Category Archives: Gliomas

Therapeutic potential of cannabinoid medicines.

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Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Cannabis Kills Cancer Cells

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“Marijuana also found to prevent pain associated with chemotherapy”

Cannabis Kills Cancer Cells

“Studies in Spain have shown findings that Tetrahydrocannabinol (THC), the active ingredient found in marijuana, can induce the death of brain cancer cells, according to scientist Guillermo Velasco and his research team from the School of Biology at Complutense University in Madrid.

In a laboratory study where mice were “engineered” to carry three varying kinds of human cancer tumor grafts, THC was introduced into the brain, triggering a self-digestion development on a cellular level, known as “autophagy.” Within this process, the research team managed to isolate the particular activation route from which this process evolved.

The research team was also conducting clinical trials in concert, on two consenting brain cancer patients, said to be suffering from a rapidly aggressive form of cancer, known as “recurrent glioblastoma multiforme.”

The team, using electron microscopes to analyze brain tissue extracted before and after the 26 to 30-day regime, found that the THC had eradicated cancer cells, leaving the healthy cells undamaged.

The findings can now lend themselves to future design in newer cancer therapies, using the concept of autophagy activation.”

More: http://guardianlv.com/2013/08/cannabis-kills-cancer-cells/

THC, found in cannabis, shown to be effective in the treatment of brain tumors

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“In 2000, scientists at the Complutense University of Madrid carried out an extensive experiment, testing the effects of THC on cancerous brain cells in laboratory rats. Their discoveries were nothing short of amazing, as THC had effectively managed to destroy all cancer cells, while leaving healthy cells unaffected.
 
 Research into the effects of THC on glioblastoma would have had the potential to revolutionize available cancer treatments, yet due to insufficient funding and poor public exposure, the science team was unable to further their research.Manuel Guzman explained that “cannabinoids are selective antitumor compounds, as they can kill tumor cells without affecting their non-transformed counterparts.” In contrast to this, chemotherapy, the prevalent anticancer treatment of today, consists of a combination of antineoplastic drugs that have devastating physical and psychological side-effects… 
 
THC works by triggering the build-up of a chemical messenger known as ceramide, which in turn induces apoptosis (or programmed cell death) in mutated tumor cells.
Subsequent research into the properties of THC has revealed that it is among the very few naturally occurring, harmless substances that are capable of inducing programmed cell death in cancerous cells. Other substances with this property include anandamide, other cannabinoids and tumor necrosis factors produced by the immune system in its attempt to fight cancer.
 
After months of effort to obtain funding for testing the medical effects of THC on human tissues, the Madrid science team was forced to abandon this project, although there is currently no effective treatment available for malignant brain tumors.” 
 
 

Marijuana Compounds Possess Synergistic Anti-Cancer Effects, Study Says

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“Marijuana’s active compounds act synergistically to inhibit the growth of cancer cells and induce malignant cell death, according to preclinical trial data published online by the journal Molecular Cancer Therapeutics.

Investigators at the University of California, Pacific Medical Center Research Institute assessed whether the administration of the non-psychoactive cannabidiol would enhance the anti-cancer effects of THC on glioblastoma (brain cancer) cells.

Researchers reported that a combination of cannabinoids showed greater anti-cancer activity than the administration of either compound individually. “We discovered that cannabidiol enhanced the ability of THC to inhibit cell proliferation and induce cell cycle arrest and apoptosis (programmed cell death),” authors reported.

Investigators concluded: “Individually, THC and cannabidiol can activate distinct pathways in glioblastoma cells that ultimately culminate in inhibition of cancer cell growth and invasion as well as induction of cell death. We hypothesized that, if the individual agents were combined, a convergence on shared pathways may ensue, leading to an enhanced ability of the combination treatment to inhibit certain cancer cell phenotypes. We found this to be true in this investigation.”

A 2008 scientific review published in the journal Cancer Research reported that the cannabinioids inhibit cell proliferation in a wide range of cancers, including brain cancer, prostate cancer, breast cancer, lung cancer, skin cancer, pancreatic cancer, and lymphoma.”

http://norml.org/news/2010/01/21/marijuana-compounds-possess-synergistic-anti-cancer-effects-study-says

Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival

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Molecular Cancer Therapeutics

“Δ9-THC and other cannabinoids can act as direct anticancer agents in multiple types of cancer in culture and in vivo. 

Individually, Δ9-THC and CBD can activate distinct pathways in glioblastoma cells that ultimately culminate in inhibition of cancer cell growth and invasion as well as induction of cell death.

We hypothesized that, if the individual agents were combined, a convergence on shared pathways may ensue leading to an enhanced ability of the combination treatment to inhibit certain cancer cell phenotypes.

