A new study from the University of California, Santa Cruz, has revealed how psilocybin, the psychedelic substance found in "magic mushrooms," changes the brain by reorganizing connections between nerve cells. The findings could eventually help scientists develop treatments for mental health conditions that capture some of psilocybin's potential benefits without producing hallucinations.
The research, published October 15 in Nature Neuroscience, found that psilocybin rapidly encourages brain cells to form new connections and helps those connections mature. At the same time, it promotes the removal of certain older connections, suggesting that its effects involve more than simply increasing communication between neurons.
Experiments in mice also revealed something especially intriguing. The researchers were able to separate the cellular changes responsible for this rewiring from a behavioral response commonly associated with psychedelic effects. This suggests that some of psilocybin's effects on brain structure may be achievable without the hallucinations typically associated with the drug.
The discovery could provide a foundation for developing medications that enhance the brain's ability to adapt and reorganize itself, a property known as neuroplasticity. Such treatments might eventually offer new approaches for depression, post-traumatic stress disorder (PTSD), and other psychiatric conditions.
The team also identified a particular group of neurons in the cerebral cortex that plays an essential role in psilocybin's effects on brain connections. Importantly, the researchers discovered that the drug does not affect every brain in the same way. Its influence depends partly on whether the brain has previously experienced chronic stress.
"I consider this work a major advance, particularly in our understanding of how psilocybin reshapes neural circuits and its potential implications for treating mental disorders," said senior author Yi Zuo, professor of molecular, cell, and developmental biology at UC Santa Cruz.
Why Scientists Are Taking a New Look at Psychedelics
Scientific interest in psychedelic drugs has changed dramatically over the past century. During the middle of the 20th century, substances such as psilocybin and LSD attracted attention from Western researchers because of their powerful effects on perception, consciousness, and mood.
Early studies suggested these compounds might have applications in psychiatric treatment. However, scientific investigations slowed substantially after the United States passed the Controlled Substances Act in 1970, which imposed strict restrictions on these substances.
In recent years, researchers have renewed their interest in psychedelics, particularly their ability to produce rapid and potentially lasting changes in brain function.
Scientists sometimes describe these compounds as "psychoplastogens" because they can stimulate neuroplasticity after a single dose. Neuroplasticity refers to the brain's capacity to change its structure and activity by forming, strengthening, reorganizing, or removing connections between neurons.
This property is particularly interesting for mental health treatment because conditions such as depression can involve disruptions in the circuits responsible for regulating mood, emotions, and behavior.
The U.S. Food and Drug Administration (FDA) has previously recognized the therapeutic potential of psychedelic research by granting Breakthrough Therapy designations to substances including psilocybin and MDMA. These designations are intended to accelerate the development and review of promising treatments for serious medical conditions.
In September 2026, the FDA took another step toward evaluating psychedelic treatments by organizing a public hearing titled "Considerations for Potential Future Therapeutic Use of Psychedelic Drugs."
Experts discussed how healthcare professionals administering psychedelic treatments should be qualified, how potential risks could be managed through Risk Evaluation and Mitigation Strategy (REMS) programs, and how future clinical trials should be designed.
As regulators examine ways psychedelic treatments might eventually become part of mainstream healthcare, researchers are increasingly focused on understanding exactly what these substances do to the brain. Identifying the cellular mechanisms behind their effects could help scientists develop treatments that are both effective and safer to administer.
Watching Psilocybin Rewire the Brain
To investigate how psilocybin changes brain structure, the UC Santa Cruz team used an advanced imaging method called two-photon microscopy.
This technology allows scientists to observe extremely small structures inside living tissue with remarkable detail. Using it, the researchers followed individual connections on neurons in living mice over several weeks, allowing them to see how those structures changed after psilocybin treatment.
Source: ScienceDaily
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