2,5-Dimethoxy-4-chloroamphetamine

Chemical compound vanc 6 verified verified 477211612 DOC DOC2DACS.svg skin-invert-image 225px 2,5-Dimethoxy-4-chloroamphetamine molecule ball.png bg-transparent 200px Ball-and-stick model of the 2,5-Dimethoxy-4-chloroamphetamine molecule Oral Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen Unscheduled F2 Anvisa Brazilian Health Regulatory Agency 2023-07-24 RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 live 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 2023-08-27 2023-08-27 Diário Oficial da União pt-BR 2023-07-25 Schedule I Anlage I Class A Unscheduled P I 12–24 hours correct CAS 123431-31-2 correct FDA 8Y1C6K0PCA 542036 correct kegg C22719 correct chemspider 472008 correct EBI 8100 DOC; 2,5-Dimethoxy-4-chloroamphetamine; 4-Chloro-2,5-dimethoxyamphetamine 1-(4-Chloro-2,5-dimethoxyphenyl)propan-2-amine 11 16 1 1 2 ClC1=C(OC)C=C(CC(C)N)C(OC)=C1 correct chemspider 1S/C11H16ClNO2/c1-7(13)4-8-5-11(15-3)9(12)6-10(8)14-2/h5-7H,4,13H2,1-3H3 correct chemspider ACRITBNCBMTINK-UHFFFAOYSA-N 2,5-Dimethoxy-4-chloroamphetamine (DOC) is a psychedelic drug of the phenethylamine, amphetamine, and DOx families. PiHKAL: A Chemical Love Story Shulgin A, Shulgin A Transform Press United States 0-9630096-0-5 978 http://www.erowid.org/library/books_online/pihkal/pihkal.shtml 30 November 2009 https://web.archive.org/web/20100103030739/http://www.erowid.org/library/books_online/pihkal/pihkal.shtml 3 January 2010 live September 1991 It is taken orally. The drug acts as a serotonin 5-HT2 receptor agonist, including of the serotonin 5-HT2A receptor. Analogues of DOC include 2C-C, DOB, DOI, DOM, among others. DOC was first described in the scientific literature by Ronald Coutts and Jerry Malicky in 1973. Coutts RT, Malicky JL The Synthesis of Some Analogs of the Hallucinogen 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM) Canadian Journal of Chemistry 51 9 1402–1409 1 May 1973 10.1139/v73-210 0008-4042 https://cdnsciencepub.com/doi/10.1139/v73-210 27 November 2025 Subsequently, it was described in greater detail by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). Recreational availability and use of DOC are rare. Palamar JJ, Fitzgerald ND The Epidemiology of Recreational Use and Availability of DOC and DOI in the United States Journal of Psychoactive Drugs 1–10 October 2025 41065346 10.1080/02791072.2025.2570937 12645445 The drug is expected to become a controlled substance in the United States in the near future as of 2025. Use and effects In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists DOC's dose as 1.5 to 3mg orally and its duration as 12 to 24hours. The effects of DOC have been reported to include closed-eye imagery, visuals, introspection, lightheadedness, disconnectedness, and spaciness, among others. In one of the reports, it was described as an "archetypical psychedelic", with the full spectrum of psychedelic effects. This was contrasted with 2C psychedelics, which were described as more subtle and gentle. Toxicity Very little data exists about the toxicity of DOC. In April 2013, a case of death due to DOC was reported. The source does not specify whether the drug alone caused the death. Bucks J 2013-04-25 "Moment of madness": rare drug implicated in student death The Saint http://www.thesaint-online.com/2013/04/moment-of-madness-rare-drug-implicated-in-student-death/ dead 2013-04-25 https://web.archive.org/web/20130428055435/http://www.thesaint-online.com/2013/04/moment-of-madness-rare-drug-implicated-in-student-death/ 2013-04-28 dmy-all In 2014, a death was reported in which DOC was directly implicated as the sole causative agent in the death of a user. The autopsy indicated pulmonary edema and a subgaleal hemorrhage. Barnett RY, Baker DD, Kelly NE, McGuire CE, Fassette TC, Gorniak JM A fatal intoxication of 2,5-dimethoxy-4-chloroamphetamine: a case report Journal of Analytical Toxicology 38 8 589–91 October 2014 25217551 10.1093/jat/bku087 free Interactions Psychedelic drug#Interactions Trip killer#Serotonergic psychedelic antidotes Pharmacology Pharmacodynamics Actions + DOC activities Target Affinity (Ki, nM) 5-HT1A 5,353–>9,200 (Ki)>10,000 (EC50 half-maximal effective concentration)<10% (Emax maximal efficacy) 5-HT1B ND No data 5-HT1D ND No data 5-HT1E ND No data 5-HT1F ND No data 5-HT2A 1.4–12 (Ki)0.6–11 (EC50 half-maximal effective concentration)58–102% (Emax maximal efficacy) 5-HT2B 32 (Ki)46 (EC50 half-maximal effective concentration)83% (Emax maximal efficacy) 5-HT2C 2–143 (Ki)15 (EC50 half-maximal effective concentration)97% (Emax maximal efficacy) 5-HT3 ND No data 5-HT4 ND No data 5-HT5A ND No data 5-HT6 ND No data 5-HT7 ND No data α1A >1,000 α1B–α1D ND No data α2A >1,000 α2B–α2C ND No data β1–β3 ND No data D1 ND No data D2 >1,000 D3–D5 ND No data TAAR1 >1,000 SERT Serotonin transporter >10,000 (Ki)>8,600 (IC50 half-maximal inhibitory concentration)Minimal (EC50 half-maximal inhibitory concentration) NET Norepinephrine transporter >7,700 (Ki)>8,400 (IC50 half-maximal inhibitory concentration)Minimal (EC50 half-maximal inhibitory concentration) DAT Dopamine transporter >10,000 (Ki)>10,000 (IC50 half-maximal inhibitory concentration)Minimal (EC50 half-maximal inhibitory concentration) Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: PDSP Database UNC https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=doc&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query zu 1 February 2025 Liu T BindingDB BDBM50013000 CHEMBL8100 Journal of Medicinal Chemistry 1990 33 3 1032–1036 10.1021/jm00165a023 2308135 https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50013000 1 February 2025 Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function Psychopharmacology (Berl) 231 5 875–888 March 2014 24142203 3945162 10.1007/s00213-013-3303-6 Rudin D, Luethi D, Hoener MC, Liechti ME Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α-Desmethyl (2C) Analogues The FASEB Journal 36 S1 2022 fasebj.2022.36.S1.R2121 0892-6638 10.1096/fasebj.2022.36.S1.R2121 free https://www.researchgate.net/publication/360423277 DOC acts as a serotonin 5-HT2A and 5-HT2C receptor agonist. Its psychedelic effects are mediated via its actions on the 5-HT2A receptor.June 2023 The drug is inactive as a monoamine releasing agent and reuptake inhibitor. Effects DOC produces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents. Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species Neuropharmacology 167 107933 May 2020 31917152 9191653 10.1016/j.neuropharm.2019.107933 http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf 2025-03-26 2025-03-27 https://web.archive.org/web/20250326111621/http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf dead DOC has shown reinforcing effects, including conditioned place preference (CPP) and self-administration, in rodents similarly to methamphetamine. Cha HJ, Jeon SY, Jang HJ, Shin J, Kim YH, Suh SK Rewarding and reinforcing effects of 4-chloro-2,5-dimethoxyamphetamine and AH-7921 in rodents Neurosci Lett 676 66–70 May 2018 29626650 10.1016/j.neulet.2018.04.009 This is analogous to other findings in which various 2C and NBOMe drugs have been found to produce dopaminergic elevations and reinforcing effects in rodents. Gil-Martins E, Barbosa DJ, Borges F, Remião F, Silva R Toxicodynamic insights of 2C and NBOMe drugs - Is there abuse potential? Toxicol Rep 14 101890 June 2025 39867514 10.1016/j.toxrep.2025.101890 11762925 2025ToxR...1401890G Kim YJ, Ma SX, Hur KH, Lee Y, Ko YH, Lee BR, Kim SK, Sung SJ, Kim KM, Kim HC, Lee SY, Jang CG New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents Arch Toxicol 95 4 1413–1429 April 2021 33515270 10.1007/s00204-021-02980-x 2021ArTox..95.1413K 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 25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential Addict Biol 25 6 e12850 November 2020 31749223 10.1111/adb.12850 free Seo JY, Hur KH, Ko YH, Kim K, Lee BR, Kim YJ, Kim SK, Kim SE, Lee YS, Kim HC, Lee SY, Jang CG A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents Brain Res Bull 152 19–26 October 2019 31279579 10.1016/j.brainresbull.2019.07.002 Jo C, Joo H, Youn DH, Kim JM, Hong YK, Lim NY, Kim KS, Park SJ, Choi SO Rewarding and Reinforcing Effects of 25H-NBOMe in Rodents Brain Sci 12 11 November 2022 1490 36358416 9688077 10.3390/brainsci12111490 free Lee JG, Hur KH, Hwang SB, Lee S, Lee SY, Jang CG Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System ACS Chem Neurosci 14 15 2658–2666 August 2023 37463338 10.1021/acschemneuro.3c00196 Kim YJ, Kook WA, Ma SX, Lee BR, Ko YH, Kim SK, Lee Y, Lee JG, Lee S, Kim KM, Lee SY, Jang CG The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents Arch Pharm Res 47 4 360–376 April 2024 38551761 10.1007/s12272-024-01491-4 Conversely however, in contrast to amphetamines like (−)-cathinone but similarly to mescaline, DOM has shown no stimulant-like or reinforcing effects in rhesus monkeys. Fantegrossi WE, Murnane KS, Reissig CJ The behavioral pharmacology of hallucinogens Biochem Pharmacol 75 1 17–33 January 2008 17977517 2247373 10.1016/j.bcp.2007.07.018 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]. Canal CE, Murnane KS The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens J Psychopharmacol 31 1 127–143 January 2017 27903793 10.1177/0269881116677104 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. 5445387 Yanagita T Intravenous self-administration of (−)-cathinone and 2-amino-1-(2,5-dimethoxy-4-methyl)phenylpropane in rhesus monkeys Drug Alcohol Depend 17 2–3 135–141 June 1986 3743404 10.1016/0376-8716(86)90004-9 Maguire DR Evaluation of potential punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in rhesus monkeys responding under a choice procedure Behav Pharmacol 35 7 378–385 October 2024 39052019 10.1097/FBP.0000000000000787 11398979 Chemistry DOC is a substituted α-methylated phenethylamine, a class of compounds commonly known as amphetamines. The phenethylamine equivalent (lacking the α-methyl group) is 2C-C. DOC has a stereocenter and (R)-(−)-DOC is the more active stereoisomer. Synthesis The chemical synthesis of DOC has been described. Detection DOC may be quantitated in blood, plasma or urine by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma DOC concentrations are expected to be in a range of 1–10 μg/L in persons using the drug recreationally, >20 μg/L in intoxicated patients and >100 μg/L in victims of acute overdosage.Disposition of toxic drugs and chemicals in man Baselt RC Biomedical Publications 2014 978-0-9626523-9-4 Seal Beach, California 2173 en Analogues Analogues of DOC include DOB, DOI, 2C-C, DODC, and ZDCM-04, among others. History DOC was first described in the scientific literature by Ronald Coutts and Jerry Malicky in 1973. Subsequently, it was described in greater detail by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines i Have Known And Loved). Society and culture Popularity Although rare on the black market, it has been available in bulk and shipped worldwide by select elite "Grey Market" Research Chemical suppliers for several years. Sales of DOC on blotting paper and in capsules was reported in late 2005 and again in late 2007. According to the DEA's Microgram from December 2007, the Concord Police Department in Contra Costa County, California, in the US, seized "a small piece of crudely lined white blotter paper without any design, suspected LSD 'blotter acid'". They added "Unusually, the paper appeared to be hand-lined using two pens, in squares measuring approximately 6 x 6 millimeters. The paper displayed fluorescence when irradiated at 365 nanometers; however, color testing for LSD with para-dimethylaminobenzaldehyde (Ehrlich's reagent) was negative. Analysis of a methanol extract by GC/MS indicated not LSD but rather DOC (not quantitated but a high loading based on the TIC)".https://www.justice.gov/dea/pr/micrograms/2007/mg1207.pdf mg1207 2013-08-13 https://web.archive.org/web/20121017234332/http://www.justice.gov/dea/pr/micrograms/2007/mg1207.pdf 2012-10-17 dead DOC is sometimes misrepresented as LSD by unscrupulous dealers. This is particularly dangerous, as DOC is not known to have the safety profile of LSD. It can be particularly unsafe, in comparison to LSD, for those suffering from hypertension, as amphetamine compounds are known to cause sharp increases in systolic blood pressure. Legal status International In December 2019, the UNODC announced scheduling recommendations placing DOC into Schedule I alongside another several research chemicals.https://www.unodc.org/LSS/Announcement/Details/021820a0-8746-42a4-9ee3-47ce50b30ca3 December 2019 – WHO: World Health Organization recommends 12 NPS for scheduling Australia Unscheduled but can be controlled as schedule II as an analogue of DOB.http://www.erowid.org/chemicals/doc/doc_law.shtml Erowid DOC Vault: Legal Status 22 April 2008 https://web.archive.org/web/20080501231821/http://www.erowid.org/chemicals/doc/doc_law.shtml 1 May 2008 live Canada Listed as a Schedule 12022-03-31 