View source for 2,5-Dimethoxy-4-methylamphetamine

{{Infobox drug
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 477211718
| drug_name = DOM
| image = DOM2DACS.svg
| width = 175px
| image2 = DOM3Dan.gif
| width2 = 200px

<!-- Clinical data -->
| pronounce = 
| tradename = 
| Drugs.com = 
| MedlinePlus = 
| licence_CA = 
| licence_EU = 
| DailyMedID = 
| licence_US = 
| pregnancy_AU = 
| pregnancy_category = 
| dependency_liability = 
| addiction_liability = 
| routes_of_administration = 
| class = [[Serotonergic psychedelic]]; [[Hallucinogen]]; [[Serotonin]] [[5-HT2 receptor|5-HT<sub>2</sub> receptor]] [[agonist]]
| ATC_prefix = 
| ATC_suffix = 

<!-- Legal status -->
| legal_AU = S9
| legal_BR = F2
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-07-25}}</ref>
| legal_CA = Schedule I
| legal_UK = Class A
| legal_US = Schedule I
| legal_status = 

<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 
| metabolism = 
| metabolites = 
| onset = 
| elimination_half-life = 
| duration_of_action = 
| excretion = 

<!-- Identifiers -->
| CAS_number = 15588-95-1
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_supplemental = <br />43061-13-8 ((''R'')-DOM)<br />43061-14-9 ((''S'')-DOM)
| PubChem = 11735949
| PubChemSubstance = 
| IUPHAR_ligand = 
| DrugBank = 
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 9910656
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = UKI9MLD5OI
| KEGG = C22736
| ChEBI = 
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 317634
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = 2,5-Dimethoxy-4-methylamphetamine; 4-Methyl-2,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-methyl-α-methylphenethylamine; Des-oxy-methyl; DOM; DMMTA; α-Me-2C-D; STP; Serenity, Tranquility, and Peace; Super Terrific Psychedelic; Stop The Police; Too Stupid to Puke;<ref name="Baggott2023" /> K-61,082<ref name="TroutDaley2024">{{cite journal | vauthors = Trout K, Daley PF | title = The origin of 2,5-dimethoxy-4-methylamphetamine (DOM, STP) | journal = Drug Test Anal | volume = 16 | issue = 12 | pages = 1496–1508 | date = December 2024 | pmid = 38419183 | doi = 10.1002/dta.3667 | url = https://shulginresearch.net/wp-content/uploads/2024/03/The-origin-of-25-dimethoxy-4-methylamphetamine-DOM-STP.-Trout.-Drug-Test.-Anal.-DOI-10.1002-dta.3667-2024.pdf}}</ref>

<!-- Chemical data -->
| IUPAC_name = 1-(2,5-dimethoxy-4-methylphenyl)propan-2-amine
| C=12 | H=19 | N=1 | O=2
| SMILES = O(c1cc(c(OC)cc1C[C@H](N)C)C)C
| StdInChI = 1S/C12H19NO2/c1-8-5-12(15-4)10(6-9(2)13)7-11(8)14-3/h5,7,9H,6,13H2,1-4H3/t9-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = NTJQREUGJKIARY-SECBINFHSA-N

<!-- Physical data -->
| melting_point = 61
}}

'''2,5-Dimethoxy-4-methylamphetamine''' ('''DOM'''), also known as '''STP''' (standing for "'''Serenity, Tranquility, and Peace'''" and/or other phrases), is a [[psychedelic drug|psychedelic]] [[drug]] of the [[substituted phenethylamine|phenethylamine]], [[substituted amphetamine|amphetamine]], and [[4-substituted-2,5-dimethoxyamphetamine|DOx]] families.<ref name="ShulginManningDaley2011">{{cite book | vauthors = Shulgin A, Manning T, Daley PF | chapter = #60. DOM | pages = 118–129 | chapter-url = https://archive.org/details/shulgin-index-vol-1/page/118/mode/1up | title = [[The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds]] | publisher = Transform Press | location = Berkeley, CA | volume = 1 | year = 2011 | isbn = 978-0-9630096-3-0 | oclc = 709667010 }}</ref><ref name="PiHKAL1991">{{cite book | author1 = [[Alexander T. Shulgin]] | author2 = [[Ann Shulgin]] | chapter = #68 DOM; STP; 2,5-DIMETHOXY-4-METHYLAMPHETAMINE | pages = 637–642 | chapter-url = https://erowid.org/library/books_online/pihkal/pihkal068.shtml | title = PiHKAL: A Chemical Love Story | date = 1991 | publisher = Transform Press | edition = 1st | location = Berkeley, CA | isbn = 978-0-9630096-0-9 | oclc = 25627628 | url = https://books.google.com/books?id=O8AdHBGybpcC }}</ref><ref name="Baggott2023">{{cite journal | vauthors = Baggott MJ | title=Learning about STP: A Forgotten Psychedelic from the Summer of Love | journal=History of Pharmacy and Pharmaceuticals | volume=65 | issue=1 | date=1 October 2023 | issn=2694-3034 | doi=10.3368/hopp.65.1.93 | doi-access=free | pages=93–116 | url=https://hopp.uwpress.org/content/wphopp/65/1/93.full.pdf | access-date=26 January 2025}}</ref><ref name="WillsErickson2012">{{cite book | vauthors = Wills B, Erickson T | chapter = Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives | veditors = Barceloux DG | title=Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants | publisher=Wiley | date=9 March 2012 | isbn=978-0-471-72760-6 | doi=10.1002/9781118105955.ch10 | pages=156–192 }}</ref><ref name="Shulgin1978">{{cite book | veditors = Iversen LL, Iversen SD, Snyder SH | vauthors = Shulgin AT | title=Stimulants | chapter=Psychotomimetic Drugs: Structure-Activity Relationships | publisher=Springer US | publication-place=Boston, MA | date=1978 | isbn=978-1-4757-0512-6 | doi=10.1007/978-1-4757-0510-2_6 | pages=243–333 | chapter-url=https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6 | url=https://books.google.com/books?id=h0_uBwAAQBAJ&pg=PA261 }}</ref> It is generally taken [[oral administration|orally]].<ref name="PiHKAL1991" /><ref name="Baggott2023" /><ref name="WillsErickson2012" />

