Escaline

Escaline (E), also known as 3,5-dimethoxy-4-ethoxyphenethylamine, is a psychedelic drug of the phenethylamine and scaline families related to mescaline.^[1] It is the 4-ethoxy analogue of mescaline (3,4,5-trimethoxyphenethylamine) and the phenethylamine (non-α-methyl) analogue of 3C-E (3,5-dimethoxy-4-ethoxyamphetamine).^[1]

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists the dose range of escaline as 40 to 60 mg of the hydrochloride salt taken orally.^[1]^[2] The duration is stated to be 8 to 12 hours, whereas the onset is not described.^[1] Escaline is approximately 5- to 8-fold more potent than mescaline.^[3]

The effects of escaline have been described relatively limitedly but have been reported to include sensory enhancement without an intellectual component, little synthesis of external sensory inputs like music or visual stimuli, easy fantasy, rational thinking and insight, pleasantness, powerful and complex intoxication, pain relief, muscle tension, motor incoordination to the extent of not being able to walk or tie one's shoelaces, body tension that outweighed the desired psychoactive effects, tachycardia, dehydration, nightmares, and next-day hangover symptoms such as tiredness and low energy.^[1]

Interactions

Pharmacology

Pharmacodynamics

The receptor interactions of escaline and analogues have been described.^[4]^[5]

Escaline produces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents.^[6]^[2] It partially substitutes for LSD in rodent drug discrimination tests.^[7]

History

Escaline was first synthesized and reported in the scientific literature by Benington and colleagues in 1954.^[8] It was later re-examined in the laboratory of David E. Nichols, who prepared a series of mescaline analogues that included escaline, proscaline, and isoproscaline and published their work in 1977.^[9]^[10]

Society and culture

Legal status

Sweden

Escaline is illegal in Sweden as of 26 January 2016.^[11]

United States

Escaline is a Schedule I controlled substance (DEA #7930) in the United States with the reason cited being that it is a positional isomer of 3,4,5-trimethoxyamphetamine (TMA).^[12]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 "Erowid Online Books : "PIHKAL" - #72 E". https://www.erowid.org/library/books_online/pihkal/pihkal072.shtml.
↑ ^2.0 ^2.1 "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology 167. May 2020. doi:10.1016/j.neuropharm.2019.107933. PMID 31917152. PMC 9191653. http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf.
↑ "Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors". ChemMedChem 3 (9): 1299–1309. September 2008. doi:10.1002/cmdc.200800133. PMID 18666267. https://www.thevespiary.org/rhodium/Rhodium/Vespiary/talk/files/1981-Structure%E2%80%93Activity-Relationships-of-Phenylalkylamines-asAgonist-Ligands-for-5-HT2A-Receptors807f.pdf.
↑ "Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines". Frontiers in Pharmacology 12. 2021. doi:10.3389/fphar.2021.794254. PMID 35222010. PMC 8865417. https://edoc.unibas.ch/87985/1/fphar-12-794254.pdf.
↑ "The polypharmacology of psychedelics reveals multiple targets for potential therapeutics". Neuron. July 2025. doi:10.1016/j.neuron.2025.06.012. PMID 40683247. https://web.archive.org/web/20250725061718/https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/7d8365fe-51f3-4a28-bf40-9999bec837f6/mmc11.pdf.
↑ "Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice". Journal of Psychopharmacology 33 (3): 406–414. March 2019. doi:10.1177/0269881119826610. PMID 30789291. PMC 6848748. https://www.researchgate.net/publication/331263972.
↑ "Dark Classics in Chemical Neuroscience: Mescaline". ACS Chemical Neuroscience 9 (10): 2448–2458. October 2018. doi:10.1021/acschemneuro.8b00215. PMID 29847089. https://shaunlacob.com/wp-content/uploads/2020/12/DC-MESCALINE.pdf. "In the case of the 3,4,5- trioxygenated compounds, binding studies at 5-HT2A and 5- HT2C receptors revealed somewhat higher affinities than mescaline but, in phosphoinositide hydrolysis assays (only for 5-HT2A), lower efficacies relative to serotonin and the full agonist mescaline (60 and 45%, respectively). More striking, however, was the observation that the new compounds did not fully substitute for LSD in LSD-trained rats, and at doses well above the mescaline EC50, only 50 and 29% appropriate responding was recorded. In view of this unexpected result, 3,5- dimethoxy-4-ethoxyphenethylamine (escaline), which is considerably more potent than mescaline in humans,128 was also tested. It was found to have about twice the affinity of mescaline for 5-HT2A receptors and was a complete agonist with very similar functional potency, but again it failed to substitute completely for LSD in the drug discrimination experiments.".
↑ "Synthesis of 4-Hydroxy- and 4-Ethoxy-3,5-dimethoxy-β-phenethylamines 1". Journal of the American Chemical Society 76 (21): 5555–5556. 1954. doi:10.1021/ja01650a084. ISSN 0002-7863. Bibcode: 1954JAChS..76.5555B.
↑ "Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogues". Journal of Medicinal Chemistry 20 (2): 299–301. February 1977. doi:10.1021/jm00212a022. PMID 836502.
↑ "Directional lipophilic character in a series of psychotomimetic phenethylamine derivatives". Life Sciences 21 (4): 569–575. August 1977. doi:10.1016/0024-3205(77)90099-6. PMID 904435.
↑ "31 nya ämnen kan klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. November 2015. http://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2015/november/31-nya-amnen-kan-klassas-som-narkotika-eller-halsofarlig-vara/.
↑ "Controlled Substances - Alphabetical Order". Diversion Control Division, Drug Enforcement Administration. U.S. Department of Justice. December 2024. https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf.

