Wikipedia

Diethyltryptamine

Diethyltryptamine
Clinical data
Other namesDET; N,N-Diethyltryptamine; N,N-DET; T-9; T9
Routes of
administration		Oral, inhalation (smoking), intramuscular, intravenous, subcutaneous[1]
Drug classNon-selective serotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
MetabolismOxidative deamination (MAO-ATooltip Monoamine oxidase A), N-oxidation, N-dealkylation[1][2][3]
Metabolites
Onset of action
Duration of action2–4 hours[1]
Excretionurine[2]
Identifiers
  • N,N-diethyl-2-(1H-indol-3-yl)ethan-2-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H20N2
Molar mass216.328 g·mol−1
3D model (JSmol)
Melting point169 to 171 °C (336 to 340 °F)
  • CCN(CC)CCC1=CNC2=C1C=CC=C2
  • InChI=1S/C14H20N2/c1-3-16(4-2)10-9-12-11-15-14-8-6-5-7-13(12)14/h5-8,11,15H,3-4,9-10H2,1-2H3 checkY
  • Key:LSSUMOWDTKZHHT-UHFFFAOYSA-N checkY
  (verify)

Diethyltryptamine (DET), also known as N,N-diethyltryptamine or T-9, is a psychedelic drug of the tryptamine family closely related to dimethyltryptamine (DMT).[1] It is taken orally, but can also be used by parenteral routes.[1]

The drug acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT2A receptor among others.[4][5] It has not been found to occur endogenously.[6] DMT is a close structural homologue of DMT and dipropyltryptamine (DPT).[1] Other analogues of DET include 4-HO-DET (ethocin), ethocybin (4-PO-DET), and 5-MeO-DET.[1]

DET was first synthesized in 1956 by Stephen Szára and subsequently described in material published in 1957.[7] More systematic studies were reported later by Szára and colleagues[2] and independently by Böszörményi and colleagues.[8]

Use and effects

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According to Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved), DET's dose range is 50 to 100 mg orally and its duration is 2 to 4 hours.[1][9] It was also assessed at oral doses of 44 to 400 mg, though 150 mg was described as "a little too much" and the 400 mg dose was simply described as "too high".[1] Its onset is 40 minutes to more than 1 hour and peak effects occurred at just over 1 hour.[1] In addition to oral administration, DET was assessed by smoking at doses of 40 to 90 mg, by subcutaneous injection at a dose of 40 mg, by intramuscular injection at a dose of 60 mg, and by intravenous injection at a dose of 60 mg.[1][10] By these routes, it has a faster onset than when taken orally.[1] The drug is said to taste terrible when smoked, like "burning plastic".[1] DET was initially assumed to be inactive orally similarly to dimethyltryptamine (DMT), but this proved to be incorrect.[1]

The effects of DET have been reported to include similar "illusions" and hallucinations" as DMT, a wave-like time course of effects, closed-eye visuals, open-eye visuals, auditory and olfactory hallucinations, synesthesia, feeling like in another world, cosmic thinking, mystical and philosophical feelings, dream-like mysteriousness of objects, greater emotional significance of objects, peoples' faces seeming "mask-like", enhanced appreciation of art, architecture, and music, feeling like a small child perceiving the world and discovering it anew, time dilation, enjoyment and euphoria, increased empathy, and emotional insights.[1][9][2] Additional effects included feeling stoned, alcohol-like intoxication, drifting of thoughts, and difficulty concentrating and cognitive impairment.[1][2] The effects of the drug were described as highly dependent on set and setting, with prominent negative reactions in unfavorable environments or with too high of doses, including unpleasantness, anxiety, paranoia, social withdrawal, and unwillingness to take the drug again, among others.[1][2] Physical effects of DET included DMT-like vegetative or autonomic symptoms, pupil dilation, sweating, slight burning and numbness of hands and feet, dizziness, vertigo, feeling sick, paleness, shakiness, muscle tremors, athetoid movements, vomiting, feeling of hollowness in the chest, pronounced tachycardia, pressor effects, and other somatic symptoms.[1][9][2] Subsequent-day effects included an afterglow, hangover, lassitude, and cognitive fuzziness.[1]

Interactions

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See also: Psychedelic drug § Interactions, and Trip killer § Serotonergic psychedelic antidotes

Pharmacology

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Pharmacodynamics

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DET activities
Target Affinity (Ki, nM)
5-HT1A 370 (Ki)
138 (EC50Tooltip half-maximal effective concentration)
98% (EmaxTooltip maximal efficacy)
5-HT2A 530 (Ki)
68–612a (EC50)
46a–90% (Emax)
5-HT2C 970 (Ki)
660a (EC50)
106%a (Emax)
SERTTooltip Serotonin transporter 1,200 (Ki)
254–258 (IC50)
NETTooltip Norepinephrine transporter >10,000 (IC50)
DATTooltip Dopamine transporter >10,000 (IC50)
Notes: The smaller the value, the more avidly drug interacts with the site. Footnotes: a = Stimulation of IP1Tooltip inositol phosphate formation. Sources: [4][5]

