Methylone

{{Short description|Entactogen drug}} {{Redirect|MDMC}} {{Distinguish|ethylone}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 457117430 | image = Methylone structure.svg | image_class = skin-invert-image | width = 235px | image2 = MDMC-3d-sticks.png | image_class2 = bg-transparent | width2 = 250px

| tradename = | pregnancy_category = | routes_of_administration = Common: oral, insufflation<ref name="KarilaBillieuxBenyamina2016" /><ref name="Oeri2021" /> Uncommon: <abbr title="Intravenous">IV</abbr> or <abbr title="Intramuscular">IM</abbr> injection, rectal<ref name="KarilaBillieuxBenyamina2016" /> | class = Serotonin–norepinephrine–dopamine releasing agent; Entactogen | ATC_prefix = None | ATC_suffix =  | legal_AU = Unscheduled | legal_BR = F2 | legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=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 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-07-25}}</ref> | legal_CA = Schedule I | legal_UK = Class B | legal_US = Schedule I | legal_DE = Anlage II | legal_UN = Schedule II [https://www.unodc.org/LSS/Substance/Details/40f647f3-b96c-4a7a-8139-88c0ff651983] | legal_status = {{abbreviation|PL|Poland}}: I-P<ref>{{cite web | title = Ustawa z dnia 15 kwietnia 2011 r. o zmianie ustawy o przeciwdziałaniu narkomanii ( Dz.U. 2011 nr 105 poz. 614 ) | url = http://isap.sejm.gov.pl/DetailsServlet?id=WDU20111050614 | publisher = Internetowy System Aktów Prawnych | access-date = 17 June 2011}}</ref>

| bioavailability = | protein_bound = | metabolism = CYP2D6, CYP1A2, CYP2B6, and CYP2C19, COMT. [https://www.researchgate.net/figure/Common-routes-of-metabolism-for-methylone-3-Hydroxy-4-methoxy-N-methylcathinone-and_fig3_326760071] | metabolites = Dihydromethylone; 3,4-dihydroxy-N-methylcathinone; Methylenedioxycathinone; 4-hydroxy-3-methoxy-N-methylcathinone; 3-hydroxy-4-methoxy-N-methylcathinone | onset = 0.5 hours<ref name="PoyatosLoFaroBerardinelli2022" /> | elimination_half-life = 5.8–6.9 hours<ref name="PoyatosLoFaroBerardinelli2022">{{cite journal | vauthors = Poyatos L, Lo Faro AF, Berardinelli D, Sprega G, Malaca S, Pichini S, Huestis MA, Papaseit E, Pérez-Mañá C, Busardò FP, Farré M | title = Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans | journal = International Journal of Molecular Sciences | volume = 23 | issue = 23 | article-number = 14636 | date = November 2022 | pmid = 36498963 | pmc = 9736016 | doi = 10.3390/ijms232314636 | doi-access = free }}</ref> | duration_of_action = 2–3.5 hours<ref name="PoyatosLoFaroBerardinelli2022" /><ref name="Oeri2021" /> | excretion =  | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 186028-79-5 | CAS_supplemental = (racemic) {{CAS|191916-41-3}} (+) | UNII_Ref = {{fdacite|changed|FDA}} | UNII = L4I4B1R01F | KEGG_Ref = {{keggcite|changed|kegg}} | KEGG = C20126 | PubChem = 27281606 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 21106350 | synonyms = 3,4-Methylenedioxy-''N''-methylcathinone; 3,4-Methylenedioxymethcathinone; MDMC; MDMCAT; β-Keto-MDMA; βk-MDMA; M1; TSND-201; TSND201; MeONE; EASE; EMM; Explosion

| IUPAC_name = 1-(1,3-Benzodioxol-5-yl)-2-(methylamino)propan-1-one | C = 11 | H = 13 | N = 1 | O = 3 | SMILES = CC(NC)C(=O)C1=CC=C(OCO2)C2=C1 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C11H13NO3/c1-7(12-2)11(13)8-3-4-9-10(5-8)15-6-14-9/h3-5,7,12H,6H2,1-2H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VKEQBMCRQDSRET-UHFFFAOYSA-N

| solubility = 357 }}  '''Methylone''', also known as '''3,4-methylenedioxy-''N''-methylcathinone''' ('''MDMC'''), is an entactogen and stimulant drug of the amphetamine, cathinone, and MDxx families related to 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy").<ref name="Oeri2021">{{cite journal | vauthors = Oeri HE | title = Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy | journal = J Psychopharmacol | volume = 35 | issue = 5 | pages = 512–536 | date = May 2021 | pmid = 32909493 | pmc = 8155739 | doi = 10.1177/0269881120920420 | url = }}</ref><ref name="KarilaBillieuxBenyamina2016">{{cite journal | vauthors = Karila L, Billieux J, Benyamina A, Lançon C, Cottencin O | title = The effects and risks associated to mephedrone and methylone in humans: A review of the preliminary evidences | journal = Brain Res Bull | volume = 126 | issue = Pt 1 | pages = 61–67 | date = September 2016 | pmid = 26995278 | doi = 10.1016/j.brainresbull.2016.03.005 }}</ref><ref name="ShulginManningDaley2011">{{cite book | vauthors = Shulgin A, Manning T, Daley PF | chapter=#93. Methylone | 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 | pages=228–230 | chapter-url=https://archive.org/details/shulgin-index-vol-1/page/228/mode/1up?view=theater }}</ref> It is the β-keto or cathinone analogue of MDMA.<ref name="ShulginManningDaley2011" /><ref name="KarilaBillieuxBenyamina2016" /> The drug is usually taken orally, but can also be administered by other routes.<ref name="Oeri2021" /><ref name="KarilaBillieuxBenyamina2016" />

It acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA).<ref name="Oeri2021" /><ref name="BaumannAyestasPartilla2012" /><ref name="BaumannPartillaLehner2013" /><ref name="ElmoreDillon-CarterPartilla2017" /> The drug has much less activity at the vesicular monoamine transporter 2 (VMAT2) than MDMA<ref name="Oeri2021" /><ref name="CozziSievertShulgin1999" /> and may have less serotonergic neurotoxicity.<ref name="Oeri2021" /><ref name="DazianiLoFaroMontana2023" /><ref name="López-ArnauCamarasaCarbó2022" /><ref name="BaumannAyestasPartilla2012" /> In contrast to certain other entactogens like MDMA, methylone does not appear to be a significant agonist of the serotonin 5-HT2 receptors.<ref name="Oeri2021" /><ref name="López-ArnauCamarasaCarbó2022" /><ref name="Warner-SchmidtStogniew2024" /><ref name="LuethiKolaczynskaWalter2019" /> Methylone is similar in its effects to MDMA, producing entactogenic effects and euphoria, but has a reputation of being gentler than MDMA and only lasts about half as long.<ref name="Oeri2021" /><ref name="Shulgin2004" /> Side effects of methylone include tachycardia, hangover, and insomnia.<ref name="Oeri2021" /> It may have reduced negative after-effects compared to MDMA.<ref name="Oeri2021" /> Methylone's onset is about 0.5{{nbsp}}hours and its duration is about 2 to 3{{nbsp}}hours.<ref name="Oeri2021" /><ref name="PoyatosLoFaroBerardinelli2022" />

Methylone was first synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s<ref name="Jesso2023">{{cite podcast | title=Entactogens, MDMA, and Bringing New Love Drugs To Market (with Matthew Baggott) | work=Adventures Through The Mind | host=James W. Jesso | date=1 June 2023 | url=https://www.jameswjesso.com/entactogens-mdma-and-bringing-new-love-drugs-to-market-matthew-baggott-attmind-177/ | access-date=27 January 2025 }}</ref> and was first described in the literature in 1996.<ref name="KarilaBillieuxBenyamina2016" /><ref name="WO9639133">{{Cite patent|country=WO|number=9639133|title=Novel N-Substituted-2-Amino-3',4'-Methylene-dioxypropiophenones|pubdate=1996-12-12|assign=Neurobiological Technologies Inc.|inventor = Jacob III P, Shulgin AT }}</ref> It was patented by Jacob and Shulgin as a potential antidepressant and antiparkinsonian agent, but was never developed or marketed for such uses.<ref name="KarilaBillieuxBenyamina2016" /><ref name="WO9639133" /> Methylone was encountered as a designer and recreational drug by 2004 and has become a controlled substance in many countries.<ref name="ShulginManningDaley2011" /><ref name="KarilaBillieuxBenyamina2016" /> Similarly to MDMA, it is being developed for the treatment of post-traumatic stress disorder (PTSD).<ref name="AdisInsight" /><ref name="Synapse" /><ref name="FierceBiotech2023" /><ref name="JonesWarner-SchmidtKwak2026">{{cite journal | vauthors = Jones A, Warner-Schmidt J, Kwak H, Stogniew M, Mandell B, Ching TH, Stein MB, Kelmendi B | title = Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD: A Randomized Clinical Trial | journal = JAMA Psychiatry | volume = | issue = | pages = | date = February 2026 | pmid = 41706459 | pmc = 12917749 | doi = 10.1001/jamapsychiatry.2025.4625 | url = }}</ref>

== Use and effects == [[Image:Comparisons md analogues.png|right|thumb|class=skin-invert-image|Structural similarities between some amphetamine-like stimulants and their 3,4-methylenedioxy- derivatives. Left: amphetamine, methamphetamine and methcathinone. Right: MDA, MDMA, and methylone.]]

Methylone substitutes for MDMA in drug discrimination tests in rodents. Methylone does not substitute for the stimulant amphetamine or for the hallucinogen DOM in animal drug discrimination tests.<ref name="DalCasonYoungGlennon1997">{{cite journal | vauthors = Dal Cason TA, Young R, Glennon RA | title = Cathinone: an investigation of several N-alkyl and methylenedioxy-substituted analogs | journal = Pharmacology, Biochemistry, and Behavior | volume = 58 | issue = 4 | pages = 1109–1116 | date = December 1997 | pmid = 9408221 | doi = 10.1016/s0091-3057(97)00323-7 | publisher = Elsevier BV | s2cid = 9704972 }}</ref> Further, also in common with MDMA, methylone acts on monoaminergic systems. ''In vitro'', methylone has one third the potency of MDMA at inhibiting platelet serotonin accumulation and about the same in its inhibiting effects on the dopamine and noradrenaline transporters.<ref>{{cite journal | vauthors = Cozzi NV, Sievert MK, Shulgin AT, Jacob III P, Ruoho AE |title=Methcathinone and 2 methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one (methylone) selectively inhibit plasma membrane catecholamine reuptake transporters |journal=Soc. Neurosci. Abs. |volume=24 |issue=341.8 |year=1998}}</ref><ref>{{cite journal | vauthors = Cozzi NV, Shulgin AT, Ruoho AE |title= Methcathinone (MCAT) and 2-methylamino-1-(3,4 methylenedioxyphenyl)propan-1-one (MDMCAT) inhibit [3H]serotonin uptake into human platelets |journal=Am. Chem. Soc. Div. Med. Chem. Abs. |volume=215 |issue=152 |year=1998}}</ref><ref name="CozziSievertShulgin1999" />

In spite of these behavioral and pharmacological similarities between methylone and MDMA, the observed subjective effects of both drugs are not completely identical. Alexander Shulgin wrote of the former:<ref name="Shulgin2004">{{cite web | url = http://www.cognitiveliberty.org/shulgin/adsarchive/cathinone.htm | title = Cathinone | Ask Dr. Shulgin Online | date = 3 June 2004 | archive-url = https://web.archive.org/web/20100413235500/http://www.cognitiveliberty.org/shulgin/adsarchive/cathinone.htm | archive-date = 2010-04-13 | access-date = 2010-01-17 }}</ref>

{{blockquote|"[Methylone] has almost the same potency of MDMA, but it does not produce the same effects. It has an almost antidepressant action, pleasant and positive, but not the unique magic of MDMA."}}

