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2,5-Dimethoxy-4-methylamphetamine
2,5-Dimethoxy-4-methylamphetamine
2,5-Dimethoxy-4-methylamphetamine
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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;[1] K-61,082[2]
Drug classSerotonergic psychedelic; Hallucinogen; Serotonin 5-HT2 receptor agonist
Legal status
Legal status
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
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)
  • O(c1cc(c(OC)cc1C[C@H](N)C)C)C
  • 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/t9-/m1/s1
  • Key:NTJQREUGJKIARY-SECBINFHSA-N checkY
  (verify)

2,5-Dimethoxy-4-methylamphetamine (DOM), also known as STP (standing for "Serenity, Tranquility, and Peace" and/or other phrases), is a psychedelic drug of the phenethylamine, amphetamine, and DOx families.[4][5][1][6][7] It is generally taken orally.[5][1][6]

DOM was first synthesized by Alexander Shulgin, and later described in his book PiHKAL: A Chemical Love Story (1991).[1] It is classified as a Schedule I controlled substance in the United States, and is similarly controlled in other parts of the world.[1] Internationally, it is a Schedule I drug under the Convention on Psychotropic Substances.[8]

Use and effects

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Effects of this drug include substantial perceptual changes such as blurred vision, multiple images, vibration of objects, visual alterations, distorted shapes, enhancement of details, slowed passage of time, increased sexual drive and pleasure, and increased contrasts. It may cause mystical experiences and changes in consciousness. It may also cause pupillary dilation and a rise in systolic blood pressure.[9]

The effects of DOM were assessed in clinical studies in the late 1960s and early 1970s and by other researchers.[2][7][10][11][12] At low doses, such as 1 to 4 mg, DOM produces effects including stimulation, euphoria, enhanced self-awareness, and mild dose-dependent perceptual disturbances.[2] At higher doses, of above 5 to 7 mg, DOM produces psychedelic effects.[2]

Side effects

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Very little is known about the toxicity of DOM.

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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Actions

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DOM activities
Target Affinity (Ki, nM)
5-HT1A 3,656–14,200 (Ki)
12,800–13,900 (EC50Tooltip half-maximal effective concentration)
54–74% (EmaxTooltip maximal efficacy)
5-HT1B >10,000
5-HT1D 209
5-HT1E 3,542
5-HT1F ND
5-HT2A 2.1–507 (Ki)
1.1–40 (EC50)
44–132% (Emax)
5-HT2B 12–41 (Ki)
128–145 (EC50)
85% (Emax)
5-HT2C 19–3,980 (Ki)
0.23–423 (EC50)
81–119% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 8,155
5-HT7 1,591
α1A 3,219
α1B >10,000
α1D ND
α2A 580
α2B 874
α2C 921
β1 >10,000
β2 49
D1–D5 >10,000
H1–H4 >10,000
M1, M2, M5 >10,000
M3, M4 ND
TAAR1 >10,000 (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 A 24,000 (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: [13][14][15][16][17][18][19][20][21][22][23][24]

DOM acts as a selective serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor full agonist.[16][15][17][18] Its psychedelic effects are mediated by its agonistic properties at the 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.[25]

The drug is inactive as a human trace amine-associated receptor 1 (TAAR1) agonist but is an agonist of the rhesus monkey TAAR1.[19] DOM is inactive as a monoamine reuptake inhibitor and releasing agent.[18] 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).[23][24]

Effects

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DOM produces the head-twitch response in rodents, a behavioral proxy of psychedelic-like effects.[26] It also substitutes for LSD in rodent drug discrimination tests.[26] 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.[26]

In contrast to amphetamines like (−)-cathinone but similarly to mescaline, DOM has shown no stimulant-like or reinforcing effects in rhesus monkeys.[27][28][29][30] Conversely however, DOC has shown reinforcing effects, including conditioned place preference (CPP) and self-administration, in rodents similarly to methamphetamine.[31] 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.[32][33][34][35][36][37][38]

