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

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...

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Autores principales: Zamberlan, Federico, Sanz, Camila, Martínez Vivot, Rocío, Pallavicini, Carla, Erowid, Fire, Erowid, Earth, Tagliazucchi, Enzo
Formato: Artículo
Lenguaje:Inglés
Publicado: Frontiers Media 2022
Materias:
ANALISIS SEMANTICO
AFINIDAD
CONCIENCIA
FENOMENOLOGIA
SUSTANCIAS PSICOACTIVAS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/14226
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-14226
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic ANALISIS SEMANTICO
AFINIDAD
CONCIENCIA
FENOMENOLOGIA
SUSTANCIAS PSICOACTIVAS
spellingShingle ANALISIS SEMANTICO
AFINIDAD
CONCIENCIA
FENOMENOLOGIA
SUSTANCIAS PSICOACTIVAS
Zamberlan, Federico
Sanz, Camila
Martínez Vivot, Rocío
Pallavicini, Carla
Erowid, Fire
Erowid, Earth
Tagliazucchi, Enzo
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
topic_facet ANALISIS SEMANTICO
AFINIDAD
CONCIENCIA
FENOMENOLOGIA
SUSTANCIAS PSICOACTIVAS
description 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-HT)2A 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 5-HT 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) 5-HT 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 5-HT, dopamine (DA), 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.
format Artículo
author Zamberlan, Federico
Sanz, Camila
Martínez Vivot, Rocío
Pallavicini, Carla
Erowid, Fire
Erowid, Earth
Tagliazucchi, Enzo
author_facet Zamberlan, Federico
Sanz, Camila
Martínez Vivot, Rocío
Pallavicini, Carla
Erowid, Fire
Erowid, Earth
Tagliazucchi, Enzo
author_sort Zamberlan, Federico
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher Frontiers Media
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/14226
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