Psilocybin therapy emphasizing the use of music.

Psilocybin therapy emphasizing the use of guided mindfulness.

Acceptability of each therapeutic approach as measured by the Theoretical Framework of Acceptability (TFA) questionnaire for music-centered and mindfulness-centered interventions.

Items cover comfort with the intervention, effort required, ethical or moral concerns, perceived effectiveness, clarity of intervention rationale, confidence in performing required activities, potential interference with other priorities, and overall acceptability. Each item is rated on a 5-point Likert scale (1 = lowest to 5 = highest). Total scores are calculated by summing all item responses, with possible scores ranging from 8 to 40. Higher scores indicate greater acceptability of the intervention.

Rates of adverse events in participants receiving their preferred versus non-preferred interventions. Adverse events include any treatment-emergent symptoms reported by participants or observed by study staff.

Rates of participant drop-outs in participants receiving their preferred versus non-preferred interventions. Drop-out is defined as missing more than 10% of scheduled visits during the active treatment period.

Rates of participant drop-outs in participants receiving music-centered versus mindfulness-centered approaches. Drop-out is defined as missing more than 10% of scheduled visits during the active treatment period.

The Montgomery-Åsberg Depression Rating Scale is a 10-item, clinician-rated scale to rate the severity of the depressive symptoms. Each item is scored from 0 (item's symptoms not present) to 6 (item's symptoms are severe). The total possible score is 60. Higher scores indicate greater severity. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Beck Depression Inventory Scale is a 21-item, patient-rated scale to rate the severity of the depressive symptoms. Each item is scored from 0 (item's symptoms not present) to 3 (item's symptoms are severe). The total possible score is 63. Higher scores indicate greater severity. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Generalized Anxiety Disorder-7 (GAD-7) is a 7-item, participant-rated measure assessing the core symptoms of generalized anxiety over the past two weeks. Each item is scored from 0 (not at all) to 3 (nearly every day), yielding a total score from 0 to 21. Higher scores indicate greater severity of anxiety symptoms. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The EQ-5D-5L is a standardized, self-reported measure of health-related quality of life across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 5-level scale reflecting increasing severity of problems. Responses are converted into a single index score, ranging from -0.59 to 1, with 1 representing the best possible health state. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) is a self-reported measure of enjoyment and satisfaction across multiple domains of daily functioning, including physical health, mood, work, household activities, social relationships, and general activities. The total score is calculated as the sum of the first 14 items, each rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Total scores range from 14 to 70, with higher scores indicating greater enjoyment and satisfaction with quality of life. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Work and Social Adjustment Scale (WSAS) is a 5-item, self-reported measure of functional impairment attributable to a mental health problem across five domains: work, home management, social leisure activities, private leisure activities, and close relationships. Each item is rated on a 9-point scale ranging from 0 (no impairment) to 8 (severe impairment). Total scores range from 0 to 40, with higher scores indicating greater functional impairment. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Gratitude Questionnaire-Six Item Form (GQ-6) is a 6-item, self-reported measure of dispositional gratitude. Items are rated on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Total scores are calculated by summing item responses, with possible scores ranging from 6 to 42. Higher scores indicate greater levels of gratitude. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Multidimensional Psychological Flexibility Inventory-24 item version (MPFI-24) is a self-reported measure of psychological flexibility across six core processes: acceptance, defusion, present-moment awareness, self-as-context, values, and committed action. Items are rated on a 6-point Likert scale ranging from 1 (never true) to 6 (always true). The total score is calculated by summing item responses after appropriate reverse scoring of psychological inflexibility items. Total scores range from 24 to 144, with higher scores indicating greater psychological flexibility. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Watts Connectedness Scale (WCS) is a self-reported measure of perceived psychological and existential connectedness, including connectedness to self, others, nature, and the broader universe. The scale consists of 23 items rated on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Total scores are calculated by summing item responses, with possible scores ranging from 23 to 161. Higher scores indicate greater perceived connectedness. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Pearlin Mastery Scale is a 7-item, self-reported measure of perceived control over life circumstances. Items are rated on a 4-point Likert scale ranging from 1 (strongly disagree) to 4 (strongly agree). Total scores are calculated by summing item responses, with possible scores ranging from 7 to 28. Higher scores indicate a greater sense of mastery or perceived control. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Cultural Formulation Interview, adapted for psychedelic therapy, will be used identify of factors relevant to participants' experiences and preferences at baseline. Post-trial interviews will be conducted to capture factors that influence the participants' experiences and treatment preferences.

