DOM
2,5-dimethoxy-4-methylamphetamine
Studies and references cited across this article, graded by evidence strength.
Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.
Data points an editor reviewed and accepted for publication.
Value Provenance
Dosing
oraltrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 0.5 mg | 0.5 mg | medium |
| Low | 1–2 mg | 1–2 mg | medium |
| Common | 3–5 mg | 3–5 mg | medium |
| Strong | 5–10 mg | 5–10 mg | medium |
| Heavy | 10+ mg | 10+ mg | medium |
| Editorial | Dose ranges from PiHKAL (Shulgin 1991): active range 3-10 mg. Snyder et al. (1967) confirmed pronounced hallucinogenic effects above 3 mg. The 1967 crisis involved 10-20 mg tablets causing mass adverse events. Threshold of 0.5 mg and tier boundaries consistent with existing database values and PiHKAL data. | ||
ReasoningReasoningDose ranges from PiHKAL (Shulgin 1991): active range 3-10 mg. Snyder et al. (1967) confirmed pronounced hallucinogenic effects above 3 mg. The 1967 crisis involved 10-20 mg tablets causing mass adverse events. Threshold of 0.5 mg and tier boundaries consistent with existing database values and PiHKAL data. Evidence basis: expert_opinion | |||
Duration
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 30–120 minutes | 30–120 minutes | medium |
| Editorial | PiHKAL reports slow onset of 30 minutes to 2 hours for full effects. This delayed onset was the critical factor in the 1967 overdose crisis. | ||
ReasoningReasoningPiHKAL reports slow onset of 30 minutes to 2 hours for full effects. This delayed onset was the critical factor in the 1967 overdose crisis. Evidence basis: expert_opinion | |||
| Come uptrace | 1–2 hours | 1–2 hours | medium |
| Editorial | Inferred from PiHKAL description of gradual onset building over 1-2 hours beyond first alerts. No formal PK data. | ||
ReasoningReasoningInferred from PiHKAL description of gradual onset building over 1-2 hours beyond first alerts. No formal PK data. Evidence basis: expert_opinion | |||
| After effectstrace | 4–16 hours | 4–16 hours | low |
| Editorial | Aftereffects window estimated from class-level phenethylamine psychedelic data and the extended pharmacological activity of DOM. Residual stimulation and mood effects may persist well beyond the subjective experience. | ||
ReasoningReasoningAftereffects window estimated from class-level phenethylamine psychedelic data and the extended pharmacological activity of DOM. Residual stimulation and mood effects may persist well beyond the subjective experience. Evidence basis: expert_opinion | |||
| Peaktrace | 3–5 hours | 3–5 hours | low |
| Editorial | Estimated from PiHKAL qualitative descriptions of sustained peak effects within the 14-20 hour total duration. No formal PK time-course data. | ||
ReasoningReasoningEstimated from PiHKAL qualitative descriptions of sustained peak effects within the 14-20 hour total duration. No formal PK time-course data. Evidence basis: expert_opinion | |||
| Offsettrace | 4–8 hours | 4–8 hours | low |
| Editorial | Estimated from total duration minus onset, come-up, and peak. PiHKAL describes gradual resolution over hours. | ||
ReasoningReasoningEstimated from total duration minus onset, come-up, and peak. PiHKAL describes gradual resolution over hours. Evidence basis: expert_opinion | |||
| Totaltrace | 14–20 hours | 14–20 hours | medium |
| Editorial | PiHKAL (Shulgin 1991) reports 14-20 hours at common doses (3-10 mg). Snyder et al. (1967) reported ~8 hours at low doses (>3 mg) in controlled setting, indicating strong dose-dependence. The 14-20 hour range represents the common-to-strong dose experience. | ||
ReasoningReasoningPiHKAL (Shulgin 1991) reports 14-20 hours at common doses (3-10 mg). Snyder et al. (1967) reported ~8 hours at low doses (>3 mg) in controlled setting, indicating strong dose-dependence. The 14-20 hour range represents the common-to-strong dose experience. Evidence basis: expert_opinion | |||
Safety
Toxicity Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Acute | low | low | low |
| Chronic | low | low | low |
| Organs Affected | cardiovascular, central nervous system | cardiovascular, central nervous system | low |
| Editorial | Classified as low acute toxicity: the 1967 mass exposure at 3-7x common doses produced severe psychological effects but no documented fatalities. No LD50 data exist. Cardiovascular effects are centrally mediated (Friedman 1978). Chronic toxicity rated low with low confidence due to absence of any chronic exposure data; 5-HT2B agonism raises theoretical cardiac valvulopathy concern but no substance-specific data exist. | ||
ReasoningReasoningClassified as low acute toxicity: the 1967 mass exposure at 3-7x common doses produced severe psychological effects but no documented fatalities. No LD50 data exist. Cardiovascular effects are centrally mediated (Friedman 1978). Chronic toxicity rated low with low confidence due to absence of any chronic exposure data; 5-HT2B agonism raises theoretical cardiac valvulopathy concern but no substance-specific data exist. Evidence basis: published_case_series | |||
Dependence Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Physical | none | none | high |
| Psychological | negligible | negligible | high |
| Compulsive Redosing | negligible | negligible | high |
| Dose Escalation | negligible | negligible | high |
| Editorial | Nichols (2016) reviews evidence that serotonergic psychedelics do not lead to dependence or addiction. Gatch et al. (2011) confirmed DOM is non-reinforcing in self-administration models. Rapid tolerance (Pauwels 1990) and extended duration create pharmacological barriers to compulsive use. | ||
ReasoningReasoningNichols (2016) reviews evidence that serotonergic psychedelics do not lead to dependence or addiction. Gatch et al. (2011) confirmed DOM is non-reinforcing in self-administration models. Rapid tolerance (Pauwels 1990) and extended duration create pharmacological barriers to compulsive use. Evidence basis: controlled_human_study | |||
Withdrawal Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Severity | none | none | high |
| Symptoms | — | — | high |
| Fatal | No | No | high |
| Medical Supervision | Not required | Not required | high |
| Editorial | Nichols (2016) reviews evidence that serotonergic psychedelics do not lead to dependence or addiction. Gatch et al. (2011) confirmed DOM is non-reinforcing in self-administration models. Rapid tolerance (Pauwels 1990) and extended duration create pharmacological barriers to compulsive use. | ||
ReasoningReasoningNichols (2016) reviews evidence that serotonergic psychedelics do not lead to dependence or addiction. Gatch et al. (2011) confirmed DOM is non-reinforcing in self-administration models. Rapid tolerance (Pauwels 1990) and extended duration create pharmacological barriers to compulsive use. Evidence basis: controlled_human_study | |||
Tolerance Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Buildup | rapid | rapid | medium |
| Half-life | 3 days | 3 days | medium |
| Full Reset | 7 days | 7 days | medium |
| Cross-tolerances | LSD, psilocybin, mescaline, DOI, DOB, DPT | LSD, psilocybin, mescaline, DOI, DOB, DPT | medium |
| Editorial | Rapid tolerance buildup strongly supported by in vitro data (Pauwels 1990: 2-hour desensitization) and in vivo human data (Snyder study: diminished response by day 3). Cross-tolerance with LSD, tryptamines, and other DOx compounds confirmed via multiple animal studies (Smith 2014, De la Fuente Revenga 2022, Halberstadt & Geyer 2011). Half-life and reset values from existing DB, consistent with class-level data. | ||
ReasoningReasoningRapid tolerance buildup strongly supported by in vitro data (Pauwels 1990: 2-hour desensitization) and in vivo human data (Snyder study: diminished response by day 3). Cross-tolerance with LSD, tryptamines, and other DOx compounds confirmed via multiple animal studies (Smith 2014, De la Fuente Revenga 2022, Halberstadt & Geyer 2011). Half-life and reset values from existing DB, consistent with class-level data. Evidence basis: controlled_human_study | |||
Effects & Profile
Contraindications
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| other Phenothiazine antipsychotic usetrace | absolute | absolute | high |
| Editorial | Clinically documented from the 1967 mass exposure event (Trout & Daley 2024). This is a substance-specific finding with strong historical evidence. | ||
ReasoningReasoningClinically documented from the 1967 mass exposure event (Trout & Daley 2024). This is a substance-specific finding with strong historical evidence. | |||
| psychiatric Psychotic disorderstrace | absolute | absolute | medium |
| Editorial | Class-level contraindication for all serotonergic psychedelics (Nichols 2016). DOM's extended duration amplifies the risk window. | ||
ReasoningReasoningClass-level contraindication for all serotonergic psychedelics (Nichols 2016). DOM's extended duration amplifies the risk window. | |||
| psychiatric Bipolar disordertrace | relative | relative | low |
| Editorial | Class-level contraindication for serotonergic psychedelics. No DOM-specific data. | ||
ReasoningReasoningClass-level contraindication for serotonergic psychedelics. No DOM-specific data. | |||
| cardiovascular Uncontrolled hypertensiontrace | relative | relative | medium |
| Editorial | Cardiovascular effects confirmed in animal studies (Friedman 1978). Extended duration amplifies cardiovascular stress exposure. No human cardiovascular outcome data. | ||
ReasoningReasoningCardiovascular effects confirmed in animal studies (Friedman 1978). Extended duration amplifies cardiovascular stress exposure. No human cardiovascular outcome data. | |||
| other Concurrent SSRI/SNRI usetrace | relative | relative | high |
| Editorial | SSRI potentiation of DOM specifically demonstrated by Eckler et al. (2004) via 5-HT2C mechanism. Substance-specific evidence. | ||
ReasoningReasoningSSRI potentiation of DOM specifically demonstrated by Eckler et al. (2004) via 5-HT2C mechanism. Substance-specific evidence. | |||
| other Concurrent tramadol usetrace | absolute | absolute | medium |
| Editorial | Class-level serotonergic concern. No DOM-specific published data, but pharmacological mechanism is well-established. | ||
ReasoningReasoningClass-level serotonergic concern. No DOM-specific published data, but pharmacological mechanism is well-established. | |||
| neurological Epilepsytrace | relative | relative | medium |
| Editorial | Seizures documented in 1967 crisis reports (Trout & Daley 2024). Applies primarily to high doses but represents a relevant risk for seizure-prone individuals at any dose. | ||
ReasoningReasoningSeizures documented in 1967 crisis reports (Trout & Daley 2024). Applies primarily to high doses but represents a relevant risk for seizure-prone individuals at any dose. | |||
| pregnancy breastfeeding Pregnancytrace | absolute | absolute | low |
| Editorial | Standard precautionary contraindication in the absence of any reproductive safety data. Class-level concern. | ||
ReasoningReasoningStandard precautionary contraindication in the absence of any reproductive safety data. Class-level concern. | |||
Timeline Phases
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 1800–5400 sec(i=0.05) | 1800–5400 sec(i=0.05) | medium |
| Editorial | Timeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. | ||
ReasoningReasoningTimeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. Evidence basis: expert_opinion | |||
| Come uptrace | 3600–7200 sec(i=0.30) | 3600–7200 sec(i=0.30) | medium |
| Editorial | Timeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. | ||
ReasoningReasoningTimeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. Evidence basis: expert_opinion | |||
| Peaktrace | 10800–18000 sec(i=1.00) | 10800–18000 sec(i=1.00) | medium |
| Editorial | Timeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. | ||
ReasoningReasoningTimeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. Evidence basis: expert_opinion | |||
| Plateautrace | 10800–21600 sec(i=0.50) | 10800–21600 sec(i=0.50) | medium |
| Editorial | Timeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. | ||
ReasoningReasoningTimeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. Evidence basis: expert_opinion | |||
| Resolutiontrace | 7200–14400 sec(i=0.20) | 7200–14400 sec(i=0.20) | medium |
| Editorial | Timeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. | ||
ReasoningReasoningTimeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. Evidence basis: expert_opinion | |||
| Afterglowtrace | 14400–57600 sec(i=0.05) | 14400–57600 sec(i=0.05) | medium |
| Editorial | Timeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. | ||
ReasoningReasoningTimeline derived from PiHKAL (total duration 14\u201320 hours at common doses, onset 30 min to 2 hours) and Snyder et al. 1967 (~8 hours at low doses). No formal pharmacokinetic time-course data exist. Phase boundaries are estimated from Shulgin's qualitative descriptions and the general pharmacological profile of long-acting phenethylamine psychedelics. The exceptionally broad peak and plateau reflect Shulgin's descriptions of sustained effects. Evidence basis: expert_opinion | |||
Dose Tier Summaries
At threshold oral doses (~0.5 mg), effects are subtle and easily dismissed: mild mood brightening, slight enhancement of colour saturation, and a gentle sense of heightened sensory awareness. Cognitive effects are minimal — a faint sense of novelty or increased appreciation for environmental detail without overt alteration of thought patterns. Physically, mild pupil dilation may be detectable. Appetite and sleep are not significantly disrupted at this level. The experience is sub-psychedelic and functionally manageable, though the slow onset (1–2 hours) means even threshold effects require patience before assessment.
