Summary: A new study shows that psilocybin, the active ingredient in magic mushrooms, temporarily alters brain networks involved in internal thinking, such as daydreaming and memory. These changes last for weeks and may increase brain flexibility and improve mental health.
The findings could pave the way for psilocybin-based treatments for depression and PTSD. The study highlights the importance of using these drugs under medical supervision.
Important facts:
- Temporary changes: Psilocybin changes brain networks for weeks, but not permanently.
- Mental flexibility: The drug increases brain flexibility and promotes mental health.
- Medical care: The results emphasize the need for trained supervision during use.
Source: WUSTL
Psilocybin mushrooms, commonly known as magic mushrooms, can induce profound changes in perception, distorting a person’s sense of place, time, and self.
Advocates have long argued that, under the right conditions, such experiences can help alleviate psychological distress a claim supported by some scientific evidence. Understanding how psilocybin affects the brain could enable scientists and clinicians to better harness its potential for therapeutic use.
Researchers at Washington University School of Medicine in St. Louis have discovered that psilocybin — the psychoactive compound in magic mushrooms — temporarily disrupts a key network of brain regions responsible for internal thought processes such as daydreaming, self-reflection, and memory recall. This disruption offers a clearer neurobiological explanation for the vivid hallucinations and altered sense of self often reported by users.
The findings not only shed light on how psilocybin produces its hallucinogenic effects but also provide a scientific foundation for exploring its use in mental health treatments. By understanding these brain changes, scientists hope to develop targeted psilocybin-based therapies for conditions like depression and post-traumatic stress disorder, potentially unlocking new avenues for care.
Co‑senior author Dr. Nico Duesenbach, a professor of neurology at the University of Florida, explained that psilocybin produces a powerful initial impact on brain networks, followed by a meaningful residual effect once the immediate influence fades. This pattern, he noted, is ideal for a potential therapeutic drug — strong enough to create change, yet not so disruptive that it damages brain function or lingers for days.
According to Duesenbach, the goal is to achieve an effect that lasts long enough to make a real difference in a patient’s mental state without causing prolonged instability. By striking this balance, psilocybin could offer a therapeutic window in which the brain is more receptive to positive change, potentially enhancing the effectiveness of psychological treatments.
The study, published in Nature on July 17, offers other scientists a guide to assessing the effects of psychiatric drugs on brain function. It could also speed up the development of drugs for various psychiatric disorders.
Psilocybin showed promise as a treatment for depression in the 1950s and 1960s, but the federal government’s restrictive drug policies effectively halted all further research in the decades that followed. In recent years, however, regulations have been relaxed, and interest in the field has revived.
Dr. Joshua S. Siegel, lead author and professor of psychiatry, explained that while much is known about the psychological and molecular or cellular effects of psilocybin, far less is understood about what happens at the level that links the two the brain’s active communication networks. To address this gap, Siegel assembled a multidisciplinary team, including brain‑imaging expert Dr. Nico U.F. Dosenbach and co‑author Dr. Ginger E. Together, they developed a method to visualize psilocybin’s impact on individual participants’ functional brain networks — the neural pathways connecting different brain regions and to relate these changes to participants’ subjective experiences.
Given the potential for challenging or distressing psychedelic experiences, each participant was supported throughout the sessions by two trained guides, who helped them prepare, provided reassurance during the experience, and assisted with post‑session integration.
On average, participants underwent 18 functional MRI scans in the days or weeks before their psilocybin sessions, with four returning six months later for follow‑up testing. Results showed that psilocybin induced profound but temporary changes in brain connectivity, most notably desynchronizing the default mode network.
After the initial desynchronization, the brain network returned to its baseline as the drug’s acute effects faded. However, subtle changes compared to pre‑psilocybin measurements persisted for weeks, while the default mode network in participants given methylphenidate remained unchanged.
“The idea is to temporarily completely eliminate this system, which is fundamental to the brain’s ability to think about itself in relation to the world,” Siegel said.
The long-term effect is that the brain becomes more flexible and potentially able to achieve a healthier state.
Typically, each person’s active brain network is as unique as a fingerprint. Psilocybin disrupted the brain network so severely that it was no longer possible to identify individuals until the acute effects wore off.
“The brains of people under the influence of psilocybin resemble each other more than they resemble themselves after the trip,” says Dosenbach. “Their individuality is temporarily lost. This confirms on a neuroscientific level what is said about the loss of a sense of identity during the trip.”
During the sessions, participants rated their feelings of transcendence, connectedness, and awe using a validated mystical experience questionnaire. Researchers then measured changes in each participant’s functional brain networks in relation to the intensity of these reported experiences. “We were able to gather highly precise data on the drug’s effects for each individual,” said co‑author Dr. Ginger E. Nicol.
Nicol noted that this approach represents a step toward more precise clinical studies. In psychiatry, it is often unclear which patients will benefit from a particular drug, the optimal dosage, or the ideal treatment frequency. As a result, clinicians typically prescribe one medication at a time and adjust the dose gradually until an effective regimen is found. This method could help tailor treatments more accurately from the outset.
“By applying this approach to clinical trials, we can identify the factors that determine who benefits and who does not, and make better use of the drugs available to us.”
Nicol, Siegel, and Duesenbach stress that their findings should not be taken as encouragement to self‑medicate with psilocybin. The substance is not approved by the U.S. Food and Drug Administration for treating depression or other conditions, and using it without professional mental health guidance carries significant risks.
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