Many drugs exert their influence through their attachment to a receptor site. Receptors are of two broad types – G-protein coupled receptors and ion channel receptors. CBD or cannabidiol is known to act at the cannabinoid receptors, CB1 and CB2. The active component of marijuana, THC, is believed to bind at the endogenous cannabinoid receptors, CB1, and CB2. Therefore, an understanding of how these receptors interact with various ligands, especially to CBD, cannabidiol, the other principal cannabinoid in marijuana and hemp, needs to be developed.
With a view to obtaining first principles explanation of the interactions, ab initio self-consistent field molecular orbital calculations have been performed on cannabidiol, endogenous cannabinoid anandamide, and Delta-9-tetrahydrocannabinol, THC, the psychoactive component in marijuana. The geometries of these drug ligands have been optimized to obtain the lowest energy structure for each compound using GAMESS with 6-311G basis set to determine if the structure or any of its analogs can fit with the receptor without steric hindrance. Electrostatic potential maps, molecular orbital contours, dipole moments, polarizabilities, and other electronic properties have been investigated to determine the effects of the electronic structure as well as geometric conformation of each. The electro-topological description of the dependence of binding of these compounds with the CB1, and CB2 is discussed, along with possible interaction 5-HT receptors as well, with an explanation derived from fundamental quantum mechanical properties. Figure 1 shows energy minimized geometry for CBD. Electronic structure and molecular orbitals are also discussed.

Cannabidiol energy optimized geometry 6311G

Anandamide, endogenous cannabinoid CB1, CB2 receptors

Dr. Sheryl Baldwin

Executive Director, Virginia Commonwealth University

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