Cannabis extracts can have dramatic effects on brain cancer, according to new research out of St. George’s, University of London, U.K.

Scientists at the university have discovered that when certain constituents of cannabis are used to treat cancer tumors in mice alongside radiotherapy treatment, the growths can “virtually disappear.”

Researchers at St. Georges studied the treatment of brain cancer tumors in the laboratory and found that the most effective treatment was to combine active chemical components of the cannabis plant called cannabinoids with radiation.

Two of these cannabis derivatives, tetrahydrocannabinol (THC – the main psychoactive agent in marijuana) and cannabidiol (CBD) were tested as part of the research into brain cancer, which is particularly difficult to treat and claims the lives of about 5,200 Britons each year. It also has a particularly poor prognosis with a rate of survival after five years of patient’s diagnosis is only around 10 percent.

Cannabinoids are the active chemicals in cannabis and are also known more specifically as phytocannabinoids. There are 85 known cannabinoids in the cannabis plant.

While THC and CBD themselves have been shown to have a significant effect reducing the size of malignant brain tumors, the researchers have found that when these chemicals are combined with radiotherapy, the growths can virtually disappear. The St. George’s, University of London research is the first to show a dramatic effect when combining THC and CBD with irradiation. Tumors growing in the brains of mice were “drastically slowed down” when THC/CBD was used with irradiation, the scientists report.

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Dr Wai Liu, Senior Research Fellow and lead researcher on the project, comments: “The results are extremely exciting. The tumours were treated in a variety of ways, either with no treatment, the cannabinoids alone, and irradiation alone or with both the cannabinoids and irradiation at the same time.

“Those treated with both irradiation and the cannabinoids saw the most beneficial results and a drastic reduction in size. In some cases, the tumors effectively disappeared in the animals. This augurs well for further research in humans in the future. At the moment this is a mostly fatal disease. The benefits of the cannabis plant elements were known before but the drastic reduction of brain cancers if used with irradiation is something new and may well prove promising for patients who are in gravely serious situations with such cancers in the future.”

The research team are discussing the possibility of combining cannabinoids with irradiation in a human clinical trial.

The research paper, published in the Molecular Cancer Therapeutics journal, entitled “The Combination of Cannabidiol and 9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model” (Mol Cancer Ther Published OnlineFirst November 14, 2014; doi:10.1158/1535-7163.MCT-14-0402), is coauthored by Katherine Ann Scott, Angus G. Dalgleish, and Wai M. Liu — all of the Department of Oncology, Division of Clinical Sciences, St George’s, University of London, U.K.

The coauthors note that 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.

They observe that “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 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261).

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 (day 21: 5.5 2.2 mm3 vs. 48.7 24.9 mm3 in the control group; P < 0.01). The researchers say that taken together, their data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, suggesting a potential clinical benefit for glioma patients by using these two treatment modalities.

A St. George’s release notes that while cannabis is a controlled substance in the U.K. and is most commonly known as a recreational drug, the cannabis plant is known for its medicinal properties and has been used to relieve symptoms associated with cancer, HIV/AIDS, multiple sclerosis, anorexia, anxiety, depression, and numerous other illnesses and conditions.

A 2013 study by a team at St George’s, University of London led by Dr Wai Liu and colleagues conducted laboratory investigations using a number of cannabinoids, either alone or in combination with each other, to measure their anti-cancer actions in relation to leukemia. Of six cannabinoids studied, each demonstrated anti-cancer properties as effective as those seen in THC. Importantly, they had an increased effect on cancer cells when combined with each other.

The study, published in the journal Anticancer Research entitled “Enhancing the Activity of Cannabidiol and Other Cannabinoids In Vitro Through Modifications to Drug Combinations and Treatment Schedules,” (Anticancer Research October 2013 vol. 33 no. 10 4373-4380) is coauthored by Katherine Ann Scott, Sini Shah, Angus George Dalgleish And Wai Man Liu, all of the Department of Oncology, Division of Clinical Sciences, St. George’s, University of London, U.K.

The researchers note that cannabinoids display a diverse range of therapeutic qualities. We explored the activity of six cannabinoids — two forms of cannabidiol (CBD), two forms of cannabigerol (CBG) and two forms of cannabigevarin (CBGV), which represent the most common cannabinoids found in the cannabis plant apart from THC. The scientists found that used both alone and in combination in leukaemic cells. Cannabinoids were cytostatic and caused a simultaneous arrest at all phases of the cell cycle. Re-culturing pre-treated cells in drug-free medium resulted in dramatic reductions in cell viability. Furthermore, combining cannabinoids was not antagonistic. The coauthors suggest that the activities of some cannabinoids are influenced by treatment schedules; therefore, it is important to carefully select the most appropriate strategy in order to maximise their efficacy.

