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

NCT07180108 | Enrolling By Invitation Phase 1 FDA Drug

• 1 other identifier: IRB00372917
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Psilocybin; Set and Setting; Music Cognition; Music-evoked autobiographical memory; Emotion; Altered State of Consciousness; Psychedelics; Memory

Outcome Measures

Primary Outcomes (17)

• Challenging Experiences Questionnaire

  The Challenging Experience Questionnaire (CEQ) is a self-report measure designed to assess the intensity and quality of difficult or distressing experiences during psychedelic states. Zero is equivalent to no challenging experiences and 5 is an extreme (more than ever before in my life). Higher CEQ = "more difficult." That's generally worse for safety and usually not what predicts the best clinical gains.

  Immediately at the end of their experimental session

• Psychological Insight Questionnaire (PIQ)

  The Psychological Insight Questionnaire (PIQ) is a validated self-report measure developed to assess psychological insight experiences following a psychedelic session. It was designed to capture the extent to which individuals gain meaningful self-related or therapeutic insights during and after acute psychedelic states. The PIQ is scored 0 (not at all) to 6 Extremely (more than ever before in my life). A higher score is associated with better outcomes.

  Immediately at end of experimental session

• Core Flow State Scale (C-FSS)

  The Core Flow State Scale (CFSS) is a validated self-report measure designed to assess the subjective experience of flow, the psychological state of deep absorption, enjoyment, and optimal engagement in an activity. The CFSS is scored from 1 (Strongly Disagree) to 5 (Strongly Agree). A higher score is better.

  Immediately at end of experimental session

• Mystical Experiences Questionnaire (MEQ-30)

  The Mystical Experience Questionnaire (MEQ) is the most widely used measure for assessing the phenomenological features of mystical-type experiences occasioned by psychedelics. The MEQ is measured from 0 (not at all) to 5 extreme (ore than ever before in my life and stronger than 4). A higher MEQ score is associated with better outcomes.

  Immediately at end of experimental session

• Experience of Unity (11D-ASC)

  A sense of oneness with the environment or the universe, dissolving boundaries between self and world. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Higher Experience of Unity scores are generally better

  Immediately after experimental session

• Change in EEG oscillatory power across canonical frequency bands (µV²/Hz)

  EEG - spectral analysis - Electroencephalography (EEG) is a non-invasive neuroimaging method that measures the brain's electrical activity via electrodes placed on the scalp. Change in EEG oscillatory power across canonical frequency bands (delta, theta, alpha, beta, gamma) during music listening under psilocybin. Analyses will be conducted at the scalp sensor level using Statistical Parametric Mapping, version 12 (SPM12). Group-level contrasts of oscillatory power changes (µV²/Hz) across music conditions

  During experimental session up to 10 hours

• Music Ratings: Autobiographical Salience

  Ratings of autobiographical salience for each song. Autobiographical salience is scored from 0 (none) to 4 (extremely autobiographically salient). More autobiographically salient music is thought to be better.

  1-day following experimental session and immediately post 1-month EEG music listening session

• Spiritual Experience - Altered States of Consciousness (ASC-11D)

  Feelings of sacredness, transcendence, or contact with a higher reality. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Higher Spiritual Experience scores are generally better.

  Immediately after experimental session

• Blissful State (11D-ASC)

  Intense feelings of happiness, peace, and contentment. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Higher Blissful State scores are generally better.

  Immediately after experimental session

• Insightfulness (11D-ASC)

  Deep personal or existential insights, perceived understanding of self or reality. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Higher Insightfulness scores are generally better.

  Immediately after experimental session

• Disembodiment (11D-ASC)

  Altered sense of the body, including floating, detachment, or out-of-body experiences. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Disembodiment scores are generally neutral or ambivalent. Mild forms may support ego dissolution and positive outcomes, but extreme disembodiment sometimes predicts challenging experiences.

  Immediately after experimental session

• Impaired Cognition & Control (11D ASC)

  Difficulty thinking clearly, controlling thoughts, or performing tasks. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Higher Impaired Cognition and Control are generally linked with confusion and less therapeutic benefit.

