Psilocybin makes the brains of depressed people more ‘flexible and fluid’
A study published in the journal ‘Nature Medicine’ confirms that psilocybin is more effective than antidepressants in the remission of depression in patients with treatment-resistant depression and, more importantly, unravels the mechanisms of action of this molecule in the human brain.

Psilocybin, one of the active components of ‘magic mushrooms’, is the rising star in psychedelic research: 62% of psychedelic clinical trials use psilocybin, far ahead of MDMA (17%) or LSD (6%), as we recently reported. Addiction psychiatrist Josep Maria Fabregas, president of Fundación Beckley Med, also acknowledged in a recent interview that «psychotherapy with psilocybin shows promising results», specifically for smoking cessation.

The evidence for psilocybin’s efficacy in treating various mental ailments is mounting. Now, a groundbreaking study published in the journal ‘Nature’ and led by renowned neuroscientists David Nutt and Robin Carhart-Harris, confirms that psilocybin is more effective than antidepressants in the remission of depression in patients with treatment-resistant depression and, more importantly, unravels the mechanisms of action of this molecule in the human brain.

60 people took part in the study, which consisted of two clinical trials: the first involved taking 10 and 25 mg of synthetic psilocybin, followed by an MRI scan after the second dose. The second trial consisted of a double blind trial receiving either 25 mg psilocybin or a placebo, followed by an MRI scan three weeks after the second dose.

The results were ‘striking and exciting’, in David Nutt’s words: ‘A depressed brain can get stuck in a rut and locked into a particular form of negative thinking. However, after taking psilocybin, patients’ brains opened up and became more flexible and fluid for up to three weeks after ingestion”.

The flexibility referred to by the researcher is reflected in the increased interconnections between the brain regions of the study participants. These patients were more likely to experience an improvement in their mood months later. These changes have not been found in people treated with standard antidepressants.

“This supports our initial predictions, and confirms that psilocybin can be a real alternative to treatments for depression,” Nutt told the BBC.

The physiology of depression

The Covid pandemic and prolonged confinement has led to an exponential increase in the number of depressed people. During the first year of the pandemic, the number of people diagnosed with depression and anxiety increased by 25% worldwide, according to the World Health Organisation.

How does depression affect the brain? According to the study published by ‘Nature’, «patients diagnosed with depression often show a negative cognitive bias, characterised by pessimism, low cognitive flexibility, rigid thought patterns and negative fixations on themselves and the future (…) Neuroimaging research has consistently found examples of abnormal brain functioning in depression (…) the default neuromodal network is associated with introspection and self-referential thinking. These cognitive functions are often overactive in depression».

While the mechanisms by which psilocybin works in the brain are not yet fully understood, up to six separate clinical trials over the past 15 years have reported «impressive improvements in depressive symptoms with psilocybin therapy», the study claims.

One of the advantages of psilocybin over traditional antidepressants is that it is sometimes enough to take psilocybin once or twice for depressive symptoms to subside, rather than every day, as is the case with psychotropic drugs.

Another of the study’s authors, Professor Robin Carhart-Harris from the UK, 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. What we do know is that some people relapse, and it may be that after a while their brains revert to the rigid patterns of activity that we see in depression.

Following this encouraging study, the team now wants to examine their theory about changes in brain connectivity in other mental disorders, such as anorexia.

Our partners
Beckley Med’s training offer articulated courses from three of the world’s leading institutions in psychedelic therapy

Think Tank founded in Great Britain in 1998 by Amanda Feilding, a pioneer in psychedelic research in the field of mental health and on Drug Policy reform.

The world’s leading psychedelic research organisation. Rick Doblin’s MAPS is a global leader in training programmes for psychedelic therapists.

The figure of Stan Grof in the history of psychedelics has reached legendary status. His legacy takes the form of a comprehensive psychedelic psychotherapy training programme.

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