generation run 2026-04-26
57 min completedmodel pipeline-v5plan not recordedrun/c62e6f0f…Selection
Verification
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The model's own caveats
none raised on this run
Reproduce
- inputs
- 25 source keys (listed under Sources)
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- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
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- none — agent transcripts are persisted from 2026-09 onward
22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | dimethoxy methylamphetamine DOM pharmacokinetics metabolism cytochrome | 1 | 1 | — |
| 2 | PubMed | DOM dimethoxy methylamphetamine tolerance serotonin receptor downregulation | 3 | 3 | — |
| 3 | PubMed | DOM 2,5-dimethoxy-4-methylamphetamine head twitch response potency hallucinogen | 5 | 4 | — |
| 4 | PubChem | 1-(2,5-dimethoxy-4-methylphenyl)propan-2-amine | 1 | 1 | — |
| 5 | ClinicalTrials.gov · absence | DOM 2,5-dimethoxy-4-methylamphetamine psychedelic | 0 | 0 | — |
| 6 | PubMed · absence | DOM STP hallucinogen drug discrimination 5-HT2A serotonin | 0 | — | — |
| 7 | OpenAlex | DOM 2,5-dimethoxy-4-methylamphetamine psychedelic serotonin | 10 | 1 | — |
| 8 | PubMed | DOM 2,5-dimethoxy-4-methylamphetamine pharmacology receptor binding | 10 | 5 | — |
| 9 | WebSearch | DOM STP legal status Schedule I DEA US UK Australia Canada | 10 | 0 | — |
| 10 | WebSearch | DOM STP Shulgin PiHKAL 1964 synthesis history | 10 | 0 | — |
| 11 | OpenAlex | DOx amphetamine hallucinogen binding affinity SAR serotonin | 8 | 2 | — |
| 12 | PubMed | PMID 38419183 | 1 | 1 | — |
| 13 | PubMed | Nichols psychedelics review 2016 Pharmacological Reviews | 2 | 2 | — |
| 14 | WebSearch | DOM STP overdose toxicity 1967 Haight-Ashbury | 10 | 1 | — |
| 15 | PubMed | Halberstadt hallucinogen head twitch response review | 2 | 1 | — |
| 16 | WebSearch (physical properties) | DOM CAS SMILES melting point physical properties | 10 | 0 | — |
| 17 | PubMed | DOM dimethoxy methylamphetamine catecholamine cardiovascular | 1 | 1 | — |
| 18 | Erowid PiHKAL #68 | DOM dose duration physical properties effects | 1 | 1 | — |
| 19 | PubMed/OpenAlex | DOM Gatch 2021 tryptamine discrimination | 5 | 2 | — |
| 20 | WebSearch | DOM STP legal status multiple jurisdictions | 10 | 0 | — |
| 21 | Multiple sources | DOM monoamine releasing agent classification verification | 3 | 2 | — |
| 22 | WebSearch | DOM monoamine releasing serotonin release dopamine | 10 | 0 | — |
86 claims by section — every cited sentence, checked against its source
safety22 · 15 ok
Claim in safety — inconclusiveinconclusiveworking →
Serotonergic psychedelics 'are generally considered physiologically safe and do not lead to dependence or addiction'supported
Considered physiologically safe, do not lead to dependence/addiction. pr.115.011478
Claim in safety — inconclusiveinconclusiveworking →
Sympathomimetic cardiovascular effects — tachycardia and hypertension — were present and are centrally mediated via serotonin receptors.supported
DOM produces BP and HR rise via central serotonin receptor stimulation. pmid:26578
Rapid cardiovascular tachyphylaxis develops to repeated dosessupported
Rapid tachyphylaxis accompanies 5-HT receptor desensitization. pmid:26578
Despite its amphetamine backbone, DOM lacks the monoamine-releasing mechanism responsible for the serotonergic neurotoxicity associated with mdma and MDA.supported
DOM has no affinity for serotonin transporter. pmid:15388280
Despite its amphetamine backbone, DOM lacks the monoamine-releasing mechanism responsible for the serotonergic neurotoxicity associated with mdma and MDA.supported
DOM does not substitute for amphetamine. DOM pharmacologically distinct from amphetamine. pmid:6771804
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Recovery half-life was 5 hours after 2-hour pretreatment, extending to 9.5–12.5 hours after prolonged (24–96 hour) pretreatment.supported
Recovery half-life 5-12.5 hours. pmid:2273941
Chronic 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.supported
Chronic DOM selectively decreases 5-HT2A/2C in olfactory nucleus. pmid:15972234
DOI-tolerant mice develop cross-tolerance to both DOI analogs and tryptamine hallucinogens (DPT)supported
DOI-tolerant mice show cross-tolerance to DPT. jpet.114.219337
DOI and lsd exhibit cross-tolerance mediated by 5-HT₂A receptor downregulation, independent of β-arrestin-2 recruitmentsupported
