Understanding Music and Mindfulness Preferences in Psilocybin-Assisted Psychotherapy

NCT07373535 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 2025-4333288527
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this pilot clinical trial is to learn whether it is feasible to individually tailor psilocybin-assisted psychotherapy (PAP) for people with treatment-resistant depression (TRD) based on their personal preferences. The study also aims to explore whether two different psychotherapy styles, music-centered and mindfulness-centered, influence how people respond to psilocybin treatment. The main questions it aims to answer are:

• Is it feasible to conduct a patient-preference randomized trial of psilocybin-assisted psychotherapy?
• Does receiving a preferred psychotherapy style improve treatment experiences or outcomes?
• How do music-centered and mindfulness-centered PAP approaches compare in their effects on improving mood and well-being? Researchers will compare music-centered PAP to mindfulness-centered PAP to see if aligning psychotherapy with individual preferences is a practical and potentially beneficial approach for improving treatment efficacy and tolerability. Participants will:
• Be adults with treatment-resistant depression
• Receive two 25 mg psilocybin (PEX010, Filament Health) sessions, spaced four weeks apart
• Experience one session with music-centered psychotherapy and one with mindfulness-centered psychotherapy
• Before treatment, rate their preference for the two psychotherapy approaches
• Be randomly assigned to receive their preferred or non-preferred approach first, followed by the other
• Complete preparation and integration sessions before and after each psilocybin session This feasibility trial will also collect information on participants' cultural and personal factors influencing psychotherapy preferences using a modified Cultural Formulation Interview, and explore physiological measures of therapeutic alliance, an important factor in psychotherapy outcomes.

Conditions

Treatment-Resistant Major Depressive Disorder

Keywords

Psilocybin; Clinical Trial; Depressive Disorder, Treatment-Resistant; Music; Mindfulness; Feasibility; Culture; Patient preference

Outcome Measures

Primary Outcomes (6)

• Enrollment Feasibility

  The proportion of participants screened as eligible who enroll in the trial.

  From screening through enrollment

• Overall Trial Completion Feasibility

  The proportion of enrolled participants who complete the trial, defined as attending ≥ 90% of required study visits.

  From enrollment through the end of active treatment (Week 10)

• Trial Completion by Preference Assignment

  The proportion of participants in the preferred and non-preferred treatment groups who complete ≥ 90% of study visits.

  From enrollment through the end of active treatment (Week 10)

• Distribution of Treatment Preferences

  The proportion of participants who choose the music-centered versus the mindfulness-centered approach as their preferred treatment at baseline.

  Baseline

• Ease of Delivering Treatment Approaches as Assessed by the NASA-TLX

  The ease of delivering the music-centered versus the mindfulness-centered as assessed by therapists' reported levels of effort with each intervention measured with the NASA Task Load Index (NASA-TLX). The NASA Task Load Index (NASA-TLX) is a self-reported measure assessing perceived workload and cognitive effort during a task that will be completed by the therapists. It evaluates six dimensions: Mental Demand, Physical Demand, Temporal Demand, Performance, Effort, and Frustration. Each dimension is rated using a continuous 0-100 visual analog scale, with anchors ranging from very low (0) to very high (100) (for Performance, 0 = poor to 100 = excellent). Higher scores reflect greater perceived workload, except for Performance, where higher scores indicate better perceived performance. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered vs. mindfulness-centered).

  End of each psilocybin treatment session (Week 3, Week 9)

• Theoretical Framework of Acceptability (TFA)

  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.

  Baseline, Weeks 3 and 9 (treatment sessions), Week 11 (follow-up)

Secondary Outcomes (22)

• Rate of Adverse Events in Music- versus Mindfulness-centered Interventions

  Baseline, Week 5 (primary endpoint), Week 11 (follow-up)

• Rate of Adverse Events in Preferred vs. Non-Preferred Interventions

  Baseline, Week 5 (primary endpoint), Week 11 (follow-up)

• Rate of Participant Drop-Outs in Preferred vs. Non-Preferred Interventions

  Baseline, Week 5 (primary endpoint), Week 11 (follow-up)

• Rate of Participant Drop-Outs in Music- versus Mindfulness-centered Interventions

  Baseline, Week 5 (primary endpoint), Week 11 (follow-up)

• Change From Baseline in MADRS Total Score to Key Endpoint

  Baseline, Week 5 (primary endpoint)

Other Outcomes (4)

• Therapeutic Alliance - Patient (WAI-SR)

  Weeks 1 and 7 (preparation sessions), Weeks 3 and 9 (treatment and integration sessions)

• Therapeutic Alliance - Therapist (WAI-SRT)

  Weeks 1 and 7 (preparation sessions), Weeks 3 and 9 (treatment and integration sessions)

