Increased low-frequency brain responses to music after psilocybin therapy for depression

J Affect Disord. 2023 Jul 15:333:321-330. doi: 10.1016/j.jad.2023.04.081. Epub 2023 Apr 23.


Background: Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following PT.

Methods: Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of psilocybin dosing sessions.

Results: Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions.

Limitations: Open-label trial. Relatively small sample size.

Conclusions: These data suggest an effect of PT on the brain's response to music, implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.

Keywords: Depression; Music; Psilocybin; Psychedelic therapy; fMRI.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / physiology
  • Brain Mapping
  • Depression
  • Hallucinogens* / therapeutic use
  • Humans
  • Magnetic Resonance Imaging / methods
  • Music*
  • Psilocybin / pharmacology
  • Psilocybin / therapeutic use


  • Hallucinogens
  • Psilocybin