Effects of psilocybin with psychological support on anhedonia in treatment-resistant depression: A randomized controlled pilot trial.
Andrew M Novick, Tiffany M Love, Rachel L Johnson, Chloe E Page, Devin P. Effinger, Danielle Sukenik, Kammy Bishop, Jacqueline Calderone, Jessica Scott, Heinrich Haller, Lauren Turow, Harmony O Soffer, Lily C. Vonesh, Michael H Allen, Stacy M. Fischer, Mary D Sammel, C Neill Epperson, Scott M. Thompson
Journal of Affective Disorders October 30, 2026 DOI: 10.1016/j.jad.2026.122676 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Pilot study Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Participants with treatment-resistant major depressive disorder |
| Interventions | Psilocybin psychological support |
| Dose | 25 mg or 1 mg |
| Duration | 8 weeks |
| Measures | Dimensional Anhedonia Rating Scale (DARS), Snaith-Hamilton Pleasure Scale (SHAPS), Montgomery-Åsberg Depression Rating Scale (MADRS) |
| Topics | Depression Psilocybin |
| Keywords | Anhedonia Randomized controlled trial |
| Key findings | Psilocybin 25 mg did not significantly improve anhedonia at the primary week 1 endpoint (DARS between-group difference 11.2, 95% CI -1.0 to 23.3). Secondary measures suggested possible benefits: greater DARS improvement at week 8 (difference 14.7, 95% CI 2.5 to 26.8), greater SHAPS improvement at week 1 only, and greater MADRS improvement in depression severity at weeks 1 and 8. The authors state these findings warrant confirmation in larger trials. |
Abstract
Anhedonia is a core feature of major depressive disorder (MDD) that is frequently resistant to available treatments. Psilocybin's specific efficacy for anhedonia remains unclear. To evaluate psilocybin's efficacy for anhedonia in treatment-resistant MDD. In this randomized, double-blind, placebo-controlled trial, 20 participants with treatment-resistant MDD received psilocybin (25 mg or 1 mg) with psychological support. The primary outcome was change in the Dimensional Anhedonia Rating Scale (DARS) score at week 1; DARS change at week 8 was a secondary outcome. The Snaith-Hamilton Pleasure Scale (SHAPS) and Montgomery-Åsberg Depression Rating Scale (MADRS) were used as additional secondary outcome measures for anhedonia and overall depression severity, respectively. The primary outcome was not statistically significant: between-group difference in DARS change at week 1 was 11.2 (95% confidence interval [CI], -1.0 to 23.3; p = 0.073). At week 8, the secondary DARS outcome indicated greater improvement in anhedonia with 25 mg (difference, 14.7; 95% CI, 2.5 to 26.8; p = 0.018). SHAPS improvement favored 25 mg at week 1 (difference, -3.2; 95% CI, -6.1 to -0.3; p = 0.029), but not week 8 (-2.1; 95% CI, -4.9 to 0.9; p = 0.168). MADRS improvement favored 25 mg at weeks 1 (-11.9; 95% CI, -19.2 to -4.5; p = 0.002) and 8 (-11.6; 95% CI, -19.0 to -4.2; p = 0.002). Psilocybin 25 mg did not significantly improve anhedonia at the primary week 1 endpoint. However, improvements on secondary measures suggest potential benefits for anhedonia and depression severity that warrant confirmation in larger trials. ClinicalTrials.govNCT06230757.
Comparable studies
Other randomized controlled trials on psilocybin for depression, 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 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
| Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. Adults with treatment-resistant depression | 2022 | Phase 2 double-blind randomized controlled trial | n = 233 |
Citations in the library
Cites 29
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
and 24 more in the library