Examining the effects of psilocybin-assisted psychotherapy on anhedonia in treatment-resistant depression
Journal of Affective Disorders – February 12, 2026
Source: OpenAlex
Summary
Psilocybin-assisted psychotherapy (PAP) shows promise in reducing anhedonia, a challenging symptom of treatment-resistant depression (TRD). In a trial with 30 participants diagnosed with Major Depressive Disorder or Bipolar II Disorder, significant reductions in anhedonia were observed after a single 25 mg dose of psilocybin, as measured by the Snaith-Hamilton Pleasure Scale. Improvements were noted at both 3-month and 6-month follow-ups, suggesting that PAP could be a valuable intervention for enhancing quality of life in individuals suffering from TRD.
Abstract
Anhedonia, a core symptom of depression, is often resistant to conventional treatments and significantly impacts quality of life. This secondary analysis aimed to evaluate the effects of psilocybin-assisted psychotherapy (PAP) on anhedonia severity in individuals with treatment-resistant depression (TRD). Participants (n = 30) with TRD and a primary diagnosis of Major Depressive Disorder or Bipolar II Disorder received at least one 25 mg dose of oral psilocybin with psychotherapy as part of a randomized, waitlist-controlled trial (NCT05029466). The primary outcome of the present secondary analysis was changes in anhedonia, measured by the Snaith-Hamilton Pleasure Scale (SHAPS). Exploratory analysis examined whether changes in anhedonia were mediated through changes in overall depression severity, measured by the Montgomery-Asberg Depression Rating Scale (MADRS). A mixed ANOVA, adjusted for sex and age, revealed a statistically significant reduction in SHAPS scores following PAP at the 2-week primary endpoint (F(8, 143.48) = 3.43, p = 0.001, n = 29) with clinically significant improvements observed at 3-month and 6-month secondary endpoints. Our findings from this preliminary analysis suggest that PAP may offer a promising intervention for addressing anhedonia in TRD, but further research with larger, placebo-controlled trials are needed to confirm these effects and elucidate potential mediators. This study adds to a growing body of evidence supporting the therapeutic potential of PAP.