Abstract
Background: Cannabinoid extracts may have anticancer properties, which can improve cancer treatment outcomes. The aim of this review is to determine the potentially utility of cannabinoids in the treatment of pancreatic cancer.Methods: A literature review focused on the biological effects of cannabinoids in cancer treatment, with a focus on pancreatic cancer, was conducted. In vitro and in vivo studies that investigated the effects of cannabinoids in pancreatic cancer were identified and potential mechanisms of action were assessed.Results: Cannabinol receptors have been identified in pancreatic cancer with several studies showing in vitro antiproliferative and proapoptotic effects. The main active substances found in cannabis plants are cannabidiol (CBD) and tetrahydrocannabinol (THC). There effects are predominately mediated through, but not limited to cannabinoid receptor-1, cannabinoid receptor-2, and G-protein-coupled receptor 55 pathways. In vitro studies consistently demonstrated tumor growth-inhibiting effects with CBD, THC, and synthetic derivatives. Synergistic treatment effects have been shown in two studies with the combination of CBD/synthetic cannabinoid receptor ligands and chemotherapy in xenograft and genetically modified spontaneous pancreatic cancer models. There are, however, no clinical studies to date showing treatment benefits in patients with pancreatic cancer.Conclusions: Cannabinoids may be an effective adjunct for the treatment of pancreatic cancer. Data on the anticancer effectiveness of various cannabinoid formulations, treatment dosing, precise mode of action, and clinical studies are lacking.
Highlights
Cannabis plants contain more than 400 chemical compounds, over 60 of them are phytocannabinoid entities, including delta8-THC (d8-THC), cannabinol (CBN), cannabicyclol (CBL), cannabichromene (CBC), and cannabigerol (CBG); THC and CBD are recognized as the two main substances, THC, CBD, and CBN have mostly been used in different studies.[8,11,12,13]
Studies reveal that the THC:CBD ratio in C. sativa is generally higher than C. indica
In a study by Michalski et al.,[49] the effects of cannabinoids in pancreatic cells were investigated, with identification of cannabinoid receptor expression in several human pancreatic cancer cell lines and human pancreatic cancer biopsies. These results indicated that activation of cannabinoid receptors, Cannabinoid receptor-2 (CB2), may induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells
Summary
There are more than 60 phytocannabinoid entities found in cannabis plant extracts, among which there are currently two of main clinical interest: cannabidiol (CBD) and tetrahydrocannabinol (THC).[7,8] Endocannabinoids are endogenous cannabinoids that include anandamide (AEA) and 2-arachidonoylglycerol (2-AG), involved in a variety of physiological and cognitive processes. In vitro and in vivo studies that investigated the effects of cannabinoids in pancreatic cancer were identified and potential mechanisms of action were assessed. In vitro studies consistently demonstrated tumor growth-inhibiting effects with CBD, THC, and synthetic derivatives. Synergistic treatment effects have been shown in two studies with the combination of CBD/synthetic cannabinoid receptor ligands and chemotherapy in xenograft and genetically modified spontaneous pancreatic cancer models. Data on the anticancer effectiveness of various cannabinoid formulations, treatment dosing, precise mode of action, and clinical studies are lacking
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