Thanks to our friends at Project CBD for allowing us to repost their article.
The oncologist â who had repeatedly told George to stop taking cannabis oil â said it was the best day of his professional career. But he wouldnât acknowledge that cannabis may have played a part in the cancerâs reversal. The oncologistâs reaction typified the skepticism of health professionals with respect to cannabis and cancer. Without solid evidence from clinical trials, most doctors dismiss the idea that cannabis could have antitumoral effects in patients. Which begs the question â How far away are we from getting the solid clinical evidence necessary to convince the medical profession that cannabis is a serious anticancer treatment?
The only way for a drug to make it into the oncologistsâ anticancer arsenal is for it to successfully pass through three phases of randomized double-blind placebo clinical trials testing safety, dosing, and efficacy.
Thirteen years have passed since the first small pilot study was conducted by Professor Manuel Guzman and his group at the Complutense University in Madrid.
They tested the safety and antitumoral action of THCÂ on a small group of patients with recurrentÂ glioblastoma, an aggressive form of brain cancer â and the results were encouraging.
ProjectÂ CBDÂ spoke to Guzman to find why, more than a decade later, progress has been so slow. One answer lies in the nature of cancer itself.
âCancer is a very complex disease,â says Guzman. âThere are at least 150 different types of cancer from a histological point of view and there are hundreds if not thousands from a molecular or genetic profile standpoint. So when we speak about cannabis or any treatment for cancer,Â first you should define what type of cancer we are dealing with because itâs really unlikely that a unique substance or a mixture of related substances, as is the case in cannabis, will be effective in all types of cancer.â
How far away are we from getting the solid clinical evidence necessary to convince the medical profession that cannabis is a serious anticancer treatment?
To this date, all cannabis-based clinical trials have focused on patients with glioblastoma.Â GWÂ Pharmaceuticals followed up Guzmanâs pilot study with a yet unpublished phase I/IIÂ trial using Sativex, a 1:1Â THC:CBDÂ sublingual tincture, alongside temozolomide, the standard chemotherapy treatment for glioblastoma.
According to a 2017Â GWÂ Pharma press release,Â administering a combination of Sativex and temozolomide increased one year survival rate by 30% and increased the median survival to 550 days from 369 days with temozolomide alone.
â[TheÂ GWÂ study] is the first and so far the only trial that has been conducted on cannabinoids and cancer that is more robust, that it is controlled by placebo, and is randomized,â says Guzman. âItâs also a double-blind trial in which neither the patient nor the doctor knows whether the patient is taking Sativex or the placebo.
âThere are at least 150 different types of cancer from a histological point of view and there are hundreds if not thousands from a molecular or genetic profile standpoint.â
âThat trial was also promising. It has enhanced our optimism that maybe cannabinoid drugs can have an anti-tumour effect, at least in glioblastoma and at least in the relapsing phase. But we have very little clinical information only for one specific type of cancer. I hope that other cancers will be treated with cannabinoids in the frame of a controlled clinical trial. But to date we have nothing.â
Two further phaseÂ IIÂ glioblastoma clinical studies are also about to commence. This time, Guzmanâs group will be assessing whether a 1:1Â THC:CBDÂ ratio combined with conventional cancer treatment is effective as a first line treatment rather than a relapsing state.
Guzman: âDoing clinical research with cannabinoids is very complicated becauseÂ THC, which to me is the main active ingredient in cannabis, is controlled by the United Nations and is a schedule 1 drug. So, it is subjected to very strong restrictions in the production, manufacturing and exporting, etc. That means many clinicians and investors get frightened. They donât want to get into so much bureaucracy and they prefer to go for substances that are not classified as schedule 1. In general, my experience is thatÂ the bar that is set for cannabinoid clinical trials is higher than for other substances.â
The notable absence of pharmaceutical companies in cannabis-based drug development may be holding up progress.
Dr. Guzman suggests the notable absence of pharmaceutical companies in cannabis-based drug development may also be holding up progress. And an Australian study (5) investigating tolerability of different cannabinoid combinations alongside chemo, radiotherapy or immunotherapy is also currently recruiting.
As exciting as these initial clinical findings might seem, progress is still painfully slow considering how long scientists like Guzman have been researching the antitumoral potential the cannabis plant holds. It seems like the odds are stacked against a cannabis-based anticancer drug ever making it to market.
