IUPAC: 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethan-1-amine · C₁₈H₂₂INO₃ · MW 427.28 g/mol · CAS 919797-19-6
25I-NBOMe. The N-(2-methoxybenzyl) derivative of the phenethylamine psychedelic 2C-I. A potent, non-selective 5-HT2 receptor agonist active in the microgram range. Widely mis-sold on blotter as "acid" — but it is not LSD, and it is meaningfully more dangerous. Street/context names: 2C-I-NBOMe, Cimbi-5, "N-bomb," "Smiles," "25I."
25I-NBOMe is a classical serotonergic psychedelic in the sense that it works — like DMT, LSD and the 2C phenethylamines — through 5-HT2A receptor agonism, driving Gq/PLC-β signaling (IP₃/DAG, intracellular Ca²⁺) in layer-V cortical pyramidal neurons. What makes it distinct is affinity. It is built from 2C-I — 4-iodo-2,5-dimethoxyphenethylamine — by adding a single N-(2-methoxybenzyl) group to the amine. That one modification increases 5-HT2A affinity by roughly an order of magnitude, taking a mid-nanomolar agonist into the low single-digit nanomolar range (curated ChEMBL Ki = 2.2 nM).
The 2,5-dimethoxyphenethylamine scaffold docks in the deep orthosteric pocket shared with serotonin, ergolines and tryptamines: the protonated amine salt-bridges Asp3.32, and the aromatic ring stacks against the Phe6.51/Phe6.52 aromatic cage of 5-HT2A.
The 4-position iodine sits in a hydrophobic subpocket lined by Gly5.42/Ser5.43, adding halogen/van-der-Waals contact. Halogenation at the 4-position is what separates 2C-I from weaker 4-H analogs and contributes to the high intrinsic potency.
The 2-methoxybenzyl arm reaches out of the orthosteric site into an extended binding pocket toward ECL2 and TM7 — the same region occupied by the N-benzyl arm of 25CN-NBOH in the 5-HT2A cryo-EM structure. This extra anchor is the structural basis of NBOMe potency.
25I-NBOMe behaves as a high-efficacy 5-HT2A agonist at Gq signaling — closer to a full agonist than the partial-agonist tryptamines — with slow off-kinetics from the deep, multi-anchor pose. Head-twitch and drug-discrimination data confirm a 5-HT2A-mediated hallucinogenic signature.
The compound is essentially non-selective across the 5-HT2 family: 5-HT2B Ki = 2.3 nM and 5-HT2C Ki = 7.0 nM. Potent 5-HT2B agonism is the receptor basis for cardiovascular and valvular concern with repeated exposure.
5-HT2A is not only cortical — it drives vascular smooth-muscle contraction. A high-efficacy, long-residence 5-HT2A agonist therefore produces intense peripheral vasoconstriction, a toxidrome not seen with LSD at equivalent psychedelic intensity.
Because oral bioavailability is poor (extensive first-pass metabolism, see §02), the drug is taken sublingually / buccally — a blotter tab held against the gum. This is the practical tell: LSD is active on blotter too, so identical-looking tabs conceal wildly different pharmacology and wildly different safety margins.
25I-NBOMe undergoes heavy first-pass metabolism, so swallowing a tab largely wastes it — which is precisely why it is dosed sublingually, letting the drug cross the oral mucosa and bypass the gut/liver on first pass. Human PK is sparse (this is an unscheduled-turned-Schedule-I research chemical, not a licensed drug), so most parameters below are reported ranges from case series and in-vitro metabolism work, and are marked as approximate.
Metabolism cascade: both aromatic methoxy groups are targets for O-demethylation, and the ring system is hydroxylated; the phenolic products are then conjugated (glucuronidation / sulfation) and cleared renally. Metabolites are generally regarded as inactive at 5-HT2A, so exposure tracks the short-lived parent.
The clinically dangerous consequence of microgram potency is dose blindness. There is no way to eyeball an active dose: 25I-NBOMe is not visible, not tastable at active amounts (users report a bitter/metallic or numbing taste, but this is unreliable), and blotters are not manufactured to any standard. Uneven "spray" distribution across a sheet means two tabs from the same batch can differ several-fold in content. Redosing because "it didn't kick in" is a recurring path to overdose and death.
Subjectively, 25I-NBOMe produces open- and closed-eye visuals, thought loops, time distortion and strong stimulation. What differentiates it clinically from the classical psychedelics is the sympathomimetic and vasoconstrictive load riding underneath the psychedelia — the direct pharmacological output of a high-efficacy, long-residence 5-HT2A/5-HT2 agonist acting on both brain and vasculature.
LSD has no established human lethal dose and does not cause the severe vasoconstriction, seizures or hyperthermia seen with NBOMe overdose. 25I-NBOMe has killed people at recreational blotter doses. If a "tab" tastes bitter/metallic, or is active in what feels like a normal LSD amount but comes with racing heart, crushing agitation and body load — treat it as a research chemical, not acid.
Layer-V pyramidal 5-HT2A agonism disrupts thalamocortical gating and drives the visual and cognitive distortions common to serotonergic psychedelics. High efficacy and slow receptor off-rate make the state intense and hard to abort once it escalates.
Marked adrenergic/serotonergic activation produces tachycardia, hypertension, mydriasis, hyperthermia and profuse sweating. In reported severe intoxications this progresses to agitated ("excited") delirium, requiring aggressive sedation and cooling.
Sustained 5-HT2A agonism on vascular smooth muscle causes intense peripheral vasoconstriction. Case reports describe limb and digital ischemia, and organ hypoperfusion — a mechanism largely absent from the classical psychedelic risk profile.
Severe overdoses are associated with seizures, rhabdomyolysis, metabolic acidosis, hyperthermia and, in the worst cases, cardiac arrest and death. Combining with other serotonergic or stimulant drugs compounds every one of these hazards.
There is essentially no therapeutic literature on 25I-NBOMe; its documented clinical footprint is a wave of emergency-department presentations and fatalities in the early-to-mid 2010s that drove emergency scheduling in many countries. Its most useful role has been the opposite of therapeutic: as the radiolabeled analog 11C-Cimbi-36 (a close NBOMe congener), the chemotype became a PET tracer for imaging 5-HT2A receptors in living brain — a legitimate research use of the same high-affinity binding that makes the street drug dangerous.
Non-moralistic and evidence-based. This is one of the genuinely dangerous psychedelics: microgram-active, mis-sold as LSD, with a documented overdose-death record. Testing your supply is not optional here — it is the single highest-yield thing you can do.
| Target | Affinity | Rel. | Mechanism |
|---|---|---|---|
|
5-HT2A
Serotonin 2A receptor (HTR2A · rat)
|
Ki = 2.2 nM
pChEMBL 8.66
|
Agonist | |
|
5-HT2B
Serotonin 2B receptor (HTR2B · human)
|
Ki = 2.3 nM
pChEMBL 8.64 · valvulopathy risk
|
Agonist | |
|
5-HT2C
Serotonin 2C receptor (HTR2C · human)
|
Ki = 7.0 nM
pChEMBL 8.15
|
Agonist |