Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

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“Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson’s and Huntington’s disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis.

Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of conventional chemotherapies, there is considerable merit in the development of cannabinoids as potential anticancer therapies.

Whilst the presence of psychoactive effects of cannabinoids could prevent any progress in this field, recent studies have shown the value of the non-psychoactive components of cannabinoids in activating apoptotic pathways, inducing anti-proliferative and anti-angiogenic effects.

The aforementioned effects are suggested to be through pathways such as ERK, Akt, mitogen-activated protein kinase (MAPK) pathways, phosphoinositide 3-kinase (PI3K) pathways and hypoxia inducible factor 1 (HIF1), all of which are important contributors to the hallmarks of cancer.

Many important questions still remain unanswered or are poorly addressed thus necessitating further research at basic pre-clinical and clinical levels. In this review, we address these issues with a view to identifying the key challenges that future research needs to address.”

http://www.ncbi.nlm.nih.gov/pubmed/26852955

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

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Ligands for cannabinoid receptors, promising anticancer agents.

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“Cannabinoid compounds are unique to cannabis and provide some interesting biological properties.

These compounds along with endocannabinoids, a group of neuromodulator compounds in the body especially in brain, express their effects by activation of G-protein-coupled cannabinoid receptors, CB1 and CB2.

There are several physiological properties attributed to the endocannabinoids including pain relief, enhancement of appetite, blood pressure lowering during shock, embryonic development, and blocking of working memory.

On the other hand, activation of endocannabinoid system may be suppresses evolution and progression of several types of cancer.

According to the results of recent studies, CB receptors are over-expressed in cancer cell lines and application of multiple cannabinoid or cannabis-derived compounds reduce tumor size through decrease of cell proliferation or induction of cell cycle arrest and apoptosis along with desirable effect on decrease of tumor-evoked pain.

Therefore, modulation of endocannabinoid system by inhibition of fatty acid amide hydrolase (FAAH), the enzyme, which metabolized endocannabinoids, or application of multiple cannabinoid or cannabis-derived compounds, may be appropriate for the treatment of several cancer subtypes. This review focuses on how cannabinoid affect different types of cancers.”

http://www.ncbi.nlm.nih.gov/pubmed/26764235

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

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Distinctive pattern of cannabinoid receptor type II (CB2) expression in adult and pediatric brain tumors.

“The efficacy of cannabinoids against high-grade glioma in animal models, mediated by two specific receptors, CB1 and CB2, raised promises for targeted treatment of the most frequent and malignant primary brain tumors.

Unlike the abundantly expressed CB1, the CB2 receptor shows a restricted distribution in normal brain. Although brain tumors constitute the second most common malignancy in children and the prevalence of histological types of brain tumors vary significantly between the adult and pediatric populations, cannabinoid receptor expression in pediatric tumors remains unknown.

In the present study, we compared the expression of the CB2 receptor in paraffin-embedded sections from primary brain tumors of adult and pediatric patients. Most glioblastomas expressed very high levels of CB2 receptors and the expression correlated with tumor grade.

Interestingly, some benign pediatric astrocytic tumors, such as subependymal giant cell astrocytoma (SEGA), which may occasionally cause mortality owing to progressive growth, also displayed high CB2 immunoreactivity.

The high levels of CB2 expression would predestine those tumors to be vulnerable to cannabinoid treatment.

In contrast, all examined cases of embryonal tumors (medulloblastoma and S-PNET), the most frequently diagnosed malignant brain tumors in childhood, showed no or trace CB2 immunoreactivity.

Our results suggest that the CB2 receptor expression depends primarily on the histopathological origin of the brain tumor cells and differentiation state, reflecting the tumor grade.”

http://www.ncbi.nlm.nih.gov/pubmed/17239827

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Endocannabinoid system in cancer cachexia.

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“More than 60% of advanced cancer patients suffer from anorexia and cachexia.

This review focuses on the possible mechanisms by which the endocannabinoid system antagonizes cachexia-anorexia processes in cancer patients and how it can be tapped for therapeutic applications.

Cannabinoids stimulate appetite and food intake…

Cannabinoid type 1 receptor activation stimulates appetite and promotes lipogenesis and energy storage.