Threshold of ~0.5 mg consistent with PiHKAL dose range (3–10 mg active, with threshold effects below this). Qualitative description inferred from class-level phenethylamine psychedelic threshold effects and Shulgin's reports.
ReasoningReasoning
Threshold of ~0.5 mg consistent with PiHKAL dose range (3–10 mg active, with threshold effects below this). Qualitative description inferred from class-level phenethylamine psychedelic threshold effects and Shulgin's reports.
Evidence basis: expert_opinion
At light oral doses (1–2 mg), perceptual shifts become unmistakable: surfaces may appear to breathe or shimmer, colours deepen, and music appreciation intensifies. Mild time distortion emerges — minutes may feel elongated. Thought connectivity increases gently, producing occasional novel associations without the overwhelming ideational flow of higher doses. Emotional tone is generally positive, with mood elevation and increased sociability. Physical effects include noticeable mydriasis, mild jaw tension, and slight body stimulation. Duration at these doses may be shorter than at common doses — Snyder et al. reported approximately 8 hours at doses just above 3 mg. Sleep will be difficult for at least 8 hours after ingestion.
Light dose range inferred from PiHKAL active range (3–10 mg) and Snyder et al. (1967) reporting pronounced effects above 3 mg, with sub-hallucinogenic/mild effects at lower doses. Duration of ~8 hours at low doses from Snyder et al.
ReasoningReasoning
Light dose range inferred from PiHKAL active range (3–10 mg) and Snyder et al. (1967) reporting pronounced effects above 3 mg, with sub-hallucinogenic/mild effects at lower doses. Duration of ~8 hours at low doses from Snyder et al.
Evidence basis: expert_opinion
At common oral doses (3–5 mg), the full psychedelic experience manifests: pronounced visual enhancement with colour intensification, geometric patterning overlaying surfaces, and drifting or morphing of objects. Closed-eye imagery becomes vivid and may synchronise with music. Time distortion is significant. Thought connectivity increases dramatically, producing introspective insights and novel conceptual associations. Emotional responses intensify — music, nature, and interpersonal interactions carry heightened meaning. Physically, mydriasis, tachycardia, dry mouth, jaw tension, and body tremors may appear. Thirst increases while urination diminishes. The experience demands commitment: effects build slowly over 1–2 hours and persist for 14–20 hours at this dose range. Sleep is impossible for the duration. Functional impairment is substantial.
Common dose range of 3–5 mg from PiHKAL (active range 3–10 mg). Qualitative effects from Shulgin's PiHKAL descriptions. Duration of 14–20 hours from PiHKAL. Physical effects (mydriasis, tachycardia, dry mouth, jaw tension, tremors, thirst) from PiHKAL.
ReasoningReasoning
Common dose range of 3–5 mg from PiHKAL (active range 3–10 mg). Qualitative effects from Shulgin's PiHKAL descriptions. Duration of 14–20 hours from PiHKAL. Physical effects (mydriasis, tachycardia, dry mouth, jaw tension, tremors, thirst) from PiHKAL.
Evidence basis: expert_opinion
At strong oral doses (5–10 mg), visual effects become immersive and commanding: open-eye geometric patterning is dense, environmental distortion is pronounced, and closed-eye imagery may become narrative or archetypal. Ego dissolution or significant ego softening can occur. Emotional intensity is profound and may oscillate unpredictably between euphoria, awe, and anxiety. Introspective depth is maximal, with potential for challenging psychological material to surface. Physical load increases: body tremors, pronounced jaw tension, tachycardia, and temperature dysregulation are common. The experience extends to the upper end of the 14–20 hour duration window. Maintaining orientation and composure requires significant psychological preparation. A trusted companion is strongly advisable.
Strong dose range of 5–10 mg derived from PiHKAL active range (3–10 mg), with Shulgin noting overwhelming effects at the upper end. Duration at upper end of 14–20 hour window from PiHKAL.
ReasoningReasoning
Strong dose range of 5–10 mg derived from PiHKAL active range (3–10 mg), with Shulgin noting overwhelming effects at the upper end. Duration at upper end of 14–20 hour window from PiHKAL.
Evidence basis: expert_opinion
At heavy oral doses (10+ mg), the experience becomes overwhelming and potentially uncontrollable. The 1967 San Francisco crisis involved doses of 10–20 mg and produced delusional behaviour, violent agitation, amnesia, severe panic, confusion, and seizures in multiple individuals. Visual and cognitive effects at this level may be indistinguishable from psychosis. Sympathomimetic cardiovascular strain — pronounced tachycardia and hypertension — poses direct physiological risk. Duration extends beyond the 14–20 hour window documented at common doses. These doses caused mass medical emergencies requiring hospital treatment. Chlorpromazine worsened outcomes when administered; benzodiazepines are the appropriate pharmacological intervention for agitation.
Heavy dose data from the 1967 Haight-Ashbury crisis (Trout & Daley 2024) documenting 10–20 mg tablets causing mass adverse events. Clinical presentations from historical medical documentation. Chlorpromazine contraindication from same source.
ReasoningReasoning
Heavy dose data from the 1967 Haight-Ashbury crisis (Trout & Daley 2024) documenting 10–20 mg tablets causing mass adverse events. Clinical presentations from historical medical documentation. Chlorpromazine contraindication from same source.
Evidence basis: published_case_series
History
backfill Jun 4, 2026
Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.
Sources
- [1]moderate2,5-Dimethoxy-4-methyl-amphetamine (STP): A New Hallucinogenic DrugSnyder SH, Faillace LA, Hollister LE · 1967 · Science
- [2]weak
- [3]moderateThe origin of 2,5-dimethoxy-4-methylamphetamine (DOM, STP)Trout K, Daley PF · 2024 · Drug Testing and Analysis
- [4]moderate1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review.Glennon RA, Dukat M · 2024 · ACS Pharmacology & Translational Science
- [5]strongThe 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effectsLuethi D et al. · 2026 · Molecular Psychiatry
- [6]moderateDiscriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rhesus monkeys: antagonism and apparent pA2 analyses.Li JX, Rice KC, France CP · 2009 · Journal of pharmacology and experimental therapeutics
- [7]strongThe discriminative stimulus properties of 2,5-dimethoxy-4-methylamphetamine (DOM): differentiation from amphetamineSilverman PB, Ho BT · 1980 · Psychopharmacologypubmed 67718048 claims checked5 verified3 partial
- [8]strongPsychedelicsNichols DE · 2016 · Pharmacological Reviews
- [9]strongAbuse liability profile of three substituted tryptaminesGatch MB, Forster MJ, Janowsky A, Eshleman AJ · 2011 · Journal of Pharmacology and Experimental Therapeutics
- [10]strongRapid desensitization and resensitization of 5-HT2 receptor mediated phosphatidyl inositol hydrolysis by serotonin agonistsPauwels PJ, Van Gompel P, Leysen JE · 1990 · Life Sciencespubmed 22739413 claims checked3 verified
- [11]moderateTolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Micede la Fuente Revenga M, Jaster AM, McGinn J, Silva G, Saha S, Gonzalez-Maeso J · 2022 · ACS Chemical Neuroscience
- [12]moderateDiscriminative Stimulus Effects of Substituted Tryptamines in RatsGatch MB, Hoch A, Carbonaro TM · 2021 · ACS Pharmacology & Translational Science
- [13]strongLocomotor and discriminative stimulus effects of NBOH hallucinogens in rodentsMunir DD, Shetty RA, Gatch MB, Sumien N, Hill RD, Priddy JA, Forster MJ · 2025 · Behavioural Pharmacology
- [14]moderateInvestigation of the 2,5-Dimethoxy Motif in Phenethylamine Serotonin 2A Receptor AgonistsMarcher-Rørsted E, Halberstadt AL, Klein AK, Chatha M, Jademyr S, Jensen AA, Kristensen JL · 2020 · ACS Chemical Neuroscience
- [15]strongStudies on chiral interactions of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane and the corresponding N-hydroxy metabolites with cytochrome P-450McGraw NP, Castagnoli N · 1981 · Journal of Medicinal Chemistrypubmed 72651165 claims checked3 verified2 partial
- [16]weak
- [17]strongA 5-HT(2C) receptor-mediated interaction between 2,5-dimethoxy-4-methylamphetamine and citalopram in the ratEckler JR, Reissig CJ, Rabin RA, Winter JC · 2004 · Pharmacology, Biochemistry, and Behaviorpubmed 153882806 claims checked6 verified
- [18]strong2,5-Dimethoxy-4-methylamphetamine (DOM)- a central component of its cardiovascular effects in rats; involvement of serotoninFriedman E, Lambert GA, Buchweitz E · 1978 · European Journal of Pharmacologypubmed 265786 claims checked6 verified
- [19]strongEffects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areasDoat-Meyerhoefer MM, Hard R, Winter JC, Rabin RA · 2005 · Pharmacology, Biochemistry, and Behaviorpubmed 159722342 claims checked2 verified
- [20]moderatePsychedelics and the human receptoromeRay TS · 2010 · PLoS ONE
- [21]moderateDifferential effects of serotonin 5-HT1A receptor agonists on the discriminative stimulus effects of the 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rats and rhesus monkeys.Li JX, Koek W, Rice KC, France CP · 2010 · Journal of pharmacology and experimental therapeutics
- [22]moderateMultiple receptors contribute to the behavioral effects of indoleamine hallucinogensHalberstadt AL, Geyer MA · 2011 · Neuropharmacology
- [23]moderateCorrelation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other speciesHalberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD · 2020 · Neuropharmacology
- [24]strongLocomotor and discriminative stimulus effects of four novel hallucinogens in rodentsGatch MB, Dolan SB, Forster MJ · 2017 · Behavioural Pharmacology
- [25]moderateTolerance and cross-tolerance to head twitch behavior elicited by phenethylamine- and tryptamine-derived hallucinogens in mice.Smith DA, Bailey JM, Williams D, Fantegrossi WE · 2014 · The Journal of pharmacology and experimental therapeutics
Claim Verification
Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.
summary12 claims7verified3partial2inconclusive
verifiedDOM occupies a distinctive position in the phenethylamine hallucinogen landscape: approximately 100 times more potent than mescaline by weight and one-thirtieth the potency of lsd[1]model confidence 95%
The abstract directly states '~100x more potent than mescaline, ~1/30 as potent as LSD,' matching the claim exactly.
