Introduction to the chemistry and pharmacology of psychedelic drugs

Psychedelic science is a multi-disciplinary field that has recently gained public attention due to high-profile studies on psychedelic-assisted therapy for difficult-to-treat mental health conditions. This Primer Review provides an overview of the chemistry and pharmacology of psychedelics, covering natural, semi-synthetic, and fully synthetic substances. It begins with a summary of important psychedelic classes and their traditional human use dating back to prehistoric times. The review examines ergolines (e.g., LSD), tryptamines (e.g., psilocybin, DMT), phenethylamines (e.g., mescaline, MDMA), arylcyclohexylamines (e.g., ketamine, PCP), and other naturally occurring drugs like muscimol and salvinorin A. Contributions from pioneers Albert Hofmann and Alexander Shulgin are briefly summarized, with references to primary literature.

Study at a glance

Abstract

The science of psychedelics is an intriguing, multi-disciplinary field that has recently been the subject of heightened public interest. This has mainly resulted from publicity associated with a number of high-profile investigations into psychedelic-assisted therapy for a range of difficult-to-treat mental health conditions. With many psychedelic substances known, including natural, semi-synthetic and fully synthetic, and a rangeof receptors, enzymes and transporters implicated in their modes of action, although very interesting, the field can appear daunting to newcomers to the area. This Primer Review is designed to give an overview of the chemistry and pharmacology of psychedelics. It is hoped that it will provide a useful resource for science undergraduates, postgraduates and their instructors, and experienced scientists who require a comprehensive and up-to-date summary of the field. The Review begins with a summary of the important classes of psychedelics and then goes on to summarise the known history of their traditional human use, dating back to prehistoric times. Following that, important classes of psychedelics are examined in more detail, namely the ergolines, such as lysergic acid diethylamide (LSD), tryptamines like psilocybin and N,N-dimethyltryptamine, phenethylamines typified by mescaline and 3,4-methylenedioxymethamphetamine (MDMA), arylcyclohexylamines including ketamine and phenylcyclohexylpiperidine (PCP), and a group of naturally occurring drugs that do not belong to any of these three classes, examples being muscimol and salvinorin A. The contributions made by early pioneers like Albert Hofmann and Alexander Shulgin are briefly summarised. References to primary literature and more specialised reviews are provided throughout.