Aleph-2

{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | drug_name = | image = Aleph-2.svg | image_class = skin-invert-image | width = 250px | image2 = Aleph-2 ball-and-stick structure.png | image_class2 = bg-transparent | width2 = 200px

<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = Oral<ref name="PiHKAL" /><ref name="ShulginManningDaley2011" /> | class = Serotonergic psychedelic; Hallucinogen; Serotonin 5-HT₂ receptor agonist | ATC_prefix = None | ATC_suffix =

<!-- Legal status --> | legal_status =

<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = 8–16{{nbsp}}hours<ref name="PiHKAL" /><ref name="ShulginManningDaley2011" /> | excretion =

<!-- Identifiers --> | CAS_number = 185562-00-9 | CAS_supplemental = | PubChem = 10264356 | PubChemSubstance = | IUPHAR_ligand = | DrugBank = DB13940 | ChemSpiderID = 8439835 | UNII = Z1I419DRZZ | KEGG = | ChEBI = | ChEMBL = 339611 | NIAID_ChemDB = | PDB_ligand = | synonyms = ALEPH-2; DOT-2; 4-Ethylthio-2,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-ethylthioamphetamine; 4-EtS-DMA

<!-- Chemical data --> | IUPAC_name = 1-(4-ethylsulfanyl-2,5-dimethoxyphenyl)propan-2-amine | C=13 | H=21 | N=1 | O=2 | S=1 | SMILES = CCSC1=C(C=C(C(=C1)OC)CC(C)N)OC | StdInChI = 1S/C13H21NO2S/c1-5-17-13-8-11(15-3)10(6-9(2)14)7-12(13)16-4/h7-9H,5-6,14H2,1-4H3 | StdInChIKey = MCYCODJKXUJSAT-UHFFFAOYSA-N }}

'''Aleph-2''', or '''ALEPH-2''', also known as '''4-ethylthio-2,5-dimethoxyamphetamine''', is a psychedelic drug of the phenethylamine, amphetamine, and DOx families.<ref name="PiHKAL">{{cite book | vauthors = Shulgin T, Shulgin A | chapter = #4 ALEPH-2 2,5-DIMETHOXY-4-ETHYLTHIOAMPHETAMINE | pages = 464–467 | chapter-url = https://www.erowid.org/library/books_online/pihkal/pihkal004.shtml | title = PiHKAL: A Chemical Love Story | date = 1991 | publisher = Transform Press | edition = 1st | location = Berkeley, CA | isbn = 978-0-9630096-0-9 | oclc = 25627628 | url = https://books.google.com/books?id=O8AdHBGybpcC }}</ref><ref name="ShulginManningDaley2011">{{cite book | vauthors = Shulgin A, Manning T, Daley PF | chapter = #4. ALEPH-2 | pages = 5 | chapter-url = https://archive.org/details/shulgin-index-vol-1/page/5/mode/1up | title = The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds | publisher = Transform Press | location = Berkeley, CA | volume = 1 | year = 2011 | isbn = 978-0-9630096-3-0 | oclc = 709667010 }}</ref><ref name="Ray2010" /> It is one of the Aleph series of compounds.<ref name="PiHKAL" /> The drug was encountered as a novel designer drug in Europe in 2023.<ref name="Aipsin">{{cite web | title=ALEPH-2 | website=АИПСИН | date=1 May 1996 | url=https://aipsin.com/newsubstance/1449/ | language=ru | access-date=1 January 2026}}</ref>

==Use and effects== In his book ''PiHKAL'' (''Phenethylamines I Have Known and Loved''), Alexander Shulgin lists Aleph-2's dose as 4 to 8{{nbsp}}mg orally and its duration as 8 to 16{{nbsp}}hours.<ref name="PiHKAL" /><ref name="ShulginManningDaley2011" /> The effects of Aleph-2 have been reported to include "almost no visual phenomena" to "extraordinary visuals and interpretations", visual distortion and movement, enhanced auditory and tactile perception, and a sensation of physical warmth, and residual shakiness and muscle tremors, among others.<ref name="PiHKAL" /><ref name="ShulginManningDaley2011" /> There is an unpredictability with the dosing and effects of Aleph-2, such that one person who took 4{{nbsp}}mg had strong effects including ending up in a fetal position, in relative hibernation for several hours, and with substantial amnesia, whereas another person who took 8{{nbsp}}mg experienced only a bare threshold including slight lightheadedness.<ref name="PiHKAL" />