In acute pharmacological studies of methylone (50–300{{nbsp}}mg) in humans, the drug produced physiological and psychological effects including increased blood pressure, heart rate, body temperature, pupil dilation, stimulation, euphoria, feelings of well-being, enhanced empathy, increased sociability, and altered perception.<ref name="pmid36873994">{{cite journal | vauthors = Poyatos L, Pérez-Mañá C, Hladun O, Núñez-Montero M, de la Rosa G, Martín S, Barriocanal AM, Carabias L, Kelmendi B, Taoussi O, Busardò FP, Fonseca F, Torrens M, Pichini S, Farré M, Papaseit E | title = Pharmacological effects of methylone and MDMA in humans | journal = Frontiers in Pharmacology | volume = 14 | issue = | article-number = 1122861 | date = 2023 | pmid = 36873994 | pmc = 9981643 | doi = 10.3389/fphar.2023.1122861 | doi-access = free }}</ref><ref name="pmid34440023">{{cite journal | vauthors = Poyatos L, Papaseit E, Olesti E, Pérez-Mañá C, Ventura M, Carbón X, Grifell M, Fonseca F, Torrens M, de la Torre R, Farré M | title = A Comparison of Acute Pharmacological Effects of Methylone and MDMA Administration in Humans and Oral Fluid Concentrations as Biomarkers of Exposure | journal = Biology | volume = 10 | issue = 8 | page = 788 | date = August 2021 | pmid = 34440023 | pmc = 8389614 | doi = 10.3390/biology10080788 | doi-access = free }}</ref> The studies found that the effects of methylone were similar to or milder than those of MDMA.<ref name="pmid36873994" /><ref name="pmid34440023" /> Methylone had a faster onset of action and its subjective effects wore off sooner than MDMA, which might lead to a redosing pattern of use.<ref name="pmid36873994" /> The misuse potential of methylone, as measured by for instance drug liking responses, appeared to be similar to that of MDMA.<ref name="pmid36873994" /> However it also has less off-target effects than MDMA which may be an advantage for medical applications.<ref>{{cite journal | vauthors = Warner-Schmidt J, Pittenger C, Stogniew M, Mandell B, Olmstead SJ, Kelmendi B | title = Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity | journal = Frontiers in Psychiatry | volume = 13 | article-number = 1041277 | date = 2022 | pmid = 36704743 | pmc = 9873307 | doi = 10.3389/fpsyt.2022.1041277 | doi-access = free }}</ref><ref name="pmid36873994" /><ref>{{cite journal | vauthors = Warner-Schmidt J, Stogniew M, Mandell B, Rowland RS, Schmidt EF, Kelmendi B | title = Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA | journal = Frontiers in Neuroscience | volume = 18 | article-number = 1353131 | date = 2024-02-07 | pmid = 38389788 | pmc = 10882719 | doi = 10.3389/fnins.2024.1353131 | doi-access = free }}</ref>

==Interactions== {{See also|MDMA#Interactions|Trip killer#Antidotes of other hallucinogens|MDMA/citalopram}}

==Pharmacology== ===Pharmacodynamics=== Methylone acts as a mixed releasing agent and reuptake inhibitor of serotonin, norepinephrine, and dopamine.<ref name="CozziSievertShulgin1999" /><ref name="NagaiNonakaSatohHisashi2007">{{cite journal | vauthors = Nagai F, Nonaka R, Satoh Hisashi Kamimura K | title = The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain | journal = European Journal of Pharmacology | volume = 559 | issue = 2–3 | pages = 132–137 | date = March 2007 | pmid = 17223101 | doi = 10.1016/j.ejphar.2006.11.075 }}</ref> In comparison to MDMA, it has approximately 3-fold lower affinity for the serotonin transporter, while its affinity for the norepinephrine and dopamine transporters is similar.<ref name="CozziSievertShulgin1999" /><ref name="NagaiNonakaSatohHisashi2007" /> Notably, methylone's affinity for the vesicular monoamine transporter 2 (VMAT2) is about 13-fold lower than that of MDMA.<ref name="CozziSievertShulgin1999" /> The results of these differences in pharmacology relative to MDMA are that methylone is less potent in terms of dose, has more balanced catecholaminergic effects relative to serotonergic effects, and behaves more like a mixed releaser and reuptake inhibitor than a predominant releaser, though methylone still has relatively robust releasing capabilities.<ref name="NagaiNonakaSatohHisashi2007" />

In addition to its monoamine-releasing actions, similarly to MDMA, methylone is a variable-potency partial agonist of the serotonin 5-HT1A, 5-HT1B, and 5-HT1D receptors.<ref name="JainGumpperSlocum2025">{{cite journal | vauthors = Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, Suomivuori CM, Huang XP, Shub L, DiBerto JF, Kim K, DeLeon C, Krumm BE, Fay JF, Keiser M, Hauser AS, Dror RO, Shoichet B, Gloriam DE, Nichols DE, Roth BL | title = The polypharmacology of psychedelics reveals multiple targets for potential therapeutics | journal = Neuron | date = July 2025 | volume = 113 | issue = 19 | pages = 3129–3142.e9 | pmid = 40683247 | doi = 10.1016/j.neuron.2025.06.012 | url = https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/7d8365fe-51f3-4a28-bf40-9999bec837f6/mmc11.pdf }}</ref> In contrast to MDMA however, methylone and its metabolites lack significant affinity for the serotonin 5-HT2A and 5-HT2C receptors and do not activate the serotonin 5-HT2B receptor.<ref name="López-ArnauCamarasaCarbó2022" /><ref name="Warner-SchmidtStogniew2024">{{cite journal | vauthors = Warner-Schmidt J, Stogniew M, Mandell B, Rowland RS, Schmidt EF, Kelmendi B | title = Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA | journal = Front Neurosci | volume = 18 | issue = | article-number = 1353131 | date = 2024 | pmid = 38389788 | pmc = 10882719 | doi = 10.3389/fnins.2024.1353131 | doi-access = free | url = }}</ref><ref name="LuethiKolaczynskaWalter2019">{{cite journal | vauthors = Luethi D, Kolaczynska KE, Walter M, Suzuki M, Rice KC, Blough BE, Hoener MC, Baumann MH, Liechti ME | title = Metabolites of the ring-substituted stimulants MDMA, methylone and MDPV differentially affect human monoaminergic systems | journal = J Psychopharmacol | volume = 33 | issue = 7 | pages = 831–841 | date = July 2019 | pmid = 31038382 | pmc = 8269116 | doi = 10.1177/0269881119844185 | url = }}</ref> On the other hand, a subsequent study found that methylone indeed showed no affinity for or agonistic activity at the serotonin 5-HT2A and 5-HT2B receptors, but was a potent and near-full agonist of the serotonin 5-HT2C receptor Gαq pathway, though not of the other assessed Gα pathways of the receptor.<ref name="JainGumpperSlocum2025" /> The absence of serotonin 5-HT2A receptor agonism with methylone may explain its absence of psychedelic effects.<ref name="JainGumpperSlocum2025" /><ref name="López-ArnauCamarasaCarbó2022" /> The lack of serotonin 5-HT2B receptor agonism with methylone may make it safer than MDMA, for instance in terms of long-term cardiac valvulopathy risk.<ref name="TagenMantuanivanHeerden2023">{{cite journal | vauthors = Tagen M, Mantuani D, van Heerden L, Holstein A, Klumpers LE, Knowles R | title = The risk of chronic psychedelic and MDMA microdosing for valvular heart disease | journal = J Psychopharmacol | volume = 37 | issue = 9 | pages = 876–890 | date = September 2023 | pmid = 37572027 | doi = 10.1177/02698811231190865 | url = }}</ref><ref name="RouaudCalderHasler2024">{{cite journal | vauthors = Rouaud A, Calder AE, Hasler G | title = Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins | journal = J Psychopharmacol | volume = 38 | issue = 3 | pages = 217–224 | date = March 2024 | pmid = 38214279 | pmc = 10944580 | doi = 10.1177/02698811231225609 | url = }}</ref><ref name="RothmanBaumann2009">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Serotonergic drugs and valvular heart disease | journal = Expert Opin Drug Saf | volume = 8 | issue = 3 | pages = 317–329 | date = May 2009 | pmid = 19505264 | pmc = 2695569 | doi = 10.1517/14740330902931524 | url = }}</ref> Methylone is inactive at the mouse and rat trace amine-associated receptor 1 (TAAR1).<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 | archive-date = 9 May 2025 }}</ref><ref name="LuethiKolaczynskaWalter2019" />

Methylone has been found to produce psychoplastogenic effects in preclinical research and showed greater effects in this regard than MDMA.<ref name="Warner-SchmidtStogniewJones2024">{{cite journal | vauthors = Warner-Schmidt J, Stogniew M, Jones A, Mandell B, Kelmendi B | title = ACNP 63rd Annual Meeting: Poster Abstracts P609-P914: P718. TSND-201 (methylone), a Rapid-Acting Neuroplastogen that Stimulates Neurite Outgrowth | journal = Neuropsychopharmacology | volume = 49 | issue = Suppl 1 | pages = 418–594 (482–483) | date = December 2024 | pmid = 39643635 | doi = 10.1038/s41386-024-02013-y | url = | doi-access = free }}</ref>

Similarly to MDMA, methylone has been found to be a monoaminergic neurotoxin in animals.<ref name="DazianiLoFaroMontana2023">{{cite journal | vauthors = Daziani G, Lo Faro AF, Montana V, Goteri G, Pesaresi M, Bambagiotti G, Montanari E, Giorgetti R, Montana A | title = Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review | journal = Int J Mol Sci | volume = 24 | issue = 7 | date = March 2023 | page = 6230 | pmid = 37047201 | pmc = 10093970 | doi = 10.3390/ijms24076230 | doi-access = free | url = }}</ref> It has specifically been found to produce serotonergic and dopaminergic neurotoxicity in rodents.<ref name="DazianiLoFaroMontana2023" /> However, in one study, moderate doses of MDMA produced serotonergic neurotoxicity in rodents whereas methylone and mephedrone did not do so, suggesting that cathinones like methylone may be less neurotoxic than their corresponding amphetamine counterparts like MDMA.<ref name="López-ArnauCamarasaCarbó2022">{{cite journal | vauthors = López-Arnau R, Camarasa J, Carbó ML, Nadal-Gratacós N, Puigseslloses P, Espinosa-Velasco M, Urquizu E, Escubedo E, Pubill D | title = 3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs | journal = Front Psychiatry | volume = 13 | issue = | article-number = 990405 | date = 2022 | pmid = 36262632 | pmc = 9574023 | doi = 10.3389/fpsyt.2022.990405 | doi-access = free | url = }}</ref><ref name="BaumannAyestasPartilla2012" />

