How psilocybin affects the Default Mode Network

Michele Koh Morollo
3 min readApr 24, 2024

A look at how psilocybin reboots the Default Mode Network to improve symptoms of depression and anxiety.

Research has showed that psychedelics like psilocybin can “reboot” the brain and help break the negative rumination and looping thought pattern that contribute to depression and anxiety. But how does this reboot happen?

What is the Default Mode Network

The key player involved in the reboot is the brain’s Default Mode Network (DNM) — an interconnected group of brain regions that are activated when the brain is in rest mode as opposed to a task-oriented, work, or decision-making mode. The DMN is most active when we are engaged in introspective functions like daydreaming, mind-wandering, imagining the past or future, contemplation, or self-criticism. Because of its implications in the realm of imagination, the DMN is also responsible for helping us to empathize with others — by imagining what it might be like to be in their shoes — and to view ourselves as distinct and different from everything else. Psychiatrist Matthew Brown described the DMN as the part of the brain that “reminds you that you are you.”

As we mature, we develop habitual ways of responding to situations, people, places, and things. Overtime, these habitual responses lead to the development of established pathways of communication between the different regions of the DMN. In the same way that well-trodden paths in a forest become the only trails that we use when we go for a hike — keeping us “safe” but also holding us back from exploring new, off-piste sections of the woods — these well-worn pathways of the DMN constrain our brains and become our “default mode” of perceiving ourselves, others, and the world.

Conditions associated with an overactive DMN

DMN activity is essential for normal, healthy brain functioning and decreased DMN activity has been associated with cognitive declined. However, an overactive DMN comes with its own problems. Overactivity in the DMN has been linked to conditions such as depression, anxiety, and Obsessive Compulsive Disorder (OCD). This is because the overactive regions of the DMN are responsible for maintaining the repeated cognitive and behavioral responses that occur when we engage in rigid thinking, hyper controlling behavior, obsessive negative thinking, criticism, and depressive rumination.

What does psilocybin do to the DMN?

Dr. Simon Ruffell, a psychiatrist and senior research associate at King’s College London describes the effects of psychedelics on the DMN as similar to “defragmenting a computer”. Brain imaging studies suggests that psychedelics like psilocybin decreases DMN activity. As a result, our sense of self — that heightened sense of “me consciousness” — temporarily dissipates and we stop worrying so much or engaging in self-focused negative thought patterns. The brain states observed in these studies have similarities to deep meditative states, where activity in the established DMN pathways decrease and increased activity is observed in pathways that previously did not communicate. By disrupting activity in established pathways of the DMN, psilocybin can help change negative thought loops by creating new pathways that encourage positive thoughts. This can result in increased psychological flexibility and openness to new ways to thinking and being.

Scientists have hypothesized that psilocybin DMN disruption creates entropy in the brain, which allows brain regions that previously never communicate to interact for the first time. According to “entropic brain theory”, the state of consciousness associated with psychedelics is akin to the mind state of early childhood, where life is still new and exciting, so we experience awe and wonder at simply being alive.

“Think of the brain as like a snowy ski slope”, said psychologist Rosalind Watts, clinical lead for Imperial College London’s psilocybin trial. “If you always ski down the same paths, they get more and more rigid, and you get stuck in a rut. A psilocybin experience is a bit like a snowplow. It smooshes through these lines and then you can ski anywhere. And suddenly, you can believe all sorts of different things. People describe it as coming out of prison.”

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