The Anatomy and Physiology of Psilocybin's Effects on Our Human Body

Psilocybin, a naturally occurring psychedelic compound found in certain mushrooms, has captured widespread attention for its potential therapeutic benefits. In this article, we aim to shed light on how psilocybin works in the body and brain, diving into the science behind its transformation into psilocin and its interactions with key brain systems.

By understanding these mechanisms—like its influence on serotonin receptors and disruption of the default mode network—we hope to offer insight into why psilocybin is seen as a tool for healing, self-exploration, and even mental health support.

That said, it's important to note that we are not licensed medical professionals and do not make any medical claims. The information provided is for educational and entertainment purposes only, meant to spark curiosity and reflection. We strongly recommend consulting a qualified healthcare provider before considering any form of treatment, including the use of psilocybin or other psychedelics. We do not advocate the use of any substance without explicit approval from a licensed medical practitioner.

Ingestion and Conversion to Psilocin

The conversion of psilocybin into psilocin in the liver activates the compound’s psychoactive effects. Psilocin is structurally similar to serotonin, as David E. Nichols notes in his review of psychedelics, this serotonin-like structure is what enables psilocin to engage with neural pathways (Nichols, 2016). However, the role of the liver in this process means that liver health and metabolism can significantly influence the experience.

A healthy liver efficiently converts psilocybin into psilocin, resulting in a smoother, more predictable onset of effects. When liver function is compromised, due to conditions like fatty liver disease or excessive alcohol consumption, the conversion process may slow down. This can lead to a delayed onset or prolonged trip.

Similarly, metabolism plays a key role in determining the duration and intensity of a psilocybin trip. Individuals with a faster metabolism might experience shorter, more intense trips because the body processes psilocin more rapidly. Conversely, those with slower metabolisms may have longer-lasting experiences, as the compound remains active in the system for an extended period.

Other factors, such as diet, hydration, and the use of certain medications, can also affect how the liver processes psilocybin. Medications that alter liver enzyme activity, particularly CYP450 enzymes, may enhance or diminish the psychoactive effects. Maintaining good liver health through proper nutrition, hydration, and avoiding substances like alcohol can contribute to a more stable and predictable psilocybin experience.

Serotonin Receptors (5-HT2A)

Once converted to psilocin, the compound binds primarily to 5-HT2A receptors, a subtype of serotonin receptors distributed throughout the brain, particularly in areas associated with cognition, perception, and consciousness like the prefrontal cortex, thalamus, and hippocampus.

In the prefrontal cortex, the activation of 5-HT2A receptors alters cognitive processing, contributing to experiences of ego dissolution, a state where the individual feels a loss of self-boundaries and unity with the external world.

In the thalamus, psilocin’s action disrupts the brain’s typical sensory relay processes, leading to vivid visual and auditory hallucinations. This is often described as the sensory "opening up" that occurs during a psilocybin experience, where users report seeing intensified colors, patterns, and shapes.

The effects on the hippocampus, which is involved in memory and emotion, also contribute to the deep introspection and emotional sensitivity many users experience during their trips.

Disruption of Default Mode Network (DMN)

Psilocybin’s interaction with the brain goes beyond just serotonin receptors. It also impacts the default mode network (DMN), a system of interconnected brain regions that is most active during introspection, daydreaming, and self-referential thinking.

By reducing activity in this network, psilocybin enables ego dissolution, where the boundaries between the self and the external world begin to blur. This phenomenon is often accompanied by a profound sense of unity and oneness with the environment, which many describe as a deeply spiritual or transformative experience.

Increased Brain Connectivity

Another major effect of psilocybin on the brain is the promotion of hyperconnectivity between regions that do not normally communicate extensively. This increased connectivity allows for novel patterns of information processing and perception. For instance, Carhart-Harris and colleagues found that under the influence of psilocybin, the visual cortex interacts more with other parts of the brain, resulting in enhanced visual perception. Colors may appear more vibrant, patterns may shift, and shapes may distort, contributing to the characteristic visual hallucinations experienced by many users (Carhart-Harris et al., 2014).

