2,5-Dimethoxy-4-methylamphetamine

DOM
Clinical data
Other names2,5-Dimethoxy-4-methylamphetamine; 4-Methyl-2,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-methyl-α-methylphenethylamine; Des-oxy-methyl; DOM; DMMTA; α-Me-2C-D; STP; Serenity, Tranquility, and Peace; Super Terrific Psychedelic; Stop The Police; Too Stupid to Puke; K-61,082
Routes of
administration		Oral
Drug classSerotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen; Stimulant; Antidepressant; Psychic energizer
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
MetabolismDemethylation
Metabolites• 2-DM-DOM
• 5-DM-DOM
• 2,5-DDM-DOM
Onset of action0.5–1.5 hours
Peak: 2–6 hours
Duration of actionLow doses: 5–8 hours
Moderate doses: 8–24 hours
High doses: possibly up to 3–4 days
Excretion5–20% unchanged
Identifiers
  • 1-(2,5-dimethoxy-4-methylphenyl)propan-2-amine
CAS Number
  • 15588-95-1 checkY
    43061-13-8 ((R)-DOM)
    43061-14-9 ((S)-DOM)
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC12H19NO2
Molar mass209.289 g·mol−1
3D model (JSmol)
Melting point61 °C (142 °F)
  • CC1=CC(=C(C=C1OC)CC(C)N)OC
  • InChI=1S/C12H19NO2/c1-8-5-12(15-4)10(6-9(2)13)7-11(8)14-3/h5,7,9H,6,13H2,1-4H3
  • Key:NTJQREUGJKIARY-UHFFFAOYSA-N checkY
  (verify)

2,5-Dimethoxy-4-methylamphetamine (DOM), also known as STP (standing for "Serenity, Tranquility, and Peace" and other phrases), is a psychedelic drug of the phenethylamine, amphetamine, and DOx families. It has stimulant and antidepressant-like effects at low doses and hallucinogenic effects at higher doses. The drug can have a very slow onset and long duration, with its duration possibly being up to a few days at high doses. It is usually taken orally.

Side effects of DOM include amphetamine-like effects, among others. The drug acts as a serotonin 5-HT2 receptor agonist, including of the serotonin 5-HT2A receptor. Analogues of DOM include mescaline, 2C-D, DOET, DOB, DOI, and Ariadne (4C-D), among others.

DOM was first synthesized and tested by Alexander Shulgin in 1963 and was later further described in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). The drug caused a small public health crisis in San Francisco in 1967 when it was introduced as a substitute for LSD, which was due to the tablets containing high doses and causing intense and very long-lived effects. DOM is classified as a Schedule I controlled substance in the United States, and is similarly controlled in other parts of the world. Internationally, it is a Schedule I drug under the Convention on Psychotropic Substances.

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved) and other publications, Alexander Shulgin lists DOM's dose as 3 to 10 mg orally and its duration as 14 to 24 hours. An estimated typical dose is about 6 mg. The (R)-enantiomer, (R)-DOM, was active at a dose of 0.5 mg, whereas DOM itself produces threshold effects only at 1 mg. The (S)-enantiomer, (S)-DOM, showed no psychoactive effects at doses of up to 2.6 mg. As such, the activity of DOM appears to reside in (R)-DOM, with this enantiomer appearing to be roughly twice as potent as racemic DOM. In a review by Richard Glennon and colleagues, the approximate hallucinogenic dose was listed as 2 to 5 mg for racemic DOM, 1.0 to 2.5 mg for (R)-DOM, and greater than 4 mg for (S)-DOM, with no known active level of the latter enantiomer. DOM is said by Shulgin to have a slow build-up, with an onset of 30 to 60 minutes and a peak of 2 to 6 hours. It may also have a very long duration of up to 3 or 4 days when taken in excessively high doses such as 14 to 30 mg. However, it is unclear the extent to which this is actually true or may just be exaggeration. DOM is about 50- to 150-fold as potent as mescaline and around 30- to 60-fold less potent than LSD.

The effects of DOM were reported by Shulgin to include feeling strange, color enhancement, closed-eye imagery, visuals, introspection and insights, fantasy, depersonalization, music and erotic enhancement, time dilation, emotional changes, mood elevation, increased empathy, stimulation, mood swings, tension, discomfort, feeling overwhelmed or like one is losing control, impairment, pupil dilation, jaw tightness, muscle tremors, feeling sick (but without nausea), other burdensome physical side effects, insomnia, and sleep disturbances. It has also been observed that DOM produces similar effects to LSD but causes less disorientation, impairment, and ego dissolution. The effects of DOM are highly dependent on set and setting, as with psychedelics in general. At lower doses of 2 to 5 mg, DOM is said to produce few or no physiological effects, no perceptual distortion, and more subtle visual, cognitive, and affective changes, but as not producing hallucinogenic effects at such doses. The drug was one of Shulgin's "magical half-dozen" psychedelic compounds in PiHKAL.

