D2-MDMA

{{cs1 config|name-list-style=vanc|display-authors=6}} {{Lowercase title}} {{Infobox drug | drug_name = d2-MDMA | image = D2-MDMA.svg | image_class = skin-invert-image | width = 250px | caption =

| legal_status =

| IUPAC_name = 1-(2,2-dideuterio-1,3-benzodioxol-5-yl)-''N''-methylpropan-2-amine | C=11 | H=15 | N=1 | O=2 | SMILES = [2H]C1(OC2=C(O1)C=C(C=C2)CC(C)NC)[2H] | StdInChI = 1S/C11H15NO2/c1-8(12-2)5-9-3-4-10-11(6-9)14-7-13-10/h3-4,6,8,12H,5,7H2,1-2H3/i7D2 | StdInChIKey = SHXWCVYOXRDMCX-RJSZUWSASA-N }}

'''d2-MDMA''', also known as '''d2-3,4-methylenedioxymethamphetamine''' or as '''deuterated-MDMA''' ('''D-MDMA'''), is an entactogen and stimulant of the phenethylamine, amphetamine, and MDxx families related to MDMA ("ecstasy").<ref name="Berquist_2020">{{cite journal | vauthors = Berquist MD, Leth-Petersen S, Kristensen JL, Fantegrossi WE | title = Locomotor effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in mice: psychostimulant effects, stereotypy, and sensitization | journal = Psychopharmacology | volume = 237 | issue = 2 | pages = 431–442 | date = February 2020 | pmid = 31729537 | pmc = 7388080 | doi = 10.1007/s00213-019-05380-3 }}</ref><ref name="Berquist_2020a">{{cite journal | vauthors = Berquist MD, Leth-Petersen S, Kristensen JL, Fantegrossi WE | title = In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation | journal = Drug and Alcohol Dependence | volume = 208 | article-number = 107850 | date = March 2020 | pmid = 31954950 | doi = 10.1016/j.drugalcdep.2020.107850 }}</ref><ref name="Berquest_2017" /><ref name="Berquest_2018" /><ref name="Chandra_Mouli_2023">{{cite journal | vauthors = Chandra Mouli HM, Vinod A, Kumari S, Tiwari AK, Kathiravan MK, Ravichandiran V, Peraman R | title = Deuterated driven new chemical entities: An optimistic way to improve therapeutic efficacy | journal = Bioorganic Chemistry | volume = 135 | article-number = 106490 | date = June 2023 | pmid = 37001472 | doi = 10.1016/j.bioorg.2023.106490 | quote = MDMA (3,4-Methylenedioxymethamphetamine) has resurfaced as an adjunct pharmacotherapy in the treatment of posttraumatic stress disorder (PTSD). Deuterium substitution at the methylenedioxy (-OCH2-O-) ring of MDMA slows down the metabolism, thereby reduces the adverse effects. Nevertheless, the d2-MDMA 9 has no differences in ED50 value as compared to its parent drug. Overall, the d2-MDMA retained the desirable subjective effects required to treat PTSD. In animal models, both MDMA and d2-MDMA affected the body temperature and locomotor activity [58]. }}</ref><ref name="Stemmerich_2022">{{cite journal | vauthors = Stemmerich K, Sewell AC, Arndt T | title = Deuterated Drugs: Weighty Times Ahead for the Lab? | journal = TIAFT Bulletin | volume = 52 | issue = 4 | date = 2022 | url = https://www.bioscientia.de/media/qr0onwah/deuterated-drugs-weighty-times_tiaft-bulletin_2022.pdf | quote = 3.3. ‘Heavy’ drugs as drugs of abuse In experiments with mice, d2-MDMA (d2-3,4- methylenedioxymethamphetamine) showed properties comparable to the stimulatory effects of MDMA [43]. Consequently, d2-MDMA could show potential as a substance of abuse. Berquist et al. [43] suggested that a different deuteration could maximise the therapeutic effect in the treatment of patients with post-traumatic stress disorder (PTSD) while minimising the adverse effects of MDMA. This may be equally true in reverse for the abusive properties, which could also be altered by appropriate deuteration of the molecule. }}</ref> It is the deuterated isotopologue of MDMA in which the hydrogen atoms on the carbon atom of the 3,4-methylenedioxy ring have been replaced with the deuterium isotopes.<ref name="Berquist_2020" /><ref name="Berquist_2020a" /><ref name="Stemmerich_2022" />

MDMA is known to produce serotonergic neurotoxicity and associated cognitive deficits and emotional and behavioral changes.<ref name="Berquist_2020" /><ref name="Berquist_2020a" /> The neurotoxicity of MDMA may be due in part to metabolism of MDMA via opening of the 3,4-methylenedioxy ring or ''O''-demethylation to form catechol metabolites like 3,4-dihydroxyamphetamine (HHA; α-methyldopamine) and 3,4-dihydroxymethamphetamine (HHMA; α,''N''-dimethyldopamine).<ref name="Berquist_2020" /><ref name="Berquist_2020a" /> These metabolites may subsequently undergo further metabolism into reactive oxygen species (ROS) that damage serotonergic neurons.<ref name="Berquist_2020" /><ref name="Berquist_2020a" /> In relation to this, d2-MDMA is thought to be resistant to metabolism in this location due to the greater amount of energy required to break deuterium–carbon bonds compared to hydrogen–carbon bonds.<ref name="Berquist_2020" /><ref name="Berquist_2020a" /> As a result, d2-MDMA may have less neurotoxic potential than MDMA.<ref name="Berquist_2020" /><ref name="Berquist_2020a" /> On the other hand, whereas the pharmacokinetics and neurotoxicity of d2-MDMA may be altered compared to MDMA, it is thought that the drug will have similar or near-identical pharmacodynamics as MDMA, for instance interactions with monoamine transporters and serotonin receptors, aside from differing metabolites.<ref name="Berquist_2020" /><ref name="Berquist_2020a" /> Due to the reduced ''O''-demethylation with d2-MDMA, ''N''-demethylation into d2-MDA may instead predominate with this compound in contrast to MDMA.<ref name="Berquist_2020" />

