A single dose of psilocybin seems to be sufficient to reclassle the brain

A single dose of psychedelic psilocybin may be sufficient to reshape specific brain network connections, which may explain how the drug helps treat certain mental health problems.

Psychedelic drugs like psilocybin, which is produced in hundreds of species of magic fungi, modifies how people perceive time, space and themselves. They are also promising in the treatment of mental health problems such as depression and anxiety. It is believed that it is done by psilocybin increasing the plasticity of the brain – its ability to modify its connections – but how it does not.

Now, Alex Kwan at Cornell University in Ithaca, New York, and his colleagues organized a series of experiences in which they injected mice with a dose of psilocybin or saline solution. A day later, they injected a genetically modified version of the rabies virus. This virus can jump through synapses, gaps between neurons, so it can be used to show which neurons connect to the region where the virus was originally injected.

Researchers have visualized the virus brain effects using analyzes and dissections to reveal which neurons had established new connections. From this, they could show that the mice which received a dose of psilocybin had strengthened the links between the retrosplenial cortex – which is associated with the imagination, memory and the integration of sensory information – and prefrontal areas, which are involved in planning and social behavior, compared to mice that received a saline solution solution.

Psilocybin also seems to reduce connections that are part of the recurring loops in the cortex. These loops make it possible to keep significant memories longer, but in certain mental health problems, they can lead to persistent concentration of negative thoughts or behaviors. The rupture of rumination cycles by weakening these loops was supposed to be a key element in the process of processing many mental health problems.

“I think this is the next step in what we have to discover,” said Michael Wheeler at Brigham and Women’s Hospital in Boston. “These types of circuits underlying connections between these associative areas could potentially be a key to unlocking their mechanisms.”

“The way the brain is renovated by psilocybine treatment is essential for its effects on mood disorders,” said Eero Castrén at Helsinki University in Finland. It is important to note, however, that psilocybin only allows remodeling, he says. What circuits are really reinforced or weakened can depend on what an animal is done and detection.

The work suggests that one day it may be possible to choose the brain connections to be reshaped, depending on the mental health which is processed. “Our study suggests an exciting avenue for future research in order to combine neuromodulation with psychedelics to precisely target specific circuits for neuronal plasticity,” wrote researchers in their article.

The study of how different activities or environments modify brain changes while taking psilocybin could also allow us to explain the phenomenon of “set and adjustment” associated with psychedelic drugs, in which the state of mind and the environment of a user can modify the effects of drugs, leading to a “good” or “bad” trip, explains Castro.

The work is at the mouse, so it remains to be seen if the same connectivity changes would occur in people after having taken psilocybin. However, Wheeler says it seems likely that the mechanism is similar. There are areas that overlap in this mouse study and a 2024 human brain scanning study showing how psilocybin seems to make certain areas more interconnected, he said.