Other · 2025
Thinking skills after psilocybin therapy for treatment-resistant depression: small gains
- Original title
- Cognitive outcomes following psilocybin-assisted therapy in treatment-resistant depression: A post-hoc analysis of a randomized, waitlist-controlled trial.
- Authors
- Johnson DE, Meshkat S, Kaczmarek ES, et al.
- Journal
- Progress in neuro-psychopharmacology & biological psychiatry, 2025
- Molecules
- Psilocybin
- Conditions
- Treatment-resistant depression, Bipolar depression
- Participants
- 26
- Evidence grade
- Low
- Source
- Read the original paper
The question
Does psilocybin-assisted therapy change thinking skills, such as mental processing speed and planning, in people whose depression has not responded to standard treatments?
What they did
Researchers went back over data from a trial of psilocybin-assisted psychotherapy involving 26 adults with treatment-resistant unipolar or bipolar depression. Participants completed two standard pen-and-paper thinking tests u the Digit Symbol Substitution Test (a measure of processing speed) and the Trail Making Test Parts A and B (measures of speed and mental flexibility) u at the start, one day after treatment, and two weeks after treatment. Statistical models tracked change over time, and a separate method checked how many individuals improved by an amount considered meaningful rather than random.
What they found
Scores improved on all the thinking tests over time (all p < .05). After accounting for improvements in depression symptoms, the gains on Trail Making Test Part A (p < .001), Part B (p < .001), and the difference score between them (p = .005) remained statistically significant, while the Digit Symbol Substitution Test result weakened and was no longer significant (p = .069). At the individual level, only 4.2 % to 12.5 % of participants showed a meaningful improvement, a rate that did not exceed what would be expected by chance.
The fine print
This was an unplanned analysis of an existing open-label trial, so everyone knew they had received psilocybin and there was no placebo comparison for the cognitive tests. Only 26 people took part, follow-up ended at two weeks, and repeating the same tests three times can improve scores simply through practice u which the authors say they cannot rule out. This summary is based on the abstract only.
What it means
Thinking-test scores rose modestly after psilocybin-assisted therapy, and the change was not fully explained by better mood, but the gains were small and could reflect practice with the tests rather than a real effect of the drug.
Evidence grade: Low. A retrospective post-hoc analysis of 26 people from an open-label trial, with no comparison group for the cognitive tests and only two weeks of follow-up.
This summary is based on the study’s published abstract.