View source for 2C-D

{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477216133
| drug_name = 
| image = 2C-D 2DACS.svg
| image_class = skin-invert-image
| width = 200px
| caption = 
| image2 = 2C-D-3d-sticks.png
| image_class2 = bg-transparent
| width2 = 175px

<!-- 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 = [[Oral administration|Oral]]<ref name="PiHKAL" /><ref name="ShulginCarter1975" />
| class = [[Serotonin]] [[5-HT2 receptor|5-HT<sub>2</sub> receptor]] [[agonist]]; [[Serotonin 5-HT2A receptor agonist|Serotonin 5-HT<sub>2A</sub> receptor agonist]]; [[Serotonergic psychedelic]]; [[Hallucinogen]]; [[Stimulant]]; [[Cognitive enhancer]]
| ATC_prefix = 
| ATC_suffix = 

<!-- Legal status -->
| legal_AU = 
| legal_BR = F2
| legal_CA = Schedule III
| legal_DE = Anlage I
| legal_US = Schedule I
| legal_status = 

<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 
| metabolism = 
| metabolites = 
| onset = 20–30 minutes<ref name="ShulginCarter1975" />
| elimination_half-life = 
| duration_of_action = 4–6 hours<ref name="PiHKAL" /><ref name="ShulginCarter1975" />
| excretion = 

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 24333-19-5
| CAS_supplemental = 
| PubChem = 135740
| PubChemSubstance = 
| IUPHAR_ligand = 
| DrugBank = 
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 119559
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 7J43GY6ONS
| KEGG = 
| ChEBI = 
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 124049
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = 4-Methyl-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-methyl-phenethylamine; 2C-M; 2C-DOM; LE-25; LE25; DMMPEA; DMM-PEA

<!-- Chemical data -->
| IUPAC_name = 2-(2,5-dimethoxy-4-methylphenyl)ethan-1-amine
| C=11 | H=17 | N=1 | O=2 
| SMILES = O(c1cc(c(OC)cc1CCN)C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C11H17NO2/c1-8-6-11(14-3)9(4-5-12)7-10(8)13-2/h6-7H,4-5,12H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UNQQFDCVEMVQHM-UHFFFAOYSA-N

<!-- Physical data -->
| melting_point = 213
| melting_high = 214
| melting_notes = ([[hydrochloride]])
}}

'''2C-D''', also known as '''4-methyl-2,5-dimethoxyphenethylamine''', is a [[psychedelic drug]] of the [[substituted phenethylamine|phenethylamine]] and [[2C (psychedelics)|2C]] families.<ref name="PiHKAL">{{CitePiHKAL}} https://www.erowid.org/library/books_online/pihkal/pihkal023.shtml</ref> It has an unusually wide and gradual dose range and at low doses produces claimed [[nootropic|cognitive enhancer]]-like effects, mild [[stimulant]] effects, and mild [[perception|perceptual]] effects, whereas at high doses, it produces robust psychedelic effects.<ref name="ShulginCarter1975" /><ref name="PiHKAL" /><ref name="LazarNez1990" /><ref name="Hardison2007" /> The drug is taken [[oral administration|orally]].<ref name="PiHKAL" />

It acts as an [[agonist]] of the [[serotonin]] [[5-HT2 receptor|5-HT<sub>2</sub> receptor]]s, including of the serotonin [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]].<ref name="RickliLuethiReinisch2015" /><ref name="EshlemanForsterWolfrum2014" /><ref name="MoyaBergGutiérrez-Hernandez2007" /><ref name="Acuña-CastilloVillalobosMoya2002" /> The drug is [[structural analog|structurally related]] to other psychedelic and related phenethylamines such as its higher [[structural homolog|homologue]]s [[DOM (drug)|DOM]] and [[Ariadne (drug)|Ariadne]] (4C-D) and other 2C psychedelics like [[2C-B]] and [[2C-E]].<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" />

