Narrative Review: Phytocannabinoids and their Potential Use as a Phytochemotherapy

Abstract

Cannabis sativa L. has been used as an herbal medicine for centuries. This plant is a natural source of cannabinoids, including Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the two major phytocannabinoids that have been a recently interested research topic on their therapeutic properties. The human endocannabinoid system generally consists of receptors, endogenous ligands, and metabolizing enzymes, and plays an important role in various physiological and pathological effects. Based on cancer therapy, phytocannabinoids have mainly been used for palliative care treatment, i.e. relieving nausea and vomiting caused by chemotherapy and stimulating appetite. Additionally, in many preclinical experiments, including in vitro and in vivo studies, cannabinoids have exhibited anticancer effects against numerous cancer cell lines through various mechanisms. For example, THC induced apoptosis of cancer cells via cannabinoid receptors by a stimulation of ceramide synthesis led to an activation of the endoplasmic reticulum stress-related signaling pathway, and the induction of autophagy through a calmodulin-activated kinase kinase β. In contrast, the anticancer activity of CBD is related to other types of receptors, i.e. orphan G-protein coupled receptor 55 (GPR55), transient receptor potential vanilloid receptor 1 (TRPV1), transient receptor potential melastatin 8 (TRPM8), which mainly relied on the stimulation of reactive oxygen species (ROS) production, leading to induced cancer cell death. Although, there are many reports on anticancer properties of phytocannabinoids, in vitro and in vivo, high quality clinical trials concerning their efficacy and safety are still essential to approve their potential use as a phytochemotherapy.