2C-D

Last updated
2C-D
2C-D 2DACS.svg
2C-D-3d-sticks.png
Clinical data
Other names4-Methyl-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-methyl-phenethylamine; 2C-M; 2C-DOM; LE-25; LE25; DMMPEA; DMM-PEA
Routes of
administration 		Oral [1] [2]
Drug class Serotonin 5-HT2 receptor agonist; Serotonergic psychedelic; Hallucinogen
Legal status
Legal status
Pharmacokinetic data
Onset of action 20–30 minutes [2]
Duration of action 4–6 hours [1] [2]
Identifiers
  • 2-(2,5-dimethoxy-4-methylphenyl)ethan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C11H17NO2
Molar mass 195.262 g·mol−1
3D model (JSmol)
Melting point 213 to 214 °C (415 to 417 °F) (hydrochloride)
  • O(c1cc(c(OC)cc1CCN)C)C
  • InChI=1S/C11H17NO2/c1-8-6-11(14-3)9(4-5-12)7-10(8)13-2/h6-7H,4-5,12H2,1-3H3 Yes check.svgY
  • Key:UNQQFDCVEMVQHM-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

2C-D, also known as 4-methyl-2,5-dimethoxyphenethylamine, is a psychedelic drug of the phenethylamine and 2C families. [1] It has an unusually wide and gradual dose range and at low doses produces claimed cognitive enhancer-like effects, mild stimulant effects, and mild perceptual effects, whereas at high doses, it produces robust psychedelic effects. [2] [1] [3] [4] The drug is taken orally. [1]

Contents

It acts as an agonist of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A receptor. [5] [6] [7] [8] The drug is structurally related to other psychedelic and related phenethylamines such as its higher homologues DOM and Ariadne (4C-D) and other 2C psychedelics like 2C-B and 2C-E. [1] [9]

2C-D was first described in the literature by Beng T. Ho and colleagues in 1970. [10] [11] Its properties and effects in humans were described by Alexander Shulgin and colleagues in 1975. [2] 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. [1] [12] [13] [14] [15] [16] [17] It was also informally studied by Darrell Lemaire as a potential "smart drug" in the 1970s and 1980s. [18] [19] [20] [3] 2C-D was first encountered as a novel designer drug by 2005. [21] It became a controlled substance in the United States in 2012. [22]

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 mg orally and its duration as 4 to 6 hours. [1] [2] He describes threshold effects as occurring at a dose of 6 mg orally and full intoxication occurring at doses of 10 to 15 mg orally. [2] Higher doses of 75 to 200 mg orally have also been described and were well-tolerated. [1] [3] The onset is said to be 20 to 30 minutes and peak effects occur after 1.5 to 2 hours. [2] Casey Hardison has described 2C-D as having a very gentle dose–response curve with an unusually wide dose range. [4]

The effects of 2C-D have been described. [2] [1] [3] At low doses, it produces perceived cognitive enhancement, mild stimulant-like effects, emotional integration, euphoria, and mild psychedelic effects such as perceptual enhancement that are much lighter than those of conventional psychedelics. [2] [1] [3] At high doses, it produces robust psychedelic effects. [1] 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. [4] [1]

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 mg orally. [1] [12] [3] Low doses of 2C-D in the range of 5 to 10 mg orally have been explored as a "smart drug" by Darrell Lemaire. [3] [19]

Interactions

2C-D is metabolized by the monoamine oxidase (MAO) enzymes MAO-A and MAO-B. [22] [23] Monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, moclobemide, and selegiline may potentiate the effects of 2C-D. [22] [23] [24] This may result in overdose and serious toxicity. [24] [22]

Pharmacology

Pharmacodynamics

2C-D activities
Target Affinity (Ki, nM)
5-HT1A 440–1,630 (Ki)
>10,000 (EC50 Tooltip half-maximal effective concentration)
<25% (Emax Tooltip maximal efficacy)
5-HT1B ND
5-HT1D ND
5-HT1E ND
5-HT1F ND
5-HT2A 23.9–32.4 (Ki)
43.5–8,130 (EC50)
6–93% (Emax)
5-HT2B ND (Ki)
230 (EC50)
77% (Emax)
5-HT2C 12.7–150 (Ki)
71.1–18,600 (EC50)
48–100% (Emax)
5-HT3 ND
5-HT4 ND
5-HT5A ND
5-HT6 ND
5-HT7 ND
α1A 12,000
α1B, α1D ND
α2A 290
α2B, α2C ND
β1–β3 ND
D1 24,000
D2 7,100
D3 >17,000
D4 ND
D5 ND
H1 >25,000
H2–H4 ND
M1–M5 ND
I1 ND
σ1, σ2 ND
TAAR1 Tooltip Trace amine-associated receptor 13,500 (Ki) (mouse)
150 (Ki) (rat)
2,000 (EC50) (mouse)
490 (EC50) (rat)
>10,000 (EC50) (human)
61% (Emax) (mouse)
55% (Emax) (rat)
SERT Tooltip Serotonin transporter31,000 (Ki)
77,000 (IC50 Tooltip half-maximal inhibitory concentration)
IA (EC50)
NET Tooltip Norepinephrine transporter>30,000 (Ki)
45,000 (IC50)
IA (EC50)
DAT Tooltip Dopamine transporter>30,000 (Ki)
626,000 (IC50)
IA (EC50)
MAO-A Tooltip Monoamine oxidase AND (IC50)
MAO-B Tooltip Monoamine oxidase B24,000 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [25] [26] [5] [6] [27] [7] [8] [28]

