DOI

Chemical structure of (R)-DOI.
Clinical data
Other names	DOI; 2,5-Dimethoxy-4-iodoamphetamine; 4-Iodo-2,5-dimethoxyamphetamine
Routes of administration	Oral
Drug class	Serotonergic psychedelic;Hallucinogen;Serotonin5-HT2 receptoragonist;Anti-inflammatory agent
ATC code	None
Legal status
Legal status	BR: Class F2 (Prohibited psychotropics)[1] CA: Schedule I
Identifiers
IUPAC name 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine
CAS Number	64584-34-5 Y[correct] 82864-06-0 ((R)-DOI) 99665-04-0 ((S)-DOI) 42203-78-1 (HCl)
PubChemCID	1229
IUPHAR/BPS	147
ChemSpider	1192 Y
UNII	Q2E57V2WS3
ChEMBL	ChEMBL6616 Y
CompTox Dashboard(EPA)	DTXSID7040520
Chemical and physical data
Formula	C11H16INO2
Molar mass	321.158 g·mol−1
3D model (JSmol)	Interactive image
Melting point	201.5 °C (394.7 °F) (hydrochloride)
Solubility in water	10 mg/mL[2]
SMILES IC(C=C1OC)=C(OC)C=C1CC(C)N
InChI InChI=1S/C11H16INO2/c1-7(13)4-8-5-11(15-3)9(12)6-10(8)14-2/h5-7H,4,13H2,1-3H3 Y Key:BGMZUEKZENQUJY-UHFFFAOYSA-N Y
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2,5-Dimethoxy-4-iodoamphetamine (DOI) is apsychedelic drug of theamphetamine and4-substituted-2,5-dimethoxyamphetamine (DOx) families.^[3][4] It is relatively little-used as arecreational drug but is frequently used inscientific research in the study of psychedelics andserotonin receptors.^[3][4]

DOI acts as apotentserotonin5-HT₂ receptoragonist, including of the serotonin5-HT_2A and5-HT_2C receptors.^[3][4] Thecompound has astereocenter, andR-(−)-DOI is the more activestereoisomer.[¹²⁵I]-R-(−)-DOI is used as aradioligand and indicator of the presence ofserotonin5-HT_2A receptors in studies.^[3]

DOI's effects have been compared toLSD, although there are differences that experienced users can distinguish.^{[citation needed]} Besides the longerduration of DOI compared to LSD, the trip tends to be moreenergetic than an LSD trip, with morebody load and a different subjective visual experience.^{[citation needed]} The after effects include residualstimulation anddifficulty sleeping, which, depending on the dose, may persist for days.^[5] While rare, DOI has sometimes been sold as a substitute for LSD, or even sold falsely as LSD, which may be dangerous because DOI does not have the same establishedsafety profile as LSD.^[6] Owing to their very long durations, which users tend to find disagreeable however, DOI and other DOx psychedelics have seen very little recreational use.^{[3][7][8][9][10]}

DOI was firstsynthesized in 1973, by Coutts and Malicky.^[3] Unlike many other psychedelic drugs, DOI is not an explicitlycontrolled substance in theUnited States.^[11] However, it could be considered a controlled substance under theFederal Analog Act. In any case, its non-controlled status has made DOI usefully accessible for use in scientific research, which has contributed to its popularity for such uses.^[3] In December 2023, theDrug Enforcement Agency (DEA) proposed making DOI aschedule I controlled substance.^[12] This proposal has been opposed by psychedelic researchers and the DEA has consequently delayed its June 2024 hearing on the proposal.^[13] Subsequently, an administrative judge recommended placement of DOI into Schedule I in June 2025, and it is likely that the drug will be scheduled.^[14]Recreational availability and use of DOI are rare.^[14]

The dose, duration, and effects of DOI have been described.^[5]

DOI is aserotonin5-HT_2A,5-HT_2B and5-HT_2C receptor agonist.^{[15][16][17][4]} It is said to be approximately 5- to 12-foldselective for the serotonin 5-HT_2A receptor over the serotonin 5-HT_2C receptor.^[25]

The drug is not amonoamine releasing agent of serotonin ordopamine.^[20]

DOI is an agonist of the rattrace amine-associated receptor 1 (TAAR1).^[26]

