Chemistry:Aleph-2

From HandWiki

Aleph-2, or ALEPH-2, also known as 4-ethylthio-2,5-dimethoxyamphetamine, is a psychedelic drug of the phenethylamine, amphetamine, and DOx families.[1][2][3] It is one of the Aleph series of compounds.[1] The drug was encountered as a novel designer drug in Europe in 2023.[4]

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists Aleph-2's dose as 4 to 8 mg orally and its duration as 8 to 16 hours.[1][2] 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.[1][2] There is an unpredictability with the dosing and effects of Aleph-2, such that one person who took 4 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 mg experienced only a bare threshold including slight lightheadedness.[1]

Interactions

Pharmacology

Pharmacodynamics

Aleph-2 activities
Target Affinity (Ki, nM)
5-HT1A 1,674
5-HT1B 2,037
5-HT1D 1,532
5-HT1E 3,088
5-HT1F ND
5-HT2A 60.4 (Ki)
0.489–0.898 (EC50)
104–108% (Emax)
5-HT2B 1.6
5-HT2C 50.3 (Ki)
0.0912–0.401 (EC50)
105–114% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 3,020
5-HT7 1,322
α1A >10,000
α1B >10,000
α1D ND
α2A 5,803
α2B 2,934
α2C 1,388
β1 6,792
β2 26.1
β3 ND
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
TAAR1 ND
SERT 1,318 (Ki)
NET >10,000 (Ki)
DAT >10,000 (Ki)
MAO-A 3,200–3,800 (IC50) (rat)
MAO-B >100,000 (IC50) (rat)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [5][6][3][7][8][9]

Aleph-2 acts as a serotonin 5-HT2 receptor agonist.[3][10] The drug is also a weak monoamine oxidase inhibitor (MAOI), with IC50 values of 3,200 nM for monoamine oxidase A (MAO-A) and >100,000 nM for monoamine oxidase B (MAO-B).[7][8] Aleph-2 produces anxiolytic effects in rodents.[10][11][12]

Chemistry

Synthesis

The chemical synthesis of Aleph-2 has been described.[1][2]

Analogues

Analogues of Aleph-2 include Aleph, Aleph-4, Aleph-6, Aleph-7, and 2C-T-2, among others.[1][2]

History

Aleph-2 was first described in the scientific literature by Alexander Shulgin in 1978.[13][14][15][16] Subsequently, it was described in greater detail by Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1] Aleph-2 was encountered as a novel designer drug in Europe in 2023.[4]

Society and culture

Canada

Aleph-2 is a controlled substance in Canada under phenethylamine blanket-ban language.[17]

United States

Aleph-2 is not an explicitly controlled substance in the United States.[18][2] However, it is a Schedule I controlled substance in this country as an isomer of 2C-T-4.[18][19]

See also

  • DOx (psychedelics)
  • Aleph (psychedelics)
  • 2C-T-2

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "#4 ALEPH-2 2,5-DIMETHOXY-4-ETHYLTHIOAMPHETAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. 1991. pp. 464–467. ISBN 978-0-9630096-0-9. OCLC 25627628. https://www.erowid.org/library/books_online/pihkal/pihkal004.shtml. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "#4. ALEPH-2". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. 1. Berkeley, CA: Transform Press. 2011. pp. 5. ISBN 978-0-9630096-3-0. OCLC 709667010. https://archive.org/details/shulgin-index-vol-1/page/5/mode/1up. 
  3. ↑ 3.0 3.1 3.2 "Psychedelics and the human receptorome". PLOS ONE 5 (2). February 2010. doi:10.1371/journal.pone.0009019. PMID 20126400. Bibcode: 2010PLoSO...5.9019R. 
  4. ↑ 4.0 4.1 "ALEPH-2" (in ru). 1 May 1996. https://aipsin.com/newsubstance/1449/. 
  5. ↑ "Kᵢ Database". 1 April 2025. 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=. 
  6. ↑ "BDBM50164337 2-(4-Ethylsulfanyl-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::CHEMBL339611". BindingDB. https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50164337. 
  7. ↑ 7.0 7.1 "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol 10. 2019. doi:10.3389/fphar.2019.01590. PMID 32038257. 
  8. ↑ 8.0 8.1 "Monoamine oxidase inhibitory properties of some methoxylated and alkylthio amphetamine derivatives: structure-activity relationships". Biochem Pharmacol 54 (12): 1361–1369. December 1997. doi:10.1016/s0006-2952(97)00405-x. PMID 9393679. https://mrtoasted.com/~vaaguh/maoi-properties-of-methoxylated-and-alkylthioamp-derivates.pdf. 
  9. ↑ "Sulfur-substituted alpha-alkyl phenethylamines as selective and reversible MAO-A inhibitors: biological activities, CoMFA analysis, and active site modeling". J Med Chem 48 (7): 2407–2419. April 2005. doi:10.1021/jm0493109. PMID 15801832. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=61e1af109f88d1c41da1f218f9403dff12b5d98d. 
  10. ↑ 10.0 10.1 "ALEPH-2, a suspected anxiolytic and putative hallucinogenic phenylisopropylamine derivative, is a 5-HT2a and 5-HT2c receptor agonist". Life Sciences 67 (26): 3241–3247. November 2000. doi:10.1016/s0024-3205(00)00906-1. PMID 11191631. 
  11. ↑ "Behavioral effects of the putative anxiolytic (+/-)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) in rats and mice". Pharmacology, Biochemistry, and Behavior 54 (2): 355–361. June 1996. doi:10.1016/0091-3057(95)02149-3. PMID 8743595. 
  12. ↑ "(+/-)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors". Naunyn-Schmiedeberg's Archives of Pharmacology 354 (5): 579–585. November 1996. doi:10.1007/BF00170831. PMID 8938655. 
  13. ↑ "Psychotomimetic Drugs: Structure-Activity Relationships". Stimulants. Boston, MA: Springer US. 1978. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6. https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6. 
  14. ↑ "Mescaline Analogs: Substitutions at the 4-Position". QuaSAR: Quantitative Structure Activity Relationships Of Analgesics, Narcotic Antagonists, And Hallucinogens. National Institute on Drug Abuse Research Monograph Series. 22. National Institute on Drug Abuse. 1978. pp. 27–37. https://archives.nida.nih.gov/sites/default/files/monograph22.pdf#page=38. Retrieved 2025-11-24. 
  15. ↑ "Hallucinogens". Burger's Medicinal Chemistry. 3 (4 ed.). New York: Wiley. 1980. pp. 1109–1137. ISBN 978-0-471-01572-7. OCLC 219960627. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6ac0c892ee380436f614d3aae0686ef617b2e0c5. 
  16. ↑ "Chemistry of Psychotomimetics". Psychotropic Agents, Part III: Alcohol and Psychotomimetics, Psychotropic Effects of Central Acting Drugs. Handbook of Experimental Pharmacology. 55. Berlin: Springer Berlin Heidelberg. 1982. pp. 3–29. doi:10.1007/978-3-642-67770-0_1. ISBN 978-3-642-67772-4. OCLC 8130916. https://bitnest.netfirms.com/external/10.1007/978-3-642-67770-0_1. 
  17. ↑ "Controlled Drugs and Substances Act". https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 
  18. ↑ 18.0 18.1 Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026, https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf 
  19. ↑ Drug Enforcement Administration (3 December 2007). "Definition of “Positional Isomer” as It Pertains to the Control of Schedule I Controlled Substances". 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. 



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