External links

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Original source: https://en.wikipedia.org/wiki/Escaline. Read more

[PiHKAL-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 "Erowid Online Books : "PIHKAL" - #72 E". https://www.erowid.org/library/books_online/pihkal/pihkal072.shtml.

[HalberstadtChathaKlein2020-2] 2.0 ^2.1 "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology 167. May 2020. doi:10.1016/j.neuropharm.2019.107933. PMID 31917152. PMC 9191653. http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf.

[BlaazerSmidKruse2008-3] "Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors". ChemMedChem 3 (9): 1299–1309. September 2008. doi:10.1002/cmdc.200800133. PMID 18666267. https://www.thevespiary.org/rhodium/Rhodium/Vespiary/talk/files/1981-Structure%E2%80%93Activity-Relationships-of-Phenylalkylamines-asAgonist-Ligands-for-5-HT2A-Receptors807f.pdf.

[KolaczynskaLuethiTrachsel2021-4] "Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines". Frontiers in Pharmacology 12. 2021. doi:10.3389/fphar.2021.794254. PMID 35222010. PMC 8865417. https://edoc.unibas.ch/87985/1/fphar-12-794254.pdf.

[JainGumpperSlocum2025-5] "The polypharmacology of psychedelics reveals multiple targets for potential therapeutics". Neuron. July 2025. doi:10.1016/j.neuron.2025.06.012. PMID 40683247. https://web.archive.org/web/20250725061718/https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/7d8365fe-51f3-4a28-bf40-9999bec837f6/mmc11.pdf.

[HalberstadtChathaChapman2019-6] "Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice". Journal of Psychopharmacology 33 (3): 406–414. March 2019. doi:10.1177/0269881119826610. PMID 30789291. PMC 6848748. https://www.researchgate.net/publication/331263972.

