Life Magazine introduced the Western world to psilocybin in this 1957 cover story
Depression improved, but not the ability to feel pleasure
STUDY: Novick AM et al, Journal of Affective Disorders 2026
STUDY TYPE: Randomized controlled trial (pilot)
FUNDING: University of Colorado Department of Psychiatry and National Institutes of Health. Several authors consult for psychedelic companies.
Background
Anhedonia often lingers after depressed mood lifts. Psilocybin raises dopamine in reward circuits through serotonin 5-HT2A receptors, so researchers tested whether it restores a sense of reward when the feeling is gone.
The Study
- 20 adults with treatment-resistant depression and prominent anhedonia; 65% were on an SSRI or SNRI.
- One dose of psilocybin 25 mg versus 1 mg (active placebo), with supportive therapy sessions.
- All 20 completed 8 weeks of follow-up.
Results
The primary outcome missed: Anhedonia scale (DARS) scores at week 1 were not significantly better on 25 mg (p = 0.073). By week 8, the 25 mg group pulled ahead. A second anhedonia scale (SHAPS) showed the reverse, favoring 25 mg at week 1 only.
Depression improved more clearly. Depression scale (MADRS) scores fell about 12 more points on 25 mg at weeks 1 and 8. On 25 mg, 45% responded and 36% remitted, versus none on 1 mg.
Patients on SSRIs or SNRIs improved as much as those not on them.
Side Effects
Euphoria and hallucinations occurred in 82% on 25 mg. One patient’s blood pressure spiked to 178/120, improved with clonidine. No serious adverse events were tied to psilocybin.
Limitations
- Only 20 patients.
- 80% guessed their dose, weakening the blind.
Practice Implications
- This trial shows potential for psilocybin in treatment resistant depression, something it hasn’t consistently moved the needle on, but not for anhedonia.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