Pharmacokinetics

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According to Alexander Shulgin, the effects of DOM typically last 14 to 20 hours, though other clinical trials indicate a duration of 7 to 8 hours.[9]

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.[39][40] They might contribute to the delayed onset and long duration of DOM.[40][39] However, these metabolites might also produce metabolism-dependent neurotoxicity.[39]

Chemistry

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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.[4][5][6][7] It is structurally related to the naturally occurring phenethylamine psychedelic mescaline (3,4,5-trimethoxyphenethylamine).[7][41]

Analogues

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See also: DOx (psychedelics) and PiHKAL § Ten classic ladies

Analogues of DOM include other DOx drugs such as DOET, DOB, DOI, DOC, and TMA, among others.[7] The α-desmethyl or phenethylamine analogue of DOM is 2C-D.[4][5] Ariadne is the α-ethyl or phenylisobutylamine analogue of DOM.[42][5]

Chemical structures of some DOM variants

The 2,6-dimethoxy positional isomer of DOM, known as Ψ-DOM, is also mentioned in PiHKAL as being active, as is the α-ethyl homologue Ariadne. Analogues where the methoxy groups at the 2,5- positions of the aromatic ring have been altered have also been synthesised and tested as part of an effort to identify the binding mode of DOM at the serotonin 5-HT2A receptor. Both the 2- and 5- O-desmethyl derivatives 2-DM-DOM and 5-DM-DOM, and the 2- and 5- ethyl analogues 2-Et-DOM and 5-Et-DOM, have been tested, but in all cases were significantly less potent than the corresponding methoxy compound, showing the importance of the oxygen lone pairs in 5-HT2A binding.[40][43]

History

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DOM was first synthesized and tested in 1963 by Alexander Shulgin, who was investigating the effect of 4-position substitutions on psychedelic amphetamines.[1][5]

In mid-1967, tablets containing 20 mg (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.[1] This short-lived appearance of DOM on the black market proved disastrous for several reasons.[1] First, the tablets contained an excessively high dose of the chemical.[1] This, combined with DOM's slow onset of action (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.[1] 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.[1]

Society and culture

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Names

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The name DOM is an acronym of the code name "des-oxy-methyl" coined by the drug's inventor Alexander Shulgin.[1]

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Australia

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DOM is schedule 9 under the Australia Poisons standard.[44] 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."[44]

Canada

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Listed as a Schedule 1, as it is an analogue of amphetamine.

United Kingdom

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

United States

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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.

See also

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References

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[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

2,5-Dimethoxy-4-methylamphetamine

View on Grokipedia
from Grokipedia
2,5-Dimethoxy-4-methylamphetamine (DOM), also known as STP, is a synthetic psychedelic compound of the and chemical classes that acts primarily as a serotonin 5-HT2A receptor agonist to elicit hallucinogenic effects. First synthesized by chemist in the , DOM produces dose-dependent alterations in , mood, and cognition, with low doses inducing mild and higher doses (above 3 mg) triggering profound visual hallucinations and introspective experiences lasting 8 to 20 hours. Its mirrors that of classical psychedelics like and , facilitating hypersynchrony in neural activity and behavioral changes characteristic of psychotomimetic states, though its extended duration has historically complicated safe use in both recreational and experimental contexts. DOM gained notoriety in the late for its potency and variable purity in street formulations, prompting empirical scrutiny of its risks, which empirical data indicate are primarily behavioral rather than directly toxic at typical doses.

