Psilocybin for Anhedonia in Unipolar and Bipolar Depression: A Systematic Review of Clinical and Preclinical Evidence

Background: Anhedonia is a debilitating core feature of mood disorders, and is associated with significant functional impairment and poor quality of life. Psilocybin has recently emerged as a novel antidepressant treatment in MDD, however, its effects on anhedonia specifically have yet to be systematically reviewed. This review evaluates available clinical and pre-clinical research, exploring whether psilocybin influences anhedonia outcomes in pre-clinical and clinical studies.

Methods: A systematic search was conducted of PubMed and Ovid databases using search terms related to psilocybin, anhedonia/reward-related processes, and MDD/BD in February 2026. Studies were screened and data were extracted independently by two reviewers (E.S.K. and S.W.).

Results: The systematic search resulted in the inclusion of eleven studies, including five clinical studies and six animal studies. Across clinical studies, reductions in anhedonia, as measured by the Snaith-Hamilton Pleasure Scale (SHAPS) or the Montgomery-Asberg Depression Rating Scale (MADRS) anhedonia factor, were consistently observed following psilocybin-assisted psychotherapy wherein two randomized clinical trials (pooled n = 274) reported greater improvements in anhedonia relative to control or comparator groups. Similarly, results from animal studies demonstrated improved reward sensitivity and motivation after psilocybin exposure.

Conclusion: Despite encouraging early findings, interpretation is limited by the small number of studies, small sample sizes, and variability in the manner of which anhedonia was measured, with most clinical studies assessing only consummatory pleasure. While current evidence suggests psilocybin may meaningfully ameliorate anhedonia, further controlled research rigorously evaluating anhedonia, using comprehensive and standardized measures, is needed