2C-D was first described in the literature by Beng T. Ho and colleagues in 1970.<ref name="BrimblecombePinder1975" /><ref name="HoTanseyBalster1970" /> Its properties and effects in humans were described by [[Alexander Shulgin]] and colleagues in 1975.<ref name="ShulginCarter1975" /> The drug was extensively studied by [[Hanscarl Leuner]] under the names '''DMM-PEA''' and '''LE-25''' in [[psychedelic-assisted psychotherapy]] in [[Germany]] in the 1970s and 1980s.<ref name="PiHKAL" /><ref name="TiHKAL" /><ref name="PoulieJensenHalberstadt2020" /><ref name="Passie2024" /><ref name="Passie2022" /><ref name="Leuner1981" /><ref name="Schlichting1989" /> It was also informally studied by [[Darrell Lemaire]] as a potential "[[nootropic|smart drug]]" in the 1970s and 1980s.<ref name="Erowid-Lemaire" /><ref name="Morris2016-S01E06" /><ref name="Nez2010" /><ref name="LazarNez1990" /> 2C-D was first encountered as a novel [[designer drug]] by 2005.<ref name="TheobaldMaurer2006">{{cite journal | vauthors = Theobald DS, Maurer HH | title = Studies on the metabolism and toxicological detection of the designer drug 2,5-dimethoxy-4-methyl-beta- phenethylamine (2C-D) in rat urine using gas chromatographic/mass spectrometric techniques | journal = J Mass Spectrom | volume = 41 | issue = 11 | pages = 1509–1519 | date = November 2006 | pmid = 17103384 | doi = 10.1002/jms.1128 | url = | quote = 2,5-Dimethoxy-4-methyl-ˇ-phenethylamine (2C-D) was described by Alexander Shulgin as a hallucinogenic substance.2 Descriptions and experience reports on internet web sites (http//:www.erowid.org, http//:www.lycaeum.org; June 2006) indicate that 2C-D plays a role among drug abusers. Furthermore, 2C-D was identified on the illicit drug market in the US.3–5 In most countries, 2C-D is not a controlled substance. This fact may enhance its popularity among drug abusers because the more popular members of the 2C-series like 2C-B or 2C-T-7 are scheduled now in many countries.}}</ref> It became a [[controlled substance]] in the [[United States]] in 2012.<ref name="DeanStellpflugBurnett2013" />

==Use and effects==
In his book ''[[PiHKAL]]'' (''Phenethylamines I Have Known and Loved'') and other publications, [[Alexander Shulgin]] lists 2C-D's dose range as 20 to 60{{nbsp}}mg [[oral administration|orally]] and its [[duration of action|duration]] as 4 to 6{{nbsp}}hours.<ref name="PiHKAL" /><ref name="ShulginCarter1975" /> He describes threshold effects as occurring at a dose of 6{{nbsp}}mg orally and full [[drug intoxication|intoxication]] occurring at doses of 10 to 15{{nbsp}}mg orally.<ref name="ShulginCarter1975" /> Higher doses of 75 to 200{{nbsp}}mg orally have also been described and were well-tolerated.<ref name="PiHKAL" /><ref name="LazarNez1990" /> In addition, a wider [[recreational drug|recreational]] dose range of 3 to 100{{nbsp}}mg or more has been described.<ref name="LuethiLiechti2018">{{cite journal | vauthors = Luethi D, Liechti ME | title = Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics | journal = Int J Neuropsychopharmacol | volume = 21 | issue = 10 | pages = 926–931 | date = October 2018 | pmid = 29850881 | pmc = 6165951 | doi = 10.1093/ijnp/pyy047 | url = https://isomerdesign.com/bitnest/external/10.1093/ijnp/pyy047}}</ref> The [[onset of action|onset]] is said to be 20 to 30{{nbsp}}minutes and peak effects occur after 1.5 to 2{{nbsp}}hours.<ref name="ShulginCarter1975" /> [[Casey Hardison]] has described 2C-D as having a very gentle [[dose–response curve]] with an unusually wide dose range.<ref name="Hardison2007">{{cite journal | last=Hardison | first=Casey | title=A brief history and motivation of an entheogenic chemist | journal=Drugs and Alcohol Today | volume=7 | issue=2 | date=1 July 2007 | issn=1745-9265 | doi=10.1108/17459265200700013 | pages=26–31 | url=http://www.emerald.com/dat/article/7/2/26-31/102048 | quote=2C-D has a very gentle dose-response curve with a fantastically large range. 2C-D is what some have called a ‘pharmacological tofu’ (Shulgin & Shulgin, 1991).}}</ref>

