Citation

Sanchez-Reyes OB, Zilberg G, McCorvy JD, Wacker D. J. Biol. Chem. 2023; e105176.

Copyright

(Copyright © 2023, American Society for Biochemistry and Molecular Biology)

DOI

10.1016/j.jbc.2023.105176

PMID

37599003

Abstract

Substance abuse is on the rise, and while many people may use illicit drugs mainly due to their rewarding effects, their societal impact can range from severe, as is the case for opioids, to promising, as is the case for psychedelics. Common with all these drugs' mechanisms of action are G protein-coupled receptors (GPCRs), which lie at the center of how these drugs mediate inebriation, lethality, and therapeutic effects. Opioids like fentanyl, cannabinoids like THC, and psychedelics like LSD all directly bind to GPCRs to initiate signaling which elicits their physiological actions. We herein review recent structural studies and provide insights into the molecular mechanisms of opioids, cannabinoids, and psychedelics at their respective GPCR subtypes. We further discuss how such mechanistic insights facilitate drug discovery, either towards the development of novel therapies to combat drug abuse, or towards harnessing therapeutic potential.

Language: en

Keywords

Pharmacology; Serotonin; Opioid; Cannabinoid; Drugs of Abuse; GPCR; Structure