Moving beyond 5-HT2A: language models map neurotransmitter receptors to experiential semantics.

Abstract

Psychedelics exhibit rapid, durable therapeutic effects across diverse psychiatric conditions, yet their broad-spectrum psychoactivity poses challenges for clinical translation. 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. 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. While 5-HT2A predictably associates with classic facets of psychedelic experience, our analysis reveals novel associations, including 5-HT1A and 5-HT1B with 'Cognitive Disruption', H1 with 'Interdimensional Communication', and 5-HT7a and 5-HT1E with 'Visual Complexity'.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

• State of the evidence: Serotonin ↑Supports

  A semantic embedding model linked 5-HT2A to classic psychedelic experience and suggested novel associations of other serotonin receptor subtypes with specific experiential categories.

  Synthesized October 19, 2026