A recent study published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging has revealed that psilocybin can induce a state of hyperconnectivity in the brain. This heightened brain connectivity is linked to profound changes in perception and a sense of unity with the universe, which many users describe as mystical experiences.
Psilocybin is a naturally occurring psychedelic compound found in certain species of mushrooms, commonly referred to as “magic mushrooms.” When ingested, psilocybin is metabolized into psilocin, which interacts with serotonin receptors in the brain, particularly the serotonin 2A receptor.
This interaction leads to altered perception, mood, and cognition, often resulting in profound changes in consciousness. Users report experiences ranging from enhanced sensory perception and visual hallucinations to feelings of unity with the universe and deep personal insight. These effects have made psilocybin a subject of interest not only for recreational use but also for its potential therapeutic benefits.
Previous studies have shown promising results, suggesting that psilocybin can help alleviate symptoms of conditions such as depression, anxiety, and addiction. However, the exact mechanisms by which psilocybin exerts its therapeutic effects were not fully understood. By examining brain activity and connectivity during psilocybin administration, the researchers aimed to uncover the neural correlates of the psychedelic experience and how these changes in brain function might contribute to the reported therapeutic benefits.
“Quality and intensity of the psychedelic experience are a potential marker of therapeutic impact. The neural correlates of that experience is therefore relevant to define,” explained study author Johannes G. Ramaekers, a professor in psychopharmacology at Maastricht University.
The researchers conducted their study on 49 healthy participants who had prior experience with psychedelic substances but had abstained for at least three months. The participants were randomly assigned to receive either a dose of psilocybin or a placebo. The psilocybin dose was carefully measured at 0.17 milligrams per kilogram of body weight, mixed with bitter lemon to mask the taste. Those in the placebo group received only bitter lemon.
Prior to the test day, participants were familiarized with the procedures and instructed to refrain from using drugs, alcohol, caffeine, and nicotine for specified periods before the test.
On the test day, participants underwent drug and alcohol screening to ensure compliance. After the administration of psilocybin or placebo, participants were placed in a magnetic resonance imaging (MRI) scanner for one hour to measure brain activity. During this time, they were asked to keep their eyes open while their brain activity was recorded using functional MRI (fMRI) scans.
These scans captured resting-state brain activity, which allowed the researchers to assess brain connectivity. Approximately six hours after administration, participants completed a questionnaire known as the 5-Dimensional Altered States of Consciousness Rating Scale to assess their subjective experiences.
Participants who received psilocybin reported significantly more intense altered states of consciousness compared to those who received a placebo. These experiences were measured using the 5-Dimensional Altered States of Consciousness Rating Scale and included feelings of oceanic boundlessness, ego dissolution, and visionary restructuralization.
Oceanic boundlessness refers to a feeling of unity and interconnectedness with the world, characterized by a profound sense of oneness. Ego dissolution involves a reduction in self-referential awareness, leading to a diminished sense of individual identity. Visionary restructuralization includes vivid visual and auditory experiences, often featuring complex, dream-like imagery and altered perceptions of reality.
The fMRI scans showed that psilocybin leads to an overall increase in brain connectivity. This hyperconnectivity was especially notable in areas of the brain responsible for integrating information across different regions, resulting in more communication between brain areas.
Four distinct patterns of brain connectivity were identified, with one pattern—characterized by global, positive phase coherence across the cortex—occurring more frequently in the psilocybin group. This pattern indicates a state of heightened integration and reduced modularity, where different brain regions communicate more freely with each other.
Furthermore, this hyperconnectivity was associated with a decrease in the amplitude of brain signals in specific regions, such as the posterior cingulate cortex and parietal areas, which are part of the default mode network. This network is typically active during self-referential thought and mind-wandering, and its decreased activity aligns with the reported experiences of ego dissolution, where users feel a diminished sense of self and increased unity with their surroundings.
“We were pleasantly surprised to learn that the brain pattern of hyperconnected regions was further characterized by lower global signal amplitude, which works as a proxy to heightened cortical arousal,” explained co-author Athena Demertzi of University of Liège. “So far, this is the first time that such approximation of arousal levels using fMRI was attempted in psychedelic research. This might be an important correlation as we move towards a full characterization of brain states under psychedelics.”
Importantly, the researchers were able to link changes in brain connectivity with the subjective experiences reported by participants. Their analysis showed that transitions to the hyperconnected brain pattern were strongly associated with feelings of oceanic boundlessness and visionary restructuralization.
“We were surprised to find such a strong association between a subjective state and an objective brain measure,” Ramaekers told PsyPost. “In particular, the frequency of transitioning into the hyperconnected state was very predictive of the intensity of the psychedelic experience.”
This suggests that the altered state of consciousness induced by psilocybin is closely tied to specific changes in brain function, particularly increased connectivity and integration across different brain regions. This finding provides evidence that “a state of hyperconnectivity between all major brain regions underlies main subjective characteristics of the psychedelic state such as the feeling of oceanic boundlessness and visual restructuring,” Ramaekers explained.
“Psychedelic drugs like psilocybin are often referred to as hallucinogens both scientifically and colloquially,” added co-author Larry Fort, a PhD candidate at the University of Liège. “As such, we expected that the hallucinatory dimensions of experience would correlate the highest with psilocybin’s hyperconnected pattern. However, hallucinatory experience had a strong, but weaker correlation with this pattern than ego-modifying experiences. This led us to formulate the term ‘egotropic’ to draw attention to these ego-modifying effects as important, perhaps even more so than their hallucinogenic counterparts.”
An important direction for future research is to explore the long-term effects of psilocybin on brain function and mental health. Studies could track changes in brain connectivity and psychological outcomes over weeks or months following a single dose of psilocybin, providing a more complete understanding of its therapeutic potential.
Including clinical populations, such as individuals with depression or anxiety, in these studies would be particularly valuable, as it would allow researchers to directly assess the clinical benefits of psilocybin and the neural changes that accompany symptom improvement.
“The present research focused on acute effects of psychedelics,” Ramaekers noted. “It is not clear yet whether the hyperconnected state also triggers longer-term changes in network connectivities.”
Demertzi concluded: “Given the resurgence in research regarding the psychotherapeutic applications of psychedelic drugs, our results are pertinent to understanding how subjective experience under psychedelics influences beneficial clinical outcomes. Is the effect driven by ego-dissolution? By hallucinations? As such, our work exemplifies how the strong inter-relatedness between egotropic effects of moderate dose psilocybin and its hyperconnected brain pattern can inform clinical focus on specific aspects of phenomenology, such as ego-dissolutions. With this information, healthcare professionals may learn how to best engineer psychedelic therapy sessions to produce the best clinical outcomes.”
The study, “Dynamic Functional Hyperconnectivity After Psilocybin Intake Is Primarily Associated With Oceanic Boundlessness,” was authored by Sepehr Mortahe, Larry D. Fort, Natasha L. Mason, Pablo Mallaroni, Johannes G. Ramaekers, and Athena Demertzi.
