The varieties of the psychedelic experience : a preliminary study of the association between the reported subjective effects and the binding affinity profiles of substituted phenet...

• Autores: Zamberlan, Federico; Sanz, Camila; Martínez Vivot, Rocío; Pallavicini, Carla; Erowid, Fire; Erowid, Earth; Tagliazucchi, Enzo
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Frontiers in Integrative Neuroscience. 2012, 12:54
• Materia: ANALISIS SEMANTICO; AFINIDAD; CONCIENCIA; FENOMENOLOGIA; SUSTANCIAS PSICOACTIVAS
• Institución: Pontificia Universidad Católica Argentina

Fil: Zamberlan, Federico. Universidad de Buenos Aires. Departamento de Física; Argentina
Fil: Zamberlan, Federico. Universidad de Buenos Aires. Instituto de Física de Buenos Aires; Argentina
Fil: Zamberlan, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sanz, Camila. Universidad de Buenos Aires. Departamento de Física; Argentina
Fil: Martínez Vivot, Rocío. Universidad de Buenos Aires. Instituto de Física de Buenos Aires; Argentina
Fil: Martínez Vivot, Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Martínez Vivot, Rocío. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Pallavicini, Carla. Universidad de Buenos Aires. Instituto de Física de Buenos Aires; Argentina
Fil: Pallavicini, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pallavicini, Carla. Fundación Para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Erowid, Fire. Erowid Center; Estados Unidos
Fil: Erowid, Earth. Erowid Center; Estados Unidos
Fil: Tagliazucchi, Enzo. Universidad de Buenos Aires. Departamento de Física; Argentina
Fil: Tagliazucchi, Enzo. Universidad de Buenos Aires. Instituto de Física de Buenos Aires; Argentina
Fil: Tagliazucchi, Enzo. Institut du Cerveau et de la Moelle épinière; Francia
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.