Psychedelics produce a wide range of phenomenological and physiological effects, some beneficial for treating mental health disorders and others associated with substantial adverse risk. Here, we present a multimodal framework linking molecular structure, receptor-level functional pharmacology, and trip-report semantics. Using experimental potencies for 41 psychedelics across 25 GPCRs, we used ligand-based, proteochemometric, and co-folding models to predict receptor activity profiles for additional compounds lacking experimental data. To capture subjective experience, we analysed ~9,000 single-substance trip reports using topic modelling to derive phenomenological embeddings. Across compounds with full experimental data, pharmacological similarity correlated with experiential similarity, but this relationship disappeared when using predicted rather than experimental potencies, suggesting that accumulated prediction error obscures the true structure–pharmacology–phenomenology relationship.

Co-authors: Alexander Hauser