âClinical trials are very much controlled by Big Pharma companies who have the financial means and resources. Philosophically speaking, Iâm against the protection of the drug, but on the other hand, the pharma companies are not going to make any movement in any field unless they have the possibility to protect, to patent their products or the indications of their products. So that makes cannabis research more complicated because cannabinoids are natural products and can be extracted from the plant by anyone.â
One way to navigate the intellectual property quagmire is to concentrate on rare conditions with an âorphanâ status.Â Developing a drug forÂ orphan diseasesÂ can be an easier route to gainingÂ FDAÂ marketing approval and enjoys various incentives such as tax breaks. Orphan status also allows for usually unpatentable substances such as isolated cannabinoids to be awarded exclusivity â and is likely the reason why the likes ofÂ GWÂ Pharmaceuticals are concentrating on rare cancers like glioblastoma.
We all have to work hand in hand to normalize cannabis use in the medical community â otherwise itâs going to be almost impossible.
Another avenue is to patent specific cannabinoid combinations and ratios.Â This is another speciality ofÂ GWÂ Pharma.
Guzman: âBasically the whole cannabis field is mined withÂ GWÂ patents. So, whenever a new company starts to get interested in the field and they make a first overview of how the patent situation is, many times they leave because they realize that everything is basically controlled byÂ GWÂ Pharma. They have been very intelligent in that respect and they are basically the owners of all the intellectual property rights, all active rights and future rights in this field. So that also scares companies.â
Strategic decisions made in drug company boardrooms stalling the development of cannabinoid-based anticancer drugs means patients like George Gannon have little alternative but to figure out how to source their own cannabis oil, with all the difficulties that entails. Given the life-or-death stakes involved, Guzman does not begrudge someoneâs decision to use cannabis oil for cancer. But he feels that a patientâs decision should be guided by common sense.
âFirst try toÂ get a standardized preparation,â Guzman says. âOne has to know at least how muchÂ THCÂ andÂ CBDÂ is present in the preparation, not âIâm just taking cannabis.â There are a million types of cannabis. So try to get to know how muchÂ THC,Â CBDÂ and other well-known active ingredients are present.
âAnd if you are using cannabis oil as a treatment, know at least that the oil has been produced withÂ good agricultural practicesÂ and isÂ not contaminatedÂ by different types of toxic substances: organic solvent residues, pesticides, heavy metals, mould etc.â
âI would include a regime of administrationÂ starting from very little, increasing over 3 or 4 weeks, until one gets a standard dose that is well tolerated and at least overtly efficient. Second, I would combineÂ THCÂ andÂ CBD, starting with moreÂ CBDÂ and then includingÂ THCÂ to get it to a final balanced preparation. I canât say exactly what is a balanced. Usually you can go for a ratio of say 1:5 ratio ofÂ THC:CBD.
âThird, as cannabinoids accumulate in the body because they are very lipophilic, in theory, receptors can desensitize and lose response. So, Iâm in favor of including someÂ âwash outâ periodsÂ from time to time when at leastÂ THCÂ is taken out. I would say for instance 3 weeks of cannabis plus 4 or 5 days of wash-out, so there is time forÂ CB1Â [cannabinoid] receptors to get re-sensitized.â
Many patients feel uncomfortable when faced with the question of whether or not to tell their oncologist about taking cannabis during cancer treatment. For Guzman, informing the medical team in charge of care is not only a matter of safety, but a major way of increasing awareness about cannabis within the medical profession itself.
âI think patients are very important, he says. âThey are key players in this effort, and they have to push for cannabis to get into mainstream medicine. And one of the ways is simply by normalizing its use by patients. And yes, itâs likely that in some instances the physician is going to react negatively. But we have to try.
âBefore I retire,â Guzman continues, âIâd like to know that using cannabis as a cancer treatment has been successful. But at the moment we donât know. There are someÂ preclinical signals, and also some very tiny clinical signals supporting that there may be an anticancer effect of cannabinoids.
âWe have to improve that. And the evidence must come from different sites. Not only controlled clinical studies, but also observational studies, case studies that are reported by doctors about individual patients, and also the active role that I believe patients must play.Â They have to push. They have to speak about it.Â We are many different actors, and altogether we have to work hand in hand, otherwise itâs going to be almost impossible.â
Mary Biles is a journalist, blogger and educator with a background in holistic health. Based between theÂ UKÂ and Spain, she is committed to accurately reporting advances in medical cannabis research.