Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural Response to Dynamic Changes in Music

Frederick S. Barrett, Katrin H. Preller, Marcus Herdener, Petr Janata, Franz X. Vollenweider

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Classic psychedelic drugs (serotonin 2A, or 5HT 2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT 2A antagonist ketanserin, to investigate the role of 5HT 2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT 2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT 2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences.

Original languageEnglish (US)
Pages (from-to)3939-3950
Number of pages12
JournalCerebral Cortex
Issue number11
StatePublished - Nov 1 2018


  • functional magnetic resonance imaging (fMRI)
  • music information retrieval
  • psychedelics
  • tonality

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


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