Tag Archives: therapeutic

Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects.

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“A multitude of physiological effects and putative pathophysiological roles have been proposed for the endogenous cannabinoid system in the gastrointestinal tract, liver and pancreas.

These range from effects on epithelial growth and regeneration, immune function, motor function, appetite control, fibrogenesis and secretion.

Cannabinoids have the potential for therapeutic application in gut and liver diseases.

Two exciting therapeutic applications in the area of reversing hepatic fibrosis as well as antineoplastic effects may have a significant impact in these diseases.

This review critically appraises the experimental and clinical evidence supporting the clinical application of cannabinoid receptor-based drugs in gastrointestinal, liver and pancreatic diseases.

Application of modern pharmacological principles will most probably expand the selective modulation of the cannabinoid system peripherally in humans.

We anticipate that, in addition to the approval in several countries of the CB(1) antagonist, rimonabant, for the treatment of obesity and associated metabolic dysfunctions, other cannabinoid modulators are likely to have an impact on human disease in the future, including hepatic fibrosis and neoplasia.”

http://www.ncbi.nlm.nih.gov/pubmed/18397936

http://www.thctotalhealthcare.com/category/liver-disease/

Components of the endocannabinoid and dopamine systems are dysregulated in Huntington’s disease: analysis of publicly available microarray datasets.

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“The endocannabinoid system (ECS) and the dopaminergic system (DAS) are two major regulators of basal ganglia function. During Huntington’s disease (HD) pathogenesis, the expression of genes in both the ECS and DAS is dysregulated…

The resulting data confirm gene expression changes observed using different approaches and provide novel insights into the consistency between changes observed in human tissue and various models, as well as disease stage- and tissue-specific transcriptional dysregulation in HD.

The major implication of the systems-wide data presented here is that therapeutic strategies targeting the ECS or DAS must consider the dynamic changes in gene expression over time and in different body areas, which occur during HD progression and the interconnectedness of the two systems.”

http://www.ncbi.nlm.nih.gov/pubmed/25692022

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

Protective and therapeutic effects of cannabis plant extract on liver cancer induced by dimethylnitrosamine in mice

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“Hepatocellular carcinomas will emerge as a major form of malignancy in the coming decades.

When these tumors are in advanced stages, few therapeutic options are available.

Therefore, it is essential to search for new treatment modalities to fight this disease.

Aim

Evaluate the possible protective and therapeutic effects of Cannabis extract on dimethylnitrosamine (DMNA)-induced hepatocarcinogenicity in mice.

Conclusion

The protective effect of cannabis extract is more pronounced in group taking cannabis before DMNA.

Cannabinoids might exert their anti-tumor effects by the direct induction of apoptosis and can decrease telomerase activity by inhibiting the expression of the TERT gene…”

http://www.sciencedirect.com/science/article/pii/S209050681400027X

 http://www.thctotalhealthcare.com/category/liver-cancer-2/

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

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“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/

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

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“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/

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

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“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.

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“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/

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

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“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/

The effects of Δ9-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis

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“Cannabis is taken as self-medication by patients with inflammatory bowel disease for symptomatic relief.

Cannabinoid receptor agonists decrease inflammation in animal models of colitis, but their effects on the disturbed motility is not known. (-)-Cannabidiol (CBD) has been shown to interact with Δ9-tetrahydrocannabinol (THC) in behavioural studies, but it remains to be established if these cannabinoids interact in vivo in inflammatory disorders.

Therefore the effects of CBD and THC alone and in combination were investigated in a model of colitis…

In this model of colitis, THC and CBD not only reduced inflammation but also lowered the occurrence of functional disturbances. Moreover the combination of CBD and THC could be beneficial therapeutically, via additive or potentiating effects.

As the two phytocannabinoids modulate the immune system and differ in their pharmacological profile, their combination could be more beneficial than either drug alone. Additionally CBD could not only potentiate the therapeutic effects of THC, but also attenuate some of its undesirable effects…”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931570/

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

Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis.

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“Recent studies have suggested immunomodulatory and anti-inflammatory effects of cannabinoid receptor 2 (CB2R) activation, which is devoid of psychoactivity. We have demonstrated the expression of CB2R in synovial tissue from patients with rheumatoid arthritis (RA), and its specific activation shows inhibitory effects on fibroblast-like synoviocytes. However, it is still unclear whether selective activation of CB2R inhibits joint inflammation or protects joint damage in RA.

CONCLUSIONS:

Activation of CB2R by HU-308 has therapeutic potential for RA to suppress synovitis and alleviate joint destruction by inhibiting the production of autoantibodies and proinflammatory cytokines.”

http://www.ncbi.nlm.nih.gov/pubmed/25601571

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