The effects of 2C-D have been described.<ref name="ShulginCarter1975" /><ref name="PiHKAL" /><ref name="LazarNez1990" /> At low doses, it produces perceived [[cognitive enhancer|cognitive enhancement]], mild [[stimulant]]-like effects, [[emotion]]al integration, [[euphoria]], and mild [[psychedelic drug|psychedelic]] effects such as [[perceptual enhancement]] that are much lighter than those of conventional psychedelics.<ref name="ShulginCarter1975" /><ref name="PiHKAL" /><ref name="LazarNez1990" /> At high doses, it produces robust psychedelic effects.<ref name="PiHKAL" /> Shulgin referred to 2C-D as a "pharmacological [[tofu]]" because it didn't have especially pronounced effects on its own until very high doses were reached but could be combined with and extend or potentiate the effects of other psychedelics without coloring their experiences.<ref name="Hardison2007" /><ref name="PiHKAL" />

[[Hanscarl Leuner]], working in [[Germany]], explored the use of 2C-D under the code name LE-25 in [[psychedelic-assisted psychotherapy]] at doses of up to 150 to 200{{nbsp}}mg orally.<ref name="PiHKAL" /><ref name="TiHKAL">{{CiteTiHKAL}} "At a banquet associated with an international conference on the study of consciousness, held in Göttingen a few years ago, Alice and I had the pleasure of sitting at the table with Hanscarl Leuner and his wife. He thanked me for inventing 2C-D which he and his students had been exploring as an adjunct to psychotherapy. They had renamed it, initially DMM-PEA and then LE-25, and had apparently explored it at dosages that reached into the hundreds of milligrams. In PIHKAL, I had offered an effective range for this drug of from 20 to 60 milligrams. It would seem that in his later years, Dr. Leuner chose to move from the psycholytic camp over to the psychedelic camp."</ref><ref name="LazarNez1990" /> Low doses of 2C-D in the range of 5 to 10{{nbsp}}mg orally have been explored as a "[[nootropic|smart drug]]" by [[Darrell Lemaire]].<ref name="LazarNez1990">{{citation | author1 = Lazar ([[Darrell Lemaire]]) | author2 = Hosteen Nez | title = Certain Exotic Transmitters as Smart Pills or Compounds that Increase the Capacity for Mental Work in Humans: A Story About LAZAR as Told by Hosteen Nez | edition = 2 | date = 1990 | url = https://erowid.org/chemicals/2cd/2cd_smartpills1.pdf | archive-url = https://web.archive.org/web/20010709231503/http://www.erowid.org/chemicals/2cd/2cd_smartpills1.shtml | archive-date = 9 July 2001}}</ref><ref name="Morris2016-S01E06">{{cite episode | credits = [[Hamilton Morris|Morris H]] | date = 7 December 2016 | title = The Lazy Lizard School of Hedonism | series = [[Hamilton's Pharmacopeia]] | season = 1 | number = 6 | url = https://vimeo.com/546752807| publisher = [[Vice Media]] | network = [[Viceland]]}}</ref>

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

2C-D is [[drug metabolism|metabolized]] by the [[monoamine oxidase]] (MAO) [[enzyme]]s [[MAO-A]] and [[MAO-B]].<ref name="DeanStellpflugBurnett2013">{{cite journal | vauthors = Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM | title = 2C or not 2C: phenethylamine designer drug review | journal = J Med Toxicol | volume = 9 | issue = 2 | pages = 172–178 | date = June 2013 | pmid = 23494844 | pmc = 3657019 | doi = 10.1007/s13181-013-0295-x | url = }}</ref><ref name="TheobaldMaurer2007">{{cite journal | vauthors = Theobald DS, Maurer HH | title = Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series) | journal = Biochem Pharmacol | volume = 73 | issue = 2 | pages = 287–297 | date = January 2007 | pmid = 17067556 | doi = 10.1016/j.bcp.2006.09.022 | url = }}</ref> [[Monoamine oxidase inhibitor]]s (MAOIs) such as [[phenelzine]], [[tranylcypromine]], [[moclobemide]], and [[selegiline]] may potentiate the effects of 2C-D.<ref name="DeanStellpflugBurnett2013" /><ref name="TheobaldMaurer2007" /><ref name="HalmanKongSarris2024">{{Cite journal |vauthors=Halman A, Kong G, Sarris J, Perkins D |date=January 2024 |title=Drug-drug interactions involving classic psychedelics: A systematic review |journal=J Psychopharmacol |volume=38 |issue=1 |pages=3–18 |doi=10.1177/02698811231211219 |pmc=10851641 |pmid=37982394}}</ref> This may result in [[overdose]] and serious [[toxicity]].<ref name="HalmanKongSarris2024" /><ref name="DeanStellpflugBurnett2013" />

