Psilocybin Breaks Depressive Cycles by Rewiring The Brain, Study Suggests

New research suggests that psilocybin, the active compound in magic mushrooms, may alleviate depression by physically rewiring the brain. The study, conducted on mice, tracked these neurological changes using a specially engineered virus. The findings potentially explain the positive outcomes observed in human clinical trials involving psilocybin for depression.

Alex Kwan, a biomedical engineer at Cornell University, explains that a key aspect of depression is rumination, characterized by an unhealthy fixation on negative thoughts. The study indicates that psilocybin might weaken or break this cycle by reducing certain feedback loops in the brain.

Depression is a major global health concern, affecting over 300 million individuals and is a leading cause of disability. Many patients find existing treatments ineffective or experience significant side effects, fueling the search for alternative therapies like psilocybin.

Psilocybin, originally derived from magic mushrooms, is currently under investigation not only for its antidepressant potential but also for its anti-inflammatory properties. Earlier research in Kwan's lab in 2021 demonstrated that psilocybin reshapes brain connections, with these alterations potentially lasting for extended periods. That said, the reality is a bit more complicated. the specific reasons behind increased connections in some neurons and decreased connections in others remained unclear.

The latest study, spearheaded by biomedical engineer Quan Jiang, delved deeper into the specific brain circuits being rewired and the mechanisms involved. Researchers employed an engineered rabies virus to trace alterations in brain connectivity. Rabies, in its natural form, spreads through neurons by crossing synapses.

Kwan clarifies that the rabies virus was used to map brain connectivity. The process involved injecting mice with either a single dose of psilocybin or a placebo, followed by the engineered virus one day later. After a week, the researchers compared the viral pathways. Fluorescent proteins were used to visualize the virus's path through the mouse brains.

The scans revealed increased connectivity between brain regions associated with sensory processing and those involved in taking action. Furthermore, connections within the cortex, the area responsible for negative thought feedback loops in humans, were reduced.

Jiang and his team also discovered that brain activity appears to influence where psilocybin-induced rewiring occurs. This raises the possibility of using techniques like magnetic stimulation to modulate specific neural activity and target the rewiring process.

While these findings require confirmation in human studies, as results from mouse studies do not always translate directly to humans, they offer a potential explanation for observations in human studies and provide insights into how psychedelics might function. The researchers suggest that combining neuromodulation with psychedelics to precisely target and rewire specific circuits presents an exciting avenue for future research.