Cannabinoid receptor type 2, but not type 1, is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders.

Posted on February 13, 2015 by David

“Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs.

There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult…

In this study, we investigated the involvement of cannabinoid system…

Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care.”

http://www.ncbi.nlm.nih.gov/pubmed/23585028

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

Δ9 -tetrahydrocannabinol and cannabidiol as potential curative agents for cancer. A critical examination of the preclinical literature.

Posted on February 13, 2015 by David

“An internet search with searchwords “cannabis cures cancer” produce a wealth of sites claiming that cannabis has this effect. These sites are freely accessible to the general public and thus contribute to public opinion. But do Δ9 -tetrahydrocannabinol (Δ9 -THC) and cannabidiol (CBD) cure cancer? In the absence of clinical data other than a safety study and case reports, preclinical data should be evaluated in terms of its predictive value. Using a strict approach where only concentrations and/or models relevant to the clinical situation are considered, the current preclinical data does not yet provide robust evidence that systemically administered Δ9 -THC will be useful for the curative treatment of cancer. There is more support for an intratumoural route of administration of higher doses of Δ9 -THC. CBD produces effects in relevant concentrations and models, although more data are needed concerning its use in conjunction with other treatment strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/25669486

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

A selective, non-toxic CB2 cannabinoid o-quinone with in vivo activity against triple negative breast cancer.

Posted on February 12, 2015 by David

“Triple-negative breast cancer (TNBC) represents a subtype of breast cancer characterized by high aggressiveness. There is no current targeted therapy for these patients whose prognosis, as a group, is very poor.

Here, we report the synthesis and evaluation of a potent antitumor agent in vivo for this type of breast cancer designed as a combination of quinone/cannabinoid pharmacophores.

This new compound (10) has been selected from a series of chromenopyrazolediones with full selectivity for the non-psychotropic CB2 cannabinoid receptor and with efficacy in inducing death of human TNBC cell lines.

The dual concept quinone/cannabinoid was supported by the fact that compound 10 exerts antitumor effect by inducing cell apoptosis through activation of CB2 receptors and through oxidative stress.

Notably, it did not show either cytotoxicity on non-cancerous human mammary epithelial cells nor toxic effects in vivo suggesting that it may be a new therapeutic tool for the management of TNBC.”

http://www.ncbi.nlm.nih.gov/pubmed/25671648

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

Activation of Cannabinoid Type Two Receptors (CB2) Diminish Inflammatory Responses in Macrophages and Brain Endothelium.

Posted on February 11, 2015 by David

“Chronic neuroinflammatory disorders (such as HIV associated neurodegeneration) require treatment that decreases production of inflammatory factors by activated microglia and macrophages and protection of blood brain barrier (BBB) injury secondary to activation of brain endothelium.

Cannabioid type 2 receptor (CB2) is highly expressed on macrophages and brain microvasular enndothelial cells (BMVEC) and is upregulated in inflammation and HIV infection. It has been shown that CB2 activation dampened inflammatory responses in macrophages and BMVEC.

In this study, we assessed by PCR array the expression of a wide range of genes increased in macrophages and BMVEC in inflammation. TNFα treatment upregulated 33 genes in primary human BMVEC, and two highly selective CB2 agonists diminished expression of 31 and 32 genes.

These results were confirmed by functional assays (BBB protection after inflammatory insult and decreased migration of monocytes across BMVEC monolayers after CB2stimulation). Similarly, CB2 stimulation in primary human macrophages led to the suppression of 35 genes out of the 50 genes upregulated by LPS. Such changes in gene expression paralleled diminished secretion of proinflammatory factors.

These results indicate the potential utility of CB2agonists for the treatment of neuroinflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/25666933

Fatty Acid Binding Proteins (FABPs) are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD).

Posted on February 11, 2015 by David

Image result for fatty acid binding proteins

“Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex.

Recent reports suggest that CBD and THC elevates the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance.

Fatty acid binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH).

By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and we demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs.

Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption.

Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD.

Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids.

These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy towards epilepsy and other neurological disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25666611

A systematic review of the antipsychotic properties of cannabidiol in humans.

Posted on February 11, 2015 by David

“Despite extensive study over the past decades, available treatments for schizophrenia are only modestly effective and cause serious metabolic and neurological side effects. Therefore, there is an urgent need for novel therapeutic targets for the treatment of schizophrenia.

A highly promising new pharmacological target in the context of schizophrenia is the endocannabinoid system…

the non-psychotropic, plant-derived cannabinoid agent cannabidiol (CBD) may have antipsychotic properties, and thus may be a promising new agent in the treatment of schizophrenia.

Here we review studies that investigated the antipsychotic properties of CBD in human subjects.