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

==Pharmacology== ===Pharmacodynamics=== {| class="wikitable floatleft" style="font-size:small;" |+ {{Nowrap|Aleph-2 activities}} |- ! Target !! Affinity (K_i, nM) |- | 5-HT_1A || 1,674 |- | 5-HT_1B || 2,037 |- | 5-HT_1D || 1,532 |- | 5-HT_1E || 3,088 |- | 5-HT_1F || {{Abbr|ND|No data}} |- | 5-HT_2A || 60.4 (K_i)<br />0.489–0.898 ({{Abbrlink|EC₅₀|half-maximal effective concentration}})<br />104–108% ({{Abbrlink|E_max|maximal efficacy}}) |- | 5-HT_2B || 1.6 |- | 5-HT_2C || 50.3 (K_i)<br />0.0912–0.401 ({{Abbr|EC₅₀|half-maximal effective concentration}})<br />105–114% ({{Abbr|E_max|maximal efficacy}}) |- | 5-HT₃ || >10,000 |- | 5-HT₄ || {{Abbr|ND|No data}} |- | 5-HT_5A || >10,000 |- | 5-HT₆ || 3,020 |- | 5-HT₇ || 1,322 |- | α_1A || >10,000 |- | α_1B || >10,000 |- | α_1D || {{Abbr|ND|No data}} |- | α_2A || 5,803 |- | α_2B || 2,934 |- | α_2C || 1,388 |- | β₁ || 6,792 |- | β₂ || 26.1 |- | β₃ || {{Abbr|ND|No data}} |- | D₁, D₂ || >10,000 |- | D₃ || 618.3 |- | D₄, D₅ || >10,000 |- | H₁–H₄ || >10,000 |- | M₁, M₂ || >10,000 |- | M₃ || 1,907 |- | M₄ || >10,000 |- | M₅ || 8,018 |- | I₁ || 319.8 |- | σ₁ || 238.9 |- | σ₂ || >10,000 |- | {{Abbrlink|TAAR1|Trace amine-associated receptor 1}} || {{Abbr|ND|No data}} |- | {{Abbrlink|SERT|Serotonin transporter}} || 1,318 (K_i) |- | {{Abbrlink|NET|Norepinephrine transporter}} || >10,000 (K_i) |- | {{Abbrlink|DAT|Dopamine transporter}} || >10,000 (K_i) |- | {{Abbrlink|MAO-A|Monoamine oxidase A}} || 3,200–3,800 ({{Abbr|IC₅₀|half-maximal inhibitory concentration}}) (rat) |- | {{Abbrlink|MAO-B|Monoamine oxidase B}} || >100,000 ({{Abbr|IC₅₀|half-maximal inhibitory concentration}}) (rat) |- |- class="sortbottom" | colspan="2" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. '''Refs:''' <ref name="PDSPKiDatabase">{{cite web | title=Kᵢ Database | website=PDSP | date=1 April 2025 | url=https://pdsp.unc.edu/kidb2/kidb/web/kis-results/index?KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=12945&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D= | access-date=1 April 2025}}</ref><ref name="BindingDB">{{cite web | vauthors = Liu T | title = BDBM50164337 2-(4-Ethylsulfanyl-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::CHEMBL339611 | work = BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50164337 | access-date=1 April 2025}}</ref><ref name="Ray2010" /><ref name="Reyes-ParadaIturriaga-VasquezCassels2019">{{cite journal | vauthors = Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK | title = Amphetamine Derivatives as Monoamine Oxidase Inhibitors | journal = Front Pharmacol | volume = 10 | issue = | article-number = 1590 | date = 2019 | pmid = 32038257 | pmc = 6989591 | doi = 10.3389/fphar.2019.01590 | doi-access = free }}</ref><ref name="ScorzaCarrauSilveira1997">{{cite journal | vauthors = Scorza MC, Carrau C, Silveira R, Zapata-Torres G, Cassels BK, Reyes-Parada M | title = Monoamine oxidase inhibitory properties of some methoxylated and alkylthio amphetamine derivatives: structure-activity relationships | journal = Biochem Pharmacol | volume = 54 | issue = 12 | pages = 1361–1369 | date = December 1997 | pmid = 9393679 | doi = 10.1016/s0006-2952(97)00405-x | url = https://mrtoasted.com/~vaaguh/maoi-properties-of-methoxylated-and-alkylthioamp-derivates.pdf}}</ref><ref name="Gallardo-GodoyFierroMcClean2005">{{cite journal | vauthors = Gallardo-Godoy A, Fierro A, McLean TH, Castillo M, Cassels BK, Reyes-Parada M, Nichols DE | title = Sulfur-substituted alpha-alkyl phenethylamines as selective and reversible MAO-A inhibitors: biological activities, CoMFA analysis, and active site modeling | journal = J Med Chem | volume = 48 | issue = 7 | pages = 2407–2419 | date = April 2005 | pmid = 15801832 | doi = 10.1021/jm0493109 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=61e1af109f88d1c41da1f218f9403dff12b5d98d| url-access = subscription }}</ref> |}

