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
Classic psychedelics such as psilocybin reliably alter consciousness, producing changes in perception, emotion, and meaning-making. Music has long been recognized as an important component of psychedelic therapy, serving to guide the experience and shape its trajectory. However, little is known about how different types of music influence outcomes, particularly music that is personally meaningful to participants. This study will investigate the effects of autobiographically salient (AS) music compared to standardized playlists during high-dose psilocybin sessions. The goal is to understand how personally relevant music modulates acute subjective experiences, emotional responses, and longer-term psychological outcomes. In addition, the study will examine brain and body responses to music under psilocybin, including how these responses differ when music is autobiographically salient. The central questions are whether AS music enhances emotional depth, psychological insight, and well-being more than non-autobiographical playlists, and whether the timing of AS music during the session influences these effects. Participants will be followed up after the psilocybin session to assess both short-term and longer-term outcomes, including well-being, mood, and meaning-making. This trial represents one of the first controlled investigations into how personalized music contributes to the therapeutic potential of psychedelics. Findings may help optimize music-based interventions in psychedelic therapy and improve understanding of the role of music in shaping altered states of consciousness.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
100
25 mg pill
Six hour playlist
A six hour playlist
A six hour playlist
A six hour playlist
A six hour playlist
Center for Psychedelics and Consciousness Research in the Behavioral Biology Research Center
Baltimore, Maryland, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: Immediately after experimental session
Brain Activity measured by Blood Oxygenation Level Dependent signal
Functional Magnetic Resonance Imaging (fMRI) is a non-invasive neuroimaging technique that measures brain activity by detecting changes in blood oxygenation (BOLD signal), which reflects local neural activity. We will be measuring a change in BOLD signal between the pre-experiment (preparation 2) and 1-week post-experiment. The main contrasts will include: * Pre vs Post (all music) * Pre vs Post (Autobiographically Salient music) * Pre vs. Post (JHC playlist music) * Pre vs Post (AMB playlist music)
Time frame: At Preparation Session 2 (before experimental session) and 1-week post experimental session
Joyful Activation (GEMS-Joy)
Cheerfulness, enthusiasm, vitality, dancing or movement impulses The Geneva Emotional Music Scale (GEMS) is a validated, music-specific instrument designed to measure the range of emotions evoked by music. GEMS is scored from 0 (not at all) to 4 (extremely). A higher Joyful Activation score is generally positive and liked to pleasurable absorption and well-being.
Time frame: 1-day after experimental session
Trait Impulsivity Questionnaire (BIS-11)
The Barratt Impulsiveness Scale (BIS-11) is one of the most widely used self-report instruments for assessing trait impulsivity. The BIS-11 is scored from 0 (Rarely/Never) to 3 (Almost Always/Always). Generally lower impulsivity is better.
Time frame: Preparation (pre experiment), 1-week post experimental session, and 1-month post experimental session
Core Dispositional Flow Scale (C DFS)
The Core Dispositional Flow Scale (CDFS) is a brief, validated self-report instrument designed to measure an individual's general tendency to experience flow across activities and contexts. The CDFS is measured from 1 (never) to 5 (always). A higher score is generally better.
Time frame: Preparation (pre experiment), 1-week post experimental session, and 1-month post post experimental session
Satisfaction With Life Scale (SWLS)
The Satisfaction With Life Scale (SWLS) is a brief self-report instrument designed to measure global cognitive judgments of one's overall life satisfaction. The SWLS is measured from 1 (strongly disagree) to 7 (strongly agree). A higher score is better.
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Time frame: Preparation (baseline), 1-week post experimental session , and 1-month post experimental session
Big Five Inventory - 10 items (BFI-10)
The Big Five Inventory-10 (BFI-10) is a short, validated self-report instrument designed to measure the five major dimensions of personality with minimal participant burden. The BFI-10 is measured from 1-Disagree strongly to 5-Agree Strongly. Depending on the personality dimension a higher (e.g., openness) or lower (e.g., neuroticism) score can be better.
Time frame: Preparation (baseline), 1-week post experimental session and 1-month post experimental session
Behavioral Activation and Inhibition (BAI)
The Behavioral Inhibition System (BIS) and Behavioral Activation System (BAS) Scales are self-report measures designed to assess individual differences in sensitivity to punishment and reward, based on Gray's Reinforcement Sensitivity Theory of personality. The BIS/BAS is measured from 1-Strongly disagree to 4- Strongly agree. Usually balance between BIS and BAS is considered most adaptive. Neither is better or worse, universally.
