Psychedelics and the human receptorome
This manuscript (2020) presents new data on the affinity of psychedelic drugs at receptors, transporters, and ion channels. Psychedelics (phenylalkylamines specifically) are not as selective as generally believed (they bind to more receptors).
Abstract
We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT2A (and possibly 5-HT2C) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these two receptors. This manuscript is a reference work on the receptor affinity pharmacology of psychedelic drugs. New data is presented on the affinity of twenty-five psychedelic drugs at fifty-one receptors, transporters, and ion channels, assayed by the National Institute of Mental Health - Psychoactive Drug Screening Program (NIMH-PDSP). In addition, comparable data gathered from the literature on ten additional drugs is also presented (mostly assayed by the NIMH-PDSP). A new method is introduced for normalizing affinity (Ki) data that factors out potency so that the multi-receptor affinity profiles of different drugs can be directly compared and contrasted. The method is then used to compare the thirty-five drugs in graphical and tabular form. It is shown that psychedelic drugs, especially phenylalkylamines, are not as selective as generally believed, interacting with forty-two of forty-nine broadly assayed sites. The thirty-five drugs of the study have very diverse patterns of interaction with different classes of receptors, emphasizing eighteen different receptors. This diversity of receptor interaction may underlie the qualitative diversity of these drugs. It should be possible to use this diverse set of drugs as probes into the roles played by the various receptor systems in the human mind.
Research Summary of 'Psychedelics and the human receptorome'
Introduction
Ray frames the paper against the prevailing view that the subjective effects of classical psychedelics are principally caused by agonism or partial agonism at 5-HT2A (and possibly 5-HT2C) receptors, a view developed in the 1980s and supported by subsequent literature. Earlier work has noted that other receptors may contribute to psychedelic effects and that different drugs produce qualitatively different experiences; Ray argues that modern high-throughput receptor assays make it timely to take a broader, “receptorome” view and to characterise multi-receptor affinity profiles across a wide panel of targets. This study sets out to assemble and present receptor binding data for thirty-five compounds so that their multi-receptor affinity profiles can be directly compared. Twenty-five compounds were assayed by the NIMH Psychoactive Drug Screening Program (NIMH‑PDSP) against a large panel of receptors, transporters and ion channels, and comparable data for ten additional compounds were gathered from the literature. Ray introduces a normalization approach to factor out differences in absolute potency so that relative affinity patterns across receptors can be compared; the primary aim is to produce a reference resource that highlights both shared and distinct receptor interactions among psychedelic and related drugs.
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Study Details
- Study Typeindividual
- Journal
- APA Citation
Ray, T. S. (2010). Psychedelics and the human receptorome. PLoS ONE, 5(2), e9019. https://doi.org/10.1371/journal.pone.0009019
References (1)
Papers cited by this study that are also in Blossom
Nichols, D. E. · Journal of Psychoactive Drugs (1986)
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Pallavicini, C., Vilas, M. G., Villarreal, M. et al. · NeuroImage (2019)
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