Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol-dimethylheptyl at the type 1 and type 2 cannabinoid receptors.

ABSTRACT:

Background and purpose

We sought to understand why (-)-cannabidiol (CBD) and (-)-cannabidiol-dimethylheptyl (CBD-DMH) exhibit distinct pharmacology, despite near identical structures.

Experimental approach

HEK293A cells expressing either human type 1 cannabinoid (CB₁ ) receptors or CB₂ receptors were treated with CBD or CBD-DMH with or without the CB₁ and CB₂ receptor agonist CP55,940, CB₁ receptor allosteric modulator Org27569 or CB₂ receptor inverse agonist SR144528. Ligand binding, cAMP levels and βarrestin1 recruitment were measured. CBD and CBD-DMH binding was simulated with models of human CB₁ or CB₂ receptors, based on the recently published crystal structures of agonist-bound (5XR

SUBMITTER: Tham M 

PROVIDER: S-EPMC6487556 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature