A conversation with scientists about cannabis therapy used against one of the deadliest cancers known: glioblastoma. The investigation moves forward with the study of cannabinoids and their antitumour effects.
The investigation about therapeutic, medicinal effects of marijuana on the human body is driving a change towards more open, tolerant policies on cannabis worldwide. A growing number of governments are changing their national legislations to include alternative therapies based on cannabis to treat many diseases, like Alzheimer's, the spasms caused by multiple sclerosis, anorexia, cachexia or glaucoma, amongst many others.
What is glioblastoma?
“Glioblastoma is a kind of primary brain tumour that is highly aggresive”, explains investigator Esther Martínez, graduate of the Universidad Politécnica de Valencia, Spain, in biotechnology. Her field of study has always been linked to oncology. PhD in biochemistry, molecular biology, biomedicine and biotechnology in Universidad Complutense de Madrid, Martínez explains: “survival is very low, 12 to 15 months after diagnosis”.
“This investigation is not new. It started more than 10 years ago, with the clinical tests performed by Manuel Guzmán in the Universidad Complutense, in Madrid”, says Dr. Mariano García de Palau, graduate of the Universitat de Barcelona and specialist/clinical advisor for treatment with cannabinoids. “Glioblastoma is deadly in all patients, adults as well as children over 2 years of age”.
García de Palau tells us the tumour can appear in almost any part of the brain. “The worst harm does not come from the formation itself, but from the pressure it applies over fundamental parts of the brain when it grows. That makes certain neurologic symptoms appear, like talking difficulties, trouble making movements, etcetera”.
“Therapies nowadays are not too effective”, says doctor Martinez. “The current treatment is based in surgery, it consists in extracting the largest possible part of the tumor. The goal now is to improve techniques of resection of the tumor, to make its return impossible. Surgery is followed by radiotherapy and chemotherapy with alkylating agents (like temozolomide). After attacking the tumour with these therapies, nothing remains. Then we wait, maybe a couple years. But this cancer shows a high recurrence, meaning it comes back after having been cured”, says García de Palau. “Then all or some of the therapies we mentioned are used again”.
“Tumour cells have cannabinoid receivers. This means they can be affected by cannabinoids such as THC or CBD. In these preclinical studies, it has been proven that THC, through cannabinoid receivers, induces cellular death in tumour cells, activating a process of apoptosis through autophagy”, says Esther Martínez. Apoptosis is a process of programmed cellular death produced by the organism itself, with the goal of controlling its development and growth. This has vital importance in eliminating damaged cells, and, in this case, preventing the appearance of cancer. The genetic signal that informs the cell when to start a process of autophagy (devouring itself) to recycle is interrupted in the cancer cycle. The new therapy seems to reestablish that signal, supposedly by a reaction of the endocannabinoid system.
“Although we know part of the molecular mechanism by which cannabinoids induce cancer cells death, there is a lot to be disentangled. Like, for instance, why these compounds have the ability to affect the tumour cells in a 'selective' kind of way. For some reason, the pro apoptosis effect is not detected in non-tumour cells, even though they have cannabinoid receivers”. Doctor Martínez points out that preclinic tests are being performed in labs to treat other types of cancer, such as prostatic cancer or breast cancer.
“It has been proven that therapies that combine cannabis with temozolomide work better than chemotherapy alone, or cannabis alone”, says García de Palau. “The route of administration of this cannabis is usually through extracts from the natural substance. It is presented in suspension in oil for oral, sublingual administration. The active elements travel from the sublingual space into the bloodstream in the carotide artery, reaching the brain in the fastest way”.
When will we learn more?
Esther Martinez tells us about the development of the investigation started more than a decade ago, with the emergence of three studies in our country. The first one, performed between 2003 and 2006, included the administration of THC via intratumour in patients following second-line treatment, after the tumor's recurrence. The second one (2014-2016), also in second line cancer, investigated and proved the safety and efficacy if cannabinoids in combination with temozolomide. Specifically, the study was performed with the drug Sativex, of GW Pharma, composed of a mix 1:1 of THC:CBD. “The third study is still pending approval by the Spanish Agency of drugs, but we are expecting that to happen soon. It would be a first line treatment, using cannabinoids in combination with conventional therapies from the beginning”, asserted the scientist.
These advances need to be taken carefully. “It is a path for investigation. The results obtained so far are promising, but more studies need to be done. There are so few treatments that any advance against glioblastoma is good. But I believe we need to create a caring regulation that helps increasing survival and life standards of patients who are willing to try. They should have the right to choose, just like the recreational marijuana consumers. The stigma over the users should disappear. Maybe that way professionals of medicine could orientate about these therapies, always in combination with conventional therapies that have a proven clinic effect”, says Martinez.
“Hope is brought by the opportunity of investigating these methods without obstacles. We hope that legalization of cannabis finally arrives so that we can perform more clinical tests”, says García de Palau.
You can find more information on the investigation of doctor Martinez in the text repository PUBMED. She is currently working in Dr. Guillermo Velasco's team in Universidad Complutense de Madrid.
Doctor Mariano García is director of the Kalapa Clinic in Barcelona. He is a member of the International Association for Cannabinoid Medicines and vocal of the Obsevatorio Español de Cannabis Medicinal.