6-Fluoro-DET

Pharmacodynamics

6-Fluoro-DET acts as a partial agonist at the serotonin 5-HT_2A receptor,^[2] but while it produces similar physiological effects to psychedelics, it does not appear to produce psychedelic effects itself even at high doses. Relatedly, 6-F-DET does not substitute for LSD in drug discrimination tests and does not produce the head-twitch response in rodents.^[2][3][4] For the preceding reasons, it saw some use as an active placebo in early clinical trials of psychedelic drugs, but was regarded as having little use otherwise,^[5] though more recent research into compounds such as AL-34662, tabernanthalog, and zalsupindole has shown that these kind of non-psychedelic serotonin 5-HT_2A agonists can have various useful applications.^{[6][7][8][9][10][11]}

A hypothesis for the lack of head-twitch response in mice and hallucinogenic effects in humans is that 6-F-DET acts as a 5-HT_2A receptor partial agonist of the G_q signaling pathway.^[2] This hypothesis explains the lack of hallucinogenic effects of other 5-HT_2A receptor ligands, which are also weak Gq agonists and below the efficacy threshold found to induce psychedelic effects, like 25N-N1-Nap, 2-Br-LSD, lisuride, tabernanthalog, and 6-MeO-DMT.^[2][10][12]

Analogues

Analogues of 6-fluoro-DET include 6-fluoro-DMT, 5-fluoro-DMT, 5-chloro-DMT, 5-bromo-DMT, 5-fluoro-AMT, 6-fluoro-AMT, 6-methyl-DMT, 6-MeO-DMT, 6-hydroxy-DMT, and bretisilocin (5-fluoro-MET), among others.