Seeing the Light Within: How Psilocybin Illuminates the Brain Even in Darkness

In the quiet darkness behind closed eyelids, most of us experience little more than the faint phosphenes that dance across our visual field—those fleeting specks of light that appear when we press our palms against our eyes or sit in complete darkness. But for those who have experienced the effects of psilocybin, the psychoactive compound found in "magic mushrooms," this darkness can transform into a canvas of vibrant imagery, geometric patterns, and sometimes fully-formed visions that rival the clarity of our waking sight. For decades, these visual experiences were dismissed as mere hallucinations—false perceptions with no basis in reality. But groundbreaking research published in Molecular Brain has revealed something remarkable: psilocybin activates the same pathways in the visual cortex as actual light, even when someone is sitting in complete darkness. This discovery not only helps explain the vivid visual experiences reported during psychedelic journeys but also offers profound insights into how our brains construct visual reality.

The Study That Illuminated the Darkness

A team of researchers led by Ram Harari, Dmitriy Getselter, and Evan Elliott at Bar-Ilan University in Israel conducted an elegant experiment to understand how psilocybin affects gene expression in the visual cortex. Using a carefully designed protocol with laboratory mice, they created four experimental groups: mice exposed to light, mice kept in darkness, mice given psilocybin and exposed to light, and mice given psilocybin but kept in darkness. After administering psilocybin (or a placebo) and exposing the mice to their respective light conditions for two and a half hours, the researchers extracted the visual cortex tissue from each mouse brain. They then performed RNA sequencing to identify which genes were being expressed in each condition. What they discovered was astonishing. The pattern of gene expression in the visual cortex of mice that received psilocybin but remained in darkness closely resembled the pattern seen in mice exposed to actual light. In fact, 76.8% of the genes modified by psilocybin were also modified by light exposure, and all of these overlapping genes changed in the same direction. "Of great interest, psilocybin induced robust gene expression changes in the visual cortex that closely mirror light-induced gene expression changes, even when the mice are kept in the dark," the researchers noted in their paper. This finding suggests that from the perspective of the visual cortex, experiencing psilocybin in darkness is remarkably similar to actually seeing light—a neurobiological basis for the vivid visual experiences reported by people during psychedelic sessions.

The Molecular Mechanics of Inner Light

To understand the significance of this discovery, we need to appreciate how vision normally works. When light enters our eyes, it stimulates photoreceptors in the retina, which send signals through the optic nerve to the visual cortex in the back of the brain. This stimulation triggers a cascade of gene expression changes that help process and interpret the visual information. The study found that specific genes known to be activated by light in the visual cortex—including Npas4, Fosb, Egr1, and Arc—were also activated by psilocybin, even in complete darkness. These genes play crucial roles in neuroplasticity, the brain's ability to reorganize and form new neural connections. Further analysis revealed that psilocybin and light specifically upregulated gene expression in glutamatergic neurons (the excitatory neurons that increase the likelihood of action potentials) across all cortical layers, while downregulating gene expression in GABAergic neurons (the inhibitory neurons that decrease the likelihood of action potentials).This shift in the balance between excitation and inhibition may be key to understanding how psilocybin creates visual experiences in the absence of external stimuli. By reducing inhibition and enhancing excitation in specific neural circuits, psilocybin may allow internally generated signals to be processed as if they were coming from the outside world.

The Role of the 5-HT2A Receptor

How does psilocybin accomplish this remarkable feat? The answer lies in its interaction with a specific type of serotonin receptor called 5-HT2A, which is abundant in the visual cortex. When psilocybin enters the body, it is metabolized to psilocin, which acts as a potent agonist of the 5-HT2A receptor. This means it binds to the receptor and activates it, similar to how a key fits into a lock and turns it. The activation of 5-HT2A receptors sets off a cascade of molecular events that ultimately leads to changes in gene expression. Research published in Nature's Molecular Psychiatry journal has shown that agonism of the 5-HT2A receptor may reduce what neuroscientists call "synaptic gain"—essentially, the sensitivity of neurons to incoming signals. This reduction in synaptic gain appears to increase self-inhibition of both early visual areas and higher visual-association regions. Paradoxically, this increased self-inhibition is accompanied by reduced inhibition from visual-association regions to earlier visual areas, indicating that top-down connectivity (the influence of higher brain regions on lower ones) is enhanced during visual imagery. In other words, psilocybin may allow the brain's higher visual processing centers to exert more influence over the primary visual cortex, potentially explaining why people can "see" complex imagery with their eyes closed.

