The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids

Abstract

As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer stem cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…548), and in vivo in the presence of a PPAR␥ antagonist (713). Furthermore, CBD is able to inhibit cancer cell invasion and metastasis (478,548,715).…”

“…548), and in vivo in the presence of a PPAR␥ antagonist (713). Furthermore, CBD is able to inhibit cancer cell invasion and metastasis (478,548,715). These actions, in highly aggressive human breast cancer cells, are in part mediated by inhibition of epidermal growth factor (EGF), NF-B, ERK/AKT, and matrix metalloproteinase 2 and 9 signaling pathways (238).…”

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

“…Other studies have shown the ability of cannabinoids to affect cellular signalling pathway/s essential for cell survival and growth Kogan, 2005). Some studies have also demonstrated and suggested the involvement of autophagy in the mechanism of cannabinoidinduced cytotoxicity (Armstrong et al 2015;Vara et al, 2011;McAllister et al, 2015).…”

Cannabidiol Reduces Leukemic Cell Size – But Is It Important?

“…The non-psychoactive nature of cannabidiol (CBD), has prompted many studies, both in vivo and in vitro , that support a role for CBD in tumor regression and inhibition of cell viability through reactive oxygen species (ROS)-driven and caspase-dependent apoptosis (reviewed by McAllister et al, 2015). However, the anti-cancer potential of CBD has not been translated into the clinic.…”