[CasselsSáez-Briones2018-7] "Dark Classics in Chemical Neuroscience: Mescaline". ACS Chemical Neuroscience 9 (10): 2448–2458. October 2018. doi:10.1021/acschemneuro.8b00215. PMID 29847089. https://shaunlacob.com/wp-content/uploads/2020/12/DC-MESCALINE.pdf. "In the case of the 3,4,5- trioxygenated compounds, binding studies at 5-HT2A and 5- HT2C receptors revealed somewhat higher affinities than mescaline but, in phosphoinositide hydrolysis assays (only for 5-HT2A), lower efficacies relative to serotonin and the full agonist mescaline (60 and 45%, respectively). More striking, however, was the observation that the new compounds did not fully substitute for LSD in LSD-trained rats, and at doses well above the mescaline EC50, only 50 and 29% appropriate responding was recorded. In view of this unexpected result, 3,5- dimethoxy-4-ethoxyphenethylamine (escaline), which is considerably more potent than mescaline in humans,128 was also tested. It was found to have about twice the affinity of mescaline for 5-HT2A receptors and was a complete agonist with very similar functional potency, but again it failed to substitute completely for LSD in the drug discrimination experiments.".

[BeningtonMorinClarke1954-8] "Synthesis of 4-Hydroxy- and 4-Ethoxy-3,5-dimethoxy-β-phenethylamines 1". Journal of the American Chemical Society 76 (21): 5555–5556. 1954. doi:10.1021/ja01650a084. ISSN 0002-7863. Bibcode: 1954JAChS..76.5555B.

[NicholsDyer1977-9] "Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogues". Journal of Medicinal Chemistry 20 (2): 299–301. February 1977. doi:10.1021/jm00212a022. PMID 836502.

[NicholsShulginDyer1977-10] "Directional lipophilic character in a series of psychotomimetic phenethylamine derivatives". Life Sciences 21 (4): 569–575. August 1977. doi:10.1016/0024-3205(77)90099-6. PMID 904435.

[11] "31 nya ämnen kan klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. November 2015. http://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2015/november/31-nya-amnen-kan-klassas-som-narkotika-eller-halsofarlig-vara/.

[USDOJ-12] "Controlled Substances - Alphabetical Order". Diversion Control Division, Drug Enforcement Administration. U.S. Department of Justice. December 2024. https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf.

