Molecular insights into GPCR mechanisms for drugs of abuse.
Omar B Sanchez-Reyes, Gregory Zilberg, John D. Mccorvy, Daniel Wacker
Journal of Biological Chemistry September 1, 2023 DOI: 10.1016/j.jbc.2023.105176 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Gpcr Cannabinoid Drugs of abuse Opioid Pharmacology Structure Molecular biology Drug research Receptor biology |
| Citations | 10 |
| Key findings | Opioids, cannabinoids, and psychedelics directly bind to GPCRs to initiate signaling, and structural studies of these interactions inform drug discovery for abuse treatment and therapeutic use. |
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.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
Cited by 3
- Biased Signaling in Psychedelic Action. The Annual Review of Pharmacology and Toxicology August 12, 2025
- Antidepressant effect of psychedelic compounds and mechanisms underlying the G protein-coupled receptors activation psychedelics: Antidepressant action and GPCR signaling. European Journal of Pharmacology July 10, 2026
- Biased signaling via serotonin 5-HT2A receptor: From structural aspects to in vitro and in vivo pharmacology. Acta Pharmaceutica Sinica B September 1, 2025
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and 21 more in the library