Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial
In an exploratory placebo-controlled within-subject trial, a single 0.3 mg/kg psilocybin session delivered within an ACT-informed psychotherapy significantly increased psychological flexibility, several mindfulness facets and values‑congruent living, with gains maintained through 16 weeks. Improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity, supporting psychological flexibility as a putative mechanism of change in psilocybin-assisted therapy for MDD.
Authors
- Richard Zeifman
- James Guss
- Deepak Cyril D’Souza
Published
Abstract
Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within a manualized psychotherapy that incorporated principles of Acceptance and Commitment Therapy. Depression severity, psychological flexibility, mindfulness, and values-congruent living were measured over a 16-weeks study period. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved following psilocybin and were maintained through week 16. Additionally, improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity following psilocybin. These findings support the theoretical premise of integrating psilocybin treatment with psychotherapeutic platforms that target psychological flexibility and add to emerging evidence that increasing psychological flexibility may be an important putative mechanism of change in psilocybin-assisted therapy for MDD and potentially, other mental health conditions.
Research Summary of 'Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial'
Introduction
In recent years there has been renewed interest in the therapeutic potential of classical psychedelics such as psilocybin for a range of neuropsychiatric conditions, including major depressive disorder (MDD). Earlier phase trials have reported rapid and sometimes long-lasting antidepressant effects after one or two doses, but the mechanisms that explain both the rapid onset and persistence of benefit remain uncertain. Proposed mechanisms include neurobiological changes (for example, neuroplasticity), acute subjective experiences (such as mystical-type experiences), and psychological or behavioural processes including increased psychological flexibility, experiential acceptance, connectedness, and revision of high-level beliefs. Sloshower and colleagues set out to examine psychological flexibility as a potential mechanism of change within an exploratory, placebo-controlled, within-subject clinical trial of psilocybin-assisted therapy for moderate to severe MDD. Specifically, the study tested whether psilocybin dosing sessions embedded in an Acceptance and Commitment Therapy (ACT)-informed psychotherapy protocol would produce changes in psychological flexibility, mindfulness facets, and values-congruent living, and whether changes in psychological flexibility or experiential acceptance were associated with reductions in depressive symptoms.
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Study Details
- Study Typeindividual
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- APA Citation
Sloshower, J., Zeifman, R. J., Guss, J., Krause, R., Safi-Aghdam, H., Pathania, S., Pittman, B., & D’Souza, D. C. (2024). Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial. Scientific Reports, 14(1). https://doi.org/10.1038/s41598-024-58318-x
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