DOM was first [[chemical synthesis|synthesized]] by [[Alexander Shulgin]], and later described in his book ''[[PiHKAL|PiHKAL: A Chemical Love Story]]'' (1991).<ref name="Baggott2023" /> It is classified as a [[Controlled Substances Act#Schedule I drugs|Schedule I]] [[controlled substance]] in the [[United States]], and is similarly controlled in other parts of the world.<ref name="Baggott2023" /> Internationally, it is a Schedule I drug under the [[Convention on Psychotropic Substances]].<ref name="INCB2003">{{cite web|url=http://www.incb.org/documents/Psychotropics/green_lists/Green_list_ENG_2014_85222_GHB.pdf |title=Green List: List of Psychotropic Substances Under International Control |date=August 2003 |edition=23rd |publisher=[[International Narcotics Control Board]] |page=4 |access-date=22 February 2014 |url-status=dead |archive-url=https://web.archive.org/web/20131219071757/http://www.incb.org/documents/Psychotropics/green_lists/Green_list_ENG_2014_85222_GHB.pdf |archive-date=19 December 2013 }}</ref>

==Effects==
Effects of this drug include substantial perceptual changes such as [[blurred vision]], multiple images, vibration of objects, visual alterations, distorted shapes, enhancement of details, [[time perception|slowed passage of time]], increased sexual drive and pleasure, and increased contrasts. It may cause [[mystical experience]]s and changes in [[consciousness]]. It may also cause [[pupillary dilation]] and a rise in [[systolic blood pressure]].<ref name="Snyder">{{cite journal|last=Snyder|first=Solomon H.|author2=Louis Faillace|author3=Leo Hollister|name-list-style=amp|date=3 November 1967|title=2,5-Dimethoxy-4-methyl-amphetamine (STP): A New Hallucinogenic Drug|url=https://pubmed.ncbi.nlm.nih.gov/4860952/|format=[[Portable Document Format|PDF]]|journal=[[Science (journal)|Science]]|volume=158|issue=3801|pages=669–670|doi=10.1126/science.158.3801.669|pmid=4860952|bibcode=1967Sci...158..669S|s2cid=24065654}}</ref>

The effects of DOM were assessed in [[clinical study|clinical studies]] in the late 1960s and early 1970s and by other researchers.<ref name="TroutDaley2024" /><ref name="Shulgin1978">{{cite book | veditors = Iversen LL, Iversen SD, Snyder SH | vauthors = Shulgin AT | title=Stimulants | chapter=Psychotomimetic Drugs: Structure-Activity Relationships | publisher=Springer US | publication-place=Boston, MA | date=1978 | isbn=978-1-4757-0512-6 | doi=10.1007/978-1-4757-0510-2_6 | pages=243–333 | chapter-url=https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6 | url=https://books.google.com/books?id=h0_uBwAAQBAJ&pg=PA261 }}</ref><ref name="SnyderFaillaceHollister1967">{{cite journal | vauthors = Snyder SH, Faillace L, Hollister L | title = 2,5-dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug | journal = Science | volume = 158 | issue = 3801 | pages = 669–670 | date = November 1967 | pmid = 4860952 | doi = 10.1126/science.158.3801.669 | bibcode = 1967Sci...158..669S | s2cid = 24065654 }}</ref><ref name="SnyderFaillaceWeingartner1968">{{cite journal | vauthors = Snyder SH, Faillace LA, Weingartner H | title = DOM (STP), a new hallucinogenic drug, and DOET: effects in normal subjects | journal = Am J Psychiatry | volume = 125 | issue = 3 | pages = 113–120 | date = September 1968 | pmid = 4385937 | doi = 10.1176/ajp.125.3.357 | url = }}</ref><ref name="WeingartnerSnyderFaillace1971">{{cite journal | vauthors = Weingartner H, Snyder SH, Faillace LA | title = DOM (STP), a new hallucinogenic drug: specific perceptual changes | journal = J Clin Pharmacol New Drugs | volume = 11 | issue = 2 | pages = 103–111 | date = 1971 | pmid = 5206471 | doi = 10.1177/009127007101100205 | url = }}</ref> At low doses, such as 1 to 4{{nbsp}}mg, DOM produces effects including [[psychostimulant|stimulation]], [[euphoriant|euphoria]], enhanced [[self-awareness]], and mild [[dose dependence|dose-dependent]] [[Hallucination|perceptual disturbance]]s.<ref name="TroutDaley2024" /> At higher doses, of above 5 to 7{{nbsp}}mg, DOM produces psychedelic effects.<ref name="TroutDaley2024" />

==Side effects==
Very little is known about the [[toxicity]] of DOM.

