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Updated: Jun 18, 2025

Tobacco Hornworm as an Insect Model System for Cannabinoid Pre-clinical Studies
Published on: December 29, 2021
Unlocking the Reverse Targeting Mechanisms of Cannabidiol: Unveiling New Therapeutic Avenues
Wen Zeng1,2, Yifei Wang1, Rui Gao1
1School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.
None:
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the main components of Cannabis sativa plants, have attracted a significant amount of attention due to their biological activities. This study identified GPR18 as the target of partial agonist CBD activating the p42/p44 MAPK pathway leading to migration of endometrial epithelial cells. Induced fit docking (IFD) showed that the affinity of THC for GPR18 is higher than that of CBD, and molecular dynamics (MD) simulations showed that CBD-GPR18 complexes at 130/200 ns might have stable conformations, potentially activating GPR18 by changing the distances of key residues in its active pocket. In contrast, THC maintains "metastable" conformations, generating a "shrinking space" leading to full agonism of THC by adding mechanical constraints in GPR18's active pocket. Steered molecular dynamics (SMD) revealed GPR18's active pocket was influenced more by CBD's partial agonism compared with THC. This combined IFD-MD-SMD method may be used to explain the mechanism of activation of partial or full agonists of GPR18.
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