Cross-tolerance between DOI and LSD. 5-HT2AR density downregulated in frontal cortex. Mechanism independent of beta-arrestin-2. acschemneuro.2c00170
Class-level cross-tolerance extends to mescaline, psilocybin, and other serotonergic hallucinogens through shared 5-HT₂A receptor downregulation.supported
DOM/mescaline are selective 5-HT2 agonists; indoleamines like LSD are relatively non-selective. Both classes induce cross-tolerance. 5-HT2A primary mediator. j.neuropharm.2011.01.017
Claim in safety — inconclusiveinconclusiveworking →
DOM does not function as a positive reinforcer in animal self-administration models and does not substitute for cocaine or methamphetamine in drug discrimination paradigms.partially supported
Low abuse liability for DOM in rodents. jpet.111.179705
Citalopram 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 responsesupported
Citalopram potentiates DOM discriminative stimulus via 5-HT2C receptor. pmid:15388280
Claim in safety — inconclusiveinconclusiveworking →
5-HT₁A agonists (buspirone, 8-OH-DPAT) attenuate DOM discriminative stimulus effects in rhesus monkeys but not in ratssupported
5-HT1A agonists attenuate DOM effects in monkeys but not rats. jpet.109.163451
Chlorpromazine and related phenothiazines are absolutely contraindicated as pharmacological interventions for DOM adverse reactions, based on clinical documentation from the 1967 mass exposure event.supported
chlorpromazine warning origins. dta.3667
Claim in safety — inconclusiveinconclusiveworking →
DOM produces centrally mediated tachycardia and hypertensionsupported
DOM produces BP and HR rise via central serotonin receptor stimulation. pmid:26578
pharmacology15 · 14 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
Li 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 populationpartially supported
DOM discriminative stimulus effects mediated by 5-HT2A receptors in rhesus monkeys. pA2 for MDL100907 = 8.61. Competitive antagonism confirmed by Schild analysis. jpet.108.145458
The 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 amphetaminesupported
DOM stimulus blocked by 5-HT antagonists, not dopamine antagonists. DOM does not substitute for amphetamine. pmid:6771804
The serotonergic basis is further supported by complete blockade of the DOM discriminative stimulus by the 5-HT antagonists cinanserin and methysergide.supported
DOM stimulus blocked by 5-HT antagonists, not dopamine antagonists. pmid:6771804
Eckler 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-100635supported
Citalopram potentiates DOM discriminative stimulus via 5-HT2C receptor. pmid:15388280
Equilibrium saturation studies in the same report confirmed that DOM has no significant affinity for the serotonin transporter (SERT), ruling out indirect serotonergic mechanisms.supported
DOM has no affinity for serotonin transporter. pmid:15388280
Cardiovascular 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.supported
DOM produces BP and HR rise via central serotonin receptor stimulation. Response abolished by spinal transection. pmid:26578
Multiple 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.supported
DOM has no affinity for serotonin transporter. pmid:15388280
Multiple 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.supported
DOM does not substitute for amphetamine. DOM pharmacologically distinct from amphetamine. pmid:6771804
Multiple 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.supported
DOM produces BP and HR rise via central serotonin receptor stimulation. pmid:26578
As Trout and Daley noted, DOM 'rapidly faded into oblivion before human pharmacodynamics and pharmacokinetics could be established'.supported
DOM rapidly faded before human pharmacodynamics/pharmacokinetics established. dta.3667
Total 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).supported
Doses >3mg cause pronounced hallucinogenic effects lasting ~8 hours. science.158.3801.669
The (R)-enantiomer forms a metabolic intermediate complex with CYP P-450, potentially inhibiting the enzyme through a mechanism-based ('suicidal') inhibition pathwaysupported
R-enantiomer forms CYP P-450 metabolic intermediate complex. N-hydroxylation is suicidal inhibitor. pmid:7265116
The (R)-(−)-enantiomer is both more pharmacologically active and preferentially oxidised by CYP P-450.partially supported
Stereoselective N-oxidation: R-enantiomer forms CYP P-450 metabolic intermediate complex. pmid:7265116
