Pancreatic cancer is a devastating disease, with a five-year survival of less than 6%. Despite years of intensive research, pancreatic cancer remains one of the deadliest cancers worldwide, with mortality nearly mirroring incidence (Ilic, World J Gastroenterol, 2016). This is due, in part, to late detection of the disease, but also the lack of effective therapeutic strategies to combat the disease. There is an unmet need for more effective treatment strategies to improve outcomes.
There is a growing body of evidence supporting the role of cannabinoids in the management of cancer due to their antineoplastic, anticachectic, and analgesic potential. Anticancer activities of cannabinoids have been demonstrated for various malignant tumors including brain, breast, skin, blood, and recently, pancreatic cancer (Michalski, Int J Cancer, 2008).
Cannabidiol (CBD) as an Adjunct to Standard of Care Treatment
Although there has been limited research on the topic, several studies have suggested a relationship between changes in the endogenous endocannabinoid system and pancreatic cancer. A 2006 study of tumor tissue in Spain found higher levels of both CB1 and CB2 receptors on human pancreatic tumor biopsies. Expression of cannabinoid receptors was detected clearly in tumor nodules, but hardly found in surrounding healthy pancreatic tissue (Carracedo, Cancer Res, 2006).
A German study on the relationship between cannabinoid receptors, endocannabinoid metabolizing enzymes, and pancreatic ductal adenocarcinomas (PDAC) in post-mortem tissue samples demonstrated that the levels of these receptors and enzymes on pancreatic cancer cells may actually effect prognosis of PDAC patients.
Compared to healthy controls, the levels of cannabinoid receptors were generally upregulated in pancreatic cancer, suggesting an active role of these receptors in pancreatic carcinogenesis. Moreover, researchers found a negative correlation between the amount of cannabinoid receptors, specifically CB1, and patient survival. The median survival in the group with low CB1 staining in cancer cells was 16 months, versus six months for the group with a high CB1 staining (p=0.0011).
Researchers were also able to show that lower levels of endocannabinoid metabolizing enzymes were associated with shorter survival (Michalski, Int J Cancer, 2008). This body of research points to a relationship between changes in the endocannabinoid system and the lethality of pancreatic cancer, suggesting that a cannabinoid-based therapy may activate cell-death pathways primarily in tumor cells.
Given the relationship that appears to exist between changes in the endocannabinoid system and PDAC, it follows that cannabinoids may have a role in the treatment of pancreatic cancer.
Research have demonstrated that cannabinoids can induce apoptosis of pancreatic cells both in vitro and in vivo. Based on examination of in vitro pancreatic tumor cells, researchers have postulated that activation of CB2 cannabinoid receptors induced apoptosis of pancreatic tumor cells, based on dose-dependent decreases in cell viability in the lines tested. Researchers were also able to selectively induce apoptosis of pancreatic tumor cells in vivo in murine models (Carracedo, Cancer Res, 2006; Carracedo, Cancer Cell, 2006).
Another in vitro study suggests that cannabinoid derivatives can induce cell death in pancreatic cancer cell lines independent of cannabinoid receptor presence, possibly due to their lipophilic nature allowing them to cross cell membranes and disrupt cellular networks (Fogoli, FEBS, 2006).
More recent in vitro research has suggested that cannabinoids induce autophagy through AMP-activated kinase (AMPK), a sensor of energy status and homeostasis in cells. Research suggests that cannabinoids increase oxidative stress, activating AMPK in malignant pancreatic cells, ultimately promoting cell death (Dando, Cell Death Dis, 2013). While the mechanism of action still needs to be fully elucidated, evidence suggests that there are anti-tumor effects of cannabinoids in pancreatic adenocarcinomas.