4-HO-DiPT

Last updated

4-HO-DiPT
4-HO-DIPT.SVG
4-HO-DiPT-3d-sticks.png
Clinical data
Other names4-OH-DiPT; 4-Hydroxy-N,N-diisopropyltryptamine; Iprocin
Routes of
administration 		Oral [1]
Drug class Non-selective serotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Legal status
Legal status
  • DE: NpSG (Industrial and scientific use only)
  • UK: Class A
  • US:Unscheduled
Pharmacokinetic data
Onset of action 15–20 minutes [1]
Elimination half-life 2.7–4.1 h (as luvesilocin s.c. Tooltip subcutaneous injection) [2]
Duration of action 2–3 hours [1]
Identifiers
  • 3-[2-(diisopropylamino)ethyl]-1H-indol-4-ol
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard 100.214.853 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C16H24N2O
Molar mass 260.381 g·mol−1
3D model (JSmol)
  • CC(C)N(CCc1c[nH]c2cccc(O)c12)C(C)C
  • InChI=1S/C16H24N2O/c1-11(2)18(12(3)4)9-8-13-10-17-14-6-5-7-15(19)16(13)14/h5-7,10-12,17,19H,8-9H2,1-4H3 Yes check.svgY
  • Key:KBRYKXCBGISXQV-UHFFFAOYSA-N Yes check.svgY
   (verify)

4-HO-DiPT, also known as 4-hydroxy-N,N-diisopropyltryptamine or as iprocin, is a psychedelic drug of the tryptamine and 4-hydroxytryptamine families related to psilocin (4-HO-DMT). [1] [3] It is taken orally. [1] The drug has an unusually fast onset, short duration, and narrow dose range. [1]

Contents

It acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT2A receptor. [4] [5] [6] [7] Unlike many other psychedelic tryptamines, the drug appears to have far lower potency as an agonist of the serotonin 5-HT2C receptor relative to the serotonin 5-HT2A receptor. [4] [5] [6] [7] It is a derivative of DiPT, a higher homologue of psilocin (4-HO-DMT) and 4-HO-DET, and a skeletal isomer of 4-HO-DPT. [1]

4-HO-DiPT was first described in the scientific literature by 1977. [3] [8] [9] It was later described in greater detail by Alexander Shulgin in his 1997 book TiHKAL (Tryptamines I Have Known and Loved). [3] [8] [1] The drug was encountered as a novel designer drug by 2005. [10] In the 2020s, a prodrug of 4-HO-DiPT known as luvesilocin (RE-104, FT-104; 4-GO-DiPT) was developed and is in clinical trials for the treatment of psychiatric disorders such as postpartum depression. [3] [11] [12] [2]

Use and effects

In his book TiHKAL (Tryptamines I Have Known and Loved) and other publications, Alexander Shulgin reported that 4-HO-DiPT had a dose range of 15 to 20 mg orally and a duration of 2 to 3 hours. [1] [13] [14] However, a wider dose range of 3 to 30 mg or more orally has also been reported. [15] Shulgin has stated that 4-HO-DiPT has an especially steep dose–response curve and narrow dose range, with doses below 10 mg producing few to no effects and doses of more than 20 mg having not been tested due to the intensity of its effects. [1] He personally found that a 20 mg dose produced an intense plus-three experience on the Shulgin Rating Scale that "flirted with" the magical plus-four transcendental peak experience. [1] The drug's onset of action is 15 to 20 minutes and peak effects occur after 20 to 30 minutes. [1] Shulgin has stated that he "truly doubt[s] that there is another psychedelic drug, anywhere, that can match [4-HO-DiPT] for speed, for intensity, for brevity, and [sensitivity] to dose, at least one that is active orally." [1]

