Examining the effects of psilocybin-assisted psychotherapy on anhedonia in treatment-resistant depression
Erica Kaczmarek, Nelson Rodriguez, Noah Chisamore, Zoe Doyle, Shakila Meshkat, Marc G Blainey, Ryan M Brudner, Shaun Ali, Kayla M Teopiz, Roger S McIntyre, Joshua D. Rosenblat
Journal of Affective Disorders February 12, 2026 DOI: 10.1016/j.jad.2026.121385 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Secondary analysis of a randomized, waitlist-controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Adults with treatment-resistant depression (major depressive disorder or bipolar II disorder) |
| Intervention | Psilocybin-assisted psychotherapy |
| Dose | 25 mg |
| Duration | 6-month follow-up |
| Topics | Depression Psilocybin Psychedelic-assisted therapy |
| Keywords | Anhedonia Depression economics Rating scale Intervention counseling Exploratory analysis Bipolar disorder Clinical psychology Psychotherapist Randomized controlled trial Exploratory research Clinical trial |
| Registration | NCT05029466 |
| Key findings | Psilocybin-assisted psychotherapy significantly reduced anhedonia severity at 2 weeks, with clinically meaningful improvements lasting up to 6 months. |
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.
Comparable studies
Other randomized controlled trials on psilocybin and psychedelic-assisted therapy, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Healthy adults, mostly hallucinogen-naïve | 2011 | Randomized controlled trial | n = 18 |
| Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder Adults aged 25–65 with DSM-IV alcohol dependence and at least 4 heavy drinking days in... | 2022 | Randomized controlled trial | n = 95 |
| Increased global integration in the brain after psilocybin therapy for depression. Patients with treatment-resistant depression and patients with major depressive disorder | 2022 | Open-label trial and double-blind phase II randomized controlled trial | |
| Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. Adults diagnosed with major depressive disorder and no unstable somatic conditions | 2023 | Double-blind, randomised clinical trial | n = 52 |
| Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin Healthy participants | 2012 | Randomized controlled trial | n = 10 |