Similarly to other classic psychedelics, DET acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors.[4][5][11] The drug has been shown to activate Gq-mediated signaling at the serotonin 5-HT2A receptor with Emax higher than 70%[12] and to produce the head-twitch response in rodents which is a behavioral proxy of psychedelic-like effects.[10][12]

DET is a very weak reversible monoamine oxidase inhibitor (MAOI), with IC50Tooltip half-maximal inhibitory concentration values of 59 μM for serotonin and 5,000 μM for tryptamine as substrates.[3] Injections of 30 mg/kg to rats resulted in 67% reduction of brain MAO-A activity 15 minutes after administration.[3] The substance may also act as a serotonin reuptake inhibitor, with low affinity but moderate potency.[5] It shows no activity as a norepinephrine or dopamine reuptake inhibitor.[5]

Pharmacokinetics

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DET demonstrates significant resistance to metabolism by monoamine oxidase A (MAO-A) compared to DMT. This may be due to the increased steric bulk of the N-ethyl substituents relative to the respective methyl groups of DMT which results in metabolic stability sufficient for oral activity.[3][13] This is also true for many other tryptamines with larger nitrogen substituents.[1]

The drug similarly to DMT is rapidly absorbed from the intraperitoneal cavity and quickly distributed through plasma, liver and brain. Most of the substance had disappeared from the aforementioned tissues 30 minutes from administration, except in the brain, where it could still be detected at 60 minutes.[3]

Likewise to DMT the substance is metabolized through 6-hydroxylation and N-dealkylation to form the corresponding intermediates.[14] These metabolites were found to be excreted in urine of about 20% of the administered dose as the glucoronide conjugate, of which the parent compound can be detected by chromatographic analysis at low concentrations (3–5%). Hepatic 6-hydroxylation of the indole ring, yields a minor, psychoactively inactive metabolite 6-hydroxy-DET (6-HO-DET) in similar concentration, with additional hydroxylation possible at alternative positions. Repeated administration of DET, or second exposure one to two weeks after the first, resulted in significant metabolic changes. The unchanged drug excreted after a later exposure was significantly lower, while the excretion of the metabolites which were measured in this case were higher than at the first exposure to DET.[2][14]

Chemistry

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DET, also known as N,N-diethyltryptamine, is a synthetic compound in the tryptamine class, structurally related to the endogenous neurotransmitter serotonin and the naturally occurring psychedelic compounds dimethyltryptamine (DMT) and dipropyltryptamine (DPT). It is the ethyl analogue of DMT.[9]

Synthesis

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The chemical synthesis of DET has been described.[1][15][16]

Analogues

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Analogues of DET include dimethyltryptamine (DMT), dipropyltryptamine (DPT), methylethyltryptamine (MET), methylpropyltryptamine (MPT), ethylpropyltryptamine (EPT), 4-HO-DET, 5-HO-DET, 6-HO-DET, 4-AcO-DET, ethocybin (4-PO-DET or CEY-19), 6F-DET, and 2-Me-DET.[1]

History

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DET was first synthesized and administered intramuscularly in a 60 mg dose by Stephen Szára in 1956. It was subsequently described in his material published in 1957.[7] More systematic studies were reported later by Szara and colleagues and independently by Böszörményi and colleagues.[8][2] Early research began as a search for “psychosis mimics” in psychiatry, then expanded into broader psychedelic and structure–activity studies. Selection of study subjects for some of these studies was criticized by Alexander Shulgin in his 1997 book TiHKAL (Tryptamines I Have Known and Loved) for its "oppressive research environment".[1] For many years, based on early clinical reports and private communications, Shulgin maintained that DET exhibited psychoactive effects only when administered via parenteral routes. He eventually revised his view, ultimately acknowledging that the substance is also orally active.[1]

Initially, DET was not classified as a controlled substance, and some early clinical and experimental psychopharmacological research used it without scheduling restrictions. By the late 1960s and early 1970s, however, increasing regulatory attention led to tighter controls and this led to DET getting placed in Schedule I internationally by the Convention on Psychotropic Substances.[17]

Modern research on DET remains limited compared to dimethyltryptamine (DMT), due to its status as a controlled substance and the predominance of focus on other tryptamines with greater prevalence in traditional or clinical contexts. Most recent studies and reviews refer to DET primarily in comparative molecular pharmacology, assessing its receptor binding and signaling at serotonin receptors.[4][5]

Society and culture

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International

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DET is listed under Schedule I of the United Nations 1971 Convention on Psychotropic Substances, placing it under international control.[17] This means that countries that are parties to the Convention are required to regulate DET production, distribution, and use, restricting it to scientific and very limited medical purposes. Possession and trade of DET without appropriate authorization is prohibited under international law.

