Psychoactive substance in 'magic' mushrooms 'rewired' the brains of people with depression in a small, promising study, scientists say

• Brain scans suggest psilocybin, found naturally in 'magic' mushrooms, can 'rewire the brain', scientists say.
• This effect may underscore the drug's potential, alongside therapy, as an antidepressant, they said.

Scientists have said that the psychoactive compound found naturally in 'magic' mushrooms could provide a valuable alternative to conventional treatments for depression.

The researchers from Imperial College London and UC San Francisco, looked at brain scans and found the drug psilocybin helped 'rewire the brain' in patients. People with depression typically experience intense connectivity between some parts of the brain, and weak connectivity between other parts. The study found that psilocybin both helped temper the intensity and boost weak connectivity.

The changes in brain activity correlated with a reduction in symptoms, the study authors said in the science journal Nature Tuesday.

David Nutt, head of the Imperial Centre for Psychedelic Research, said in a statement of the findings: "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.

The World Health Organization estimates that 5% of adults – or 280 million people – worldwide suffer from depression. The best-performing antidepressants often have side effects, can make symptoms worse if stopped suddenly, and don't work for everyone. The use of mind-altering drugs, like psilocybin, for treatment in mental health isn't new, but research into the field has been difficult to undertake given the substances are illegal in most countries.

Whilst welcoming the findings, researchers warned against taking psychedelics without supervision.

"It might sound trite to say, but I think psilocybin therapy opens up the mind, and that's its strength," Robin Carhart-Harris, former head of the Imperial Centre for Psychedelic Research, told the Times. "But that's also arguably where the risk comes in, which is why it needs to be managed and to happen alongside psychological support."

To get the results, scientists assessed the impact of lab-made psilocybin on the brains of participants in two clinical trials conducted in 2016 and 2020. The first trial, a study of 16 participants who received two weekly doses of the drug alongside therapy, revealed "rapid" and "substantial" reductions in depression severity six months after treatment, the study's authors said.

A second trial studied 59 people with major depressive disorders. One group received psilocybin and the other received the antidepressant drug escitalopram, branded as Lexapro. One group received two doses of 25mg of psilocybin, three weeks apart, and six weeks of a dummy drug; and the other group received two doses of 1mg of psilocybin, three weeks apart, and six weeks of daily doses of Lexapro.

There were no changes in the brain network in response to Lexapro, the study authors said. But with psilocybin, brain neural pathways became more interconnected, and correlated with improvements in depression symptom severity three weeks after therapy, they said.

Despite promising results, the researchers and independent experts cautioned that more research was needed.

"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," study author Carhart-Harris said in a statement.

Carhart-Harris said the same mechanism might work for other mental illnesses, such as anorexia or addiction.

"We now need to test if this is the case, and if it is, then we have found something important," he said.