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Cited by 71Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorForensic Toxicology and Drug Analysis

The Varieties of the Psychedelic Experience: A Preliminary Study of the Association Between the Reported Subjective Effects and the Binding Affinity Profiles of Substituted Phenethylamines and Tryptamines

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Zamberlan, Federico, Sanz, Camila, Martínez Vivot, Rocío, Pallavicini, Carla, Erowid, Fire, Erowid, Earth, Tagliazucchi, Enzo·2018·Frontiers in Integrative Neuroscience
DOI 10.3389/fnint.2018.00054PMC PMC6235949
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Abstract

Classic psychedelics are substances of paramount cultural and neuroscientific importance. A distinctive feature of psychedelic drugs is the wide range of potential subjective effects they can elicit, known to be deeply influenced by the internal state of the user (“set”) and the surroundings (“setting”). The observation of cross-tolerance and a series of empirical studies in humans and animal models support agonism at the serotonin 5-HT2A receptor as a common mechanism for the action of psychedelics. The diversity of subjective effects elicited by different compounds has been attributed to the variables of “set” and “setting”, to the binding affinities for other serotonin receptor subtypes, and to the heterogeneity of transduction pathways initiated by conformational receptor states as they interact with different ligands (“functional selectivity”). Here we investigate the complementary (i.e. not mutually exclusive) possibility that such variety is also related to the binding affinity for a range of neurotransmitters and monoamine transporters including (but not limited to) serotonin receptors. Building on two independent binding affinity datasets (compared to “in silico” estimates) in combination with natural language processing tools applied to a large repository of reports of psychedelic experiences (Erowid’s Experience Vaults), we obtained preliminary evidence supporting that the similarity between the binding affinity profiles of psychoactive substituted phenethylamines and tryptamines is correlated with the semantic similarity of the associated reports. We also showed that the highest correlation was achieved by considering the combined binding affinity for the serotonin, dopamine, glutamate, muscarinic and opioid receptors, and for the Ca+ channel. Applying dimensionality reduction techniques to the reports, we linked the compounds, receptors, transporters and the Ca+ channel to distinct fingerprints of the reported subjective effects. To the extent that the existing binding affinity data is based on a low number of displacement curves that requires further replication, our analysis produced preliminary evidence consistent with the involvement of different binding sites in the reported subjective effects elicited by psychedelics. Beyond the study of this particular class of drugs, we provide a methodological framework to explore the relationship between the binding affinity profiles and the reported subjective effects of other psychoactive compounds.

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  • A compilation of reports for a broad range of substances shows that interactions of serotonin, dopamine, glutamate, and opioid receptors all contribute to aspects of the subjective experience.

    “Furthermore, a compilation of reports for a broad range of substances shows that interactions of serotonin, dopamine, glutamate, and opioid receptors all contribute to aspects of the subjective experience [20].”

    From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [20]

    The Abstract and Results report that, across psychedelic phenethylamines and tryptamines, binding affinities involving serotonin, dopamine, glutamate, and opioid receptors helped predict similarities in reported subjective effects (page numbers unavailable). The paper calls this preliminary, correlational evidence; it does not establish that interactions at each receptor type causally contribute to experience across a broad range of substances. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Zamberlan, F., Sanz, C., Martínez Vivot, R., Pallavicini, C., Erowid, F., Erowid, E., & Tagliazucchi, E.
Affiliations
  • Universidad de Buenos Aires (AR)
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
Corresponding author
Tagliazucchi, Enzo
ORCID
Venue
Frontiers in Integrative Neuroscience
Publisher
Frontiers Media SA
Published
2018-11-08
Volume
12
Pages
54-54
ISSN
1662-5145 (ISSN-L)
DOI
10.3389/fnint.2018.00054
PMC
PMC6235949
OpenAlex
W2900445331
Cited by
71
References
8
Citations by year
2026: 3 · 2025: 9 · 2024: 14 · 2023: 13 · 2022: 15 · 2021: 7 · 2020: 7 · 2019: 3
FWCI
4.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Integrative Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
  • Americanae (AECID Library) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Greater South Information System
Funders
European Commission (702681 - MIDOC - DLV-702681)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
Keywords
psychedelics, subjective effects, tryptamine, 5-HT2A receptor, functional selectivity, set and setting, cross-tolerance, monoamine transporters, muscarinic receptors, opioid receptors, calcium channels, receptor fingerprints

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