==Interactions==
{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

==Pharmacology==
===Pharmacodynamics===
====Actions====
{| class="wikitable floatleft" style="font-size:small;"
|+ {{Nowrap|DOM activities}}
|-
! [[Biological target|Target]] !! [[Affinity (pharmacology)|Affinity]] (K<sub>i</sub>, nM)
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 3,656–14,200 (K<sub>i</sub>)<br />12,800–13,900 ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}})<br />54–74% ({{Abbrlink|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || >10,000
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 209
|-
| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || 3,542
|-
| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 2.1–507 (K<sub>i</sub>)<br />1.1–40 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />44–132% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 12–41 (K<sub>i</sub>)<br />128–145 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />85% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 19–3,980 (K<sub>i</sub>)<br />0.23–423 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />81–119% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT3 receptor|5-HT<sub>3</sub>]] || >10,000
|-
| [[5-HT4 receptor|5-HT<sub>4</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT5A receptor|5-HT<sub>5A</sub>]] || >10,000
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || 8,155
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || 1,591
|-
| [[α1A-adrenergic receptor|α<sub>1A</sub>]] || 3,219
|-
| [[α1B-adrenergic receptor|α<sub>1B</sub>]] || >10,000
|-
| [[α1D-adrenergic receptor|α<sub>1D</sub>]] || {{Abbr|ND|No data}}
|-
| [[α2A-adrenergic receptor|α<sub>2A</sub>]] || 580
|-
| [[α2B-adrenergic receptor|α<sub>2B</sub>]] || 874
|-
| [[α2C-adrenergic receptor|α<sub>2C</sub>]] || 921
|-
| [[β1-adrenergic receptor|β<sub>1</sub>]] || >10,000
|-
| [[β2-adrenergic receptor|β<sub>2</sub>]] || 49
|-
| [[D1 receptor|D<sub>1</sub>]]–[[D5 receptor|D<sub>5</sub>]] || >10,000
|-
| [[H1 receptor|H<sub>1</sub>]]–[[H4 receptor|H<sub>4</sub>]] || >10,000
|-
| [[Muscarinic acetylcholine M1 receptor|M<sub>1</sub>]], [[Muscarinic acetylcholine M2 receptor|M<sub>2</sub>]], [[Muscarinic acetylcholine M5 receptor|M<sub>5</sub>]] || >10,000
|-
| [[Muscarinic acetylcholine M3 receptor|M<sub>3</sub>]], [[Muscarinic acetylcholine M4 receptor|M<sub>4</sub>]] || {{Abbr|ND|No data}}
|-
| [[Trace amine-associated receptor 1|TAAR<sub>1</sub>]] || >10,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| [[Imidazoline I1 receptor|I<sub>1</sub>]] || >10,000
|-
| [[Sigma-1 receptor|σ<sub>1</sub>]], [[Sigma-2 receptor|σ<sub>2</sub>]] || >10,000
|-
| {{Abbrlink|SERT|Serotonin transporter}} || >100,000 (K<sub>i</sub>)<br />>100,000 ({{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />>100,000 ({{Abbr|EC<sub>50</sub>|half-maximal inhibitory concentration}})
|-
| {{Abbrlink|NET|Norepinephrine transporter}} || >100,000 (K<sub>i</sub>)<br />>70,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />>100,000 ({{Abbr|EC<sub>50</sub>|half-maximal inhibitory concentration}})
|-
| {{Abbrlink|DAT|Dopamine transporter}} || >100,000 (K<sub>i</sub>)<br />64,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />>42,000 ({{Abbr|EC<sub>50</sub>|half-maximal inhibitory concentration}})
|-
| {{Abbrlink|MAO-A|Monoamine oxidase A}} || 24,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}}) (rat)
|-
| {{Abbrlink|MAO-B|Monoamine oxidase B}} || >100,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}}) (rat)
|- class="sortbottom"
| colspan="2" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. '''Refs:''' <ref name="PDSPKiDatabase">{{cite web | title=PDSP Database | website=UNC | url=https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=DOM&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | language=zu | access-date=1 February 2025}}</ref><ref name="BindingDB">{{cite web | last=Liu | first=Tiqing | title=BindingDB BDBM50005265 (+/-)2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine::(-)2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine::(Rec)2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine; compound with 2-(2,5-dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine::2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine::2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine((R)-(-)-DOM)::2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine(DOM)::CHEMBL8600::DOM::DOM,R(-)::Racemic DOM | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50005265 | access-date=1 February 2025}}</ref><ref name="Ray2010" /><ref name="LuethiRudinHoener2022" /><ref name="EshlemanForsterWolfrum2014" /><ref name="EshlemanWolfrumReed2018" /><ref name="LewinMillerGilmour2011" /><ref name="ÅstrandGuerrieriVikingsson2020">{{cite journal | vauthors = Åstrand A, Guerrieri D, Vikingsson S, Kronstrand R, Green H | title = In vitro characterization of new psychoactive substances at the μ-opioid, CB1, 5HT<sub>1A</sub>, and 5-HT<sub>2A</sub> receptors-On-target receptor potency and efficacy, and off-target effects | journal = Forensic Science International | volume = 317 | pages = 110553 | date = December 2020 | pmid = 33160102 | doi = 10.1016/j.forsciint.2020.110553 | doi-access = free }}</ref><ref name="vanWijngaardenSoudijn1997">{{cite book | vauthors = van Wijngaarden I, Soudijn W | title=Pharmacochemistry Library | chapter=5-HT2A, 5-HT2B and 5-HT2C receptor ligands | publisher=Elsevier | volume=27 | date=1997 | isbn=978-0-444-82041-9 | doi=10.1016/s0165-7208(97)80013-x | pages=161–197}}</ref><ref name="Acuña-CastilloVillalobosMoya2002">{{cite journal | vauthors = Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP | title = Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors | journal = Br J Pharmacol | volume = 136 | issue = 4 | pages = 510–519 | date = June 2002 | pmid = 12055129 | pmc = 1573376 | doi = 10.1038/sj.bjp.0704747 | url = }}</ref><ref name="Reyes-ParadaIturriaga-VasquezCassels2019" /><ref name="ScorzaCarrauSilveira1997" />
|}

