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Psychedelics and the Human Receptorome

Publication Psychedelics and the Human Receptorome 2024-06-08

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We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT2A (andpossibly 5-HT2C) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective forthese two receptors. This manuscript is a reference work on the receptor affinity pharmacology of psychedelic drugs. Newdata 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 affinityprofiles of different drugs can be directly compared and contrasted. The method is then used to compare the thirty-fivedrugs in graphical and tabular form. It is shown that psychedelic drugs, especially phenylalkylamines, are not as selective asgenerally believed, interacting with forty-two of forty-nine broadly assayed sites. The thirty-five drugs of the study have verydiverse patterns of interaction with different classes of receptors, emphasizing eighteen different receptors. This diversity ofreceptor interaction may underlie the qualitative diversity of these drugs. It should be possible
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