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

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“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.

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“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.

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“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.

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“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

Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms.

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“Substance dependence and schizophrenia are both associated with dopaminergic dysfunction.

It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function.

These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/23820822

“There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence.”  http://www.ncbi.nlm.nih.gov/pubmed/25873042

Hemp (Cannabis sativa L.).

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“Hemp (Cannabis sativa L.) suspension culture cells were transformed with Agrobacterium tumefaciens strain EHA101 carrying the binary plasmid pNOV3635. The plasmid contains a phosphomannose isomerase (PMI) selectable marker gene. Cells transformed with PMI are capable of metabolizing the selective agent mannose, whereas cells not expressing the gene are incapable of using the carbon source and will stop growing. Callus masses proliferating on selection medium were screened for PMI expression using a chlorophenol red assay. Genomic DNA was extracted from putatively transformed callus lines, and the presence of the PMI gene was confirmed using PCR and Southern hybridization. Using this method, an average transformation frequency of 31.23% ± 0.14 was obtained for all transformation experiments, with a range of 15.1-55.3%.”

http://www.ncbi.nlm.nih.gov/pubmed/25416268

The effects of Cannabis sativa L. seed (hempseed) in the ovariectomized rat model of menopause.

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“Cannabis sativa L. has been used for the treatment of various gynecological diseases in traditional medicine.

The potential of this plant to protect against complications of menopause has been raised but rarely studied.

The effects of hempseed on plasma lipid and lipoprotein profiles, estradiol and calcium levels were evaluated.

These results suggest that hempseed may improve post-ovariectomy complications in rats.”

http://www.ncbi.nlm.nih.gov/pubmed/21069097

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/

 

Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target.

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Figure 2

“Glioblastoma (GBM) is the most common form of primary adult brain tumors…

It is, therefore, essential to discover master regulators that control GBM invasiveness and target them therapeutically.

We demonstrate here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of GBM cell lines and primary GBM cells.

Furthermore, we show that a non-toxic compound, cannabidiol, significantly down-regulates Id-1 gene expression and associated glioma cell invasiveness…

Our results suggest that Id-1 regulates multiple tumor-promoting pathways in GBM, and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of GBM patients.

We previously showed a strong correlation between Id-1 expression and the invasive and metastatic behavior of breast cancer cells.”

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells… CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells…  Moreover, reducing Id-1 expression with cannabinoids could also provide a therapeutic strategy for the treatment of additional aggressive cancers because Id-1 expression was found to be up-regulated during the progression of almost all types…”  http://mct.aacrjournals.org/content/6/11/2921.long

“In this report, we show that Id-1 is a key regulator of brain tumor cell invasiveness and neurosphere growth, and that Id-1 expression is specifically up-regulated in tissues from patients with high-grade gliomas. Importantly, we demonstrate that targeting Id-1 expression using either genetic approaches or the non-toxic cannabinoid, cannabidiol (CBD), leads to a significant reduction in the invasion of both GBM cell lines and patient-derived primary GBM cultures. CBD also significantly inhibits GBM dispersal ex vivo, and reduces tumor growth and Id-1 expression in vivo.

Consistent with the breast cancer study, we found that the non-psychoactive cannabinoid CBD significantly down-regulated Id-1 expression in serum-derived and primary GBM cells. As expected, we observed robust inhibition of glioma cell invasiveness.

In conclusion, our results establish Id-1 as a key regulator of both invasion and stemness in GBM cells and demonstrate that the non-toxic cannabinoid compound CBD down-regulates Id-1 expression and tumor aggressiveness in culture and in vivo.

The data also shed light on some of the key pathways that control GBM cell dispersal and progression. A greater understanding of these pathways may lead to more effective therapies for cancer patients including the additional refinement of cannabinoid analogs targeting Id-1.

We expect our efforts to ultimately translate to the development of future clinical trials with nontoxic compounds that target the expression of Id-1, a master regulator of GBM aggressiveness.

With its lack of systemic toxicity and psychoactivity, CBD is an ideal candidate agent in this regard and may prove useful in combination with front-line agents for the treatment of patients with aggressive and high-grade GBM tumors.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594064/

“McAllister Lab… Cannabidiol inhibits tumor (glioblastoma) progression in mouse models of brain cancer. Mice bearing human brain tumors derived from glioblastoma were treated with the naturally occurring cannabinoid, cannabidiol (CBD).”  http://www.cpmcri-currents.org/our-people/discovery-investigators/mcallister-lab

“New Study Finds Cannabis Compound Could Have Even Greater Reach in Inhibiting Aggressive Cancer than Previously Thought. Researchers at California Pacific Medical Center Research Institute (CPMCRI, a Sutter Health affiliate) have found that a compound in cannabis previously shown to decrease metastatic breast cancer now shows promise in stopping aggressive brain cancer as well. The findings are particularly important given the safety of the cannabis compound and the fact that patients with advanced brain cancer have few options for treatment.”  http://www.cpmc.org/about/press/news2012/cannabis-brain.html

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

Glioblastoma progression in mouse models of brain cancer, after treatment with CBD

The evolving role of the endocannabinoid system in gynaecological cancer.

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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