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

Friederike Holze; Nirmal Singh; Matthias E Liechti; Deepak Cyril D'Souza

doi:10.1016/j.bpsc.2024.01.007

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

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Feb 1:S2451-9022(24)00020-X. doi: 10.1016/j.bpsc.2024.01.007. Online ahead of print.

Authors

Friederike Holze¹, Nirmal Singh², Matthias E Liechti³, Deepak Cyril D'Souza⁴

Affiliations

¹ Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. Electronic address: friederike.holze@usb.ch.
² Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut; Clinical Neuroscience Research Unit, Connecticut Mental Health Center, New Haven, Connecticut.
³ Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
⁴ Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut; Clinical Neuroscience Research Unit, Connecticut Mental Health Center, New Haven, Connecticut; VA Connecticut Healthcare System, West Haven, Connecticut. Electronic address: deepak.dsouza@yale.edu.

PMID: 38301886
DOI: 10.1016/j.bpsc.2024.01.007

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