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v t e Phenethylamines
Phenethylamines	Psychedelics: 25B-NBOMe 25C-NBOMe 25D-NBOMe 25I-NBOMe 25N-NBOMe 2C-B 2C-B-AN 2C-Bn 2C-Bu 2C-C 2C-CN 2C-CP 2C-D 2C-E 2C-EF 2C-F 2C-G 2C-G-1 2C-G-2 2C-G-3 2C-G-4 2C-G-5 2C-G-6 2C-G-N 2C-H 2C-I 2C-iP 2C-N 2C-NH2 2C-O 2C-O-4 2C-P 2C-Ph 2C-SE 2C-T 2C-T-2 2C-T-3 2C-T-4 2C-T-5 2C-T-6 2C-T-7 2C-T-8 2C-T-9 2C-T-10 2C-T-11 2C-T-12 2C-T-13 2C-T-14 2C-T-15 2C-T-16 2C-T-17 2C-T-18 2C-T-19 2C-T-20 2C-T-21 2C-T-22 2C-T-22.5 2C-T-23 2C-T-24 2C-T-25 2C-T-27 2C-T-28 2C-T-30 2C-T-31 2C-T-32 2C-T-33 2C-TFE 2C-TFM 2C-YN 2C-V Allylescaline DESOXY Escaline Isoproscaline Jimscaline Macromerine MEPEA Mescaline Metaescaline Methallylescaline Proscaline Psi-2C-T-4 TCB-2 Stimulants: Phenylethanolamine Hordenine Phenethylamine α-Methylphenethylamine (amphetamine) β-Methylphenethylamine m-Methylphenethylamine N-Methylphenethylamine o-Methylphenethylamine p-Methylphenethylamine Methylphenidate Entactogens: Lophophine MDPEA MDMPEA Others: BOH DMPEA
Amphetamines	Psychedelics: 3C-BZ 3C-E 3C-P Aleph Beatrice Bromo-DragonFLY D-Deprenyl DMA DMCPA DMMDA DOB DOC DOEF DOET DOI DOM DON DOPR DOTFM Ganesha MMDA MMDA-2 Psi-DOM TMA TeMA Stimulants: 2-FA 2-FMA 3-FA 3-FMA Acridorex Alfetamine Amfecloral Amfepentorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Benfluorex Benzphetamine Cathine Clobenzorex Dimethylamphetamine Ephedrine Etilamfetamine Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Flucetorex Fludorex Formetorex Furfenorex Gepefrine 4-Hydroxyamphetamine Iofetamine Isopropylamphetamine Lefetamine Lisdexamfetamine Mefenorex Metaraminol Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxyphenamine MMA Morforex Norfenfluramine L -Norpseudoephedrine N,alpha-Diethylphenylethylamine Oxifentorex Oxilofrine Ortetamine PBA PCA Phenpromethamine PFA PFMA PIA PMA PMEA PMMA Phenylpropanolamine Pholedrine Prenylamine Propylamphetamine Pseudoephedrine Sibutramine Tiflorex Tranylcypromine Xylopropamine Zylofuramine Entactogens: 4-FA 4-FMA 4-MA 4-MMA 4-MTA 5-APB 5-APDB 5-EAPB 5-IT 5-MAPB 5-MAPDB 6-APB 6-APDB 6-Chloro-MDMA 6-EAPB 6-IT 6-MAPB 6-MAPDB EDA IAP 2,3-MDA 3,4-MDA (tenamfetamine) MDEA MDHMA MDMA (midomafetamine) MDOH Methamnetamine MMDMA Naphthylaminopropane TAP Others: 3,4-DCA Amiflamine DiFMDA Selegiline (also D -Deprenyl)
Phentermines	Stimulants: Chlorphentermine Cloforex Clortermine Etolorex Mephentermine Pentorex Phentermine Entactogens: MDPH MDMPH Others: Cericlamine
Cathinones	Stimulants: 3-FMC 4-MC 4-BMC 4-CMC 4-EMC 4-FMC 4-MEC 4-MeMABP 4-MPD Amfepramone Benzedrone Brephedrone Buphedrone Bupropion Cathinone Dimethylcathinone Ethcathinone Eutylone Hydroxybupropion Methcathinone Methedrone NEB N-Ethylhexedrone N-Ethylpentedrone Pentedrone Pentylone Radafaxine Entactogens: 3,4-DMMC 3-MMC Butylone Ethylone Methylone Methylenedioxycathinone Mephedrone
Phenylisobutylamines	Entactogens: 4-CAB 4-MAB Ariadne BDB Butylone EBDB Eutylone MBDB Stimulants: Phenylisobutylamine
Phenylalkylpyrrolidines	Stimulants: α-PBP α-PHP α-PPP α-PVP MDPBP MDPPP MDPV 4-MePBP 4-MePHP 4-MePPP MOPPP MOPVP MPBP MPHP MPPP Naphyrone PEP Prolintane Pyrovalerone
Catecholamines (and close relatives)	6-FNE 6-OHDA a-Me-DA a-Me-TRA Adrenochrome Ciladopa D -DOPA (Dextrodopa) Dimetofrine Dopamine Epinephrine Epinine Etilefrine Ethylnorepinephrine Fenclonine Ibopamine Isoprenaline Isoetarine L -DOPA (Levodopa) L -DOPS (Droxidopa) L -Phenylalanine L -Tyrosine m-Tyramine Metanephrine Metaraminol Metaterol Metirosine Methyldopa N,N-Dimethyldopamine Nordefrin (Levonordefrin) Norepinephrine Norfenefrine (m-Octopamine) Normetanephrine Orciprenaline p-Octopamine p-Tyramine Phenylephrine Synephrine
Miscellaneous	AL-LAD Amidephrine Arbutamine Cafedrine Denopamine Desvenlafaxine Diphenidine Dizocilpine Dobutamine Dopexamine Ephenidine Etafedrine ETH-LAD Famprofazone Fluorolintane Hexapradol IP-LAD Lysergic acid amide Lysergic acid 2-butyl amide Lysergic acid 2,4-dimethylazetidide Lysergic acid diethylamide Methoxamine Methoxphenidine MT-45 PARGY-LAD Phenibut PRO-LAD Pronethalol Salbutamol (Levosalbutamol) Solriamfetol Theodrenaline Thiamphenicol UWA-101