Fig. 7: Non-psychedelics do not achieve 5-HT2A Gq-signaling efficacy threshold.
From: Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential
A Effect of (+)-lysergic acid diethylamide (LSD), psilocin, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), N,N-diethyltryptamine (DET), lisuride, ( + )−2-bromolysergic acid diethylamide (2-Br-LSD), 6-methoxy-N,N-dimethyltryptamine (6-MeO-DMT), and 6-fluoro-N,N-diethyltryptamine (6-F-DET) on 5-HT2A receptor Gq dissociation (red) and β-arrestin2 (blue) recruitment. The BRET data for LSD, psilocin, and 5-MeO-DMT are from Fig. 1; the data for 2-Br-LSD were published previously11. Data represent the mean and SEM from three independent experiments. B Effect of LSD, psilocin, 5-MeO-DMT (F4,26 = 3.09, p = 0.0331), DET, lisuride, 2-Br-LSD, 6-MeO-DMT (F5,26 = 4.19, p = 0.0063), and 6-F-DET (F4,23 = 13.49, p < 0.0001) on the head-twitch response (HTR) in mice. The HTR data for LSD, DET, psilocin, lisuride, and 2-Br-LSD were re-analyzed from published experiments9,11,78,85. HTR counts from individual male C57BL/6 J mice as well as group means are shown. P-values are provided if there were significant differences between groups (Tukey’s test). C Scatter plot and linear regression showing the correlation between 5-HT2A receptor Gq-efficacy (EMAX values) and HTR magnitude (maximum counts per minute induced by each drug). Pearson’s correlation coefficient R is shown. The p-value is 2-tailed. Drug doses are presented as mg/kg. Source data are provided as a Source Data file.