• Linguistic Synchrony

  Weeks 1 and 7 (preparation sessions), Weeks 3 and 9 (treatment and integration sessions)

Study Arms (2)

Preferred treatment

EXPERIMENTAL

Drug: Psilocybin 25mg; Other: Music-centered psilocybin-assisted therapy; Other: Mindfulness-centered psilocybin-assisted therapy

Non-preferred treatment

EXPERIMENTAL

Drug: Psilocybin 25mg; Other: Music-centered psilocybin-assisted therapy; Other: Mindfulness-centered psilocybin-assisted therapy

Interventions

Psilocybin 25mg DRUG

Psilocybin 25mg

Also known as: PEX010(25)

Non-preferred treatment; Preferred treatment

Music-centered psilocybin-assisted therapy OTHER

Psilocybin therapy emphasizing the use of music.

Non-preferred treatment; Preferred treatment

Mindfulness-centered psilocybin-assisted therapy OTHER

Psilocybin therapy emphasizing the use of guided mindfulness.

Non-preferred treatment; Preferred treatment

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 21 years of age at screening.
• Diagnosis of unipolar Major Depressive Disorder (MDD) according to diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), confirmed by a study psychiatrist using the Mini International Neuropsychiatric Interview (MINI) version 7.0.2.
• Failure to achieve remission from at least two trials of evidence-based oral antidepressants, in the current episode, of adequate dose and duration.
• Moderate to severe symptoms according to the clinician-administered Montgomery-Åsberg Depression Rating Scale (MADRS): total score ≥ 25 on screening.
• Active follow-up in psychiatry.
• Able and willing to give informed consent to participate in the study, and for the study clinicians to communicate with their psychiatrist throughout the intervention phase of the study.
• Available and willing to comply with all study assessments.
• Stable psychotropic medications for at least eight weeks at the time of enrollment.
• Able to read and understand French and/or English.
• Has at least one identified support person, including a friend or family member, who agrees to accompany patient home (or to an otherwise safe destination) following the psilocybin treatment sessions.

You may not qualify if:

• Deemed to be greater than low risk of suicide on psychiatric interview.
• Currently or previously diagnosed with any of the following, according to available information and psychiatric interview: major depression with psychotic features, schizophrenia spectrum or other psychotic disorders, and/or bipolar affective disorder I or related disorders.
• Current or past diagnosis of personality disorder deemed to pose a significant risk for safety and/or trial compliance.
• Family history (first-degree relative) of psychosis.
• Current or recent (\< six months) substance use disorder, except for tobacco use disorder.
• Deemed to be greater than low risk of future substance use disorder.
• Currently receiving and deemed to be unsuitable, on psychiatric interview, to discontinue medications with significant serotonin 2A antagonism (e.g., trazodone) or known potential for serious interactions with psilocybin including serotonin syndrome (e.g., monoamine oxidase inhibitors), seizures (e.g., lithium), or which may affect psilocybin pharmacokinetics (e.g. UDG modulators, aldehyde dehydrogenase inhibitors).
• Unwilling or unable to maintain current psychotropic medications throughout the treatment phase of the trial.
• Currently undergoing psychotherapy that will not remain stable for the duration of the study or was initiated within 21 days of baseline.
• Prior use of serotonergic psychedelics in the past year and/or more than five life-time uses.
• Use of any serotonergic psychedelic or ketamine, or any other illicit substance during the active treatment period of the trial.
• Medical contraindications:
• Current or past history of seizure disorder with the exception of infantile febrile seizures.
• Significant cardiovascular disease including uncontrolled blood pressure (\> 140/90mmHg), clinically significant arrhythmia, heart failure, coronary artery disease, history of ischemic or hemorrhagic stroke, or history of myocardial infarction.
• Abnormal and clinically significant results on the physical examination, laboratory investigations, or ECG at screening.

Sponsors & Collaborators

• Kyle Greenway: lead

Study Sites (2)

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Jewish General Hospital

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Patient Preference

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Patient Satisfaction; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

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

Study Officials

• Kyle T Greenway, MD

  Jewish General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Psychiatrist and Investigator

Model Details: A 10-week, pilot patient-preference clinical trial with two four-week treatment phases. At baseline, enrolled patients with TRD will rate their preferences for music-centered and mindfulness-centered approaches to PAP. Treatment phase one (weeks 1-4): patients will receive either their preferred or non-preferred treatment approach over 4 weeks, based on a simple 50:50 randomization. The key endpoint will occur in week 5. No treatment will take place between weeks 5-6. Treatment phase two (weeks 7-10): patients will be crossed-over to receive the other treatment approach over four weeks.

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 28, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)