4-HO-DET

Use and effects

In his book TiHKAL (Tryptamines I Have Known and Loved) and other publications, Alexander Shulgin variably lists the dose range of 4-HO-DET as 10 to 25mg orally, either as 4-HO-DET itself or as presumed prodrugs like ethocybin (4-PO-DET) or 4-AcO-DET, and its duration as 2 to 6hours. Threshold effects are said to occur at doses of 5 to 15mg, whereas loss of contact with reality is said to occur at doses over 30mg. However, strong effects have also been reported at a dose of 15mg of ethocybin. A typical dose estimate has been reported to be around 17.5mg. The onset of 4-HO-DET is described as being around 30 to 45minutes.

The drug has been reported to be very similar to psilocin and psilocybin in its qualitative effects but to be somewhat shorter in duration, for instance as short as 2 to 3hours. The effects of 4-HO-DET, either as 4-HO-DET itself or as presumed prodrugs, have been reported to include closed-eye visuals, open-eye visuals such as fire light turning into bursts of color, potential for intense psychedelic visuals, auditory hallucinations, time dilation, temporal and spatial disorientation, body image disturbance, musical immersion, derealization, ego death, feeling like one has ceased to exist, feelings of oneness with the universe or reality, ineffability, "sparkly-ness", powerful emotions including feelings of intense love, peace, acceptance, awe, reverence, and joy, feelings of sadness, uncomfortableness, and feeling overwhelmed.

Other effects included feeling intoxicated, sedation, restlessness, loss of language ability, impaired concentration, compulsion to talk and interact with others, and lack of erotic feelings. At very high doses, effects including temporary psychosis, depersonalization, mystical experiences, delirium, schizophrenia-like behavior, catatonia, and paranoia have been found to occur. Physical effects have been reported to include stomach and abdominal discomfort, appetite loss, jaw tightening, body tremors, motor incoordination, body disturbance, diuretic effects, and increased blood pressure.

Interactions

Pharmacology

Pharmacodynamics

4-HO-DET acts as a potent non-selective serotonin receptor agonist, including of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. It may also act as a serotonin reuptake inhibitor, with low affinity but moderate potency. The drug showed no significant activity at various other assessed targets, including adrenergic receptors (α2A-, α2B, α2C), dopamine receptors (D2–D5), muscarinic acetylcholine receptors (M4), and the dopamine transporter (DAT).

It induces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. Its potency for inducing the head-twitch response in mice is approximately 2-fold lower than that of psilocin.

Chemistry

4-HO-DET, also known as 4-hydroxy-N,N-diethyltryptamine, is a substituted tryptamine and 4-hydroxytryptamine. It is the 4-hydroxy derivative of N,N-diethyltryptamine (DET) and is a close analogue of psilocin (4-hydroxy-N,N-dimethyltryptamine; 4-HO-DMT).

Synthesis

The chemical synthesis of 4-HO-DET has been described.

Analogues

4-HO-DET is the N,N-diethyl analogue of psilocin (4-HO-DMT). Other analogues of 4-HO-DET include diethyltryptamine (DET), 5-MeO-DET, 4-HO-DPT, 4-HO-MET, 4-HO-EPT, and 5-HO-DET, among others. The acetate ester of 4-HO-DET is known as 4-AcO-DET and the phosphate ester is known as ethocybin (4-PO-DET or CEY-19). These compounds are assumed to be prodrugs of 4-HO-DET, as has been shown with the acetate and phosphate esters of other methylated tryptamines such as psilocin (e.g., psilocybin (4-PO-DMT) and 4-AcO-DMT).

History

4-HO-DET was first described in the literature by 1963. It was developed by Albert Hofmann and Franz Troxler at Sandoz in the 1950s and went by the developmental code name CZ-74. Along with its presumed prodrug ethocybin (4-PO-DET; CEY-19), 4-HO-DET was one of the earliest structurally modified or synthetic psychedelic tryptamines to be developed. It was used along with ethocybin in clinical studies of psychedelic-assisted psychotherapy by the German researchers Hanscarl Leuner and Gerhard Baer in the 1960s. The drug was synthesized and studied, along with many other 4-hydroxytryptamines, by David Repke and colleagues in the 1970s and 1980s. It was later additionally described by Alexander Shulgin in his 1997 book TiHKAL (Tryptamines I Have Known and Loved). 4-HO-DET was encountered as a novel designer drug in Europe in 2005.