2C-D acts as a partial agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. [5] [6] [7] [8]

Chemistry

Synthesis

The chemical synthesis of 2C-D has been described. [1] [11] [29]

Analogues

Analogues of 2C-D include 2C-B, 2C-E, 2C-P, other 2Cs, DOM (α-methyl-2C-D), Ariadne (4C-D; α-ethyl-2C-D), 5C-D (α-propyl-2C-D), and TWEETIOs like 2CD-5-ETO, among others. [1] [9]

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. [10] [11] They described its synthesis and pharmacological effects in animals. [10] [11] 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. [2] Shulgin had first tested 2C-D at sub-threshold doses in 1964 and 1965. [30] Subsequently, he tested it at higher doses in 1974 and 1975 and discovered its psychoactive effects. [31]

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. [1] [12] [13] [14] [15] [16] [17] Darrell Lemaire, under the pseudonyms Hosteen Nez and/or Lazar, studied 2C-D at low doses as a potential "smart drug" in the 1970s and 1980s. [18] [19] [20] [3]

2C-D was encountered as a novel recreational designer drug in the United States by 2005. [21] 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. [21] The drug became a Schedule I controlled substance in the United States in 2012. [22]

Society and culture

Canada

As of October 31, 2016; 2C-D is a controlled substance (Schedule III) in Canada. [32]

China

As of October 2015 2C-D is a controlled substance in China. [33]

Denmark

2C-D is added to the list of Schedule B controlled substances. [34]

Finland

Listed in the government decree on psychoactive substances banned from the consumer market. [35] [36]

Germany

2C-D is an Anlage I controlled drug.

Sweden

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. [37]

United States

2C-D became a 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. [38] On a state level, both Oklahoma and Pennsylvania list 2C-D under schedule I.

