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

Adam W Levin; Rafaelle Lancelotta; Nathan D Sepeda; Natalie Gukasyan; Sandeep Nayak; Theodore L Wagener; Frederick S Barrett; Roland R Griffiths; Alan K Davis

doi:10.1371/journal.pone.0300501

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

PLoS One. 2024 Mar 14;19(3):e0300501. doi: 10.1371/journal.pone.0300501. eCollection 2024.

Authors

Adam W Levin^{1

2}, Rafaelle Lancelotta¹, Nathan D Sepeda^{1

3}, Natalie Gukasyan³, Sandeep Nayak³, Theodore L Wagener^{4

5}, Frederick S Barrett³, Roland R Griffiths³, Alan K Davis^{1

3}

Affiliations

¹ The Ohio State University, Center for Psychedelic Drug Research and Education, Columbus, Ohio, United States of America.
² Department of Psychiatry, The Ohio State University, Columbus, Ohio, United States of America.
³ Johns Hopkins University, Center for Psychedelic and Consciousness Research, Baltimore, Maryland, United States of America.
⁴ Center for Tobacco Research, The Ohio State University James Comprehensive Cancer Center, Columbus, Ohio, United States of America.
⁵ Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.

Abstract

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 < .001 for insight). Stronger total alliance one week after the final psilocybin session predicted depression scores at 4 weeks (r = -.85, p < .001), 3 months (r = -.52, p = .010), 6 months (r = -.77, p < .001), and 12 months (r = -.61, p = .001) post-intervention. These findings highlight the importance of the therapeutic relationship in PAT. Future research should explore therapist and participant characteristics which maximize the therapeutic alliance and evaluate its relationship to treatment outcomes. Trial registration: Registration: Clinicaltrials.gov NCT03181529. https://classic.clinicaltrials.gov/ct2/show/NCT03181529.

Copyright: © 2024 Levin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Randomized Controlled Trial

MeSH terms

Adult
Depressive Disorder, Major* / drug therapy
Humans
Psilocybin / therapeutic use
Therapeutic Alliance*
Treatment Outcome

Substances

Psilocybin

Associated data

ClinicalTrials.gov/NCT03181529

Grants and funding

This study was funded in part by a crowd-sourced funding campaign organized by Tim Ferriss and a grant from the Riverstyx Foundation. AKD, NDA, NG, SN, FSB, and RRG are supported by funding from Tim Ferriss, Matt Mullenweg, Craig Nerenberg, Blake Mycoskie, the Steven and Alexandra Cohen Foundation. AKD, RL, and AWL are supported by the Center for Psychedelic Drug Research and Education in the College of Social Work at Ohio State University, funded by anonymous private donors. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AKD and RL are board members of Source Research Foundation. AKD is a Lead Trainer at Fluence. FB is a scientific advisor for WavePaths, Ltd and Mindstate Design Labs, Inc, and has provided consultation services for Gilgamesh Pharmaceuticals, Inc. These organizations were not involved in the design/execution of this study or the interpretation or communication of findings.