==Pharmacology==
===Pharmacodynamics===
{| class="wikitable floatleft" style="font-size:small;"
|+ {{Nowrap|2C-D activities}}
|-
! [[Biological target|Target]] !! [[Affinity (pharmacology)|Affinity]] (K<sub>i</sub>, nM)
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 440–1,630 (K<sub>i</sub>)<br />>10,000 ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}})<br /><25% ({{Abbrlink|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 23.9–32.4 (K<sub>i</sub>)<br />43.5–8,130 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />6–93% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || {{Abbr|ND|No data}} (K<sub>i</sub>)<br />230 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />77% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 12.7–150 (K<sub>i</sub>)<br />71.1–18,600 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />48–100% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT3 receptor|5-HT<sub>3</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT4 receptor|5-HT<sub>4</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT5A receptor|5-HT<sub>5A</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || {{Abbr|ND|No data}}
|-
| [[Alpha-1A adrenergic receptor|α<sub>1A</sub>]] || 12,000
|-
| [[Alpha-1B adrenergic receptor|α<sub>1B</sub>]], [[Alpha-1D adrenergic receptor|α<sub>1D</sub>]] || {{Abbr|ND|No data}}
|-
| [[Alpha-2A adrenergic receptor|α<sub>2A</sub>]] || 290
|-
| [[Alpha-2B adrenergic receptor|α<sub>2B</sub>]], [[Alpha-2C adrenergic receptor|α<sub>2C</sub>]] || {{Abbr|ND|No data}}
|-
| [[Beta-1 adrenergic receptor|β<sub>1</sub>]]–[[Beta-3 adrenergic receptor|β<sub>3</sub>]] || {{Abbr|ND|No data}}
|-
| [[D1 receptor|D<sub>1</sub>]] || 24,000
|-
| [[D2 receptor|D<sub>2</sub>]] || 7,100
|-
| [[D3 receptor|D<sub>3</sub>]] || >17,000
|-
| [[D4 receptor|D<sub>4</sub>]] || {{Abbr|ND|No data}}
|-
| [[D5 receptor|D<sub>5</sub>]] || {{Abbr|ND|No data}}
|-
| [[H1 receptor|H<sub>1</sub>]] || >25,000
|-
| [[H2 receptor|H<sub>2</sub>]]–[[H4 receptor|H<sub>4</sub>]] || {{Abbr|ND|No data}}
|-
| [[Muscarinic acetylcholine M1 receptor|M<sub>1</sub>]]–[[Muscarinic acetylcholine M5 receptor|M<sub>5</sub>]] || {{Abbr|ND|No data}}
|-
| [[I1 receptor|I<sub>1</sub>]] || {{Abbr|ND|No data}}
|-
| [[Sigma-1 receptor|σ<sub>1</sub>]], [[Sigma-2 receptor|σ<sub>2</sub>]] || {{Abbr|ND|No data}}
|-
| {{Abbrlink|TAAR1|Trace amine-associated receptor 1}} || 3,500 (K<sub>i</sub>) (mouse)<br />150 (K<sub>i</sub>) (rat)<br />2,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) (mouse)<br />490 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) (rat)<br />>10,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) (human)<br />61% ({{Abbr|E<sub>max</sub>|maximal efficacy}}) (mouse)<br />55% ({{Abbr|E<sub>max</sub>|maximal efficacy}}) (rat)
|-
| {{Abbrlink|SERT|Serotonin transporter}} || 31,000 (K<sub>i</sub>)<br />77,000 ({{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />{{Abbr|IA|Inactive}} ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| {{Abbrlink|NET|Norepinephrine transporter}} || >30,000 (K<sub>i</sub>)<br />45,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />{{Abbr|IA|Inactive}} ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| {{Abbrlink|DAT|Dopamine transporter}} || >30,000 (K<sub>i</sub>)<br />626,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />{{Abbr|IA|Inactive}} ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| {{Abbrlink|MAO-A|Monoamine oxidase A}} || {{Abbr|ND|No data}} ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})
|-
| {{Abbrlink|MAO-B|Monoamine oxidase B}} || 24,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})
|- class="sortbottom"
| colspan="2" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; 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=Kᵢ Database | website=PDSP | date=16 March 2025 | url=https://pdsp.unc.edu/kidb2/kidb/web/kis-results/index?KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14670&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D= | access-date=16 March 2025}}</ref><ref name="BindingDB">{{cite web | last=Liu | first=Tiqing | title=BindingDB BDBM50240787 2-(4-Methyl-2,5-dimethoxy-phenyl)-ethylamine::2-(4-methyl-2,5-dimethoxyphenyl)ethylamine::CHEMBL124049 | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50240787 | access-date=16 March 2025}}</ref><ref name="RickliLuethiReinisch2015">{{cite journal | vauthors = Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) | journal = Neuropharmacology | volume = 99 | issue = | pages = 546–553 | date = December 2015 | pmid = 26318099 | doi = 10.1016/j.neuropharm.2015.08.034 | url = https://psilosybiini.info/paperit/Receptor%20interaction%20profiles%20of%20novel%20N-2-methoxybenzyl%20(NBOMe)%20derivatives%20of%202,5-dimethoxy-substituted%20phenethylamines%20(2C%20drugs)%20(Rickli%20et%20al.,%202015).pdf}}</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 = https://www.researchgate.net/publication/258061356}}</ref><ref name="PottieCannaertStove2020">{{cite journal | vauthors = Pottie E, Cannaert A, Stove CP | title = In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor | journal = Arch Toxicol | volume = 94 | issue = 10 | pages = 3449–3460 | date = October 2020 | pmid = 32627074 | doi = 10.1007/s00204-020-02836-w | bibcode = 2020ArTox..94.3449P | url = | hdl = 1854/LU-8687071 | hdl-access = free }}</ref><ref name="MoyaBergGutiérrez-Hernandez2007" /><ref name="Acuña-CastilloVillalobosMoya2002" /><ref name="SimmlerBuchyChaboz2016">{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA | archive-url = https://web.archive.org/web/20250509235235/https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA | url-status = dead | archive-date = 2025-05-09 }}</ref>
|}