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN   0-9630096-0-5. OCLC   25627628. https://www.erowid.org/library/books_online/pihkal/pihkal023.shtml
  2. 1 2 3 4 5 6 7 8 9 10 11 Shulgin AT, Carter MF (1975). "Centrally active phenethylamines". Psychopharmacol Commun. 1 (1): 93–98. PMID   1223994. Archived from the original on 2025-07-12.
  3. 1 2 3 4 5 6 7 8 Lazar (Darrell Lemaire); Hosteen Nez (1990), 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 (2 ed.), archived from the original (PDF) on 9 July 2001
  4. 1 2 3 Hardison, Casey (1 July 2007). "A brief history and motivation of an entheogenic chemist". Drugs and Alcohol Today. 7 (2): 26–31. doi:10.1108/17459265200700013. ISSN   1745-9265. 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).
  5. 1 2 3 Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME (December 2015). "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)" (PDF). Neuropharmacology. 99: 546–553. doi:10.1016/j.neuropharm.2015.08.034. PMID   26318099.
  6. 1 2 3 Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB (March 2014). "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. doi:10.1007/s00213-013-3303-6. PMC   3945162 . PMID   24142203.
  7. 1 2 3 Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP (June 2007). "Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors" (PDF). J Pharmacol Exp Ther. 321 (3): 1054–1061. doi:10.1124/jpet.106.117507. PMID   17337633.
  8. 1 2 3 Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP (June 2002). "Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors". Br J Pharmacol. 136 (4): 510–519. doi:10.1038/sj.bjp.0704747. PMC   1573376 . PMID   12055129.
  9. 1 2 Trachsel, D.; Lehmann, D.; Enzensperger, C. (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. ISBN   978-3-03788-700-4. OCLC   858805226. Archived from the original on 21 August 2025.
  10. 1 2 3 Brimblecombe RW, Pinder RM (1975). "Phenylalkylamines and Their Derivatives". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 55–97.
  11. 1 2 3 4 Ho BT, Tansey LW, Balster RL, An R, McIsaac WM, Harris RT (January 1970). "Amphetamine analogs. II. Methylated phenethylamines". Journal of Medicinal Chemistry. 13 (1): 134–135. doi:10.1021/jm00295a034. PMID   5412084.
  12. 1 2 3 Shulgin, Alexander; Shulgin, Ann (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN   0-9630096-9-9. OCLC   38503252. "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."
  13. 1 2 Poulie CB, Jensen AA, Halberstadt AL, Kristensen JL (December 2020). "DARK Classics in Chemical Neuroscience: NBOMes". ACS Chem Neurosci. 11 (23): 3860–3869. doi:10.1021/acschemneuro.9b00528. PMC   9191638 . PMID   31657895. 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
  14. 1 2 Passie, Torsten (2024). "A history of the European Medical Society for Psycholytic Therapy (EPT) 1964–1974". Drug Science, Policy and Law. 10. doi: 10.1177/20503245231221154 . ISSN   2050-3245 . Retrieved 14 November 2025. 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.
  15. 1 2 Passie, Torsten (7 November 2022). "History of the Use of Hallucinogens in Psychiatric Treatment". In Grob, Charles S.; Grigsby, Jim (eds.). Handbook of Medical Hallucinogens. Guilford Publications. pp. 95–118. ISBN   978-1-4625-5189-7. 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.
  16. 1 2 Leuner, Hanscarl (1981). Halluzinogene: psychische Grenzzustände in Forschung und Psychotherapie [Hallucinogens: Altered Psychological States in Research and Psychotherapy] (in German). Huber. ISBN   978-3-456-80933-5.
  17. 1 2 Michael Schlichting. Psychotrope Eigenschaften des Phenäthylamins DMM-PEA (2,5-dimethoxy-4-methyl-phenathylamin)[Psychotropic Properties of the Phenethylamine DMM-PEA (2,5-dimethoxy-4-methyl-phenethylamine)] (Thesis). Göttingen, Germany: Göttingen University.
  18. 1 2 "Erowid Darrell Lemaire Vault". erowid.org. Retrieved 14 November 2025.
  19. 1 2 3 Morris H (7 December 2016). "The Lazy Lizard School of Hedonism". Hamilton's Pharmacopeia . Season 1. Episode 6. Vice Media. Viceland.
  20. 1 2 Hosteen Nez (Darrell Lemaire) (2010). "Notes About Psychoactive Compounds" (PDF). In Targ, Russell; Radin, Dean (eds.). Radiant Minds: Scientists Explore the Dimensions of Consciousness. Millay. pp. 201–207. ISBN   978-0-615-29633-3.
  21. 1 2 3 Theobald DS, Maurer HH (November 2006). "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". J Mass Spectrom. 41 (11): 1509–1519. doi:10.1002/jms.1128. PMID   17103384. 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.
  22. 1 2 3 4 5 Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM (June 2013). "2C or not 2C: phenethylamine designer drug review". J Med Toxicol. 9 (2): 172–178. doi:10.1007/s13181-013-0295-x. PMC   3657019 . PMID   23494844.
  23. 1 2 Theobald DS, Maurer HH (January 2007). "Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series)". Biochem Pharmacol. 73 (2): 287–297. doi:10.1016/j.bcp.2006.09.022. PMID   17067556.
  24. 1 2 Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC   10851641 . PMID   37982394.
  25. ↑ "Kᵢ Database". PDSP. 16 March 2025. Retrieved 16 March 2025.
  26. ↑ Liu, Tiqing. "BindingDB BDBM50240787 2-(4-Methyl-2,5-dimethoxy-phenyl)-ethylamine::2-(4-methyl-2,5-dimethoxyphenyl)ethylamine::CHEMBL124049". BindingDB. Retrieved 16 March 2025.
  27. ↑ Pottie E, Cannaert A, Stove CP (October 2020). "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor". Arch Toxicol. 94 (10): 3449–3460. Bibcode:2020ArTox..94.3449P. doi:10.1007/s00204-020-02836-w. hdl: 1854/LU-8687071 . PMID   32627074.
  28. ↑ Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (April 2016). "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1" (PDF). J Pharmacol Exp Ther. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID   26791601. Archived from the original (PDF) on 2025-05-09.
  29. ↑ Shulgin, A.; Manning, T.; Daley, P.F. (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds . Vol. 1. Berkeley: Transform Press. ISBN   978-0-9630096-3-0.
  30. ↑ https://isomerdesign.com/pihkal/notebooks/transcripts/p1/p1.94.pdf
  31. ↑ https://isomerdesign.com/pihkal/notebooks/transcripts/p1/p1.175.pdf
  32. ↑ "Canada Gazette – Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". 4 May 2016.
  33. ↑ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
  34. ↑ "Retsinformation".
  35. ↑ "FINLEX ® - Ajantasainen lainsäädäntö: Valtioneuvoston asetus kuluttajamarkkinoilta… 1130/2014".
  36. ↑ "FINLEX ® - Säädökset alkuperäisinä: Valtioneuvoston asetus kuluttajamarkkinoilta… 733/2021".
  37. ↑ Johansson, Morgan. "Svensk författningssamling" (PDF). Archived from the original (PDF) on September 29, 2013. Retrieved January 24, 2022.
  38. ↑ "S. 3187". Archived from the original on 2012-12-14. Retrieved 2012-07-11.
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