How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change
This re-analysis of the psilocybin (25mg) versus escitalopram (antidepressant, 6 weeks) RCT finds that in the psilocybin arm, experiential avoidance reductions led to improvements in mental health outcomes (e.g. depression severity). Note: the trial itself was insignificant on the primary measure of depression.
Authors
- Richard Zeifman
- Robin Carhart-Harris
- Mark Wagner
Published
Abstract
Background
Psilocybin therapy is receiving attention as a mental health intervention with transdiagnostic potential. In line with psychotherapeutic research, qualitative research has highlighted the role of reductions in experiential avoidance (and increases in connectedness) within psilocybin therapy. However, no quantitative research has examined experiential avoidance as a mechanism underlying psilocybin therapy's therapeutic effects.
Method
Data was used from a double-blind randomized controlled trial that compared psilocybin therapy (two 25 mg psilocybin session plus daily placebo for six weeks) with escitalopram (two 1 mg psilocybin sessions plus 10-20 mg daily escitalopram for six weeks) among individuals with major depressive disorder (N = 59). All participants received psychological support. Experiential avoidance, connectedness, and treatment outcomes were measured at pre-treatment and at a 6 week primary endpoint. Acute psilocybin experiences and psychological insight were also measured.
Results
With psilocybin therapy, but not escitalopram, improvements in mental health outcomes (i.e., well-being, depression severity, suicidal ideation, and trait anxiety) occurred via reductions in experiential avoidance. Exploratory analyses suggested that improvements in mental health (except for suicidal ideation) via reduction in experiential avoidance were serially mediated through increases in connectedness. Additionally, experiences of ego dissolution and psychological insight predicted reductions in experiential avoidance following psilocybin therapy.
Limitations
Difficulties inferring temporal causality, maintaining blindness to condition, and reliance upon self-report.
Conclusions
These results provide support for the role of reduced experiential avoidance as a putative mechanism underlying psilocybin therapy's positive therapeutic outcomes. The present findings may help to tailor, refine, and optimize psilocybin therapy and its delivery.
Research Summary of 'How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change'
Introduction
A growing literature indicates that psilocybin therapy—administration of psilocybin alongside psychological support—can improve a range of mental health outcomes including depressive and anxious symptoms, suicidal ideation, and subjective well-being. Prior qualitative and survey-based work has highlighted reductions in experiential avoidance (defined as unwillingness to remain in contact with distress and rigid efforts to minimise it) and increases in connectedness as recurrent themes reported by participants after psychedelic experiences. However, quantitative, controlled tests of experiential avoidance as a mechanism of change in psilocybin therapy have been lacking, and many prior studies relied on non-clinical convenience samples and measures with contested validity. Zeifman and colleagues set out to test whether reductions in experiential avoidance mediate improvements in mental health following psilocybin therapy, and whether this mediation differs from that seen with a standard antidepressant (escitalopram). The study also explored whether increases in connectedness might act as a serial mediator (i.e., reductions in experiential avoidance leading to greater connectedness, which then leads to better outcomes) and whether specific acute features of the psilocybin experience (ego dissolution, mystical-type experiences, emotional breakthrough, psychological insight) predict reductions in experiential avoidance.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Zeifman, R. J., Wagner, A. C., Monson, C. M., & Carhart-Harris, R. L. (2023). How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change. Journal of Affective Disorders, 334, 100-112. https://doi.org/10.1016/j.jad.2023.04.105
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