Psilocybin appears to alter brain networks linked to repetitive negative thoughts, which may explain how the drug helps to treat some mental health conditions
By Chris Simms
29 August 2025
The hallucinogen psilocybin is produced in hundreds of species of magic mushroom
A single dose of the psychedelic compound psilocybin could be enough to remodel connections of specific brain networks, which may explain how the drug helps to treat some mental health conditions.
Psychedelic drugs like psilocybin, which is produced in hundreds of species of magic mushroom, alter how people perceive time, space and themselves. They also show promise in the treatment of mental health conditions like depression and anxiety. It is thought that this is through psilocybin increasing the brain’s plasticity – its ability to change its connections – but how it does this hasn’t been clear.
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Now, Alex Kwan at Cornell University in Ithaca, New York, and his colleagues have run a series of experiments in which they injected mice with either a dose of psilocybin or saline solution. A day later, they injected a genetically modified version of the rabies virus. This virus can jump across synapses, the gaps between neurons, so it can be used to show which neurons connect to the region where the virus was originally injected.
The researchers visualised the brain-wide effects of the virus using scans and dissections to reveal which neurons had made new connections. From this, they could show that mice that were given a dose of psilocybin had strengthened connections between the retrosplenial cortex – which is associated with imagination, memory and integrating sensory information – and the prefrontal areas, which are involved in planning and social behaviour, when compared with the mice that were given saline solution.
Psilocybin also seems to decrease connections that are part of recurrent loops in the cortex. These loops allow important memories to be retained for longer, but in some mental health conditions they can lead to a persistent focus on negative thoughts or behaviours. Breaking cycles of rumination by weakening these loops has been hypothesised as a key part of the process for treating many mental health conditions.