Psilocybin Causes Disruption in Vital Brain Networks, Potentially Clarifying Its Antidepressant Benefits.


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Psilocybin, the active component in magic mushrooms, has shown potential as a revolutionary treatment for major depression, but there are still many unknowns about its effects on the brain. A new preprint, not yet peer-reviewed, delves into how psilocybin influences brain networks.

After years of strict drug regulations and societal resistance impeding much-needed research, there is growing recognition of the potential benefits of psychedelic therapies. Earlier this year, Australia made history by legalizing MDMA and psilocybin for psychiatric use, and research continues to yield promising results.

Despite psilocybin’s promise in treating severe depression, many questions remain about its long-term effects.

In 2022, a study from Imperial College London and the University of California, San Francisco, found that psilocybin promotes a more adaptable and fluid state in the brain, alleviating some of the rigid patterns associated with depression. However, it was unclear how long these changes persisted.

Now, a team led by Professor Robin Carhart-Harris has uncovered how psilocybin affects crucial brain networks like the default mode network (DMN).

In a new preprint, the authors describe a study involving seven adults aged 18 to 45. These participants underwent brain scans after receiving psilocybin (25 milligrams), the stimulant methylphenidate (Ritalin), or no drugs. All participants had previous experience with psychedelics, with none having taken them in the past six months and none having psychiatric disorders. Follow-up scans were conducted at three weeks and six months.

Using precision functional mapping, the researchers compared brain network connectivity in each patient between baseline scans (when they were drug-free) and after taking psilocybin. Methylphenidate served as a control because it shares stimulating effects with psilocybin but lacks its psychedelic properties.

The study authors reported that psilocybin caused significant disruption in connectivity across brain networks, with more than a threefold greater impact on functional networks compared to methylphenidate. This disruption was driven by the desynchronization of brain activity.

The authors further noted that this desynchronization was most pronounced in the default mode network (DMN). Other psychedelics like LSD are known to alter the DMN, which is associated with the feeling of ego dissolution, where individuals perceive themselves as interconnected with the world.

Interestingly, the observed network desynchronization persisted for weeks but appeared to resolve after six months. This finding is significant as clinical trials have shown that a single high dose of psilocybin can have enduring positive effects on depression symptoms.

Although further research is needed, the authors propose that this phenomenon may partly explain how psilocybin achieves its impressive therapeutic effects. They suggest that the persistent suppression of connectivity between the hippocampus and DMN could be a potential mechanism underlying psilocybin’s pro-plasticity and antidepressant effects.

This research marks a significant advancement in a field that offers new hope for patients for whom other treatments have proven ineffective. The preprint, a preliminary scientific paper awaiting peer review, is accessible through medRxiv.


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