How Does Psilocybin Work in the Brain?

The Default Mode Network Explained

You may think that specific areas of the brain carry out specific tasks, but through brain imaging research, we’ve discovered that the brain operates in “networks,” calling on multiple different brain regions to work together to achieve various tasks.These tasks can be anything from decision-making, introspection, and emotional-processing, to directing attention and retrieving memories, and can require varying levels of connectivity, which varies over time in response to fluctuations in emotional and cognitive states (Lettieri et al., 2021).The Default Mode Network (DMN) is most commonly referred to when discussing psychedelics and our brain.
It’s characterized by the connectivity of certain regions of our brain, namely the anterior medial frontal cortex, ventral medial prefrontal cortex, posterior cingulate cortex, precuneus, inferior parietal lobule, and middle temporal gyrus that come together to achieve tasks like:Self-reflection/DaydreamingEmotional processingSocial interactionMental explorationConstruction of personal narratives (Azarias et al., 2025)Psilocybin, Serotonin & the Default Mode NetworkPsilocybin is a psychoactive compound found in “magic mushrooms” that benefits our body and mind in a way we’re just beginning to understand. As any good mycologist knows, the benefits of medicinal mushrooms are far reaching, and not just the psychedelic ones.When ingested, psilocybin turns into a related compound called psilocin, which is a serotonin 5‐HT 2A receptor (5‐HT2AR) agonist, which means it mimics the serotonin that’s found in our body.Serotonin wears many hats, from regulating our nervous system to aiding in digestion, and its receptors are found all over the body, but it’s most widely known for being the “happy chemical” in our brain, responsible for emotional stability and satisfaction.

The 5‐HT 2A receptor is what “holds” or “activates” serotonin and is concentrated in our brain matter (the cerebral cortex), more specifically in the areas that handle decision making, social behavior and personality, but also in the visual cortex, responsible for processing visual information.The default mode network happens to be saturated in these 5‐HT 2A receptors. Our natural serotonin acts as a stabilizer for this network, helping it maintain a coherent “narrative” of who you are.However, in many people with depression or anxiety, the DMN becomes overactive or “rigid.” It gets stuck in a loop of rumination—the same negative thoughts about the self, over and over (Zhou et al., 2020).This is why disrupting these rigid thought patterns by flooding the serotonin receptors with psilocin can cause changes in our thoughts and behaviors for the better, especially with the increase in neuroplasticity, meaning the brain’s heightened ability to change, adapt or rewire.