Cancer: Enhacing the Efficacy of Cancer Treatment with CBD

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

Yasmin-Karim, M. Moreau 

2018

KEY TAKEAWAYS:

• Previous findings report CBD’s ability to inhibit tumor invasion and cancer metastasis
• 50% of dogs over 10 years of age have cancer and 20% of cats will develop cancer in their lifetime
  
• Superior tumor cell killing was achieved with CBD than with 4 Gy (unit of radiation dose) of RT alone
• Results support a greater effectiveness in killing tumor cells when combining CBD and radiotherapy (RT)
• CBD use in combination with RT increased the survival rates of the studied mice
• There is a clear demonstration of a bigger survival rate of CBD-treated mice comparing with the control group (no treatment)
• In situ (in the exact local) delivery of CBD with smart biomaterials allows bigger concentrations of CBD to reach its target
• CBD treatment occasioned an 80% survival rate (vs 50% in the control group) in mice with tumors, whereas the use of smart biomaterials loaded with CBD resulted in a 100% survival rates 

OBJECTIVES & HYPOTHESIS → Findings have reported CBD’s ability to inhibit tumor invasion and cancer metastasis. This indicates that CBD use in combination with other therapies, as radiotherapy (RT), could enhance the effectiveness of cancer treatments, while reducing RT doses to minimize its toxicities. Moreover, CBD’s biochemistry imposes inherent limits to intravenous and orally administration, which impacts its effectiveness as an anticancer agent. By these means, the study’s main objective was to explore the potential for enhancing the effectiveness of pancreatic and lung tumor cell kill via: (1) combination of CBD with RT and (2) use of smart radiotherapy biomaterials (SRB) loaded with CBD for sustained in situ delivery, which boosts CBD concentration at its target.

Smart biomaterials: intelligently custom-made materials with particular properties

In situ: in the exact location (of the tumor)

METHODS → Cultures of lung cancer cell lines, from both human and mouse and pancreatic cancer mouse cell lines were grown. Later on, these colonies were counted and a percent survival was calculated. In the in vivo study, cancer mouse models were created by subcutaneously implanting tumor cells.  Mice were then randomized into different cohorts: intratumoral injection of CBD (5 mg/kg); methanol injection in one control group; SRBs loaded with CBD (5mg/kg); SRBs loaded with methanol in the other control group.

RESULTS → In the in vitro studies, results showed greater effective tumor cell killing when combining CBD and RT. Although the synergy effect is well observed when combining both treatments, results demonstrate an even more surprising outcome – 5 μg of CBD was found to achieve greater tumor cell killing than 4 Gy (unit of radiation dose) of RT.

 Graphic 1: In vitro antitumor effect of cannabinoid (CBD). Percent survival of tumor cells is shown in the y-axis and CBD concentration in the x-axis. Graphic shows there’s a less percent survival of tumor cells when using 5 μg of CBD alone than when using 4 Gy of RT alone.

Meanwhile, in vivo studies revealed major increase in survival when employing CBD, in particular when using smart biomaterials for sustained delivery of CBD to tumor cells. Direct intratumoral injection of CBD demonstrates slight increase survival benefit compared to untreated mice. Later on, when comparing mice treated with empty SRBs, mice treated with CBD and mice treated with CBD-loaded SRB, the results shows significantly increased survival for the mice with CBD-loaded SRBs relative to the other groups. These can be explained by the fact that in situ delivery achieved with CBD-SRB allows direct delivery of 100% of the CBD to the tumor while minimizing off-target potential toxicities (which have so far limited clinical translation). Finally, in yet another study, the benefit of prolonged exposure of tumors to CBD is again observed, with 100% of the mice alive in the CBD-SRB group, compared to 80% of mice alive in the CBD group and only 50% in control group.

Graphic 2: Pilot study showing increased survival benefit of pancreatic tumor treated with (C) direct intratumoral injection of CBD compared to control and (D) using SRBs for sustained delivery of CBD.

Altogether, these results offer an approach for leveraging the antineoplastic activity of CBD to achieve enhanced therapeutic efficacy during cancer treatment with the possibility of addressing RT-related toxicity and CBD’s low bioavailability.