Psilocybin, a compound in magic mushrooms, opens up the brains of depressed people, making them less fixed in negative thinking patterns, according to a new study.
The findings indicate the compound could be an alternative approach to treating depression, researchers suggested.
Psilocybin was found to make the brain more flexible and work differently than antidepressants even weeks after use.
Researchers said brain activity patterns in depression can become rigid and restricted - but psilocybin could help the brain to break out of the rut in a way traditional therapies cannot.
The compound is one of a number of psychedelics being explored as a potential therapy for psychiatric disorders.
Professor David Nutt, head of the Imperial Centre for Psychedelic Research, said: "These findings are important because 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.
"This supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments."
The paper's senior author Professor Robin Carhart-Harris, former head of the Imperial Centre for Psychedelic Research said: "The effect seen with psilocybin is consistent across two studies, related to people getting better, and was not seen with a conventional antidepressant."
He continued: "In previous studies we had seen a similar effect in the brain when people were scanned whilst on a psychedelic, but here we're seeing it weeks after treatment for depression, which suggests a 'carry over' of the acute drug action."
The new findings are based on analysis of brain scans from around 60 people receiving treatment for depression, led by Imperial College London's Centre for Psychedelic Research.
The team behind the study believes it may have untangled how psilocybin works on the brain.
The results, taken from two combined studies, reveal that people who responded to psilocybin-assisted therapy showed increased brain connectivity not just during their treatment, but up to three weeks afterwards.
This opening up effect was associated with people reporting improvements in their depression.
Researchers noted similar changes in brain connectivity were not seen in those treated with a conventional antidepressant - escitalopram - suggesting the psychedelic works differently in treating depression.
According to the team, the findings, published in the journal Nature Medicine, are a promising advance for psilocybin therapy, with the effects replicated across two studies.
But the authors caution that while the findings are encouraging, patients with depression should not attempt to self-medicate with psilocybin, as taking magic mushrooms or psilocybin in the absence of trial conditions may not have a positive outcome.