~100x more potent than mescaline, ~1/30 as potent as LSD.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveDOM was first synthesized by Alexander Shulgin at Dow Chemical Company in 1963–1964 and became the first widely distributed phenethylamine psychedelic when approximately 5,000 high-dose tablets entered circulation in San Francisco during the 1967 Summer of Love — an event that produced a mass medical crisis and accelerated federal scheduling[3]model confidence 70%
The abstract confirms Shulgin's role and Owsley Stanley's 1967 distribution broadly, but specific details (5,000 tablets, 1963–1964 synthesis date, 'first widely distributed') are not confirmed in the abstract text; they may be in the full review.
Historical account of DOM development, Shulgin's role, Owsley Stanley's 1967 distribution, chlorpromazine warning origins.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe only controlled human study remains Snyder, Faillace, and Hollister's 1967 report in Science[1]model confidence 75%
The abstract confirms this is the 'first' controlled human study but does not assert it is the 'only' one; absence of subsequent studies cannot be inferred from the abstract.
First controlled human study of DOM/STP.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOM's contemporary significance is primarily as a reference training compound in animal drug discrimination studies and as the founding member of the DOx structure-activity series.[4]model confidence 85%
Abstract confirms DOM was the first DOx member identified as hallucinogenic and the paper covers the full DOx SAR series, supporting both claims.
DOM was the first member identified as hallucinogenic. DOx are 5-HT2 agonists. SAR, binding, behavioral pharmacology covered.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOM acts as a full agonist at serotonin 5-HT₂A and 5-HT₂C receptors, with in vitro EC₅₀ values at 5-HT₂A in the range of 2–56 nM across assay systems[5]model confidence 95%
Abstract directly confirms 5-HT2 receptor subtypes as primary targets and in vitro 5-HT2A activities in the 2–56 nM range.
5-HT2 receptor subtypes primary targets. In vitro 5-HT2A activities 2-56 nM.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialThe 5-HT₂A mechanism is confirmed by Schild analysis: the selective antagonist MDL100907 produces competitive rightward shifts of the DOM dose-response curve (pA₂ = 8.61), and dopamine antagonists exert no blocking effect.[6]model confidence 80%
Abstract confirms pA2 = 8.61 for MDL100907 via Schild analysis, but does not mention dopamine antagonists—that element comes from a different citation (citation [22]).
pA2 for MDL100907 = 8.61. Competitive antagonism confirmed by Schild analysis.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialThe 5-HT₂A mechanism is confirmed by Schild analysis: the selective antagonist MDL100907 produces competitive rightward shifts of the DOM dose-response curve (pA₂ = 8.61), and dopamine antagonists exert no blocking effect.[7]model confidence 75%
Abstract confirms dopamine antagonists do not block DOM and DOM does not substitute for amphetamine, but pA2 = 8.61 and the Schild analysis are not in this abstract—those come from citation [2].
DOM stimulus blocked by 5-HT antagonists, not dopamine antagonists.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOM does not produce physical dependence or function as a positive reinforcer in self-administration paradigms[8]model confidence 90%
Abstract explicitly states serotonergic hallucinogens 'do not lead to dependence/addiction,' directly supporting the claim.
Considered physiologically safe, do not lead to dependence/addiction.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOM does not produce physical dependence or function as a positive reinforcer in self-administration paradigms[9]model confidence 85%
Abstract notes 'low abuse liability for DOM in rodents,' consistent with DOM not functioning as a positive reinforcer.
Low abuse liability for DOM in rodents.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedTolerance develops within hours of exposure through rapid 5-HT₂ receptor desensitization, with near-complete loss of receptor-mediated signalling observed within 2 hours in vitro[10]model confidence 95%
Abstract directly confirms 'DOM causes nearly full 5-HT2 desensitization in 2 hours.'
DOM causes nearly full 5-HT2 desensitization in 2 hours.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialCross-tolerance extends to lsd, psilocybin, and mescaline via shared 5-HT₂A downregulation[11]model confidence 80%
Abstract confirms cross-tolerance between DOI and LSD and 5-HT2A downregulation as the mechanism, but does not specifically mention psilocybin or mescaline.
Cross-tolerance between DOI and LSD. 5-HT2AR density downregulated in frontal cortex.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPublished human pharmacokinetics — bioavailability, plasma half-life, volume of distribution — remain entirely uncharacterized.[3]model confidence 95%
Abstract explicitly states DOM 'rapidly faded before human pharmacodynamics/pharmacokinetics established,' directly supporting that PK parameters remain uncharacterized.
DOM rapidly faded before human pharmacodynamics/pharmacokinetics established.
checked by claude-sonnet-4-6 · Apr 26, 2026
history8 claims4verified1partial3inconclusive
inconclusiveSargent on February 3, 1964, following ingestion of 2.3 mg[3]model confidence 70%
The abstract covers DOM's history broadly but does not mention Sargent, the specific date (February 3, 1964), or the dose (2.3 mg). These specific details are not confirmed in the abstract.
Historical account of DOM development, Shulgin's role, Owsley Stanley's 1967 distribution, chlorpromazine warning origins.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe study reported that doses exceeding 3 mg produced 'pronounced hallucinogenic effects lasting about 8 hours,' established DOM as approximately 100 times more potent than mescaline and one-thirtieth the potency of lsd, and observed that psychological effects were 'not accentuated by chlorpromazine'[1]model confidence 85%
Abstract confirms the dose threshold (>3 mg), 8-hour duration, and both potency comparisons. The chlorpromazine finding is not in the abstract but is a primary research paper where full-text likely contains this finding; the major claims are confirmed.
Doses >3mg cause pronounced hallucinogenic effects lasting ~8 hours. ~100x more potent than mescaline, ~1/30 as potent as LSD.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe compound was assigned the internal code K-61,082[3]model confidence 65%
Abstract covers DOM's development history but does not mention the internal code K-61,082. This specific detail is not confirmed in the abstract.
Historical account of DOM development, Shulgin's role.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveSmith estimated that for every patient who sought treatment, approximately 39 more were experiencing effects in the community without medical attention.[3]model confidence 65%
Abstract covers the 1967 distribution and its aftermath broadly but does not confirm the specific 1:39 ratio attributed to Smith.
Historical account of DOM development, Shulgin's role, Owsley Stanley's 1967 distribution.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedFollowing scheduling, DOM rapidly disappeared from the illicit drug supply.[3]model confidence 80%
Abstract confirms 'DOM rapidly faded,' consistent with disappearing from the illicit supply after scheduling, within a paper covering this regulatory history.
DOM rapidly faded before human pharmacodynamics/pharmacokinetics established.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialIt has been continuously employed as a reference training compound in animal drug discrimination studies spanning decades and serves as the founding member of the DOx structure-activity relationship series, which includes doi, dob, and related analogs[6]model confidence 70%
Abstract demonstrates DOM's use in drug discrimination studies (reference training compound), supporting that aspect. The founding DOx member claim is not covered by this paper's abstract.
DOM discriminative stimulus effects mediated by 5-HT2A receptors in rhesus monkeys.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedIt has been continuously employed as a reference training compound in animal drug discrimination studies spanning decades and serves as the founding member of the DOx structure-activity relationship series, which includes doi, dob, and related analogs[13]model confidence 90%
Abstract confirms DOM is used as a reference training drug in recent discrimination studies (25X-NBOH compounds tested against DOM), demonstrating its continued use spanning decades.
Four 25X-NBOH compounds tested against DOM discriminative stimulus. Confirms DOM as standard reference hallucinogen.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedIt has been continuously employed as a reference training compound in animal drug discrimination studies spanning decades and serves as the founding member of the DOx structure-activity relationship series, which includes doi, dob, and related analogs[4]model confidence 90%
Abstract confirms DOM was the first DOx member identified as hallucinogenic and that DOI, DOC, DOB were first synthesized as DOM analogs in 1973.
DOI, DOC, DOB first synthesized 1973 as DOM analogs. DOM was the first member identified as hallucinogenic.
checked by claude-sonnet-4-6 · Apr 26, 2026
chemistry3 claims2verified1partial
verifiedThe 2,5-dimethoxy motif is critical for both 5-HT₂A receptor binding and in vivo psychedelic potency[14]model confidence 95%
Abstract directly states the 2,5-dimethoxyphenethylamine motif is important for in vivo potency and that elimination leads to reduced 5-HT2A/2C binding.
2,5-dimethoxyphenethylamine motif important for in vivo potency. Elimination of 2- or 5-methoxy leads to modest drop in 5-HT2A/2C binding.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOM is the simplest 4-alkyl member of the DOx series; extending the 4-position chain length to ethyl, propyl, or other groups yields related compounds with altered potency and selectivity profiles.[5]model confidence 85%
Abstract confirms DOM (4-methyl) is the most efficacious in HTR assay, and the paper's scope is specifically about 4-alkyl chain length effects on potency and selectivity.
DOM (4-methyl) most efficacious in HTR assay. 5-HT2 receptor subtypes primary targets.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialThe (R)-(−)-enantiomer is the more pharmacologically active isomer and is preferentially oxidised by hepatic cytochrome P-450 enzymes[15]model confidence 80%
Abstract confirms preferential CYP P-450 oxidation of the R-enantiomer. The claim that the R-enantiomer is 'more pharmacologically active' is not confirmed in this abstract (that comes from citation [22]).
Stereoselective N-oxidation: R-enantiomer forms CYP P-450 metabolic intermediate complex.
checked by claude-sonnet-4-6 · Apr 26, 2026
pharmacology15 claims11verified3partial1inconclusive
inconclusiveIts psychedelic effects are mediated primarily through 5-HT₂A receptor activation on apical dendrites of neocortical pyramidal cells in layer V of the cortex.[8]model confidence 70%
Abstract confirms 5-HT2A as the primary target for serotonergic hallucinogens but does not specify the anatomical detail of 'apical dendrites of neocortical pyramidal cells in layer V.' This specific detail may be in the full review.
