New brain mapping research from a leading group of psychedelics researchers deepens our understanding of how psilocybin works in the brain, first 'dissolving' and then expanding brain connections. 

Certain parts of depressed people's brains became more interconnected and flexible after two doses of psilocybin, and these changes lasted up to three weeks after treatment.

Just last year, a small landmark trial from Nutt and colleagues showed psilocybin coupled with psychological therapy was at least as effective as taking a common antidepressant, escitalopram – a drug that often comes with impactful side effects of weight gain, lack of libido, and insomnia. Many Indigenous peoples have long used magic mushrooms and other plants for their healing and hallucinogenic properties.

Neuropsychopharmacologist David Nutt of the Imperial College London States That,

"For the first time we find that psilocybin works differently from conventional antidepressants – making the brain more flexible and fluid, and less entrenched in the negative thinking patterns associated with depression."

In only the last two decades or so has there been a cautious resurgence in clinical research, fronted by the researchers behind this latest study, to understand whether psilocybin may help to alleviate depression and anxiety, and how psychedelic drugs affect the brain more generally.

In a 2018 brain-imaging study of 20 people with depressive symptoms, psilocybin also appeared to enhance people's emotional response, rather than blunting it like antidepressants tend to do.

But observing positive benefits among small groups of people is one thing; untangling what's happening in the brain is another challenge altogether – and so far, the mechanisms of how psilocybin works in the brain have remained poorly understood.

Analyzing brain scans of nearly 60 people with clinical depression involved in two previous trials, Nutt and colleagues found people receiving psilocybin had greater connectivity between brain regions that are rich in serotonin receptors and usually segregated in depressed patients.

The effect was "rapid, sustained" and strongest in people who reported their depressive systems had eased. Their brain networks were more interconnected and flexible, one day after treatment and, in some people, three weeks later.

No such changes were observed in people on antidepressants, which also target serotonin receptors.

"This supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments," says Nutt.