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 M. Nayak, Theodore L Wagener, Frederick S. Barrett, Roland R. Griffiths, Alan K. Davis
PLoS One March 14, 2024 DOI: 10.1371/journal.pone.0300501 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Adults with major depressive disorder |
| Intervention | Psilocybin-assisted therapy |
| Dose | 20mg/70kg and 30mg/70kg |
| Duration | 12-month follow-up |
| Topics | Psychedelic-assisted therapy Depression Psilocybin |
| Keywords | Psilocybin research Therapeutic relationships Mental health Depression treatment |
| Citations | 65 |
| Registration | NCT03181529 |
| Key findings | A stronger therapeutic alliance before and after psilocybin sessions predicted lower depression scores up to 12 months later, and was correlated with more intense mystical experiences and psychological insight. |
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 .
Comparable studies
Other randomized controlled trials on psilocybin and psychedelic-assisted therapy, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Healthy adults, mostly hallucinogen-naïve | 2011 | Randomized controlled trial | n = 18 |
| Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder Adults aged 25–65 with DSM-IV alcohol dependence and at least 4 heavy drinking days in... | 2022 | Randomized controlled trial | n = 95 |
| Increased global integration in the brain after psilocybin therapy for depression. Patients with treatment-resistant depression and patients with major depressive disorder | 2022 | Open-label trial and double-blind phase II randomized controlled trial | |
| Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. Adults diagnosed with major depressive disorder and no unstable somatic conditions | 2023 | Double-blind, randomised clinical trial | n = 52 |
| Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin Healthy participants | 2012 | Randomized controlled trial | n = 10 |
Citations in the library
Cited by 69
- Psychedelic-assisted psychotherapy: where is the psychotherapy research? Psychopharmacology August 1, 2024
- Quality of reporting on psychological interventions in psychedelic treatments: a systematic review. The Lancet Psychiatry 2025
- Psychedelics assisting therapy, or therapy assisting psychedelics? The importance of psychotherapy in psychedelic-assisted therapy. Frontiers in Psychology February 5, 2025
- Personal psychedelic experience of psychedelic therapists during training: should it be required, optional, or prohibited? International Review of Psychiatry June 12, 2024
- Psilocybin increases emotional empathy in patients with major depression. Molecular Psychiatry June 1, 2025
and 64 more in the library
Cites 45
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
and 40 more in the library