Alpha Waves and the Gates of Perception

Another fascinating aspect of psilocybin's effect on vision involves brain waves called alpha oscillations. When our eyes are closed, the visual cortex typically generates alpha waves (8-12 Hz), which act as an inhibitory mechanism to suppress visual processing in the absence of input. Studies have shown that psilocybin reduces this alpha inhibition during eyes-closed periods. This reduction may effectively "open the gates" to the visual cortex, allowing internally generated signals that would normally be filtered out to be processed as visual experiences. Devon Stoliker and colleagues at Monash University in Australia found that "decreased sensitivity to neural inputs is associated with the perception of eyes-closed visual imagery" under psilocybin. This suggests that by making the visual system less responsive to external inputs, psilocybin may paradoxically enhance its responsiveness to internal signals generated by other brain regions.

From Elementary to Complex Imagery

The visual experiences induced by psilocybin aren't uniform—they range from simple geometric patterns to complex, fully-formed scenes. Researchers have categorized these experiences into two main types: elementary imagery and complex imagery. Elementary imagery includes light flashes, moving line orientations, and geometric figures with recurrent patterns. These simpler visual experiences are associated primarily with activity in the early visual area, corresponding to the primary visual cortex. Complex imagery, on the other hand, involves visualizations of semantic content such as scenes, people, and objects. These more elaborate visual experiences are associated with activity in both the visual cortex and higher-order visual association areas, as well as regions involved in memory and emotion. The progression from elementary to complex imagery during a psychedelic experience may reflect the gradual recruitment of additional brain networks as the effects of psilocybin deepen. Initially, changes in the primary visual cortex may generate simple geometric patterns, but as higher-order visual processing regions and memory networks become involved, these patterns can evolve into more complex, meaningful scenes.

Implications for Understanding Consciousness

Beyond explaining the visual aspects of psychedelic experiences, this research has profound implications for our understanding of consciousness and perception. The finding that psilocybin can activate the visual cortex in a manner similar to actual light challenges the conventional view that our perceptions are primarily driven by sensory input from the external world. Instead, it suggests that the brain actively constructs our visual experience through a complex interplay of bottom-up sensory information and top-down interpretive processes. Under normal conditions, this construction process is heavily constrained by sensory input, creating a shared reality that aligns with the physical world. But psilocybin appears to loosen these constraints, allowing the brain's internal generative processes to play a more dominant role in creating visual experience. This perspective aligns with predictive processing theories of perception, which propose that the brain constantly generates predictions about the sensory inputs it expects to receive and updates these predictions based on actual sensory data. According to these theories, what we perceive is not the sensory data itself but the brain's best prediction of what that data represents. By altering the balance between prediction and sensory input, psilocybin may reveal the constructive nature of perception that normally operates behind the scenes of our conscious awareness.

Therapeutic Potential of Visual Experiences

For those considering psychedelic therapy but uncertain about the visual aspects of the experience, understanding the neurobiological basis of these effects may provide reassurance. Rather than being random hallucinations, the visual experiences induced by psilocybin appear to involve organized neural processes similar to normal vision. Moreover, these visual experiences may contribute to the therapeutic benefits of psychedelic therapy. Many participants in clinical trials report that the visual component of their psychedelic experience conveyed meaningful insights or emotional content that helped them process difficult experiences or gain new perspectives. The ability of psilocybin to enhance top-down connectivity in the visual system may allow for the visual expression of emotional and autobiographical content that is normally confined to verbal or conceptual forms. This visual expression might facilitate emotional processing and integration in ways that talk therapy alone cannot achieve. Additionally, the reduced self-inhibition observed in the visual cortex under psilocybin may parallel similar changes in brain regions involved in self-referential processing, potentially contributing to the experience of "ego dissolution" often reported during psychedelic sessions. This temporary relaxation of rigid self-concepts is frequently cited as a mechanism through which psychedelic therapy helps people overcome entrenched patterns of thought and behavior.