Chemical Properties

Molecular Structure and Synthesis

2,5-Dimethoxy-4-methylamphetamine (DOM) possesses the molecular formula C12H19NO2 and a of 209.29 g/mol. Its IUPAC name is 1-(2,5-dimethoxy-4-methylphenyl)propan-2-amine, reflecting its structure as a derivative with an backbone substituted by methoxy groups at the 2- and 5-positions and a at the 4-position of the aromatic ring. This configuration positions DOM as a ring-substituted analog of (1-phenylpropan-2-amine), sharing structural similarities with analogs through its methoxy substitutions on the phenyl ring. DOM was first synthesized by chemist in 1964 through pathways involving methoxy-substituted aromatic precursors. Common laboratory synthesis routes employ of the corresponding derivative or reduction of a nitropropene intermediate, often starting from 2,5-dimethoxy-4-methylbenzaldehyde condensed with via a Henry reaction, followed by reduction with agents such as lithium aluminum hydride. These methods yield the racemic hydrochloride salt, which crystallizes upon acidification and cooling of the reaction mixture. In research settings, structural confirmation and purity assessment of DOM rely on spectroscopic and chromatographic techniques, including (NMR) spectroscopy for elucidating proton and carbon environments, and gas chromatography-mass spectrometry (GC-MS) for identification via impact ionization and retention time matching against standards. GC-MS protocols typically utilize non-polar columns like DB-1 MS, operating in split mode with molecular ions at m/z 209 for the underivatized base. These analytical approaches ensure verification of the compound's identity and exclude impurities from synthetic byproducts.

Physical and Chemical Characteristics

2,5-Dimethoxy-4-methylamphetamine (DOM) is typically encountered in its salt form as an off-white to white crystalline powder. The salt exhibits a of 187.6 °C, while the melts at approximately 60-61 °C. The compound demonstrates limited water solubility in its free base form, rendering it insoluble in aqueous media but readily soluble in organic solvents such as (up to 10 mg/mL), (5 mg/mL), and (14 mg/mL). In contrast, the salt possesses greater aqueous solubility, facilitating its dissolution in water for certain applications. DOM's (logP) of 2.24 reflects moderate , influencing its partitioning behavior in biphasic systems. The compound remains stable under standard ambient conditions as a crystalline solid but decomposes upon heating, releasing toxic vapors including nitrogen oxides. In comparison to structural analogs such as (DOB) and (DOI), DOM shares a conserved 2,5-dimethoxyphenethylamine core that imparts similar baseline chemical reactivity, including resistance to under neutral conditions. Differences arise from the 4-substituent: the in DOM yields a lower molecular weight (base: 209 Da) and distinct mass spectrometric fragmentation patterns, with prominent EI-MS ions at m/z 209 (M⁺), 194, 178, and 135, contrasting with bromine- or iodine-induced heavier isotopes and fragments in DOB and DOI. further differentiates DOM via characteristic absorptions at 1045 cm⁻¹ (C-O stretch) and 1213 cm⁻¹ (C-N stretch), aligning closely yet uniquely with the DOx series due to methoxy substitutions.

Pharmacological Mechanisms

Pharmacodynamics

2,5-Dimethoxy-4-methylamphetamine (DOM) functions primarily as a full at serotonin 5-HT_{2A} receptors, exhibiting high binding affinity with Ki values typically in the low nanomolar range. This receptor activation triggers G-protein-coupled signaling cascades, including G_q/11-mediated stimulation, accumulation, and intracellular calcium release, which underpin its characteristic serotonergic effects. DOM demonstrates moderate affinity for 5-HT_{2C} receptors and alpha-2 adrenergic receptors, but these bindings are substantially weaker than at 5-HT_{2A} sites, rendering them ancillary to the compound's core pharmacodynamic profile. Although structurally related to amphetamines, DOM induces limited and serotonin release through reversal, distinguishing its mechanism from non-hallucinogenic stimulants that rely more heavily on vesicular depletion and efflux. In rodent models, DOM provokes a dose-dependent head-twitch response, serving as an empirical indicator of 5-HT_{2A} , with the effect antagonized by selective 5-HT_{2A} blockers and absent in receptor strains. This behavioral correlates with receptor occupancy and activation potency across serotonergic hallucinogens.

