Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 5 (2), e9019

Psychedelics and the Human Receptorome

Affiliations

Psychedelics and the Human Receptorome

Thomas S Ray. PLoS One.

Erratum in

  • PLoS One. 2010;5(3). doi: 10.1371/annotation/e580a864-cf13-40c2-9bd9-b9687a6f0fe4

Abstract

We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT(2A) (and possibly 5-HT(2C)) 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 (K(i)) 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.

Conflict of interest statement

Competing Interests: The NIMH-PDSP actually produced the affinity data for twenty-five drugs, and provided it exclusively to the author. This does not alter the author's adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Twenty-five drugs assayed for this study by the NIMH-PDPS.
Twenty-five drugs assayed for this study by the NIMH-PDPS against fifty-one receptors, transporters and ion-channels. The twenty-five drugs include sixteen phenylalkylamines, eight tryptamines, and one ergoline. The three control drugs on the right include one representative from each structural class, and are believed to be non-psychedelic.
Figure 2
Figure 2. Ten drugs whose receptor profiles were collected from the literature.
Ten drugs whose receptor profiles were collected from the literature. All but ibogaine, THC, and morphine were assayed by the NIMH-PDSP.
Figure 3
Figure 3. Receptor affinity profiles of DOB and DOI, ordered by decreasing affinity.
The vertical axis is normalized pKi (npKi). Horizontal axis is a list of forty-two receptors, arranged in order of decreasing affinity for each individual drug. Colors correspond to classes of receptors, and are the same as used in Fig. S1. The black vertical bars represent a 100-fold drop in affinity relative to the receptor with the highest affinity. As a rule of thumb, this is presumed to be the limit of perceptible receptor interaction. Receptors to the right of the black bar should be imperceptible, while receptors to the left of the black bar should be perceptible, increasingly so the further left they are.
Figure 4
Figure 4. Thirty-five drugs arranged in order of decreasing breadth, increasing selectivity.
The thirty-five drugs are arranged in order of decreasing breadth and increasing selectivity, based on the breadth indices B, Bsq, and Bexp. Although the three indices provide different orderings, the orderings are quite similar at the two extremes of the table (greatest and least breadth) where most of the attention is likely to be focused. The drugs with the broadest receptor interactions (least selective) are found at the left of the figure, and the drugs with the narrowest receptor interactions (most selective) are found at the right of the figure.
Figure 5
Figure 5. Forty-two receptors arranged in order of decreasing interaction with the full set of thirty-five drugs.
The forty-two receptors are arranged in order of decreasing interaction with the full set of thirty-five drugs, based on the breadth statistics, B, Bsq. and Bexp. The receptors with the greatest interactions are found at the left of the figures, and the receptors with the least interactions are found at the right of the figures. The black vertical bars represent a 100-fold drop in affinity relative to the receptor with the highest affinity at each drug. As a rule of thumb, this is presumed to be the limit of perceptible receptor interaction. Drugs to the right of the black bar should have imperceptible interactions with the receptor, while drugs to the left of the black bar should have perceptible interactions with the receptor, increasingly so the further left they are.

Similar articles

See all similar articles

Cited by 38 PubMed Central articles

See all "Cited by" articles

References

    1. Nichols DE. Hallucinogens. Pharmacology & Therapeutics. 2004;101:131–81. - PubMed
    1. Glennon RA, Young R, Rosecrans JA. Antagonism of the effects of the hallucinogen DOM and the purported 5-HT agonist quipazine by 5-HT2 antagonists. Eur J Pharmacol. 1983;91:189–96. - PubMed
    1. Glennon RA, Titeler M, McKenney JD. Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences. 1984;35:2505–11. - PubMed
    1. Glennon RA, Titeler M, Young R. Structure-activity relationships and mechanism of action of hallucinogenic agents based on drug discrimination and radioligand binding studies. Psychopharmacol Bull. 1986;22:953–8. - PubMed
    1. Glennon RA, Darmani NA, Martin BR. Multiple populations of serotonin receptors may modulate the behavioral effects of serotonergic agents. Life Sci. 1991;48:2493–8. - PubMed

Publication types

MeSH terms

Feedback