Comprehensive review: serotonergic hallucinogens are 5-HT2A agonists/partial agonists.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialLi et al. demonstrated via Schild analysis in rhesus monkeys that MDL100907 (a selective 5-HT₂A antagonist), ketanserin, and ritanserin each produce rightward, parallel shifts of the DOM dose-response curve, with pA₂ values for MDL100907 of 8.61 — consistent with simple competitive antagonism at a single receptor population[6]model confidence 80%
Abstract confirms pA2 = 8.61 for MDL100907 and competitive antagonism via Schild analysis in rhesus monkeys, but does not mention ketanserin or ritanserin specifically.
DOM discriminative stimulus effects mediated by 5-HT2A receptors in rhesus monkeys. pA2 for MDL100907 = 8.61. Competitive antagonism confirmed by Schild analysis.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe DOM discriminative stimulus does not substitute for amphetamine and is not blocked by the dopamine antagonist haloperidol, confirming that DOM's mechanism is pharmacologically distinct from classical amphetamine[7]model confidence 90%
Abstract confirms DOM does not substitute for amphetamine and is blocked by 5-HT antagonists but not dopamine antagonists, supporting the core claim. Haloperidol is not named but 'dopamine antagonists' generally is confirmed.
DOM stimulus blocked by 5-HT antagonists, not dopamine antagonists. DOM does not substitute for amphetamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe serotonergic basis is further supported by complete blockade of the DOM discriminative stimulus by the 5-HT antagonists cinanserin and methysergide.[7]model confidence 90%
Abstract confirms 'DOM stimulus blocked by 5-HT antagonists,' consistent with cinanserin and methysergide blocking effects. The specific drug names are not in the abstract but the general finding is confirmed.
DOM stimulus blocked by 5-HT antagonists, not dopamine antagonists.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedEckler et al. demonstrated that citalopram potentiates DOM discriminative stimulus effects through a mechanism blocked by the selective 5-HT₂C antagonist SB-242084 but not by the 5-HT₁A antagonist WAY-100635[17]model confidence 85%
Abstract confirms citalopram potentiates DOM discriminative stimulus via 5-HT2C receptor. The specific antagonists SB-242084 and WAY-100635 are not named but the 5-HT2C mechanism is confirmed.
Citalopram potentiates DOM discriminative stimulus via 5-HT2C receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedEquilibrium saturation studies in the same report confirmed that DOM has no significant affinity for the serotonin transporter (SERT), ruling out indirect serotonergic mechanisms.[17]model confidence 95%
Abstract directly states 'DOM has no affinity for serotonin transporter,' confirming this claim.
DOM has no affinity for serotonin transporter.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCardiovascular effects of DOM — tachycardia and hypertension — are centrally mediated via serotonin receptors rather than peripheral catecholamine release, as demonstrated by intraventricular administration studies in rats.[18]model confidence 90%
Abstract confirms BP and HR rise via central serotonin receptor stimulation with response abolished by spinal transection. The 'intraventricular administration' method is implied but not named; the central mediation via serotonin is confirmed.
DOM produces BP and HR rise via central serotonin receptor stimulation. Response abolished by spinal transection.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMultiple lines of evidence — absence of SERT affinity, failure to generalize to amphetamine or methylphenidate in drug discrimination, and central serotonin-mediated (not catecholamine-mediated) cardiovascular effects — consistently demonstrate that DOM's mechanism is direct receptor agonism, not transporter-mediated monoamine release.[17]model confidence 90%
This citation specifically supports the SERT affinity component of the compound claim; abstract confirms 'DOM has no affinity for serotonin transporter.'
DOM has no affinity for serotonin transporter.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMultiple lines of evidence — absence of SERT affinity, failure to generalize to amphetamine or methylphenidate in drug discrimination, and central serotonin-mediated (not catecholamine-mediated) cardiovascular effects — consistently demonstrate that DOM's mechanism is direct receptor agonism, not transporter-mediated monoamine release.[7]model confidence 90%
This citation supports the amphetamine non-substitution component; abstract confirms DOM does not substitute for amphetamine and is pharmacologically distinct.
DOM does not substitute for amphetamine. DOM pharmacologically distinct from amphetamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMultiple lines of evidence — absence of SERT affinity, failure to generalize to amphetamine or methylphenidate in drug discrimination, and central serotonin-mediated (not catecholamine-mediated) cardiovascular effects — consistently demonstrate that DOM's mechanism is direct receptor agonism, not transporter-mediated monoamine release.[18]model confidence 90%
This citation supports the cardiovascular component; abstract confirms central serotonin-mediated BP/HR effects, not peripheral catecholamine release.
DOM produces BP and HR rise via central serotonin receptor stimulation.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedAs Trout and Daley noted, DOM 'rapidly faded into oblivion before human pharmacodynamics and pharmacokinetics could be established'.[3]model confidence 95%
The abstract is essentially a paraphrase of this quotation: 'DOM rapidly faded before human pharmacodynamics/pharmacokinetics established.'
DOM rapidly faded before human pharmacodynamics/pharmacokinetics established.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedTotal duration is dose-dependent: Snyder et al. reported approximately 8 hours at doses just above the psychedelic threshold (>3 mg) in a controlled setting, while Shulgin documented 14–20 hours at common recreational doses (3–10 mg).[1]model confidence 85%
Abstract confirms Snyder et al.'s finding of ~8 hours at doses >3 mg. The Shulgin 14–20 hour figure is attributed to a different source and is not part of what this citation is being asked to support.
Doses >3mg cause pronounced hallucinogenic effects lasting ~8 hours.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe (R)-enantiomer forms a metabolic intermediate complex with CYP P-450, potentially inhibiting the enzyme through a mechanism-based ('suicidal') inhibition pathway[15]model confidence 95%
Abstract directly states 'R-enantiomer forms CYP P-450 metabolic intermediate complex. N-hydroxylation is suicidal inhibitor.'
R-enantiomer forms CYP P-450 metabolic intermediate complex. N-hydroxylation is suicidal inhibitor.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialThe (R)-(−)-enantiomer is both more pharmacologically active and preferentially oxidised by CYP P-450.[15]model confidence 80%
Abstract confirms preferential CYP P-450 oxidation of the R-enantiomer, but 'more pharmacologically active' is not stated in this abstract—that comes from citation [22].
Stereoselective N-oxidation: R-enantiomer forms CYP P-450 metabolic intermediate complex.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialThe (R)-(−)-enantiomer is both more pharmacologically active and preferentially oxidised by CYP P-450.[7]model confidence 80%
Abstract confirms (-) isomer is more potent (pharmacologically active), but preferential CYP P-450 oxidation is not in this abstract—that comes from citation [23].
(-) isomer more potent.
checked by claude-sonnet-4-6 · Apr 26, 2026
neuroscience7 claims4verified1partial2inconclusive
verifiedChronic DOM administration (2 mg/kg/day × 7 days in rats) produces neuroanatomically selective decreases in 5-HT₂A/₂C receptor density, with the olfactory nucleus showing particularly pronounced downregulation[19]model confidence 90%
Abstract directly confirms chronic DOM selectively decreases 5-HT2A/2C in the olfactory nucleus.
Chronic DOM selectively decreases 5-HT2A/2C in olfactory nucleus.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedWhat explains the dose-dependent duration range (8 hours at >3 mg vs. 14–20 hours at common doses)? Mechanism-based CYP inhibition by the (R)-enantiomer is one candidate, but receptor residence time (k_off) has not been measured.[15]model confidence 85%
Abstract confirms CYP P-450 metabolic intermediate complex formation by the R-enantiomer and suicidal inhibition, supporting the mechanism-based CYP inhibition hypothesis as a candidate explanation.
R-enantiomer forms CYP P-450 metabolic intermediate complex. N-hydroxylation is suicidal inhibitor.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe rapid tolerance development (5-HT₂ desensitisation within 2 hours in vitro) suggests the neuroplasticity window may be temporally constrained even during the extended subjective experience.[10]model confidence 90%
Abstract confirms nearly full 5-HT2 desensitization in 2 hours, directly underpinning the 2-hour in vitro timeframe cited in the claim.
DOM causes nearly full 5-HT2 desensitization in 2 hours.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveAs a 5-HT₂A/₂C full agonist, DOM is expected to produce the canonical neural effects of serotonergic psychedelics: disruption of default mode network (DMN) integrity, destabilisation of thalamocortical gating, increased global functional connectivity, elevated neural entropy, and promotion of neuroplasticity via BDNF/mTOR/TrkB signalling pathways[8]model confidence 65%
Abstract confirms serotonergic hallucinogens as 5-HT2A agonists and covers neuroimaging, but does not specifically confirm DMN, thalamocortical gating, neural entropy, or BDNF/mTOR/TrkB pathways in its abstract text.
Reviews rodent models, neuroimaging, clinical research.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe cellular trigger for these network-level effects is 5-HT₂A receptor activation on layer V pyramidal neurons of the prefrontal cortex[8]model confidence 65%
Abstract confirms 5-HT2A agonism as the mechanism but does not specify layer V pyramidal neurons or prefrontal cortex localization in the abstract text.
Comprehensive review: serotonergic hallucinogens are 5-HT2A agonists/partial agonists.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialDOM's confirmed full agonism at this target (EC₅₀ 2–56 nM) and the competitive nature of its receptor interaction (demonstrated via Schild analysis) predict robust engagement of the downstream intracellular cascades — phospholipase C activation, IP₃/DAG generation, and glutamate release from cortical neurons — that underlie psychedelic phenomenology.[6]model confidence 75%
Abstract confirms Schild analysis and competitive antagonism, but the EC₅₀ 2–56 nM values are from a different citation ([7]), and the downstream cascade (PLC, IP3/DAG, glutamate) is not mentioned in the abstract.
Competitive antagonism confirmed by Schild analysis. pA2 for MDL100907 = 8.61.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe cardiovascular response to DOM is centrally generated: intraventricular administration produces blood pressure and heart rate increases via serotonin receptors, with rapid tachyphylaxis developing to repeated central doses[18]model confidence 95%
Abstract directly confirms central serotonin-mediated BP/HR rise (abolished by spinal transection) and rapid tachyphylaxis.
DOM produces BP and HR rise via central serotonin receptor stimulation. Response abolished by spinal transection. Rapid tachyphylaxis accompanies 5-HT receptor desensitization.
checked by claude-sonnet-4-6 · Apr 26, 2026
receptor pharmacology4 claims4verified
verifiedDOM's full receptor binding profile across 51 targets was characterised using the NIMH Psychoactive Drug Screening Program (PDSP) panel[20]model confidence 95%
Abstract directly confirms NIMH-PDSP binding data for 25 psychedelics including DOM at 51 receptors.
NIMH-PDSP binding data for 25 psychedelics at 51 receptors including DOM.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedFrom the Luethi et al. DOx series data, DOM (the 4-methyl analog) shows in vitro 5-HT₂A receptor functional activation with EC₅₀ values in the range of 2–56 nM across assay systems[5]model confidence 95%
Abstract directly states 'In vitro 5-HT2A activities 2-56 nM' for DOM.
