Dimethyltryptamine (DMT)
Targets in the model
20
each with a measured Kᵢ
A one-compartment model of what Dimethyltryptamine (DMT) 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
No absorption step: the whole dose enters the plasma compartment at t=0. F is 1 by definition, not by assumption. Bioavailability for this route is 1, both properties of the route rather than of Dimethyltryptamine (DMT).
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 366 nM.
Reported milestones
4 Acute tolerance at 30 min
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 25 mg intravenous bolus, followed by 1 mg/min infusion.
The study gave DMT as a bolus, an infusion, or both. The sandbox models a single dose, so the bolus times are the ones that correspond; the infusion findings are kept because they bear directly on what the model assumes.
- 1
Peak effect2 minmental
Both bolus doses, 15 mg and 25 mg, rapidly induced very intense psychedelic effects that peaked within 2 min. The boluses produced more negative subjective effects and more anxiety than the infusions did.
Vogt SB et al., Translational Psychiatry 2023 — Stated in the abstract. Two minutes is 0.033 h, which is where the marker sits.
- 2
Early elimination half-life5 minphysiological
Early plasma elimination half-life 5.0-5.8 min, followed after 15-20 min by a longer late elimination phase with a half-life of 14-16 min.
Vogt SB et al., Translational Psychiatry 2023 — Stated in the abstract. Two elimination phases are exactly what the sandbox's one-compartment model cannot represent, which is worth seeing on the axis.
- 3
Effects over15 minmental
After the infusion was stopped, all drug effects decreased rapidly and had completely subsided within 15 min.
Vogt SB et al., Translational Psychiatry 2023 — Stated in the abstract. This is 15 min after the infusion ended, not 15 min after dosing; on a single-bolus axis it marks how fast the offset is, not the moment it happens.
- 4
Acute tolerance30 min(30 min–1.50 h)mental
Under continuous infusion, subjective effects were stable from 30 to 90 min even though plasma concentrations kept rising — the authors read this as acute tolerance to continuous administration.
Vogt SB et al., Translational Psychiatry 2023 — Stated in the abstract. The sandbox assumes no tolerance and no receptor reserve, so for this compound the model is known to be wrong in this window and in this direction.
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 plasma0
Modelled maximum of 948 nM total plasma concentration.
Peak effect site9 min
Modelled maximum of 366 nM at the effect site — the concentration the occupancy below is computed from.
Effect site down to a tenth1 h 7 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-HT10%
- Serotonin (5-HT) receptor0%
- 5-HT2A0%
- 5-HT60%
- 5-HT1D0%
- 5-HT70%
- 5-HT2B0%
- 5-HT1A0%
- 5-HT2C0%
- Alpha2B0%
- Alpha2C0%
- D10%
- 5-HT1E0%
- 5-HT5A0%
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
- hippocampal formation
- amygdala
- midbrain
- retina
- spinal cord
- pituitary gland
- cerebellum
Peripheral & autonomic
- smooth muscle
- small intestine
- kidney
- adrenal gland
- duodenum
- spleen
- heart muscle
- colon
- liver
- urinary bladder
- stomach 1
- skeletal muscle
Parameters
The whole model is these five numbers plus the route. Each says whether anyone measured it for Dimethyltryptamine (DMT). Edit any of them; nothing here is written back to the archive.
How long the plasma concentration takes to halve once absorption is over.
Half-life rows of 0.085, 0.285 and 1.648 h are held in this archive for DMT; the two short values agree with its very rapid clearance by monoamine oxidase and 0.25 h sits between them.
Apparent volume the dose would occupy at the plasma concentration. Large means the compound leaves the blood for tissue.
Class prior reduced for a small, rapidly cleared tryptamine.
The share of plasma drug not bound to protein. Only unbound drug crosses into the brain.
Low binding assumed.
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.
Very fast: inhaled DMT reaches peak effect in minutes, so the effect site must equilibrate almost as fast as plasma rises.