Australia

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DET is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).[18] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.

Germany

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DET is controlled under Anlage I BtMG (Narcotics Act, Schedule I).[19] as of January 24, 1974.[20] It is illegal to manufacture, possess, import, export, buy, sell, procure or dispense it without a license.[21]

Italy

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DET is a Schedule I controlled substance.[22]

New Zealand

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DET is a Class A controlled substance in New Zealand.[23]

Switzerland

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DET is a controlled substance specifically named under Verzeichnis D.[24]

United Kingdom

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DET is a Class A controlled substance.[25]

United States

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DET is a Schedule I controlled substance.[26]

Research

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Psychosis model

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Early studies of DET as well as other psychedelics were focused on their presumed psychotomimetic properties.[27] Researchers theorized that abnormal metabolites of endogenous chemicals such as tryptamine, serotonin, and tryptophan could be the explanation for mental disorders such as schizophrenia, or psychosis.[28] DET, along with other synthetic psychedelics, was administered to both patients and healthy volunteers to understand its effects and as a possible biological model for psychosis. With the progression of science and pharmacological understanding, this belief has been dismissed by most researchers.[29][30]

Mushroom production

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Although DET is a synthetic compound with no known natural sources, it has been used in conjunction with the mycelium of Psilocybe cubensis to biosynthetically produce the chemicals ethocybin (4-PO-DET) and ethocin (4-HO-DET). Isolation of the alkaloids resulted in 3.3% ethocybin and 0.01-0.8% ethocin.[6]