DOM acts as a [[binding selectivity|selective]] [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub>]], [[5-HT2B receptor|5-HT<sub>2B</sub>]], and [[5-HT2C receptor|5-HT<sub>2C</sub> receptor]] [[full agonist]].<ref name="LuethiRudinHoener2022">{{cite journal | vauthors = Luethi D, Rudin D, Hoener MC, Liechti ME | title=Monoamine Receptor and Transporter Interaction Profiles of 4-Alkyl-Substituted 2,5-Dimethoxyamphetamines | journal=The FASEB Journal | volume=36 | issue=S1 | date=2022 | issn=0892-6638 | doi=10.1096/fasebj.2022.36.S1.R2691 | page= | doi-access=free | url=https://www.researchgate.net/publication/360369275 }}</ref><ref name="Ray2010">{{cite journal | vauthors = Ray TS | title = Psychedelics and the human receptorome | journal = PLOS ONE | volume = 5 | issue = 2 | pages = e9019 | date = February 2010 | pmid = 20126400 | pmc = 2814854 | doi = 10.1371/journal.pone.0009019 | doi-access = free | bibcode = 2010PLoSO...5.9019R }}</ref><ref name="EshlemanForsterWolfrum2014">{{cite journal | vauthors = Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB | title = Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function | journal = Psychopharmacology (Berl) | volume = 231 | issue = 5 | pages = 875–888 | date = March 2014 | pmid = 24142203 | pmc = 3945162 | doi = 10.1007/s00213-013-3303-6 | url = }}</ref><ref name="EshlemanWolfrumReed2018" /> Its psychedelic effects are mediated by its [[agonist]]ic properties at the 5-HT<sub>2A</sub> receptor. Due to its selectivity, DOM is often used in [[scientific research]] in studies of the [[5-HT2|5-HT<sub>2</sub> receptor]] subfamily. DOM is a [[chirality (chemistry)|chiral]] molecule, and ''R''-(−)-DOM is the more active [[enantiomer]], functioning as a potent agonist of these receptors.<ref>{{cite journal |last=Sanders-Bush |first=E |author2=Burris, KD |author3=Knoth, K |date=September 1988 |title=Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis |journal=[[Journal of Pharmacology and Experimental Therapeutics|The Journal of Pharmacology and Experimental Therapeutics]] |volume=246 |issue=3 |pages=924–928 |doi=10.1016/S0022-3565(25)22189-9 |pmid=2843634 }}</ref>

