Psilocybin is a hallucinogen that alters the brain’s reaction to a substance called serotonin and, when broken down by the liver (into “psilocin”), causes an altered state of consciousness and perception in users.
Hallucinogenic mushrooms promise medical benefits, but we’re only now beginning to understand how they could help treat depression.
Up to 30% of depressed people do not respond to antidepressant treatment. This may be due to biological differences between patients and because the reaction to drugs often takes a long time, leading some people to drop out of treatment.
Therefore, it is urgent to expand the range of drugs available to treat depressed people.
In recent years, attention has turned to psychedelics such as psilocybin, the active compound in “magic mushrooms”.
Although a number of clinical studies have shown that psilocybin can quickly cure depression, even in cancer patients, little is known about how psilocybin works directly in the brain.
But two recent studies, published in The New England Journal of Medicine and Nature Medicine, have shed light on this mysterious process.
Psilocybin is a hallucinogen that alters the brain’s reaction to a substance called serotonin. When broken down by the liver (into “psilocin”), it causes an altered state of consciousness and perception in users.
Previous studies using functional magnetic resonance imaging (FMRI) of the brain have shown that psilocybin appears to reduce activity in the medial prefrontal cortex, an area of the brain that helps regulate a range of cognitive functions, including attention, l inhibition of control, habits and memory. The compound also reduces the connections between this region and the posterior cingulate cortex, which may participate in the regulation of memory and emotions.
The active connection between these two brain regions is usually a feature of the brain’s “default mode network”. This network is active when we rest and focus internally, perhaps remembering the past, imagining the future or thinking about ourselves or others.
By reducing network activity, psilocybin could eliminate the constraints of the inner self. There are users who report having an “open mind”, with a greater perception of the world around them.
Interestingly, mental brooding, the state of being “stuck” in negative thoughts, particularly about oneself, is a hallmark of depression. And we know that patients with higher levels of negative rumination tend to exhibit more default mode network activity (RMP) than other resting networks. They literally begin to react less to the world around them.
But it remains to be seen whether symptoms of depression are causing this change in activity or whether people with a more active default mode network are more prone to depression.
The most compelling evidence of how psilocybin works comes from a randomized double-blind study (the gold standard of clinical trials) that compared a group of people with depression treated with psilocybin with another group who received the existing escitalopram antidepressant. something that has never been done before has been tried before.
The exam was further analyzed using FMRI images of the brain and the results were compared to the FMRI results of another recent clinical exam.
Just a day after the first dose of psilocybin, FMR measurements revealed an overall increase in connectivity between the various brain networks, which are typically reduced in people with major depression. And the standard mode network was simultaneously reduced while connectivity between it and other networks increased, confirming earlier smaller studies.
The substance caused a greater increase in connectivity in some people than others. But studies have shown that people with the greatest increase in connection between networks also experienced significant improvement in symptoms six months later.
The brains of the people who took escitalopram showed no change in connectivity between the standard modality and other brain networks six weeks after starting treatment. It’s possible this drug may make changes later, but the rapid onset of psilocybin’s antidepressant effects means it may be ideal for people who don’t respond to existing antidepressants.
The study proposes that the observed effect may occur because psilocybin has a more concentrated action than escitalopram on brain receptors known as “5-HT2A serotonergic receptors”. These receptors are activated by serotonin and are active in all networked brain regions, including the default mode network.
We already know that the level of binding of these receptors to psilocybin causes psychedelic effects, but exactly how this activation generates changes in network connectivity remains to be explored.
The end of traditional antidepressants?
These findings raise the question of whether alteration of brain network activity is necessary for the treatment of depression.
Many people taking traditional antidepressants still report an improvement in their symptoms without them. And in fact, the study showed that six weeks after starting treatment, both groups had reduced symptoms.
According to some depression rating scales, psilocybin had the greatest effect on general mental well-being. And a greater percentage of patients treated with psilocybin showed a clinical reaction than those treated with escitalopram (70% versus 48%).
Additionally, more patients in the psilocybin group still had a reduction in symptoms after six weeks (57% versus 28%). The fact that some patients have not responded to psilocybin or have relapsed after treatment only demonstrates how difficult it can be to treat depression.
Another important point is that mental health professionals attended both treatment groups during and after the study. The success of psilocybin largely depends on the environment in which it is administered. In other words, using it for self-medication is a bad idea.
Additionally, psilocybin-assisted therapy patients have been carefully screened based on their history to avoid the risk of psychosis and other harmful effects.
Regardless of the caveats, these studies are incredibly promising and could expand the treatment options available to patients with depression. And internalized negative thought processes are not specific to depression. In due course, other ailments such as addiction and anxiety may also benefit from psilocybin-assisted therapy.
*Clare Tweedy is a professor of neuroscience at the University of Leeds in the UK..
This article was originally posted on the academic news site The conversation and republished under a Creative Commons license. read here the original version (in English).
‘This text was originally published in https://www.bbc.com/portuguese/geral-61760572‘
Source: Terra
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