Pharmacokinetics

DOM is typically administered orally and demonstrates good , with onset of pharmacological effects occurring 1-2 hours after ingestion of doses ranging from 2 to 14 mg. Peak effects generally manifest around 4-6 hours post-administration, aligning with inferred plasma concentration maxima based on the temporal profile of its prolonged action, which extends 14-20 hours in total. Metabolism occurs primarily in the liver via the 2D6 () isoform, which catalyzes the formation of hydroxy-DOM as the principal metabolite through of the 4-methyl group. This pathway predominates, with identified as the sole enzyme responsible for the major biotransformation in studies using human liver microsomes. Elimination in humans remains limited due to sparse clinical pharmacokinetic investigations, but approximately 20% of an oral dose is recovered unchanged in , indicating partial renal alongside metabolized fractions. The extended duration of effects suggests a on the order of 10-14 hours, though direct measurements are unavailable and inferred from observational and animal . Pharmacokinetic variability is influenced by genetic polymorphisms in , with poor metabolizers exhibiting reduced enzyme activity and potentially prolonged clearance, as observed in population studies of similar substrates. As a lipophilic compound, DOM may distribute into adipose tissues, contributing to its slow release and extended elimination phase, though quantitative distribution data in humans is lacking.

User Effects and Experiences

Psychological Effects

At oral doses ranging from 2 to 4 mg, DOM produces mild psychological effects including stimulation, euphoria, enhanced self-awareness, and subtle perceptual changes such as color enhancement and minor visual distortions. Higher doses of 5 to 10 mg elicit more intense hallucinogenic phenomena, including pronounced visual hallucinations, (e.g., auditory-visual cross-modal experiences), and distorted where intervals feel elongated or compressed. These effects scale non-linearly with dose, with threshold perceptual shifts at lower levels giving way to overwhelming sensory alterations at higher ones, as reported in early clinical administrations. User experiences vary, with some reporting profound ego dissolution—characterized by a loss of self-boundaries and unity with surroundings—alongside mystical or introspective states akin to those from . In contrast, others encounter anxiety, , or cognitive disorientation, particularly during the peak phase, as documented in uncontrolled settings where the drug circulated under the street name STP. These divergent outcomes likely stem from set, setting, and individual susceptibility, with surveys from that era noting heightened under influence. The psychological profile is further complicated by DOM's extended duration of 14 to 20 hours, exceeding users' expectations of shorter LSD-like trips and often amplifying distress through prolonged immersion in , as evidenced by anecdotal and observational reports from initial exposures. This mismatch contributed to panic in some cases, where perceived interminable effects fostered fears of permanent impairment.

Physiological Effects

DOM induces sympathomimetic cardiovascular effects, including with heart rates often elevating to 120-140 beats per minute and increases in systolic , as observed in human administrations and consistent with its amphetamine-derived structure activating adrenergic pathways. These changes arise from central stimulation of noradrenergic systems, measurable via and sphygmomanometry during acute intoxication phases. Mydriasis, or pupillary dilation, occurs prominently due to combined serotonergic and , leading to reduced light response documented in clinical evaluations. Thermoregulatory disruption manifests as , with core body temperatures rising above baseline levels in both human subjects and animal models, linked to impaired heat dissipation from serotonin-mediated hypothalamic effects. At elevated doses, this can contribute to autonomic instability resembling early features, such as exacerbated and diaphoresis, verified through temperature monitoring in experimental settings. The backbone of DOM drives suppression via enhanced signaling in hypothalamic feeding centers, quantifiable by reduced during its 14-20 hour duration of action. Prolonged results from sustained arousal, including elevated sympathetic tone that delays sleep onset and fragments rest, as tracked in polysomnographic assessments of similar phenethylamines.

