Psilocin
Targets in the model
16
each with a measured Kᵢ
A one-compartment model of what Psilocin might do over time, at a dose and by a route you choose. The affinities driving the occupancy calculation are measured and this archive holds them; the pharmacokinetics are mostly estimated, and the table at the foot of the page says which is which. The measured dossier · method
The input
First-order gastrointestinal absorption with a rate constant giving a peak near one hour, and a bioavailability reduced by first-pass metabolism. Both are class placeholders; where a compound has a published oral F it overrides this. Bioavailability for this route is 0.3 and the absorption rate constant 1.2 h⁻¹, both properties of the route rather than of Psilocin.
Modelled concentration
3 h 36 min
One compartment with first-order absorption. It cannot show a distribution phase, so the first minutes after an intravenous dose are the least trustworthy part of the curve. Peak effect-site concentration is 31 nM.
Reported milestones
4 Eyes-open and eyes-closed EEG converge at 2.50 h
Times at which a named human study recorded an effect. These are observations, not model output: they stay where the study put them however you change the settings, so where a marker and the curve disagree, the curve is what is wrong. Each one names its study and what was read to confirm it, including how the study was designed. Except where a marker states its own dose, all of them were measured at 20 mg psilocybin dihydrate, oral.
The studies dosed psilocybin, which is dephosphorylated to psilocin before it reaches the brain. The sandbox models psilocin, so these are the times of an oral psilocybin dose: 20 mg for the entries from Ley et al., and the dose stated on each marker that came from another one.
- 1
Blood pressure raised1.00 hphysiologicalat 315 µg/kg psilocybin, oral
Mean arterial blood pressure was moderately elevated at 60 min, and only at the highest dose (315 µg/kg). Neither ECG nor body temperature was affected at any dose.
Hasler F et al., Psychopharmacology (Berl) 2004 — From the Hasler abstract. The dose is 315 µg/kg — about 22 mg for a 70 kg person, close to but not identical with the 20 mg reference dose used for the other entries here.
- 2
Cortical integration redistributed1.33 hphysiologicalat 19 mg psilocybin, oral
fMRI began about 80 min post-dose. Against the same participants' no-psilocybin session, global functional connectivity fell in sensory cortex during the eyes-closed conditions — strongest in occipital areas, by up to 39% (Cohen's d = −0.55) — and rose in associative cortex, by up to 72% (d = 0.53); during the eyes-open movie it rose in both. The gap between eyes-closed and eyes-open connectivity narrowed in every network, by 85% in the visual network. Functional modularity fell in all four conditions.
Stoliker D et al., Nature 2026 — Times from Methods, 'Study design'; the percentages and effect sizes from Results, 'Psilocybin redistributes cortical GFC', 'Eyes-closed and eyes-open GFC converge' and 'Decreased functional modularity'. The percentages are the paper's own, at the vertex or network of largest change, not a whole-cortex average. Open-label and unblinded: the comparison is each participant's own session a week earlier, which is a real control for a connectivity measure and a weak one for anything a participant reports. 80 min is when the block began; the paper does not say when it ended, and the four run lengths (8:00, 6:30, 11:24, 6:00) cannot place the end without inventing the gaps between them, so no window is drawn. The dose is 19 mg, one below the 20 mg the Ley entries were measured at.
- 3
Peak plasma psilocin2.10 h(1.00 h–5.00 h)physiological
Peak plasma psilocin concentration of 17 ng/mL (range 9.6-34) reached at a median 2.1 h, range 1.0-5.0 h. Plasma elimination half-life 2.3 h.
Ley L et al., Neuropsychopharmacology 2023 — Stated in the Results, 'Plasma drug concentrations'. This is a concentration, not an effect — it is the one point on this list directly comparable with the modelled curve.
- 4
Eyes-open and eyes-closed EEG converge2.50 hphysiologicalat 19 mg psilocybin, oral
EEG began about 150 min post-dose, after a room transfer and 20–40 min of cap setup. The difference between eyes-open and eyes-closed alpha power was 48% smaller than at baseline (Cohen's d = −0.79). The power spectrum was broader: theta, alpha and, to a lesser extent, beta power fell while gamma rose modestly during the eyes-closed conditions, concentrated in frontal channels, and those changes were attenuated during the eyes-open movie.
