The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder

We examined if the therapeutic alliance between study participants and intervention facilitators in a psilocybin-assisted therapy (PAT) trial changed over time and whether there were relationships between alliance, acute psilocybin experiences, and depression outcomes. In a randomized, waiting list-controlled clinical trial for major depressive disorder in adults (N = 24), participants were randomized to an immediate (N = 13) or delayed (N = 11) condition with two oral doses of psilocybin (20mg/70kg and 30mg/70kg). Ratings of therapeutic alliance significantly increased from the final preparation session to one-week post-intervention (p =.03, d =.43). A stronger total alliance at the final preparation session predicted depression scores at 4 weeks (r = -.65, p =.002), 6 months (r = -.47, p =.036), and 12 months (r = -.54, p =.014) post-intervention. A stronger total alliance in the final preparation session was correlated with higher peak ratings of mystical experiences (r =.49, p =.027) and psychological insight (r =.52, p =.040), and peak ratings of mystical experience and psychological insight were correlated with depression scores at 4 weeks (r = -.45, p =.030 for mystical; r = -.75, p