Psilocybin Alters Claustrum Activity in the Human Brain

American scientists have discovered that taking psilocybin changes the activity of the claustrum—a small, bilateral sheet of gray matter adjacent to the inner layers of the cerebral cortex. Along with this, changes were also observed in its functional connections with other brain regions: the auditory cortex, the default mode network, and areas responsible for cognitive functions. According to the researchers, the claustrum may serve as a “command center” for psilocybin’s effects on the brain and its therapeutic potential, as reported in NeuroImage.

In recent years, scientists have devoted significant attention to studying psilocybin (the active component in hallucinogenic mushrooms) as a potential treatment for affective disorders. In 2016, researchers demonstrated that the psychedelic helps with severe depression, and in 2018, psilocybin therapy received “breakthrough” status from the FDA. However, exactly how psilocybin affects the brain remains unclear. It is well established that, at the neurotransmitter level, it acts on serotonin receptors (mainly 5-HT2A), but its effects on brain activity and functional connectivity are less obvious, even though studies show that psilocybin alters activity in the anterior cingulate and prefrontal cortex in patients with depression.

Frederick Barrett from the Johns Hopkins University School of Medicine hypothesized that there is a kind of command center for these changes in brain activity—a region that psilocybin primarily affects, which then influences other areas. To test this, the team conducted an fMRI experiment with 15 volunteers, all of whom had previously participated in similar psychedelic studies. The authors also noted that all participants had many years of meditation experience, but none reported meditating during the experiment itself.

The scanning was conducted in two stages: during the first, participants took psilocybin (at a dose of 10 milligrams per 70 kilograms of body weight), and during the second, they received a placebo. All substances were administered under identical conditions—participants wore eye masks and headphones while lying on a gurney. After an hour and forty minutes, they were taken to the MRI scanner, where their brain activity was measured at rest. Six hours after taking the drug or placebo, participants also completed questionnaires about their mental state.

The researchers found that, compared to placebo, psilocybin significantly (p < 0.05) reduced the amplitude of low-frequency fluctuations in the claustrum—a small, bilateral sheet of gray matter adjacent to the inner cortex and connected by neural pathways to various brain regions. Under psilocybin, there was also a weakened functional connection between the right claustrum and the auditory cortex (p < 0.001) and the default mode network (p < 0.0001), as well as a strengthened connection with the frontotemporal network responsible for cognitive control (p < 0.001). The functional connection between the left claustrum and the frontotemporal network was also increased (p < 0.0001). In the questionnaires, participants reported increased feelings of happiness, loss of time perception, and other psychological effects typical of psychedelics when compared to placebo.

The authors clarified that the observed changes in brain activity were specific to the claustrum: similar changes in functional connectivity were not found in other regions such as the insula or putamen. It appears that the claustrum is a key structure for psilocybin’s action on the brain, and its regulation of other structures may explain the drug’s therapeutic effects. However, the researchers caution that the sample had limitations: all participants were over 50 years old and had many years of meditation experience, so the findings may not be generalizable to the broader population.

While the question of how psilocybin and other psychedelics work in affective disorders remains open, scientists suggest a comprehensive approach. Recently, British researchers introduced a new neuroimaging method that combines analysis of neuronal and neurotransmitter activity, which has helped clarify how psychedelics affect the brain.