Further study of cancer-cachexia pathophysiology and the role of endocannabinoids will help us to develop cannabinoids without psychotropic properties, which will help cancer patients suffering from cachexia and improve outcomes of clinical antitumor therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17563462

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The endocannabinoid signaling system in cancer.

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“The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer.

This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancerpathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters.

We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/23602129

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Spontaneous regression of septum pellucidum/forniceal pilocytic astrocytomas–possible role of Cannabis inhalation.

“The purpose of this report is to document spontaneous regression of pilocytic astrocytomas of the septum pellucidum and to discuss the possible role of cannabis in promoting regression.

We report two children with septum pellucidum/forniceal pilocytic astrocytoma (PA) tumors… Neither patient received any conventional adjuvant treatment.

The tumors regressed over the same period of time that cannabis was consumed via inhalation, raising the possibility that the cannabis played a role in the tumor regression.”

http://www.ncbi.nlm.nih.gov/pubmed/21336992

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Targeting astrocytomas and invading immune cells with cannabinoids: a promising therapeutic avenue.

“The last quarter century has borne witness to great advances in both the detection and treatment of numerous cancers. Even so, malignancies of the central nervous system, especially high-grade astrocytomas, continue to thwart our best efforts toward effective chemotherapeutic strategies.

With prognosis remaining bleak, the time for serious consideration of alternative therapies has arrived. Various preparations of the marijuana plant, Cannabis sativa, and related synthetic and endogenous compounds, may constitute just such an alternative.

Cannabinoids, although much maligned historically for their psychotropic effects and clear abuse potential, have long been used medicinally and are now staging an impressive comeback, as recent studies have begun to explore their powerful anti-tumoral properties.

In this study, we review in vitro and in vivo evidence supporting the use of cannabinoids for treatment of brain tumors. We further propose the continued intense investigation of cannabinoid efficacies as novel anti-cancer agents, especially in models recapitulating such properties within the unique environment of the brain.”

http://www.ncbi.nlm.nih.gov/pubmed/17952648

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The Expression Level of CB1 and CB2 Receptors Determines Their Efficacy at Inducing Apoptosis in Astrocytomas

“Cannabinoids represent unique compounds for treating tumors, including astrocytomas.

One of the most promising therapeutic uses of cannabinoids is linked to their ability to induce apoptosis in tumors, including in astrocytoma…

Remarkably, cannabinoids applied at high concentration induce apoptosis in all subclones independently of CB1, CB2…

…the treatment of tumors with high concentrations of cannabinoids should not be overlooked. In fact, stereotaxic injection of high concentrations of cannabinoids will eradicate a significant portion of C6 astrocytomas…”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806825/

 

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Cannabinoid and cannabinoid-like receptors in microglia, astrocytes and astrocytomas

“…compounds targeting cannabinoid-like receptors constitute promising therapeutics to manage neuroinflammation and eradicate malignant astrocytomas.

Importantly, the selective targeting of cannabinoid-like receptors should provide therapeutic relieve without inducing the typical psychotropic effects and possible addictive properties…

 Taken together, the studies outlined in this review suggest that stereotactic injection of high concentrations of CBD could constitute a useful regimen for neurosurgeons to use in the treatment of malignant astrocytomas and of excessive/chronic neuroinflammation.

Such a treatment could provide therapeutic effects both directly, by killing the astrocytoma and limiting its propagation, and indirectly, by reducing the accumulation of activated microglia or invading peripheral immune cells.

The fact that non-psychotropic cannabinoids acting through CB-like receptors affect such fundamental processes involved in microglial cell activation and astrocytoma propagation constitutes, in my opinion, one of the most exciting areas of research in our search for new chemotherapeutic agents to treat malignant brain tumors and new anti-inflammatory agents to temper the damage linked to chronic neuroinflammation.

Furthermore, the curative properties of cannabinoids do not overlap with currently available medicines, and therefore cannabinoid-based treatments constitute a new therapeutic platform.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919281/

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Cannabinoid receptors in human astroglial tumors.

“…cannabinoids are reported to inhibit the growth of tumors, including gliomas. These effects have been claimed to be mediated via cannabinoid receptors 1 and 2 (CB1, CB2).

We conclude that cannabinoid therapy of human gliomas targets not only receptors on tumor, but also on other cell types…”

http://www.ncbi.nlm.nih.gov/pubmed/16893424

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