Increased 5-HT 2A receptor signalling efficacy differentiates serotonergic psychedelics from non-psychedelics
bioRxiv (Cold Spring Harbor Laboratory) June 16, 2024 Aurelija Ippolito, Sridhar R. Vasudevan, Shaun Hurley et al. 1 citation preprint
All psychedelic drugs tested were unbiased, partial agonists at the 5-HT2A receptor, activating G-protein and β-arrestin2 pathways equally. Non-psychedelic drugs lisuride and TBG were not biased either, but they showed the lowest signalling efficacy among all compounds. Low efficacy at the 5-HT2A receptor, not biased signalling, may explain why some 5-HT2A agonists are not psychedelic.