{| class="wikitable" style="font-size:small;" |+ {{Nowrap|Monoamine release of methylone and related agents ({{Abbrlink|EC50|Half maximal effective concentration}}, nM)}} |- ! Compound !! data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} !! data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} !! data-sort-type="number" | {{abbrlink|DA|Dopamine}} !! Ref |- | Dextroamphetamine || 698–1,765 || 6.6–7.2 || 5.8–24.8 || <ref name="RothmanBaumannDersch2001">{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref><ref name="BaumannPartillaLehner2013">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref> |- | Dextromethamphetamine || 736–1,292 || 12.3–13.8 || 8.5–24.5 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannAyestasPartilla2012">{{cite journal | vauthors = Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV | title = The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue | journal = Neuropsychopharmacology | volume = 37 | issue = 5 | pages = 1192–1203 | year = 2012 | pmid = 22169943 | pmc = 3306880 | doi = 10.1038/npp.2011.304 }}</ref> |- | {{Abbrlink|MDA|Methylenedioxyamphetamine}} || 160–162 || 47–108 || 106–190 || <ref name="SetolaHufeisenGrande-Allen2003" /><ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken [NJ] | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}</ref><ref name="BrandtWaltersPartilla2020" /> |- | {{Abbrlink|MDMA|Methylenedioxymethamphetamine}} || 49.6–72 || 54.1–110 || 51.2–278 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannAyestasPartilla2012" /><ref name="MarusichAntonazzoBlough2016">{{cite journal | vauthors = Marusich JA, Antonazzo KR, Blough BE, Brandt SD, Kavanagh PV, Partilla JS, Baumann MH | title = The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue | journal = Neuropharmacology | volume = 101 | pages = 68–75 | date = February 2016 | pmid = 26362361 | pmc = 4681602 | doi = 10.1016/j.neuropharm.2015.09.004 }}</ref><ref name="SetolaHufeisenGrande-Allen2003">{{cite journal | vauthors = Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL | title = 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro | journal = Molecular Pharmacology | volume = 63 | issue = 6 | pages = 1223–1229 | date = June 2003 | pmid = 12761331 | doi = 10.1124/mol.63.6.1223 | s2cid = 839426 }}</ref><ref name="BrandtWaltersPartilla2020">{{cite journal | vauthors = Brandt SD, Walters HM, Partilla JS, Blough BE, Kavanagh PV, Baumann MH | title = The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats | journal = Psychopharmacology (Berl) | volume = 237 | issue = 12 | pages = 3703–3714 | date = December 2020 | pmid = 32875347 | doi = 10.1007/s00213-020-05648-z | url = | pmc = 7686291 }}</ref> |- | Cathinone || 6,100–7,595 || 23.6–25.6 || 34.8–83.1 || <ref name="Blough2008" /><ref name="BloughDeckerLandavazo2019">{{cite journal | vauthors = Blough BE, Decker AM, Landavazo A, Namjoshi OA, Partilla JS, Baumann MH, Rothman RB | title = The dopamine, serotonin and norepinephrine releasing activities of a series of methcathinone analogs in male rat brain synaptosomes | journal = Psychopharmacology | volume = 236 | issue = 3 | pages = 915–924 | date = March 2019 | pmid = 30341459 | pmc = 6475490 | doi = 10.1007/s00213-018-5063-9 }}</ref><ref name="FitzgeraldGannonWalther2024">{{cite journal | vauthors = Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE | title = Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones | journal = Neuropharmacology | volume = 245 | issue = | article-number = 109827 | date = March 2024 | pmid = 38154512 | doi = 10.1016/j.neuropharm.2023.109827 | pmc = 10842458 | url = }}</ref> |- | Methcathinone || 2,592–5,853 || 22–26.1 || 12.5–49.9 || <ref name="Blough2008" /><ref name="BloughDeckerLandavazo2019" /><ref name="Shalabi2017">{{cite thesis | vauthors = Shalabi AR | date = 14 December 2017 | title = Structure-Activity Relationship Studies of Bupropion and Related 3-Substituted Methcathinone Analogues at Monoamine Transporters | website = VCU Scholars Compass | doi = 10.25772/M4E1-3549 }}</ref><ref name="WaltherShalabiBaumann2019">{{cite journal | vauthors = Walther D, Shalabi AR, Baumann MH, Glennon RA | date = January 2019 | title = Systematic Structure-Activity Studies on Selected 2-, 3-, and 4-Monosubstituted Synthetic Methcathinone Analogs as Monoamine Transporter Releasing Agents | journal = ACS Chemical Neuroscience | volume = 10 | issue = 1 | pages = 740–745 | doi = 10.1021/acschemneuro.8b00524 | pmc = 8269283 | pmid = 30354055 }}</ref><ref name="FitzgeraldGannonWalther2024" /> |- | {{Abbrlink|MDC|Methylenedioxycathinone}} || 966 || 394 || 370 || <ref name="ElmoreDillon-CarterPartilla2017" /> |- | Methylone ({{Abbr|MDMC|methylenedioxymethcathinone}}) || 234–708 || 140–270 || 117–220 || <ref name="BaumannAyestasPartilla2012" /><ref name="BaumannPartillaLehner2013" /><ref name="Sakloth2015">{{cite thesis | vauthors = Sakloth F | date = 11 December 2015 | title = Psychoactive synthetic cathinones (or 'bath salts'): Investigation of mechanisms of action | website = VCU Scholars Compass | doi = 10.25772/AY8R-PW77 }}</ref><ref name="GlatfelterWaltherEvans-Brown2021">{{cite journal | vauthors = Glatfelter GC, Walther D, Evans-Brown M, Baumann MH | date = April 2021 | title = Eutylone and Its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation | journal = ACS Chemical Neuroscience | volume = 12 | issue = 7 | pages = 1170–1177 | doi = 10.1021/acschemneuro.0c00797 | pmc = 9423000 | pmid = 33689284 }}</ref><ref name="ElmoreDillon-CarterPartilla2017">{{cite journal | vauthors = Elmore JS, Dillon-Carter O, Partilla JS, Ellefsen KN, Concheiro M, Suzuki M, Rice KC, Huestis MA, Baumann MH | date = February 2017 | title = Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats | journal = Neuropsychopharmacology | volume = 42 | issue = 3 | pages = 649–660 | doi = 10.1038/npp.2016.213 | pmc = 5240186 | pmid = 27658484 }}</ref> |- | Mephedrone || 118.3–122 || 58–62.7 || 49.1–51 || <ref name="BaumannAyestasPartilla2012" /><ref name="BaumannPartillaLehner2013" /><ref name="BloughDeckerLandavazo2019" /><ref name="WaltherShalabiBaumann2019" /><ref name="BonanoBanksKolanos2015">{{cite journal | vauthors = Bonano JS, Banks ML, Kolanos R, Sakloth F, Barnier ML, Glennon RA, Cozzi NV, Partilla JS, Baumann MH, Negus SS | title = Quantitative structure-activity relationship analysis of the pharmacology of para-substituted methcathinone analogues | journal = Br J Pharmacol | volume = 172 | issue = 10 | pages = 2433–2444 | date = May 2015 | pmid = 25438806 | pmc = 4409897 | doi = 10.1111/bph.13030 | url = }}</ref> |- | colspan="5" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. '''Refs:'''<ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}</ref><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = https://zenodo.org/record/1235860 }}</ref> |}

===Pharmacokinetics=== The two major metabolic pathways in mammals for methylone are ''N''-demethylation to methylenedioxycathinone (MDC), and demethylation followed by ''O''-methylation of the 3- or 4-hydroxy group to 4-hydroxy-3-methoxymethcathinone (HMMC) or 3-hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC). Another metabolite is 3,4-dihydroxymethcathinone (HHMC).<ref name="ElmoreDillon-CarterPartilla2017" /><ref name="LuethiKolaczynskaWalter2019"/> When 5 mg/kg of methylone was administered to rats, it was found that around 26% was excreted as HMMC within the first 48 hours (less than 3% excreted unchanged).<ref>{{cite journal | vauthors = Kamata HT, Shima N, Zaitsu K, Kamata T, Miki A, Nishikawa M, Katagi M, Tsuchihashi H | title = Metabolism of the recently encountered designer drug, methylone, in humans and rats | journal = Xenobiotica; the Fate of Foreign Compounds in Biological Systems | volume = 36 | issue = 8 | pages = 709–723 | date = August 2006 | pmid = 16891251 | doi = 10.1080/00498250600780191 | s2cid = 10875717 }}</ref> The mean elimination half-lives of methylone in humans following oral administration of doses of 50 to 200{{nbsp}}mg ranged from 5.8 to 6.9{{nbsp}}hours.<ref name="PoyatosLoFaroBerardinelli2022" /> The onset of action and duration of action of methylone in humans are 0.5{{nbsp}}hours and 2.5 to 3.0{{nbsp}}hours, respectively.<ref name="PoyatosLoFaroBerardinelli2022" />

