Magic Mushrooms Lead to Weeks-Long Brain Desynchronization, Study Finds

Once criticized for their psychedelic properties, magic mushrooms are now garnering attention for their potential therapeutic benefits in treating a variety of mental health issues. Despite this growing interest, the neurological effects of psilocybin, the psychoactive compound in these mushrooms, remain largely unexplored. This knowledge gap makes it challenging to predict how psilocybin could ultimately be used in medical treatments.

A recent study led researchers from Washington University School of Medicine, sought to bridge this gap by examining brain changes in seven healthy adults before, during, and after taking a high dose of psilocybin. The findings, published in Nature, identified disruptions in brain connectivity that persisted for weeks in some areas.

The research aimed to understand how psilocybin's biochemical effects translate into large-scale behavioral changes that could either benefit or hinder individuals with different psychological needs.

Psilocybin mimics serotonin's affinity for the 5-HT2A receptor, leading to well-documented effects such as euphoria and altered perceptions of self, time, space, sound, and colour. Animal studies have shown that activating these receptors can lead to long-lasting effects by promoting neural plasticity – the brain's ability to form new connections and adapt. This plasticity makes psilocybin a promising candidate for treating stubborn psychological conditions. However, whether these effects translate to humans was unclear.

In the study, researchers used functional magnetic resonance imaging (fMRI) scans to monitor volunteers before, immediately after, and 21 days following a 25-milligram dose of psilocybin. For comparison, the subjects also received a 40-milligram dose of the stimulant methylphenidate on separate occasions, with similar scans taken.

The results showed significant disruptions in functional connectivity across the brain's cortex after the psilocybin dose. Major changes were also observed in the default mode network (DMN), a group of brain regions most active when a person is awake but not engaged in a specific task. Previous studies in rats suggested that psilocybin causes nerve cells to fall out of sync, temporarily erasing the patterns that underlie our sense of self.

Interestingly, performing a simple auditory-visual matching task during scans after the psilocybin dose seemed to stabilize the DMN, reducing disruption severity. Three weeks later, the cortex had mostly returned to pre-dose synchronization. However, the anterior hippocampus, a region involved in perception and memory, continued to show persistent functional changes.

“Understanding the relationship between psilocybin's pharmacology and its effects within a neurological framework could pave the way for new treatments for depression, post-traumatic stress, and other conditions. While we are still far from seeing psilocybin prescribed in clinical settings, studies like this bring us closer to unlocking the therapeutic potential of this fascinating compound,” said Joshua Siegel, psychiatrist at Washington University School of Medicine.

Reference: Siegel, J.S., Subramanian, S., Perry, D. et al. Psilocybin desynchronizes the human brain. Nature (2024). https://doi.org/10.1038/s41586-024-07624-5