The drug is inactive as a human [[trace amine-associated receptor 1]] (TAAR1) agonist but is an agonist of the [[rhesus monkey]] TAAR1.<ref name="LewinMillerGilmour2011">{{cite journal | vauthors = Lewin AH, Miller GM, Gilmour B | title = Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | journal = Bioorg Med Chem | volume = 19 | issue = 23 | pages = 7044–7048 | date = December 2011 | pmid = 22037049 | pmc = 3236098 | doi = 10.1016/j.bmc.2011.10.007 | url = }}</ref> DOM is inactive as a [[monoamine reuptake inhibitor]] and [[monoamine releasing agent|releasing agent]].<ref name="EshlemanWolfrumReed2018">{{cite journal | vauthors = Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A | title = Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors | journal = Biochem Pharmacol | volume = 158 | issue = | pages = 27–34 | date = December 2018 | pmid = 30261175 | pmc = 6298744 | doi = 10.1016/j.bcp.2018.09.024 | url = }}</ref> It is a very weak [[monoamine oxidase inhibitor]] (MAOI), specifically of [[monoamine oxidase A]] (MAO-A), whereas it was inactive at [[monoamine oxidase B]] (MAO-B).<ref name="Reyes-ParadaIturriaga-VasquezCassels2019">{{cite journal | vauthors = Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK | title = Amphetamine Derivatives as Monoamine Oxidase Inhibitors | journal = Front Pharmacol | volume = 10 | issue = | pages = 1590 | date = 2019 | pmid = 32038257 | pmc = 6989591 | doi = 10.3389/fphar.2019.01590 | doi-access = free | url = }}</ref><ref name="ScorzaCarrauSilveira1997">{{cite journal | vauthors = Scorza MC, Carrau C, Silveira R, Zapata-Torres G, Cassels BK, Reyes-Parada M | title = Monoamine oxidase inhibitory properties of some methoxylated and alkylthio amphetamine derivatives: structure-activity relationships | journal = Biochem Pharmacol | volume = 54 | issue = 12 | pages = 1361–1369 | date = December 1997 | pmid = 9393679 | doi = 10.1016/s0006-2952(97)00405-x | url = }}</ref>

====Effects====
DOM produces the [[head-twitch response]] in rodents, a behavioral proxy of [[psychedelic drug|psychedelic]]-like effects.<ref name="HalberstadtChathaKlein2020">{{cite journal | vauthors = Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD | title = Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species | journal = Neuropharmacology | volume = 167 | issue = | pages = 107933 | date = May 2020 | pmid = 31917152 | pmc = 9191653 | doi = 10.1016/j.neuropharm.2019.107933 | url = http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf}}</ref> It also substitutes for [[LSD]] in rodent [[drug discrimination]] tests.<ref name="HalberstadtChathaKlein2020" /> DOM is widely used as a psychedelic training drug in rodent drug discrimination assays and many other [[serotonergic psychedelic]]s have been shown to generalize to it.<ref name="HalberstadtChathaKlein2020" />

