Mescaline
Targets in the model
7
each with a measured Kᵢ
A one-compartment model of what Mescaline 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 Mescaline.
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 1,058 nM.
Reported milestones
1 Peak plasma mescaline at 2.30 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 500 mg mescaline hydrochloride, oral.
The study established 500 mg mescaline hydrochloride, 100 µg LSD and 20 mg psilocybin as equivalent in overall intensity. The three sets of times on this site are therefore comparable with each other.
- 1
Peak plasma mescaline2.30 h(1.50 h–4.00 h)physiological
Peak plasma concentration of 1217 ng/mL (range 721-1822) reached at a median 2.3 h, range 1.5-4.0 h. Plasma elimination half-life 3.6 h.
Ley L et al., Neuropsychopharmacology 2023 — Stated in the Results. The authors note this corrects an older figure of 6 h, which came from a small study tracking radiolabelled mescaline and its metabolites together and so overstated the half-life of mescaline itself.
- 2
Effects over11.1 hmental
Mean total duration of acute subjective effects 11.1 h, the longest of the three. The authors attribute the difference from LSD to a later plasma peak and a broader peak plateau, not to slower elimination — the comedown was equally fast and the half-lives were both about 3.5 h.
Ley L et al., Neuropsychopharmacology 2023 — Duration means from the abstract; the attribution is stated in both Results and Discussion. Onset and time to maximal effect are reported as significantly later than LSD, but the numbers are in a table not present in the machine-readable text and are not given here.
- 3
Next-day effects12.0 h(12.0 h–24.0 h)physiological
Mescaline was the only one of the three to produce significantly more adverse effects than placebo in the subacute window of 12-24 h after dosing, on the List of Complaints.
Ley L et al., Neuropsychopharmacology 2023 — Stated in the abstract and in Results, 'Autonomic and adverse effects'. The authors suggest it follows from the later onset and longer duration.
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 plasma2 h 10 min
Modelled maximum of 2.63e+3 nM total plasma concentration.
Peak effect site3 h 7 min
Modelled maximum of 1.06e+3 nM at the effect site — the concentration the occupancy below is computed from.
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.
This archive holds no pChEMBL value for the pair, and holds one for others of this compound — so the absence is ChEMBL’s, not a gap in the harvest. ChEMBL withholds a pChEMBL where the activity is not a comparable, meaningful result: an inexact relation, an unrecognised type, or a screen the depositor marked inactive. The concentration is shown because it is what the archive holds, and it is ranked below everything vouched for because it is not evidence of binding. Ketamine against the APE1 endonuclease is the example that earned this footnote: ChEMBL records that screen as inactive, and read as an affinity it made a DNA-repair enzyme ketamine’s tightest binder by two orders of magnitude.
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
- amygdala
- hippocampal formation
- midbrain
- pituitary gland
- cerebellum
- spinal cord
- retina
Peripheral & autonomic
- kidney
- spleen
- pancreas
- urinary bladder
- heart muscle
- colon
- thyroid gland
- duodenum
- smooth muscle
- lung
- small intestine
- salivary gland
Parameters
The whole model is these five numbers plus the route. Each says whether anyone measured it for Mescaline. Edit any of them; nothing here is written back to the archive.
How long the plasma concentration takes to halve once absorption is over.
Mescaline's effects are reported to last far longer than most compounds here, which implies a longer half-life than the class prior.
Apparent volume the dose would occupy at the plasma concentration. Large means the compound leaves the blood for tissue.
Class prior, slightly reduced for a relatively polar phenethylamine.
The share of plasma drug not bound to protein. Only unbound drug crosses into the brain.
Low protein binding assumed; mescaline is among the more polar compounds here.
Unbound brain concentration divided by unbound plasma. Below 1 implies active efflux; 1 is passive equilibration.
Reduced below unity: mescaline's polarity makes free entry into the brain less likely than for the tryptamines.
How fast the receptor compartment follows plasma. Small values put the peak effect long after the peak concentration.
Slower than the prior, consistent with a long reported onset.