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

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 May;9(5):472-489. doi: 10.1016/j.bpsc.2024.01.007. Epub 2024 Feb 1.

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.

Keywords: Adverse effects; DMT; Efficacy; LSD; Mechanisms of action; Mescaline; Pharmacokinetics; Psilocybin; Psychedelics; Serotonin.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Comparative Study

MeSH terms

  • Hallucinogens* / pharmacokinetics
  • Hallucinogens* / pharmacology
  • Humans
  • Lysergic Acid Diethylamide* / pharmacokinetics
  • Lysergic Acid Diethylamide* / pharmacology
  • Psilocybin* / pharmacokinetics
  • Psilocybin* / pharmacology
  • Serotonin 5-HT2 Receptor Agonists / pharmacokinetics
  • Serotonin 5-HT2 Receptor Agonists / pharmacology

Substances

  • Hallucinogens
  • Psilocybin
  • Lysergic Acid Diethylamide
  • Serotonin 5-HT2 Receptor Agonists