PRoMiSS: Psilocybin and the Role of Music in Set and Setting

Summary

The goal of this clinical trial is to understand how personally meaningful, autobiographically salient music compares to standardized playlists when combined with psilocybin in healthy adults ages 21 to 75. The main questions it aims to answer are:

Does autobiographically salient music lead to stronger emotional responses to music, greater acute subjective effects, and more lasting improvements in mood, affect, and well-being compared to standardized or ambient playlists?

How are brain and body responses - including EEG activity, respiration, heart rate, and skin conductance - influenced by autobiographically salient music under psilocybin?

Do brain and body responses to specific music features differ when the music is autobiographically salient compared to non-salient playlists?

Researchers will compare five music conditions: three conditions where an 80-minute block of autobiographically salient music is placed at different points in the 6-hour psilocybin session (0-80 minutes, 80-160 minutes, or 240-320 minutes), a standardized Johns Hopkins psilocybin playlist, and an ambient playlist with no autobiographical content.

Participants will:

* Take a single oral dose of psilocybin (25 mg) during one study session
* Listen to one of the five music conditions while reclining in a comfortable setting
* Complete questionnaires about emotions, acute, subjective effects, insight, etc.
* Undergo EEG and physiological monitoring (respiration, heart rate, skin conductance) during the session
* Complete MRI brain scans before the session and 1 week after psilocybin
* Return for follow-ups at 1 day, 1 week, and 1 month after psilocybin
* At 1 month, complete a qualitative interview and a nondrug EEG music listening session, where the participant's hear either music from the participant's own psilocybin session or music from another participant's session

Conditions

• Psilocybin
• Music Intervention

Interventions

DRUG

Psilocybin (high dose)

25 mg pill

BEHAVIORAL

Playlist 1

Six hour playlist

BEHAVIORAL

Playlist 2

A six hour playlist

BEHAVIORAL

Playlist 3

A six hour playlist

BEHAVIORAL

Playlist 4

A six hour playlist

BEHAVIORAL

Playlist 5

A six hour playlist

Sponsors & Collaborators

• Steven & Alexandra Cohen Foundation

  collaborator OTHER

• Johns Hopkins University

  lead OTHER

Principal Investigators

• Frederick S Barrett, PhD · Johns Hopkins University

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

21 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-08-12

Primary Completion

2028-06-30

Completion

2028-08-31

FDA Drug

Yes

Countries

• United States

Study Locations