The Challenging Experience Questionnaire-7 item version (CEQ-7) is a self-reported measure assessing the intensity of challenging experiences during a treatment session. Participants rate 7 statements on a 6-point Likert scale ranging from 0 (not at all) to 5 (extremely). Total scores are calculated by summing all item responses, with possible scores ranging from 0 to 35. Higher scores indicate greater intensity of challenging experiences. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Acceptance/Avoidance-Promoting Experiences Questionnaire - Short Form (APEQ-SF) is a 21-item, self-reported measure assessing the extent to which participants experience acceptance-promoting versus avoidance-promoting psychological processes during a treatment session. Items are answered dichotomously as 0 (No, not at all) or 1 (Yes, extremely or absolutely). Total scores are calculated by summing item responses, with possible scores ranging from 0 to 21. Higher scores indicate greater engagement in acceptance-promoting experiences relative to avoidance. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Imprinting Questionnaire is a 5-item, self-reported measure assessing the extent to which participants experience hallucinations influenced by previously seen content. Items include vivid visual hallucinations, hallucinations resembling recently or previously seen media (e.g., television, video games, paintings), and hallucinations resembling recently or previously seen non-media scenes (e.g., landscapes, cities). Participants respond dichotomously (0 = No, not at all; 1 = Yes, extremely or absolutely). Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Mystical Experience Questionnaire-4 item version (MEQ-4) is a self-reported measure assessing the intensity of mystical-type experiences during a treatment session. Participants rate 4 statements on a 6-point Likert scale ranging from 0 (none) to 5 (extreme). Total scores are calculated by summing all item responses, with possible scores ranging from 0 to 20. Higher scores indicate stronger mystical-type experiences. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Awe Experience Scale - Short Form (AWE-SF) is a 12-item, self-reported measure assessing the intensity of awe experienced during a treatment session across six factors: Time, Self-Loss, Connectedness, Vastness, Physiological Changes, and Accommodation. Items are rated on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Total scores are calculated by averaging all item responses, with possible scores ranging from 1 to 7. Higher scores indicate stronger experiences of awe. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Modified Psychedelic Communitas Scale is an 8-item, self-reported measure assessing the sense of relational connection, shared humanity, and social bonding experienced with facilitators during a treatment session. Items include feeling a bond, a sense of belonging, harmony, sharing, equality, irrelevance of social status, resolution of ego-related tensions, and strong connection with facilitators. Participants rate each item on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Total scores are calculated by summing item responses, with possible scores ranging from 8 to 56. Higher scores indicate stronger communitas experiences. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

The Psychedelic Music Questionnaire - Short Form (PMQ-SF) is a self-reported measure assessing participants' experiences of music during a psychedelic treatment session. Items assess the extent to which the music was supportive, meaningful, personally resonant, aesthetically appreciated, emotionally engaging, and helped participants gain new insights, as well as any negative reactions such as feeling distracted, irritated, or unsafe. Participants rate 15 items on a 5-point Likert scale ranging from 1 (not at all) to 5 (extremely). Total scores are calculated by summing item responses, with possible scores ranging from 15 to 75. Higher scores indicate more positive and engaging experiences with the music. Scores will be compared by preference group (preferred vs. non-preferred) .

The Working Alliance Inventory - Short Revised (WAI-SR, Therapist version) is a 10-item, self-reported measure assessing therapists' perception of the therapeutic alliance during treatment sessions. Items evaluate agreement on goals and tasks, mutual understanding, collaboration, respect, and concern for the patient's welfare. Therapists rate each item on a 5-point Likert scale ranging from 1 (seldom) to 5 (always). Total scores are calculated by summing item responses, with possible scores ranging from 10 to 50. Higher scores indicate a stronger perceived therapeutic alliance. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

Linguistic synchrony between the participant and clinicians will be quantified using Natural Language Processing (NLP) applied to session transcripts. The measure has no predefined minimum or maximum value; higher values indicate greater alignment in language use between the participant and clinicians. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).

Cardiovascular synchrony between the participant and clinicians will be assessed using electrocardiography (ECG)-derived heart rate variability (HRV) and respiratory sinus arrhythmia (RSA). A validated surrogate synchrony method will be applied to quantify the extent of physiological alignment between the participant and clinicians during therapy sessions. The measure has no predefined minimum or maximum value; higher values indicate greater cardiovascular synchrony. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered versus mindfulness-centered).