The effects of DOM were formally assessed in clinical studies by Solomon H. Snyder and Leo Hollister and colleagues in the late 1960s and early 1970s. At low doses, such as 1 to 4 mg, DOM produced effects including stimulation, euphoria, enhanced self-awareness, and mild dose-dependent perceptual disturbances. At higher doses, of above 5 to 7 mg, DOM produces marked and full psychedelic effects. Hallucinogenic effects were said to start at doses of more than 3 to 5 mg. Other effects of the drug were also described. Although Shulgin described the effects of DOM as typically lasting 14 to 20 hours, clinical studies with low doses reported a duration of only 5 to 8 hours, but with a lack of an unexpectedly long duration even at doses of up to 14 mg. Another source listed the average duration as only 8 to 15 hours at doses of 5 or 10 mg. The reasons for these discrepancies are unclear. The onset was 0.5 to 1.5 hours and peak effects occurred after 3 to 5 hours.

Low doses of DOM have been used as a stimulant, such as by the Grateful Dead. This may be the first known instance of psychedelic microdosing. The related drug DOET is also implicated as having stimulant and "psychic energizer" effects at low doses, which notably greatly impressed Shulgin.

Interactions

The typical antipsychotic and serotonin 5-HT2A receptor antagonist chlorpromazine has been reported to partially reduce the effects of DOM.

Side effects

Side effects of DOM include sweating, muscle tremors, and large increases in heart rate. These are said to be worrisome and not seen with other psychedelics like LSD. (S)-DOM produces increased heart rate and blood pressure but no psychoactive effects, in contrast to (R)-DOM. It may be importantly involved in the physical side effects of DOM, such that enantiopure (R)-DOM might be better-tolerated.

Tolerance

Repeated administration of DOM results in rapid tolerance development. In one study, in which five people were given 6 mg DOM for 3 days, there were "extremely intense" effects the first day, but diminished effects on the third day, ranging from "moderately strong" to "felt absolutely nothing". In another study, in which two people were given gradually increasing doses from 1 to 12 mg over 8 days, there was development of marked partial tolerance to the effects of DOM. Tolerance developed to both the psychoactive and physiological effects of the drug.

Overdose

Overdose of DOM can have a very long duration and result in an amphetamine psychosis-like state. It is said to have pronounced hallucinogenic effects as well as amphetamine-like side effects in overdose.

Pharmacology

Pharmacodynamics

Actions

DOM activities
TargetAffinity (Ki, nM)
5-HT1A3,656–14,200 (Ki)
12,800–13,900 (EC50Tooltip half-maximal effective concentration)
54–74% (EmaxTooltip maximal efficacy)
5-HT1B>10,000
5-HT1D209
5-HT1E3,542
5-HT1FND
5-HT2A2.1–507 (Ki)
1.1–40 (EC50)
44–132% (Emax)
5-HT2B12–149 (Ki)
128–688 (EC50)
85–91% (Emax)
5-HT2C19–3,980 (Ki)
0.23–423 (EC50)
81–119% (Emax)
5-HT3>10,000
5-HT4ND
5-HT5A>10,000
5-HT68,155
5-HT71,591
α1A3,219–7,393
α1B>10,000
α1DND
α2A580–>4,970
α2B874
α2C921
β1>10,000
β249
D1–D5>10,000
H1–H4>10,000
M1, M2, M5>10,000
M3, M4ND
TAAR1>30,000 (EC50)
I1>10,000
σ1, σ2>10,000
SERTTooltip Serotonin transporter>100,000 (Ki)
>100,000 (IC50Tooltip half-maximal inhibitory concentration)
>100,000 (EC50)
NETTooltip Norepinephrine transporter>100,000 (Ki)
>70,000 (IC50)
>100,000 (EC50)
DATTooltip Dopamine transporter>100,000 (Ki)
64,000 (IC50)
>42,000 (EC50)
MAO-ATooltip Monoamine oxidase A24,000 (IC50) (rat)
MAO-BTooltip 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:

DOM acts as a selective serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor full agonist. Its psychedelic effects are thought to be mediated by its agonistic properties at the serotonin 5-HT2A receptor. Due to its selectivity, DOM is often used in scientific research in studies of the 5-HT2 receptor subfamily. DOM is a chiral molecule, and R-(−)-DOM is the more active enantiomer, functioning as a potent agonist of these receptors.

The drug is inactive as a human trace amine-associated receptor 1 (TAAR1) agonist but is an agonist of the rhesus monkey TAAR1. DOM is inactive as a monoamine reuptake inhibitor and releasing agent. It is a very weak monoamine oxidase inhibitor (MAOI), specifically of monoamine oxidase A (MAO-A), whereas it was inactive at monoamine oxidase B (MAO-B).

