Aleph-2

Last updated

Aleph-2
Aleph-2.svg
Clinical data
Other namesALEPH-2; DOT-2; 4-Ethylthio-2,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-ethylthioamphetamine; 4-EtS-DMA
Routes of
administration 		Oral [1] [2]
Drug class Serotonergic psychedelic; Hallucinogen; Serotonin 5-HT2 receptor agonist
ATC code
  • None
Pharmacokinetic data
Duration of action 8–16 hours [1] [2]
Identifiers
  • 1-(4-ethylsulfanyl-2,5-dimethoxyphenyl)propan-2-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C13H21NO2S
Molar mass 255.38 g·mol−1
3D model (JSmol)
  • CCSC1=C(C=C(C(=C1)OC)CC(C)N)OC
  • InChI=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
  • Key: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. [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]

Contents

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 Tooltip half-maximal effective concentration)
104–108% (Emax Tooltip maximal efficacy)
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 Tooltip Trace amine-associated receptor 1ND
SERT Tooltip Serotonin transporter1,318 (Ki)
NET Tooltip Norepinephrine transporter>10,000 (Ki)
DAT Tooltip Dopamine transporter>10,000 (Ki)
MAO-A Tooltip Monoamine oxidase A3,200–3,800 (IC50) (rat)
MAO-B Tooltip Monoamine oxidase 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 Tooltip half-maximal inhibitory concentration 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

References

  1. 1 2 3 4 5 6 7 8 9 10 Shulgin T, Shulgin A (1991). "#4 ALEPH-2 2,5-DIMETHOXY-4-ETHYLTHIOAMPHETAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. pp. 464–467. ISBN   978-0-9630096-0-9. OCLC   25627628.
  2. 1 2 3 4 5 6 7 8 Shulgin A, Manning T, Daley PF (2011). "#4. ALEPH-2". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds . Vol. 1. Berkeley, CA: Transform Press. p. 5. ISBN   978-0-9630096-3-0. OCLC   709667010.
  3. 1 2 3 Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2) e9019. Bibcode:2010PLoSO...5.9019R. doi: 10.1371/journal.pone.0009019 . PMC   2814854 . PMID   20126400.
  4. 1 2 "ALEPH-2". АИПСИН (in Russian). 1 May 1996. Retrieved 1 January 2026.
  5. ↑ "Kᵢ Database". PDSP. 1 April 2025. Retrieved 1 April 2025.
  6. ↑ Liu T. "BDBM50164337 2-(4-Ethylsulfanyl-2,5-dimethoxy-phenyl)-1-methyl-ethylamine::CHEMBL339611". BindingDB. Retrieved 1 April 2025.
  7. 1 2 Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol. 10 1590. doi: 10.3389/fphar.2019.01590 . PMC   6989591 . PMID   32038257.
  8. 1 2 Scorza MC, Carrau C, Silveira R, Zapata-Torres G, Cassels BK, Reyes-Parada M (December 1997). "Monoamine oxidase inhibitory properties of some methoxylated and alkylthio amphetamine derivatives: structure-activity relationships" (PDF). Biochem Pharmacol. 54 (12): 1361–1369. doi:10.1016/s0006-2952(97)00405-x. PMID   9393679.
  9. ↑ Gallardo-Godoy A, Fierro A, McLean TH, Castillo M, Cassels BK, Reyes-Parada M, et al. (April 2005). "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. doi:10.1021/jm0493109. PMID   15801832.
  10. 1 2 Acuña-Castillo C, Scorza C, Reyes-Parada M, Cassels BK, Huidobro-Toro JP (November 2000). "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. doi:10.1016/s0024-3205(00)00906-1. PMID   11191631.
  11. ↑ Scorza MC, Reyes-Parada M, Silveira R, Viola H, Medina JH, Viana MB, et al. (June 1996). "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. doi:10.1016/0091-3057(95)02149-3. PMID   8743595.
  12. ↑ Reyes-Parada M, Scorza C, Romero V, Silveira R, Medina JH, Andrus D, et al. (November 1996). "(+/-)-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. doi:10.1007/BF00170831. PMID   8938655.
  13. ↑ Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN   978-1-4757-0512-6.
  14. ↑ Braun U, Braun G, Jacob P, Nichols DE, Shulgin AT (1978). "Mescaline Analogs: Substitutions at the 4-Position" (PDF). In Barnett G, Trsic M, Willette RE (eds.). QuaSAR: Quantitative Structure Activity Relationships Of Analgesics, Narcotic Antagonists, And Hallucinogens (PDF). National Institute on Drug Abuse Research Monograph Series. Vol. 22. National Institute on Drug Abuse. pp. 27–37. PMID   101882. Archived from the original (PDF) on 2023-08-05. Retrieved 2025-11-24.
  15. ↑ Shulgin AT (1980). "Hallucinogens". In Burger A, Wolf ME (eds.). Burger's Medicinal Chemistry. Vol. 3 (4 ed.). New York: Wiley. pp. 1109–1137. ISBN   978-0-471-01572-7. OCLC   219960627.
  16. ↑ Shulgin AT (1982). "Chemistry of Psychotomimetics". In Hoffmeister F, Stille G (eds.). Psychotropic Agents, Part III: Alcohol and Psychotomimetics, Psychotropic Effects of Central Acting Drugs. Handbook of Experimental Pharmacology. Vol. 55. Berlin: Springer Berlin Heidelberg. pp. 3–29. doi:10.1007/978-3-642-67770-0_1. ISBN   978-3-642-67772-4. OCLC   8130916.
  17. ↑ "Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.
  18. 1 2 Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) (PDF), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026
  19. ↑ Drug Enforcement Administration (3 December 2007). "Definition of "Positional Isomer" as It Pertains to the Control of Schedule I Controlled Substances". Federal Register.
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