Society and culture

Legal status

Canada

4-HO-DET is not a controlled substance in Canada as of 2025.

Finland

Scheduled in the "government decree on psychoactive substances banned from the consumer market".

Sweden

Sveriges riksdags health ministry Statens folkhälsoinstitut classified 4-HO-DET as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Nov 1, 2005, in their regulation SFS 2005:733 listed as 4-hydroxi-N,N-diethyltryptamin (4-HO-DET), making it illegal to sell or possess.

United States

4-HO-DET is unscheduled in the United States, but purchase, sale, or possession for human consumption could be prosecuted under the Federal Analogue Act.

Research

4-HO-DET, under the code name CZ-74 and along with ethocybin (CEY-19), has been studied in psychedelic-assisted psychotherapy.

References

References

1. (2021). "Novel Psychoactive Substances: Classification, Pharmacology and Toxicology". Academic Press.
2. (September 1997). "#16 4-HO-DET". Transform Press.
3. (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology.
4. (1994). "Structure-activity relationships of the classic hallucinogens and their analogs". NIDA Research Monograph.
5. (2003). "Hallucinogens: A Forensic Drug Handbook". Elsevier Science.
6. (1982). "Indolealkylamine and phenalkylamine hallucinogens: a brief overview". Neuroscience and Biobehavioral Reviews.
7. (2018). "Chemistry and Structure-Activity Relationships of Psychedelics".
8. (1976). "Psychopharmacological Agents: Use, Misuse and Abuse". Academic Press.
9. (April 2023). "Pharmacologic Activity of Substituted Tryptamines at 5-Hydroxytryptamine (5-HT)_2A Receptor (5-HT_2AR), 5-HT_2CR, 5-HT_1AR, and Serotonin Transporter". The Journal of Pharmacology and Experimental Therapeutics.
10. (April 2021). "Investigation of the Structure-Activity Relationships of Psilocybin Analogues". ACS Pharmacology & Translational Science.
11. (April 2023). "Receptor Binding Profiles for Tryptamine Psychedelics and Effects of 4-Propionoxy-N,N-dimethyltryptamine in Mice". ACS Pharmacology & Translational Science.
12. (March 1990). "Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes". Neuropharmacology.
13. (February 11, 1999). "Improvements to the Synthesis of Psilocybin and a Facile Method for Preparing the O-Acetyl Prodrug of Psilocin". Synthesis.
14. "Esters of indoles".
15. (9 March 2021). "Handbook of Medical Hallucinogens". Guilford Publications.
16. (7 November 2022). "Handbook of Medical Hallucinogens". Guilford Publications.
17. (1965). "Two new short-acting hallucinogens of the psilocybin group". Neuropsychopharmacology.
18. (1977). "Psilocin analogs. 1. Synthesis of 3‐[2‐(dialkylamino)ethyl] ‐and 3‐[2‐(cycloalkylamino)ethyl] indol‐4‐ols". Journal of Heterocyclic Chemistry.
19. (1982). "Psilocin analogs. III. Synthesis of 5‐methoxy‐ and 5‐hydroxy‐1,2,3,4‐tetrahydro‐9 H ‐pyrido[3,4‐ b ]indoles". Journal of Heterocyclic Chemistry.
20. "EMCDDA–Europol Annual Report on the implementation of Council Decision 2005/387/JHA". European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).
21. "Controlled Drugs and Substances Act".
22. (19 December 2014). "Valtioneuvoston asetus kuluttajamarkkinoilta kielletyistä psykoaktiivisista aineista". Finnish Ministry of Justice.
23. (6 October 2005). "Förordning om ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor;". Svensk författningssamling (Swedish Code of Statutes).
24. "21 U.S. Code § 841 - Prohibited acts A".