Magic mushrooms were once criticized for their psychedelic properties, but are now attracting increasing attention for their mind-altering potential as a therapy for a wide range of mental health conditions.
However, surprisingly little is known about the various neurological effects of the psychoactive compound psilocybin in the fungus, making it difficult to predict how the drug will ultimately be useful as a medicine for society.
A study led by Joshua Siegel, a psychiatrist at the University of Washington School of Medicine, found that changes occurred in the brains of seven healthy adults before, during, and after taking a high dose of psilocybin. Disruptions in connectivity were found that persisted for weeks in some parts of the brain.
The findings fill gaps in our understanding of how psilocybin’s biochemical impact translates into large-scale behavioral changes that can help or hinder people with different psychological needs.
“Today we know a lot about the psychological effects and the molecular/cellular effects of psilocybin,” Siegel says.
“But we don’t know much about what happens at the level that connects the two: the level of functional brain networks.”
Magic mushrooms weave their glamour by mimicking serotonin’s affinity for the 5-HT2A receptor. The subjective effects are well known, usually including euphoria combined with distortions of self-perception, time, space, sound and color.
Animal models confirm that short-term activation of these receptors in areas where they are abundant, such as the medial frontal lobe, produces long-lasting effects by loosening established pathways and promoting new connections.
It is precisely this ‘plasticity’ of the nervous system that allows our brains to adapt. This makes psilocybin an attractive drug for treating mental disorders that are stubbornly resistant to change.
Whether these conclusions apply to humans, however, is unclear. So Siegel and his team performed functional MRI scans on volunteers before they took a generous 25 milligrams of psilocybin. Further scans were performed immediately after their dosing and again 21 days later.
For comparison, the subjects were also given a 40-milligram dose of the stimulant methylphenidate at separate times and a similar series of scans were taken.
The scans clearly showed a significant disruption in functional connectivity in the cortex of the brain after the psilocybin dose. Deeper in the brain, large changes were also seen in a group of regions that are most active when we are awake but not engaged in a task, known as the default mode network (DMN).
Based on previous studies in rats, the researchers suspected that the widespread disruption was due to populations of nerve cells that normally coordinate their activities falling out of sync, temporarily erasing the unique patterns that define our sense of self.
“The brains of people who use psilocybin are more similar to each other than they are to the brains of people who no longer trip,” says neurologist and lead author Nico Dosenbach.
“Their individuality is temporarily wiped away. This confirms, on a neuroscientific level, what people say about losing their sense of self during a trip.”
Oddly enough, giving the volunteers a simple auditory-visual matching task after their psilocybin dose while they were being scanned seemed to “ground” their DMN, reducing the severity of the disruption.
Scans performed three weeks after psilocybin treatment showed that the cortex had largely returned to its pre-dose synchronization. However, a region called the anterior hippocampus, which is involved in a range of cognitive processes that include perception and memory, continued to show a persistent functional change.
By linking our knowledge of the pharmacology of psilocybin with self-reported and cultural knowledge of its effects within a neurological framework, we can point the way to treatments that alleviate depression or reduce post-traumatic stress, and caution against its use in situations where disruption may pose significant risks.
It may be a while before we run to the doctor for a dose of mushrooms to get our brains moving again, but studies like this one are bringing us one step closer to understanding the fascinating relationship between our brains and this magical group of fungi.
This research was published in Nature.