(R)-DOI and several otherserotonergic psychedelics, includingTCB-2,LSD, andLA-SS-Az, have been found to showpotent inhibition oftumor necrosis factor alpha (TNFα)-inducedinflammation.^[27][28][29] (R)-DOI was the most active of the assessed drugs and showed extremely high potency that was in thepicomolar range and was an order of magnitude more potent than its action as ahallucinogen. TNFα may play a mediating role in thepathophysiology of degenerative inflammatory conditions likerheumatoid arthritis andAlzheimer's disease. (R)-DOI has also been found to block pulmonary inflammation, mucus hyperproduction, airway hyperresponsiveness, and to turn off key genes in pulmonary immune response, effects which block the development of allergicasthma inanimal models.^[30] These findings could make DOI and other serotonin 5-HT_2A agonists novel treatments for inflammatory conditions.^[31]

DOI has been shown to induce rapid growth and reorganization ofdendritic spines andsynaptic connections with otherneurons, processes known to underlieneuroplasticity, and hence to be apsychoplastogen.^[32]

DOI, also known as 2,5-dimethoxy-4-iodoamphetamine or as 2,5-dimethoxy-4-iodo-α-methylphenethylamine, is asubstituted phenethylamine andamphetaminederivative and a member of theDOx family of drugs. It isstructurally related to thenaturally occurring phenethylamine psychedelicmescaline (3,4,5-trimethoxyphenethylamine). Other closely related DOx drugs includeDOM,DOB,DOC, andDOF, among many others.

DOI was first synthesized byAlexander Shulgin.^[5] Theradioactiveiodine-125 form of DOI for PET imaging was first developed in the lab ofDavid E. Nichols.

In January 2007, British police reported that three young men had fallen ill, reportedly, after taking DOI at a rave inBiggleswade, nearMilton Keynes, and warned others who had taken it to seek medical attention. This would appear to be the first indication that DOI has found more widespread use as arecreational drug in the UK.^[33]

South Australian man Cody Edwards who brutally murdered Synamin Bell controversially plead guilty to the lesser sentence ofmanslaughter after attesting that the drug DOI had inducedparanoia, and that he had subsequently acted in ‘self-defence’ when he had beaten the mother-of-three to death with a dumbbell, resulting in over fifty wounds.^[34]

TheStandard for the Uniform Scheduling of Medicines and Poisons (SUSMP) of Australia does not list DOI as a prohibited substance.^[35]

Listed as aSchedule 1^[36] as it is an analogue of amphetamine.^[37] The CDSA was updated as a result of theSafe Streets and Communities Act, changing amphetamines fromSchedule 3 toSchedule 1.^[38]

Illegal since 8 April 2007.^[39]

DOI is classified as a psychoactive substance banned from the consumer market in Finland.^[40]

Sveriges riksdag added DOI to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of August 30, 2007, published byMedical Products Agency in their regulation LVFS 2007:10 listed as DOI, 4-jod-2,5-dimetoxi-amfetamin.^[41]

As of 2023, DOI is not scheduled in the United States,^[11] but it is likely that DOI would be considered an analog (ofDOB), in which case, sales or possession could be prosecuted under theFederal Analogue Act. In December 2023, the USDrug Enforcement Administration (DEA) issued anotice of proposed rulemaking that would classify both DOI and2,5-dimethoxy-4-chloroamphetamine (DOC) as schedule I controlled substances.^[12] However, in May 2024, it was reported that the DEA's June 10, 2024 hearing on scheduling of DOI and DOC had been postponed.^[13][42] This followed opposition to the proposal by psychedelic researchers.^[13] DOI is frequently used inscientific research due in considerable part to its non-scheduled status,^[3][4] and DOI becoming a controlled substance would cause problems for scientists.^[12][13]

DOI is a Schedule I controlled substance in the state of Florida.^[43]

• DOx
• 5-HT_2A receptor § Anti-inflammatory effects

• DOI - PsychonautWiki
• DOI - Erowid
• DOI - Lycaeum
• DOI - PiHKAL - Erowid
• DOI - PiHKAL - Isomer Design
• DOI (2,5-Dimethoxy-4-iodoamphetamine): A Potent & Unique Psychedelic Compound - Tripsitter

• Drugs not assigned an ATC code
• 5-HT2A agonists
• 5-HT2B agonists
• 5-HT2C agonists
• Anti-inflammatory agents
• Designer drugs
• DOx (psychedelics)
• Iodobenzene derivatives
• PET radiotracers
• PiHKAL
• Psychoplastogens
• Psychedelic phenethylamines
• TAAR1 agonists
• TNF inhibitors

• CS1 Brazilian Portuguese-language sources (pt-br)
• CS1 Zulu-language sources (zu)
• Articles with short description
• Short description is different from Wikidata
• Infobox drug articles with non-default infobox title
• Chemical pages without DrugBank identifier
• Articles without KEGG source
• All articles with unsourced statements
• Articles with unsourced statements from February 2025