Cannabinoids Anticancer Mechanisms

The palliative effects of cannabinoids on cancer-related symptoms are well established. In fact, many drugs comprised of delta-9-tetrahydrocannabinol (THC) or its synthetic analogues are currently approved in Canada for use in the management of chemotherapy-induced nausea and vomiting, pain relief, and appetite stimulation.

While this may provide adequate treatment to the symptoms endured by cancer patients, what if cannabis can all together treat and cure cancer?

Latest discoveries on cannabinoids and their anticancer properties focus on their molecular mechanisms of action and have been discussed in a recently published review article in Current Oncology, a peer-reviewed journal (Velasco, Sanchez, & Guzman, 2016). It is important to begin by understanding that our body possesses an endogenous cannabinoid system.

Endogenous meaning these substances originated from within our organism. In fact, we have endocannabinoids, their receptors and a suite of enzymes responsible for their synthesis, transport and degradation. Cannabinoids such as THC from cannabis are able to exert their biological effects by binding to the same receptors as endogenous cannabinoids. Cannabinoids from cannabis are able to bind to endogenous receptors, namely cannabinoid-specific receptors CB1 and CB2. These receptors have been found in many types of cancer cells providing a novel approach to the targeted treatment of various types of cancer.

Several studies have highlighted the importance of cannabinoid receptors in the suppression of tumour growth. In a study using a mouse model of colon cancer, the deletion of CB1 receptors accelerated intestinal tumour growth. Conversely, in another study on colon cancer induced mice, increased levels of endocannabinoids resulted in decreased levels of cancerous precursors. Studies have also shown that when endocannabinoid degrading enzymes are removed, tumour growth in mice saw a marked decrease.

Cancer cells are rogue cells that grow and proliferate at a rapid and unregulated pace. These cells occur frequently in our body and are recognized and destroyed by our immune cells. When this fails, cancer cells over-proliferate leading to the formation of tumours, otherwise known as tumorigenesis. Cannabinoids primarily affect cancer cell proliferation by triggering pathways leading to programmed cell death or apoptosis.

Studies have shown that THC and other cannabinoids when bound to CB1 and CB2 receptors can stimulate the production of an apoptosis-inducing compound known as ceramide. This lipid molecule has even been termed the “tumour suppressor lipid” due to its damaging effects on cancer cells.

Due to the emergence of such promising preclinical data surrounding cannabinoids, clinical trials are underway to assess their anticancer and antitumour effects. Although only in phase I of clinical trials involving 9 patients with glioblastoma, a form of brain cancer, the intracranial administration of THC has led to a decrease in tumour growth rate observed by magnetic resonance imaging. In 2 patients, treatment with THC has led to the regulation of pivotal biomarkers involved in programmed cell death, inhibition of cell proliferation and a decrease in growth factors responsible for vasculature formation in tumours.

It should also be noted that these patients have recurrent glioblastoma meaning conventional therapy had previously failed. While these findings are encouraging, no statistical significance can be ascertained due to the limited number of patients involved in this study.

Ongoing clinical trials involving combinational therapy with oral chemotherapy drugs and THC and cannabidiol (CBD) are underway. These trials are currently in phase II and will likely shed some light on the efficacy of cannabinoid therapy in the treatment of cancer patients.

Cannabis provides a real treasure trove of compounds including THC and CBD and their interaction in symphony is still poorly understood. This will prove to be an issue for the acceptance of cannabis as a therapeutic drug since pure compounds are preferred for standardization over complex molecular cocktails. Other challenges include the route of administration as intracranial delivery has its obvious limitations.

Future research is urgently needed and we should anticipate an approach more focused on oral or oromucosal routes of administration and comparisons of pure substances versus cannabis extracts containing the complete mixture of cannabinoids.

Works Cited

Velasco, G., Sanchez, C., & Guzman, M. (2016). Anticancer mechanisms of cannabinoids. Current Oncology, 23(2): S23-S32.