Lipid nanoparticles as an emerging platform for cannabinoid delivery: physicochemical optimization and biocompatibility.

Posted on May 23, 2015 by David

“This work aims at developing and optimizing a valuable oral delivery carrier for the cannabinoid derivative CB13, which presents a high therapeutic potential in chronic pain states that respond poorly to conventional analgesics, but also shows highly unfavorable physicochemical properties.

CB13-loaded lipid nanoparticles (LNP) formulations were developed…

The LNP formulation proposed proved to be a promising carrier for the oral delivery of CB13, a cannabinoid with high therapeutic potential in chronic pain states that currently lack a valid oral treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25996463

A CB2-Selective Cannabinoid Suppresses T-Cell Activities and Increases Tregs and IL-10.

Posted on May 20, 2015 by David

“We have previously shown that agonists selective for the cannabinoid receptor 2 (CB2), including O-1966, inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ graft rejection, predominantly through effects on T-cells. Current studies explored the mechanism of this immunosuppression by O-1966 using mouse spleen cells…

These data support the potential of CB2-selective agonists as useful therapeutic agents to prolong graft survival in transplant patients, and strengthens their potential as a new class of immunosuppressive agents with broader applicability.”

http://www.ncbi.nlm.nih.gov/pubmed/25980325

[Cannabinoids in medicine].

Posted on May 18, 2015 by David

“Cannabinoids have been known for many centuries because of their various effects in healthcare. They are primarily effective in reducing nausea, vomiting, pain, anorexia, spasticity and depression. Some other effects are known, all seem to be mediated by cannabinoid receptors in the central nervous system. In the past years, medical use has been proven in several studies. Today, the therapeutical use of cannabinoids in medicine is increasing, and access was made easier. Especially in pain-management and palliative care, they seem to be a valuable therapeutic option.”

http://www.ncbi.nlm.nih.gov/pubmed/19165445

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

Posted on May 16, 2015 by David

“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 and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes.

Posted on May 16, 2015 by David

“Cannabinoids are known to possess therapeutic properties including inhibition of oxidation, NMDA receptor-activation, and inflammation.

The present study evaluates the ability of CBD to reduce oxidative stress, preserve BRB function, and prevent neural cell death in experimental diabetes…

These results demonstrate that CBD treatment reduces neurotoxicity, inflammation, and BRB breakdown in diabetic animals through activities that may involve inhibition of p38 MAP kinase.

The nonpsychotropic CBD is a promising candidate for anti-inflammatory and neuroprotective therapeutics.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592672/

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

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

Posted on May 12, 2015 by David

“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.

Posted on May 11, 2015 by David

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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.

Posted on May 11, 2015 by David

“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.

Posted on May 11, 2015 by David

“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

A novel hemp seed meal protein hydrolysate reduces oxidative stress factors in spontaneously hypertensive rats.

Posted on May 10, 2015 by David

“This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH) in spontaneously hypertensive rats (SHR)…

The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity.”

http://www.ncbi.nlm.nih.gov/pubmed/25493943

“Cannabis sativa L., also commonly called industrial hemp seed, is historically an important source of food, fibre, dietary oil and medicine; the seed contains about 30% oil and 25% protein…

Proteins from both plant and animal sources, including those of hemp seed, have been isolated and recognized as essential sources of bioactive peptides capable of exerting various in vitro and in vivo activities, such as antioxidant, antihypertensive, antimicrobial, opioid, antithrombotic, hypocholesterolemic, appetite-reducing, mineral-binding, immunomodulatory and cytomodulatory…

HMH may serve as an important ingredient to formulate antioxidant diets with potential therapeutic effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276990/

http://www.thctotalhealthcare.com/category/hypertension-high-blood-pressure/