Differential in Vitro Activation Profiles for Psychedelic versus Non-psychedelic Ergolines at the 5-HT2A Receptor
Emerging Trends in Drugs, Addictions, and Health December 14, 2024 E. Pottie, G.c. Glatfelter, M.h. Baumann et al.
Serotonergic psychedelics like LSD, mescaline, and psilocin produce their subjective effects by activating the serotonin 2A receptor (5-HT2AR). Some structurally similar ergolines, such as lisuride, do not evoke psychedelic effects. In cell-based assays, the known psychedelic AL-LAD activated 5-HT2AR with higher intrinsic efficacy (137–167%) than LSD, while the non-psychedelic lisuride showed markedly decreased efficacy (49%) in one pathway and no activation in another. The results suggest that ergoline compounds may require a threshold level of 5-HT2AR activation across two signaling pathways to produce psychedelic effects, a hypothesis that needs further investigation.