Medicinal Cannabis and Cancer: what is new??
The FDA has approved several drugs that we will call cannabinoid-based (i.e. they are not naturally derived but synthetic): dronabinol (Marinol and Syndros, delta-9-THC), and nabilone (Cesamet, THC-similar). As of June 25, 2018, the FDA approved Epidiolex (cannabidiol naturally derived from cannabis) for two rare and severe forms of epilepsy, marking the first time a non-synthetic cannabinoid has been approved in the United States. However, the first regulatory approval for a naturally-derived cannabis product in North America was given by Health Canada for nabiximols (Sativex) for symptomatic relief of neuropathic pain (2005) and muscle spasticity (2010) from multiple sclerosis. Nabiximols is a formulated extract of C. sativa with a THC:CBD ratio of 1:1 as well as other cannabinoid and non-cannabinoid components.
Terpenoids and flavonoids are responsible for the color and aroma of plants and also serve biological functions.
An hypothesis that has received a lot of attention is that cannabis has benefits on cancer that is maximized by an 'entourage effect', meaning that all the individual components of the plant work together to create an effect that's greater than the effect of any one component. Blasco-Benito et al published in 2018 a study that compared the antitumor effects of THC alone compared to a whole plant extract and found that the extract was more potent than THC in cell culture and animal models of ER+, HER+ and triple negative breast cancer. Likewise, the extract was synergistic with tamoxifen, lapatinib and cisplatin chemotherapy in those respective cancer types. The authors also identified that the enhanced potency of the extract did not appear to be due to the 5 most abundant terpenes in the extract, consistent with the theory that the potency was due to the cannabinoid content.
In another Taha et al conducted a retrospective observational study and reviewed the charts of 140 patients with advanced melanoma, non-small cell lung cancer and renal cell carcinoma who received nivolumab. 89 patients received nivolumab and 51 patients received cannabis with nivolumab. The authors found that the only significant factor that lowered the response rate to immunotherapy was cannabis (37.5% for nivolumab, 15.9% who received both (odds ratio 3.13; 95% CI 1.24-8.13, p=0.02). However, progression-free survival and overall survival was not effected by cannabis. Since this is a retrospective study and subject to numerous confounding factors, it is mainly a precautionary study that warrants additional research before making any definitive conclusions.
1. Abrams DI. Cannabis and cancer - decoding the connection. San Fran Med 89(5): 28-29 2016
2. Guindon J and Hohmann AG. The endocannabinoid system and cancer: therapeutic implication. Br J Pharm 163: 1447-63 2011
3. Casanova ML, Blazquez C, Martinez-Palacio J et al. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J Clin Invest 111(1):43-50 2003
4. Guzman M, Duarte MJ, Blazquez C et al. A pilot clinical study of delta-9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer 95:197-203 2006
5. Twelves C, Short S, Wright S et al. A two-part safety and exploratory efficacy randomized double-blind placebo-controlled study of a 1:1 ratio of the cannabinoids cannabidiol and delta-9-tetrahydrocannabinol (CBD:THC) plus dose-intense temozolomide in patients with recurrent glioblastoma multiforme (GB). J Clin Onc 35: 2046 (abstract) 2017
6. Blasco-Benito S, Seijo-Vila M, Caro-Villalobos M, et al. Appraising the 'entourage effect': Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer. Biochem Pharm published online 6/27/18
7. Hay M, Thomas DW, Craighead JL et al. Clinical development success rates for investigational drugs. Nature Biotechnology 32:40-51 2014)
8. Taha T, Talhamy S, Wollner M, et al. The effect of cannabis use on tumor response to nivolumab in patients with advanced malignancies. Oral presentation at: ESMO 2017 Congress; Abstract 1545PD 2017
9. Maida V, Daeninck PJ. A user's guide to cannabinoid therapies in oncology. Curr Onc 23(6): 398-406 2016
10. Sledzinski P, Zyeland J, Slomski R et al. The current state and future perspectives of cannabinoids in cancer biology. Cancer Med 7(3): 765-75 2018
11. Abrams DI. Using medical cannabis in an oncology practice. Onc J 1-4 2016
12. Abrams DI. Integrating cannabis into cancer care. Curr oncol 23(S2):S8-14 2016
13. Abrams DI, Guzman M. Cannabis in cancer care. Clin Pharm Ther published online 2015
|Tags:NewsEvidence Based ResearchCancer|