Up to 30% of depressed people do not respond to antidepressant treatmentand this could be due to the differences in biology between patients and the fact that it often takes a long time to respond to medications, with some people giving up after a while, so there is a urgent need to expand the repertoire of drugs available to depressed people.
In recent years, attention has turned to psychedelics such as psilocybin as a cure for depressionthe active compound of “magic mushrooms”, and despite a series of clinical studies showing that psilocybin can do this, even for cancer-related anxiety and depression, Little is known about the process of using psilocybin as a cure for depression.
Now two recent studies, published on The New England Journal of Medicine And Nature Medicineshed light on this mysterious process, determining that psilocybin is a hallucinogen that alters the brain’s response to a chemical called serotonin, and when broken down by the liver (into “psilocin”), it causes an altered state of consciousness and perception in users.
Previous studiesusing functional MRI brain scan (fMRI), have shown that psilocybin as a cure for depression appears to reduce activity in the medial prefrontal cortexan area of the brain that helps regulate a range of cognitive functions, including attention, inhibitory control, habits, and memory.
The compound also reduces the connections between this area and the posterior cingulate cortex, an area that may play a role in regulating memory and emotions.
An active connection between these two brain areas is normally a feature of the brain’s “default mode network”, with this network being active when we rest and focus internally, perhaps remembering the past, imagining the future or thinking about ourselves or to the others.
By reducing network activity, using psilocybin as a cure for depression could remove the constraints of the internal “self”, with users reporting a “open mind ”with a greater perception of the world around them.
Interestingly, brooding, a state where one is “stuck” in negative thoughts, particularly about oneself, is a hallmark of depression, and we know that patients with higher levels of negative rumination they tend to exhibit greater network activity in default mode than other networks at rest, literally becoming less responsive to the world around them.
It remains to be seen, however, whether symptoms of depression cause this impaired activity or whether those with a more active default mode network are more prone to depression.
The study investigating psilocybin as a cure for depression
The strongest evidence of how psilocybin works as a cure for depressioncomes from a double-blind, randomized controlled trial (the gold standard of clinical trials) that compared a group of depressed people they hired psilocybin as a cure for depression, with those who were taking the drug antidepressant escitalopramsomething that had never been done before.
The study was further analyzed using fMRI brain scans and the results were compared with other fMRI results from another recent clinical study.
Just one day after the first dose of psilocybin as a cure for depression, the fMRI measurements revealed a general increase in connectivity between various brain networks, which are typically reduced in those with severe depression. The default mode network was simultaneously reduced, while connectivity between it and other networks was increased, in support of earlier and smaller studies.
Therefore, the use of psilocybin as a cure for depression it has increased connectivity more in some people than in othersbut studies have shown that the people who had the greatest push to connect between networks also had the greater improvement in their symptoms six months later.
The brains of the people who were hiring escitalopramon the other hand, showed no change in the connectivity between the default modality and other brain networks six weeks after the start of treatment.
It is possible that escitalopram may make changes later, but the rapid onset of the antidepressant effect of psilocybin means that it might be ideal for people who don’t respond to existing antidepressants.
The study proposes that the observed effect may be due to the fact that using psilocybin as a cure for depression has a more concentrated action on the receptors in the brain called “5-HT2A serotonergic receptors” compared to escitalopram.
These receptors are activated by serotonin and are active in all brain areas of the network, including the network by default. We already know that the level of psilocybin binding to these receptors leads to psychedelic effects, however how their activation leads to changes in network connectivity is yet to be explored.
This raises the question of whether altered activity of the brain networks is required to treat depression, not least because many people taking traditional antidepressants still report an improvement in their symptoms without them. In fact, the study showed that, six weeks after starting treatment, both groups reported an improvement in their symptoms.
According to some depression rating scales, however, psilocybin had the greatest effect on general mental well-being, and a greater proportion of patients treated with psilocybin showed a clinical response than those treated with escitalopram (70% vs 48%). .
Even more patients in the psilocybin group were still in remission at six weeks (57% versus 28%). The fact that some patients still do not respond to psilocybin, or that they relapse after treatment, shows how difficult it can be to cure depression, and mental health professionals have supported both treatment groups during and after the process.
The success of psilocybin is highly dependent on the environment in which it is taken. This means that it is a bad idea to use it for self-medication, plus patients have been carefully selected for psilocybin-assisted therapy based on their history to avoid the risk of psychosis and other adverse effects.
Regardless of the caveats, these studies are incredibly promising and bring us closer to expanding the treatment options available to patients with depression, among other things finally, internalized negative thought processes are not specific to depression. In due course, other ailments, such as addiction or anxiety, may also benefit from psilocybin-assisted therapy.
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