Molecular insights into GPCR mechanisms for drugs of abuse.
The Journal of biological chemistry – September 01, 2023
Source: PubMed
Summary
Recent breakthroughs reveal how common drugs like opioids and cannabinoids interact with cellular receptors called GPCRs. Scientists mapped the precise structure of these receptors, showing how different drugs of abuse bind to them. This explains why opioids, serotonin-based psychedelics, and cannabinoids affect the brain and body so differently, opening paths for safer treatments.
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 tetrahydrocannabinol, and psychedelics like lysergic acid diethylamide 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 toward the development of novel therapies to combat drug abuse or toward harnessing therapeutic potential.