The (R)-(−)-enantiomer is both more pharmacologically active and preferentially oxidised by CYP P-450.partially supported
(-) isomer more potent. pmid:6771804
summary12 · 10 ok
DOM occupies a distinctive position in the phenethylamine hallucinogen landscape: approximately 100 times more potent than mescaline by weight and one-thirtieth the potency of lsdsupported
~100x more potent than mescaline, ~1/30 as potent as LSD. science.158.3801.669
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
DOM'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.supported
DOM was the first member identified as hallucinogenic. DOx are 5-HT2 agonists. SAR, binding, behavioral pharmacology covered. acsptsci.4c00157
DOM 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 systemssupported
5-HT2 receptor subtypes primary targets. In vitro 5-HT2A activities 2-56 nM. s41380-025-03325-1
The 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.partially supported
pA2 for MDL100907 = 8.61. Competitive antagonism confirmed by Schild analysis. jpet.108.145458
The 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.partially supported
DOM stimulus blocked by 5-HT antagonists, not dopamine antagonists. pmid:6771804
DOM does not produce physical dependence or function as a positive reinforcer in self-administration paradigmssupported
Considered physiologically safe, do not lead to dependence/addiction. pr.115.011478
DOM does not produce physical dependence or function as a positive reinforcer in self-administration paradigmssupported
Low abuse liability for DOM in rodents. jpet.111.179705
Tolerance develops within hours of exposure through rapid 5-HT₂ receptor desensitization, with near-complete loss of receptor-mediated signalling observed within 2 hours in vitrosupported
DOM causes nearly full 5-HT2 desensitization in 2 hours. pmid:2273941
Cross-tolerance extends to lsd, psilocybin, and mescaline via shared 5-HT₂A downregulationpartially supported
Cross-tolerance between DOI and LSD. 5-HT2AR density downregulated in frontal cortex. acschemneuro.2c00170
Published human pharmacokinetics — bioavailability, plasma half-life, volume of distribution — remain entirely uncharacterized.supported
DOM rapidly faded before human pharmacodynamics/pharmacokinetics established. dta.3667
history8 · 5 ok
Claim in history — inconclusiveinconclusiveworking →
The 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'supported
Doses >3mg cause pronounced hallucinogenic effects lasting ~8 hours. ~100x more potent than mescaline, ~1/30 as potent as LSD. science.158.3801.669
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Following scheduling, DOM rapidly disappeared from the illicit drug supply.supported
DOM rapidly faded before human pharmacodynamics/pharmacokinetics established. dta.3667
It 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 analogspartially supported
DOM discriminative stimulus effects mediated by 5-HT2A receptors in rhesus monkeys. jpet.108.145458
It 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 analogssupported
Four 25X-NBOH compounds tested against DOM discriminative stimulus. Confirms DOM as standard reference hallucinogen. fbp.0000000000000802
It 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 analogssupported
DOI, DOC, DOB first synthesized 1973 as DOM analogs. DOM was the first member identified as hallucinogenic. acsptsci.4c00157
comparative-pharmacology7 · 7 ok
DOM (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.supported
DOM (4-methyl) most efficacious in HTR assay. 5-HT2 receptor subtypes primary targets. In vitro 5-HT2A activities 2-56 nM. s41380-025-03325-1
DOM (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.supported
DOI, DOC, DOB first synthesized 1973 as DOM analogs. SAR, binding, behavioral pharmacology covered. acsptsci.4c00157
Halberstadt et al. established strong correlations between HTR potency and subjective effects across species for phenethylamine hallucinogens including DOM.supported
Strong correlation (r=0.9448) between HTR in mice and hallucinogenic potencies in humans. DOM used as training drug in rat discrimination. j.neuropharm.2019.107933
DOM-trained animals reliably generalise to other serotonergic hallucinogens, including lsd, tryptamine psychedelics (DPT, DMT analogs), and NBOMe compoundssupported
DOM used as training drug. DIPT fully substituted at ED50=1.94 mg/kg. jpet.111.179705
DOM-trained animals reliably generalise to other serotonergic hallucinogens, including lsd, tryptamine psychedelics (DPT, DMT analogs), and NBOMe compoundssupported
25B-NBOMe, 25C-NBOMe, 25I-NBOMe, 5-MeO-DALT tested against DOM. All fully or nearly substituted for DOM. fbp.0000000000000309
DOM does not substitute for amphetamine, cocaine, methamphetamine, or phencyclidine, confirming its pharmacological dissimilarity from psychostimulants and dissociatives.partially supported
DOM does not substitute for amphetamine. DOM pharmacologically distinct from amphetamine. pmid:6771804
Snyder et al. established DOM's potency at approximately 100× mescaline and 1/30× lsd by weightsupported
~100x more potent than mescaline, ~1/30 as potent as LSD. science.158.3801.669
neuroscience7 · 5 ok
Chronic 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 downregulationsupported
Chronic DOM selectively decreases 5-HT2A/2C in olfactory nucleus. pmid:15972234
What 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.supported
R-enantiomer forms CYP P-450 metabolic intermediate complex. N-hydroxylation is suicidal inhibitor. pmid:7265116
The 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.supported
DOM causes nearly full 5-HT2 desensitization in 2 hours. pmid:2273941
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
DOM'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.partially supported
Competitive antagonism confirmed by Schild analysis. pA2 for MDL100907 = 8.61. jpet.108.145458
The 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 dosessupported
DOM produces BP and HR rise via central serotonin receptor stimulation. Response abolished by spinal transection. Rapid tachyphylaxis accompanies 5-HT receptor desensitization. pmid:26578
pharmacokinetic-detail4 · 4 ok
Duration is dose-dependent: approximately 8 hours at threshold psychedelic doses (>3 mg) extending to 14–20 hours at common doses (3–10 mg).partially supported
Doses >3mg cause pronounced hallucinogenic effects lasting ~8 hours. science.158.3801.669
The 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.supported
DOM rapidly faded before human pharmacodynamics/pharmacokinetics established. dta.3667
The (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.supported
R-enantiomer forms CYP P-450 metabolic intermediate complex. N-hydroxylation is suicidal inhibitor. pmid:7265116
The (R)-(−)-enantiomer is the more potent isomer in both receptor binding and in vivo behavioural assayssupported
(-) isomer more potent. pmid:6771804
receptor-pharmacology4 · 4 ok
DOM's full receptor binding profile across 51 targets was characterised using the NIMH Psychoactive Drug Screening Program (PDSP) panelsupported
NIMH-PDSP binding data for 25 psychedelics at 51 receptors including DOM. journal.pone.0009019
From 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 systemssupported
In vitro 5-HT2A activities 2-56 nM. s41380-025-03325-1
This 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.supported
Citalopram potentiates DOM discriminative stimulus via 5-HT2C receptor. 5-HT2C contributes to DOM effects. pmid:15388280
The 2,5-dimethoxy motif on the phenethylamine ring is essential for both 5-HT₂A binding and in vivo psychedelic potencysupported
Elimination of 2- or 5-methoxy leads to modest drop in 5-HT2A/2C binding. 2,5-dimethoxyphenethylamine motif important for in vivo potency. acschemneuro.0c00129
chemistry3 · 3 ok
The 2,5-dimethoxy motif is critical for both 5-HT₂A receptor binding and in vivo psychedelic potencysupported
2,5-dimethoxyphenethylamine motif important for in vivo potency. Elimination of 2- or 5-methoxy leads to modest drop in 5-HT2A/2C binding. acschemneuro.0c00129
DOM 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.supported
DOM (4-methyl) most efficacious in HTR assay. 5-HT2 receptor subtypes primary targets. s41380-025-03325-1
The (R)-(−)-enantiomer is the more pharmacologically active isomer and is preferentially oxidised by hepatic cytochrome P-450 enzymespartially supported
Stereoselective N-oxidation: R-enantiomer forms CYP P-450 metabolic intermediate complex. pmid:7265116
clinical-evidence3 · 1 ok
The 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'.supported
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. science.158.3801.669
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
effects-overview1 · 0 ok
Claim in effects-overview — inconclusiveinconclusiveworking →