Dr Liu commented at the time: “This study is a critical step in unpicking the mysteries of cannabis as a source of medicine. The cannabinoids examined have minimal, if any, hallucinogenic side effects, and their properties as anti-cancer agents are promising. These agents are able to interfere with the development of cancerous cells, stopping them in their tracks and preventing them from growing. In some cases, by using specific dosage patterns, they can destroy cancer cells on their own. Used in combination with existing treatment, we could discover some highly effective strategies for tackling cancer. Significantly, these compounds are inexpensive to produce and making better use of their unique properties could result in much more cost effective anti-cancer drugs in future.”

A 2010 German study published in the journal Drug & Alcohol Dependence entitled “Diminished gray matter in the hippocampus of cannabis users: Possible protective effects of cannabidiol” (Volume 114, Issues 2-3, Pages 242–245, April 1, 2011 DOI: http://dx.doi.org/10.1016/j.drugalcdep.2010.09.020)), coauthored by Traute Demirakca, Alexander Sartorius, Gabriele Ende, Nadja Meyer, and Helga Welzel of the Department of Neuroimaging, Central Institute of Mental Health, Mannheim, Germany; Gisela Skopp of the Institute of Forensic and Traffic Medicine, University Hospital, Heidelberg, Germany; and Karl Mann and Derik Hermann of the Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany, notes that chronic cannabis use has been associated with memory deficits and a volume reduction of the hippocampus, but none of the studies accounted for different effects of tetrahydrocannabinol (THC) and cannabidiol (CBD).

Using a voxel based morphometry approach optimized for small subcortical structures (DARTEL), the researchers measured gray matter (GM) concentration and volume of the hippocampus in 11 chronic recreational cannabis users and 13 healthy controls, and correlated with THC and CBD from hair analyses. GM volume was calculated by modulating VBM using Jacobian determinants derived from the spatial normalization.

The investigators found that cannabis users showed lower GM volume located in a cluster of the right anterior hippocampus. In a regression analysis an inverse correlation of the ratio THC/CBD with the volume of the right hippocampus was observed. Cannabidiol also correlated positively with GM concentration (unmodulated VBM data), but not with GM volume (modulated VBM) in the bilateral hippocampus.

The coauthors conclude that lower volume in the right hippocampus in chronic cannabis users was corroborated, and higher THC and lower CBD were associated with this volume reduction indicating neurotoxic effects of THC and neuroprotective effects of CBD. They say this confirms existing preclinical and clinical results, and as a possible mechanism the influence of cannabinoids on hippocampal neurogenesis is suggested.

The other side of the same coin is that the impact of THC has not been found to be consistently positive, as neuroscientists at the University of Texas find the brain’s grey matter could be much more vulnerable than white matter to THC-CBD effects.

While the medical case for the use of cannabinoids continues to be made in a wide range of research efforts touching on several disease indications, there is also a gap between studies that reveal health benefits from cannabis and the potentially long-term damage that smoking marijuana may cause over a prolonged period of use. Recently, UT Dallas’ Center for BrainHealth study that was published in the Proceedings of the National Academy of Sciences (PNAS) revealed that MRI imagery revealed abnormalities in the brains of people who had smoked cannabis from a young age into mature adulthood.

Dr. Sina Aslan, founder and president of Advance MRI, LLC and adjunct assistant professor at The University of Texas at Dallas, explained that their study was unique in that “. . . it combines three different MRI techniques to evaluate different brain characteristics.” Aslan went on to note that, “the results suggest increases in connectivity, both structural and functional that may be compensating for gray matter losses. Eventually, however, the structural connectivity or ‘wiring’ of the brain starts degrading with prolonged marijuana use.”

The use of cannabis in medicine still remains a complex and politicized issue. However, with science and research putting a finer point on the pros and cons of cannabis in treating diseases, the medical community is coming closer to finding an appropriate middle ground that lets patients benefit for their use without incurring unhealthy repercussions.

For more information, visit:
http://www.sgul.ac.uk/

Sources:
St George’s, University of London
Molecular Cancer Therapeutics
Anticancer Research
Drug & Alcohol Dependence

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