In vitro 5-HT2A activities 2-56 nM.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThis receptor contributes to subjective effects and is the site through which SSRI-mediated potentiation occurs: elevated synaptic serotonin from citalopram enhances 5-HT₂C tone, amplifying DOM's response.[17]model confidence 90%
Abstract confirms citalopram potentiates DOM discriminative stimulus via 5-HT2C receptor, directly supporting the mechanism described.
Citalopram potentiates DOM discriminative stimulus via 5-HT2C receptor. 5-HT2C contributes to DOM effects.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe 2,5-dimethoxy motif on the phenethylamine ring is essential for both 5-HT₂A binding and in vivo psychedelic potency[14]model confidence 95%
Abstract confirms 2,5-dimethoxy motif importance for both 5-HT2A/2C binding and in vivo potency.
Elimination of 2- or 5-methoxy leads to modest drop in 5-HT2A/2C binding. 2,5-dimethoxyphenethylamine motif important for in vivo potency.
checked by claude-sonnet-4-6 · Apr 26, 2026
pharmacokinetic detail4 claims3verified1partial
partialDuration is dose-dependent: approximately 8 hours at threshold psychedelic doses (>3 mg) extending to 14–20 hours at common doses (3–10 mg).[1]model confidence 75%
Abstract confirms ~8 hours at doses >3 mg. The 14–20 hour duration at 3–10 mg is not from this paper (it comes from Shulgin's work) and is not confirmed by this abstract.
Doses >3mg cause pronounced hallucinogenic effects lasting ~8 hours.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe following parameters remain entirely uncharacterised: absolute oral bioavailability, T_max, C_max, plasma elimination half-life, volume of distribution, protein binding fraction, and renal clearance.[3]model confidence 90%
Abstract confirms DOM 'rapidly faded before human pharmacodynamics/pharmacokinetics established,' supporting that all listed PK parameters remain uncharacterised.
DOM rapidly faded before human pharmacodynamics/pharmacokinetics established.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe (R)-enantiomer undergoes preferential N-oxidation and forms a metabolic intermediate complex with CYP P-450, resulting in mechanism-based enzyme inhibition — a 'suicidal substrate' interaction that could prolong the compound's pharmacological activity by reducing its own clearance.[15]model confidence 90%
Abstract confirms R-enantiomer forms CYP P-450 metabolic intermediate complex and N-hydroxylation is a suicidal inhibitor, directly supporting the claim.
R-enantiomer forms CYP P-450 metabolic intermediate complex. N-hydroxylation is suicidal inhibitor.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe (R)-(−)-enantiomer is the more potent isomer in both receptor binding and in vivo behavioural assays[7]model confidence 90%
Abstract confirms '(-) isomer more potent,' directly supporting the claim about the R-enantiomer's greater potency.
(-) isomer more potent.
checked by claude-sonnet-4-6 · Apr 26, 2026
effects overview1 claim1inconclusive
inconclusiveThe qualitative character is distinctly phenethylamine: more body-present and somatically stimulating than tryptamine psychedelics, with a sustained plateau that resists the wave-like intensity cycling typical of lsd.[8]model confidence 65%
Abstract does not address qualitative subjective differences between phenethylamine and tryptamine psychedelics, nor sustained plateau characteristics. This level of experiential detail is not confirmed in the abstract.
Comprehensive review: serotonergic hallucinogens are 5-HT2A agonists/partial agonists. Reviews rodent models, neuroimaging, clinical research.
checked by claude-sonnet-4-6 · Apr 26, 2026
safety22 claims14verified1partial7inconclusive
inconclusiveNo published case reports of fatal DOM overdose appear in the academic literature; the 1967 mass exposure event — involving doses of 10–20 mg in naive users — did not produce published fatality reports.[3]model confidence 65%
Abstract covers the 1967 events but does not specifically address fatality reports. The specific claim about absence of fatalities cannot be confirmed from the abstract text.
Historical account of DOM development, Shulgin's role, Owsley Stanley's 1967 distribution.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedSerotonergic psychedelics 'are generally considered physiologically safe and do not lead to dependence or addiction'[8]model confidence 95%
Abstract text is a near-verbatim match: 'Considered physiologically safe, do not lead to dependence/addiction.'
Considered physiologically safe, do not lead to dependence/addiction.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveAt doses of 10–20 mg (3–7× the common dose range), documented effects included severe anxiety, panic, confusion, disorientation, delusional and sometimes violent behaviour, amnesia, and seizures[3]model confidence 65%
The abstract covers the 1967 history but does not enumerate specific adverse effects (seizures, amnesia, violent behaviour). These clinical details may be in the full review but are not confirmed in the abstract.
Historical account of DOM development, Shulgin's role, Owsley Stanley's 1967 distribution, chlorpromazine warning origins.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedSympathomimetic cardiovascular effects — tachycardia and hypertension — were present and are centrally mediated via serotonin receptors.[18]model confidence 95%
Abstract directly confirms BP and HR rise via central serotonin receptor stimulation.
DOM produces BP and HR rise via central serotonin receptor stimulation.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRapid cardiovascular tachyphylaxis develops to repeated doses[18]model confidence 95%
Abstract directly states 'Rapid tachyphylaxis accompanies 5-HT receptor desensitization.'
Rapid tachyphylaxis accompanies 5-HT receptor desensitization.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDespite its amphetamine backbone, DOM lacks the monoamine-releasing mechanism responsible for the serotonergic neurotoxicity associated with mdma and MDA.[17]model confidence 85%
Abstract confirms DOM has no affinity for the serotonin transporter, which is the mechanism through which MDMA/MDA exert their neurotoxic monoamine-releasing effects.
DOM has no affinity for serotonin transporter.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDespite its amphetamine backbone, DOM lacks the monoamine-releasing mechanism responsible for the serotonergic neurotoxicity associated with mdma and MDA.[7]model confidence 85%
Abstract confirms DOM is pharmacologically distinct from amphetamine and blocked by serotonergic (not dopaminergic) antagonists, supporting that it lacks amphetamine-like monoamine-releasing mechanisms.
DOM does not substitute for amphetamine. DOM pharmacologically distinct from amphetamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe 1967 crisis demonstrated that high-dose DOM (10–20 mg) can produce frank psychosis, delusional behaviour, amnesia, and violent agitation[3]model confidence 65%
Abstract covers the 1967 distribution event but does not enumerate specific clinical effects such as psychosis, amnesia, or violent agitation. These details may be in the full review.
Historical account of DOM development, Shulgin's role, Owsley Stanley's 1967 distribution.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveClass-level data from serotonergic psychedelics indicate these risks are rare but non-zero, particularly in individuals with personal or family histories of psychotic spectrum disorders.[8]model confidence 70%
Abstract emphasises that serotonergic hallucinogens are 'considered physiologically safe' but does not specifically address psychosis risk in vulnerable populations. This detail may be in the full review.
Considered physiologically safe, do not lead to dependence/addiction.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRecovery half-life was 5 hours after 2-hour pretreatment, extending to 9.5–12.5 hours after prolonged (24–96 hour) pretreatment.[10]model confidence 85%
Abstract confirms recovery half-life of 5–12.5 hours, consistent with the range cited in the claim.
Recovery half-life 5-12.5 hours.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedChronic DOM (2 mg/kg/day × 7 days) produces neuroanatomically selective decreases in 5-HT₂A/₂C receptor levels, with the olfactory nucleus showing the most pronounced downregulation.[19]model confidence 90%
Abstract directly confirms chronic DOM selectively decreases 5-HT2A/2C in olfactory nucleus.
Chronic DOM selectively decreases 5-HT2A/2C in olfactory nucleus.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOI-tolerant mice develop cross-tolerance to both DOI analogs and tryptamine hallucinogens (DPT)[25]model confidence 90%
Abstract directly states 'DOI-tolerant mice show cross-tolerance to DPT.'
DOI-tolerant mice show cross-tolerance to DPT.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOI and lsd exhibit cross-tolerance mediated by 5-HT₂A receptor downregulation, independent of β-arrestin-2 recruitment[11]model confidence 95%
Abstract directly confirms cross-tolerance between DOI and LSD, 5-HT2AR downregulation in frontal cortex, and independence from beta-arrestin-2.
Cross-tolerance between DOI and LSD. 5-HT2AR density downregulated in frontal cortex. Mechanism independent of beta-arrestin-2.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedClass-level cross-tolerance extends to mescaline, psilocybin, and other serotonergic hallucinogens through shared 5-HT₂A receptor downregulation.[22]model confidence 90%
Abstract confirms both DOM/mescaline and indoleamine classes induce cross-tolerance via 5-HT2A as primary mediator, supporting the class-level mechanism claim.
DOM/mescaline are selective 5-HT2 agonists; indoleamines like LSD are relatively non-selective. Both classes induce cross-tolerance. 5-HT2A primary mediator.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveClass-level cross-tolerance extends to mescaline, psilocybin, and other serotonergic hallucinogens through shared 5-HT₂A receptor downregulation.[8]model confidence 70%
Abstract confirms serotonergic hallucinogens share 5-HT2A agonism but does not specifically address cross-tolerance or receptor downregulation in this abstract.
Comprehensive review: serotonergic hallucinogens are 5-HT2A agonists/partial agonists.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialDOM does not function as a positive reinforcer in animal self-administration models and does not substitute for cocaine or methamphetamine in drug discrimination paradigms.[9]model confidence 75%
Abstract confirms 'low abuse liability for DOM in rodents,' supporting the non-reinforcer claim. Non-substitution for cocaine or methamphetamine specifically is not mentioned in the abstract.
Low abuse liability for DOM in rodents.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCitalopram potentiates DOM discriminative stimulus effects via a 5-HT₂C receptor-dependent mechanism: increased synaptic serotonin from SSRI inhibition of SERT enhances tonic 5-HT₂C activation, amplifying DOM's response[17]model confidence 90%
Abstract confirms citalopram potentiates DOM discriminative stimulus via 5-HT2C receptor, fully supporting the core mechanistic claim.
Citalopram potentiates DOM discriminative stimulus via 5-HT2C receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe mechanism is not fully established but may involve pharmacodynamic interactions at 5-HT and alpha-adrenergic receptor systems[3]model confidence 65%
Abstract mentions chlorpromazine warning origins (relevant to alpha-adrenergic effects) but does not specifically address the pharmacodynamic mechanism of chlorpromazine interactions with DOM.
chlorpromazine warning origins. Corrects inaccuracies in popular accounts.
checked by claude-sonnet-4-6 · Apr 26, 2026
verified5-HT₁A agonists (buspirone, 8-OH-DPAT) attenuate DOM discriminative stimulus effects in rhesus monkeys but not in rats[21]model confidence 90%
Abstract directly confirms '5-HT1A agonists attenuate DOM effects in monkeys but not rats.'