The effects of 4-HO-DiPT have been reported to include introspective changes, insights and realizations, mild object distortion, slight color effects, rainbow halos around objects, very little in the way of closed-eye visuals, little in terms of psychedelic visuals or sensory changes in general, mild stimulation, mild elation, light tension, orgasmic enhancement, and powerful religious-esque experiences. [1] Other effects included sensations of muscle loosening, leg tremors, chill-like sensations, and vague body malaise. [1] Shulgin has stated that he doubts that 4-HO-DiPT could be distinguished from psilocin (4-HO-DMT) in any blinded clinical study. [16] Due to its rapid onset and short duration among other qualities, 4-HO-DiPT has been described as a "good 'novice' introduction to hallucinogens". [1]

Luvesilocin (RE104; 4-GO-DiPT) Drug Effects Questionnaire (DEQ) "feel high" ratings at doses of 5 to 40 mg (equivalent to ~4-32 mg 4-HO-DiPT) via subcutaneous injection over 6 hours. Effects of luvesilocin at different doses on the Drug Effects Questionnaire over 6 hours.png
Luvesilocin (RE104; 4-GO-DiPT) Drug Effects Questionnaire (DEQ) "feel high" ratings at doses of 5 to 40 mg (equivalent to ~4–32 mg 4-HO-DiPT) via subcutaneous injection over 6 hours.

The effects of 4-HO-DiPT have been clinically studied in the form of its prodrug luvesilocin (RE-104; FT-104; 4-GO-DiPT). [2] Luvesilocin was evaluated at doses of 5 to 40 mg (equivalent to ~4–32 mg 4-HO-DiPT) by subcutaneous injection in this study. [2] It was specifically assessed in terms of modified Drug Effects Questionnaire (DEQ) ratings, Mystical Experience Questionnaire (MEQ) ratings, and adverse effects. [2]

Interactions

Pharmacology

Pharmacodynamics

4-HO-DiPT activities
Target Affinity (Ki, nM)
5-HT1A 5,700–>10,000 (Ki)
1,147–3,900 (EC50 Tooltip half-maximal effective concentration)
36–70% (Emax Tooltip maximal efficacy)
5-HT1B >10,000 (Ki)
597–>10,000 (EC50)
95% (Emax)
5-HT1D 1,860 (Ki)
496–8,827 (EC50)
64–124% (Emax)
5-HT1E >10,000 (Ki)
852–>10,000 (EC50)
79% (Emax)
5-HT1F ND (Ki)
557 (EC50)
<20–59% (Emax)
5-HT2A 120–922 (Ki)
6.8–334 (EC50)
74–106% (Emax)
5-HT2B 85 (Ki)
5.1–460 (EC50)
55–110% (Emax)
5-HT2C 2.8–>10,000 (Ki)
180–6,442 (EC50)
72–104% (Emax)
5-HT3 ND
5-HT4 ND (Ki)
>10,000 (EC50)
IA (Emax)
5-HT5A >10,000 (Ki)
243–5,074 (EC50)
56–66% (Emax)
5-HT6 >10,000 (Ki)
697–2,415 (EC50)
55–56% (Emax)
5-HT7 >10,000 (Ki)
ND (EC50)
<20% (Emax)
α1A >12,000
α1B, α1D ND
α2A 15,000
α2B, α2C >10,000
β1–β3 ND
D1–D3 >25,000
D4, D5 >10,000
H1 9,800–>10,000
H2 >10,000
H3, H4 ND
M1–M3 ND
M4 1,725
M5 ND
I1 ND
σ1 816–1,063
σ2 2,215
TAAR1 Tooltip Trace amine-associated receptor 1>15,000 (Ki) (mouse)
>15,000 (Ki) (rat)
ND (EC50) (human)
SERT Tooltip Serotonin transporter419–1,800 (Ki)
163–2,400 (IC50 Tooltip half-maximal inhibitory concentration)
IA (EC50)
NET Tooltip Norepinephrine transporter11,000 (Ki)
46,000 (IC50)
IA (EC50)
DAT Tooltip Dopamine transporter>26,000 (Ki)
>100,000 (IC50)
IA (EC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [4] [5] [6] [7] [17] [18] [19] [20]

