Psilocybin may “reset” the depressed brain

By Fei Sato

A small study involving 19 patients with treatment resistant depression was recently published in the journal Scientific Reports.

The study was led by the Psychedelic Research Group, from Imperial College London.

This is not the first study showing the effects of psilocybin on depression. For a review of previous studies, see here and here.

In the current study, patients were given a single dose of psilocybin, the psychoactive ingredient found in “magic mushrooms”. The researchers performed fMRI brain scans on these patients before the dose, one day after and five weeks later.

After one week, 63% of patients were no longer depressed. After 5 weeks, 47% of patients were no longer depressed. Within the brain, psilocybin decreased activity in the amygdala – a part of the brain related to strong emotions, such as fear and anxiety. The decreased amygdala activity correlated with reductions in depressive symptoms. There was an increase in connectivity within the default mode network (DMN) – the DMN is a network of three regions which are primarily active when a person is not involved in a task, but rather is at rest and thinking about their life. For this reason the DMN is commonly associated with self-awareness or self-cognition. This increase in DMN activity was correlated with the antidepressant effects of psilocybin.

Figure 1. fMRI images showing the cerebral blood flow (CBF) before and after psilocybin treatment. A decrease in CBF is noted in the amygdala after psilocybin treatment. The decrease in amygdala CBF correlates with levels of depression.

These results are interesting as they add another piece to the puzzle on how psychedelics may alleviate depressive symptoms. It was previously shown that psychedelics such as psilocybin, LSD and ayahuasca actually disrupt or reduce connectivity of the DMN during ‘the trip’. Now we know that there is a rebound type effect that leads to a subsequent increase in DMN connectivity weeks later.

The researchers have proposed that psilocybin can “reset” the brain. By disrupting the DMN initially, participants are able to decrease the perceptual filters associated with their sense of self. In the weeks afterwards, patients can then start to “integrate” all the new information they have received during the trip, which is hypothesised to be related to the increase in DMN connectivity and thoughts of the self. Such ideas have been outlined in a paper by Robin Carhart-Harris and colleagues.

According to BBC news, Dr Carhart-Harris said the depressed brain was being “clammed up” and the psychedelic experience “reset” it. “Patients were very ready to use this analogy. Without any priming they would say, ‘I’ve been reset, reborn, rebooted’, and one patient said his brain had been defragged and cleaned up”, he said.

Prof Mitul Mehta, from the Institute of Psychiatry at King’s College London, told BBC: “What is impressive about these preliminary findings is that brain changes occurred in the networks we know are involved in depression, after just a single dose of psilocybin.

“This provides a clear rationale to now look at the longer-term mechanisms in controlled studies.” The team at Imperial College told patients not to self medicate. A larger scale study with a control group is now needed to confirm these results.

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