Psilocybin’s Effects Linked to Brain Activity Desynchronization
American researchers have visualized brain activity in healthy volunteers before, during, and after taking a high dose of psilocybin using functional MRI. They found that this psychedelic causes deep desynchronization of functional connections in both the cortex and subcortical structures, most strongly affecting the brain’s default mode network, which is responsible for the perception of time, space, and self-identity. After the acute effects of the substance wear off, this desynchronization subsides, but some changes in neurobiological functions persist for weeks, helping to explain the mechanisms behind psilocybin’s long-term effects. The study was published in Nature, which also featured an editorial on its website.
Psilocybin, like other psychedelics, acts on serotonin 5-HT2A receptors, causing significant changes in the perception of ego, time, and space during its effects. In clinical trials, a single high dose of the drug (about 25 milligrams) administered with the support of specially trained psychotherapists led to rapid and lasting reductions in symptoms of depression, addiction, and other mental disorders. While much is known about the molecular mechanisms and psychological effects of psilocybin, its action at the neurobiological level connecting these aspects remains poorly understood.
To address this gap, Nico Dosenbach from Washington University in St. Louis, along with colleagues from various U.S. research centers, recruited seven healthy adult volunteers (ages 18–45) for the experiment. With an interval of 1–2 weeks, each participant received a single dose of 25 milligrams of psilocybin and 40 milligrams of the psychostimulant methylphenidate (which produces similar physical effects but no psychedelic action), both administered in the presence of two psychedelic therapy specialists. Several weeks before, during, and for three weeks after administration, participants underwent regular functional MRI scans (an average of 18 scans per person). Four participants returned 6–12 months later for a repeat psilocybin session with fMRI.
During each fMRI session, volunteers had to lie still and look at a fixed point for at least two 15-minute intervals. They also completed perception tests, where they indicated whether an image on a computer screen matched a word played through headphones. Additionally, each session included an assessment of the psychedelic experience using the MEQ30 questionnaire.
The results showed that during the acute effects of psilocybin, there were large-scale and widespread changes in the brain’s functional networks, affecting nearly all aspects of brain activity. Specifically, there was a desynchronization of functional connectivity, blurring the boundaries between brain networks by reducing integration within networks and segregation between them. As a result, the individual differences typically seen in normal fMRI patterns disappeared among participants. In the cortex, the greatest changes affected associative networks, while in the subcortex and overall, the default mode network (which supports baseline perception and functioning when not engaged in specific tasks) was most impacted. These changes in functional connectivity correlated with the volunteers’ subjective psychedelic experiences. No such changes were observed with methylphenidate.
When volunteers performed the perception task, the signs of desynchronization were reduced compared to the resting state. This may explain why using an eye mask and soundproofing from outside noise helps patients immerse more deeply in psychedelic therapy, while external distractions and social interaction can ease negative psychedelic experiences.
Most of the acute neurobiological effects were reversible after psilocybin wore off. However, changes in connections between the default mode network and the anterior hippocampus (involved in emotion and memory formation) persisted for weeks. Such lasting changes in networks responsible for self-perception, emotions, and life interpretation suggest that psilocybin makes the brain’s functional connections more flexible. With professional support, this may help weaken the rigid, maladaptive thought and behavior patterns seen in psychological and neuropsychiatric disorders.
Beyond understanding psilocybin’s neurobiological effects, these findings may provide an objective way to assess its effectiveness in clinical use through functional MRI. Whether similar changes in brain connectivity occur with other psychedelics, as well as with MDMA and ketamine, remains to be determined in future research.
Previously, British researchers used various types of functional MRI to observe the human brain during the acute effects of LSD. They also recorded large-scale changes in activity with desynchronization, especially pronounced in the default mode network.