Human × Psilocybin

A journey of what happens when you take psilocybin.

  1. 1Down to the stomach

    A mushroom goes down like any other food: chewed, swallowed, along the gullet and into the stomach. What it carries is psilocybin, a small molecule the fungus makes.

    1A prodrug

    For now it does nothing: the body has to change psilocybin before it can act. The hollow dots are psilocybin; they fill in once it has changed.

  2. 2Losing the phosphate

    Psilocybin carries a phosphate group. Enzymes called phosphatases cut it off: a little in the acid of the stomach, most in the lining of the gut, and the liver finishes what’s left.

    2Psilocin

    What remains is psilocin, the molecule that does the work. Without its phosphate it has lost its charge and dissolves in fat, and that matters in a moment.

  3. 3Liver, heart, everywhere

    Psilocin passes through the gut wall into the veins that drain the intestine. They run to the liver first, which clears some of it, then to the heart, which pumps it round the body and up to the brain.

    3About two hours

    The level in the blood climbs for about two hours, then falls away. The curve follows an average person; real people vary a lot.

  4. 4The blood-brain barrier

    The brain is guarded. The cells lining its blood vessels are sealed tightly to each other, so most of what’s in the blood can’t get through.

    4Psilocin slips through

    Psilocin is small and dissolves in fat, so it slips straight through the cells’ oily membranes. Psilocybin, still holding its charged phosphate, mostly bounces off.

  5. 5Onto the receptor

    Psilocin is shaped almost exactly like serotonin, one of the brain’s own messengers, so it fits serotonin’s docks. The one that matters most is the 5-HT2A receptor.

    5Easier to set off

    These sit thickest on the big pyramidal neurons of the cortex. When psilocin docks, the neuron fires more easily. The more receptors are taken, the stronger people say the effects are.

  6. 6Some lights go off

    You’d expect something this strong to light the brain up. Mostly it does the opposite: in scans, activity falls in the medial prefrontal cortex at the front and the posterior cingulate at the back.

    6The default mode network

    Both are hubs of the default mode network, the system busy with the self: daydreaming, remembering, planning, the running story of who we are.

    6More gets through

    The thalamus, which filters what the senses send up, quietens, yet its links to the rest of the cortex grow. The visual cortex talks to far more of the brain, which may be why people see with their eyes closed.

    6Still being drawn

    Not every study agrees. Some early PET scans found the front of the brain working harder, and much of the thalamus and visual work was done with LSD.

  7. 7Offline

    The default mode network usually works as one tight unit, its parts in step. On psilocybin it falls out of step.

    7The biggest change

    In 2024 a team scanned the same people again and again. This was the biggest change of all: strongest in the default mode network, and several times bigger than anything a stimulant did.

    7Fewer walls

    Networks that normally keep to themselves start talking to each other. The part of us that narrates goes quiet, and everything else is free to connect.

  8. 8The aperture opens

    This chapter is a way of putting it, not a measurement. With the filters down, it can feel as if a sensory aperture opens wider than usual, and more comes through at once.

    8The quantum plenum

    We think of what’s on the other side as the quantum plenum: the full field that everything is part of. That’s our language for the experience, not physics, and no scanner can see it.

    8Steady reports

    People’s reports have been steady for decades: edges soften, the sense of a separate self loosens, and they feel connected to something much larger.

  9. 9Coming back

    All the while the liver tags psilocin with a sugar acid so the kidneys can flush it out. The level in the blood halves every two to three hours.

    9Back in step

    By about six hours most of the effects have gone, and the networks fall back into step.

    9Not everything snaps back

    In the 2024 study, the link between the hippocampus, where memories are made, and the default mode network stayed weaker for weeks. It’s one lead on why a single session can be felt for so long.

Close-up
Sources

2 · Losing the phosphate

3 · Into the blood

5 · Onto the receptor

6 · Some lights go off

7 · Offline

9 · Coming back

The 3D body