Diversity of molecular targets and signaling pathways for CBD

Pharmacol Res Perspect. 2020 Dec;8(6):e00682. doi: 10.1002/prp2.682.

Abstract

Cannabidiol (CBD) is the second most abundant component of the Cannabis plant and is known to have effects distinct from Δ9 -tetrahydrocannabinol (THC). Many studies that examined the behavioral effects of CBD concluded that it lacks the psychotomimetic effects attributed to THC. However, CBD was shown to have a broad spectrum of effects on several conditions such as anxiety, inflammation, neuropathic pain, and epilepsy. It is currently thought that CBD engages different targets and hence CBD's effects are thought to be due to multiple molecular mechanisms of action. A well-accepted set of targets include GPCRs and ion channels, with the serotonin 5-HT1A receptor and the transient receptor potential cation channel TRPV1 channel being the two main targets. CBD has also been thought to target G protein-coupled receptors (GPCRs) such as cannabinoid and opioid receptors. Other studies have suggested a role for additional GPCRs and ion channels as targets of CBD. Currently, the clinical efficacy of CBD is not completely understood. Evidence derived from randomized clinical trials, in vitro and in vivo models and real-world observations support the use of CBD as a drug treatment option for anxiety, neuropathy, and many other conditions. Hence an understanding of the current status of the field as it relates to the targets for CBD is of great interest so, in this review, we include findings from recent studies that highlight these main targets.

Keywords: Gi/0 coupled receptors; binding sites; cannabidiol; ion channels; µ-CB1 heteromers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cannabidiol / administration & dosage*
  • Cannabidiol / metabolism*
  • Humans
  • Molecular Targeted Therapy / methods*
  • Molecular Targeted Therapy / trends
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / agonists
  • Receptor, Cannabinoid, CB2 / metabolism
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptors, Dopamine / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology

Substances

  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Receptors, Dopamine
  • Receptors, G-Protein-Coupled
  • Receptor, Serotonin, 5-HT1A
  • Cannabidiol