Cannabinoids in the Modulation of Oxidative Signaling

Abstract

Cannabis sativa-derived compounds, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and components of the endocannabinoids system, such as N-arachidonoylethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), are extensively studied to investigate their numerous biological effects, including powerful antioxidant effects. Indeed, a series of recent studies have indicated that many disorders are characterized by alterations in the intracellular antioxidant system, which lead to biological macromolecule damage. These pathological conditions are characterized by an unbalanced, and most often increased, reactive oxygen species (ROS) production. For this study, it was of interest to investigate and recapitulate the antioxidant properties of these natural compounds, for the most part CBD and THC, on the production of ROS and the modulation of the intracellular redox state, with an emphasis on their use in various pathological conditions in which the reduction of ROS can be clinically useful, such as neurodegenerative disorders, inflammatory conditions, autoimmunity, and cancers. The further development of ROS-based fundamental research focused on cannabis sativa-derived compounds could be beneficial for future clinical applications.

Keywords: ROS; cancer; cannabinoids; inflammation; neurodegeneration; oxidative stress.

Figure 1

Schematic representation of the antioxidant effects of Cannabis sativa derivatives. Both of the two main phytocannabinoids, THC and CBD, have been found to be beneficial to different classes of pathologies owing to their antioxidant effects.

Figure 2

Schematic overview of CBD inhibitory effects on ROS cellular production. CBD modulation of oxidative stress is the basis of its effectiveness in ameliorating the symptoms of disease.

Figure 3

Cannabinoids and neurodegenerative diseases. In many neurological disorders there are incremented secretions of neurotoxic agents, such as ROS. The increment of ROS leads to NFkB activation and transduction, with the subsequent production of pro-inflammatory cytokines, such as TNF-α, IL-6, IFN-β and IL-1β. In neurological disorders, the action of CBD and THC provides neuroprotective effects through antioxidant and anti-inflammatory properties and through the activation of CB1 and CB2 to alleviate neurotoxicity.