By Narda Robinson, DO, DVM
Questions about cannabis, including its risks, benefits and legality, just keep coming. Fortunately, as data accrue, evidence is growing that can support and inform our recommendations regarding cannabis, both pro and con.
Take, for instance, the questions that our clients are beginning to ask about treating tumors with cannabis. An informative website run by the National Cancer Institute (NCI) provides a well-referenced page called “Cannabis and Cannabinoids—Health Professional Version (PDQ).”1 This page discusses the history, preclinical studies and human clinical trials regarding cannabis for cancer patients. The authors summarize the adverse effects and update the site regularly.
Written and maintained by the PDQ Integrative, Alternative and Complementary Therapies editorial board, a group that is editorially independent of NCI, the web page—found here—is provided “as a resource to inform and assist clinicians who care for cancer patients, providing comprehensive, peer-reviewed, evidence-based information about the use of cannabis and cannabinoids in the treatment of people with cancer.”
On the anti-tumor activity of cannabis, the NCI summary describes a pilot clinical trial involving nine human patients diagnosed with recurrent glioblastoma multiforme.2 All nine patients had failed standard approaches of surgery and radiation therapy and showed clear evidence of tumor progression. The study included four men and five women with a mean age of 55, constituting a cohort considered representative of recurrent glioblastoma multiforme patients seen in private practice.
In that this was a Phase 1 clinical trial, the primary end point was determination of the safety of intracranial cannabinoid administration, although the researchers also measured the effects of delta-9-tetrahydrocannabinol (THC) on the length of survival and a variety of tumor cell parameters.
All patients received a craniotomy in which surgeons resected the recurring tumor and created a cavity within it that would receive a solution imbued with THC. Researchers confirmed the diagnosis of glioblastoma multiforme with a biopsy for every case. They then placed an infusion catheter into the resection cavity, providing an avenue for daily deposition of an aliquot of THC solution (100 mg/ml) into the brain following several days of postoperative recovery.
Patients were monitored through a battery of tests after the procedure, including repeated neurological and other examinations as well as multiple magnetic resonance imaging and computed tomography scans. This intensive surveillance watched not only for potential toxicity of the intracerebral THC administration but also changes in tumor size.
Over the follow-up period, THC administration did not cause any significant alterations in neurologic, biochemical, hematologic and general physical parameters. Overall, THC delivery intracranially was found to be safe and mostly devoid of psychoactive effects.
Two of the nine patients in this group survived for approximately one year; median survival after the surgical operation for the tumor relapse was 24 weeks. In one of the patients who survived longer than expected, growth of the “extremely aggressive recurrent glioblastoma multiforme in the left temporal lobe” was “curbed for about nine weeks.”
Initially, the patient showed clear improvement of clinical symptoms (e.g., dysphasia and cranial hypertension disappeared and hemiparesis). In another patient, the tumor continued to grow, but clinical symptoms such as headache and hallucinations disappeared and motor function improved.
Researchers then examined the effects of THC on cells taken from the glioblastoma tumor biopsies. They found that THC reduced the number of viable cells in the cultures at least in part by promoting apoptosis. THC tended to decrease the vascularization of tumors in the cells from two patients, but the effect did not reach statistical significance.
Overall, the safety profile of THC in this pioneering study along with its potential anti-proliferative effects on tumor cells set the stage for future trials, not only with intratumoral injection but also other avenues of administration.
For example, a placebo-controlled clinical trial is being planned in the United Kingdom, again involving patients with recurrent glioblastoma. In this experiment, patients in the active treatment group will receive a cannabis product called Sativex along with temozolomide, an alkylating agent and oral chemotherapy drug. Sativex comes as a medicinal extract oromucosal spray and contains equal parts of THC and cannabidiol, or CBD, which is the nonpsychoactive cannabinoid found in predominance in hemp.
Mechanism of Action
How do cannabinoids fight tumors? A 2012 opinion piece in Nature Reviews summarized the general mechanisms of cannabinoid antitumor effects.3 In brief, cannabinoids hinder tumor progression by several means, including apoptosis induction (as aforementioned), inhibition of cancer cell proliferation and blockage of tumor angiogenesis through down-regulation of vascular endothelial growth factor in cancer cells.
Cannabinoids also harbor the potential to reduce the likelihood of metastasis by modulating biochemicals involved in the adhesion, migration and invasiveness of cancer cells. These chemicals include matrix metalloproteinase 2 (MMP2), tissue inhibitor of matrix metaolloproteinases 1 (TIMP1) and inhibitor of DNA binding 1 (ID1), as well as possibly other targets.
As the authors commented in this review, “Few plant species have been the subject of so much scientific, clinical and social debate as Cannabis sativa L. (marijuana). Preparations from this plant have been used for many centuries both medicinally and recreationally. However, the chemical structures of their unique active components—the cannabinoids—were not elucidated until the 1960s. Three decades later, the first solid clues on cannabinoid molecular action were established, which led to an impressive expansion of basic cannabinoid research and to a renaissance in the study of the therapeutic effects of cannabinoids in various fields, including oncology.”
Indeed, the best way forward may not be foregoing modern advancements in clinical oncology treatments but in blending the two in a truly integrative manner. As evidenced by a 2014 paper in Molecular Cancer Therapeutics, cannabinoids such as THC and CBD may be able to prime cells such as those from high-grade glioma to respond more favorably to ionizing radiation.4
This suggests a clinical benefit for glioma patients by utilizing both radiation and cannabis in combination, potentially allowing clinicians to treat with lower doses of radiation without sacrificing effectiveness.
- National Cancer Institute: PDQ Cannabis and Cannabinoids. Bethesda, MD: National Cancer Institute. Date last modified 04-21-16. Available at: www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq. Accessed on 04-28-16.
- Guzman M, Duarte MJ, Blazquez C, et al. “A pilot clinical study of delta-9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme.” British Journal of Cancer. 2006;95:197-203.
- Velasco G, Sanchez C, and Guzman M. “Towards the use of cannabinoids as antitumour agents.” Nature Reviews—Cancer. 2012;12:436-444.
- Scott KA, Dalgleish AG, and Liu WM. “The combination of cannabidiol and delta-9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model.” Mol Cancer Ther. 2014;1-13.
Dr. Narda Robinson, Dipl. ABMA, FAAMA, is an assistant professor at Colorado State University and president and CEO of CureCora, an integrative medical education center in Fort Collins, Colo. Columnists’ opinions do not necessarily reflect those of Veterinary Practice News.
Originally published in the June 2016 issue of Veterinary Practice News. Did you enjoy this article? Then subscribe today!