In a recent study published in Nature Communications, researchers identified 5-hydroxytryptamine 2A (5-HT2A) receptor (5-HT2AR) signaling pathways associated with psychedelic potential.
Interest in classical or serotonergic psychedelics has resurged, given their potential to induce rapid, sustained therapeutic effects. Psychedelics are limited by their hallucinogenic effects and can cause confusion and anxiety. Although a recent preclinical study suggested the possibility of disentangling psychedelics from their therapeutic properties, it is unclear which signaling pathways and receptors mediate psychedelic effects.
Serotonergic psychedelics are derivatives of different chemical scaffolds, including lysergamides, tryptamines, and phenethylamines, which all activate the G protein-coupled receptor (GPCR), 5-HT2AR. GPCR-targeting ligands stabilize some conformations of the receptor, energetically favoring coupling to transducer proteins.