Magic mushroom compound ‘rewires the brain for people with depression’

Psilocybin, the psychedelic compound found in magic mushrooms, could be used to help treat depression, with new human trials resulting in a “promising advance” which could help where traditional therapies may not.

Scientists at Imperial College London said their study suggests the compound “opens up” communication between different parts of the brain, and works therapeutically to alleviate depression. They said it could possibly provide treatment for other psychiatric conditions that are marked by fixed patterns of thinking.

The researchers said psilocybin is one of a number of psychedelics being explored as a potential therapy for psychiatric disorders.

Several studies have trialled a synthesised form of the drug to treat patients with depression and anxiety, with promising results.

The latest 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 self-reported improvements in their depression.

However, similar changes in brain connectivity were not seen in those treated with a conventional antidepressant (called escitalopram), suggesting the psychedelic works differently in treating depression.

The paper’s senior author, Professor Robin Carhart-Harris, former head of the Imperial Centre for Psychedelic Research, and who is now based at the University of California in San Francisco, said: “The effect seen with psilocybin is consistent across two studies, related to people getting better, and was not seen with a conventional antidepressant.

“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.”

In the latest study, a team led by Imperial’s Centre for Psychedelic Research analysed fMRI scans of almost 60 participants with treatment-resistant depression, who undertook two trials. In the first trial all the participants received psilocybin.

In the second, the participants were not told whether they had been given psilocybin or a placebo that turned out to be escitalopram, an SSRI (selective serotonin reuptake inhibitor) antidepressant.

In addition to the drugs, all participants also received talking therapies with registered mental health professionals and brain scans were taken before, and then one day or three weeks after participants received psilocybin therapy.

Both trials found improvements with psilocybin therapy, as measured by improved participant scores on clinical questionnaires.

The scans, which were done before and after treatment, showed the psilocybin treatment reduced connections within brain areas that are tightly connected in depression, and increased connections to other regions of the brain that had not been well integrated and are more segregated in depressed patients.

They found a correlation between this effect and symptom improvement in both trials – while the strength and duration of effect varied between participants, it was strongest in those who reported an improvement in symptoms.

Professor Carhart-Harris said: “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.”

The authors warned that while their findings are encouraging, the trials took place under controlled, clinical conditions, using regulated doses of psilocybin formulated in a laboratory, and involved extensive psychological support before, during and after dosing, provided by mental health professionals.

They said patients with depression should not attempt to self-medicate with psilocybin, as taking magic mushrooms or psilocybin in the absence of these careful safeguards may not have a positive outcome.

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.”

Professor Carhart-Harris added: “One exciting implication of our findings is that we have discovered a fundamental mechanism via which psychedelic therapy works not just for depression, but 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.”

The research is published in the journal Nature Medicine.