In contrast to [[amphetamine-type stimulant|amphetamine]]s like [[(–)-cathinone]] but similarly to [[mescaline]], DOM has shown no [[stimulant]]-like or [[positive reinforcement|reinforcing]] effects in rhesus monkeys.<ref name="FantegrossiMurnaneReissig2008">{{cite journal | vauthors = Fantegrossi WE, Murnane KS, Reissig CJ | title = The behavioral pharmacology of hallucinogens | journal = Biochem Pharmacol | volume = 75 | issue = 1 | pages = 17–33 | date = January 2008 | pmid = 17977517 | pmc = 2247373 | doi = 10.1016/j.bcp.2007.07.018 | url = | quote = Despite the reasonably constant recreational use of hallucinogens since at least the early 1970s [44], the reinforcing effects of hallucinogens have not been widely investigated in laboratory animals. Indeed, one of the earliest studies on the reinforcing effects of drugs using the intravenous self-administration procedure in rhesus monkeys found that no animal initiated self-injection of mescaline either spontaneously or after one month of programmed administration [45]. Likewise, the phenethylamine hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) was not effective in maintaining self-administration in rhesus monkeys [46]. Nevertheless, the hallucinogen-like phenethylamine 3,4-methylenedioxymethamphetamine (MDMA) has been shown to act as a reinforcer in intravenous self-administration paradigms in baboons [47], rhesus monkeys [48 – 50], rats [51] and mice [52]. }}</ref><ref name="CanalMurnane2017">{{cite journal | vauthors = Canal CE, Murnane KS | title = The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens | journal = J Psychopharmacol | volume = 31 | issue = 1 | pages = 127–143 | date = January 2017 | pmid = 27903793 | doi = 10.1177/0269881116677104 | pmc = 5445387 | url = | quote = One of the earliest studies on the reinforcing effects of drugs using the intravenous self-administration procedure in rhesus monkeys found that no animal initiated self-injection of mescaline either spontaneously or after one month of programmed administration, [...] (Deneau et al., 1969). The lack of mescaline self-administration stood in contrast to positive findings of self-administration of morphine, codeine, cocaine, amphetamine, pentobarbital, ethanol, and caffeine. A subsequent study with rhesus monkeys using 2,5-dimethoxy-4-methylamphetamine (DOM; Yanagita, 1986) provided similar results as the mescaline study. These findings have withstood the test of time, as the primary literature is virtually devoid of any accounts of self-administration of [classical hallucinogens (CH)], suggesting that there are very limited conditions under which laboratory animals voluntarily consume CH. }}</ref><ref name="Yanagita1986">{{cite journal | vauthors = Yanagita T | title = Intravenous self-administration of (-)-cathinone and 2-amino-1-(2,5-dimethoxy-4-methyl)phenylpropane in rhesus monkeys | journal = Drug Alcohol Depend | volume = 17 | issue = 2–3 | pages = 135–141 | date = June 1986 | pmid = 3743404| doi = 10.1016/0376-8716(86)90004-9 | url = }}</ref><ref name="Maguire2024">{{cite journal | vauthors = Maguire DR | title = Evaluation of potential punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in rhesus monkeys responding under a choice procedure | journal = Behav Pharmacol | volume = 35 | issue = 7 | pages = 378–385 | date = October 2024 | pmid = 39052019 | doi = 10.1097/FBP.0000000000000787 | pmc = 11398979 | pmc-embargo-date = October 1, 2025 | url = }}</ref> Conversely however, [[DOC (drug)|DOC]] has shown reinforcing effects, including [[conditioned place preference]] (CPP) and [[self-administration]], in rodents similarly to [[methamphetamine]].<ref name="ChaJeonJang2018">{{cite journal | vauthors = Cha HJ, Jeon SY, Jang HJ, Shin J, Kim YH, Suh SK | title = Rewarding and reinforcing effects of 4-chloro-2,5-dimethoxyamphetamine and AH-7921 in rodents | journal = Neurosci Lett | volume = 676 | issue = | pages = 66–70 | date = May 2018 | pmid = 29626650 | doi = 10.1016/j.neulet.2018.04.009 | url = }}</ref> This is analogous to other findings in which various [[2C (psychedelics)|2C]] and [[NBOMe]] [[drug]]s have been found to produce [[dopaminergic]] elevations and reinforcing effects in rodents.<ref name="Gil-MartinsBarbosaBorges2025">{{cite journal | vauthors = Gil-Martins E, Barbosa DJ, Borges F, Remião F, Silva R | title = Toxicodynamic insights of 2C and NBOMe drugs - Is there abuse potential? | journal = Toxicol Rep | volume = 14 | issue = | pages = 101890 | date = June 2025 | pmid = 39867514 | doi = 10.1016/j.toxrep.2025.101890 | url = | pmc = 11762925 | bibcode = 2025ToxR...1401890G }}</ref><ref name="KimMaHur2021">{{cite journal | vauthors = Kim YJ, Ma SX, Hur KH, Lee Y, Ko YH, Lee BR, Kim SK, Sung SJ, Kim KM, Kim HC, Lee SY, Jang CG | title = New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents | journal = Arch Toxicol | volume = 95 | issue = 4 | pages = 1413–1429 | date = April 2021 | pmid = 33515270 | doi = 10.1007/s00204-021-02980-x | bibcode = 2021ArTox..95.1413K | url = }}</ref><ref name="CustodioSaysonBotanas2020">{{cite journal | vauthors = Custodio RJ, Sayson LV, Botanas CJ, Abiero A, You KY, Kim M, Lee HJ, Yoo SY, Lee KW, Lee YS, Seo JW, Ryu IS, Kim HJ, Cheong JH | title = 25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential | journal = Addict Biol | volume = 25 | issue = 6 | pages = e12850 | date = November 2020 | pmid = 31749223 | doi = 10.1111/adb.12850 | url = }}</ref><ref name="SeoHurKo2019">{{cite journal | vauthors = Seo JY, Hur KH, Ko YH, Kim K, Lee BR, Kim YJ, Kim SK, Kim SE, Lee YS, Kim HC, Lee SY, Jang CG | title = A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents | journal = Brain Res Bull | volume = 152 | issue = | pages = 19–26 | date = October 2019 | pmid = 31279579 | doi = 10.1016/j.brainresbull.2019.07.002 | url = }}</ref><ref name="JoJooYoun2022">{{cite journal | vauthors = Jo C, Joo H, Youn DH, Kim JM, Hong YK, Lim NY, Kim KS, Park SJ, Choi SO | title = Rewarding and Reinforcing Effects of 25H-NBOMe in Rodents | journal = Brain Sci | volume = 12 | issue = 11 | date = November 2022 | page = 1490 | pmid = 36358416 | pmc = 9688077 | doi = 10.3390/brainsci12111490 | doi-access = free | url = }}</ref><ref name="LeeHurHwang2023">{{cite journal | vauthors = Lee JG, Hur KH, Hwang SB, Lee S, Lee SY, Jang CG | title = Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System | journal = ACS Chem Neurosci | volume = 14 | issue = 15 | pages = 2658–2666 | date = August 2023 | pmid = 37463338 | doi = 10.1021/acschemneuro.3c00196 | url = }}</ref><ref name="KimKookMa2024">{{cite journal | vauthors = Kim YJ, Kook WA, Ma SX, Lee BR, Ko YH, Kim SK, Lee Y, Lee JG, Lee S, Kim KM, Lee SY, Jang CG | title = The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents | journal = Arch Pharm Res | volume = 47 | issue = 4 | pages = 360–376 | date = April 2024 | pmid = 38551761 | doi = 10.1007/s12272-024-01491-4 | url = }}</ref>

===Pharmacokinetics===
According to [[Alexander Shulgin]], the effects of DOM typically last 14 to 20 hours, though other clinical trials indicate a duration of 7 to 8 hours.<ref name=Snyder />