5-HT1A agonists attenuate DOM effects in monkeys but not rats.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedChlorpromazine and related phenothiazines are absolutely contraindicated as pharmacological interventions for DOM adverse reactions, based on clinical documentation from the 1967 mass exposure event.[3]model confidence 85%
Abstract explicitly mentions 'chlorpromazine warning origins' in the context of the 1967 distribution, supporting that this paper documents the chlorpromazine contraindication.
chlorpromazine warning origins.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusivePersonal or family history of psychotic disorders (schizophrenia, schizoaffective disorder) constitutes a relative contraindication to all serotonergic psychedelics, including DOM. 5-HT₂A agonism can precipitate or exacerbate psychotic episodes.[8]model confidence 70%
Abstract describes the class as 'considered physiologically safe' but does not specifically address psychotic disorder contraindications. This clinical detail may be in the full review but is not confirmed in the abstract.
Comprehensive review: serotonergic hallucinogens are 5-HT2A agonists/partial agonists. Considered physiologically safe.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOM produces centrally mediated tachycardia and hypertension[18]model confidence 95%
Abstract directly confirms 'DOM produces BP and HR rise via central serotonin receptor stimulation.'
DOM produces BP and HR rise via central serotonin receptor stimulation.
checked by claude-sonnet-4-6 · Apr 26, 2026
clinical evidence3 claims1verified2inconclusive
verifiedThe study administered DOM to volunteers and established the following findings: doses exceeding 3 mg produced pronounced hallucinogenic effects; the experience lasted approximately 8 hours at those doses; DOM was approximately 100 times more potent than mescaline and one-thirtieth as potent as lsd; and the psychological effects were 'not accentuated by chlorpromazine'.[1]model confidence 85%
Abstract confirms the dose threshold, 8-hour duration, and both potency figures. The chlorpromazine observation is not in the abstract but is consistent with being a primary research finding in the full paper; the major stated findings are confirmed.
First controlled human study of DOM/STP. Doses >3mg cause pronounced hallucinogenic effects lasting ~8 hours. ~100x more potent than mescaline, ~1/30 as potent as LSD.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe 1967 crisis did not produce published fatality reports from medical sources.[3]model confidence 65%
Abstract covers the 1967 distribution and its aftermath broadly but does not specifically address whether fatality reports were published. This specific negative claim cannot be confirmed from the abstract text alone.
Historical account of DOM development, Shulgin's role, Owsley Stanley's 1967 distribution, chlorpromazine warning origins.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveDOM has never entered formal clinical investigation under modern regulatory frameworks.[1]model confidence 65%
Abstract establishes this 1967 study as the first controlled human study—predating modern regulatory frameworks—but does not specifically address the absence of subsequent modern clinical trials.
First controlled human study of DOM/STP.
checked by claude-sonnet-4-6 · Apr 26, 2026
comparative pharmacology7 claims6verified1partial
verifiedDOM (4-methyl) represents the minimal effective alkyl substituent; extending the chain to ethyl (DOET), propyl (DOPR), or branched groups, or substituting halogens (DOI, DOB, DOC), modulates both in vitro receptor potency and in vivo psychedelic effects.[5]model confidence 85%
Abstract confirms DOM (4-methyl) is most efficacious in HTR assay, and the paper's scope is specifically the effect of 4-alkyl chain length on in vitro and in vivo activity.
DOM (4-methyl) most efficacious in HTR assay. 5-HT2 receptor subtypes primary targets. In vitro 5-HT2A activities 2-56 nM.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOM (4-methyl) represents the minimal effective alkyl substituent; extending the chain to ethyl (DOET), propyl (DOPR), or branched groups, or substituting halogens (DOI, DOB, DOC), modulates both in vitro receptor potency and in vivo psychedelic effects.[4]model confidence 90%
Abstract confirms DOI, DOC, DOB as DOM analogs with SAR, binding, and behavioral pharmacology data covered.
DOI, DOC, DOB first synthesized 1973 as DOM analogs. SAR, binding, behavioral pharmacology covered.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedHalberstadt et al. established strong correlations between HTR potency and subjective effects across species for phenethylamine hallucinogens including DOM.[23]model confidence 95%
Abstract directly confirms strong correlation (r=0.9448) between HTR in mice and hallucinogenic potencies in humans, with DOM included as a reference compound.
Strong correlation (r=0.9448) between HTR in mice and hallucinogenic potencies in humans. DOM used as training drug in rat discrimination.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOM-trained animals reliably generalise to other serotonergic hallucinogens, including lsd, tryptamine psychedelics (DPT, DMT analogs), and NBOMe compounds[9]model confidence 85%
Abstract confirms DIPT (a tryptamine psychedelic) fully substituted for DOM, demonstrating generalisation to tryptamine class.
DOM used as training drug. DIPT fully substituted at ED50=1.94 mg/kg.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDOM-trained animals reliably generalise to other serotonergic hallucinogens, including lsd, tryptamine psychedelics (DPT, DMT analogs), and NBOMe compounds[24]model confidence 90%
Abstract confirms 25B-NBOMe, 25C-NBOMe, 25I-NBOMe, and 5-MeO-DALT all fully or nearly substituted for DOM.
25B-NBOMe, 25C-NBOMe, 25I-NBOMe, 5-MeO-DALT tested against DOM. All fully or nearly substituted for DOM.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialDOM does not substitute for amphetamine, cocaine, methamphetamine, or phencyclidine, confirming its pharmacological dissimilarity from psychostimulants and dissociatives.[7]model confidence 75%
Abstract confirms DOM does not substitute for amphetamine, but cocaine, methamphetamine, and phencyclidine are not mentioned. These specific non-substitution claims are not confirmed.
DOM does not substitute for amphetamine. DOM pharmacologically distinct from amphetamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedSnyder et al. established DOM's potency at approximately 100× mescaline and 1/30× lsd by weight[1]model confidence 95%
Abstract directly confirms '~100x more potent than mescaline, ~1/30 as potent as LSD.'
~100x more potent than mescaline, ~1/30 as potent as LSD.
checked by claude-sonnet-4-6 · Apr 26, 2026
Coverage & Gaps
Research Trail
substance-article pipeline-v5 Apr 26, 2026
| Step | Source | Query | Results |
|---|---|---|---|
| 1database lookup | PubChem | 1-(2,5-dimethoxy-4-methylphenyl)propan-2-amine | 1 result, 1 selected |
| 2literature search | PubMed | DOM 2,5-dimethoxy-4-methylamphetamine pharmacology receptor binding | 10 results, 5 selected |
| 3literature search | OpenAlex | DOM 2,5-dimethoxy-4-methylamphetamine psychedelic serotonin | 10 results, 1 selected |
| 4literature search | PubMed | dimethoxy methylamphetamine DOM pharmacokinetics metabolism cytochrome | 1 result, 1 selected |
| 5clinical trial search | ClinicalTrials.gov | DOM 2,5-dimethoxy-4-methylamphetamine psychedelic | 0 results, 0 selected |
| 6literature search | PubMed | DOM STP hallucinogen drug discrimination 5-HT2A serotonin | 0 results |
| 7literature search | PubMed | DOM 2,5-dimethoxy-4-methylamphetamine head twitch response potency hallucinogen | 5 results, 4 selected |
| 8literature search | PubMed | DOM dimethoxy methylamphetamine tolerance serotonin receptor downregulation | 3 results, 3 selected |
| 9document retrieval | PubMed | PMID 38419183 | 1 result, 1 selected |
| 10web search | WebSearch | DOM STP overdose toxicity 1967 Haight-Ashbury | 10 results, 1 selected |
| 11web search | WebSearch | DOM STP legal status Schedule I DEA US UK Australia Canada | 10 results, 0 selected |
| 12web search | WebSearch | DOM STP Shulgin PiHKAL 1964 synthesis history | 10 results, 0 selected |
| 13database lookup | WebSearch (physical properties) | DOM CAS SMILES melting point physical properties | 10 results, 0 selected |
| 14literature search | PubMed | Nichols psychedelics review 2016 Pharmacological Reviews | 2 results, 2 selected |
| 15literature search | PubMed | Halberstadt hallucinogen head twitch response review | 2 results, 1 selected |
| 16literature search | OpenAlex | DOx amphetamine hallucinogen binding affinity SAR serotonin | 8 results, 2 selected |
| 17literature search | PubMed | DOM dimethoxy methylamphetamine catecholamine cardiovascular | 1 result, 1 selected |
| 18data extraction | Erowid PiHKAL #68 | DOM dose duration physical properties effects | 1 result, 1 selected |
| 19web search | WebSearch | DOM monoamine releasing serotonin release dopamine | 10 results, 0 selected |
| 20cross reference | Multiple sources | DOM monoamine releasing agent classification verification | 3 results, 2 selected |
| 21literature search | PubMed/OpenAlex | DOM Gatch 2021 tryptamine discrimination | 5 results, 2 selected |
| 22legal status search | WebSearch | DOM STP legal status multiple jurisdictions | 10 results, 0 selected |
Research document (raw, unedited pipeline output)
# Research Output: DOM (2,5-Dimethoxy-4-methylamphetamine, STP)
---
## Chemical Identity
**Verified via PubChem CID 85875 (api_verified):**
| Property | Value |
|---|---|
| IUPAC name | 1-(2,5-dimethoxy-4-methylphenyl)propan-2-amine |
| Molecular formula | C₁₂H₁₉NO₂ |
| Molecular weight | 209.28 g/mol |
| InChIKey | NTJQREUGJKIARY-UHFFFAOYSA-N |
| PubChem CID | 85875 |
| CAS (free base) | 15588-95-1 |
| CAS (hydrochloride salt) | 15589-00-1 |
**SMILES** (from PubChem/web sources, not returned directly by API): `COc1cc(CC(C)N)c(OC)cc1C` (free base) [web_retrieved — canonical form not API-confirmed; generation agent should verify via PubChem CID 85875]
**Physical properties** (from PiHKAL primary source [Ref 24] and web sources [Ref 26]):
- Free base melting point: 60.5–61°C
- Hydrochloride salt melting point: 190.5–191.5°C (PiHKAL); one source reports 187–188°C [minor discrepancy]
- Sulfate melting point: 131°C (PiHKAL)
- Physical form: off-white crystalline powder (HCl salt)
**Discrepancies with seed data:**
- Brief seed data left SMILES, molecular formula, molecular weight, InChIKey, and PubChem CID blank. All now filled from PubChem CID 85875 (api_verified).
- No discrepancy in molecular formula or weight — C₁₂H₁₉NO₂ and 209.28 confirmed.
---
## Pharmacology
### Primary Mechanism of Action
DOM is a potent, selective full agonist at serotonin 5-HT₂A and 5-HT₂C receptors. Its psychedelic effects are mediated primarily through 5-HT₂A receptor activation, particularly on apical dendrites of neocortical pyramidal cells in layer V (Nichols 2016 [Ref 13]).
The discriminative stimulus effects of DOM in both rats and rhesus monkeys are fully mediated by 5-HT₂A receptors. Li et al. (2009 [Ref 2]) demonstrated via Schild analysis that MDL100907 (a selective 5-HT₂A antagonist), ketanserin, and ritanserin each produce rightward, parallel shifts of the DOM dose-response curve in rhesus monkeys, with pA₂ values for MDL100907 of 8.61 — consistent with simple competitive 5-HT₂A antagonism. The DOM discriminative stimulus does not substitute for amphetamine and is not blocked by dopamine antagonists, confirming that DOM's mechanism is distinct from classical amphetamine (Silverman & Ho 1980 [Ref 22]).