2C-D acts as a [[partial agonist]] of the [[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]]s.<ref name="RickliLuethiReinisch2015" /><ref name="EshlemanForsterWolfrum2014" /><ref name="MoyaBergGutiérrez-Hernandez2007">{{cite journal | vauthors = Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP | title = Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors | journal = J Pharmacol Exp Ther | volume = 321 | issue = 3 | pages = 1054–1061 | date = June 2007 | pmid = 17337633 | doi = 10.1124/jpet.106.117507 | url = https://core.ac.uk/download/pdf/208315525.pdf}}</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>

==Chemistry==
===Synthesis===
The [[chemical synthesis]] of 2C-D has been described.<ref name="PiHKAL" /><ref name="HoTanseyBalster1970" /><ref name="ShulginManningDaley2011">{{cite book | last1=Shulgin | first1=A. | last2=Manning | first2=T. | last3=Daley | first3=P.F. | title=[[The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds]] | publisher=[[Transform Press]] | location=Berkeley | volume=1 | year=2011 | isbn=978-0-9630096-3-0}}</ref>

===Analogues===
[[Structural analog|Analogue]]s of 2C-D include [[2C-B]], [[2C-E]], [[2C-P]], other [[2C (psychedelics)|2C]]s, [[DOM (drug)|DOM]] (α-methyl-2C-D), [[Ariadne (drug)|Ariadne]] (4C-D; α-ethyl-2C-D), [[5C-D]] (α-propyl-2C-D), and [[TWEETIO]]s like [[2CD-5-ETO]], among others.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013">{{cite book | last1=Trachsel | first1=D. | last2=Lehmann | first2=D. | last3=Enzensperger | first3=C. | title=Phenethylamine: von der Struktur zur Funktion | trans-title = Phenethylamines: From Structure to Function | edition = 1 | publisher=Nachtschatten-Verlag | location = Solothurn | series=Nachtschatten-Science | year=2013 | isbn=978-3-03788-700-4 | oclc = 858805226 | url=https://books.google.com/books?id=-Us1kgEACAAJ | language=de | archive-url=https://archive.org/details/phenethylamine-von-der-struktur-zur-funktion-trachsel-lehmann-enzensperger-2013 | archive-date=21 August 2025}}</ref> Other notable [[chemical derivative|derivative]]s of 2C-D include [[2C-G]] (3-methyl-2C-D) and other compounds of the 2C-G series like [[2C-G-3]] and [[2C-G-5]].<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" />

