We May Finally Know How Magic Mushrooms Work To Relieve Depression

By: Clare Watson | Science Alert

For many people with treatment-resistant depression, in recent years hope has been offered by psychedelics such as psilocybin, the key active ingredient in magic mushrooms. It appears that psychedelics may ‘flip the switch‘ on rigid brain networks, but we haven’t been entirely sure how that works.

Now, 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, the study found.

“These findings are important,” says neuropsychopharmacologist David Nutt of the Imperial College London (ICL).

“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.”

Many Indigenous peoples have long used magic mushrooms and other plants for their healing and hallucinogenic properties.

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.

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.

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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.

Analysing 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.

The findings echo a recent 2020 study that similarly reported changes in brain network connectivity up to a month after a single dose of psilocybin, but of course, much more research is needed.

“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,” says neuroscientist Robin Carhart-Harris, also from ICL’s Centre for Psychedelic Research.

“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.”

While the findings are intriguing – especially for those among us who wrestle with ruminating thoughts, manage mental health problems, or are just curious about how our brains work – we also need to remember this is early research, where people were given psilocybin in a controlled environment, supported by mental health professionals who helped them talk through any hallucination experiences.

It’s also just one possible interpretation, from two small but high-quality trials, of what can be a profoundly life-altering and possibly frightening experience. Other studies looking at how psilocybin works in the brain have hinted it could dissolve ego, and we haven’t even begun to scratch the surface of why some people benefit from psilocybin therapy but not others.

Plus, people with a history of psychosis were excluded from the trials for safety reasons, so there are sadly some people who might not benefit and need other care.

Nevertheless, the researchers are hopeful these findings might lay the groundwork for more research investigating psilocybin’s potential to treat other mental illnesses, ones also marked by rigid thought patterns.

“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,” says Carhart-Harris.

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

The study was published in Nature Medicine.

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