Receptor binding profiles and behavioral effects of psilocybin analogs
The FASEB Journal May 1, 2022 Grant C. Glatfelter, David R. Manke, Andrew R. Chadayne et al. 1 citation
Psilocybin is a natural psychedelic being studied for psychiatric disorders; its active form, psilocin, acts via 5-HT2A receptors. Several psilocybin analogs, like psilacetin, have emerged as new psychoactive substances. This study examined in vitro receptor affinities for a series of psilocybin analogs with different N-alkyl or 4-position substitutions, and in vivo head twitch responses (HTRs) in male C57BL/6J mice after psilocybin, psilacetin, or psilocin administration. All analogs showed low to mid nM affinities for 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C receptors; non-serotonergic affinities were weaker. In mice, the potency order for HTRs was psilocin > psilacetin > psilocybin. HTRs from all three compounds (0.6 mg/kg) were blocked by the 5-HT2A antagonist M100907 (0.01 mg/kg), indicating 5-HT2A involvement. Psilacetin may be an alternative prodrug for psilocin with possible independent psychedelic activity.