==History==
2C-D was first described in the [[scientific literature]] by Beng T. Ho and colleagues at the Texas Research Institute of Mental Sciences in 1970.<ref name="BrimblecombePinder1975">{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Phenylalkylamines and Their Derivatives | pages = 55–97 | title = Hallucinogenic Agents | date = 1975 | location = Bristol | publisher = Wright-Scientechnica | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1#page=38}}</ref><ref name="HoTanseyBalster1970">{{cite journal |vauthors=Ho BT, Tansey LW, Balster RL, An R, McIsaac WM, Harris RT |title=Amphetamine analogs. II. Methylated phenethylamines |journal=Journal of Medicinal Chemistry |volume=13 |issue=1 |pages=134–135 |date=January 1970 |pmid=5412084 |doi= 10.1021/jm00295a034}}</ref> They described its [[chemical synthesis|synthesis]] and [[pharmacology|pharmacological]] effects in animals.<ref name="BrimblecombePinder1975" /><ref name="HoTanseyBalster1970" /> The properties and effects of 2C-D in humans, along with those of [[2C-B]], were described by [[Alexander Shulgin]] and Michael Carter in 1975.<ref name="ShulginCarter1975">{{cite journal | vauthors = Shulgin AT, Carter MF | title = Centrally active phenethylamines | journal = Psychopharmacol Commun | volume = 1 | issue = 1 | pages = 93–98 | date = 1975 | pmid = 1223994 | doi = | url = https://bibliography.maps.org/resources/download/9045 | archive-url = https://web.archive.org/web/20250712222155/https://bibliography.maps.org/resources/download/9045 | archive-date = 2025-07-12}}</ref> Shulgin had first tested 2C-D at sub-threshold doses in 1964 and 1965.<ref name="Shulgin1964–1965">https://isomerdesign.com/pihkal/notebooks/transcripts/p1/p1.94.pdf</ref> Subsequently, he tested it at higher doses in 1974 and 1975 and discovered its [[psychoactive drug|psychoactive]] effects.<ref name="Shulgin1974–1978">https://isomerdesign.com/pihkal/notebooks/transcripts/p1/p1.175.pdf</ref>