See also

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References

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  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z Shulgin A, Shulgin A (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. https://www.erowid.org/library/books_online/tihkal/tihkal03.shtml
  2. ^ a b c d e f g h i j k Szara S, Rockland LH, Rosenthal D, Handlon JH (September 1966). "Psychological effects and metabolism of N,N-diethyltryptamine in man". Archives of General Psychiatry. 15 (3): 320–329. doi:10.1001/archpsyc.1966.01730150096014. PMID 5330062.
  3. ^ a b c d e Huszti Z, Borsy J (August 1964). "The effect of diethyltryptamine and its derivatives on monoamine oxidase". Biochemical Pharmacology. 13 (8): 1151–1156. doi:10.1016/0006-2952(64)90116-9. PMID 14222512.
  4. ^ a b c d Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology. 231 (21): 4135–4144. doi:10.1007/s00213-014-3557-7. PMC 4194234. PMID 24800892.
  5. ^ a b c d e f Kozell LB, Eshleman AJ, Swanson TL, Bloom SH, Wolfrum KM, Schmachtenberg JL, et al. (April 2023). "Pharmacologic Activity of Substituted Tryptamines at 5-Hydroxytryptamine (5-HT)2A Receptor (5-HT2AR), 5-HT2CR, 5-HT1AR, and Serotonin Transporter". The Journal of Pharmacology and Experimental Therapeutics. 385 (1): 62–75. doi:10.1124/jpet.122.001454. PMC 10029822. PMID 36669875.
  6. ^ a b Gartz J (1989). "Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe". Journal of Basic Microbiology. 29 (6): 347–352. doi:10.1002/jobm.3620290608. PMID 2614674. S2CID 43308695.
  7. ^ a b Szára S (1957). Psychotropic Drugs: The Comparison of the Psychotic Effect of Tryptamine Derivatives with the Effects of Mescaline and LSD-25 in Self-Experiments (Book chapter). Amsterdam: Elsevier. pp. 460–467.
  8. ^ a b Boszormenyi Z, Der P, Nagy T (January 1959). "Observations on the psychotogenic effect of N-N diethyltryptamine, a new tryptamine derivative". The Journal of Mental Science. 105 (438): 171–181. doi:10.1192/bjp.105.438.171. PMID 13641966.
  9. ^ a b c d Malaca S, Lo Faro AF, Tamborra A, Pichini S, Busardò FP, Huestis MA (December 2020). "Toxicology and Analysis of Psychoactive Tryptamines". International Journal of Molecular Sciences. 21 (23): 9279. doi:10.3390/ijms21239279. PMC 7730282. PMID 33291798. Diethyltryptamine (DET): DET is the ethyl analogue of DMT. It is orally active because the ethyl group prevents MAO degradation. The active dose is 50–100 mg, with psychoactive effects lasting 2–4 h [70,71]. DET's most common effects include slight generalized tremors to gross athletic movements, visual distortion, hypersensitivity to light, visual hallucinations, auditory perceptual distortions and olfactory hallucinations [72].
  10. ^ a b Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species" (PDF). Neuropharmacology. 167 107933. doi:10.1016/j.neuropharm.2019.107933. PMC 9191653. PMID 31917152. Table 4 Human potency data for selected hallucinogens. [...]
  11. ^ Winter JC (September 1969). "Behavioral effects of N,N-diethyltryptamine: absence of antagonism by xylamidine tosylate". The Journal of Pharmacology and Experimental Therapeutics. 169 (1): 7–16. doi:10.1016/S0022-3565(25)28342-2. PMID 5306645.
  12. ^ a b Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, et al. (December 2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nature Communications. 14 (1) 8221. Bibcode:2023NatCo..14.8221W. doi:10.1038/s41467-023-44016-1. PMC 10724237. PMID 38102107.
  13. ^ US 20240286998, Wallach J, Dybek M, "Fluorinated tryptamine compounds, analogues thereof, and methods using same", issued 29 August 2024 
  14. ^ a b Szara S (1968). "Discussion of the fate and metabolism of some hallucinogenic indolealkylamines". In Garattini S, Shore PA (eds.). Pharmacology, Behavior, and Clinical Aspects, Proceedings of a Symposium held at the College of Physicians and Surgeons, Columbia University, New York. Biological Role of Indolealkylamine Derivates - Proceedings of a Symposium held at The College of Physicians and Surgeons, Columbia University, New York, New York, 10–12 May 1967. Vol. 6. Academic Press. pp. 230–1. doi:10.1016/s1054-3589(08)60321-x. ISBN 978-0-12-032906-9. PMID 5658326. {{cite book}}: |journal= ignored (help)
  15. ^ Kalir A, Szara S (November 1963). "Synthesis and Pharmacological Activity of Fluorinated Tryptamine Derivatives". Journal of Medicinal Chemistry. 6 (6): 716–719. doi:10.1021/jm00342a019. PMID 14184932.
  16. ^ Wang YY, Chen C (2007). "Synthesis of Deuterium Labeled Tryptamine Derivatives". Journal of the Chinese Chemical Society. 54 (5): 1363–1368. doi:10.1002/jccs.200700194. ISSN 2192-6549.
  17. ^ a b Board IN (August 2003). "List of psychotropic substances under international control" (PDF). Archived (PDF) from the original on 2 March 2007. Retrieved 30 March 2007.
  18. ^ "Poisons Standard". Federal Register of Legislation. Australian Government. October 2015.
  19. ^ "Anlage I BtMG" (in German). Bundesministerium der Justiz und für Verbraucherschutz [Federal Ministry of Justice and Consumer Protection]. Retrieved December 10, 2019.
  20. ^ "Sechste Verordnung über die den Betäubungsmitteln gleichgestellten Stoffe" (PDF). Bundesgesetzblatt Jahrgang 1974 Teil I Nr. 6 (in German). Bundesanzeiger Verlag. January 23, 1974. pp. 97–98. Retrieved January 7, 2020.
  21. ^ "§ 29 BtMG" (in German). Bundesministerium der Justiz und für Verbraucherschutz [Federal Ministry of Justice and Consumer Protection]. Retrieved December 10, 2019.
  22. ^ "Tabella I" (PDF) (in Italian). Ministero della Salute [Ministry of Health]. p. 8. Retrieved January 7, 2020.
  23. ^ "Schedule 1 Class A controlled drugs". "Reprint as at 13 August 2019: Misuse of Drugs Act 1975". Parliamentary Counsel Office. Retrieved January 7, 2020.
  24. ^ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020.
  25. ^ "Part I: Class A Drugs". "Misuse of Drugs Act 1971". UK Government. Retrieved January 7, 2020.
  26. ^ "Controlled Substances: by CSA Schedule" (PDF). U.S. Department of Justice. August 21, 2019. p. 4. Retrieved January 7, 2020.
  27. ^ Böszörmenyi Z (1960). "Psilocybin and diethyltryptamine: Two tryptamine hallucinogens". Neuro-psychopharm. 2: 226–229.
  28. ^ Khazan N, McCash D (April 1965). "Effects of LSD-25, n,n-dimethyltryptamine (DMT), and N,N-diethyltryptamine (DET) on the photic evoked responses in the unanesthetized rabbit". Archives Internationales de Pharmacodynamie et de Therapie. 154 (2): 474–483. PMID 5839429.
  29. ^ Friesen P (October 2022). "Psychosis and psychedelics: Historical entanglements and contemporary contrasts". Transcultural Psychiatry. 59 (5): 592–609. doi:10.1177/13634615221129116. PMC 9660273. PMID 36300247.
  30. ^ Sabé M, Sulstarova A, Glangetas A, De Pieri M, Mallet L, Curtis L, et al. (March 2025). "Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies". Molecular Psychiatry. 30 (3): 1223–1255. doi:10.1038/s41380-024-02800-5. PMC 11835720. PMID 39592825.
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