What happens in the brain on psilocybin? A close look with repeated brain scans
Photo: Sandip Kalal on Unsplash
The question
People who take psilocybin (the active compound in "magic mushrooms") often say their sense of time, space and self dissolves for a few hours. What is actually happening in the brain while this happens? And does anything change in the brain after the experience is over?
A team at Washington University in St. Louis, led by Joshua Siegel and Nico Dosenbach, set out to map this in unusual detail.
Who took part and what happened
Seven healthy adults, aged 18 to 45, took part. All had used a psychedelic at least once before, but not in the previous six months. People with conditions such as depression, psychosis or addiction were not included.
The researchers used an approach called precision functional mapping. Instead of scanning many people once, they scanned a few people many times, on average about 18 brain scans each (using fMRI, a type of MRI that tracks blood flow as a sign of brain activity). Scans took place before, during and for up to three weeks after the drug sessions.
Each person had two drug sessions, one to two weeks apart, in random order: a high dose of psilocybin (25 mg) and, for comparison, methylphenidate (40 mg, a stimulant also known as Ritalin). Methylphenidate was chosen because it also raises heart rate and alertness, so it helps separate "being stimulated" from psilocybin's specific effects. Four participants returned six to twelve months later for a second psilocybin session to see if the results repeated.
The team focused on functional connectivity (how closely the activity of different brain regions rises and falls together) and especially on the default mode network (a set of brain areas that is busiest when we are not focused on a task, and is linked to our sense of self, memories and daydreaming).
What they found
- A big, brain-wide shift. During the psilocybin experience, the normal patterns of connection across the brain were strongly disrupted. The change was more than three times larger than with methylphenidate, even though both drugs raised heart rate similarly.
- "Desynchronization". Brain regions that usually work in step fell out of step. The boundaries between brain networks became blurrier. The strongest effects were in the default mode network.
- Individual "fingerprints" faded. Each person's brain normally has a recognizable connection pattern. During psilocybin, these patterns changed so much that individuals became harder to tell apart until the effects wore off.
- Brain change matched the experience. People whose brain networks changed more also reported stronger subjective experiences.
- Focusing on a task reduced the effect. When participants did a simple task during the session, the disruption was smaller.
- Most of it went back to normal. Brain-wide patterns largely returned to baseline within days to three weeks. One change lasted longer: weaker connection between the default mode network and the front part of the hippocampus (a brain area involved in memory and sense of place and self), which was still visible about three weeks later.
What this study does not tell us
- Only seven people. Each was studied in great depth, but seven healthy volunteers are not a population.
- Healthy volunteers, not patients. The study says nothing direct about depression or any other condition. The authors themselves say clinical research is needed.
- Hard to stay blind. Although the drug order was randomized and meant to be blinded, a high dose of psilocybin is easy to recognize.
- Meaning of the lasting change is unclear. The weaker hippocampus connection might relate to the brain becoming more flexible (sometimes called neuroplasticity), but this was not tested directly.
- Clinical conditions. Participants were screened and supervised by professionals in a research setting.
Why it matters
This study gives one of the most detailed pictures so far of how psilocybin changes brain activity, in the same people, before, during and after. It links a common description of the experience (the sense of self loosening) to a measurable effect on the default mode network. It also hints that something small may persist for weeks. These are early findings in a few healthy people, and they raise good questions for future research rather than settle them.
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: Siegel JS, Subramanian S, Perry D, Kay BP, Gordon EM, Laumann TO, et al., Dosenbach NUF (2024). Psilocybin desynchronizes the human brain. Nature, 632(8023), 131–138. doi:10.1038/s41586-024-07624-5 · PubMed · Full text
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