  Immediately after experimental session

• Anxiety (11D-ASC)

  Fear, unease, or paranoid thoughts during the experience. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Higher Anxiety is generally linked with lower acute well-being, though may sometimes precede later benefit if well-supported.

  Immediately after experimental session

• Complex Imagery (11D-ASC)

  Vivid, detailed visual imagery of objects, scenes, or entities. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Complex Imagery is generally neutral. Vivid imagery contributes to meaningfulness but is not a consistent predictor of therapeutic change.

  Immediately after experimental session

• Elementary Imagery (11D-ASC)

  Simple visual patterns such as colors, shapes, or geometric forms. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Elementary Imagery is generally neutral. It is a common perceptual effect of psilocybin but is not strongly tied to long-term outcomes.

  Immediately after experimental session

• Audio-Visual Synesthesia (11D-ASC)

  Cross-modal experiences, such as hearing colors or seeing sounds. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Audio-Visual Synesthesia is generally neutral. It is an interesting phenomenology, but has weak association with outcomes.

  Immediately after experimental session

• Changed Meaning of Percepts (11D-ASC)

  Altered interpretation of ordinary sensory stimuli, often with symbolic or novel significance. The 11D-ASC is a self-report questionnaire designed to assess the phenomenology of altered states of consciousness induced by psychedelics and other methods (e.g., meditation, sensory deprivation). There are 11 dimensions. Questions are scored from 0 (No, not more than usual) to 100 (Yes, much more than usual). Changed Meaning of Percepts can be positive or negative. It can enhance therapeutic meaning and insight (positive), but in some cases may drive paranoia or misinterpretation (negative).

  Immediately after experimental session

Secondary Outcomes (16)

• Brain Activity measured by Blood Oxygenation Level Dependent signal

  At Preparation Session 2 (before experimental session) and 1-week post experimental session

• Joyful Activation (GEMS-Joy)

  1-day after experimental session

• Trait Impulsivity Questionnaire (BIS-11)

  Preparation (pre experiment), 1-week post experimental session, and 1-month post experimental session

• Core Dispositional Flow Scale (C DFS)

  Preparation (pre experiment), 1-week post experimental session, and 1-month post post experimental session

• Satisfaction With Life Scale (SWLS)

  Preparation (baseline), 1-week post experimental session , and 1-month post experimental session

Study Arms (1)

6 hour playlist of music

EXPERIMENTAL

A 6 hour playlist of music.

Drug: Psilocybin (high dose); Behavioral: Playlist 1; Behavioral: Playlist 2; Behavioral: Playlist 3; Behavioral: Playlist 4; Behavioral: Playlist 5

Interventions

Psilocybin (high dose) DRUG

25 mg pill

Also known as: DMF#037635 (Type II), Purisys LLC, Psilocybin Drug Substance

6 hour playlist of music

Playlist 1 BEHAVIORAL

Six hour playlist

6 hour playlist of music

Playlist 2 BEHAVIORAL

A six hour playlist

6 hour playlist of music

Playlist 3 BEHAVIORAL

A six hour playlist

6 hour playlist of music

Playlist 4 BEHAVIORAL

A six hour playlist

6 hour playlist of music

Playlist 5 BEHAVIORAL

A six hour playlist

6 hour playlist of music

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fluent in English
• No hearing impairment
• Right-handed
• Have a screening weight ≥ 40 kg (88.18 lbs) with BMI ≥16.
• Be medically stable as determined by screening for medical problems via a personal interview, a medical history, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days.
• Agree to refrain from using any psychoactive drugs within 24 hours of each drug administration. The exceptions are caffeine and nicotine, which can be consumed before arriving for drug administration sessions.
• Agree not to take any as needed (PRN) medications on the mornings of drug sessions
• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
• Agree not to use any hair conditioner 24-hours before EEG sessions (Visits 3, 4, and 7)
• Females of child-bearing potential must agree to use highly effective methods of contraception (defined as use of an intrauterine device, vaginal ring, or implanted or oral hormonal contraceptives) during the study
• Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti- inflammatory drugs, and common doses of vitamins and minerals.
• Have limited lifetime use of hallucinogens, if any (the following criteria are preferred: no use in the past 5 years; total hallucinogen use less than 10 times)
• Proof of COVID-19 vaccination.

