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Review
. 2023 Aug 9;28(16):5980.
doi: 10.3390/molecules28165980.

Molecular and Cellular Mechanisms of Action of Cannabidiol

Nadia Martinez Naya  1 , Jazmin Kelly  1 , Giuliana Corna  2   3 , Michele Golino  2   4 , Antonio Abbate  1   2 , Stefano Toldo  1
Affiliations
Review

Molecular and Cellular Mechanisms of Action of Cannabidiol

Nadia Martinez Naya et al. Molecules. .

Abstract

Cannabidiol (CBD) is the primary non-psychoactive chemical from Cannabis Sativa, a plant used for centuries for both recreational and medicinal purposes. CBD lacks the psychotropic effects of Δ9-tetrahydrocannabinol (Δ9-THC) and has shown great therapeutic potential. CBD exerts a wide spectrum of effects at a molecular, cellular, and organ level, affecting inflammation, oxidative damage, cell survival, pain, vasodilation, and excitability, among others, modifying many physiological and pathophysiological processes. There is evidence that CBD may be effective in treating several human disorders, like anxiety, chronic pain, psychiatric pathologies, cardiovascular diseases, and even cancer. Multiple cellular and pre-clinical studies using animal models of disease and several human trials have shown that CBD has an overall safe profile. In this review article, we summarize the pharmacokinetics data, the putative mechanisms of action of CBD, and the physiological effects reported in pre-clinical studies to give a comprehensive list of the findings and major effects attributed to this compound.

Keywords: CBD; cannabidiol; inflammation; mechanisms; molecular target.

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Conflict of interest statement

Antonio Abbate received research grant funding and has served as a paid scientific advisor to Implicit Biosciences, Kiniksa, Lilly, Merck, Novartis, Novo Nordisk, Olatec, R-Pharm, Serpin Pharma, and Swedish Orphan Biovitrum. Stefano Toldo has served as a paid scientific advisor to Cardiol Therapeutics and Novo Nordisk, and received research grant funding from Kiniksa, Olatec, Serpin Pharma, and Cardiol Therapeutics.

Figures

Figure 1
Figure 1
CBD and Δ9-THC chemical structures: cyclohexene ring (A–C) and aromatic ring (B).
Figure 2
Figure 2
CBD receptors and intracellular signaling. (A) CBD interacts with several cell surface and nuclear receptors, antagonizing PI3K/AKT, MAPK/ERK, and JAK/STAT pathways. CBD inhibits through PPARγ receptor DNA transcription of proinflammatory mediators. Moreover, CBD modifies membrane and organelle calcium channels, altering intracellular signaling. (B) CBD exerts indirect effects on cannabidiol receptors and affects the uptake of adenosine and GABA, reinforcing their signaling.
Figure 3
Figure 3
CBD effect on NF-κB pathway signaling. CBD decreases IRAK-1 and reverses the IkB degradation, ultimately reducing NF-κB translocation to the nucleus. Also, CBD suppresses NF-κB-mediated transcription by increasing anti-inflammatory STAT3 phosphorylation.
Figure 4
Figure 4
Immune cells regulated by CBD. CBD affects every stage of cellular inflammation, impacting the functionality of a wide range of immune cells by modifying a variety of mechanisms in favor of its immunosuppressive effect.
Figure 5
Figure 5
Effect of CBD ion channels. Myocardial action potential. Phase 0 (Depolarization); INa: Sodium current. Phase 1 (Sodium Channels Close). Phase 2 (Plateau); Ito: Transient outward potassium current; NCX: Sodium-calcium exchange; ICaL: Calcium current, calcium channel Type L. Phase 3 (Rapid Repolarization); IKur: potassium ultrarapid delayed rectifier current; IKs: Potassium slow-delayed rectifier; Ikr: Potassium rapid-activating delayed rectifier. Phase 4 (Resting Potential) IK-ATP: ATP-sensitive potassium channel; IKACh: muscarinic potassium channel.
See this image and copyright information in PMC

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