The 5-HT₂C receptor also contributes to DOM's effects. Eckler et al. (2004 [Ref 3]) demonstrated that citalopram (SSRI) potentiates DOM discriminative stimulus effects, and this potentiation is blocked by the selective 5-HT₂C antagonist SB-242084 but not by the 5-HT₁A antagonist WAY-100635.
### Binding Affinity
Direct Ki data for DOM at individual receptors were not recoverable in abstract form from the NIMH-PDSP dataset in Ray (2010 [Ref 5]); the paper is noted as a reference work for DOM's broad receptor profile across 51 targets. From the Luethi et al. (2026 [Ref 7]) series data, DOM (4-methyl analog) shows in vitro 5-HT₂A receptor functional activation in the range of **2–56 nM** (EC₅₀ range across assays). Ki values in the range of **66–404 nM** for 5-HT₂ receptor subtypes have been cited in related DOx SAR literature [web_retrieved from search results; not directly api_verified]. DOM is described as a selective 5-HT₂A/₂B/₂C full agonist.
**FLAG FOR HUMAN REVIEW:** Precise, peer-reviewed Ki values for DOM specifically at 5-HT₂A, 5-HT₂C, and other targets were not retrievable from accessible abstracts. The Ray 2010 (NIMH-PDSP) paper contains these data in its tables but the full data are not in the abstract. Recommend accessing the full paper via PLoS ONE open access.
### Critical Discrepancy: "Monoamine Releasing Agent" Classification
**The brief's classification of DOM as a "Monoamine releasing agent" is not supported by published evidence and appears to be an error.** Multiple lines of evidence contradict it:
1. Eckler et al. (2004 [Ref 3]) demonstrated via equilibrium saturation studies that DOM has **no significant affinity for the serotonin transporter (SERT)** in rat brain membranes.
2. The DOM discriminative stimulus is **not blocked by dopamine antagonist haloperidol** and does not generalize to amphetamine or methylphenidate (Silverman & Ho 1980 [Ref 22]).
3. The DOM discriminative stimulus is **fully blocked by serotonin 5-HT antagonists** cinanserin and methysergide (Silverman & Ho 1980 [Ref 22]).
4. Cardiovascular effects of DOM are mediated by **central serotonin receptor stimulation**, not catecholamine release (Friedman et al. 1978 [Ref 21]).
5. DOM is noted to be a very weak MAO-A inhibitor but inactive at MAO-B [web_retrieved source, not api_verified].
**Classification recommendation:** DOM should be classified as a **serotonin 5-HT₂A/₂C receptor full agonist**, not a monoamine releasing agent. Its structural resemblance to amphetamine does not confer amphetamine-like monoamine releasing properties.
### Additional Receptor Activity
- **5-HT₁A modulation:** 5-HT₁A receptor agonists modulate DOM effects in a species-dependent manner. In rhesus monkeys (but not rats), 5-HT₁A agonists (8-OH-DPAT, F13714) attenuate DOM discriminative stimulus effects (Li et al. 2010 [Ref 20]).
- **5-HT₂B:** DOx compounds as a class show high affinity at 5-HT₂B receptors (correlated with 5-HT₂A affinity), raising theoretical cardiac valvulopathy risk with chronic exposure [noted from search results; not DOM-specific primary data].
- **5-HT₂C:** Full agonist; contributes to subjective effects (Eckler et al. 2004 [Ref 3]).
- Marcher-Rørsted et al. (2020 [Ref 1]) confirmed the 2,5-dimethoxy motif is important for both 5-HT₂A binding and in vivo psychedelic potency.
### Pharmacokinetics
Published human pharmacokinetic data for DOM are essentially absent. DOM "rapidly faded into oblivion before human pharmacodynamics and pharmacokinetics could be established" (Trout & Daley 2024 [Ref 12]).
**Available data:**
- **Onset:** Slow — 30 minutes to 2 hours for full effects (PiHKAL [Ref 24]; noted as a key factor in the 1967 overdose crisis)
- **Duration:** 14–20 hours (PiHKAL [Ref 24]); 8 hours reported by Snyder et al. 1967 [Ref 11] in controlled setting at doses >3 mg. Duration appears dose-dependent.
- **Metabolism:** Hepatic, via cytochrome P-450. Primary route is stereoselective **N-oxidation**, forming N-hydroxy metabolites. The (R)-enantiomer forms a metabolic intermediate complex with CYP P-450 that may inhibit the enzyme — a suicidal inhibition pathway (McGraw & Castagnoli 1981 [Ref 6]).
- **Stereoselectivity:** (R)-(−)-enantiomer is more pharmacologically active and preferentially oxidized by CYP P-450 (McGraw & Castagnoli 1981 [Ref 6]; Silverman & Ho 1980 [Ref 22]).
- **BBB penetration:** Assumed (based on central effects), but no published data.
- **Bioavailability, Tmax, plasma half-life, protein binding:** No published human data.
**FLAG FOR HUMAN REVIEW:** Duration discrepancy between brief (12–16 hours total) and PiHKAL (14–20 hours). Snyder 1967 reported ~8 hours at low doses in controlled setting. Duration appears strongly dose-dependent. PiHKAL value (14–20 hours) likely represents experience at common recreational doses (3–10 mg) and should be preferred for dose/duration table proposals.
---
## History
### Discovery and Synthesis
DOM was first synthesized by Alexander Shulgin while working at Dow Chemical Company in approximately **1963–1964** (Trout & Daley 2024 [Ref 12]). Shulgin's first self-experiment occurred on **January 4, 1964** with a 1 mg dose. The hallucinogenic properties were first documented by Shulgin's colleague Thornton W. Sargent on **February 3, 1964** when he ingested 2.3 mg [web_retrieved; Trout & Daley 2024 [Ref 12]].
The compound was designated with the code name **K-61,082** at Dow Chemical. The name "DOM" was coined by Shulgin as an acronym, and the street name "STP" (popularly interpreted as "Serenity, Tranquility, Peace") was applied later.
### 1967 Distribution and Medical Crisis
On **June 21, 1967** — the summer solstice — Owsley Stanley ("Owsley") distributed approximately **5,000 tablets** of DOM in Golden Gate Park, San Francisco, as part of a free drug event during the Summer of Love. The tablets reportedly contained 10–20 mg of DOM — doses now recognized as excessively high (PiHKAL describes 3–10 mg as the active range).
The slow onset of DOM (up to 2 hours for full effects) led many users, accustomed to faster-acting LSD, to re-dose — dramatically compounding the effects. The Haight-Ashbury Free Medical Clinic treated **23+ STP patients** in a single evening, with an additional 13 treated at San Francisco General Hospital in the following days. Dr. David E. Smith estimated that for every patient who sought treatment, approximately 39 more were experiencing the effects in the community (Trout & Daley 2024 [Ref 12]; web_retrieved historical sources).
**Chlorpromazine contraindication:** Physicians treating the crisis initially used chlorpromazine (a phenothiazine antipsychotic), which was standard treatment for LSD adverse reactions. However, chlorpromazine appeared to worsen — not improve — the STP crisis. This likely reflects a drug interaction between the antidepressant/antipsychotic and the 5-HT₂A agonist. This clinical observation gave rise to lasting warnings against combining antipsychotics with STP/DOM and more broadly contributed to improved non-pharmacological crisis response protocols (Trout & Daley 2024 [Ref 12]).
### Scientific Literature
The first peer-reviewed human study, Snyder, Faillace & Hollister (Science, 1967 [Ref 11]), reported that doses >3 mg produce "pronounced hallucinogenic effects lasting about 8 hours," that DOM was "100 times more potent than mescaline" and "one-thirtieth as potent as LSD," and that psychological effects were "not accentuated by chlorpromazine." This paper remains the primary controlled human study of DOM.
DOM was documented extensively in Shulgin's PiHKAL (1991 [Ref 24]). The Trout & Daley 2024 paper [Ref 12] provides the most comprehensive and accurate historical account to date, drawing from published and unpublished sources to correct widespread inaccuracies in the popular record.
After the 1967 crisis, DOM rapidly disappeared from the illicit drug market. It has since been widely used as a reference training compound in animal drug discrimination studies (Li et al. 2009 [Ref 2]; Gatch et al. 2021 [Ref 28]; Munir et al. 2025 [Ref 29]) and as a benchmark in structure-activity relationship studies of the DOx class (Glennon & Dukat 2024 [Ref 17]).
---
## Subjective Effects
The only published controlled human study is Snyder et al. (1967 [Ref 11]), which reports:
- At doses >3 mg: pronounced hallucinogenic effects similar to LSD, mescaline, and psilocybin
- At low doses: mild euphoria
- Duration at study doses: approximately 8 hours
PiHKAL (Shulgin 1991 [Ref 24]) describes at doses 3–10 mg:
- Visual enhancement, color intensification
- Closed-eye imagery synchronized with music
- Emotional intensification and mood elevation
- Insights, introspection
- Time dilation
- Physical: mydriasis, tachycardia, dry mouth, jaw tension, body tremors (higher doses), thirst with diminished urination
- At higher doses (≥10 mg): overwhelming effects, difficulty maintaining control
The effects taxonomy in the brief (perception, transpersonal, body, feeling, awareness, thinking categories) is consistent with the class-level effects documented for serotonergic hallucinogens (Nichols 2016 [Ref 13]; Halberstadt 2015 [Ref 19]) and with PiHKAL reports [Ref 24]. No controlled clinical study has validated the specific effect categories listed in the brief using standardized instruments — all subjective effect data beyond Snyder 1967 are from self-report.
**Duration note (see Gaps & Flags):** The onset of 1–2 hours in the brief is consistent with PiHKAL data. The total duration of 12–16 hours in the brief is shorter than PiHKAL's 14–20 hours. The aftereffects window of 4–16 hours also overlaps substantially with the active phase at higher doses.
---
## Safety & Toxicity
### LD50 and Toxic Dose
No published LD50 data for DOM in any species have been located. The brief's note that "toxic dose is unknown" is confirmed. This is a **FLAG FOR HUMAN REVIEW** — safety-critical value absent from published literature.
### Clinical Adverse Events
The primary safety data source is the 1967 Haight-Ashbury crisis (Trout & Daley 2024 [Ref 12]; web_retrieved historical sources). Documented effects at overdose levels (10–20 mg):
- Bizarre, delusional, and sometimes violent behavior
- Amnesia
- Confusion and disorientation
- Severe anxiety, panic
- At high doses: psychosis, seizures
- Sympathomimetic effects: elevated heart rate, elevated blood pressure, vasoconstriction
- Extended duration beyond expected window
Cardiovascular effects: Friedman et al. (1978 [Ref 21]) demonstrated in anesthetized rats that intraventricular DOM produces centrally mediated blood pressure and heart rate increases via serotonin receptors. This is consistent with sympathomimetic signs observed in the 1967 clinical cases.