Effects

DOM produces the head-twitch response in rodents, a behavioral proxy of psychedelic-like effects. The head-twitch response produced by DOM is robust. It also substitutes for LSD in rodent drug discrimination tests. DOM is widely used as a psychedelic training drug in rodent drug discrimination assays and many other serotonergic psychedelics have been shown to generalize to it. Other effects of DOM in rodents include hyperlocomotion at lower doses, hypolocomotion at higher doses, and hypothermia at high doses.

In contrast to amphetamines like (−)-cathinone but similarly to mescaline, DOM has shown no stimulant-like or reinforcing effects in rhesus monkeys. Conversely however, DOC has shown reinforcing effects, including conditioned place preference (CPP) and self-administration, in rodents similarly to methamphetamine. This is analogous to other findings in which various 2C and NBOMe drugs have been found to produce dopaminergic elevations and reinforcing effects in rodents.

DOM has potent anti-inflammatory effects, which may have medical applications.

Pharmacokinetics

The pharmacokinetics of DOM, including in humans, have been very limitedly studied. The drug crosses the blood–brain barrier in rodents. Metabolites of DOM like 2-O-desmethyl-DOM (2-DM-DOM) and 5-O-desmethyl-DOM (5-DM-DOM) are pharmacologically active and show psychedelic-like effects in animal studies. They might contribute to the delayed onset and long duration of DOM in humans. However, these metabolites might also produce metabolism-dependent neurotoxicity via conversion into 2,5-DDM-DOM and subsequent transformation. 2,5-DDM-DOM is similar in chemical structure to 6-hydroxydopamine (6-OHDA) and has likewise been found to be a potent neurotoxin. About 5 to 20% of a dose of DOM is excreted unchanged in humans.

Chemistry

Sample of DOM.

DOM, also known as 2,5-dimethoxy-4-methylamphetamine or as 2,5-dimethoxy-4-methyl-α-methylphenethylamine, is a substituted phenethylamine and amphetamine and is a member of the DOx group of drugs. It is structurally related to the naturally occurring phenethylamine psychedelic mescaline (3,4,5-trimethoxyphenethylamine).

Properties

The chemical properties of DOM have been described.

Synthesis

The chemical synthesis of DOM has been described.

Analogues and derivatives

Analogues of DOM include other DOx drugs such as DOET, DOB, DOI, DOC, and TMA, among others. The α-desmethyl or phenethylamine analogue of DOM is 2C-D. Ariadne is the α-ethyl or phenylisobutylamine homologue of DOM. DOM analogues with the 2- and/or 5-methoxy groups replaced have been studied, for instance 2-DM-DOM (2-OH-DOM), 5-DM-DOM (5-OH-DOM), 2,5-DDM-DOM, 2-TOM (2-thio-DOM), 5-TOM (5-thio-TOM), bis-TOM (2,5-dithio-TOM), TOMSO (5-TOM-sulfoxide), and others.

Chemical structures of DOM analogues and derivatives

History

DOM was first synthesized and tested in 1963 by Alexander Shulgin, who was investigating the effect of 4-position substitutions on psychedelic amphetamines. His 15-year-old son Theodore "Ted" Shulgin assisted in the synthesis of DOM by performing the first step of the synthesis at Dow Chemical Company on June 22, 1963 during a brief period when he was interested in chemistry. Later, Alexander Shulgin completed the synthesis on November 30, 1963. He initially discovered the effects of DOM on January 4, 1964, when he ingested a 1 mg dose orally. The hallucinogenic effects of DOM were discovered on February 3, 1964 by Shulgin's colleague Thornton W. Sargent when he ingested 2.3 mg. The first clearly psychedelic experience occurred with a dose of 4.1 mg on November 6, 1964. Shulgin hoped that Dow Chemical Company would develop DOM for medical purposes.

In mid-1967, tablets containing 20 mg and later 10 mg of DOM were widely distributed in the Haight-Ashbury District of San Francisco under the name of STP, having been manufactured by underground chemists Owsley Stanley and Tim Scully. This short-lived appearance of DOM on the black market proved disastrous for several reasons. First, the tablets contained an excessively high dose of the chemical. This, combined with DOM's slow onset (which encouraged some users, familiar with drugs that have quicker onsets, such as LSD, to re-dose) and its remarkably long duration, caused many users to panic and sent some to the emergency room. Second, treatment of such overdoses was complicated by the fact that no one at the time knew that the tablets called STP were, in fact, DOM, and there was no effective antidote. Many people with DOM intoxication were treated by David E. Smith and colleagues at the Haight Ashbury Free Clinic as well as at San Francisco General Hospital.

