Moving beyond 5-HT<sub>2A</sub>: language models map neurotransmitter receptors to experiential semantics.
Abstract
<h4>Rationale</h4>Psychedelics exhibit rapid, durable therapeutic effects across diverse psychiatric conditions, yet their broad-spectrum psychoactivity poses challenges for clinical translation.<h4>Objectives</h4>As a proof-of-concept, we aimed to quantify associations between 19 neurotransmitter receptors and the subjective effects of 21 psychedelic drugs with broadly assayed binding profiles.<h4>Methods</h4>We used a custom Global Vectors for Word Representation (GloVe)-based semantic embedding model trained on 4,496 firsthand experience reports and integrated it with receptor affinities to identify candidate receptor-linked semantic patterns related to distinct psychoactive effects without imposing predefined categorization systems.<h4>Results</h4>While 5-HT<sub>2A</sub> predictably associates with classic facets of psychedelic experience, our analysis reveals novel associations, including 5-HT<sub>1A</sub> and 5-HT<sub>1B</sub> with 'Cognitive Disruption', H<sub>1</sub> with 'Interdimensional Communication', and 5-HT<sub>7a</sub> and 5-HT<sub>1E</sub> with 'Visual Complexity'.
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