[[Metabolite]]s of DOM like 2-''O''-desmethyl-DOM (2-DM-DOM) and 5-''O''-desmethyl-DOM (5-DM-DOM) are [[pharmacology|pharmacologically active]] and show [[psychedelic drug|psychedelic]]-like effects in [[animal study|animal studies]].<ref name="Glennon2017">{{cite journal | vauthors = Glennon RA | title = The 2014 Philip S. Portoghese Medicinal Chemistry Lectureship: The "Phenylalkylaminome" with a Focus on Selected Drugs of Abuse | journal = J Med Chem | volume = 60 | issue = 7 | pages = 2605–2628 | date = April 2017 | pmid = 28244748 | pmc = 5824997 | doi = 10.1021/acs.jmedchem.7b00085 | url = }}</ref><ref name="EcklerChang-FongRabin2003">{{cite journal | vauthors = Eckler JR, Chang-Fong J, Rabin RA, Smith C, Teitler M, Glennon RA, Winter JC | title = Behavioral characterization of 2-O-desmethyl and 5-O-desmethyl metabolites of the phenylethylamine hallucinogen DOM | journal = Pharmacol Biochem Behav | volume = 75 | issue = 4 | pages = 845–852 | date = July 2003 | pmid = 12957227 | doi = 10.1016/s0091-3057(03)00159-x | url = }}</ref> They might contribute to the delayed [[onset of action|onset]] and long [[duration of action|duration]] of DOM.<ref name="EcklerChang-FongRabin2003" /><ref name="Glennon2017" /> However, these metabolites might also produce [[drug metabolism|metabolism]]-dependent [[neurotoxicity]].<ref name="Glennon2017" />

==Chemistry==
[[File:DOM, STP (Serenity, Tranquillity & Peace) - 53627337701.jpg|thumb|Sample of DOM.]]

DOM, also known as 2,5-dimethoxy-4-methylamphetamine or as 2,5-dimethoxy-4-methyl-α-methylphenethylamine, is a [[substituted phenethylamine]] and [[substituted amphetamine|amphetamine]] and is a member of the [[DOx]] group of drugs.<ref name="ShulginManningDaley2011" /><ref name="PiHKAL1991" /><ref name="WillsErickson2012" /><ref name="Shulgin1978" /> It is [[structural analog|structurally related]] to the [[natural product|naturally occurring]] phenethylamine psychedelic [[mescaline]] (3,4,5-trimethoxyphenethylamine).<ref name="Shulgin1978" /><ref name="HassanBoschSingh2017">{{cite journal | vauthors = Hassan Z, Bosch OG, Singh D, Narayanan S, Kasinather BV, Seifritz E, Kornhuber J, Quednow BB, Müller CP | title = Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs | journal = Front Psychiatry | volume = 8 | issue = | pages = 152 | date = 2017 | pmid = 28868040 | pmc = 5563308 | doi = 10.3389/fpsyt.2017.00152 | doi-access = free | url = | quote = The next, even though less accidental, producer of NPS hallucinogens was Alexander T. Shulgin, who synthesized hundreds of novel hallucinogenic tryptamines and phenylethylamines in his home laboratory. He described the synthesis of these compounds and also their psychotomimetic effects experienced in self-experiments in detail in his books PIHKAL and TIHKAL (199, 200). He created several dimethoxy-substituted phenylethylamines, such as DOM, 2,5-dimethoxy-4-bromoamphetamine (DOB), 2,5-dimethoxy-4-iodoamphetamine (DOI), and 2,5-dimethoxy-4-ethylamphetamine (DOET), which all display strong hallucinogenic properties. These drugs usually have much longer durations of action (12–30 h) and are much more potent agonists at 5-HT2A-Rs (50- to 175-fold) compared to their related phenylethylamine derivative mescaline (duration of action: 4–8 h) (189, 199, 200). }}</ref> [[Structural analog|Analogue]]s of DOM include other DOx drugs such as [[2,5-dimethoxy-4-ethylamphetamine|DOET]], [[2,5-dimethoxy-4-bromoamphetamine|DOB]], [[2,5-dimethoxy-4-iodoamphetamine|DOI]], [[2,5-dimethoxy-4-chloroamphetamine|DOC]], and [[2,4,5-trimethoxyamphetamine|TMA]], among others.<ref name="Shulgin1978" /> The α-desmethyl or phenethylamine analogue of DOM is [[2C-D]].<ref name="ShulginManningDaley2011" /><ref name="PiHKAL1991" /> [[Ariadne (drug)|Ariadne]] is the α-ethyl or [[phenylisobutylamine]] analogue of DOM.<ref name="CunninghamBockSerrano2023">{{cite journal | vauthors = Cunningham MJ, Bock HA, Serrano IC, Bechand B, Vidyadhara DJ, Bonniwell EM, Lankri D, Duggan P, Nazarova AL, Cao AB, Calkins MM, Khirsariya P, Hwu C, Katritch V, Chandra SS, McCorvy JD, Sames D | title = Pharmacological Mechanism of the Non-hallucinogenic 5-HT<sub>2A</sub> Agonist Ariadne and Analogs | journal = ACS Chemical Neuroscience | volume = 14 | issue = 1 | pages = 119–135 | date = January 2023 | pmid = 36521179 | pmc = 10147382 | doi = 10.1021/acschemneuro.2c00597 }}</ref><ref name="PiHKAL1991" />

