Skip to content

How Does Psilocybin Therapy Work? an Exploration of Experiential Avoidance as a Putative Mechanism of Change

Richard J. Zeifman

June 17, 2024 DOI: 10.32920/26052859 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Quasi-experimental study and randomized controlled trial Qualitative
Sample size 87
Population Healthy individuals and adults with major depressive disorder
Interventions Psilocybin Escitalopram
Dose 1 mg and 25 mg
Duration Up to 6-month follow-up
Topics Anxiety Psilocybin
Keywords Mechanism biology Experiential learning Experiential avoidance Psychotherapist Hallucinogen Cognitive psychology Cognitive science Epistemology
Citations 1
Key findings Psilocybin therapy reduces experiential avoidance, and these reductions predict improvements in mental health outcomes such as well-being, depression, anxiety, and suicidal ideation.

Abstract

Although psilocybin therapy is currently receiving attention as a novel intervention for a wide range of mental health concerns, limited research has examined the underlying psychological mechanisms (i.e., how) through which psilocybin therapy may bring about positive therapeutic changes. Qualitative research highlights the role of reductions in experiential avoidance (i.e., avoidance or suppression of aversive states) within psilocybin therapy. However, no quantitative research has examined experiential avoidance as a mechanism of change underlying psilocybin therapy's effects. Accordingly, the purpose of this dissertation is to investigate whether psilocybin therapy: (a) leads to reductions in experiential avoidance and (b) improved mental health (e.g., increased well-being and decreased depression severity, anxiety, and suicidal ideation) via reductions in experiential avoidance. This dissertation examined these questions within two studies that included the administration of psilocybin. Study 1 was a quasiexperimental study that examined the effect of administering 1 mg (very low-dose) psilocybin and 25 mg (high-dose) psilocybin to healthy individuals (N = 28). Relative to participants' experiential avoidance when they enrolled in the study, no significant reductions in experiential avoidance were observed throughout the study. Non-significant increases in experiential avoidance were observed following 1 mg psilocybin. Subsequently, significant reductions in experiential avoidance were observed 2 and 4 weeks after 25 mg psilocybin. These reductions in experiential avoidance following 25 mg psilocybin were significantly greater than those observed following 1 mg psilocybin. Decreases in experiential avoidance were sustained at 3 months (but not at 6 months) after 25 mg psilocybin. Reductions in experiential avoidance that occurred 2 weeks after 25 mg psilocybin (but not 1 mg psilocybin) predicted improvements in mental health (i.e., increases in well-being and decreases in depressed and anxious mood) 4 weeks after 25 mg psilocybin. Relative to 1 mg psilocybin, reductions in experiential avoidance following 25 mg psilocybin was a significantly greater predictor of changes in anxious mood (but failed to reach significance for well-being and depressed mood). Study 2 was a randomized controlled trial that compared psilocybin therapy with escitalopram (a selective serotonin reuptake inhibitor) for major depressive disorder (N = 59). Relative to escitalopram, psilocybin therapy led to significant reductions in experiential avoidance. Within the psilocybin therapy (but not the escitalopram) condition, reductions in experiential avoidance indirectly affected improvements in mental health (i.e., increased well-being and decreased depression severity, suicidal ideation, and trait anxiety). These indirect effects were significantly larger in the psilocybin therapy condition (for well-being, depression severity, and trait anxiety but not for suicidal ideation), providing evidence for the role of experiential avoidance being specific to psilocybin therapy. These results provide preliminary support for the positive effects of psilocybin therapy on experiential avoidance and the potential role of experiential avoidance as a putative mechanism underlying psilocybin therapy’s positive therapeutic outcomes. Limitations of the present studies include difficulties surrounding establishing temporal causality, issues with the experimental designs, relatively small sample sizes, and reliance upon self-report. The present findings may help to tailor and refine psilocybin therapy and its delivery as a transdiagnostic mental health intervention.

Comparable studies

Other randomized controlled trials on psilocybin for anxiety, most cited first.

Study Year Design Participants
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety 2016 Randomized controlled trial n = 51
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression 2016 Double-blind, placebo-controlled, crossover trial n = 29
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... 2006 Double-blind study n = 36
Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Adults with advanced-stage cancer and anxiety 2010 Double-blind, placebo-controlled study n = 12
Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies Healthy human subjects 2010 Pooled analysis of double-blind placebo-controlled experimental studies n = 110

Explore topics

By condition and practice