Up to 30% of people with depression don’t respond to treatment with antidepressants. This may be down to differences in biology between patients and the fact that it often takes a long time to respond to the drugs – with some people giving up after a while. So there is an urgent need to expand the repertoire of drugs available to people with depression.
In recent years, attention has turned to psychedelics such as psilocybin, the active compound in “magic mushrooms”. Despite a number of clinical trials showing that psilocybin can rapidly treat depression, including for cancer-related anxiety and depression, little is known about how psilocybin actually works to relieve depression in the brain.
Now two recent studies, published in The New England Journal of Medicine and Nature Medicine, have shed some light on this mysterious process.
Psilocybin is a hallucinogen that changes the brain’s response to a chemical 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 MRI (fMRI) brain scanning, have shown that psilocybin seems to reduce activity in the medial prefrontal cortex, an area of the brain that helps regulate a number of cognitive functions, including attention, inhibitory control, habits and memory. The compound also decreases 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”. This network is active when we rest and focus internally, perhaps reminiscing about the past, envisioning the future or thinking about ourselves or others. By reducing the activity of the network, psilocybin may well be removing the constraints of the internal “self” – with users reporting an “opened mind” with increased perception of the world around them.