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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Psilocybin (high dose)
  25 mg pill
• Поведенческое Playlist 1
  Six hour playlist
• Поведенческое Playlist 2
  A six hour playlist
• Поведенческое Playlist 3
  A six hour playlist
• Поведенческое Playlist 4
  A six hour playlist
• Поведенческое Playlist 5
  A six hour playlist

Первичные конечные точки

• Challenging Experiences Questionnaire [Срок оценки: Immediately at the end of their experimental session]
• Psychological Insight Questionnaire (PIQ) [Срок оценки: Immediately at end of experimental session]
• Core Flow State Scale (C-FSS) [Срок оценки: Immediately at end of experimental session]
• Mystical Experiences Questionnaire (MEQ-30) [Срок оценки: Immediately at end of experimental session]
• Experience of Unity (11D-ASC) [Срок оценки: Immediately after experimental session]
• Change in EEG oscillatory power across canonical frequency bands (µV²/Hz) [Срок оценки: During experimental session up to 10 hours]
• Music Ratings: Autobiographical Salience [Срок оценки: 1-day following experimental session and immediately post 1-month EEG music listening session]
• Spiritual Experience - Altered States of Consciousness (ASC-11D) [Срок оценки: Immediately after experimental session]
• Blissful State (11D-ASC) [Срок оценки: Immediately after experimental session]
• Insightfulness (11D-ASC) [Срок оценки: Immediately after experimental session]

Вторичные конечные точки (12)

• Brain Activity measured by Blood Oxygenation Level Dependent signal [Срок оценки: At Preparation Session 2 (before experimental session) and 1-week post experimental session]
• Joyful Activation (GEMS-Joy) [Срок оценки: 1-day after experimental session]
• Trait Impulsivity Questionnaire (BIS-11) [Срок оценки: Preparation (pre experiment), 1-week post experimental session, and 1-month post experimental session]
• Core Dispositional Flow Scale (C DFS) [Срок оценки: Preparation (pre experiment), 1-week post experimental session, and 1-month post post experimental session]
• Satisfaction With Life Scale (SWLS) [Срок оценки: Preparation (baseline), 1-week post experimental session , and 1-month post experimental session]
• Big Five Inventory - 10 items (BFI-10) [Срок оценки: Preparation (baseline), 1-week post experimental session and 1-month post experimental session]
• Behavioral Activation and Inhibition (BAI) [Срок оценки: Preparation (baseline), 1-week post experimental session and 1-month post experimental session]
• Barcelona Music Reward Questionnaire (BMRQ) [Срок оценки: Preparation (baseline), 1-week post experimental session and 1-month post experimental session.]
• Wonder (GEMS-Wonder) [Срок оценки: 1-day after experimental session]
• Transcendence (GEMS-Transcendence) [Срок оценки: 1-day after experimental session]
• Tenderness (GEMS-Tenderness) [Срок оценки: 1-day after experimental session]
• Peacefulness (GEMS-Peacefulness) [Срок оценки: 1-day after experimental session]

Критерии участия

Критерии включения

• • 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.

Критерии исключения

• • 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Center for Psychedelics and Consciousness Research in the Behavioral Biology Research Cent — Baltimore

Публикации

• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT07180108 · IRB00372917

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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