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Psilocybin Pharmacokinetics
- sofiamanne
- May 28
- 3 min read
The Importance of Understanding How Drugs Work
When you ingest psilocybin, something remarkable happens: your brain begins a dialogue with the substance. But what kind of dialogue is it? How long does it last? And why do some people feel radically transformed, while others feel little at all?
To understand the answers, we must start with a topic that’s often overlooked in the popular psychedelic conversation: pharmacokinetics—how a drug moves through the body. Industries have long failed psychedelic research due to upheld stigma which reinforces borders that inherently discourage research.
This isn’t just scientific trivia. Understanding the pharmacokinetics of psychedelics like psilocybin is essential for safe, effective, and ethical use—whether in clinical trials, therapeutic settings, or personal journeys.
For the ethical and beneficial use of drugs it is imperative that we as users understand how drugs work and interact with the body. The understanding of how drugs target cells, organs, and pathways is how we can begin to explore using drugs to manipulate these pathways for the benefit of people.
Why Psychedelics are any Different From Other Drug Classes
Most drugs target specific tissues or receptors in the body. Think of painkillers dulling the nerves or antibiotics eliminating bacteria. But psychedelics are different. They target consciousness itself.
Psilocybin’s active form, psilocin, interacts with 5HT2A serotonin receptors in the brain’s neocortex—a region that sets humans apart from most animals. Unlike other drug studies, where animal models offer insight, psychedelics push us into territory that’s deeply human and poorly understood. Can consciousness be as simple as electrical impulses from neuron to neuron?
To truly grasp their effects, we need a fusion of biology, neuroscience, psychology, and philosophy. At the center of this complex web lies a simple question: How does this substance move through us, and what does it do once it gets there?
What the Research Tells Us
A recent systematic review explored 1,848 published studies about psilocin and using various criteria selected 14 which were relevant and further synthesized their findings. Below is what we can take away from their findings:
🌀 Absorption
Orally ingested psilocybin has a highly variable onset, due to factors like stomach contents and metabolism.
IV administration reaches peak concentration faster (no surprise), but it’s not user-friendly or practical outside a laboratory setting.
🔬 Metabolism
Various isoforms of CYP450 are responsible for metabolism of psilocybin.
CYP2D6 is an enzyme which is highly responsible for the conversion of psilocybin to psilocin.
MAO which you may recognize typically metabolizes serotonin reducing its bioavailability was found to also break down Psilocin.
This finding in MAO is further suggestive and supports that Psilocin acts much like serotonin in our brains.
🧠 Serotonergic System Changes in The Brain
Via 5HT2A receptors psilocin changes typical default mode network connectivity thus increasing neurological and mental ‘flexibility’.
Psilocin increases neuroplasticity, increases dendritic spine density and synaptic strength which suggests their effects are likely more than acute.
With physical changes in parts of the brain which control emotional regulation you can assume lasting and persistent changes in the people themselves.
Moving Forward
Science can’t fully explain what happens when a person reconnects with their inner child, or sees their grief dissolve into light—but it can tell us what’s happening under the hood. The understanding of metabolism of psilocybin opens the door for further studies which hone in on how individual differences amongst people can impact their metabolism for psychedelics.
In a culture racing to legalize and monetize psychedelics, understanding the mechanisms beneath the magic is critical. Pharmacokinetics gives us a grounded, biological lens to view psychedelics.
The more we know about how psilocybin moves through the body, the better we can:
Design safer clinical protocols.
Predict individual reactions and contraindications.
Explore how set, setting, and metabolism interact.
Build bridges between science and spirituality.
How This Ties into Lucids Mission
Here at Lucid we aim to make space for ethical exploration and genuine healing. And in doing so, we give psychedelics the respect they deserve—not just as tools for transformation, but as substances that must be handled with knowledge, intention, and care.
Curious to dive deeper into the science of psychedelics? Stay tuned for our upcoming posts on all different types of psychedelics and their implications.
Written by: Sofia Manne
Edited with: Open AI
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