Psilocybin Study Reveals How Magic Mushrooms Disrupt Brain Networks

Psilocybin and functional brain networks

Magic mushrooms, once condemned for their psychedelic effects, are now drawing growing interest because those same consciousness-altering qualities may offer treatment for a broad range of mental health conditions.

Even so, relatively little is understood about the many neurological effects of psilocybin, the fungi’s psychoactive compound. That uncertainty makes it harder to foresee exactly how the drug could eventually serve communities as a medicine.

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

These results help address gaps in knowledge of how psilocybin’s biochemical effects become large-scale behavioural changes that could either assist or hinder people with differing psychological requirements.

"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 affect the brain

Magic mushrooms exert their appeal by imitating serotonin’s attraction to the 5-HT2A receptor. Their subjective effects are familiar, usually involving euphoria alongside altered perceptions of the self, time, space, sound and colour.

Research in animal models has shown that briefly stimulating these receptors in areas where they occur at high concentrations, including the medial frontal lobe, produces lasting effects. It appears to do so by relaxing established pathways and encouraging fresh connections.

This nervous system ‘plasticity’ is what enables the brain to adapt. It also makes psilocybin an attractive potential medicine for psychological disorders that prove particularly resistant to change.

Brain scans after a 25-milligram psilocybin dose

It remains uncertain, however, whether those findings can be extended to humans. To investigate, Siegel’s team carried out functional magnetic resonance imaging scans on volunteers before they took a substantial 25 milligrams of psilocybin. They were scanned again immediately after the dose and once more 21 days later.

As a comparison, participants were also given 40-milligram doses of the stimulant methylphenidate on separate occasions and underwent a comparable set of scans.

Following the psilocybin dose, the scans revealed pronounced disruption in functional connectivity throughout the brain’s cortex. Significant shifts also occurred deeper in the brain, within a collection of regions called the default mode network (DMN), which is most active when we are awake but not engaged in a task.

Drawing on earlier rat studies, the researchers proposed that the widespread disruption arose because normally coordinated populations of nerve cells became desynchronised. For a time, this may remove the distinctive patterns that create our feeling of being an individual 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."

Interestingly, when volunteers 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.

Three weeks after psilocybin treatment, scans indicated that the cortex had largely resumed its pre-dose synchronisation. A part of the brain known as the anterior hippocampus, involved in cognitive functions relating to perception and memory, nevertheless continued to display a sustained functional alteration.

Bringing together knowledge of psilocybin pharmacology with people’s self-reports 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 its use where such disruption may create substantial dangers.

We may still be a long way from asking a doctor for a dose of mushrooms to put our minds back in order. However, research such as this brings us closer to understanding the remarkable relationship between the brain and this magical family of fungi.

This research was published in Nature.