4-HO-DiPT acts as an agonist of serotonin receptors, including the serotonin 5-HT2A and 5-HT2B receptors. [4] [5] [6] [7] [18] It may also act as a serotonin reuptake inhibitor, although its potency is variable across studies. [4] [5] [6] [7] The drug appears to activate the serotonin 5-HT2C receptor with low potency and much lower than for the serotonin 5-HT2A receptor. [4] [5] [6] [7] However, in another study, it was only about 2.5-fold more potent as an agonist of the serotonin 5-HT2A receptor relative to the serotonin 5-HT2C receptor. [19] The drug activates other serotonin receptors with lower potency as well. [19] Unlike many other tryptamines, 4-HO-DiPT is not a ligand of the rodent trace amine-associated receptor 1 (TAAR1). [4] [20]

The drug has been found to produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. [3] [14] [5] In addition, it has fully efficacious anti-inflammatory effects in preclinical research. [3] [18] 4-HO-DiPT has also been found to produce anxiolytic effects in rodents. [19]

Pharmacokinetics

The pharmacokinetics of 4-HO-DiPT have been studied. [17] [2] The elimination half-life of 4-HO-DiPT in humans when given in the form of its prodrug luvesilocin (4-GO-DiPT) by subcutaneous injection has been found to range from 2.7 to 4.1 hours. [2] The average experience duration was 3.6 hours at a dose of 30 mg in the study. [2]

Chemistry

4-HO-DiPT, also known as 4-hydroxy-N,N-diisopropyltryptamine, is a substituted tryptamine. [1] It is a synthetic analogue of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) and of the naturally occurring serotonergic psychedelics psilocin (4-HO-DMT) and psilocybin (4-PO-DMT). [1] > [3]

Synthesis

The chemical synthesis of 4-HO-DiPT has been described. [1]

Analogues

4-HO-DiPT is closely related to analogues including diisopropyltryptamine (DiPT), 5-MeO-DiPT, psilocin (4-HO-DMT), 4-HO-DET (ethocin), 4-HO-MET (metocin), 4-HO-MiPT (miprocin), 4-HO-DPT (deprocin), 4-HO-MPT (meprocin), 4-HO-DALT (dalocin), 4-HO-MALT (malocin), and 5-HO-DiPT, among others. [1] 4-AcO-DiPT (ipracetin), 4-PrO-DiPT, and luvesilocin (4-GO-DiPT) are ester prodrugs of 4-HO-DiPT. [3] [5] [2]

History

4-HO-DiPT was first described in the scientific literature by David Repke and colleagues in 1977. [3] [8] [9] Subsequently, its effects in humans were described by Alexander Shulgin in his 1997 book TiHKAL (Tryptamines I Have Known and Loved). [3] [8] [1] The drug was encountered as a novel designer drug in Europe by 2005. [10] Luvesilocin (4-GO-DiPT), a prodrug of 4-HO-DiPT, was first described in 2021. [3] [21]

Society and culture

4-HO-DiPT powder. 4-Hydroxy-N,N-diisopropyltryptamine.jpg
4-HO-DiPT powder.

Finland

Scheduled in government decree on psychoactive substances banned from the consumer market. [22]

Germany

Scheduled in New Psychoactive Substances Act (NpSG). Use of covered substances is permitted only for industrial and scientific purposes.

