Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial

This re-analysis of a single-blind, placebo-controlled study (n=19) of psilocybin (21mg/70kg) in combination with therapy (ACT, 8x) finds that psychological flexibility, mindfulness, and living according to one’s values improved after psilocybin and stayed better through the 16-week study period. It also shows that greater psychological flexibility and experiential acceptance were linked with lower depression scores after psilocybin.

Abstract of Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression

“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.”

Authors: Jordan Sloshower, Richard J. Zeifman, Jeffrey Guss, Robert Krause, Hamideh Safi-Aghdam, Surbhi Pathania, Brian Pittman & Deepak Cyril D’Souza

Summary of Abstract of Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression

Psilocybin, an alkaloid found in the Psilocybe genus of mushrooms, may have rapid acting and persisting therapeutic effects across a number of mental health conditions, including depression, anxiety, and substance use disorders.

Psilocybin-assisted therapy may produce rapid and sustained antidepressant effects via neurobiological, psychological, cognitive/behavioral and spiritual mechanisms, including increased psychological flexibility and experiential acceptance, increased connectedness, relaxation and revision of high-level beliefs, and emotional breakthrough.

Multiple potential mechanisms may contribute to the therapeutic effects of psilocybin-assisted therapy, and it remains unclear which psychotherapeutic models are optimal. We selected Acceptance and Commitment Therapy (ACT) as our therapeutic approach.

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Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial

https://doi.org/10.1038/s41598-024-58318-x

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Cite this paper (APA)

Sloshower, J., Zeifman, R. J., Guss, J., Krause, R., Safi-Aghdam, H., Pathania, S., ... & 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 Reports14(1), 8833.

Study details

Compounds studied
Psilocybin

Topics studied
Depression

Study characteristics
Original Re-analysis Placebo-Controlled Single-Blind Within-Subject Re-analysis

Participants
19 Humans

Institutes

Institutes associated with this publication

Yale University
The Yale Psychedelic Science Group was established in 2016.

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 21 mg | 1x

Linked Research Papers

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Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial
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