Can Marijuana Cure Cancer? Pharmaceutical Company Developing Cannabis Medicine To Treat Brain Cancer

Posted on February 10, 2017 by David

“Can Marijuana Cure Cancer? Pharmaceutical Company Developing Cannabis Medicine To Treat Brain Cancer” http://www.ibtimes.com/can-marijuana-cure-cancer-pharmaceutical-company-developing-cannabis-medicine-treat-2489282

“GW Pharmaceuticals Achieves Positive Results in Phase 2 Proof of Concept Study in Glioma” http://ir.gwpharm.com/releasedetail.cfm?ReleaseID=1010672

“Cannabinoid Drug Prolongs the Life of Brain Tumor Patients in Phase II Trials” http://labiotech.eu/gw-pharmaceuticals-brain-tumor/

“Drug Company Claims to Have Marijuana Treatment That Could Increase Lifespan of Brain Cancer Patients” http://www.complex.com/life/2017/02/gw-pharmaceuticals-claims-to-have-treatment-that-could-increase-lifespan-of-brain-cancer-patients

“GW Pharma’s cannabis-derived combo med helps brain cancer patients” http://www.fiercebiotech.com/biotech/gw-pharma-s-cannabis-derived-combo-med-helps-brain-cancer-patients

“GW pharmaceuticals to develop oncology portfolio after cannabis medication shows promising results” http://www.telegraph.co.uk/business/2017/02/07/gw-pharmaceuticals-develop-oncology-portfolio-cannabis-medication/

“GW Pharma is touting claims that a combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) produced positive survival benefits in a small study of 21 patients with recurrent glioblastoma multiforme, a common form of brain cancer.” https://endpts.com/gw-touts-positive-survival-benefit-in-small-brain-cancer-study-ablynx-files-for-ultra-rare-disease-drug-ok/

“GW Pharmaceuticals Is Set to Benefit as Cannabis Takes on Cancer” https://www.thestreet.com/story/13996559/1/gw-pharmaceuticals-is-set-to-benefit-as-cannabis-takes-on-cancer.html

“GW Pharmaceuticals Achieves Positive Results In Phase 2 Proof Of Concept Study In Glioma” https://www.clinicalleader.com/doc/gw-pharmaceuticals-phase-proof-of-concept-study-in-glioma-0001

“Here’s How Marijuana May Help Brain Cancer Patients Live Longer” http://www.menshealth.com/health/marijuana-drug-treats-brain-cancer?utm_source=facebook.com&utm_medium=social&utm_campaign=sharebutton

“New pharmaceutical drug uses marijuana to treat brain cancer” http://blog.sfgate.com/smellthetruth/2017/02/09/new-pharmaceutical-drug-uses-marijuana-to-treat-brain-cancer/

“Medicine’s Secret Weapon Against Brain Cancer Is Weed” https://www.inverse.com/article/27578-cancer-treatment-marijuana-gw-pharmaceuticals?utm_source=facebook.com&utm_medium=on_site&utm_campaign=desktop

“The Next Big Brain Cancer Drug Could Come from Marijuana” http://fortune.com/2017/02/07/gw-pharmaceuticals-marijuana-brain-cancer/

“Can Weed Cure Cancer? Marijuana Helps Fight Glioblastoma Multiforme, One Of The Deadliest Forms Of Brain Cancer” http://www.medicaldaily.com/marijuana-just-might-help-cure-one-deadliest-forms-brain-cancer-410947

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

Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture.

Posted on November 10, 2016 by David

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“Evidence suggests that the non-psychotropic cannabis-derived compound, cannabidiol (CBD), has anti-neoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM).

DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM.

Here we studied the anti-proliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures.

This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system (CNS) toxicity.

We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells.

Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells.

Co-treatment regiments combining CBD and DNA-damaging agents produced synergistic anti-proliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs.

Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells.

Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little-to-no therapeutic window when considering NPCs.”

https://www.ncbi.nlm.nih.gov/pubmed/27821713

“Definition of antineoplastic: inhibiting or preventing the growth and spread of tumors or malignant cells” http://www.merriam-webster.com/dictionary/antineoplastic

Cannabinoids Inhibit Glioma Cell Invasion by Down-regulating Matrix Metalloproteinase-2 Expression

Posted on October 11, 2016 by David

Cancer Research: 68 (6)

“Cannabinoids, the active components of Cannabis sativa L. and their derivatives, inhibit tumor growth in laboratory animals by inducing apoptosis of tumor cells and impairing tumor angiogenesis.

It has also been reported that these compounds inhibit tumor cell spreading.

Here, we evaluated the effect of cannabinoids on matrix metalloproteinase (MMP) expression and its effect on tumor cell invasion.

Local administration of Δ⁹-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down-regulated MMP-2 expression in gliomas generated in mice.

This cannabinoid-induced inhibition of MMP-2 expression in gliomas.

As MMP-2 up-regulation is associated with high progression and poor prognosis of gliomas and many other tumors, MMP-2 down-regulation constitutes a new hallmark of cannabinoid antitumoral activity.

As selective CB₂ receptor activation to mice has been shown to inhibit the growth and angiogenesis of gliomas, skin carcinomas and melanomas, our observations further support the possibility of finding cannabinoid-based antitumoral strategies devoid of nondesired psychotropic side effects.”

http://cancerres.aacrjournals.org/content/68/6/1945

Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization.

Posted on September 17, 2016 by David

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“Autophagy is considered primarily a cell survival process, although it can also lead to cell death. However, the factors that dictate the shift between these 2 opposite outcomes remain largely unknown. In this work, we used Δ⁹-tetrahydrocannabinol (THC, the main active component of marijuana, a compound that triggers autophagy-mediated cancer cell death) and nutrient deprivation (an autophagic stimulus that triggers cytoprotective autophagy) to investigate the precise molecular mechanisms responsible for the activation of cytotoxic autophagy in cancer cells. By using a wide array of experimental approaches we show that THC (but not nutrient deprivation) increases the dihydroceramide:ceramide ratio in the endoplasmic reticulum of glioma cells, and this alteration is directed to autophagosomes and autolysosomes to promote lysosomal membrane permeabilization, cathepsin release and the subsequent activation of apoptotic cell death. These findings pave the way to clarify the regulatory mechanisms that determine the selective activation of autophagy-mediated cancer cell death.”

http://www.ncbi.nlm.nih.gov/pubmed/27635674

Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system.

Posted on September 11, 2016 by David

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“Pediatric low-grade gliomas (P-LGG) consist of a mixed group of brain tumors that correspond to the majority of CNS tumors in children.

Notably, they may exhibit spontaneous involution after subtotal surgical removal (STR). In this study, we investigated molecular indicators of spontaneous involution in P-LGG.

CONCLUSIONS:

The P-LGG, which remained stable or that presented spontaneous involution after STR, showed significantly higher CNR1 expression at the time of diagnosis.

We hypothesize that high expression levels of CNR1 provide tumor susceptibility to the antitumor effects of circulating endocannabinoids like anandamide, resulting in tumor involution.

This corroborates with reports suggesting that CNR1 agonists and activators of the endocannabinoid system may represent therapeutic opportunities for children with LGG.

We also suggest that CNR1 may be a prognostic marker for P-LGG.

This is the first time spontaneous involution of P-LGG has been suggested to be induced by endocannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/27613640

Anticancer and antioxidant properties of terpinolene in rat brain cells.

Posted on July 12, 2016 by David

“Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species.

Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.” http://www.ncbi.nlm.nih.gov/pubmed/24084350

“Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. The major components in Bedrocan smoke were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene.” http://www.ncbi.nlm.nih.gov/pubmed/20118579

“The sedative effect of inhaled terpinolene in mice and its structure-activity relationships.” http://www.ncbi.nlm.nih.gov/pubmed/23339024

“Anticancer and antioxidant properties of terpinolene in rat brain cells.” http://www.ncbi.nlm.nih.gov/pubmed/24084350

Cannabinoid signalling in glioma cells

Posted on July 9, 2016 by David

SpringerPlus Cover Image

“Cannabinoids, originally derived from Cannabis sativa, as well as their endogenous and synthetic counterparts, were shown to induce apoptosis of glioma cells in vitro and tumour regression in vivo via their specific receptors, cannabinoid receptors CB1 and/or CB2.

CB2 are abnormally expressed in human gliomas and glioma cell lines. Most of the analysed gliomas expressed significant levels of CB2 receptor and the extent of CB2 expression in the tumour specimens was related to tumour malignancy.

A synthetic cannabinoid, WIN 55,212-2, down-regulated the Akt and Erk signalling pathways in C6 glioma cells that resulted in reduction of phosphorylated Bad levels, mitochondrial depolarization and activation of caspase cascade leading to apoptosis.

We examined whether synthetic cannabinoids with different receptor specificity: WIN55,212-2 (a non-selective CB1/CB2 agonist) and JWH133 (a CB2-selective agonist) affect survival of four human glioma cell lines and three primary human glioma cell lines.

WIN-55,212-2 decreased cell viability in all examined cell lines and induced cell death. Susceptibility of the cells to JWH133 treatment correlated with the CB2 expression. Cannabinoids triggered a decrease of mitochondrial membrane potential, cleavage of caspase-9 and effector caspases.

Induction of cell death by cannabinoid treatment led to the generation of a pro-apoptotic sphingolipid ceramide and disruption of signalling pathways crucial for regulation of proliferation and survival. Increased ceramide levels induced ER-stress and autophagy in drug-treated glioblastoma cells.

We conclude that cannabinoids are efficient inhibitors of human glioma cells growth, once the cells express specific type of cannabinoid receptor.”

http://springerplus.springeropen.com/articles/10.1186/2193-1801-4-S1-L11

The Influence of Biomechanical Properties and Cannabinoids on Tumor Invasion.

Posted on May 6, 2016 by David

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“Cannabinoids are known to have an anti-tumorous effect, but the underlying mechanisms are only sparsely understood. Mechanical characteristics of tumor cells represent a promising marker to distinguish between tumor cells and the healthy tissue.

We tested the hypothesis whether cannabinoids influence the tumor cell specific mechanical and migratory properties and if these factors are a prognostic marker for the invasiveness of tumor cells.

Here we could show that a “generalized stiffness” is a profound marker for the invasiveness of a tumor cell population in our model and thus might be of high clinical relevance for drug testing.

Additionally cannabinoids were shown to be of potential use for therapeutic approaches of glioblastoma.”

http://www.ncbi.nlm.nih.gov/pubmed/27149140

“Glioblastomas (GBM) are tumors that arise from astrocytes—the star-shaped cells that make up the “glue-like,” or supportive tissue of the brain. These tumors are usually highly malignant (cancerous) because the cells reproduce quickly and they are supported by a large network of blood vessels. Glioblastomas are generally found in the cerebral hemispheres of the brain, but can be found anywhere in the brain or spinal cord.” http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html?referrer=https://www.google.com/

Targeting Cannabinoid Receptors in Brain Tumors

Posted on May 4, 2016 by David

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“Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances — the endocannabinoids — that activate specific cell surface receptors.

Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis.

Of interest, cannabinoids seem to be selective antitumoral compounds as they kill glioma cells but not their nontransformed astroglial counterparts.

On the basis of these preclinical findings, a pilot clinical study of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) in patients with recurrent glioblastoma multiforme has been recently run. The fair safety profile of Δ⁹-THC, together with its possible growth-inhibiting action on tumor cells, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”

http://link.springer.com/chapter/10.1007%2F978-0-387-74349-3_17

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Posted on April 19, 2016 by David

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“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601