Psilocybin Study Reveals Persistent Changes in the Brain

Once condemned for their psychedelic effects, magic mushrooms are drawing growing interest because the same mind-altering properties may offer treatment for a broad range of mental health problems.

Even so, little is understood about the varied neurological impact of psilocybin, the fungus's psychoactive compound. That uncertainty makes it hard to forecast how the drug could eventually serve communities as a medicine.

A Washington University School of Medicine study, led by psychiatrist Joshua Siegel, monitored brain changes in seven healthy adults before, during and after they received a high dose of psilocybin. It found connectivity disruptions that remained in certain brain areas for weeks.

These results address gaps in understanding how psilocybin's biochemical effects become large-scale behavioural changes that could either help or hinder people with differing psychological needs.

"These days, we know a lot about the psychological effects and the molecular/cellular effects of psilocybin," says Siegel.

"But we don't know much about what happens at the level that connects the two – the level of functional brain networks."

How magic mushrooms and psilocybin affect the brain

Magic mushrooms produce their effects by imitating serotonin's attraction to the 5-HT2A receptor. Their subjective effects are familiar: they commonly involve euphoria alongside altered perceptions of the self, time, space, sound and colour.

Research in animal models shows that briefly stimulating these receptors in areas where they are especially dense, including the medial frontal lobe, can create lasting effects. It does so by relaxing established neural pathways and encouraging new connections.

This nervous-system 'plasticity' is what enables the brain to adapt. It also makes psilocybin a potentially attractive drug for psychological conditions that are particularly resistant to change.

Brain scans reveal changes in functional connectivity

It remains uncertain, however, whether the same findings apply in humans. To investigate, Siegel and colleagues used functional magnetic resonance imaging to scan volunteers before they received a substantial 25-milligram dose of psilocybin. They carried out further scans straight after the dose and again 21 days later.

For comparison, participants were also given 40 milligrams of the stimulant methylphenidate on separate occasions and underwent a comparable set of scans.

Following psilocybin, the scans showed marked disruption to functional connectivity throughout the brain's cortex. Substantial changes also appeared deeper in the brain, within a collection of regions that is most active when people are awake but not engaged in a task: the default mode network (DMN).

Drawing on earlier rat studies, the researchers proposed that this broad disruption arose when groups of nerve cells that normally synchronise their activity became unsynchronised. This may temporarily remove the distinctive patterns underlying our sense of self.

"The brains of people on psilocybin look more similar to each other than to their untripping selves," says neurologist and senior author Nico Dosenbach.

"Their individuality is temporarily wiped out. This verifies, at a neuroscientific level, what people say about losing their sense of self during a trip."

Persistent effects after psilocybin treatment

Interestingly, when participants completed a straightforward audio-visual matching task while being scanned after taking psilocybin, it appeared to 'ground' their DMN and lessen the extent of the disruption.

By three weeks after psilocybin treatment, scans indicated that the cortex had largely regained its pre-dose synchronisation. A region known as the anterior hippocampus, which contributes to several cognitive functions involving perception and memory, nevertheless continued to display a lasting functional alteration.

Bringing together current knowledge of psilocybin pharmacology with self-reported experiences and cultural understanding of its effects, within a neurological framework, may guide treatments for depression or post-traumatic stress. It could also help warn against using it where such disruption may present considerable risks.

We may still be some distance from asking a doctor for mushrooms to restore our minds to working order. However, studies such as this move us closer to understanding the remarkable relationship between the brain and this magical group of fungi.

The research was published in Nature.