Risks and Adverse Outcomes

Acute Adverse Reactions

Acute psychiatric adverse reactions to DOM include intense panic attacks, , and hallucinatory experiences that may precipitate or belligerent behavior. In controlled studies, users reported rapid mood swings, depersonalization, and overwhelming anxiety, exacerbated by the compound's long duration of action (16-24 hours). During the 1967 Haight-Ashbury incidents, acute panic reactions were frequent, with approximately 60 individuals seeking treatment at the local for "freak-outs" involving disorientation and hallucinations, and at least 13 hospitalizations noted for severe reactions. Physiological acute effects feature , , sweating, , and , often compounded by the drug's extended effects leading to immobility and from inadequate fluid intake. Cardiovascular strain manifests as increased and blood pressure elevation, posing risks of arrhythmias or exacerbated in predisposed users; confirm pressor responses and at doses of 1-4 mg/kg intravenously. Misdosed street samples in 1967, containing up to 20-30 mg per tablet versus therapeutic 2-3 mg, overwhelmed emergency services with cases of prolonged distress and physiological exhaustion. Pharmacological interactions, particularly with monoamine oxidase inhibitors (MAOIs), heighten risks of serotonin toxicity due to DOM's serotonergic agonism at 5-HT2A receptors combined with inhibited serotonin breakdown, potentially yielding symptoms like hyperthermia, rigidity, and seizures; this potentiation mirrors patterns observed with related psychedelics. Overdose scenarios from impure or high-potency samples have prompted emergency interventions, including sedatives for agitation control.

Chronic and Long-Term Risks

Repeated administration of DOM has been associated with potential neurotoxic effects, primarily inferred from its mechanism as a serotonergic releasing large quantities of serotonin, which may lead to depletion and subsequent in neural tissues. Rodent studies on analogous substituted amphetamines demonstrate serotonin damage and dendritic alterations following chronic exposure, though direct evidence for DOM remains limited to acute glutamate efflux observations without confirmed long-term histopathological changes. Hallucinogen persisting perception disorder (HPPD), characterized by ongoing visual disturbances such as trails, halos, or geometric patterns persisting months or years after cessation, has been reported in users of DOM and other hallucinogenic phenethylamines, albeit based predominantly on anecdotal case series lacking controlled cohorts. These perceptual anomalies may arise from disinhibition of excitatory-inhibitory cortical balance disrupted by repeated agonism, but prevalence is low and causality unestablished due to confounding polydrug use and pre-existing vulnerabilities. Chronic DOM use may exacerbate latent psychiatric conditions, with isolated reports of persistent in heavy psychotomimetic abusers, potentially via sustained dopaminergic-serotonergic imbalance unmasking predispositions to schizophrenia-spectrum disorders. However, robust longitudinal human data are absent, and such outcomes are rare compared to classical stimulants. Evidence for addiction liability is scant, with no systematic human studies documenting or withdrawal syndromes specific to DOM; its with other psychedelics like indicates minimal reinforcing properties beyond psychological craving in susceptible individuals. Abuse potential appears lower than for dopaminergic amphetamines, though self-administration data in non-human models substituting for DOM are inconclusive.

Therapeutic Potential and Research

Preclinical and Animal Studies

In rodent models, DOM elicits the head-twitch response (HTR), a rapid oscillatory head movement serving as a proxy for 5-HT2A receptor-mediated hallucinogenic activity, with potency correlating to its serotonergic . This response is dose-dependent, peaking at 1-3 mg/kg in mice, and is blocked by 5-HT2A antagonists like , confirming mechanistic specificity. Recent investigations have quantified DOM's impact on motor behavior, revealing significant gait alterations in mice, including reduced stride length and increased stance time, attributable to 5-HT2A/2C receptor activation at doses of 0.3-3 mg/kg subcutaneously. These changes mimic disruptions in coordination observed with other classical psychedelics and are attenuated by selective 5-HT2A antagonists, underscoring receptor mediation while highlighting potential locomotor side effects that may limit translational relevance. In nonhuman primates, DOM demonstrates aversive properties under self-administration paradigms. In rhesus monkeys trained to choose between fentanyl and food, response-contingent DOM (0.03-0.32 mg/kg) dose-dependently decreased selections, functioning as a independent of gross behavioral disruption, likely via 5-HT2A agonism-induced . This contrasts with reinforcing opioids and suggests DOM's limited abuse potential in higher-order models, though such effects may not uniformly predict human reinforcement dynamics due to differences in subjective valuation. Explorations of therapeutic proxies, such as fear , rely on analogs like DOI (2,5-dimethoxy-4-iodoamphetamine), which accelerates learning in rats via single 1.5 mg/kg doses, enhancing prefrontal dendritic spine density and markers like BDNF and Arc within 24 hours. DOI also upregulates immediate-early genes (e.g., c-Fos, /2) in neocortical neurons, promoting structural remodeling tied to 5-HT2A signaling. Given DOM's structural and pharmacological similarity to DOI, analogous may occur, but direct DOM data are sparse, and preclinical fear models exhibit variability across strains, cautioning against overextrapolation to efficacy amid absent DOM-specific enhancements. Overall, while animal data affirm DOM's robust 5-HT2A-driven behavioral signatures, including plasticity proxies, punishing profiles temper optimism for broad therapeutic translation, as motor assays poorly capture human phenomenology and aversion may reflect rather than targeted benefit.