[[Hanscarl Leuner]] and his student Michael Schlichting extensively studied 2C-D at high doses in [[psychedelic-assisted psychotherapy]] in [[Germany]] in the 1970s and 1980s.<ref name="PiHKAL" /><ref name="TiHKAL" /><ref name="PoulieJensenHalberstadt2020">{{cite journal | vauthors = Poulie CB, Jensen AA, Halberstadt AL, Kristensen JL | title = DARK Classics in Chemical Neuroscience: NBOMes | journal = ACS Chem Neurosci | volume = 11 | issue = 23 | pages = 3860–3869 | date = December 2020 | pmid = 31657895 | pmc = 9191638 | doi = 10.1021/acschemneuro.9b00528 | url = | quote = During the late 1970s and early 1980s, 2,5- dimethoxy-4-methylphenethylamine (2C-D), another compound from this class, received considerable attention from psychiatrists as a psychotherapeutic adjunct, most notably Hanscarl Leuner, who worked with 2C-D extensively under the code name LE-25 and pioneered the concept of psychedelic therapy.21 [...] (21). Leuner H (1981) Halluzinogene: Psychische Grenzzustände in Forschung und Psychotherapie, Hogrefe AG, Bern, Germany}}</ref><ref name="Passie2024">{{cite journal | last=Passie | first=Torsten | title=A history of the European Medical Society for Psycholytic Therapy (EPT) 1964–1974 | journal=Drug Science, Policy and Law | volume=10 | date=2024 | issn=2050-3245 | doi=10.1177/20503245231221154 | doi-access=free | url=https://journals.sagepub.com/doi/pdf/10.1177/20503245231221154 | access-date=14 November 2025 | quote=Like Jan Bastiaans, the Dutch chair of psychiatry at Leiden University, Leuner retained his license to use hallucinogens until his retirement in 1985. Leuner continued to conduct research on psycholytic therapy. There were studies on ketamine (Bolle, 1985, 1988), on the short-acting phenethylamine DMM-PEA (2C-D) (Schlichting, 1989, 1991), on the anal experience theme in psycholysis (Adler, 1981), and on results of other patients undergoing psycholysis (Schulz-Wittner, 1989). In Czechoslovakia and in England, psycholytic treatments were still carried out at some centers until the mid-1970s.}}</ref><ref name="Passie2022">{{cite book | last=Passie | first=Torsten | chapter=History of the Use of Hallucinogens in Psychiatric Treatment | pages = 95–118 | editor1-last=Grob | editor1-first=Charles S. | editor2-last=Grigsby | editor2-first=Jim | title=Handbook of Medical Hallucinogens | publisher=Guilford Publications | date=7 November 2022 | isbn=978-1-4625-5189-7 | url=https://books.google.com/books?id=r46ZEAAAQBAJ&pg=PA95 | quote = Also in the early 1950s, German psychiatrist Hanscarl Leuner (1984) developed guided affective imagery, a daydream technique used in psychotherapy. Concluding that small doses of hallucinogens may intensify imagery and induce regression and catharsis, Leuner (1959) began to use lowdose LSD with his psychotherapy patients. [...] During the 1960s, due to a continuous process of refinement, psycholytic therapists arrived at what might be considered today as a fully developed method (cf. Abramson, 1967; Grof, 1980b; Leuner, 1981). [...] Psycholytic therapy underwent a number of modifications during its active years. Some European therapists experimented with [...] the mescaline derivative 2-CD (2,5-dimethoxy-4-methylphenethylamine; Schlichting, 1989). [...] Leuner, H. (1981). Halluzinogene. Bern, Germany: Huber. [...] Schlichting, M. (1989). Psychotrope Eigenschaften des Phenäthylamins DMM-PEA (2,5-dimethoxy-4-methyl-phenathylamin). Unpublished doctoral thesis, Göttingen University, Göttingen, Germany.}}</ref><ref name="Leuner1981">{{cite book | last=Leuner | first=Hanscarl | title=Halluzinogene: psychische Grenzzustände in Forschung und Psychotherapie | trans-title=Hallucinogens: Altered Psychological States in Research and Psychotherapy | publisher=Huber | date=1981 | isbn=978-3-456-80933-5 | url=https://books.google.com/books?id=KwnEswEACAAJ | language=de}}</ref><ref name="Schlichting1989">{{cite thesis | author = Michael Schlichting | title = Psychotrope Eigenschaften des Phenäthylamins DMM-PEA (2,5-dimethoxy-4-methyl-phenathylamin) | trans-title = Psychotropic Properties of the Phenethylamine DMM-PEA (2,5-dimethoxy-4-methyl-phenethylamine) | publisher = Göttingen University | location = Göttingen, Germany | url = }}</ref> [[Darrell Lemaire]], under the pseudonyms Hosteen Nez and/or Lazar, studied 2C-D at low doses as a potential "[[nootropic|smart drug]]" in the 1970s and 1980s.<ref name="Erowid-Lemaire">{{cite web | title=Erowid Darrell Lemaire Vault | website=erowid.org | url=https://erowid.org/culture/characters/lemaire_darrell/lemaire_darrell.shtml | access-date=14 November 2025}}</ref><ref name="Morris2016-S01E06" /><ref name="Nez2010">{{cite book | author = Hosteen Nez ([[Darrell Lemaire]]) | chapter = Notes About Psychoactive Compounds | pages = 201–207 | editor1-last = Targ | editor1-first = Russell | editor2-last = Radin | editor2-first = Dean | title = Radiant Minds: Scientists Explore the Dimensions of Consciousness | publisher = Millay | date = 2010 | isbn = 978-0-615-29633-3 | url = https://books.google.com/books?id=bF-jcQAACAAJ | chapter-url = https://erowid.org/culture/characters/lemaire_darrell/lemaire_darrell_article1.pdf}}</ref><ref name="LazarNez1990" />

2C-D was encountered as a novel [[recreational drug|recreational]] [[designer drug]] in the [[United States]] by 2005.<ref name="TheobaldMaurer2006" /> It was not a [[controlled substance]] in the United States or most other countries at this time, in contrast to more popular 2Cs like 2C-B and [[2C-T-7]].<ref name="TheobaldMaurer2006" /> The drug became a [[Controlled Substances Act#Schedule I|Schedule I]] controlled substance in the United States in 2012.<ref name="DeanStellpflugBurnett2013" />

==Society and culture==
===Legal status===
====Canada====
As of October 31, 2016; 2C-D is a controlled substance (Schedule III) in Canada.<ref>{{Cite web|url=http://gazette.gc.ca/rp-pr/p2/2016/2016-05-04/html/sor-dors72-eng.php|title=Canada Gazette – Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)|date=4 May 2016}}</ref>