==Chemistry== Methylone is the substituted cathinone analogue of 3,4-methylenedioxymethamphetamine (MDMA) and the 3,4-methylenedioxy analogue of methcathinone.<ref name="ShulginManningDaley2011" /> The only structural difference of methylone with respect to MDMA is the substitution of two hydrogen atoms by one oxygen atom in the β position of the phenethylamine core, forming a ketone group.<ref name="CozziSievertShulgin1999">{{cite journal | vauthors = Cozzi NV, Sievert MK, Shulgin AT, Jacob P, Ruoho AE | title = Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines | journal = European Journal of Pharmacology | volume = 381 | issue = 1 | pages = 63–69 | date = September 1999 | pmid = 10528135 | doi = 10.1016/S0014-2999(99)00538-5 }}</ref>

===Synthesis=== The chemical synthesis of methylone has been described.<ref name="ShulginManningDaley2011" />

==History== Methylone was first synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s.<ref name="Jesso2023"/><ref name="KarilaBillieuxBenyamina2016" /><ref name="WO9639133"/> This was after the publication of Shulgin's PiHKAL (1991), and so methylone is not included in this book.<ref name="PiHKAL">{{cite book | vauthors = Shulgin AT, Shulgin A | url = https://www.erowid.org/library/books_online/pihkal/ | title = PiHKAL: A Chemical Love Story | date = 1991 | publisher = Transform Press | isbn = 978-0-9630096-0-9 | edition = 1st | location = Berkeley, CA | oclc = 25627628 }}</ref> However, it was subsequently included in ''The Shulgin Index'' (2011).<ref name="ShulginManningDaley2011" /> The drug was patented by Jacob and Shulgin as a potential antidepressant and antiparkinsonian agent, but was never developed or marketed.<ref name="KarilaBillieuxBenyamina2016" /><ref name="WO9639133" /> This was the first time that methylone was described in the literature.<ref name="WO9639133" /> The drug was first described in the scientific literature by 1997.<ref name="DalCasonYoungGlennon1997" /> Methylone was encountered as a designer and recreational drug by 2004.<ref name="ShulginManningDaley2011" /><ref name="KarilaBillieuxBenyamina2016" /> It has become a controlled substance in many countries.<ref name="KarilaBillieuxBenyamina2016" />

==Society and culture== thumb|right|Methylone in powder form

===Names and etymology=== "Methylone" is also a trademarked brand name for an injectable form of methylprednisolone, a corticosteroid hormone used to treat arthritis and severe allergic reactions; hence, methylone may be confused with it. Aside from context, they can be distinguished by the fact that the name will usually be capitalized when referring to the prescription drug.

A proposed alternate name is βk-MDMA, or beta-keto-MDMA. While this nomenclature has not caught on because the name "methylone" became widely used before the conflicting Methylone trademark was noticed, the analogous names for related chemicals βk-MDEA and βk-MBDB have become the established names for those substances.

===Commercial distribution=== thumb|left|upright|Bottles of ''Explosion''

Analysis of "Explosion" has confirmed that the active ingredient is methylone.<ref>{{cite web |url=http://www.erowid.org/chemicals/methylone/methylone_info1.shtml |title=Methylone sold under "Explosion" and "Inpact" brand names in the Netherlands and Japan |archive-url=https://web.archive.org/web/20090304225847/http://www.erowid.org/chemicals/methylone/methylone_info1.shtml |archive-date=2009-03-04 |date=Apr 2005 |website=www.erowid.org}}</ref>{{Unreliable source?|date=May 2014}} Many other formulations marketed as household chemicals, as well as the pure powder, have been sold.

===Legal status=== ====Netherlands==== In the Netherlands, methylone is not yet listed under the Opium Law, but is covered under the medicine act. Because methylone is not registered officially, it is forbidden to trade in methylone. The Minister of Health has asked the Coordination point Assessment and Monitoring new drugs group (CAM) to gather information about this substance, resulting possibly in an official risk assessment.<ref>{{cite journal | vauthors = van Amsterdam JG, Best W, Opperhuizen A, de Wolff FA | title = Evaluation of a procedure to assess the adverse effects of illicit drugs | journal = Regulatory Toxicology and Pharmacology | volume = 39 | issue = 1 | pages = 1–4 | date = February 2004 | pmid = 14746774 | doi = 10.1016/j.yrtph.2003.09.001 | publisher = Elsevier BV | hdl = 10029/12622 | hdl-access = free }}</ref> Until now, no research has been conducted on the toxicity of methylone, so nothing is known about the harmfulness of this new drug.

====New Zealand==== In New Zealand, although methylone is not explicitly scheduled and falls outside the strict definitions of an "amphetamine analogue" in the Misuse of Drugs Act, it is considered to be "substantially similar" to methcathinone and is thus considered by law enforcement authorities to be a Class C illegal drug. Methylone was sold in New Zealand for around 6 months from November 2005 to April 2006 as an MDMA substitute, under the name "Ease". The product was withdrawn after legal disputes with the government.<ref name="TVNZ_697050">{{cite news |url=http://tvnz.co.nz/view/page/411424/697050 |title=Party pill sparks official concern |date=7 April 2006 |work=One News |access-date=23 October 2011 |url-status=live |archive-url=https://web.archive.org/web/20120209003752/http://tvnz.co.nz/view/page/411424/697050 |archive-date=9 February 2012 }}</ref><ref>{{cite web |url=http://www.scoop.co.nz/stories/GE0604/S00032.htm |title=EASE trial terminated after conflicting advice |archive-url=https://web.archive.org/web/20120929074649/http://www.scoop.co.nz/stories/GE0604/S00032.htm |archive-date=2012-09-29 |website=scoop.co.nz |date=April 9, 2006}}</ref>