Psilocybin also affects the amygdala, the brain’s emotional processing center, reducing negative emotional responses while heightening emotional sensitivity. This can explain why some individuals experience profound emotional breakthroughs, gaining new perspectives on deeply rooted issues or trauma.

Sympathetic Nervous System

Aside from its psychological effects, psilocybin also induces mild physiological changes that one should take notice of before embarking on a potential trip. These changes are mainly driven by its effect on the sympathetic nervous system, which triggers the body’s fight-or-flight response. Users often experience increased heart rate, dilated pupils, and changes in body temperature. However, as Passie et al. (2002) note, these effects are generally mild and manageable, especially in comparison to the profound alterations in consciousness that the substance provokes.

Given these physiological and psychological effects, the importance of "set" (mindset) and "setting" (environment) cannot be overstated. Psilocybin not only amplifies sensory and emotional experiences but also induces subtle physical changes that can heighten sensitivity to the surrounding environment. A calm, reflective mindset and a safe, supportive environment are crucial to ensuring that both the mind and body respond positively to the trip. Without this preparation, psilocybin’s tendency to enhance emotions and perceptions could result in discomfort or anxiety, making it harder to navigate the experience.

Metabolism and Excretion

After the compound is metabolized in the liver, psilocin is eventually excreted through the kidneys. Although most of the compound is removed from the body within hours, its effects on brain activity and perception linger, with psychological effects sometimes lasting for several hours or even days. These effects include altered consciousness, emotional breakthroughs, and enhanced sensory perception, which can lead to feelings of afterglow, where individuals report heightened mental clarity, emotional peace, and deeper insights following the trip.

However, some users may experience nausea, dizziness, or headaches during the trip, while others report anxiety, paranoia, or confusion, particularly if they are in an unsupportive environment or unprepared mentally. In terms of how long psilocin remains traceable in the body, it is typically detectable in blood and urine for up to 24 hours after ingestion, although its psychological effects are usually gone within 6 to 12 hours, depending on dosage and individual metabolism. Hair follicle tests, however, can detect traces of psilocin for up to 90 days, although such testing is rare.

Because the psychological effects of psilocybin can impair cognitive function and motor skills, it is advised to wait at least 24 hours after the trip has ended before operating machinery or driving a car. Even if the acute effects have worn off, lingering shifts in perception or reduced motor coordination could pose a risk when handling potentially dangerous tasks. It’s important to ensure full cognitive clarity and physical coordination before engaging in such activities.

Conclusion

From its conversion into psilocin and subsequent binding to serotonin receptors, to the disruption of the default mode network and promotion of hyperconnectivity, psilocybin’s impact extends deep into the neurobiology of perception, cognition, and emotion.

As research continues to shed light on these mechanisms, psilocybin’s potential as a therapeutic tool for treating mental health conditions and fostering personal growth is becoming increasingly evident. Whether viewed through the lens of neuroscience or spirituality, psilocybin offers a window into the vast possibilities of human consciousness and emotional healing.

Works Cited

• Nichols, David E. "Psychedelics." Pharmacological Reviews, vol. 68, no. 2, 2016, pp. 264-355.

• Carhart-Harris, Robin L., et al. "The Entropic Brain: A Theory of Conscious States Informed by Neuroimaging Research with Psychedelics." Frontiers in Human Neuroscience, vol. 8, 2014, pp. 20.

• Vollenweider, Franz X., and Michael Kometer. "The Neurobiology of Psychedelic Drugs: Implications for the Treatment of Mood Disorders." Nature Reviews Neuroscience, vol. 11, no. 9, 2010, pp. 642-651.

• Passie, Torsten, et al. "The Pharmacology of Psilocybin." Addiction Biology, vol. 7, no. 4, 2002, pp. 357-364.