Human Studies and Limitations

Human studies on DOM (2,5-dimethoxy-4-methylamphetamine) have been limited primarily to small-scale investigations in the involving normal volunteers, which documented its potent hallucinogenic effects but highlighted significant variability in onset, duration, and subjective intensity. In these trials, doses around 2-3 mg produced effects resembling but lasting 14-20 hours, with reports of visual distortions, altered , and insights, though some participants experienced anxiety or physical discomfort due to its amphetamine-like . These early experiments suggested potential for psychotherapeutic , akin to other serotonergic hallucinogens, but lacked structured protocols for treating specific disorders and were discontinued amid regulatory scrutiny and reports of adverse recreational outcomes. No randomized controlled trials (RCTs) specific to DOM's therapeutic efficacy have been conducted, leaving claims of benefits—such as enhanced or anecdotal relief from cluster headaches—unsupported by rigorous evidence and reliant on biased self-reports from unregulated use. User accounts, often disseminated through non-peer-reviewed channels, overstate consistency while underreporting risks like prolonged distress or cardiovascular strain, compounded by DOM's structure that introduces amphetamine-mediated sympathomimetic effects absent in pure tryptamines like . This evidentiary gap persists, with no FDA-approved protocols or modern clinical investigations, as DOM's dual hallucinogenic-stimulant profile raises safety concerns that preclude safe or repeated administration in vulnerable populations. Limitations in available data stem from methodological flaws in historical studies, including small sample sizes (typically under 10 participants), absence of blinding, and reliance on subjective scales prone to expectancy effects, particularly in an era of enthusiastic psychedelic research before standardized guidelines. Contemporary enthusiasm for psychedelics has prioritized compounds with cleaner safety margins, sidelining DOM due to its potential for neurotoxicity and addiction liability akin to amphetamines, rather than pursuing costly trials without preliminary animal proxies indicating broad therapeutic windows. Thus, any inferred benefits remain speculative, demanding skepticism toward extrapolations from descriptive volunteer data or unverified reports.

Historical Development

Early Synthesis and Discovery

Alexander T. Shulgin first synthesized 2,5-dimethoxy-4-methylamphetamine (DOM) in 1963 while working as a at in . This compound emerged from Shulgin's systematic exploration of ring-substituted amphetamines, building on earlier work with trimethoxyamphetamine (TMA) variants such as 2,4,5-trimethoxyamphetamine (TMA-2). By replacing the 4-methoxy group of TMA-2 with a methyl , Shulgin aimed to probe structure-activity relationships for enhanced psychoactive properties, drawing from the framework of , which features methoxy groups at positions corresponding to 3,4,5 on the ring (or 2,4,5 in standard numbering). Initial characterization of DOM highlighted its relation to mescaline analogs, with preliminary assessments indicating approximately 100-fold greater potency on a milligram basis compared to . Shulgin documented the synthesis and basic properties in his private laboratory notebooks, employing standard methods such as of the corresponding precursor with amphetamine-forming reagents. These records, later detailed in his 1991 PiHKAL (Phenethylamines I Have Known and Loved), provided the foundational chemical description, including the compound's at the alpha carbon and its racemic preparation. The synthesis reflected a deliberate, iterative approach to modifying substituents to optimize hallucinogenic effects, prioritizing variations at the para position (4) for potential receptor affinity improvements over prior TMA compounds. No verified pre-1963 syntheses of DOM appear in chemical , establishing Shulgin's work as the origin of the compound's documented preparation.

