2C-D

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Template:Infobox drug

2C-D, also known as 4-methyl-2,5-dimethoxyphenethylamine, is a psychedelic drug of the phenethylamine and 2C families.<ref name="PiHKAL">Template: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 cognitive enhancer-like effects, mild stimulant effects, and mild 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 orally.<ref name="PiHKAL" />

It acts as an agonist of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A receptor.<ref name="RickliLuethiReinisch2015" /><ref name="EshlemanForsterWolfrum2014" /><ref name="MoyaBergGutiérrez-Hernandez2007" /><ref name="Acuña-CastilloVillalobosMoya2002" /> 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.<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 "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">Template:Cite journal</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 60Template:Nbspmg orally and its duration as 4 to 6Template:Nbsphours.<ref name="PiHKAL" /><ref name="ShulginCarter1975" /> He describes threshold effects as occurring at a dose of 6Template:Nbspmg orally and full intoxication occurring at doses of 10 to 15Template:Nbspmg orally.<ref name="ShulginCarter1975" /> Higher doses of 75 to 200Template:Nbspmg orally have also been described and were well-tolerated.<ref name="PiHKAL" /><ref name="LazarNez1990" /> In addition, a wider recreational dose range of 3 to 100Template:Nbspmg or more has been described.<ref name="LuethiLiechti2018">Template:Cite journal</ref> The onset is said to be 20 to 30Template:Nbspminutes and peak effects occur after 1.5 to 2Template:Nbsphours.<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">Template:Cite journal</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 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.<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 200Template:Nbspmg orally.<ref name="PiHKAL" /><ref name="TiHKAL">Template: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 10Template:Nbspmg orally have been explored as a "smart drug" by Darrell Lemaire.<ref name="LazarNez1990">Template:Citation</ref><ref name="Morris2016-S01E06">Template:Cite episode</ref>

Interactions

Template:See also

2C-D is metabolized by the monoamine oxidase (MAO) enzymes MAO-A and MAO-B.<ref name="DeanStellpflugBurnett2013">Template:Cite journal</ref><ref name="TheobaldMaurer2007">Template:Cite journal</ref> Monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, moclobemide, and selegiline may potentiate the effects of 2C-D.<ref name="DeanStellpflugBurnett2013" /><ref name="TheobaldMaurer2007" /><ref name="HalmanKongSarris2024">Template:Cite journal</ref> This may result in overdose and serious toxicity.<ref name="HalmanKongSarris2024" /><ref name="DeanStellpflugBurnett2013" />

Pharmacology

Pharmacodynamics

Template:Nowrap
Target Affinity (Ki, nM)
5-HT1A 440–1,630 (Ki)
>10,000 (Template:Abbrlink)
<25% (Template:Abbrlink)
5-HT1B Template:Abbr
5-HT1D Template:Abbr
5-HT1E Template:Abbr
5-HT1F Template:Abbr
5-HT2A 23.9–32.4 (Ki)
43.5–8,130 (Template:Abbr)
6–93% (Template:Abbr)
5-HT2B Template:Abbr (Ki)
230 (Template:Abbr)
77% (Template:Abbr)
5-HT2C 12.7–150 (Ki)
71.1–18,600 (Template:Abbr)
48–100% (Template:Abbr)
5-HT3 Template:Abbr
5-HT4 Template:Abbr
5-HT5A Template:Abbr
5-HT6 Template:Abbr
5-HT7 Template:Abbr
α1A 12,000
α1B, α1D Template:Abbr
α2A 290
α2B, α2C Template:Abbr
β1β3 Template:Abbr
D1 24,000
D2 7,100
D3 >17,000
D4 Template:Abbr
D5 Template:Abbr
H1 >25,000
H2H4 Template:Abbr
M1M5 Template:Abbr
I1 Template:Abbr
σ1, σ2 Template:Abbr
Template:Abbrlink 3,500 (Ki) (mouse)
150 (Ki) (rat)
2,000 (Template:Abbr) (mouse)
490 (Template:Abbr) (rat)
>10,000 (Template:Abbr) (human)
61% (Template:Abbr) (mouse)
55% (Template:Abbr) (rat)
Template:Abbrlink 31,000 (Ki)
77,000 (Template:Abbrlink)
Template:Abbr (Template:Abbr)
Template:Abbrlink >30,000 (Ki)
45,000 (Template:Abbr)
Template:Abbr (Template:Abbr)
Template:Abbrlink >30,000 (Ki)
626,000 (Template:Abbr)
Template:Abbr (Template:Abbr)
Template:Abbrlink Template:Abbr (Template:Abbr)
Template:Abbrlink 24,000 (Template:Abbr)
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">Template:Cite web</ref><ref name="BindingDB">Template:Cite web</ref><ref name="RickliLuethiReinisch2015">Template:Cite journal</ref><ref name="EshlemanForsterWolfrum2014">Template:Cite journal</ref><ref name="PottieCannaertStove2020">Template:Cite journal</ref><ref name="MoyaBergGutiérrez-Hernandez2007" /><ref name="Acuña-CastilloVillalobosMoya2002" /><ref name="SimmlerBuchyChaboz2016">Template:Cite journal</ref>

2C-D acts as a partial agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors.<ref name="RickliLuethiReinisch2015" /><ref name="EshlemanForsterWolfrum2014" /><ref name="MoyaBergGutiérrez-Hernandez2007">Template:Cite journal</ref><ref name="Acuña-CastilloVillalobosMoya2002">Template:Cite journal</ref>

Chemistry

Synthesis

The chemical synthesis of 2C-D has been described.<ref name="PiHKAL" /><ref name="HoTanseyBalster1970" /><ref name="ShulginManningDaley2011">Template:Cite book</ref>

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.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013">Template:Cite book</ref> Other notable derivatives 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">Template:Cite book</ref><ref name="HoTanseyBalster1970">Template:Cite journal</ref> They described its synthesis and 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">Template:Cite journal</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 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">Template:Cite journal</ref><ref name="Passie2024">Template:Cite journal</ref><ref name="Passie2022">Template:Cite book</ref><ref name="Leuner1981">Template:Cite book</ref><ref name="Schlichting1989">Template:Cite thesis</ref> 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.<ref name="Erowid-Lemaire">Template:Cite web</ref><ref name="Morris2016-S01E06" /><ref name="Nez2010">Template:Cite book</ref><ref name="LazarNez1990" />

2C-D was encountered as a novel 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 Schedule I controlled substance in the United States in 2012.<ref name="DeanStellpflugBurnett2013" />

Society and culture

Canada

As of October 31, 2016; 2C-D is a controlled substance (Schedule III) in Canada.<ref>Template:Cite web</ref>

China

As of October 2015 2C-D is a controlled substance in China.<ref>Template:Cite web</ref>

Denmark

2C-D is added to the list of Schedule B controlled substances.<ref>Template:Cite web</ref>

Finland

Listed in the government decree on psychoactive substances banned from the consumer market.<ref>Template:Cite web</ref><ref>Template:Cite web</ref>

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.<ref>Template:Cite web</ref>

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.<ref>Template:Cite web</ref> On a state level, both Oklahoma and Pennsylvania list 2C-D under schedule I.

See also

References

Template:Reflist

Template:Psychedelics Template:Serotonin receptor modulators Template:TAAR1 modulators Template:Phenethylamines