Cannabidiol modulation of oxidative stress and signalling

Abstract

Cannabidiol (CBD), one of the primary non-euphoric components in the Cannabis sativa L. plant, has undergone clinical development over the last number of years as a therapeutic for patients with Lennox-Gastaut syndrome and Dravet syndromes. This phytocannabinoid demonstrates functional and pharmacological diversity, and research data indicate that CBD is a comparable antioxidant to common antioxidants. This review gathers the latest knowledge regarding the impact of CBD on oxidative signalling, with focus on the proclivity of CBD to regulate antioxidants and control the production of reactive oxygen species. CBD is considered an attractive therapeutic agent for neuroimmune disorders, and a body of literature indicates that CBD can regulate redox function at multiple levels, with a range of downstream effects on cells and tissues. However, pro-oxidant capacity of CBD has also been reported, and hence caution must be applied when considering CBD from a therapeutic standpoint. Such pro- and antioxidant functions of CBD may be cell- and model-dependent, and may also be influenced by CBD dose, the duration of CBD treatment and the underlying pathology.

Cannabidiol Induces Cell Death in Human Lung Cancer Cells and Cancer Stem Cells

“…Interestingly. CBD exhibits both pro-and antioxidant functions (reviewed in [42]) dependent on CBD dose, incubation time, and more importantly, cell type. With respect to the H69 and H1299 cells, there was a modest increase in ROS levels in response to CBD both in adherent cells and in the spheres, comparable to the A549 spheres, again supporting that the effects of CBD are cell context-dependent.…”

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

“…CBD can also activate the TRPV1 channel, serotonin 1A (5-HT 1A ) receptors, and opioid receptors [24,172]. CBD has anti-inflammatory, anti-oxidative, anti-epileptic, analgesic, anti-neoplastic, sedative, neuroprotective, and anti-anxiety activities [173][174][175][176][177][178][179][180][181][182][183][184][185][186][187][188]. Moreover, CBD inhibits sebocyte lipogenesis by activating the TRPV4 ion channel that interferes with the pro-lipogenic ERK1/2 MAPK pathway [189].…”

Lipid-Based Molecules on Signaling Pathways in Autism Spectrum Disorder

“…According to primary findings, cannabinoids (CBs) regulate the redox balance by altering the level and activity of antioxidant molecules [ 70 ]. CBs target the regulation of redox-sensitive transcription factors, such as Nrf2 in microglia, indicating an important key role of Nrf2 in initiating the transcription of antioxidant and cytoprotective genes [ 70 ]. CB modulates the expression of the antioxidant enzyme heme oxygenase 1, suggesting a role for CBD in regulating cellular ROS levels [ 70 ].…”

“…CBs target the regulation of redox-sensitive transcription factors, such as Nrf2 in microglia, indicating an important key role of Nrf2 in initiating the transcription of antioxidant and cytoprotective genes [ 70 ]. CB modulates the expression of the antioxidant enzyme heme oxygenase 1, suggesting a role for CBD in regulating cellular ROS levels [ 70 ]. CB can also modulate the important antioxidation protein superoxide dismutase and its metabolized activities, such as Cu-, Zn-, and Mn-SOD [ 70 ], and upregulate GSH levels, as well as, simultaneously, SOD1 and GPx activity, based on the finding that the administration of CB reduces the oxidized glutathione ratio (GSH/GSSG) in myocardial tissue of diabetic mice and prevents GSH depletion in cardiac tissue following cardiotoxicity [ 70 ].…”

“…CB modulates the expression of the antioxidant enzyme heme oxygenase 1, suggesting a role for CBD in regulating cellular ROS levels [ 70 ]. CB can also modulate the important antioxidation protein superoxide dismutase and its metabolized activities, such as Cu-, Zn-, and Mn-SOD [ 70 ], and upregulate GSH levels, as well as, simultaneously, SOD1 and GPx activity, based on the finding that the administration of CB reduces the oxidized glutathione ratio (GSH/GSSG) in myocardial tissue of diabetic mice and prevents GSH depletion in cardiac tissue following cardiotoxicity [ 70 ]. As endocannabinoid (eCB) interrupts free radical chain reactions via the electrophilic aromatic molecular region [ 70 ], eCB is closely related to antioxidant capacities.…”