Magic mushrooms are having a major comeback. Once a symbol of the hippie era, their active ingredient, psilocybin, is now being studied for its potential to treat mental health issues like depression and PTSD. Alongside other psychedelics like ketamine and MDMA, psilocybin is becoming part of a new wave of mental health treatments.

The Ups and Downs of Psychedelic Therapy

The path to accepting psychedelic therapy hasn't been smooth. In 2019, the FDA approved a type of ketamine for treatment-resistant depression. However, in June 2024, they rejected MDMA for PTSD therapy, even though it is approved in Australia for limited use. Meanwhile, healthcare providers in Oregon are already using psilocybin for treating depression. The drug hasn't yet received federal approval in the U.S.

Understanding Psilocybin's Effects on the Brain

Despite psilocybin's potential, its long-term impact on the brain is not fully understood. A research team from Washington University School of Medicine has now documented brain changes before, during, and after a single dose of psilocybin over several weeks. Participants also took Ritalin as a control to mimic some effects of the psilocybin high.

Resetting Brain Networks

Psilocybin seems to "reset" brain networks that are active during rest, like when you're daydreaming. These networks control our sense of self, time, and space. Although most changes were temporary, one connection showed lasting changes for weeks. Some participants' brain networks even looked like those of completely different people.

Generally, brain regions synchronize their activity. Psilocybin disrupts these connections, making the brain more flexible and able to form new networks. This could help explain how magic mushrooms "contribute to persistent changes...in brain regions that are responsible for controlling a person’s sense of self, emotion, and life-narrative," said Petros Petridis at the NYU Langone Center for Psychedelic Medicine .

Magical Mystery Tour of the Brain

The brain has about 100 billion neurons and trillions of connections. Local networks handle tasks like processing vision and sound, while brain-wide networks handle complex tasks like decision-making and self-reflection.

Earlier studies focused on local networks. For instance, in rodents, psilocybin helped regrow neural connections that often degrade in people with severe depression. Scientists identified a receptor that psilocybin binds to, triggering this growth. But we still didn't know psilocybin's full effect on the human brain.

Previous research used fMRI to study this by giving people with severe depression a dose of psilocybin. They found that the drug desynchronized brain networks, essentially "rebooting" them out of a depressive state.

Daydream Believer: The New Study

The new study tracked brain activity in seven adults without mental health issues before, during, and three weeks after taking psilocybin. Participants were given a dose similar to that used in clinical trials for depression. They performed two tasks during brain scans: focusing on white crosshairs and matching images to word prompts.

Tracking brain connections over time in the same person can "minimize the effects of individual differences in brain networks organization," according to Petridis. Psilocybin immediately desynchronized a brain-wide network, creating a unique brain activity "fingerprint." This network is involved when our mind wanders, such as reliving memories or imagining future scenarios.

The drug also disrupted local networks in the cortex, which handles perception and decision-making. However, this disruption was less during the image-audio task, suggesting focused tasks can reduce psilocybin's effects.

Therapeutic Implications

Psilocybin's effects were temporary, except for one persistent disruption. A link between the default mode network and parts of the brain involved in memory and emotion was altered for weeks. This could be why psilocybin helps make the brain more flexible and open to change. People with rigid, negative thought patterns, like those with depression or PTSD, might find it easier to adopt new perspectives.

Petros Petridis explained, "In other words, psilocybin could open the door to change, allowing the therapist to lead the patient through" .

Next Steps in Research

The study's findings are promising but limited, as only seven volunteers were studied. These participants did not have mental health conditions, so their response to psilocybin may differ from those seeking its therapeutic benefits. Larger studies are needed to understand how psilocybin affects people with various mental health issues.

The psychedelic therapy market could be worth over $10 billion by 2027. Understanding how these drugs affect the brain could lead to new treatments with fewer side effects.