Psilocybin, the psychoactive compound present in certain varieties of mushrooms, physically alters connections in the brain, according to research that reveals new possibilities for treating depression.
The research, published in Nature Neuroscience, was conducted by researchers at the University of California, Santa Cruz, and found that the psychoactive compound promotes the rapid formation of connections between brain cells, effectively rewiring the brain after it has experienced chronic stress, and even under conditions where no hallucinogenic experiences are produced.
The findings reveal that the biological processes behind such changes can operate independently from those associated with psilocybin’s well-characterized psychedelic effects.
Connections Between Neurons
The researchers behind the study employed advanced imaging techniques with living mice to track tiny structures known as dendritic spines, which are responsible for helping neurons communicate with one another.
During the experiments, researchers found that within 24 hours of psilocybin being administered, the mice experienced a surge in the formation of new dendritic spines, many of which also matured and established stable neural connections that persisted for several weeks.
“These newly formed connections can integrate into existing neural circuitry and persist over time, leaving a lasting structural trace of psilocybin’s effects on the brain,” said lead author Jacob Baker, a doctoral researcher at UC Santa Cruz, in a statement.
Different Effects
One intriguing finding involved the differences between the way healthy and chronically stressed mice’s brains were impacted by psilocybin during the study. When healthy mice were treated with the drug, it appeared to promote the stimulation of new connections, while also promoting the removal of some that already existed.
By comparison, mice subjected to chronic stress revealed an even greater increase in new connections, while helping prevent the loss of those that already existed.
“These findings challenge the prevailing view that psilocybin simply increases neural connectivity and suggest that its effects depend on the brain’s underlying condition,” said senior author Yi Zuo, a professor at UC Santa Cruz, in a statement.
No Psychedelic Experiences Required
One of the most significant findings the team made involved the use of genetic techniques that helped them determine if the structural changes they observed required the same brain activity associated with the psychedelic experiences commonly associated with psilocybin’s use.
To help investigate this, the team manipulated serotonin receptors in certain neurons, which helped reveal that psilocybin could promote the formation of new neural connections, but without triggering what is known as the head-twitch response—a behavioral indication used in the study of psychedelic drugs and their effects in experiments involving mice.
The study also revealed that in some cases, mice could exhibit this key indicator of psychedelic effects without the same structural changes occurring within the brain.
Reshaping Brain Circuits
Fundamentally, the new research suggests that psilocybin’s ability to reshape brain circuits may be separable from its hallucinogenic effects, meaning that scientists may be able to develop future medications that promote neural plasticity without necessarily causing psychoactive experiences.
Although the team’s findings are preliminary, they suggest that new effective treatments for humans involving psilocybin therapy could be on the horizon.
“This provides a new perspective on how psychedelics might help restore neural circuits disrupted by stress,” Zuo said, adding that the team’s research offers “potentially important implications for understanding their therapeutic effects in depression and other psychiatric disorders.”
The recent study, “5-HT2A receptors in layer 5 pyramidal neurons mediate the neuroplastic but not the hallucinogenic effects of psilocybin,” was published in Nature Neuroscience.
Micah Hanks is the Editor-in-Chief and Co-Founder of The Debrief. A longtime reporter on science, defense, and technology with a focus on space and astronomy, he can be reached at micah@thedebrief.org. Follow him on X @MicahHanks, and at micahhanks.com.