Understanding Music and Mindfulness Preferences in Psilocybin-Assisted Psychotherapy

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.