Society and culture

Names

The name DOM is an acronym of the code name "des-oxy-methyl" coined by the drug's inventor Alexander Shulgin. The drug was also initially known by the code name K-61,082 and is widely known by its nickname STP. The STP name has been said to stand for various acronyms, including Serenity, Tranquility, and Peace, Super Terrific Psychedelic, Stop The Police, and Too Stupid to Puke, among others.

DOM (STP) was featured in the 1968 psychedelic film Psych-Out.

Australia

DOM is schedule 9 under the Australia Poisons standard. A schedule 9 substance is a "Substances 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."

Canada

DOM is a Schedule I controlled substance in Canada.

United Kingdom

DOM is a Class A drug in the United Kingdom under the Misuse of Drugs Act 1971.

United States

DOM is Schedule I in the United States. This means it is illegal to manufacture, buy, possess, or distribute (make, trade, own or give) without a DEA license.

Research

DOM, along with DOET, was of interest in the potential treatment of psychiatric disorders such as depression in the 1960s. Subsequently, the related compound Ariadne (4C-D; BL-3912; Dimoxamine) was investigated in the 1970s, but was not marketed either.

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 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Baggott MJ (1 October 2023). "Learning about STP: A Forgotten Psychedelic from the Summer of Love" (PDF). History of Pharmacy and Pharmaceuticals. 65 (1): 93–116. doi:10.3368/hopp.65.1.93. ISSN 2694-3034. Retrieved 26 January 2025.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 Trout K, Daley PF (December 2024). "The origin of 2,5-dimethoxy-4-methylamphetamine (DOM, STP)" (PDF). Drug Testing and Analysis. 16 (12): 1496–1508. doi:10.1002/dta.3667. PMID 38419183.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Alexander T. Shulgin, Ann Shulgin (1991). "#68 DOM; STP; 2,5-DIMETHOXY-4-METHYLAMPHETAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. pp. 637–642. ISBN 978-0-9630096-0-9. OCLC 25627628.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Shulgin AT (1977). "Profiles of Psychedelic Drugs: 5. STP". Journal of Psychedelic Drugs. 9 (2): 171–172. doi:10.1080/02791072.1977.10472044. ISSN 0022-393X. Archived from the original on 2025-07-12.
  5. ↑ Anvisa (2023-07-24). "RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-07-25). Archived from the original on 2023-08-27. Retrieved 2023-08-27.
  6. 1 2 3 4 5 6 7 Glennon RA (April 2017). "The 2014 Philip S. Portoghese Medicinal Chemistry Lectureship: The "Phenylalkylaminome" with a Focus on Selected Drugs of Abuse". Journal of Medicinal Chemistry. 60 (7): 2605–2628. doi:10.1021/acs.jmedchem.7b00085. PMC 5824997. PMID 28244748. However, there was some concern that 2-DM-DOM and 5-DM-DOM might undergo further O-demethylation in vivo to a hydroquinone. It had been shown years earlier that DOM can undergo metabolic bis-demethylation to a hydroquinone, and that the hydroquinone undergoes oxidation to a para-quinone (and/or a cyclic iminoquinone) that reacts irreversibly with various proteins.44 As a consequence, this approach was not pursued because of potential risks of neurotoxicity. [...] 44. Jacob P. 3rd; Kline, T., Castagnoli, N. Jr. Chemical and biological studies of 1-(2,5-dihydroxy-4- methylphenyl)-2-aminopropane, an analogue of 6-hydroxydopamine. J Med Chem. 1979; 22:662– 671. [PubMed: 458821]
  7. 1 2 3 4 5 Eckler JR, Chang-Fong J, Rabin RA, Smith C, Teitler M, Glennon RA, et al. (July 2003). "Behavioral characterization of 2-O-desmethyl and 5-O-desmethyl metabolites of the phenylethylamine hallucinogen DOM". Pharmacology, Biochemistry, and Behavior. 75 (4): 845–852. doi:10.1016/s0091-3057(03)00159-x. PMID 12957227.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Snyder SH, Faillace L, Hollister L (November 1967). "2,5-dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug". Science. 158 (3801). New York, N.Y.: 669–670. Bibcode:1967Sci...158..669S. doi:10.1126/science.158.3801.669. PMID 4860952. S2CID 24065654.
  9. 1 2 3 4 Shulgin A, Manning T, Daley PF (2011). "#60. DOM". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley, CA: Transform Press. pp. 118–129. ISBN 978-0-9630096-3-0. OCLC 709667010.
  10. 1 2 3 Wills B, Erickson T (9 March 2012). "Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives". In Barceloux DG (ed.). Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Wiley. pp. 156–192. doi:10.1002/9781118105955.ch10. ISBN 978-0-471-72760-6.
