The antitumor action of cannabinoids on glioma tumorigenesis.

Posted on December 5, 2014 by David

“Cannabinoids are a class of chemical compounds with a wide spectrum of pharmacological effects, mediated by two specific plasma membrane receptors (CB1 and CB2).

Recently, CB1 and CB2 expression levels have been detected in human tumors, including those of brain.

Cannabinoids-endocannabinoids exert anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types, both in vitro and in vivo in animal models, after local or systemic administration.

We present the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.”

http://www.ncbi.nlm.nih.gov/pubmed/25472761

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

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model.

Posted on November 16, 2014 by David

“High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful.

Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis.

In an attempt to improve treatment outcome, we have investigated the effect of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261).

Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS).

Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS.

…increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis.

These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation.

Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities.”

http://www.ncbi.nlm.nih.gov/pubmed/25398831

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

Anti-Cancer Effects In Active Component Of Marijuana

Posted on July 21, 2014 by David

“Guillermo Velasco and colleagues, at Complutense University, Spain, have provided evidence that suggests that cannabinoids such as the main active component of marijuana (THC) have anticancer effects on human brain cancer cells.

In the study, THC was found to induce the death of various human brain cancer cell lines and primary cultured human brain cancer cells by a process known as autophagy. Consistent with the in vitro data, administration of THC to mice with human tumors decreased tumor growth and induced the tumor cells to undergo autophagy.

As analysis of tumors from two patients with recurrent glioblastoma multiforme (a highly aggressive brain tumor) receiving intracranial THC administration showed signs of autophagy, the authors suggest that cannabinoid administration may provide a new approach to targeting human cancers.”

http://www.medicalnewstoday.com/releases/144770.php

“Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673842/

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

Posted on March 4, 2014 by David

“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

Endocannabinoid system in cancer cachexia.

Posted on March 1, 2014 by David

Image result for current opinion in clinical nutrition & metabolic care

“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

The endocannabinoid signaling system in cancer.

Posted on March 1, 2014 by David

“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

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

Posted on January 27, 2014 by David

“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

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

Posted on January 27, 2014 by David

“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

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

Posted on January 27, 2014 by David

“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/

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

Posted on January 27, 2014 by David

“…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/