====United Kingdom==== In the United Kingdom, methylone is illegal since the 16/04/2010 revision of the misuse of drugs act. Before this it was not specifically mentioned in United Kingdom (U.K.) law as the β-ketone was not covered under the Misuse of Drugs Act. In March 2010, plans were announced to make methylone and other cathinones, Class B drugs, "within weeks". While delayed by dissatisfaction in the Advisory Council on the Misuse of Drugs, the revision was rushed through by the government with little regard for the views of the council. The importation of the compound was banned immediately.<ref>{{cite news|url=https://news.bbc.co.uk/1/hi/uk/8599814.stm|title=Suspected mephedrone-type compound seized at airport |date=1 April 2010|publisher=BBC News|access-date=3 April 2010}}</ref>

====Sweden==== ''Sveriges riksdag'' added methylone to schedule I (''"substances, plant materials and fungi which normally do not have medical use"'') as narcotics in Sweden as of Oct 1, 2010, published by ''Medical Products Agency'' in their regulation LVFS 2010:23 listed as Metylon, 2-metylamino-1-(3,4-metylendioxifenyl)propan-1-on.<ref>{{cite web |url=http://www.lakemedelsverket.se/upload/lvfs/LVFS_2010_23.pdf |title=Läkemedelsverkets föreskrifter - LVFS och HSLF-FS |publisher=Läkemedelsverket - Swedish Medical Products Agency |access-date=2010-10-07 |url-status=live |archive-url=https://web.archive.org/web/20110216190305/http://www.lakemedelsverket.se/upload/lvfs/LVFS_2010_23.pdf |archive-date=2011-02-16 }}</ref> Methylone 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 Nov 1, 2005, in their regulation SFS 2005:733 listed as 3,4-metylendioximetkatinon (Metylon).<ref>{{cite web |url=http://www.notisum.se/rnp/sls/sfs/20050733.pdf |title=Förordning om ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor; |website=notisum.se |language=sv|access-date=2015-10-10 |url-status=live |archive-url=https://web.archive.org/web/20160304112946/http://www.notisum.se/rnp/sls/sfs/20050733.pdf |archive-date=2016-03-04 }}</ref>

====Canada==== Although not listed as a Schedule 1<ref name="CDSA Schedule I: Amphetamines">{{cite web|url=http://isomerdesign.com/Cdsa/schedule.php?schedule=1&section=18.5&structure=C|title=Controlled Drugs and Substances Act: Legislative history · Schedule I · Section 19: Tramadol [Proposed]; Amphetamines|website=isomerdesign.com|access-date=28 March 2018|url-status=live|archive-url=https://web.archive.org/web/20131110200556/http://isomerdesign.com/Cdsa/schedule.php?schedule=1&section=18.5&structure=C|archive-date=10 November 2013}}</ref> substance, Health Canada reports that methylone falls under the scheduling as an analogue of amphetamine. However, methylone bears the exact chemical difference between amphetamine and cathinone – and cathinone is listed as not being an analogue of amphetamine, possibly implying that methylone is unscheduled in Canada.<ref name="Definitions and Interpretations">{{cite web|url=http://isomerdesign.com/Cdsa/definitions.php?structure=C|title=Controlled Drugs and Substances Act: Definitions and Interpretations|website=isomerdesign.com|access-date=28 March 2018|url-status=live|archive-url=https://web.archive.org/web/20131110213450/http://isomerdesign.com/Cdsa/definitions.php?structure=C|archive-date=10 November 2013}}</ref> The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1; however, methylone was not added.<ref name="Safe Streets Act">{{cite web|url=http://www.justice.gc.ca/eng/news-nouv/nr-cp/2012/doc_32759.html|title=The Safe Streets and Communities Act Four Components Coming into Force|date=18 October 2012|access-date=28 March 2018|archive-url=https://web.archive.org/web/20121018122345/http://www.justice.gc.ca/eng/news-nouv/nr-cp/2012/doc_32759.html|archive-date=18 October 2012}}</ref>

====United States==== In October 2011, the DEA issued an emergency ban on methylone. It was made illegal to possess and distribute.<ref>{{cite web|title=Chemicals Used in 'Bath Salts' Now Under Federal Control and Regulation|url=https://www.justice.gov/dea/divisions/hq/2011/hq102111.shtml|publisher=USA Dept of Justice|access-date=22 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140425083923/http://www.justice.gov/dea/divisions/hq/2011/hq102111.shtml|archive-date=25 April 2014}}</ref><ref>{{cite web|title=Schedules of Controlled Substances: Placement of Methylone Into Schedule I|url=http://www.deadiversion.usdoj.gov/fed_regs/rules/2012/fr1017.htm|access-date=22 April 2014 |website=usdoj.gov|url-status=live|archive-url=https://web.archive.org/web/20140417130900/http://www.deadiversion.usdoj.gov/fed_regs/rules/2012/fr1017.htm|archive-date=17 April 2014}}</ref> On April 4, 2013, the DEA placed methylone as a Schedule 1 substance under the CSA.<ref>{{cite web|title=Schedules of Controlled Substances: Placement of Methylone Into Schedule I|url=https://www.federalregister.gov/articles/2013/04/12/2013-08673/schedules-of-controlled-substances-placement-of-methylone-into-schedule-i |website=federalregister.gov|access-date=22 April 2014|date=2014-04-12|url-status=live|archive-url=https://web.archive.org/web/20141215042354/https://www.federalregister.gov/articles/2013/04/12/2013-08673/schedules-of-controlled-substances-placement-of-methylone-into-schedule-i|archive-date=15 December 2014}}</ref>