Aleph-2 acts as a serotonin 5-HT₂ receptor agonist.<ref name="Ray2010">{{cite journal | vauthors = Ray TS | title = Psychedelics and the human receptorome | journal = PLOS ONE | volume = 5 | issue = 2 |article-number=e9019 | date = February 2010 | pmid = 20126400 | pmc = 2814854 | doi = 10.1371/journal.pone.0009019 | doi-access = free | bibcode = 2010PLoSO...5.9019R }}</ref><ref name="Acuña-CastilloScorzaReyes-Parada2000" /> The drug is also a weak monoamine oxidase inhibitor (MAOI), with {{Abbrlink|IC₅₀|half-maximal inhibitory concentration}} values of 3,200{{nbsp}}nM for monoamine oxidase A (MAO-A) and >100,000{{nbsp}}nM for monoamine oxidase B (MAO-B).<ref name="Reyes-ParadaIturriaga-VasquezCassels2019" /><ref name="ScorzaCarrauSilveira1997" /> Aleph-2 produces anxiolytic effects in rodents.<ref name="Acuña-CastilloScorzaReyes-Parada2000">{{cite journal | vauthors = Acuña-Castillo C, Scorza C, Reyes-Parada M, Cassels BK, Huidobro-Toro JP | title = ALEPH-2, a suspected anxiolytic and putative hallucinogenic phenylisopropylamine derivative, is a 5-HT2a and 5-HT2c receptor agonist | journal = Life Sciences | volume = 67 | issue = 26 | pages = 3241–3247 | date = November 2000 | pmid = 11191631 | doi = 10.1016/s0024-3205(00)00906-1 }}</ref><ref name="ScorzaReyes-ParadaSilveira1996">{{cite journal | vauthors = Scorza MC, Reyes-Parada M, Silveira R, Viola H, Medina JH, Viana MB, Zangrossi H, Graeff FG | title = Behavioral effects of the putative anxiolytic (+/-)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) in rats and mice | journal = Pharmacology, Biochemistry, and Behavior | volume = 54 | issue = 2 | pages = 355–361 | date = June 1996 | pmid = 8743595 | doi = 10.1016/0091-3057(95)02149-3 }}</ref><ref name="Reyes-ParadaScorzaRomero1996">{{cite journal | vauthors = Reyes-Parada M, Scorza C, Romero V, Silveira R, Medina JH, Andrus D, Nichols DE, Cassels BK | title = (+/-)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 354 | issue = 5 | pages = 579–585 | date = November 1996 | pmid = 8938655 | doi = 10.1007/BF00170831 }}</ref>

==Chemistry== ===Synthesis=== The chemical synthesis of Aleph-2 has been described.<ref name="PiHKAL" /><ref name="ShulginManningDaley2011" />

===Analogues=== Analogues of Aleph-2 include Aleph, Aleph-4, Aleph-6, Aleph-7, and 2C-T-2, among others.<ref name="PiHKAL" /><ref name="ShulginManningDaley2011" />

