Every month, the BCSP brings you one essential read to keep you up to date with the leading topics in psychedelic science. This month, postdoctoral researcher Sean Noah explains “Psilocybin desynchronizes the human brain,” published in 2024 in Nature.
A new article called “Psilocybin desynchronizes the human brain,” published in Nature, describes the results of a study of psilocybin’s effects in the brains of healthy human volunteers. The study involved oral administration of 25 milligrams of psilocybin and used functional magnetic resonance imaging (fMRI) to examine changes in brain activity during the active drug effects and—over a few weeks post-oral administration—after the psychedelic experience, too.
Changes in functional connectivity
The study showed while psilocybin is active in the body, it caused significant changes to functional connectivity in the brain. Functional connectivity is a measurement of relationships among brain areas from fMRI data. The connection is inferred from joint activity—when fMRI recordings show that two brain areas are consistently active at the same time, they can be said to be functionally connected. Functional connectivity analysis can reveal connections between brain areas that are not obvious from just inspecting what brain areas are near each other: sometimes, areas can be functionally connected even when they are widely separated across the brain.
Psilocybin decreased the functional connectivity within groups of interconnected brain areas that are commonly observed in the human brain under normal wakeful conditions, like the default mode network. In other words, regions of the brain that are usually interconnected end up more isolated from each other, under the influence of psilocybin.
Furthermore, functional connectivity between two areas of the brain—the anterior portion of the hippocampus and the default mode network—remained altered up to three weeks after psilocybin administration. These findings might be a clue as to how a single dose of psilocybin can create long-term antidepressant effects that have been observed in other studies. No other significant alteration in functional connectivity was detectable after this long interval, so an explanation of the long-term effects of a single psychedelic dose on mood and behavior might involve these brain areas.
Functional connectivity between two brain areas is a measurement of how similar the activity in those two areas is over time. Neuroimaging researchers often assume that when two brain areas fluctuate similarly, they are connected in some way. They could be directly anatomically connected, such that activity in one area triggers activity in the coupled area, or they could be indirectly connected, perhaps both receiving inputs from a common third area or a common upstream process. Parallel time courses of activity among brain areas may suggest that they are jointly contributing to a shared psychological process. For example, the disparate set of areas spanning the brain known as the ‘default mode network’ is often linked to introspection or self-awareness.
Scientists have explored many of these connected brain networks and the roles they might play in normal waking consciousness. If psilocybin acutely alters a given network, that hints at how this and other psychedelics might have their characteristic subjective effects. Changes in one’s sense of self, visual perception, or emotional reactivity could be reflected in an alteration of the brain networks that normally contribute to these psychological functions.
A deep dive into individual brains
Unlike previous fMRI studies that examined the effects of psilocybin in the human brain, this study focused on changes in functional connectivity occurring within individual brains across time, rather than just looking at averages across a group of study participants. Closely examining individuals’ brains allowed the researchers to precisely measure changes to brain networks, the exact configurations of which often vary substantially from person to person.
To accomplish this feat, the researchers performed fMRI scans on five different days for each study participant before any drug administration. These scans formed a baseline dataset for each participant, allowing researchers to see how much the participants’ patterns of functional connectivity varied from day to day, in the absence of any drug effects. This was an important way to reduce the likelihood that a difference in functional connectivity observed between pre- and post-psilocybin MRI scans could be attributed simply to day-to-day changes in the measure.
The researchers took several other steps to rigorously assess functional connectivity changes brought on by psilocybin. The study involved a comparison of psilocybin to the stimulant drug methylphenidate (Ritalin) to control for general drug effects. The psilocybin administration was followed by nine separate MRI scans over the course of a month to closely track any lasting changes in brain activity that might have occurred after the acute effects of the drug had subsided. The researchers also performed a replication study almost a year after the initial psilocybin administration to evaluate how well their initial findings held up.
The researchers—and the study participants—went to great lengths with this experiment. Altogether, each of the seven participants in the study underwent three drug administration sessions and 24 separate MRI scans over the course of about a year. What’s more, the researchers shared their study data online via the publishing journal’s website.
Want to read more? Dive into the full article.