Sweden

Sveriges riksdags health ministry Statens folkhälsoinstitut classified 4-HO-DiPT 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 Mar 1, 2005, in their regulation SFS 2005:26 listed as 4-hydroxi-N,N-diisopropyltryptamin (4-HO-DIPT), making it illegal to sell or possess. [23]

United States

4-HO-DiPT is not scheduled at the federal level in the United States, [24] but it is possible that it could be considered an analog of 5-MeO-DiPT, in which case purchase, sale, or possession could be prosecuted under the Federal Analog Act. The United States Drug Enforcement Administration (DEA) proposed scheduling 4-HO-DiPT in January 2022, but due to an effective public response, it withdrew its proposal in July 2022. [3]

Florida

"4-Hydroxy-N,N-diisopropyltryptamine" is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in Florida. [25]

Research

Luvesilocin

Luvesilocin (RE-104, FT-104; 4-GO-DiPT), a prodrug of 4-HO-DiPT. Luvesilocin.svg
Luvesilocin (RE-104, FT-104; 4-GO-DiPT), a prodrug of 4-HO-DiPT.

Luvesilocin (developmental code names RE-104, FT-104; O-glutaryl-4-HO-DiPT or 4-GO-DiPT), a prodrug of 4-HO-DiPT, has entered phase 2 clinical trials for treatment of psychiatric conditions such as postpartum depression and treatment-resistant depression. [11] [26] [27] [28]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 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/tihkal17.shtml
  2. 1 2 3 4 5 6 7 8 9 10 Ludbrook G, Bryson N, Taylor B, Hocevar-Trnka J, Johnson MW, Hirman J, et al. (2025). "Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous RE104: A Double-Blind, Randomized, Single Ascending Dose Placebo-Controlled Study". J Clin Psychopharmacol. 45 (5): 441–453. doi:10.1097/JCP.0000000000002047. PMC   12379775 . PMID   40685873.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 "4-HO-DiPT". Psychedelic Science Review. 23 June 2022. Retrieved 8 October 2025.
  4. 1 2 3 4 5 6 7 Rickli A, Moning OD, Hoener MC, Liechti ME (August 2016). "Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens" (PDF). Eur Neuropsychopharmacol. 26 (8): 1327–1337. doi:10.1016/j.euroneuro.2016.05.001. PMID   27216487.
  5. 1 2 3 4 5 6 7 8 Klein AK, Chatha M, Laskowski LJ, Anderson EI, Brandt SD, Chapman SJ, et al. (April 2021). "Investigation of the Structure-Activity Relationships of Psilocybin Analogues". ACS Pharmacol Transl Sci. 4 (2): 533–542. doi:10.1021/acsptsci.0c00176. PMC   8033608 . PMID   33860183.
  6. 1 2 3 4 5 6 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". J Pharmacol Exp Ther. 385 (1): 62–75. doi:10.1124/jpet.122.001454. PMC   10029822 . PMID   36669875.
  7. 1 2 3 4 5 6 Glatfelter GC, Naeem M, Pham DN, Golen JA, Chadeayne AR, Manke DR, et al. (April 2023). "Receptor Binding Profiles for Tryptamine Psychedelics and Effects of 4-Propionoxy-N,N-dimethyltryptamine in Mice". ACS Pharmacol Transl Sci. 6 (4): 567–577. doi:10.1021/acsptsci.2c00222. PMC   10111620 . PMID   37082754.
  8. 1 2 3 4 Zamberlan F, Sanz C, Martínez Vivot R, Pallavicini C, Erowid F, Erowid E, et al. (2018). "The Varieties of the Psychedelic Experience: A Preliminary Study of the Association Between the Reported Subjective Effects and the Binding Affinity Profiles of Substituted Phenethylamines and Tryptamines". Front Integr Neurosci. 12 54. doi: 10.3389/fnint.2018.00054 . PMC   6235949 . PMID   30467466. 4-OH-DiPT (4-Hydroxy-diisopropyltryptamine): substituted tryptamine, first synthesized by Repke et al. (1977) and investigated in humans by A. Shulgin (Shulgin and Shulgin, 1997).