  11. 1 2 3 4 5 6 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.
  12. 1 2 3 4 5 6 7 8 9 10 Luethi D, Glatfelter GC, Pottie E, Sellitti F, Maitland AD, Gonzalez NR, et al. (November 2025). "The 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effects" (PDF). Molecular Psychiatry. 31 (3): 1799–1809. doi:10.1038/s41380-025-03325-1. PMC 12916490. PMID 41193673.
  13. 1 2 3 Luethi D, Rudin D, Hoener MC, Liechti ME (2022). "Monoamine Receptor and Transporter Interaction Profiles of 4-Alkyl-Substituted 2,5-Dimethoxyamphetamines". The FASEB Journal. 36 (S1) fasebj.2022.36.S1.R2691. doi:10.1096/fasebj.2022.36.S1.R2691. ISSN 0892-6638.
  14. 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.
  15. 1 2 3 Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB (March 2014). "Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function". Psychopharmacology. 231 (5). Berl: 875–888. doi:10.1007/s00213-013-3303-6. PMC 3945162. PMID 24142203.
  16. 1 2 3 4 Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A (December 2018). "Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors". Biochemical Pharmacology. 158: 27–34. doi:10.1016/j.bcp.2018.09.024. PMC 6298744. PMID 30261175.
  17. ↑ "Green List: List of Psychotropic Substances Under International Control" (PDF) (23rd ed.). International Narcotics Control Board. August 2003. p. 4. Archived from the original (PDF) on 19 December 2013. Retrieved 22 February 2014.
  18. 1 2 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. Archived from the original on 13 July 2025.
  19. 1 2 Jacob P, Shulgin AT (1994). "Structure-Activity Relationships of the Classic Hallucinogens and Their Analogs". In Lin GC, Glennon RA (eds.). Hallucinogens: An Update (PDF). National Institute on Drug Abuse Research Monograph Series. Vol. 146. National Institute on Drug Abuse. pp. 74–91. PMID 8742795. Archived from the original on 13 July 2025.
  20. ↑ Glennon RA, Rosecrans JA (1982). "Indolealkylamine and phenalkylamine hallucinogens: a brief overview". Neuroscience and Biobehavioral Reviews. 6 (4): 489–497. doi:10.1016/0149-7634(82)90030-6. PMID 6757811.
  21. ↑ Snyder SH, Faillace LA, Weingartner H (September 1968). "DOM (STP), a new hallucinogenic drug, and DOET: effects in normal subjects". The American Journal of Psychiatry. 125 (3): 113–120. doi:10.1176/ajp.125.3.357. PMID 4385937.
  22. ↑ Weingartner H, Snyder SH, Faillace LA (1971). "DOM (STP), a new hallucinogenic drug: specific perceptual changes". The Journal of Clinical Pharmacology and New Drugs. 11 (2): 103–111. doi:10.1177/009127007101100205. PMID 5206471.
  23. 1 2 3 4 Hollister LE, Macnicol MF, Gillespie HK (1969). "An hallucinogenic amphetamine analog (DOM) in man". Psychopharmacologia. 14 (1): 62–73. doi:10.1007/BF00401535. PMID 5351858.
  24. 1 2 Angrist B, Rotrosen J, Gershon S (April 1974). "Assessment of tolerance to the hallucinogenic effects of DOM". Psychopharmacologia. 36 (3): 203–207. doi:10.1007/BF00421802. PMID 4844244.
  25. ↑ "PDSP Database". UNC (in Zulu). Retrieved 1 February 2025.
  26. ↑ Liu T. "BindingDB BDBM50005265 (+/-)2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine::(-)2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine::(Rec)2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine; compound with 2-(2,5-dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine::2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine::2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine((R)-(-)-DOM)::2-(2,5-Dimethoxy-4-methyl-phenyl)-1-methyl-ethylamine(DOM)::CHEMBL8600::DOM::DOM,R(-)::Racemic DOM". BindingDB. Retrieved 1 February 2025.
  27. 1 2 Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorganic & Medicinal Chemistry. 19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007. PMC 3236098. PMID 22037049.
  28. ↑ Åstrand A, Guerrieri D, Vikingsson S, Kronstrand R, Green H (December 2020). "In vitro characterization of new psychoactive substances at the μ-opioid, CB1, 5HT1A, and 5-HT2A receptors-On-target receptor potency and efficacy, and off-target effects". Forensic Science International. 317 110553. doi:10.1016/j.forsciint.2020.110553. PMID 33160102.
  29. ↑ van Wijngaarden I, Soudijn W (1997). "5-HT2A, 5-HT2B and 5-HT2C receptor ligands". Pharmacochemistry Library. Vol. 27. Elsevier. pp. 161–197. doi:10.1016/s0165-7208(97)80013-x. ISBN 978-0-444-82041-9.