Results show the ability of CBD to counteract psychotic symptoms and cognitive impairment associated with cannabis use as well as with acute THC administration.

In addition, CBD may lower the risk for developing psychosis that is related to cannabis use.

These effects are possibly mediated by opposite effects of CBD and THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex.

The first small-scale clinical studies with CBD treatment of patients with psychotic symptoms further confirm the potential of CBD as an effective, safe and well-tolerated antipsychotic compound, although large randomised clinical trials will be needed before this novel therapy can be introduced into clinical practice.”

http://www.ncbi.nlm.nih.gov/pubmed/25667194

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

Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of Cannabidiol in breast cancer.

Posted on February 11, 2015 by David

“The anti-tumor role and mechanisms of Cannabidiol (CBD), a non-psychotropic cannabinoid compound, are not well studied especially in triple-negative breast cancer (TNBC).

In the present study, we analyzed CBD’s anti-tumorigenic activity against highly aggressive breast cancer cell lines including TNBC subtype.

We show here -for the first time-that CBD significantly inhibits epidermal growth factor (EGF)-induced proliferation and chemotaxis of breast cancer cells.

Further studies revealed that CBD inhibits EGF-induced activation of EGFR, ERK, AKT and NF-kB signaling pathways as well as MMP2 and MMP9 secretion.

In addition, we demonstrated that CBD inhibits tumor growth and metastasis in different mouse model systems.

Analysis of molecular mechanisms revealed that CBD significantly inhibits the recruitment of tumor-associated macrophages in primary tumor stroma and secondary lung metastases…

In summary, our study shows -for the first time-that CBD inhibits breast cancer growth and metastasis through novel mechanisms by inhibiting EGF/EGFR signaling and modulating the tumor microenvironment.

These results also indicate that CBD can be used as a novel therapeutic option to inhibit growth and metastasis of highly aggressive breast cancer subtypes including TNBC, which currently have limited therapeutic options and are associated with poor prognosis and low survival rates.”

http://www.ncbi.nlm.nih.gov/pubmed/25660577

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

Antidepressant-like effects of the cannabinoid receptor ligands in the forced swimming test in mice: Mechanism of action and possible interactions with cholinergic system.

Posted on February 11, 2015 by David

“The purpose of the experiments was to explore the role of the endocannabinoid system, through cannabinoid (CB) receptor ligands, nicotine and scopolamine, in the depression-related responses using the forced swimming test (FST) in mice…

Our results provide clear evidence that the endocannabinoid system participates in the depression-related behavior and through interactions with cholinergic system modulate these kind of responses.”

http://www.ncbi.nlm.nih.gov/pubmed/25660201

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

THE EFFECT OF PHYTOCANNABINOIDS ON AIRWAY HYPERRESPONSIVENESS, AIRWAY INFLAMMATION AND COUGH.

Posted on February 7, 2015 by David

“Cannabis has been demonstrated to have bronchodilator, anti-inflammatory and anti-tussive activity in the airways, but, information on the active cannabinoids, their receptors and the mechanisms for their effects is limited.

We compared the effects of Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, cannabidiolic acid and tetrahydrocannabivarin…

The other cannabinoids did not influence cholinergic transmission and only Δ9-THC demonstrated effects on airway hyperresponsiveness, anti-inflammatory activity and antitussive activity in the airways.”

http://www.ncbi.nlm.nih.gov/pubmed/25655949

http://jpet.aspetjournals.org/content/early/2015/02/05/jpet.114.221283.long

Cannabinoid Receptor CB2 Is Involved in Tetrahydrocannabinol-Induced Anti-Inflammation against Lipopolysaccharide in MG-63 Cells.

Posted on February 6, 2015 by David

“Cannabinoid Δ9-tetrahydrocannabinol (THC) is effective in treating osteoarthritis (OA)…

Activation of cannabinoid receptor CB2 reduces inflammation; whether the activation CB2 is involved in THC-induced therapeutic action for OA is still unknown.

We hypothesized that the activation of CB2 is involved in THC-induced anti-inflammation in the MG-63 cells exposed to LPS, and the anti-inflammation is mediated by cofilin-1…

We found that THC suppressed the release of proinflammatory factors, including tumor necrosis factor α (TNF-α), interleukin- (IL-) 1β, IL-6, and IL-8, decreased nuclear factor-κB (NF-κB) expression, and inhibited the upregulation of cofilin-1 protein in the LPS-stimulated MG-63 cells.

These results suggested that CB2 is involved in the THC-induced anti-inflammation in LPS-stimulated MG-63 cells, and the anti-inflammation may be mediated by cofilin-1.”

http://www.ncbi.nlm.nih.gov/pubmed/25653478

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310496/

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