1960s Emergence and Incidents

In June 1967, during the in San Francisco's district, 2,5-dimethoxy-4-methylamphetamine (DOM), marketed under the street name STP—standing for "Serenity, Tranquility, Peace"—was widely distributed as a purportedly short-acting psychedelic alternative to , which had been banned in the previous year. Approximately 5,000 tablets were given away for free at a summer solstice event in on June 21, organized by underground chemist , marking DOM's rapid emergence into use. The drug's slow , combined with its unexpectedly prolonged duration of 24 to 72 hours—far exceeding the "short trip" implied by its branding—led users to mistakenly redose, believing the initial doses ineffective, which precipitated widespread overdoses. This mislabeling and adulteration in street batches, often involving impure or high-potency formulations, resulted in thousands of emergency room visits in the following weeks, overwhelming local health services in as unprepared users experienced extended intense hallucinations, anxiety, and physical distress such as elevated body temperature and dehydration. Empirical reports from the Haight-Ashbury Medical Clinic documented cases of prolonged "freak-outs" attributable to DOM's potent serotonergic effects rather than acute toxicity, with symptoms resolving without long-term harm in most instances but straining resources amid the influx of young, novice . Media coverage, including sensationalized accounts in outlets like the , amplified perceptions of DOM as a uniquely dangerous substance, though causal analysis points primarily to dosing errors and lack of user over inherent lethality. The incidents fueled a broader backlash against psychedelics, contributing to heightened public and regulatory scrutiny during the peak, as the resource strain on emergency systems and reports of psychological distress among festival-goers underscored the risks of unregulated distribution to an unprepared population. Despite its role in the era's experimental ethos, DOM's rollout exemplified how pharmacological mismatches—such as underestimating amphetamine-like persistence in a hallucinogenic profile—exacerbated adverse outcomes in communal settings lacking medical oversight.

Post-1970 Developments

In the wake of its designation as a Schedule I controlled substance under the , systematic clinical research on 2,5-dimethoxy-4-methylamphetamine (DOM) largely ceased in the United States, curtailing federally funded investigations into its psychoactive properties due to prohibitions on non-exempt human experimentation. Independent pharmacological inquiries persisted sporadically, but progress stalled amid regulatory barriers and lingering caution from earlier overdose reports associated with impure street formulations. Alexander Shulgin's 1991 publication : A Chemical Love Story, co-authored with , documented detailed syntheses and subjective dose-response data for DOM (entry #68), including its hydrochloride salt preparation yielding material with a melting point of 187–188 °C. This compendium, drawing from private explorations, reignited niche interest among organic chemists and psychopharmacologists in analogs, facilitating clandestine reproductions and extensions of the series despite legal risks. However, it did not spur institutional therapeutic trials, as DOM's protracted duration of action—typically 14 to 24 hours—posed logistical and safety challenges for controlled settings. From the 1980s through the , scientific attention shifted toward analytical and toxicological methodologies for DOM detection in forensic contexts, reflecting its occasional reemergence in illicit markets as a . Studies elucidated its pathways, identifying demethylenation as a primary route mediated by isoenzymes, enabling proof-of-ingestion via urinary metabolites in rat models. Complementary techniques, such as coupled with , were developed to quantify DOM and related 4-alkyl-2,5-dimethoxyamphetamines in human urine, aiding differentiation from structural mimics in overdose investigations. These efforts underscored persistent but low-level abuse patterns, yet yielded no advancements in clinical applications, prioritizing through identification over exploratory efficacy. Into the 2020s, preclinical investigations have centered on DOM's neuropharmacological mechanisms in animal models, emphasizing serotonin receptor interactions without advancing to human paradigms. Experiments in mice revealed DOM-induced gait disruptions attributable to 5-HT2A/2C agonism, dissectable via selective antagonists, highlighting its motor effects as proxies for hallucinogenic signaling. Parallel work documented enduring alterations in dendritic spine dynamics following DOM administration, suggesting potential plasticity enhancements akin to other serotonergic psychedelics, though limited to ex vivo brain slice analyses. Additional assays in rhesus monkeys evaluated DOM's reinforcing properties under choice procedures, indicating minimal abuse liability via weak punishing effects, reflective of broader hesitancy to pursue therapeutic translation amid historical precedents of misuse. This mechanistic focus persists amid regulatory stasis, with no evident resurgence in applied psychopharmacology.

