The Pharmacodynamics of Psilocybin and Its Impact on the Human Body

At MycoMind, we aim to make the science behind psychedelics accessible and informative for everyone. When we talk about psilocybin, one of the most well-known psychedelic compounds, we’re diving into a complex process that involves various systems in the brain and body. Whether you’re curious about its therapeutic potential or just fascinated by how it works, we’re here to break it down for you.

Join us as we dive into the science behind psilocybin’s journey in the brain, its role in neuroplasticity, and why it might hold the key to treating mental health conditions like depression, anxiety, and PTSD.

Just as a disclaimer, we do not make any medical claims nor are we licensed medical professionals. All the knowledge we bring to you is intended for educational and entertainment purposes only. If you are considering taking any form of a psychedelic substance we advice you consult with your main medical wellness practitioner to find the best path for you.

1. Psilocybin’s Journey: From Prodrug to Psilocin

When you take psilocybin, your body doesn’t immediately feel its effects. That’s because psilocybin is a prodrug, meaning it needs to be converted into its active form before it starts working. After ingestion, enzymes in the liver quickly convert psilocybin into psilocin, the compound that interacts with your brain. Psilocin is responsible for the altered perceptions, mood shifts, and consciousness changes you experience (Passie et al. 123).

2. Psilocin and Serotonin: The 5-HT2A Connection

Once psilocybin becomes psilocin, it heads straight for the serotonin receptors in your brain, specifically the 5-HT2A receptors. These receptors are key players in how we perceive the world around us—they’re located in areas of the brain that handle cognition, perception, and consciousness, like the prefrontal cortex and thalamus. Psilocin partially activates these receptors, which is why you start to experience the hallucinogenic effects. But it’s not all about hallucinations—psilocin also interacts with other serotonin receptors, like 5-HT1A, which can bring about calming, anti-anxiety effects during the experience (Nichols 16).

3. Disrupting the Default Mode Network (DMN)

One of the most profound things psilocybin does is disrupt your Default Mode Network (DMN). The DMN is a group of brain regions that work together when you’re in a state of introspection or self-referential thought—it’s where your sense of self or ego resides. When psilocybin reduces activity in this network, it creates an experience known as ego dissolution, where you may feel like the boundaries between yourself and the world blur. Many people describe this as a sense of unity or oneness, and it’s often linked to feelings of spiritual awakening or deep personal insight (Carhart-Harris et al. 12).

4. Boosting Brain Connectivity

Psilocybin doesn’t just disrupt normal brain activity—it also enhances communication between areas of the brain that don’t typically interact. This is called increased global functional connectivity, and it can lead to new thought patterns, enhanced creativity, and shifts in sensory perception. This boost in brain connectivity is a big reason why many people report emotionally or spiritually significant experiences during psilocybin trips (Petri et al. 43).

5. The Role of Dopamine and Norepinephrine

While psilocybin’s primary action is on serotonin, it also taps into other neurotransmitter systems. Psilocin can stimulate the release of dopamine, a neurotransmitter tied to feelings of euphoria and alertness, in certain areas of the brain like the striatum. It also influences norepinephrine, which could explain some of the physiological changes you might notice during a trip, like increased heart rate, blood pressure, and sensory awareness (Nichols 20).

6. Inside the Brain: Intracellular Signaling and Synaptic Plasticity

When psilocin activates those 5-HT2A receptors, it triggers a chain of events inside your neurons. This involves secondary messengers and processes like phosphoinositide hydrolysis, which affect how excitable neurons are and how well they can adapt or form new connections. This is why many people report long-lasting psychological benefits, such as better emotional regulation or reduced anxiety and depression after a psilocybin trip. The trip isn’t just a fleeting experience—it can lead to changes in brain structure and function (Vollenweider and Kometer 611).

7. Tolerance: Why Repeated Use Has Diminishing Effects

If you’ve ever wondered why psilocybin loses its punch when taken repeatedly over a short period, it’s because your 5-HT2A receptors become desensitized. With repeated use, the body builds up tolerance, making it harder to achieve the same effects. But don’t worry—after a few days or a week, your receptors bounce back to normal, and the tolerance fades away (Passie et al. 130).

8. Psilocybin and Neuroplasticity: Rewiring the Brain

One of the most exciting things about psilocybin is its potential to boost neuroplasticity—the brain’s ability to form new connections and pathways. Some research suggests psilocybin may stimulate the growth of dendritic spines, which are essential for neural communication. This may be one reason why psilocybin shows promise in treating conditions like depression, anxiety, PTSD, and addiction. By encouraging the brain to develop new, healthier ways of thinking, psilocybin could help people break out of negative thought patterns and develop healthier emotional responses (Ly et al. 346).

9. Psilocybin’s Physiological Effects

Psilocybin’s effects aren’t just limited to the mind. You may notice some physiological changes as well, thanks to its interaction with serotonin and norepinephrine systems. Some common effects include:

• Increased heart rate and blood pressure: Psilocybin activates the sympathetic nervous system, leading to heightened physiological responses.

• Pupil dilation (mydriasis): A hallmark of serotonergic psychedelics.

• Mild increases in body temperature and sweating: Psilocybin can influence the hypothalamus, which controls body temperature (Nichols 24).

These effects are usually mild and temporary but are part of the broader influence that psilocybin has on the body’s autonomic nervous system.

Wrapping It Up: Why It All Matters

At its core, psilocybin is much more than a simple “magic” mushroom. Its effects on the brain and body are profound, altering how we think, feel, and perceive the world. By interacting with various neurotransmitter systems and increasing brain connectivity, psilocybin holds significant promise for treating mental health conditions like depression, anxiety, and PTSD. However, we still have much to learn about its long-term impacts and full therapeutic potential.

Our mission at MycoMind is to help you understand the science behind psilocybin and its role in personal transformation. By staying informed, you can make educated decisions about your mental health and well-being.

Works Cited

• Carhart-Harris, Robin L., et al. "The Default-Mode, Ego-Functions and Free-Energy: A Neurobiological Account of Freudian Ideas." Brain: A Journal of Neurology, vol. 135, no. 3, 2012, pp. 1150-1160.

• Ly, Calvin, et al. "Psychedelics Promote Structural and Functional Neural Plasticity." Cell Reports, vol. 23, no. 11, 2018, pp. 3170-3182.

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

• Passie, Torsten, et al. "The Pharmacology of Psilocybin." Addiction Biology, vol. 7, no. 2, 2002, pp. 123-134.

• Petri, Giovanni, et al. "Homological Scaffolds of Brain Functional Networks." Journal of the Royal Society Interface, vol. 11, no. 101, 2014, pp. 43-45.

• 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.