  30. ↑ Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP (June 2002). "Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors". British Journal of Pharmacology. 136 (4): 510–519. doi:10.1038/sj.bjp.0704747. PMC 1573376. PMID 12055129.
  31. 1 2 Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Frontiers in Pharmacology. 10 1590. doi:10.3389/fphar.2019.01590. PMC 6989591. PMID 32038257.
  32. 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". Biochemical Pharmacology. 54 (12): 1361–1369. doi:10.1016/s0006-2952(97)00405-x. PMID 9393679.
  33. ↑ Sanders-Bush E, Burris KD, Knoth K (September 1988). "Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis". The Journal of Pharmacology and Experimental Therapeutics. 246 (3): 924–928. doi:10.1016/S0022-3565(25)22189-9. PMID 2843634.
  34. 1 2 3 4 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. Archived from the original (PDF) on 2025-03-26. Retrieved 2025-03-27.
  35. ↑ Fantegrossi WE, Murnane KS, Reissig CJ (January 2008). "The behavioral pharmacology of hallucinogens". Biochemical Pharmacology. 75 (1): 17–33. doi:10.1016/j.bcp.2007.07.018. PMC 2247373. PMID 17977517. Despite the reasonably constant recreational use of hallucinogens since at least the early 1970s [44], the reinforcing effects of hallucinogens have not been widely investigated in laboratory animals. Indeed, one of the earliest studies on the reinforcing effects of drugs using the intravenous self-administration procedure in rhesus monkeys found that no animal initiated self-injection of mescaline either spontaneously or after one month of programmed administration [45]. Likewise, the phenethylamine hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) was not effective in maintaining self-administration in rhesus monkeys [46]. Nevertheless, the hallucinogen-like phenethylamine 3,4-methylenedioxymethamphetamine (MDMA) has been shown to act as a reinforcer in intravenous self-administration paradigms in baboons [47], rhesus monkeys [48 – 50], rats [51] and mice [52].
  36. ↑ Canal CE, Murnane KS (January 2017). "The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens". Journal of Psychopharmacology. 31 (1). Oxford, England: 127–143. doi:10.1177/0269881116677104. PMC 5445387. PMID 27903793. One of the earliest studies on the reinforcing effects of drugs using the intravenous self-administration procedure in rhesus monkeys found that no animal initiated self-injection of mescaline either spontaneously or after one month of programmed administration, [...] (Deneau et al., 1969). The lack of mescaline self-administration stood in contrast to positive findings of self-administration of morphine, codeine, cocaine, amphetamine, pentobarbital, ethanol, and caffeine. A subsequent study with rhesus monkeys using 2,5-dimethoxy-4-methylamphetamine (DOM; Yanagita, 1986) provided similar results as the mescaline study. These findings have withstood the test of time, as the primary literature is virtually devoid of any accounts of self-administration of [classical hallucinogens (CH)], suggesting that there are very limited conditions under which laboratory animals voluntarily consume CH.
  37. ↑ Yanagita T (June 1986). "Intravenous self-administration of (−)-cathinone and 2-amino-1-(2,5-dimethoxy-4-methyl)phenylpropane in rhesus monkeys". Drug and Alcohol Dependence. 17 (2–3): 135–141. doi:10.1016/0376-8716(86)90004-9. PMID 3743404.
  38. ↑ Maguire DR (October 2024). "Evaluation of potential punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in rhesus monkeys responding under a choice procedure". Behavioural Pharmacology. 35 (7): 378–385. doi:10.1097/FBP.0000000000000787. PMC 11398979. PMID 39052019.
  39. ↑ Cha HJ, Jeon SY, Jang HJ, Shin J, Kim YH, Suh SK (May 2018). "Rewarding and reinforcing effects of 4-chloro-2,5-dimethoxyamphetamine and AH-7921 in rodents". Neuroscience Letters. 676: 66–70. doi:10.1016/j.neulet.2018.04.009. PMID 29626650.
  40. ↑ Gil-Martins E, Barbosa DJ, Borges F, Remião F, Silva R (June 2025). "Toxicodynamic insights of 2C and NBOMe drugs - Is there abuse potential?". Toxicology Reports. 14 101890. Bibcode:2025ToxR...1401890G. doi:10.1016/j.toxrep.2025.101890. PMC 11762925. PMID 39867514.
  41. ↑ Kim YJ, Ma SX, Hur KH, Lee Y, Ko YH, Lee BR, et al. (April 2021). "New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents". Archives of Toxicology. 95 (4): 1413–1429. Bibcode:2021ArTox..95.1413K. doi:10.1007/s00204-021-02980-x. PMID 33515270.
