The Polypharmacological Effects of Cannabidiol

Abstract

Cannabidiol (CBD) is a major phytocannabinoid present in Cannabis sativa (Linneo, 1753). This naturally occurring secondary metabolite does not induce intoxication or exhibit the characteristic profile of drugs of abuse from cannabis like Δ⁹-tetrahydrocannabinol (∆⁹-THC) does. In contrast to ∆⁹-THC, our knowledge of the neuro-molecular mechanisms of CBD is limited, and its pharmacology, which appears to be complex, has not yet been fully elucidated. The study of the pharmacological effects of CBD has grown exponentially in recent years, making it necessary to generate frequently updated reports on this important metabolite. In this article, a rationalized integration of the mechanisms of action of CBD on molecular targets and pharmacological implications in animal models and human diseases, such as epilepsy, pain, neuropsychiatric disorders, Alzheimer's disease, and inflammatory diseases, are presented. We identify around 56 different molecular targets for CBD, including enzymes and ion channels/metabotropic receptors involved in neurologic conditions. Herein, we compiled the knowledge found in the scientific literature on the multiple mechanisms of actions of CBD. The in vitro and in vivo findings are essential for fully understanding the polypharmacological nature of this natural product.

Keywords: Cannabis sativa L.; cannabidiol; multi-target; neurological conditions; polypharmacology.

Figure 1

Secondary metabolites of Cannabis sativa L. [5].

Figure 2

Chemical structures of cannabidiol and tetrahydrocannabinol.

Figure 3

Structure of cannabidiol (CBD) and its role such as agonist or * = positive allosteric modulator (PAM), antagonist, # = inverse agonist, and & = negative allosteric modulator (NAM) on multi-target receptors and enzymes associates with developed of diseases in vivo. Created with BioRender.com.

Figure 4

Molecular mechanism of CBD on epilepsy. Dotted lines refer to mechanisms recently suggested as probable based on in vitro experiments, which require verification on in vivo models. Created with Biorender.com.

Figure 5

Molecular mechanism of CBD on anxiety described in rat model. Dotted lines refer to hypothesized mechanisms. Created with Biorender.com.