Recent research has shed new light on the powerful and long-lasting effects of psilocybin, the active compound in magic mushrooms. While it’s widely recognized that psilocybin can induce mind-bending experiences, new findings suggest that the impact of this psychedelic substance on the brain can extend far beyond the duration of a few hours, with changes in brain function persisting for weeks.
Psilocybin and brain rewiring
A study led by Dr. Joshua Siegel and his team at Washington University School of Medicine in St. Louis has provided some insight into how psilocybin disrupts and rewires the brain. Published in the journal Nature, the research explores the neural mechanisms behind the psychedelic experience and offers a potential explanation for psilocybin’s therapeutic benefits, particularly in the treatment of severe depression.
At the heart of psilocybin’s impact is its ability to disrupt the brain’s default mode network (DMN). The DMN is a group of interconnected brain regions that is active when the mind is at rest, such as when daydreaming or reflecting on oneself. This network is crucial in maintaining a sense of self and is linked to perceptions of space and time.
Study design
The study involved a randomized control trial with seven participants who were given either a 25mg dose of psilocybin or 40mg of methylphenidate (a common stimulant used in ADHD treatment). The participants were kept unaware of which drug they received, and after a week or two, they were given the drug they did not initially receive. The participants underwent multiple MRI scans before, during, and after taking the substances to observe changes in brain activity.
Lasting effects on brain connectivity
The findings revealed that psilocybin caused a significant loss of synchronization within the DMN, unlike the effects seen with methylphenidate. This disruption is believed to be responsible for the altered states of consciousness experienced during a psychedelic trip, where the user can experience a loss of their sense of self, space, and time.
Interestingly, while most of the brain returned to its normal state the day after the psilocybin experience, the study noted that communication between the DMN and the anterior hippocampus—a brain region responsible for memory and spatial navigation—remained altered for up to three weeks. This prolonged effect suggests that psilocybin induces a lasting increase in brain plasticity, which is the ability of the brain to rewire itself by forming new neural connections 1
Implications for mental health treatment
This extended change in connectivity may explain why individuals often report a heightened sense of flexibility in their thinking and self-perception long after the psychedelic effects of psilocybin have worn off. Researchers believe that neural plasticity could be the key to psilocybin’s success in treating conditions such as treatment-resistant depression. By temporarily disrupting deep-set patterns of negative thinking and self-criticism, psilocybin may allow the brain to forge new, healthier connections that can be reinforced through therapy.
With this and other research, the potential of psilocybin as a therapeutic tool is gaining recognition within the scientific community. Small clinical trials have shown that just one or two doses of psilocybin, administered in a controlled therapeutic setting, can lead to dramatic and long-lasting improvements in people with major depressive disorder (MDD), particularly in cases where traditional antidepressants have failed. These promising results have led the U.S. Food and Drug Administration (FDA) to designate psilocybin as a breakthrough therapy for depression, opening the door to more extensive research and potential future approval as a treatment.
The prolonged impact of psilocybin on mental health
Psilocybin works by interacting with serotonin receptors in the brain. Serotonin, often referred to as the “feel-good” hormone, plays a key role in regulating mood, anxiety, and happiness. In people with depression, anxiety, or post-traumatic stress disorder (PTSD), serotonin levels are often low. Traditional antidepressants, known as selective serotonin reuptake inhibitors (SSRIs), work by increasing the availability of serotonin in the brain. However, these medications can take weeks to show effects and may not work for everyone. In contrast, psychedelics like psilocybin can induce noticeable changes in brain connectivity within just 30 minutes, according to pharmacologist Brian Roth from the University of North Carolina at Chapel Hill. These changes lead to a “disorganized brain” state, where normal communication patterns are disrupted, leading to an altered state of consciousness. This disorganization can be therapeutic, particularly for individuals with depression, who often experience rigid and self-critical thinking patterns.
The future of psilocybin research
The growing body of evidence supporting psilocybin’s efficacy in treating mental health conditions is exciting, but it’s important to note that not everyone is a suitable candidate for psychedelic therapy. Individuals with a history of psychosis or those currently taking SSRIs may not benefit from psilocybin treatment, and careful screening is necessary to ensure patient safety. As research continues, the potential applications of psilocybin in mental health treatment may expand, with some scientists exploring the possibility of microdosing—taking very small amounts of psilocybin regularly—as a way to maintain brain health and well-being without the full psychedelic experience. However, the benefits of microdosing remain a topic of debate, with some researchers cautioning that more rigorous studies are needed to validate its efficacy.
Ultimately, while the journey of psilocybin to a recognized therapeutic tool is still unfolding, the findings from recent studies like Dr. Siegel’s offer hope for new, effective treatments for some of the most challenging mental health conditions.
References
- Siegel, Joshua S, et al. “Psilocybin Desynchronizes the Human Brain.” Nature, 17 July 2024, https://doi.org/10.1038/s41586-024-07624-5. Accessed 19 July 2024. ↩︎