d2-MDMA produces hyperlocomotion, stereotypy, and sensitization in rodents similarly to MDMA and with comparable potency.<ref name="Berquist_2020" /> However, there were some slight differences between d2-MDMA and MDMA in terms of these effects at certain doses.<ref name="Berquist_2020" /> In addition, d2-MDMA at high doses might be less lethal via serotonin syndrome in rodents than MDMA based on preliminary findings.<ref name="Berquist_2020" /> d2-MDMA fully substitutes for MDMA in rodent drug discrimination tests and with equal potency and efficacy.<ref name="Berquist_2020a" /> The drug produced hyperthermia in rodents similarly to d2-MDMA, but this effect was shorter-lasting and of lower magnitude in comparison.<ref name="Berquist_2020a" /> However, this might have simply been related to potency differences in terms of this effect.<ref name="Berquist_2020a" /> The ''in-vitro'' pharmacodynamics and other effects of d2-MDMA have not yet been studied or reported.<ref name="Berquist_2020a" />

d2-MDMA was studied by William E. Fantegrossi and colleagues and described by these researchers in 2017,<ref name="Berquest_2017">{{cite conference | vauthors = Berquest MD, Leth-Petersen S, Fantegrossi WE | date = 2017 | title = Poster 2-29 Locomotor stimulant effects of MDMA and its putatively less toxic deuterated form in mice | page = 33 | url = https://ww2.uthscsa.edu/artt/print/bbcprogram2017.pdf#page=35 | conference = 2017 Behavior, Biology, and Chemistry: Translational Research in Addiction }}</ref> 2018,<ref name="Berquest_2018">{{cite conference | vauthors = Berquest MD, Leth-Petersen S, Fantegrossi WE | date = 2018 | title = Poster 2-17 Thermoregulatory and discriminative stimulus effects of MDMA and its putatively less toxic deuterated form in rodents | page = 31 | url = https://ww2.uthscsa.edu/artt/print/BBCProgram2018.pdf#page=33 | conference = 2018 Behavior, Biology, and Chemistry: Translational Research in Addiction }}</ref> and 2020.<ref name="Berquist_2020" /><ref name="Berquist_2020a" /> It is of potential interest for use in medicine as a better-tolerated and safer alternative to MDMA in the treatment of conditions like post-traumatic stress disorder (PTSD) and social anxiety disorder.<ref name="Berquist_2020" /><ref name="Berquist_2020a" /> On the other hand, d2-MDMA also has potential to emerge as a novel designer recreational drug.<ref name="Stemmerich_2022" /> Deuterated analogues of MDMA have been patented by Nicholas Cozzi and Paul Daley of the Alexander Shulgin Research Institute (ASRI).<ref name="US12221428">{{cite patent | country = US | number = 12221428 | inventor = Cozzi NV, Daley PF | title = Use of deuterated empathogens as therapeutic agents | pubdate = 2025-02-11 | gdate = 11 February 2025 | fdate = 2024-06-14 | pridate = 2021-08-23 | assign1 = Alexander Shulgin Research Institute Inc | url = https://patents.google.com/patent/US12221428B2/en | assign = Alexander Shulgin Research Institute Inc. }}</ref><ref name="US12043605">{{cite patent | country = US | number = 12043605 | inventor = Cozzi NV, Daley PF | title = Deuterated empathogens | pubdate = 2024-07-23 | gdate = 23 July 2024 | fdate = 2022-08-23 | pridate = 2021-08-23 | assign1 = Alexander Shulgin Research Institute Inc | url = https://patents.google.com/patent/US12043605B2/en | assign = Alexander Shulgin Research Institute Inc. }}</ref>

Other deuterated and related analogues of MDMA, such as MDMA-d3, have also been described.<ref name="BaumannWaltherDaley2026">{{cite journal | vauthors = Baumann MR, Walther D, Daley P, Cozzi N | date = 2026 | title = Effects of Deuteration or Fluorination of MDMA-Like Empathogen Compounds on Monoamine Transporter Activities (Abstract ID: 228967) | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 393 | issue = 5 | article-number = 104084 | doi = 10.1016/j.jpet.2026.104084 }}</ref>

== See also == * Substituted methylenedioxyphenethylamine * List of investigational hallucinogens and entactogens * DFMDMA, EIDA, and IDA * ODMA, SeDMA, and TMDA * SDMA (3-thio-MDMA) * 4-D (4-trideuteromescaline) * α,α-Dideuterophenethylamine * MDMA/citalopram

== References == {{Reflist}}

Category:Designer drugs Category:Deuterated psychedelics Category:Entactogens Category:Methamphetamines Category:Methylenedioxyamphetamines Category:Serotonin-norepinephrine-dopamine releasing agents Category:Serotonin receptor agonists Category:Stimulants