  42. ↑ Custodio RJ, Sayson LV, Botanas CJ, Abiero A, You KY, Kim M, et al. (November 2020). "25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential". Addiction Biology. 25 (6) e12850. doi:10.1111/adb.12850. PMID 31749223.
  43. ↑ Seo JY, Hur KH, Ko YH, Kim K, Lee BR, Kim YJ, et al. (October 2019). "A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents". Brain Research Bulletin. 152: 19–26. doi:10.1016/j.brainresbull.2019.07.002. PMID 31279579.
  44. ↑ Jo C, Joo H, Youn DH, Kim JM, Hong YK, Lim NY, et al. (November 2022). "Rewarding and Reinforcing Effects of 25H-NBOMe in Rodents". Brain Sciences. 12 (11): 1490. doi:10.3390/brainsci12111490. PMC 9688077. PMID 36358416.
  45. ↑ Lee JG, Hur KH, Hwang SB, Lee S, Lee SY, Jang CG (August 2023). "Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System". ACS Chemical Neuroscience. 14 (15): 2658–2666. doi:10.1021/acschemneuro.3c00196. PMID 37463338.
  46. ↑ Kim YJ, Kook WA, Ma SX, Lee BR, Ko YH, Kim SK, et al. (April 2024). "The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents". Archives of Pharmacal Research. 47 (4): 360–376. doi:10.1007/s12272-024-01491-4. PMID 38551761.
  47. ↑ 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 Pharmacology & Translational Science. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179.
  48. ↑ 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. The third principal metabolic route common to the hallucinogenic drugs is oxidation. Benzylic oxidation had been reported with both DOM (60.22aa) and DOET (60.22bb) (61, 62). Of greater theoretical interest is oxidative cyclization to form an indole species, reminiscent of the conversion of epinephrine to adrenochrome. Many of the hallucinogens are in fact indoles, and since the phenethylamine chain has the exact atom composition of indole itself, there has been frequent speculation that there might be some metabolic conversion from one family to the other. It has been shown (63) that one of the metabolites of DOM (2,5-dihydroxy[-4-methyl]phenylisopropylamine, 60.17), which bears a close chemical and pharmacological resemblance to the potent neurodegenerative agent 6-hydroxydopamine (60.18) (64), can undergo a facile oxidative cyclization to form a 5-hydroxyindole. The intermediate iminoquinone is potentially very reactive with nucleophilic agents found in normal body chemistry, and may be important in any explanation of biological activity.
  49. ↑ Castagnoli N (1978). "Drug Metabolism: Review of Principles and the Fate of One-Ring Psychotomimetics". Stimulants. Boston, MA: Springer US. pp. 335–387. doi:10.1007/978-1-4757-0510-2_7. ISBN 978-1-4757-0512-6. Retrieved 3 February 2026. FIG. 9. Metabolic pathways for amine III (DOM). [...] The third general metabolic pathway for 111 is oxidative O-demethylation of the methyl phenyl ether groups. All three possible O-demethylated metabolites, compounds 118-120, have been characterized in rabbit liver homogenates (Zweig and Castagnoli, 1975, 1977). The p-hydroquinone 120 is an analog of the sympatholytic agent 6-hydroxydopamine (107) and has been shown to possess some of the neurodegenerative properties of 6-hydroxydopamine (Butcher, 1975). Similar to 6-hydroxydopamine (Blank et ai., 1972), hydroquinone 120 undergoes facile oxidation to form the quinone 129 (Fig. 10), which cyclizes to the iminoquinone 130 (Zweig and Castagnoli, 1974). In the absence of nucleophiles, 130 is relatively stable at pH 7.4. As the pH is raised, however, proton rearrangements take place, eventually leading to the indole 132 via the indolinine 131. In view of the ease with which the hydroquinone 120 undergoes oxidation at pH 7.4, it is somewhat surprising that this compound survives the one hour pH 7.4 incubation. This stabilization may be analogous to the inhibition by liver constituents of hydroxylamine auto-oxidation. It should prove of interest to determine the nature and significance of the protection of these substances from air oxidation. [...] FIG. 10. Oxidative cyclization of p-hydroquinone metabolite derived from DOM. [...]
  50. ↑ Jacob P, Kline T, Castagnoli N (June 1979). "Chemical and biological studies of 1-(2,5-dihydroxy-4-methylphenyl)-2-aminopropane, an analogue of 6-hydroxydopamine". Journal of Medicinal Chemistry. 22 (6): 662–671. doi:10.1021/jm00192a011. PMID 458821.