[[Image:DOM-25-varients.png|280px|thumb|right|Chemical structures of some DOM variants]]

The 2,6-dimethoxy positional isomer of DOM, known as [[Psi-DOM|Ψ-DOM]], is also mentioned in ''PiHKAL'' as being active, as is the α-ethyl homologue [[Ariadne (psychedelic)|Ariadne]]. Analogues where the methoxy groups at the 2,5- positions of the aromatic ring have been altered have also been synthesised and tested as part of an effort to identify the binding mode of DOM at the serotonin [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]]. Both the 2- and 5- O-desmethyl derivatives 2-DM-DOM and 5-DM-DOM, and the 2- and 5- ethyl analogues 2-Et-DOM and 5-Et-DOM, have been tested, but in all cases were significantly less potent than the corresponding methoxy compound, showing the importance of the oxygen lone pairs in 5-HT<sub>2A</sub> binding.<ref name="EcklerChang-FongRabin2003" /><ref name="Braden2007">{{Cite thesis |title=Towards a Biophysical Basis of Hallucinogen Action |url=https://books.google.com/books?id=sz4zbKBniZQC |last=Braden |first=Michael Robert |date=May 2007 |publisher=Purdue University |access-date=28 February 2012 |oclc=703618147 }}</ref>

==History==
STP was first synthesized and tested in 1963 by [[Alexander Shulgin]], who was investigating the effect of 4-position substitutions on psychedelic amphetamines.<ref name="Baggott2023" /><ref name="PiHKAL1991" />

In mid-1967, tablets containing 20{{nbsp}}mg (later 10{{nbsp}}mg) of STP were widely distributed in the [[Haight-Ashbury|Haight-Ashbury District]] of [[San Francisco]] under the name of STP, having been manufactured by underground chemists [[Owsley Stanley]] and [[Tim Scully]].<ref name="Baggott2023" /> This short-lived appearance of STP on the [[black market]] proved disastrous for several reasons.<ref name="Baggott2023" /> First, the tablets contained an excessively high dose of the chemical.<ref name="Baggott2023" /> This, combined with DOM's slow [[onset of action]] (which encouraged some users, familiar with drugs that have quicker onsets, such as [[LSD]], to re-dose) and its remarkably long [[duration of action|duration]], caused many users to [[panic attack|panic]] and sent some to the [[emergency room]].<ref name="Baggott2023" /> Second, treatment of such [[overdose]]s was complicated by the fact that no one at the time knew that the tablets called STP were, in fact, DOM, and there was no effective [[antidote]].<ref name="Baggott2023" />

==Society and culture==
===Legal status===
====Australia====
DOM is schedule 9 under the Australia [[Standard for the Uniform Scheduling of Medicines and Poisons|Poisons standard]].<ref name="Poisons Standard">Poison Standard https://www.comlaw.gov.au/Details/F2015L01534/Html/Text#_Toc420496379 {{webarchive|url=https://web.archive.org/web/20151222222450/https://www.comlaw.gov.au/Details/F2015L01534/Html/Text |date=2015-12-22 }}</ref> A schedule 9 substance is a "Substances which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities."<ref name="Poisons Standard" />

====Canada====
Listed as a [[Controlled Drugs and Substances Act#Schedule I|Schedule 1]], as it is an analogue of amphetamine.

====United Kingdom====
DOM is a [[Class A drug]] in the United Kingdom under the [[Misuse of Drugs Act 1971]].

====United States====
DOM is Schedule I in the United States. This means it is illegal to manufacture, buy, possess, or distribute (make, trade, own or give) without a DEA license.

==See also==
* [[ASR-2001]]

==References==
{{Reflist}}

==External links==
* [https://isomerdesign.com/pihkal/explore/68 DOM - Isomer Design]
* [https://psychonautwiki.org/wiki/DOM DOM - PsychonautWiki]
* [http://www.erowid.org/chemicals/dom/dom.shtml Erowid DOM Vault]
* [http://www.erowid.org/library/books_online/pihkal/pihkal068.shtml DOM - PiHKAL - Erowid]
* [http://pihkal.info/read.php?domain=pk&id=68 DOM - PiHKAL - Isomer Design]
* [https://tripsitter.com/dom/ What is DOM? The Serenity Psychedelic - Tripsitter]

{{Psychedelics}}
{{Serotonin receptor modulators}}
{{TAAR modulators}}
{{Phenethylamines}}

{{DEFAULTSORT:Dimethoxy-4-methylamphetamine, 2,5-}}
[[Category:5-HT2A agonists]]
[[Category:5-HT2B agonists]]
[[Category:5-HT2C agonists]]
[[Category:Alexander Shulgin]]
[[Category:Designer drugs]]
[[Category:DOx (psychedelics)]]
[[Category:Psychedelic phenethylamines]]
[[Category:TAAR1 agonists]]