Stoliker D et al., Nature 2026 — From Results, 'Context modulates power and complexity', with the timing from Methods. Same open-label design as the entry above. This is the second modality's version of that entry's convergence result, recorded about 70 min later in the same session — two measurements at two times, which is the only reason one study puts two physiological markers on this axis.
- 5
Effects over4.90 hmental
Mean total duration of acute subjective effects 4.9 h — the shortest of the three classic psychedelics compared, significantly shorter than both LSD and mescaline.
Ley L et al., Neuropsychopharmacology 2023 — Duration means are given in the abstract and Results. Offset is the point at which the participant's own 'any drug effect' rating fell back to 10% of their maximum.
1 milestone falls outside the 12 h window and is not shown. Widen the window to reach it.
Model landmarks
These are not observations. Each one is a feature of the curve above, read off the figure and moving with it whenever you change a parameter.
Dose given0
The model starts here.
Peak plasma1 h 28 min
Modelled maximum of 64.3 nM total plasma concentration.
Peak effect site1 h 55 min
Modelled maximum of 31.2 nM at the effect site — the concentration the occupancy below is computed from.
Effect site down to a tenth9 h 54 min
A threshold this model picked, not a clinical endpoint. A first-order curve never reaches zero.
Modelled receptor occupancy at 3 h 36 min
O = C/(C+Kᵢ) at the effect-site concentration above. The Kᵢ is measured and this archive holds it; the C is modelled. Equilibrium is assumed at every instant, with no receptor reserve, no active metabolite and no tolerance.
- 5-HT2B83%
- 5-HT2C70%
- 5-HT2A66%
- 5-HT1D55%
- D154%
- 5-HT1E34%
- 5-HT1A32%
- 5-HT5A25%
- 5-HT724%
- 5-HT624%
- D319%
- 5-HT1B7%
- SERT3%
- Alpha2B2%
The archive holds measurements of this pair that disagree by more than a hundredfold, so the single number beside it is not settled. The strongest is shown — in this archive the strongest measurement is usually the best one rather than an outlier, because weak values are disproportionately old tissue preparations — but the range is what the sources actually support: 5-HT2A 12–2,300 nM across 10.
Modelled regional engagement
Occupancy at each target multiplied by that target’s transcript level in the region, summed. This product is the model speaking. A dossier’s Systems plate deliberately refuses to compute it, because there it would read as a finding; here it is an output with its assumptions on the page. Transcript is not receptor density, and a region shaded here is a region where the model says binding could occur, not one shown to be affected.
And nothing checks it. The concentration plot above carries reported milestones because human studies state times; this figure has no counterpart. The human imaging work this archive cites reports connectivity change across a cortical parcellation, which is a different quantity in a different set of regions — the atlas holds the cortex as one — so it can neither confirm nor contradict the shading here, and translating it onto these thirteen regions would assert a correspondence nobody has published.
Brain
Body
Shading is on a fixed scale — the strongest engagement reached anywhere during the whole run — so the figures dim as the compound clears instead of renormalising to whatever the current instant happens to hold. Outlines from the EMBL-EBI Anatomogram, the same plates the dossiers use.
Brain regions
- basal ganglia
- cerebral cortex
- hypothalamus
- hippocampal formation
- amygdala
- retina
- midbrain
- spinal cord
- cerebellum
- pituitary gland
Peripheral & autonomic
- smooth muscle
- adrenal gland
- small intestine
- colon
- duodenum
- stomach 1
- heart muscle
- liver
- urinary bladder
- kidney
- thyroid gland
- lung
Parameters
The whole model is these five numbers plus the route. Each says whether anyone measured it for Psilocin. Edit any of them; nothing here is written back to the archive.
How long the plasma concentration takes to halve once absorption is over.
Terminal half-life values of 1.91, 1.96 and 2.42 h are held in this archive's own activities table for psilocin; 2.1 is the midpoint of that range.
Apparent volume the dose would occupy at the plasma concentration. Large means the compound leaves the blood for tissue.
Class prior.
The share of plasma drug not bound to protein. Only unbound drug crosses into the brain.
Class prior adjusted upward: psilocin is a small polar tryptamine and is not reported to be highly bound.
Unbound brain concentration divided by unbound plasma. Below 1 implies active efflux; 1 is passive equilibration.
Passive equilibration assumed.
How fast the receptor compartment follows plasma. Small values put the peak effect long after the peak concentration.
Class prior.