The active compound in magic mushrooms helps to unlock rigid patterns of brain connectivity associated with depression, according to a new study in the journal Nature Medicine.

The psychedelic molecule psilocybin has been shown to trigger a more flexible and expansive brain state that lasts for several weeks, correlated with reductions in depressive symptoms.

Depression tends to go hand-in-hand with heightened brain network modularity, whereby connectivity patterns within key brain regions are excessively strong while communication between different networks is restricted. This has been associated with a reduction in cognitive flexibility and a tendency to get stuck in cycles of negative thoughts.

Yet brain scans have indicated that psychedelics detonate a riot of connectivity throughout the brain, causing networks that wouldn’t normally communicate with one another to interact, resulting in more flexible patterns of thought and cognition. This explosion of brain activity is believed to underlie the apparent anti-depressant properties of psilocybin and other psychedelics.

In their new study, researchers from Imperial College London and the University of California, San Francisco, show that this more flamboyant brain state can persist for up to three weeks, resulting in durable improvements in symptomology.

“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,” explained study author Professor Robin Carhart-Harris in a statement.

The researchers analyzed data from two separate trials involving depressed patients. In the first of these, all participants were treated with psilocybin and had their brain activity scanned using functional magnetic resonance imaging (fMRI) before and one day after ingesting the drug. Participants in the second study, meanwhile, were treated with either psilocybin or the selective serotonin reuptake inhibitor (SSRI) escitalopram, and had their brains scanned before treatment and again three weeks later.

“In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in fMRI brain network modularity, implying that psilocybin’s antidepressant action may depend on a global increase in brain network integration,” write the researchers.

Importantly, this increased brain connectivity was strongly correlated with the efficacy of the treatment, and those who experienced the greatest reductions in depression continued to display a more “open” pattern of functional connectivity at the three-week mark. “This ‘liberating’ action of psilocybin is paralleled by subjective reports of ‘emotional release’ as well as subacute increases in behavioral optimism, cognitive flexibility and psychological flexibility after taking a psychedelic drug,” write the authors.

In contrast, they explain that “the antidepressant response to escitalopram was milder and no changes in brain network organization were observed.”

Commenting on these findings, study author Professor David Nutt revealed that “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,” he said.

Citing the need for further studies, however, Professor Carhart-Harris explained that “we don’t yet know how long the changes in brain activity seen with psilocybin therapy last and we need to do more research to understand this.”

“We do know that some people relapse, and it may be that after a while their brains revert to the rigid patterns of activity we see in depression.”