A systematic review of the pharmacokinetics of classical serotonergic psychedelic compounds in healthy adult subjects

Introduction: Despite renewed investigations into classical psychedelic compounds, their pharmacokinetic profiles remain incompletely understood. Methods: This systematic review collated data from healthy adult volunteers on the pharmacokinetic properties of lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), mescaline, and 5-methoxy- N,N -dimethyltryptamine (5-MEO-DMT). Results: We identified 32 eligible trials. LSD was the most studied compound, followed by DMT, split between intravenous (IV) and oral formulations. Psilocybin was also frequently studied. Mescaline was reported in two trials, with IV LSD, IV psilocybin, inhalation 5-MEO-DMT, and intranasal 5-MEO-DMT reported in single studies. Key findings include dose proportional C max values for LSD and psilocybin, alongside differences between oral and IV formulations of DMT that may be clinically significant. Discussion: This systematic review highlights key variations in absorption, distribution, and elimination between the studied compounds that may have important implications in both clinical and research settings.