==History== Aleph-2 was first described in the scientific literature by Alexander Shulgin in 1978.<ref name="Shulgin1978">{{cite book | vauthors = Shulgin AT | chapter=Psychotomimetic Drugs: Structure-Activity Relationships | veditors = Iversen LL, Iversen SD, Snyder SH | title=Stimulants | publisher=Springer US | publication-place=Boston, MA | date=1978 | isbn=978-1-4757-0512-6 | doi=10.1007/978-1-4757-0510-2_6 | pages=243–333 | chapter-url=https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6 | url=https://books.google.com/books?id=h0_uBwAAQBAJ&pg=PA261}}</ref><ref name="BraunBraunJacob1978">{{cite book | vauthors = Braun U, Braun G, Jacob P, Nichols DE, Shulgin AT | chapter = Mescaline Analogs: Substitutions at the 4-Position | pages = 27–37 | veditors = Barnett G, Trsic M, Willette RE | title = QuaSAR: Quantitative Structure Activity Relationships Of Analgesics, Narcotic Antagonists, And Hallucinogens | series = National Institute on Drug Abuse Research Monograph Series | volume = 22 | date = 1978 | issue = 22 | publisher = National Institute on Drug Abuse | pmid = 101882 | url = https://archives.nida.nih.gov/sites/default/files/monograph22.pdf | chapter-url = https://archives.nida.nih.gov/sites/default/files/monograph22.pdf#page=38 | archive-date = 2023-08-05 | access-date = 2025-11-24 | archive-url = https://web.archive.org/web/20230805004421/https://archives.nida.nih.gov/sites/default/files/monograph22.pdf | url-status = dead }}</ref><ref name="Shulgin1980">{{cite book | vauthors = Shulgin AT | chapter = Hallucinogens | pages = 1109–1137 | chapter-url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6ac0c892ee380436f614d3aae0686ef617b2e0c5 | veditors = Burger A, Wolf ME | title = Burger's Medicinal Chemistry | edition = 4 | volume = 3 | date = 1980 | publisher = Wiley | location = New York | isbn = 978-0-471-01572-7 | oclc = 219960627 | url = https://books.google.com/books?id=2b3wAAAAMAAJ}}</ref><ref name="Shulgin1982">{{cite book | vauthors = Shulgin AT | veditors = Hoffmeister F, Stille G | chapter = Chemistry of Psychotomimetics | title = Psychotropic Agents, Part III: Alcohol and Psychotomimetics, Psychotropic Effects of Central Acting Drugs | location = Berlin | volume = 55 | issue = Part 3 | pages = 3–29 | date = 1982 | doi = 10.1007/978-3-642-67770-0_1 | series = Handbook of Experimental Pharmacology | publisher = Springer Berlin Heidelberg | isbn = 978-3-642-67772-4 | oclc = 8130916 | url = https://books.google.com/books?id=mrT8CAAAQBAJ | chapter-url = https://bitnest.netfirms.com/external/10.1007/978-3-642-67770-0_1}}</ref> Subsequently, it was described in greater detail by Shulgin in his 1991 book ''PiHKAL'' (''Phenethylamines I Have Known and Loved'').<ref name="PiHKAL" /> Aleph-2 was encountered as a novel designer drug in Europe in 2023.<ref name="Aipsin" />

==Society and culture== ===Legal status=== ====Canada==== Aleph-2 is a controlled substance in Canada under phenethylamine blanket-ban language.<ref name="CDSA">{{cite web | title=Controlled Drugs and Substances Act | website=Department of Justice Canada | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html | access-date=19 January 2026}}</ref>

====United States==== Aleph-2 is not an explicitly controlled substance in the United States.<ref name="OrangeBook2026">{{citation | title = Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) | date = January 2026 | publisher = U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division | location = United States | url = https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf}}</ref><ref name="ShulginManningDaley2011" /> However, it is a Schedule I controlled substance in this country as an isomer of 2C-T-4.<ref name="OrangeBook2026" /><ref name="DEA2007">{{cite web | author=Drug Enforcement Administration | title=Definition of “Positional Isomer” as It Pertains to the Control of Schedule I Controlled Substances | website=Federal Register | date=3 December 2007 | url=https://www.federalregister.gov/documents/2007/12/03/E7-23413/definition-of-positional-isomer-as-it-pertains-to-the-control-of-schedule-i-controlled-substances}}</ref>

== See also == * DOx (psychedelics) * Aleph (psychedelics) * 2C-T-2

== References == {{Reflist}}

== External links == * [https://isomerdesign.com/pihkal/explore/4 Aleph-2 - Isomer Design] * [https://www.erowid.org/library/books_online/pihkal/pihkal004.shtml Aleph-2 - PiHKAL - Erowid] * [https://isomerdesign.com/pihkal/read/pk/4 Aleph-2 - PiHKAL - Isomer Design] * [https://archive.org/details/shulgin-index-vol-1/page/5/mode/1up?view=theater Aleph-2 - The Shulgin Index]

{{Psychedelics}} {{Serotonin receptor modulators}} {{Monoamine metabolism modulators}} {{Phenethylamines}}

Category:5-HT2A agonists Category:5-HT2C agonists Category:Anxiolytics Category:Designer drugs Category:DOx (psychedelics) Category:Ethylthio compounds Category:Monoamine oxidase inhibitors Category:PiHKAL Category:Psychedelic phenethylamines