spec sheet10 rows
DOI (2,5-dimethoxy-4-iodoamphetamine) is a potent, long-acting psychedelic amphetamine of the DOx family bearing an iodine substituent at the 4 position of the ring. It acts as a high-affinity agonist at serotonin 5-HT2A receptors, and its radioiodinated form ([125I]DOI) became the standard agonist radioligand for mapping and quantifying 5-HT2A and 5-HT2C receptor populations in brain and peripheral tissue. Because its hallucinogenic potency correlates closely with 5-HT2A affinity, DOI is widely used as a reference tool compound in drug discrimination and head-twitch assays that define the class. Beyond its psychoactive effects, the (R)-enantiomer has attracted interest for potent anti-inflammatory activity mediated through peripheral 5-HT2A receptors, alongside more recent findings of 5-HT2A-dependent anxiolytic and antinociceptive effects in rodent models. In humans it produces a prolonged psychedelic state with a stimulant character and the vasoconstriction typical of the DOx series.
- Long, visual, energetic psychedelic character
- Well-characterized high-affinity 5-HT2A agonist
- High-affinity 5-HT2A agonist and standard radioligand probe
- Vasoconstriction and heavy body load
- Long duration makes redosing risky
- Overheating, agitation, seizures at overdose
Mechanism
DOI is a 2,5-dimethoxy-4-iodo amphetamine and one of the most-studied ligands in pharmacology. Its core action is agonism at the 5-HT2A receptor, the receptor that drives the classic psychedelic state, with high affinity also at 5-HT2C; radiolabeled DOI is a standard tool for quantifying these receptors in the lab. The amphetamine backbone slows breakdown and adds a stimulant component, and the sustained 5-HT2A action produces its long duration and vasoconstriction.
receptor fingerprint
receptoragonist
5-HT2C receptoragonist
Safetyrisks and cautions, not medical advice
DOI is potent at low milligram amounts and long-lasting, so misjudging strength is easy, and like other DOx compounds it causes vasoconstriction and a heavy body load; overdoses can bring agitation, hyperthermia (dangerous overheating), and seizures. It should not be combined with MAOIs, vasoconstrictors, or other strongly serotonergic drugs because of serotonin toxicity and additive vessel narrowing. People with heart or circulatory conditions or a history of psychosis should avoid it. Not medical advice.
Subjective profileweighing the evidence above
Best left in the lab, which is where nearly all of its history sits. It is potent, very long, and heavy on vasoconstriction, judging the amount is easy to get wrong, and overdoses have brought agitation, hyperthermia and seizures. Nothing about the experience justifies that margin.
Resources
This entry is here for reference.
Research
- 1988first citedRadioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD an…
- 2025most recentIUPHAR Article: Psilocybin induces long-lasting effects via 5-HT2A receptors in mouse models of…
- 1.In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor
- 2.Autoradiographic characterization of (+-)-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane ([125I]DOI) binding to 5-HT2 and 5-HT1c receptors in rat brain
- 3.Hallucinogenic drug interactions at human brain 5-HT2 receptors: implications for treating LSD-induced hallucinogenesis.
- 4.Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens.
- 5.Antagonism of 5-hydroxytryptamine2 receptor-mediated phosphatidylinositol turnover by d-lysergic acid diethylamide.
- 6.Serotonin 5-HT2A receptor activation blocks TNF-α mediated inflammation in vivo.
- 7.5-HT(2) receptor activation alleviates airway inflammation and structural remodeling in a chronic mouse asthma model.
- 8.Psychedelics and Anti-inflammatory Activity in Animal Models.
- 9.IUPHAR Article: Psilocybin induces long-lasting effects via 5-HT2A receptors in mouse models of chronic pain.
- 10.Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI.
- 11.Role of the 5-HT₂A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice.
- 12.Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT₂A receptors, in mice.
13 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Why is DOI important in research?
Its radiolabeled form is a standard laboratory tool for mapping and measuring 5-HT2A serotonin receptors.
How does it work?
Mainly through high-affinity agonism at the 5-HT2A serotonin receptor.
Is it long-lasting?
Yes. Like other DOx amphetamines it has a slow onset and a long plateau, so redosing is easy to misjudge.
Adverse effects
- Vasoconstriction and heavy body load
- Long duration makes redosing risky
- Overheating, agitation, seizures at overdose