Time frame: Preparation (baseline), 1-week post experimental session and 1-month post experimental session
Barcelona Music Reward Questionnaire (BMRQ)
The Barcelona Music Reward Questionnaire (BMRQ) is a 20-item self-report scale that assesses individual differences in the sensitivity to music-induced reward across five domains: Musical Seeking, Emotion Evocation, Mood Regulation, Social Reward, and Sensory-Motor responses. Scores are summed within each domain and can also be aggregated into a global score. The BMRQ is measured from 1 (Completely disagree) to 5 (Completely agree). Generally a higher score is better, reflecting stronger emotional, motivational, and social responses to musical experience.
Time frame: Preparation (baseline), 1-week post experimental session and 1-month post experimental session.
Wonder (GEMS-Wonder)
Feelings of awe, amazement, transcendence in response to music The Geneva Emotional Music Scale (GEMS) is a validated, music-specific instrument designed to measure the range of emotions evoked by music. GEMS is scored from 0 (not at all) to 4 (extremely). A higher Wonder score is strongly aligned with mystical-type experiences and positive outcomes in psilocybin research (e.g., meaning, connectedness)
Time frame: 1-day after experimental session
Transcendence (GEMS-Transcendence)
Spiritual uplift, timelessness, and "beyond-the-self" states The Geneva Emotional Music Scale (GEMS) is a validated, music-specific instrument designed to measure the range of emotions evoked by music. GEMS is scored from 0 (not at all) to 4 (extremely). A higher Transcendence score is closely tied to beneficial mystical experiencers and long-term well-being gains.
Time frame: 1-day after experimental session
Tenderness (GEMS-Tenderness)
Warmth, empathy, affection, emotional closeness The Geneva Emotional Music Scale (GEMS) is a validated, music-specific instrument designed to measure the range of emotions evoked by music. GEMS is scored from 0 (not at all) to 4 (extremely). A higher Tenderness score supports prosocial feelings and can lead to increased compassion and positive social outcomes.
Time frame: 1-day after experimental session
Peacefulness (GEMS-Peacefulness)
Calmness, relaxation, inner quiet. The Geneva Emotional Music Scale (GEMS) is a validated, music-specific instrument designed to measure the range of emotions evoked by music. GEMS is scored from 0 (not at all) to 4 (extremely). A higher Peacefulness score is associated with positive acute states, reduced anxiety, and therapeutic benefit under supportive conditions.
Time frame: 1-day after experimental session
Power (GEMS-Power)
Strong, energetic, dominant feelings of drive or determination The Geneva Emotional Music Scale (GEMS) is a validated, music-specific instrument designed to measure the range of emotions evoked by music. GEMS is scored from 0 (not at all) to 4 (extremely). Power can be positive and support motivation and agency but is not consistently linked to psilocybin outcomes; sometimes associated with intensity that can become challenging. P
Time frame: 1-day after experimental session
Tension (GEMS-Tension)
Unease, restlessness, suspense, emotional strain. The Geneva Emotional Music Scale (GEMS) is a validated, music-specific instrument designed to measure the range of emotions evoked by music. GEMS is scored from 0 (not at all) to 4 (extremely). High Tension scores are often associated with challenging experiences and negative acute outcomes, though mild tension may precede later therapeutic insights.
Time frame: 1-day after experimental session
Sadness (GEMS-Sadness)
Unease, restlessness, suspense, emotional strain. The Geneva Emotional Music Scale (GEMS) is a validated, music-specific instrument designed to measure the range of emotions evoked by music. GEMS is scored from 0 (not at all) to 4 (extremely). Sadness can be cathartic and meaning-enhancing but excessive sadness may contribute to difficult experiences.
Time frame: 1-day after experimental session
Negative-Affect Composite Factor (STAI, DASS-21, POMS Total Mood Disturbance, PANAS-Negative Affect)
Composite index of negative mood/affect derived from four validated self-report measures: State-Trait Anxiety Inventory (STAI) : 0-3 per item; lower is better. Depression, Anxiety, Stress (DASS-21), 0-3 per item; lower is better. Profile of Mood States (POMS)-Total Mood Disturbance (TMD): 0-4 per item; lower TMD is better. Positive and Negative Affect Schedule (PANAS)-Negative Affect (NA) subscale: 0-4 per item; lower NA is better.
Time frame: Baseline; Pre-session; 1-day post-session; 1-week post-session; 1-month post-session; 1-day follow-up after the 1-month assessment.