Beyond Psychedelics: Implications for Clinical Conditions

The insights gained from studying psilocybin's effects on the visual cortex extend beyond psychedelic experiences to enhance our understanding of various clinical conditions involving altered visual perception. Charles Bonnet Syndrome, for instance, involves complex visual hallucinations in people with visual impairment. The finding that reduced input to the visual cortex (in this case, due to psilocybin rather than visual impairment) can lead to increased internal generation of visual content may help explain the mechanisms underlying this condition. Similarly, the visual hallucinations experienced in conditions like schizophrenia, Parkinson's disease, and certain types of dementia might involve disruptions to the balance between bottom-up sensory input and top-down predictive processes similar to those induced by psilocybin. By elucidating the neural mechanisms through which psilocybin affects visual processing, this research opens new avenues for understanding and potentially treating these conditions. If we can identify the specific receptor systems and neural circuits involved in different types of visual hallucinations, we may be able to develop more targeted interventions for patients suffering from these symptoms.

The Future of Visual Neuroscience

The discovery that psilocybin activates the same pathways in the visual cortex as light represents just the beginning of what promises to be a fruitful area of research. Future studies will likely explore questions such as:

• How do the subjective qualities of psilocybin-induced visual experiences correlate with specific patterns of gene expression in the visual cortex?
• Are there individual differences in the visual effects of psilocybin, and if so, what genetic or neurobiological factors contribute to these differences?
• Can the insights gained from studying psilocybin's effects on vision lead to new treatments for conditions involving visual hallucinations or visual processing deficits?
• How do other psychedelic compounds compare to psilocybin in their effects on the visual system?

As researchers continue to explore these questions, we may gain not only a deeper understanding of psychedelic experiences but also new insights into the fundamental nature of visual perception and consciousness itself.

Conclusion: The Inner Light of Consciousness

The finding that psilocybin activates the same pathways in the visual cortex as light, even in total darkness, offers a compelling scientific explanation for the vivid visual experiences reported during psychedelic journeys. Far from being mere hallucinations, these experiences appear to involve organized neural processes similar to those involved in normal vision. This research challenges our conventional understanding of perception as a passive reception of sensory information from the external world. Instead, it suggests that perception is an active, constructive process in which the brain generates predictions and interpretations based on both sensory input and internal states. By temporarily altering the balance between bottom-up sensory information and top-down predictive processes, psilocybin may reveal the constructive nature of perception that normally operates behind the scenes of our conscious awareness. In doing so, it offers a unique window into the inner workings of the mind and the neural basis of consciousness. For those considering psychedelic therapy, understanding the neurobiological basis of visual effects may help demystify these experiences and place them in a scientific context. Rather than being random or meaningless hallucinations, the visual component of psychedelic experiences appears to involve organized neural processes that may contribute to their therapeutic potential. As we continue to explore the effects of psilocybin on the brain, we may not only develop new treatments for mental health conditions but also gain profound insights into the nature of perception, consciousness, and reality itself. In the words of the poet William Blake, we may learn to "see a world in a grain of sand, and a heaven in a wild flower"—or perhaps, in this case, in the humble psilocybin mushroom.

References

1. Harari, R., Getselter, D., & Elliott, E. (2025). The psychedelic psilocybin and light exposure have similar and synergistic effects on gene expression patterns in the visual cortex. Molecular Brain, 18(1), 1-15. https://doi.org/10.1186/s13041-025-01191-0
2. Stoliker, D., Preller, K. H., Novelli, L., Anticevic, A., Egan, G. F., Vollenweider, F. X., & Razi, A. (2024). Neural mechanisms of psychedelic visual imagery. Molecular Psychiatry, 30, 1259-1266. https://doi.org/10.1038/s41380-024-02632-3
3. Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L., Kaelen, M., Droog, W., Murphy, K., ... & Nutt, D. J. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences, 113(17), 4853-4858. https://doi.org/10.1073/pnas.1518377113
4. Kometer, M., Schmidt, A., Jäncke, L., & Vollenweider, F. X. (2013). Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations. Journal of Neuroscience, 33(25), 10544-10551. https://doi.org/10.1523/JNEUROSCI.3007-12.2013

The original article can be found here: https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-025-01191-0