Institute of Neurosciences and Medicine (INM)

Structural and Functional Organisation of the Brain (INM-1)

Long-term Effect of Psilocybin on Brain Activity Discovered

A new study shows that psilocybin, the active compound in “magic mushrooms,” not only has an immediate impact on brain activity but can also trigger longer-lasting changes. Researchers see this as a potential approach for therapeutic effects in mental disorders such as depression. The study has now been published in the journal Molecular Psychiatry.

The researchers from Bristol, London, San Francisco, Jülich, and Düsseldorf administered therapeutically relevant doses of psilocybin (0.3 or 1.0 mg per kg of body weight) to rats. Using permanently implanted Neuropixels probes, which allow for recording the activity of individual neurons and entire networks, they examined the effects of the psychedelic in three regions of the medial prefrontal cortex – including the infralimbic area, which is associated with emotions, self-control, and stress processing. For comparison, the scientists injected saline solution.

Langzeiteffekt von Psilocybin auf Hirnaktivität entdeckt — A LFP spectrograms from a single recording channel in the infralimbic cortex of one rat, aligned to rest and operant task 15 min epochs pre- and post-injection of 0.3 mg/kg psilocybin (top row spectrograms) and saline (bottom row). Note the sustained power around 100 Hz during the rest block after injection of 0.3 mg/kg psilocybin. B Average time course of ~100 Hz high frequency oscillation 1/f power difference at baseline and post-injection, shown as a difference in power between 0.3 mg/kg psilocybin and saline. Grey shaded and white backgrounds delineate rest and operant task blocks respectively. Bars above trace mark times of significant difference to saline.

After psilocybin administration, rapid rhythmic oscillations at around 100 Hz occurred, particularly in the infralimbic area. These signal changes lasted for about an hour. At the same time, the overall activity of the nerve cells and the complexity of their activity patterns decreased. These effects were particularly pronounced in resting states, less so during an attention test task. Interestingly, a long-term effect was also observed: one, two, and six days after treatment, gradually increasing oscillations in the beta and low-gamma range (20–60 Hz) appeared, again specifically in the infralimbic cortex.

The study concludes that psilocybin not only triggers short-term effects but can also alter the functioning of specific brain networks in the longer term. The findings point to mechanisms that are difficult to detect using conventional imaging methods in the human brain. These changes may be a clue to how psychedelics promote brain plasticity – the brain’s ability to adapt and reorganize. This very feature is considered a possible key to their therapeutic effects, for example in depression.

Original publication:
Purple, R.J., Gupta, R., Thomas, C.W. et al. Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin. Mol Psychiatry (2025). https://doi.org/10.1038/s41380-025-03182-y