What brain scans showed after psilocybin therapy for depression
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The question
Several trials suggest psilocybin therapy can ease depression, at least for a while. But how? This study looked inside the brain to find out. The researchers asked: does the way brain regions "talk" to each other change after psilocybin therapy, and is that change linked to how much people's mood improves?
One idea is that in depression, the brain gets stuck in rigid patterns. Groups of brain regions (called networks) may become too separate from one another. Scientists measure this as modularity (how divided the brain is into separate, inward-looking clusters).
Who took part and what happened
The team re-analyzed brain scans from two earlier trials at Imperial College London. They used fMRI (a scanner that tracks blood flow as a sign of brain activity) while people rested with their eyes closed.
- Trial 1 (open-label): people with treatment-resistant depression (depression that had not improved with earlier treatments). Everyone knew they were getting psilocybin: 10 mg first, then 25 mg a week later. Scans were done before treatment and one day after the 25 mg dose. Usable scans came from 16 people.
- Trial 2 (double-blind randomized trial): people with major depression. One group got two 25 mg doses of psilocybin three weeks apart plus a daily placebo pill. The other group got two tiny 1 mg doses plus the antidepressant escitalopram (a common SSRI) daily for six weeks. Scans were done before treatment and three weeks after the second dose. Usable scans came from 22 people on psilocybin and 21 on escitalopram.
Everyone in both trials also had psychological support from trained mental health professionals.
What they found
- In both trials, modularity went down after psilocybin therapy. In plain words, brain networks became less walled-off and more connected to each other. The authors call this "global integration."
- The bigger this change, the more people's depression improved. In the randomized trial the link was moderate (correlation r = 0.42). In the open-label trial it was somewhat stronger (r = 0.54).
- In the open-label trial, brain changes seen one day after treatment were linked to how people were doing six months later.
- In the escitalopram group, modularity did not change, and their mood improvement was milder.
- Networks involved in attention and flexible thinking became more "dynamic" (switching connections more easily) after psilocybin, and this also tracked with improvement.
This paper focused on brain scans. It did not report new safety data.
What this study does not tell us
- It shows a link, not proof of cause. Talking therapy, expectations and other factors may have played a part.
- The groups were small: fewer than 60 people in total.
- The two trials differed in scan timing (one day vs. three weeks), scanners and how depressed people were at the start, so some detailed findings did not repeat across trials.
- The difference in brain change between psilocybin and escitalopram was not statistically confirmed in a direct comparison.
- Brain scans before treatment did not predict who would improve.
- We don't know how long these brain changes last. The researchers noted some people relapse.
Why it matters
This study offers a possible picture of what changes in the brain after psilocybin therapy: a shift from rigid, separated patterns toward more open communication between networks. It fits a wider idea that depression involves feeling "stuck," in mind and in brain. The findings are early and need to be tested in larger studies. The researchers themselves warned that people with depression should not try to self-medicate with psilocybin.
This is a summary of published research for general information. It is not medical advice. The study took place in a clinical research setting with medical screening and professional support.
Source: Daws RE, Timmermann C, Giribaldi B, Sexton JD, Wall MB, Erritzoe D, Roseman L, Nutt D, Carhart-Harris R (2022). Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine, 28(4), 844–851. doi:10.1038/s41591-022-01744-z · PubMed
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