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Learn more: PMC Disclaimer | PMC Copyright Notice ACS Med Chem Lett . 2025 Mar 19;16(4):500–503. doi: 10.1021/acsmedchemlett.5c00103 Search in PMC Search in PubMed View in NLM Catalog Add to search Unveiling Reality: Psychedelics, Neural Filtering, and the Future of Psychiatric Medicine Robert B Kargbo Robert B Kargbo 1 API & DP Development, CMC Lead, Usona Institute, 2881 Woods Hollow Road, Madison, Wisconsin 53711, United States Find articles by Robert B Kargbo 1, * Author information Article notes Copyright and License information 1 API & DP Development, CMC Lead, Usona Institute, 2881 Woods Hollow Road, Madison, Wisconsin 53711, United States * E-mail: [email protected] . Received 2025 Feb 25; Accepted 2025 Mar 12; Collection date 2025 Apr 10. © 2025 American Chemical Society PMC Copyright notice PMCID: PMC11995219 PMID: 40236553 Abstract Psychedelics and AI modulate cognitive frameworks, disrupt rigid thought patterns, and enhance neuroplasticity, offering therapeutic potential for depression, PTSD, and addiction. Relaxing neural filters reveal altered states of consciousness, challenging perceptions of reality. This Viewpoint explores their neurobiological mechanisms and AI’s role in augmenting psychiatric treatments. Keywords: psychedelics, neural filtering, consciousness, neuroplasticity, artificial intelligence, psychiatric medicine Earthly Stillness, Cosmic Motion We exist on a planet spinning at over 1,000 miles per hour, orbiting the Sun at nearly 67,000 miles per hour, and traversing the galaxy at speeds exceeding 500,000 miles per hour—yet we remain completely unaware of these immense cosmic velocities. 1 This is because, on this cosmic scale, we do not feel constant motion; rather, we only sense acceleration or deceleration. The vestibular system in our inner ear detects changes in velocity but not uniform motion at the cosmic scale. 2 This principle allows passengers in a smoothly moving car or airplane to feel at rest despite moving at high speeds. Our brain filters out constant motion to maintain equilibrium, allowing us to focus on relevant environmental changes. This obliviousness is not a cosmic accident but a fundamental feature of human physiology. Our vestibular and neural filtering systems have evolved to suppress overwhelming external and internal “noise,” ensuring we only perceive what is essential for immediate survival. 2 The Illusion of Stability: How Neural Filtering Shapes Perception and the Promise of Psychedelics As we read this Viewpoint on our devices, they appear stable, allowing us to focus without overwhelming distractions. However, this perceived stability is an illusion created by our brain’s ability to filter vast amounts of sensory input. Our sensory experience is a constructed reality, a necessity for daily life. At the molecular level, our devices are trillions of atoms in constant quantum flux, shifting every millisecond. Beyond this, the surface we sit upon, and indeed the Earth itself, is spinning at over 1,000 mph while orbiting the Sun at an even greater velocity. 1 Our physiology, operating 24/7 since birth, ensures that these overwhelming realities remain outside our conscious awareness. Life as we know it would become incomprehensible if we were to perceive every fluctuation. This filtering is not an imperfection but a sophisticated adaptation, ensuring we only process the most relevant stimuli for survival. However, what if these perceptual filters obscure more than they reveal? For centuries, mystics, shamans, and contemplative traditions have described expanded states of consciousness in which the illusion of separation dissolves. Mindfulness, meditation, and psychedelics may offer a temporary unveiling of these mechanisms, granting access to a broader spectrum of reality. 3 Recognizing the profound precision of our neural gating systems can inspire gratitude for the seamless experience of consciousness while also unlocking new frontiers in psychiatric medicine, cognitive exploration, and human potential. The ability to modulate these filters opens infinite possibilities—innovation, inspiration, and deep introspection—each moment, offering a window into the limitless nature of perception and well-being. Artificial Intelligence (AI) and the Nature of Discovery AI was once thought to be “mysterious” but is becoming widely used in various aspects of our lives as we gain more understanding, revealing awareness that has always been there but was filtered out by our brains or cognitive biology. AI enables processing of large data sets that could otherwise overwhelm our brain circuitry or be filtered out to prevent overload. Recent AI-driven neuroimaging studies suggest that AI can predict the effects of psychedelics on brain networks, identifying key regions associated with altered states of consciousness. 