  51. ↑ Butcher LL (1975). "Degenerative processes after punctate intracerebral administration of 6-hydroxydopamine". Journal of Neural Transmission. 37 (3): 189–203. doi:10.1007/BF01670128. PMID 1185165. Similarly, 1-(2,5-dihydroxy-4-methylphenyl)-2-aminopropane was not a more potent cytotoxin than 6-OHDA even though this new neurotoxin has a propane side chain which renders it immune to monoamine oxidase. [...] The neurotoxin 1-(2,5-dihydroxy-4-methylphenyl)-2-aminopropane-HC1 (DIMPAP) was synthesized by Dr. Nell Castagnoli, University of California Medical Center, San Francisco, CA, U.S.A. [...] Fig. 28. Chemical structure of 1-(2, 5-dihydroxy-4-methylphenyl)-2-aminopropaneHC1 (DIMPAP) [...] The extent of zone-3 damage: after intrastriatal infusion of various doses of DIMPAP is depicted in figures 29–33. No significant difference exists between the non-selective damage produced by DIMPAP and similar doses of 6-OHDA (e.g., compare Figs. 29–33 with Figs. 25–30 in Butcher et al., 1974). Furthermore, nialamide pre-treatment does not alter the destructive potency of either 6-OHDA or DIMPAP (compare Figs. 34–38 with Figs. 39–43 and Figs. 44–47).
  52. ↑ Hassan Z, Bosch OG, Singh D, Narayanan S, Kasinather BV, Seifritz E, et al. (2017). "Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs". Frontiers in Psychiatry. 8 152. doi:10.3389/fpsyt.2017.00152. PMC 5563308. PMID 28868040. The next, even though less accidental, producer of NPS hallucinogens was Alexander T. Shulgin, who synthesized hundreds of novel hallucinogenic tryptamines and phenylethylamines in his home laboratory. He described the synthesis of these compounds and also their psychotomimetic effects experienced in self-experiments in detail in his books PIHKAL and TIHKAL (199, 200). He created several dimethoxy-substituted phenylethylamines, such as DOM, 2,5-dimethoxy-4-bromoamphetamine (DOB), 2,5-dimethoxy-4-iodoamphetamine (DOI), and 2,5-dimethoxy-4-ethylamphetamine (DOET), which all display strong hallucinogenic properties. These drugs usually have much longer durations of action (12–30 h) and are much more potent agonists at 5-HT2A-Rs (50- to 175-fold) compared to their related phenylethylamine derivative mescaline (duration of action: 4–8 h) (189, 199, 200).
  53. 1 2 Cunningham MJ, Bock HA, Serrano IC, Bechand B, Vidyadhara DJ, Bonniwell EM, et al. (January 2023). "Pharmacological Mechanism of the Non-hallucinogenic 5-HT2A Agonist Ariadne and Analogs". ACS Chemical Neuroscience. 14 (1): 119–135. doi:10.1021/acschemneuro.2c00597. PMC 10147382. PMID 36521179.
  54. ↑ Braden MR (May 2007). Towards a Biophysical Basis of Hallucinogen Action (Thesis). Purdue University. OCLC 703618147. Retrieved 28 February 2012.
  55. ↑ Meyers FH, Rose AJ, Smith DE (1968). "Incidents Involving the Haight-Ashbury Population and Some Uncommonly Used Drugs". Journal of Psychedelic Drugs. 1 (2): 139–146. doi:10.1080/02791072.1968.10524531. ISSN 0022-393X.
  56. ↑ Smith DE (1969). "The Psychotomimetic Amphetamines with Special Reference to DOM (STP) Toxicity". Journal of Psychedelic Drugs. 2 (2): 37–41. doi:10.1080/02791072.1969.10524413. ISSN 0022-393X.
  57. ↑ Markert J (23 May 2013). Hooked in Film: Substance Abuse on the Big Screen. Bloomsbury Publishing USA. pp. 224–. ISBN 979-8-216-22555-3. Retrieved 12 February 2026. Psych-Out (1968) is thematically similar to The Trip, but with a more evolved storyline. Its primary "educational" value was to warn the viewer that while LSD is fine, one should at all costs avoid STP: "Don't get near that stuff. [You] don't know what's in it. They say it's LSD, cocaine, and methadrine." Another character chimes in: "It's like driving a Ferrari with the gas pedal strapped to the floor. It's nothing to play with." To drive home the admonition, Strasberg's character shortly thereafter is given some STP and freaks out: she sees fireballs in her mind's eye and attempts to flee them by running across a San Francisco bridge while cars careen around her. This was a critical warning to audiences when the film was released. In 1967, tablets containing DOM (2.5-Dimethoxy-4-methylamphetamine) were widely distributed in the Haight-Ashbury district of San Francisco under the name STP, which stood for Serenity-Tranquility-Peace. The short-lived appearance of DOM proved disastrous for several reasons. [...]
  58. 1 2 Poison Standard https://www.comlaw.gov.au/Details/F2015L01534/Html/Text#_Toc420496379 Archived 2015-12-22 at the Wayback Machine
  59. ↑ "Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.
  60. ↑ 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