* Arizona: :: Effective February 16, 2012, methylenedioxymethcathinone (methylone) was classified as a dangerous drug, making it a felony to knowingly possess, use, possess for sale, manufacture, administer, transport for sale, import into the state, or offer to transport for sale or import into this state, sell, transfer or offer to sell or transfer. A.R.S. 13-3401(6)(c)(xliii), 2012 Ariz. Legis. Serv. Ch. 1 (H.B. 2356). * Florida: :: In January 2011, it was reported that Florida Attorney General Pam Bondi issued an emergency ban on MDPV, Methylone, Mephedrone, 3-methoxymethcathinone, 3-fluoromethcathinone, and 4-fluoromethcathinone as media attention on products labeled as "bath salts" grew. These chemicals are now Schedule I under Florida law.<ref>{{cite web |url=http://myfloridalegal.com/webfiles.nsf/WF/RMAS-98NQAK/$file/History-of-AGs-Scheduling-Actions.pdf |title=Florida Synthetic Drug Scheduling Actions - 2011-2014 |website=myfloridalegal.com|access-date=2017-04-08 |url-status=live |archive-url=https://web.archive.org/web/20150320074110/http://myfloridalegal.com/webfiles.nsf/WF/RMAS-98NQAK/$file/History-of-AGs-Scheduling-Actions.pdf |archive-date=2015-03-20 }}</ref> * Louisiana: :: In January 2011, Louisiana Governor Bobby Jindal emergency scheduled 3,4-methylenedioxymethcathinone (methylone), 3,4-methyenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), 4-methoxymethcathinone (methedrone), 4-fluoromethcathinone (flephedrone), and 3-fluoromethcathinone (3-FMC). * Michigan: :: Schedule 1 controlled substance in 2012. * Tennessee: :: On May 5, 2011, Tennessee Governor Bill Haslam signed a law making it a crime to knowingly produce, manufacture, distribute, sell, offer for sale or possess with intent produce, manufacture, distribute, sell, or offer for sale any product containing 3,4-methylenedioxymethcathinone (methylone), 3,4-methyenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), 4-methoxymethcathinone (methedrone), 4-fluoromethcathinone (flephedrone), and 3-fluoromethcathinone (3-FMC).<ref>{{cite web|url=http://state.tn.us/sos/acts/107/pub/pc0169.pdf|title=Welcome to the Tennessee Secretary of State's Website – Tennessee Secretary of State|website=state.tn.us|access-date=28 March 2018|url-status=live|archive-url=https://web.archive.org/web/20130901093741/http://state.tn.us/sos/acts/107/pub/pc0169.pdf|archive-date=1 September 2013}}</ref> * Texas: :: In September 2011, Texas added 3,4-methylenedioxy-''N''-methylcathinone to the Penalty Group 2 listing of the Health and Safety Code. Possession of a substance in penalty group 2 is a minimum of a state jail felony.

==Research== ===Post-traumatic stress disorder=== {{See also|List of investigational hallucinogens and entactogens}}

Under the developmental code TSND-201, methylone is under development by Transcend Therapeutics for the treatment of post-traumatic stress disorder (PTSD).<ref name="AdisInsight">{{cite web | date = 24 July 2024 | title = Methylone - Transcend Therapeutics | website = AdisInsight | url = https://adisinsight.springer.com/drugs/800072616 | access-date = 24 October 2024 }}</ref><ref name="Synapse">{{cite web | date = 20 September 2024 | title = Delving into the Latest Updates on Methylone with Synapse | website = Synapse | url = https://synapse.patsnap.com/drug/2c777b7e3faf48f18fad88d817c0ec7f | access-date = 24 October 2024 }}</ref><ref name="FierceBiotech2023">{{cite web | vauthors = Bayer M | date = 5 December 2023 | title = PTSD treatment is on the cusp of a paradigm shift. This biotech hopes to Transcend the competition | website = Fierce Biotech | url = https://www.fiercebiotech.com/biotech/budding-psychiatry-biotech-looks-transcend-ptsd-competition-sample-phase-2-data | access-date = 24 October 2024 }}</ref><ref name="JonesWarner-SchmidtKwak2026" /> As of December 2025, it is in phase 2 clinical trials for this indication,<ref name="AdisInsight" /><ref name="Synapse" /> and the FDA has granted Breakthrough Therapy designation.<ref>{{cite web | vauthors = PRNewswire | date = 2025-07-10 | title = Transcend Therapeutics Receives Breakthrough Therapy Designation for TSND- 201 (methylone) for the Treatment of PTSD | language = en-US | website = Transcend Therapeutics © | url = https://transcendtherapeutics.com/transcend-therapeutics-receives-breakthrough-therapy-designation-for-tsnd-201-methylone-for-the-treatment-of-ptsd/ | access-date = 2026-03-28 }}</ref><ref>{{cite journal | vauthors = Warner-Schmidt J, Stogniew M, Mandell B, Kelmendi B | date = February 2026 | title = Methylone promotes neurite outgrowth and has long-lasting effects on fear extinction learning | journal = Neuropsychopharmacology | volume = 51 | issue = 3 | pages = 631–640 | doi = 10.1038/s41386-025-02206-z | pmc = 12823647 | pmid = 40849539 }}</ref> The efficacy and safety findings of a phase 2 trial have been published.<ref name="JonesWarner-SchmidtKwak2026" /> In 2026, Otsuka Pharmaceutical and Transcend Therapeutics announced an agreement under which Otsuka is set to acquire Transcend for $700 million at closing. The deal includes up to $525 million in additional contingent consideration based on future sales milestones related to assets in development.<ref>{{cite web | date = 2026-03-27 | title = Otsuka Pharmaceutical to Acquire Transcend Therapeutics - Expands Otsuka portfolio in psychiatric and neurological fields and aims to accelerate development of Transcend’s portfolio, including the TSND-201 program for post-traumatic stress disorder (PTSD) | website = Otsuka Pharmaceutical Co., Ltd. | url = https://www.otsuka.co.jp/en/company/newsreleases/2026/20260327_2.html | access-date = 2026-03-28 }}</ref> In April 2026, the FDA issued a National Priority Voucher for the development of methylone for PTSD.<ref>{{Cite web |last= |first= |date=2026-04-24 |title=FDA Accelerates Action on Treatments for Serious Mental Illness Following Executive Order |url=https://www.fda.gov/news-events/press-announcements/fda-accelerates-action-treatments-serious-mental-illness-following-executive-order |access-date=2026-04-24 |website=FDA |language=en}}</ref>

==References== {{Reflist}}

==External links== * [https://isomerdesign.com/pihkal/explore/2041 Methylone - Isomer Design] * [https://psychonautwiki.org/wiki/Methylone Methylone - PsychonautWiki] * [https://www.erowid.org/chemicals/methylone/methylone.shtml Methylone - Erowid] * [https://archive.org/details/shulgin-index-vol-1/page/228/mode/1up?view=theater Methylone - The Shulgin Index]

Category:5-HT1A agonists Category:5-HT1B agonists Category:5-HT1D agonists Category:5-HT2C agonists Category:Alexander Shulgin Category:Designer drugs Category:Entactogens Category:Euphoriants Category:Experimental entactogens Category:Methylenedioxycathinones Category:Monoaminergic neurotoxins Category:Psychoplastogens Category:Serotonin-norepinephrine-dopamine releasing agents Category:Serotonin–norepinephrine–dopamine reuptake inhibitors