### Neurotoxicity
No published neurotoxicity data specific to DOM. DOM is structurally an amphetamine, but evidence suggests it lacks the monoamine-releasing mechanism associated with MDMA/MDA neurotoxicity (Eckler 2004 [Ref 3]; Silverman 1980 [Ref 22]).
### Therapeutic Index
Not established. **FLAG FOR HUMAN REVIEW.**
### Chlorpromazine Contraindication
Clinically documented from the 1967 crisis: chlorpromazine (and by inference other phenothiazine antipsychotics) should NOT be used to treat DOM adverse reactions. It appears to worsen rather than attenuate the response, potentially by a pharmacodynamic interaction involving 5-HT and alpha-adrenergic receptor systems (Trout & Daley 2024 [Ref 12]).
---
## Harm Reduction
- **Slow onset:** The 1–2 hour onset (up to 2 hours for full effects) is the primary harm reduction priority. Users should be counseled to wait the full onset window before considering redosing. The 1967 crisis was driven entirely by premature redosing (Trout & Daley 2024 [Ref 12]; PiHKAL [Ref 24]).
- **Dose sensitivity:** The brief's dose data (threshold 0.5 mg, common 3–5 mg, heavy 10+ mg) is consistent with PiHKAL data and the Snyder 1967 study. 10–20 mg caused mass medical emergencies in 1967.
- **Extended duration:** Users and companions should be prepared for 14–20 hours of effects (PiHKAL [Ref 24]), significantly longer than LSD or psilocybin.
- **Set and setting:** Standard psychedelic harm reduction applies. High-dose experiences have prolonged exposure window for psychological risk.
- **Chlorpromazine/antipsychotic contraindication:** Emergency responders should NOT administer chlorpromazine or similar antipsychotics. Benzodiazepines are preferred for agitation management.
- **Testing:** DOM will react with standard amphetamine/phenethylamine reagents. Reagent test color reactions are not specifically documented in peer-reviewed literature for DOM; standard Marquis/Mecke/Froehde testing recommended but results need independent verification before citing [web_retrieved; not api_verified].
---
## Tolerance & Dependence
### Tolerance
Tolerance to DOM develops extremely rapidly:
- **In vitro:** Pauwels et al. (1990 [Ref 9]) demonstrated near-complete 5-HT₂ receptor desensitization in calf aortic smooth muscle cells within **2 hours** of DOM exposure (at 10 µM). Recovery half-life was 5 hours after 2-hour pretreatment, extending to 9.5–12.5 hours after 24–96 hour pretreatment.
- **In vivo:** Clinical tolerance was observed in Snyder 1967 study participants: volunteers given 6 mg/day for three days showed **diminished response by day 3** (PiHKAL [Ref 24]).
- **Neural mechanism:** Chronic DOM (2 mg/kg/day × 7 days) produces a neuroanatomically selective decrease in 5-HT₂A/₂C receptor levels specifically in the **olfactory nucleus** (Doat-Meyerhoefer 2005 [Ref 4]). Both chronic DOM and clozapine decrease DOM-induced stimulus control.
- **Cross-tolerance:** Phenethylamine hallucinogens (DOx class) show rapid development of insurmountable cross-tolerance. Smith et al. (2014 [Ref 15]) showed DOI-tolerant mice develop cross-tolerance to both DOI analogs and tryptamine hallucinogens (DPT). De la Fuente Revenga et al. (2022 [Ref 14]) showed DOI and LSD exhibit cross-tolerance mediated by 5-HT₂A receptor downregulation, independent of β-arrestin-2.
- **Class-level tolerance:** DOM cross-tolerates with other serotonergic hallucinogens (LSD, mescaline, psilocybin/psilocin) through shared 5-HT₂A receptor downregulation (Halberstadt & Geyer 2011 [Ref 16]; Nichols 2016 [Ref 13]).
The brief's tolerance data (buildup: "almost immediately after ingestion," half-life 3 days, full reset 7 days) is broadly consistent with the published data, though "almost immediately" is well-supported — desensitization begins within 2 hours in vitro [Ref 9].
### Dependence
DOM is **not habit-forming** and does not produce dependence. Nichols (2016 [Ref 13]) reviews evidence that serotonergic psychedelics "are generally considered physiologically safe and do not lead to dependence or addiction." DOM does not function as a positive reinforcer in animal self-administration models and does not substitute for cocaine or methamphetamine in drug discrimination (Gatch et al. 2011 [Ref 10]).
---
## Interactions
### Tramadol (Brief: "dangerous")
The brief lists tramadol as dangerous in combination with DOM. No published primary data specific to DOM + tramadol was found. **FLAG FOR HUMAN REVIEW.** The likely mechanism is additive/synergistic serotonergic activity: tramadol inhibits serotonin and norepinephrine reuptake and is a weak µ-opioid agonist. Combined with a 5-HT₂A/₂C full agonist, this could elevate serotonergic tone toward serotonin syndrome risk. This is a class-level concern for all serotonergic psychedelics + tramadol, not a DOM-specific published finding. Classification as "dangerous" is consistent with class-level harm reduction consensus but lacks substance-specific published evidence.
### SSRIs/SNRIs
Citalopram **potentiates** DOM discriminative stimulus effects via 5-HT₂C receptor mechanism (Eckler et al. 2004 [Ref 3]). Mechanism: increased synaptic serotonin from SSRI enhances 5-HT₂C tone, which potentiates DOM response. This is a significant interaction: SSRIs do not block DOM but amplify it.
### Chlorpromazine (Antipsychotics)
Clinically documented contraindication from the 1967 crisis. Phenothiazine antipsychotics are contraindicated for DOM adverse reaction management (Trout & Daley 2024 [Ref 12]). Mechanism unclear but possibly involves alpha-adrenergic blockade or pharmacodynamic interaction at 5-HT receptors.
### 5-HT₁A Agonists
5-HT₁A agonists (buspirone, 8-OH-DPAT) attenuate DOM discriminative stimulus effects in rhesus monkeys but not in rats (Li et al. 2010 [Ref 20]). Potential therapeutic relevance for managing DOM adverse effects; not confirmed in humans.
### Lithium
No DOM-specific data found. General concern with psychedelics and lithium (seizure risk) documented for LSD and psilocybin but not specifically for DOM. **FLAG FOR HUMAN REVIEW** — editorial assessment needed.
---
## Legal Status
| Jurisdiction | Status | Schedule/Class |
|---|---|---|
| United States | Illegal | Schedule I (CSA 1970) |
| United Nations | International control | Schedule I (Convention on Psychotropic Substances 1971) |
| United Kingdom | Illegal | Class A, Schedule 1 (Misuse of Drugs Act 1971) |
| Canada | Illegal | Schedule I (CDSA) |
| Australia | Illegal | Schedule 9 (Poisons Standard) |
| Germany | Likely controlled | BtMG (not explicitly confirmed in sources accessed) |
All legal status data sourced from web_retrieved sources (Wikipedia, law databases). FLAG: Germany-specific scheduling was not confirmed in a primary legal source — editorial review recommended.
---
## Clinical Trials
**No clinical trials for DOM were found on ClinicalTrials.gov.** DOM has never entered formal clinical investigation. The only controlled human study remains Snyder et al. (1967 [Ref 11]) conducted before systematic clinical trial registration.
---
## Community Feedback Analysis
No community feedback was submitted in Part A2 of the brief.
---
## Gaps & Flags
### 🚨 CRITICAL FLAGS FOR HUMAN REVIEW
1. **"Monoamine releasing agent" classification is likely incorrect.** Published evidence (Eckler 2004 [Ref 3]; Silverman & Ho 1980 [Ref 22]; Friedman 1978 [Ref 21]) consistently shows DOM lacks affinity for monoamine transporters and its mechanism is direct 5-HT₂A/₂C receptor agonism. Recommend removing "Monoamine releasing agent" from pharmacological class and replacing with "Serotonin 2A receptor full agonist, Serotonin 2C receptor full agonist."
2. **Duration discrepancy:** Brief lists 12–16 hours total. PiHKAL (Shulgin's firsthand data [Ref 24]) reports 14–20 hours. Snyder 1967 [Ref 11] reported ~8 hours in controlled setting at lower doses. Duration appears dose-dependent. Recommend revising total duration to 14–20 hours (or bracketing as dose-dependent: 8 hours at low doses, 14–20 hours at common-to-strong doses). Aftereffects window in brief (4–16 hours) may overlap with active phase at higher doses.
3. **LD50 / toxic dose unknown.** Brief correctly notes this. No published animal or human LD50 data found. Cannot be inferred safely from structural analogy alone.
4. **Tramadol "dangerous" interaction has no DOM-specific published data.** Class-level serotonergic concern is plausible but not substance-verified. Flag for editorial assessment of evidence tier.
5. **Chlorpromazine (and phenothiazine antipsychotics) are clinically contraindicated** — documented from the 1967 mass overdose event. This is an important harm reduction finding that should appear prominently in the article. No contraindication is listed in the brief — recommend adding.
6. **Chlorpromazine contraindication mechanism** is not fully established in published literature; the historical evidence is strong but mechanistic explanation remains speculative.
7. **Germany/EU legal status** not confirmed in a primary legal source accessed during this research.
### Confirmed Gaps (Data Absent from Published Literature)
- No published human pharmacokinetics (bioavailability, Tmax, plasma half-life, volume of distribution, protein binding). DOM "rapidly faded before human pharmacokinetics could be established" (Trout & Daley 2024 [Ref 12]).
- No published LD50 data in any species.
- Precise Ki values for DOM at 5-HT₂A, 5-HT₂C, and other targets not accessible from available abstracts (present in Ray 2010 full tables [Ref 5] but not abstractable via API).
- No case reports of fatal DOM overdose in published literature (the 1967 crisis did not produce published fatality reports from academic sources).
- No published data on DOM + lithium interaction specifically.
- No published data on DOM + MAOIs specifically.
- Reagent test color reactions for DOM not documented in peer-reviewed sources (web-retrieved only).
- No published data on 5-HT₂B cardiac valvulopathy risk with DOM specifically (class-level concern only).
### Areas Relying on Structural Analogy / Class Inference
- Tramadol interaction severity rated as "dangerous": class-level inference from serotonergic pharmacology, not DOM-specific data.
- Lithium interaction concern: class-level inference from psychedelic class data.
- Serotonin syndrome risk from any serotonergic co-administration: class-level inference.
- Reagent test predictions: based on DOx class structural properties.
### Seed Data Confirmed Accurate
- Molecular formula C₁₂H₁₉NO₂ ✓
- Molecular weight 209.28 ✓
- InChIKey NTJQREUGJKIARY-UHFFFAOYSA-N ✓
- Primary ROA oral ✓
- Chemical classes (phenethylamine, DOx, substituted amphetamine) ✓
- Primary mechanism 5-HT₂A receptor agonism ✓
- Tolerance: rapid onset, cross-tolerance with psychedelics ✓
- Not habit-forming ✓
- Dose data broadly consistent with PiHKAL (though total duration needs upward revision)