We found this to be true in this investigation.

CBD enhances the inhibitory effects of Δ9-THC on glioblastoma cell growth.

Cannabidiol significantly improved the inhibitory effects of Δ9-tetrahydrocannabinol on glioblastoma cell proliferation and survival.

The Combination Treatment of Δ9-THC and Cannabidiol Inhibits Cell Cycle and Induces Apoptosis.

Our results suggest that the addition of CBD to Δ9-THC may improve the overall effectiveness of Δ9-THC in the treatment of glioblastoma in cancer patients.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806496/

http://mct.aacrjournals.org/content/9/1/180.full

“CBD Enhances the Anticancer Effects of THC”  https://www.scribd.com/document/50154001/CBD-Enhances-the-Anticancer-Effects-of-THC-Journal-MCT-Marcu

Marijuana Ingredient Inhibits VEGF Pathway Required For Brain Tumor Blood Vessels

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“Cannabinoids, the active ingredients in marijuana, restrict the sprouting of blood vessels to brain tumors by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).

“Blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available,” said Manuel Guzmán, professor of biochemistry and molecular biology, with the Complutense University in Madrid, Spain, and the study’s principal investigator.

“The present findings provide a novel pharmacological target for cannabinoid-based therapies.””

More: http://www.sciencedaily.com/releases/2004/08/040816085401.htm

“Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas.” http://cancerres.aacrjournals.org/content/64/16/5617.long

Inhibition of tumor angiogenesis by cannabinoids

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“Cannabinoids, the active components of marijuana and their derivatives, inhibit tumor growth in animal models… Because the generation of a new vascular supply (angiogenesis) is causally involved in the progression of the majority of solid tumors, the aim of this study was to test whether cannabinoids inhibit tumor angiogenesis.”

Figure 1.

“PRINCIPAL FINDINGS

1. Cannabinoid administration inhibits tumor angiogenesis

2. Cannabinoid administration inhibits vascular endothelial cell migration and survival

3. Cannabinoid administration inhibits tumor expression of proangiogenic factors and improves other markers of tumor malignancy

 

 …In the context of the renaissance in the study of the therapeutic effects of cannabinoids, our findings show that these compounds may be considered promising anti-tumoral agents as they inhibit tumor angiogenesis and growth in vivo with no significant side effects.

 This report provides a mechanistic basis for the anti-tumoral action of cannabinoids and a novel pharmacological target for cannabinoid-based anti-tumoral therapies…”

Full text:  http://www.fasebj.org/content/17/3/529.full

Amphiregulin is a factor for resistance of glioma cells to cannabinoid-induced apoptosis.

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“Gliomas, one of the most malignant forms of cancer, exhibit high resistance to conventional therapies. Identification of the molecular mechanisms responsible for this resistance is therefore of great interest to improve the efficacy of the treatments against these tumors. Delta9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the ability of these compounds to induce apoptosis of tumor cells.

…we identified the epidermal growth factor receptor ligand amphiregulin as a candidate factor to mediate the resistance of glioma cells to cannabinoid treatment… in vivo silencing of amphiregulin rendered the resistant tumors xenografts sensitive to cannabinoid antitumoral action.

Amphiregulin expression was associated with increased extracellular signal-regulated kinase (ERK) activation, which mediated the resistance to THC by blunting the expression of p8 and TRB3-two genes involved in cannabinoid-induced apoptosis of glioma cells.

 Our findings therefore identify Amphirregulin as a factor for resistance of glioma cells to THC-induced apoptosis and contribute to unraveling the molecular bases underlying the emerging notion that targeted inhibition of the EGFR pathway can improve the efficacy of antitumoral therapies.”

http://www.ncbi.nlm.nih.gov/pubmed/19229996

Stimulation of the midkine/ALK axis renders glioma cells resistant to cannabinoid antitumoral action

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“Δ9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the stimulation of autophagy-mediated apoptosis in tumor cells. 

…Altogether, our findings identify Mdk as a pivotal factor involved in the resistance of glioma cells to THC pro-autophagic and antitumoral action, and suggest that selective targeting of the Mdk/ALK axis could help to improve the efficacy of antitumoral therapies for gliomas.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131933/

Stimulation of ALK by the growth factor midkine renders glioma cells resistant to autophagy-mediated cell death

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“Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, promotes cancer cell death via autophagy stimulation.

We find that activation of the tyrosine kinase receptor ALK by its ligand midkine interferes with the signaling mechanism by which THC promotes autophagy-mediated glioma cell death.”

 http://www.ncbi.nlm.nih.gov/pubmed/21593591