4 This opens possibilities for refining psychedelic-assisted therapies and improving precision medicine approaches in psychiatry. Furthermore, the SARS-CoV-2 virus was “mysterious” when it shut down the world in 2019, but it has become less enigmatic after rigorous scientific inquiry. As we continue to harness tools like AI, we may unveil many aspects of psychedelics and consciousness that are natural phenomena waiting to be revealed. Our limitations are often self-imposed, yet the scope of scientific pursuit is only beginning to unfold. Are psychedelic experiences mere hallucinations, or do they unveil more profound layers of reality? Examining the neuroscience behind psychedelic-induced states brings us closer to understanding not only how the brain constructs reality but also how its filtering mechanisms contribute to both mental health and disease. By temporarily suspending these filters, mindfulness, meditation, and psychedelics may allow individuals to experience aspects of consciousness that have always existed but were previously inaccessible. Neural Filtering and the Default Mode Network (DMN) Our inability to sense Earth’s motion is a striking example of the brain’s filtering capabilities. Evolutionarily, it was far more advantageous for early humans to detect immediate threats—predators, social cues, and shifting environmental conditions—than to process cosmic-scale phenomena. This need for selective attention shaped the human nervous system into a sophisticated predictive engine, constantly refining a stable model of reality while discarding irrelevant sensory inputs. 5 The DMN is at the core of this process, a collection of interconnected brain regions that govern self-referential thought, autobiographical memory, and social cognition. 6 The DMN is crucial for maintaining a coherent sense of identity. However, excessive DMN activity has been linked to disorders such as depression and anxiety, where individuals become trapped in repetitive, maladaptive thought loops. 7 Psychedelics as DMN Disruptors and Cognitive Expansions Functional neuroimaging studies reveal that psychedelics temporarily suppress DMN activity, producing what researchers describe as ego dissolution. 7 This phenomenon—often characterized by a loss of self-boundaries and an expanded awareness of interconnectedness—is correlated with profound emotional breakthroughs and enduring shifts in perception. From a neuroscientific standpoint, this suggests that the brain is not fabricating entirely new experiences but rather accessing more profound layers of cognition that are typically filtered out. The ability of psychedelics to disrupt entrenched cognitive patterns underlies their therapeutic efficacy in conditions such as treatment-resistant depression, post-traumatic stress disorder (PTSD), and addiction. By loosening the rigid constraints imposed by the DMN, these compounds enable individuals to reframe deeply ingrained narratives, allowing for greater psychological flexibility and emotional resilience. 7 Neuroplasticity and the REBUS Model Beyond their immediate effects on perception, psychedelics also promote neuroplasticity—the brain’s ability to rewire itself by forming new synaptic connections. One leading framework for understanding this phenomenon is the REBUS model (Relaxed Beliefs Under Psychedelics). 8 As depicted in Figure 1 , psychedelics weaken top-down predictive coding, allowing previously suppressed information to surface. By relaxing these constraints, the brain enters a state of heightened plasticity, where old assumptions can be reconsidered, and new cognitive patterns can emerge. 8 This model helps explain the sustained therapeutic benefits observed in psychedelic-assisted therapy. Figure 1. Open in a new tab REBUS Model—Psychedelics Relax Cognitive Constraints to Enable New Insights. Adapted with permission from ref ( 8 ). Published 2019 by ASPET under the terms of a Creative Commons CC-BY license. Neuroimaging studies support this model, demonstrating that psychedelics enhance cross-talk between brain regions that typically operate in isolation. Additionally, psychedelics interact with serotonin 5-HT2A receptors, stimulate glutamate pathways, and increase the release of brain-derived neurotrophic factors (BDNF)—all of which contribute to enhanced synaptic plasticity and cognitive flexibility. 9 Although it can be tempting to fixate on the extraordinary insights that psychedelics offer, the steady baseline they disrupt is itself remarkable. Our neural architecture filters out vast cosmic motion, thereby ensuring equilibrium. Similarly, our bodies suppress constant “noise” from the heart and the trillions of microbes in our microbiome. If these sounds and signals were not filtered, they might flood our awareness like a perpetual vacuum cleaner, obscuring the external world. However, abnormalities such as heart murmurs or erratic bowel sounds become diagnostically significant when these filters break down in disease states. Furthermore, in conditions like schizophrenia, a breakdown in these filters may lead to an overwhelming influx of sensory information, resulting in hallucinations and delusions. Research suggests that an overactive dopamine system plays a key role in this breakdown. 10 DMN likewise anchors our sense of self-daily, enabling relationships and coherent life narratives. Even amid the immense tension in the world, remembering the miracle inherent in each breath—and what that entails—reinvigorates our gratitude for the intricate processes sustaining our lives. Balancing appreciation for these vital filters with an openness to exploring states that transcend them is a nuanced challenge for both neuroscience and mental health, one that AI-driven models are beginning to quantify with increasing accuracy. Mystical Experiences and the Nature of Reality Psychedelic experiences often involve a sense of unity, timelessness, and interconnectedness—qualities traditionally associated with mystical states. 