You may not qualify if:

• Unusually low reward response to music (defined as a majority of responses of "1" on the BMRQ)
• Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing highly effective means of contraception
• Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation), prolonged corrected QT interval (QTc) interval (i.e., QTc \> 450 msec), artificial heart valve, or transient ischemic attack (TIA) in the past year
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• Currently taking psychoactive prescription medication on a regular (e.g., daily) basis - exceptions may be made at the discretion of the study team physician for participants taking medications with short half-life if participants are able to abstain from taking the medication during session days (e.g. methylphenidate taken for attention or hyperactivity)
• Currently taking on a regular (e.g., daily) basis any medications that have a primary centrally-acting serotonergic effect, including Monoamine Oxidase Inhibitors (MAOIs). For individuals who have intermittent or PRN use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
• Current or past history of meeting Diagnostic and Statistical Manual (DSM-5) criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I Disorder
• Current or history within one year of meeting DSM-5 criteria for a moderate or severe substance use disorder. If a nicotine user, consuming the equivalent of more than 10 cigarettes per day.
• Have a first-degree relative with schizophrenia spectrum or other psychotic disorders, or bipolar disorder with mania (except substance/medication-induced or due to another medical condition)
• Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
• History of a medically significant suicide attempt as assessed by a study team clinician
• Standard MRI contraindications: head trauma, claustrophobia incompatible with scanning, contraindicated medical devices, prior history as a metal worker and/or certain metallic objects in the body -- must complete MRI screening form and be approved by MRI technologist before each scan
• History of migraine.
• History of angiotensin-converting enzyme inhibitor (ACEi) angioedema

Sponsors & Collaborators

• Johns Hopkins University: lead
• Steven & Alexandra Cohen Foundation: collaborator

Study Sites (1)

Center for Psychedelics and Consciousness Research in the Behavioral Biology Research Center

Baltimore, Maryland, 21224, United States

Location

Related Publications (4)

• Barrett FS, Robbins H, Smooke D, Brown JL, Griffiths RR. Qualitative and Quantitative Features of Music Reported to Support Peak Mystical Experiences during Psychedelic Therapy Sessions. Front Psychol. 2017 Jul 25;8:1238. doi: 10.3389/fpsyg.2017.01238. eCollection 2017.

  PMID: 28790944 BACKGROUND

• Barrett FS, Grimm KJ, Robins RW, Wildschut T, Sedikides C, Janata P. Music-evoked nostalgia: affect, memory, and personality. Emotion. 2010 Jun;10(3):390-403. doi: 10.1037/a0019006.

  PMID: 20515227 BACKGROUND

• Kaelen M, Giribaldi B, Raine J, Evans L, Timmerman C, Rodriguez N, Roseman L, Feilding A, Nutt D, Carhart-Harris R. The hidden therapist: evidence for a central role of music in psychedelic therapy. Psychopharmacology (Berl). 2018 Feb;235(2):505-519. doi: 10.1007/s00213-017-4820-5. Epub 2018 Feb 2.

  PMID: 29396616 BACKGROUND

• Golden TL, Magsamen S, Sandu CC, Lin S, Roebuck GM, Shi KM, Barrett FS. Effects of Setting on Psychedelic Experiences, Therapies, and Outcomes: A Rapid Scoping Review of the Literature. Curr Top Behav Neurosci. 2022;56:35-70. doi: 10.1007/7854_2021_298.

  PMID: 35138585 BACKGROUND

Related Links

• Center for Psychedelics and Consciousness Research website

MeSH Terms

Interventions

Psilocybin

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Frederick S Barrett, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open-label psilocybin (25mg) but music condition is randomized.

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: September 18, 2025
• Study Start: August 12, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 18, 2025

Record last verified: 2025-09

Locations

US (1)