  9. 1 2 Repke DB, Ferguson WJ, Bates DK (1977). "Psilocin analogs. 1. Synthesis of 3-[2-(dialkylamino)ethyl] -and 3-[2-(cycloalkylamino)ethyl] indol-4-ols". Journal of Heterocyclic Chemistry. 14 (1): 71–74. doi: 10.1002/jhet.5570140113 . ISSN   0022-152X.
  10. 1 2 https://isomerdesign.com/bitnest/external/EMCDDA/New-Drugs-In-Europe-2005
  11. 1 2 "RE 104". AdisInsight. 23 September 2025. Retrieved 8 October 2025.
  12. ↑ Bryson N, Alexander R, Asnis-Alibozek A, Ehlers MD (June 2024). "RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine". ACS Chem Neurosci. 15 (12): 2386–2395. doi:10.1021/acschemneuro.4c00058. PMC   11191588 . PMID   38758589.
  13. ↑ Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN   978-0-12-433951-4.
  14. 1 2 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. [...]
  15. ↑ Luethi D, Liechti ME (October 2018). "Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics". Int J Neuropsychopharmacol. 21 (10): 926–931. doi:10.1093/ijnp/pyy047. PMC   6165951 . PMID   29850881.
  16. ↑ Shulgin A, Shulgin A (September 1997). "#21. 4-HO-MET". Isomer Design. Transform Press. Retrieved 28 November 2023. With [4-HO-MET], some of the original observations suggested that it was more potent than psilocin, certainly more dramatic. But at the bottom line, I doubt that this ethyl homologue, or the isopropyl homologue 4-HO-DIPT for that matter, could be distinguished from the methyl counterpart psilocin in any blind clinical study.
  17. 1 2 Bryson N, Alexander R, Asnis-Alibozek A, Ehlers MD (June 2024). "RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine". ACS Chem Neurosci. 15 (12): 2386–2395. doi:10.1021/acschemneuro.4c00058. PMC   11191588 . PMID   38758589.
  18. 1 2 3 Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC   8033619 . PMID   33860179.
  19. 1 2 3 4 Kelly TJ, Bonniwell EM, Mu L, Liu X, Hu Y, Friedman V, et al. (April 2024). "Psilocybin analog 4-OH-DiPT enhances fear extinction and GABAergic inhibition of principal neurons in the basolateral amygdala". Neuropsychopharmacology. 49 (5): 854–863. doi:10.1038/s41386-023-01744-8. PMC   10948882 . PMID   37752222.
  20. 1 2 Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (April 2016). "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1" (PDF). J Pharmacol Exp Ther. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID   26791601. Archived from the original (PDF) on 9 May 2025.
  21. ↑ Bryson N. Tryptamine prodrugs. US 2021/0403425 A1, Field Trip Psychedelics, Inc0. Published online April 5, 2022. Accessed May 27, 2022. https://patents.google.com/patent/US11292765B2/en?q=field+trip+health&assignee=Field+Trip+Psychedelics+Inc.
  22. ↑ "FINLEX ® - Säädökset alkuperäisinä: Valtioneuvoston asetus kuluttajamarkkinoilta… 1130/2014". www.finlex.fi. Retrieved 8 April 2023.
  23. ↑ "Svensk författningssamling" [Swedish Code of Statutes](PDF) (in Swedish). Archived from the original (PDF) on 29 September 2013. Retrieved 25 September 2013.
  24. ↑ "21 CFR — SCHEDULES OF CONTROLLED SUBSTANCES §1308.11 Schedule I." Archived from the original on 27 August 2009. Retrieved 17 December 2014.
  25. ↑ "Statutes & Constitution :View Statutes : Online Sunshine". leg.state.fl.us. Retrieved 8 April 2023.
  26. ↑ "Field Trip Announces First Dosings in Phase I Clinical Study of FT-104" (Press release). 21 July 2022.
  27. ↑ "An Inside Look into Field Trip's Next-Generation Psychedelic, FT-104". 11 August 2022.
  28. ↑ "WIPO - Search International and National Patent Collections". patentscope.wipo.int. Retrieved 8 April 2023.
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