7 Many individuals rank these experiences among the most meaningful of their lives, suggesting that psychedelics do not simply distort perception but may temporarily unveil more profound layers of consciousness. Natural phenomena such as lightning and eclipses were historically attributed to divine forces until scientific progress revealed their underlying mechanisms. Similarly, what we now describe as “mystical” psychedelic experiences may one day be explained through neuroscience without diminishing their significance. From this perspective, psychedelics do not create new realities; they may reveal pre-existing aspects of consciousness that the DMN typically filters out. Biological Filters: The Blood–Brain Barrier Analogy The cognitive filtering performed by the DMN can be likened to the blood–brain barrier (BBB), a biological filter that selectively regulates the passage of molecules into the brain. 11 This intricate system prevents harmful substances from entering the central nervous system, allowing essential nutrients to pass. As illustrated in Figure 2 , the BBB comprises endothelial cells, tight junctions, and transporter proteins, all working together to maintain homeostasis. 11 This selective permeability mirrors the brain’s cognitive filters, which prioritize stability but can also constrain perception. Figure 2. Open in a new tab Blood–Brain Barrier—A Biological Model of Neural Filtering. Adapted with permission from ref ( 11 ). Published 2019 by StatPearls Publishing under the terms of a Creative Commons CC-BY license. Understanding these dual filtering mechanisms—biological and cognitive—offers insights into the stability of ordinary consciousness and the transformative potential unlocked when these filters are temporarily relaxed. Clinical Implications: Psychedelics in Psychiatry The resurgence of psychedelic research has demonstrated its remarkable efficacy in treating a range of psychiatric disorders. Psilocybin-assisted therapy, in particular, has shown rapid and enduring reductions in symptoms of depression, anxiety, and addiction. 9 Under guided therapeutic conditions, patients often report profound shifts in perspective, increased emotional openness, and a renewed sense of purpose. By modulating the DMN, promoting neuroplasticity, and fostering transformative experiences, psychedelics provide a unique therapeutic pathway distinct from conventional pharmacological approaches. Even after a single administration, the durability of these effects underscores their potential as paradigm-shifting interventions in mental health treatment. 9 Conclusion: Toward a Fuller Understanding of Consciousness Our inability to perceive Earth’s rapid motion underscores the elegance of our neural filters—mechanisms that construct a stable yet inherently limited sense of reality. While these filters serve a crucial role, they also confine us to a narrow window of perception. Mindfulness, meditation, and psychedelics, by transiently relaxing these constraints, provide a rare opportunity to explore consciousness beyond its habitual boundaries. By resetting maladaptive cognitive patterns, enhancing neuroplasticity, and offering profound existential insights, psychedelics may hold immense promise for psychiatric medicine. More broadly, they challenge us to reconsider the nature of perception, inviting a deeper inquiry into the vast, uncharted territories of human consciousness. As science continues to unveil the neurobiological basis of psychedelic experiences, we stand at the threshold of a new era—one where psychiatry, neuroscience, and philosophy converge to expand our understanding of the mind and its boundless potential. By integrating AI into psychedelic research, we can refine our comprehension of consciousness and revolutionize therapeutic approaches to mental health. More importantly, mindfulness, medication, and psychedelics do not fabricate alternate realities but reveal more profound layers of human consciousness that have always existed, merely hidden by the brain’s filtering systems. The renewed interest in psychedelics, such as psilocybin, MDMA, and LSD, for treating mental health conditions like depression, PTSD, and addiction has brought to light both the promise and the challenges of these substances in modern medicine. 1 Psychedelics have shown potential in cases where traditional treatments fail, but the application of these compounds remains limited by several critical challenges. These include the inability to predict how individual patients will respond to specific psychedelics, the unpredictable durability of therapeutic effects, and an incomplete understanding of the influence of genetic, epigenetic, and microbiome factors. 2 Additionally, the role of set and setting—the mindset and environment during treatment—is considered critical but remains poorly understood. Acknowledgments The author thanks Bill Linton and the entire Usona Institute team for fostering an environment of creativity, curiosity and passion. 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