sustained by oxidative stress and p38 mitogen-activated protein kinase (MAPK) activation, and that CBD reduces inflammation by blocking these processes…

Retinal inflammation and degeneration in uveitis are caused by oxidative stress.

CBD exerts anti-inflammatory and neuroprotective effects by a mechanism that involves blocking oxidative stress and activation of p38 MAPK and microglia.”

http://www.ncbi.nlm.nih.gov/pubmed/19052649

Endocannabinoid and ceramide levels are altered in patients with colorectal cancer.

Posted on by

“Endocannabinoids and ceramides have demonstrated growth inhibition, cell death induction and pro-apoptotic activity in cancer research.

In the present study, we describe the profiles of two major endocannabinoids, ceramides, free fatty acids and relevant metabolic enzymes in 47 pairs of human colorectal cancer tissues and adjacent non-tumor tissues…

Elevation of AEA and alteration of ceramides (C16, C24, C18, C20) may qualify as potential endogenous biomarkers and novel drug targets for colorectal cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/25975960

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

AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells.

Posted on by

“Human cutaneous melanoma is an aggressive and chemotherapy-resistant type of cancer. AM251 is a cannabinoid type 1 (CB1) receptor antagonist/inverse agonist with off-target antitumor activity against pancreatic and colon cancer cells. The current study aimed to characterize the in-vitro antimelanoma activity of AM251…

This study provides the first evidence of a proapoptotic effect and G2/M cell cycle arrest of AM251 on A375 cells. This compound may be a potential prototype for the development of promising diarylpyrazole derivatives to be evaluated in human cutaneous melanoma.”

http://www.ncbi.nlm.nih.gov/pubmed/25974027

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

The Lysophosphatidylinositol Receptor GPR55 Modulates Pain Perception in the Periaqueduactal Grey.

Posted on by

“Emerging evidence indicates the involvement of GPR55 and its proposed endogenous ligand, lysophosphatidylinositol (LPI), in nociception…

Thus, we provide the first pharmacological evidence that GPR55 activation at central levels is pronociceptive, suggesting that interfering with GPR55 signaling in the PAG may promote analgesia.”

http://www.ncbi.nlm.nih.gov/pubmed/25972448

Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.

Posted on by

“The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer.

Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25970609

Astroglial type-1 cannabinoid receptors (CB1): A new player in the tripartite synapse.

Posted on by

“The endocannabinoid system is an important regulator of physiological functions. In the brain, this control is mainly exerted through the type-1-cannabinoid (CB1) receptors. CB1 receptors are abundant at neuron terminals where their stimulation inhibits neurotransmitter release. However, CB1receptors are also expressed in astrocytes and recent studies showed that astroglial cannabinoid signalling is a key element of the tripartite synapse. In this review we discuss the different mechanisms by which astroglial CB1 receptors control synaptic transmission and plasticity. The recent involvement of astroglial CB1 receptors in the effects of cannabinoids on memory highlights their key roles in cognitive processes and further indicates that astrocytes are central active elements of high order brain functions.”

http://www.ncbi.nlm.nih.gov/pubmed/25967266

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

Posted on by

“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.

Posted on by

Image result for "Human reproduction update" 2015 Jul-Aug

“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