United States

2,5-Dimethoxy-4-methylamphetamine (DOM), also known as STP, was subject to emergency regulatory action by the U.S. in 1967 following widespread distribution of misdosed tablets in San Francisco's district, which caused numerous medical emergencies due to unexpectedly high potency. The Bureau of Drug Abuse Control identified the substance as DOM, an experimental compound originally synthesized by , prompting immediate seizure and public warnings as part of pre-Controlled Substances Act enforcement. Under the Comprehensive Drug Abuse Prevention and Control Act of 1970, DOM was permanently classified as a Schedule I by the (DEA), indicating a high potential for abuse, no currently accepted medical use in treatment , and a lack of accepted safety for use under medical supervision. This designation, codified in 21 CFR § 1308.11, subjects possession, distribution, and manufacture to severe federal penalties, including up to 20 years imprisonment and fines exceeding $1 million for trafficking offenses. DEA forensic laboratories have tracked seizures of DOM in tablets and powders, with national reports documenting sporadic encounters amid broader enforcement. Structural variants of DOM fall under the (21 U.S.C. § 813), enacted in 1986 as part of the Anti-Drug Abuse Act, which treats substances substantially similar in chemical structure and effect to Schedule I hallucinogens like DOM as controlled if intended for human consumption. This provision has enabled prosecution of series analogues without individual scheduling. At the state level, mirrors the federal Schedule I classification under Health and Safety Code § 11054(e)(5), treating DOM as a restricted dangerous drug with possession penalized as a under § 11377, carrying up to one year in county jail and fines up to $1,000, though enhancements apply for quantities indicating intent to sell or prior convictions, escalating to charges with 16 months to three years in . Enforcement data from highlights increased penalties in analog cases, prioritizing deterrence through mandatory minimums for repeat offenders.

International Controls

2,5-Dimethoxy-4-methylamphetamine (DOM) is controlled under Schedule I of the [Convention on Psychotropic Substances](/page/Convention_on_Psychotropic Substances) of 1971, which mandates signatory states to prohibit its production, manufacture, export, import, distribution, trade, and possession except for strictly limited medical or scientific purposes, with requirements for licensing, record-keeping, and international reporting. In Canada, DOM is scheduled under the as a prohibited substance akin to other hallucinogenic amphetamines, subjecting unauthorized possession, trafficking, production, and importation to criminal penalties including fines and imprisonment up to 10 years for trafficking offenses. The classifies DOM as a Class A drug under the , encompassing structurally related derivatives with hallucinogenic properties, thereby imposing severe penalties for possession (up to 7 years imprisonment) and supply (up to life imprisonment with unlimited fines). Australia prohibits DOM federally under the Criminal Code Act 1995, listing it with trafficable (0.75 grams) and commercial (2.0 grams) quantity thresholds for aggravated importation or manufacturing offenses punishable by , alongside state-level bans such as in under the Drug Misuse and Trafficking Act 1985 as a prohibited hallucinogenic substance. European Union member states generally enforce Schedule I controls in alignment with the 1971 UN Convention, with DOM subject to national implementations prohibiting non-research activities; while the EU's monitors novel psychoactive substances, DOM's longstanding scheduling precludes , though enforcement varies by jurisdiction with some emphasis on over strict prosecution for personal possession in select countries.

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