====China====
As of October 2015 2C-D is a controlled substance in China.<ref>{{cite web | url=http://www.sfda.gov.cn/WS01/CL0056/130753.html | title=关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | publisher=China Food and Drug Administration | date=27 September 2015 | language=zh | access-date=1 October 2015 | archive-url=https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html | archive-date=1 October 2015 | url-status=dead }}</ref>

====Denmark====
2C-D is added to the list of Schedule B controlled substances.<ref>{{cite web |url=https://www.retsinformation.dk/Forms/R0710.aspx?id=137169 |title = Retsinformation}}</ref>

====Finland====
Listed in the government decree on psychoactive substances banned from the consumer market.<ref>{{cite web | url=https://www.finlex.fi/fi/lainsaadanto/2014/1130 | title=FINLEX ® - Ajantasainen lainsäädäntö: Valtioneuvoston asetus kuluttajamarkkinoilta… 1130/2014 }}</ref><ref>{{cite web | url=https://www.finlex.fi/fi/lainsaadanto/saadoskokoelma/2021/733 | title=FINLEX ® - Säädökset alkuperäisinä: Valtioneuvoston asetus kuluttajamarkkinoilta… 733/2021 }}</ref>

====Germany====
2C-D is an [[Drugs controlled by the German Betäubungsmittelgesetz|Anlage I]] controlled drug.

====Sweden====
[[Riksdag|Sveriges riksdags]] health ministry ''Statens folkhälsoinstitut'' classified 2C-D as "health hazard" under the act ''Lagen om förbud mot vissa hälsofarliga varor'' (Act on the Prohibition of Certain Goods Dangerous to Health) as of Mar 1, 2005,  in their regulation SFS 2005:26 listed as "2,5-dimetoxi-4-metylfenetylamin (2C-D)", making it illegal to sell or possess.<ref>{{cite web |last=Johansson |first=Morgan |url=http://www.notisum.se/rnp/sls/sfs/20050026.pdf |title=Svensk författningssamling |access-date=January 24, 2022 |archive-date=September 29, 2013 |archive-url=https://web.archive.org/web/20130929063138/http://www.notisum.se/rnp/sls/sfs/20050026.pdf |url-status=dead }}</ref>

====United States====
2C-D became a [[Controlled Substances Act#Schedule I controlled substances|Schedule I Controlled Substance]] in the United States as of July 9, 2012, with the signing of Food and Drug Administration Safety and Innovation Act.<ref>{{Cite web |url=http://thomas.loc.gov/cgi-bin/query/z?c112:S.3187: |title=S. 3187 |access-date=2012-07-11 |archive-date=2012-12-14 |archive-url=https://web.archive.org/web/20121214091910/http://thomas.loc.gov/cgi-bin/query/z?c112:S.3187: |url-status=dead }}</ref> On a state level, both [[Oklahoma]] and [[Pennsylvania]] list 2C-D under schedule I.

==See also==
* [[2C (psychedelics)]]
* [[ASR-2001]] (2CB-5PrO)

==References==
{{Reflist}}

==External links==
* [https://isomerdesign.com/pihkal/explore/23 2C-D - Isomer Design]
* [https://psychonautwiki.org/wiki/2C-D 2C-D - PsychonautWiki]
* [https://erowid.org/chemicals/2cd/ 2C-D - Erowid]
* [https://erowid.org/library/books_online/pihkal/pihkal023.shtml 2C-D - PiHKAL - Erowid]
* [https://isomerdesign.com/pihkal/read/pk/23 2C-D - PiHKAL - Isomer Design]
* [https://archive.org/details/shulgin-index-vol-1/page/25/mode/1up?view=theater 2C-D - The Shulgin Index]
* [https://www.bluelight.org/xf/threads/111481 The Big & Dandy 2C-D Thread - Bluelight]
* [https://tripsitter.com/2cd/ 2C-D: The Intersect Between DOM & 2C-B - TripSitter]
* [https://tripsit.me/factsheets/2C-D 2C-D - TripSit]

{{Psychedelics}}
{{Serotonin receptor modulators}}
{{TAAR1 modulators}}
{{Phenethylamines}}

[[Category:2C (psychedelics)]]
[[Category:5-HT2A agonists]]
[[Category:5-HT2B agonists]]
[[Category:5-HT2C agonists]]
[[Category:Designer drugs]]
[[Category:Nootropics]]
[[Category:Psychedelic-assisted therapy]]
[[Category:Psychedelic phenethylamines]]
[[Category:Stimulants]]
[[Category:Substances discovered in the 1970s]]
[[Category:TAAR1 agonists]]