Schedule I http://isomerdesign.com/Cdsa/schedule.php?schedule=1&section=18.5&structure=C live https://archive.today/20220331223632/http://isomerdesign.com/Cdsa/schedule.php?schedule=1&section=18.5&structure=C 2022-03-31 2022-03-31 Controlled Drugs and Substances Act Canadian Legal Information Institute as it is an analogue of amphetamine.Controlled Drugs and Substances Act http://isomerdesign.com/Cdsa/definitions.php?structure=C Definitions and interpretations Canadian Legal Information Institute 2022-03-31 2013-11-10 https://web.archive.org/web/20131110213450/http://isomerdesign.com/Cdsa/definitions.php?structure=C dead The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1. Backgrounder: The Safe Streets and Communities Act Four Components Coming Into Force Canadian Department of Justice http://www.justice.gc.ca/eng/news-nouv/nr-cp/2012/doc_32759.html https://web.archive.org/web/20121018122345/http://www.justice.gc.ca/eng/news-nouv/nr-cp/2012/doc_32759.html 2012-10-18 China As of October 2015 DOC is a controlled substance in China.http://www.sfda.gov.cn/WS01/CL0056/130753.html 关于印发《非药用类麻醉药品和精神药品列管办法》的通知 China Food and Drug Administration 27 September 2015 zh 1 October 2015 https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html 1 October 2015 dead Denmark Denmark added DOC to the list of Schedule I controlled substances as of 8.4.2007. Germany Scheduled in Anlage I since 22.1.2010. New Zealand Scheduled. Sweden Sveriges riksdag added DOC to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of Aug 30, 2007, published by Medical Products Agency in their regulation LVFS 2007:10 listed as DOC, 4-klor-2,5-dimetoxi-amfetamin.http://www.lakemedelsverket.se/upload/lvfs/LVFS_2007-10.pdf Läkemedelsverkets föreskrifter - LVFS och HSLF-FS | Läkemedelsverket DOC was first classified by Sveriges riksdags health ministry Statens folkhälsoinstitut as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Jul 1, 2004, in their regulation SFS 2004:486 listed as 4-klor-2,5-dimetoxiamfetamin (DOC).Förordning om ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor http://www.notisum.se/rnp/sls/sfs/20040486.pdf https://web.archive.org/web/20180915141627/http://www.notisum.se/rnp/sls/sfs/20040486.pdf 15 September 2018 Swedish 27 May 2004 United Kingdom Class A. United States DOC is not scheduled or controlled at the federal level in the United States,http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm PART 1308 - Section 1308.11 Schedule I www.deadiversion.usdoj.gov 31 March 2018 27 August 2009 https://web.archive.org/web/20090827043725/http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm dead but the Department of Justice considers it to be an analogue of DOBhttps://www.justice.gov/dea/pr/micrograms/2007/mg1007.pdf DEA Resources, Microgram, October 2007 2012-10-03 https://web.archive.org/web/20121017234351/http://www.justice.gov/dea/pr/micrograms/2007/mg1007.pdf 2012-10-17 dead and, as such, possession or sale could be prosecuted under the Federal Analogue Act. In December 2023, the US Drug Enforcement Administration issued a notice of proposed rulemaking that would classify both 2,5-dimethoxy-4-chloroamphetamine and 2,5-dimethoxy-4-iodoamphetamine as schedule I controlled substances.https://www.regulations.gov/document/DEA-2022-0026-0001/comment Schedules of Controlled Substances: Placement of 2,5-dimethoxy-4-iodoamphetamine (DOI) and 2,5-dimethoxy-4-chloroamphetamine (DOC) in Schedule I www.regulations.gov In the United States, the analogues DMA, DOB, and DOM are Schedule I controlled substances. Florida DOC is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess.http://leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&URL=0800-0899/0893/0893.html The 2017 Florida Statutes - Title XLVI - CRIMES - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL leg.state.fl.us 31 March 2018 See also DOx (psychedelics) References External links DOC - Isomer Design DOC - PsychonautWiki DOC - Erowid DOC - PiHKAL - Erowid DOC - PiHKAL - Isomer Design DOC - The Shulgin Index DOC (4-Chloro-2,5-Dimethoxyamphetamine): Everything You Need to Know - Tripsitter Category:5-HT2A agonists Category:5-HT2B agonists Category:5-HT2C agonists Category:Chlorobenzene derivatives Category:Designer drugs Category:DOx (psychedelics) Category:PiHKAL Category:Psychedelic phenethylamines