A non-hallucinogenic LSD analog with therapeutic potential for mood disorders.

ABSTRACT: Hallucinations limit widespread therapeutic use of psychedelics as rapidly acting antidepressants. Here we profiled the non-hallucinogenic lysergic acid diethylamide (LSD) analog 2-bromo-LSD (2-Br-LSD) at more than 33 aminergic G protein-coupled receptors (GPCRs). 2-Br-LSD shows partial agonism at several aminergic GPCRs, including 5-HT_2A, and does not induce the head-twitch response (HTR) in mice, supporting its classification as a non-hallucinogenic 5-HT_2A partial agonist. Unlike LSD, 2-Br-LSD lacks 5-HT_2B agonism, an effect linked to cardiac valvulopathy. Additionally, 2-Br-LSD produces weak 5-HT_2A β-arrestin recruitment and internalization in vitro and does not induce tolerance in vivo after repeated administration. 2-Br-LSD induces dendritog

SUBMITTER: Lewis V 

PROVIDER: S-EPMC10112881 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature