Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile

Psychedelic compounds such as psilocybin, LSD, DMT, 5-MeO-DMT, and mescaline, all serotonin 2A receptor agonists, are under investigation as potential treatments. This review summarizes current clinical research on these five compounds, covering mechanisms of action, pharmacokinetics, pharmacodynamics, efficacy, and safety. Evidence for therapeutic indications remains scarce except for psilocybin for depression. No differences in psychedelic effects were noted beyond effect duration, and it is unclear whether different receptor profiles contribute to therapeutic potential. More research is needed to differentiate these compounds for various therapeutic uses.

Study at a glance

Abstract

Psychedelic compounds, including psilocybin, LSD (lysergic acid diethylamide), DMT (N,N -dimethyltryptamine), and 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), all of which are serotonin 2A receptor agonists, are being investigated as potential treatments. This review aims to summarize the current clinical research on these 4 compounds and mescaline to guide future research. Their mechanism(s) of action, pharmacokinetics, pharmacodynamics, efficacy, and safety were reviewed. While evidence for therapeutic indications, with the exception of psilocybin for depression, is still relatively scarce, we noted no differences in psychedelic effects beyond effect duration. Therefore, it remains unclear whether different receptor profiles contribute to the therapeutic potential of these compounds. More research is needed to differentiate these compounds in order to inform which compounds might be best for different therapeutic uses.