generation run 2026-05-07
80 min completedmodel pipeline-v5plan not recordedrun/457f97d4…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
Reproduce
- inputs
- 24 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | 2C-E 2,5-dimethoxy-4-ethylphenethylamine hallucinogen psychedelic pharmacology | 1 | 1 | 2C-E is the parent compound of 25E-NBOH; pharmacology data provides context |
| 2 | PubChem | 25E-NBOH | 1 | 1 | Only result; confirms chemical identity from brief |
| 3 | PubMed | 25CN-NBOH serotonin 5-HT2A selective agonist receptor | 10 | 3 | 25CN-NBOH is closest well-studied structural analog to 25E-NBOH; relevant for class pharmacology context |
| 4 | PubMed | NBOMe NBOMes 5-HT2A agonist potent psychedelic binding | 3 | 3 | Key pharmacological references for NBOMe/NBOH class |
| 5 | ClinicalTrials.gov · absence | 25E-NBOH NBOH psychedelic phenethylamine | 0 | — | Expected - 25E-NBOH is an emerging NPS with no clinical development |
| 6 | PubMed | 25E-NBOH phenethylamine NBOH psychedelic | 2 | 2 | Both directly relevant - only published papers with 25E-NBOH-specific data |
| 7 | OpenAlex | 25x-NBOH psychedelic phenethylamine receptor | 10 | 4 | High-citation papers with direct relevance to NBOH/NBOMe pharmacology |
| 8 | PubChem | CID 135391539 | 1 | 1 | Verifies chemical identity |
| 9 | WebSearch | 25E-NBOH legal status scheduling US UK EU controlled substance analog | 10 | 4 | Legal status critical data; forensic paper is direct primary source for 25E-NBOH |
| 10 | PsychonautWiki | 25E-NBOH dose duration effects safety | 1 | 3 | Harm reduction dose reference; labeled as community data |
| 11 | PMC | 25E-NBOH behavioral pharmacology data | 1 | 3 | Full quantitative pharmacological data for 25E-NBOH |
| 12 | WebSearch | NBOH series Martin Hansen University Copenhagen 2010 discovery | 10 | 1 | Key historical paper establishing NBOH class origin |
| 13 | PubMed | Locomotor and discriminative stimulus effects of NBOH hallucinogens | 1 | 1 | Most important direct 25E-NBOH behavioral data |
| 14 | WebSearch | 25E-NBOH dose range human experience | 10 | 1 | Only available dose data; labeled as community reports |
| 15 | PubMed | NBOMe blotting paper severe toxicity beware | 1 | 1 | Relevant clinical safety reference for NBOH class |
| 16 | PsychonautWiki | dose duration effects safety 25E-NBOH | 1 | 2 | Only quantitative dose data available; labeled as community-report source |
| 17 | PubChem + PubMed + OpenAlex | 25E-NBOH data synthesis | 31 | 1 | Final cross-reference confirming consistency across sources |
| 18 | PubMed | DARK classics NBOMe ACS chemical neuroscience 2020 | 1 | 1 | Major review of NBOMe/NBOH class covering all key aspects |
70 claims by section — every cited sentence, checked against its source
safety20 · 14 ok
Halberstadt reviewed 51 published cases of NBOMe toxicity identifying the following complications:supported
Reviews 51 cases of NBOMe toxicity. Rhabdomyolysis identified as common complication. 7854_2016_64
Class-level risks include vasoconstriction (mediated by alpha-1A adrenoceptor binding), seizures, hyperthermia, and rhabdomyolysissupported
Comprehensive review of NBOMe structure-activity relationships, behavioral pharmacology, metabolism, and toxicity. Reviews 51 cases of NBOMe toxicity. Rhabdomyolysis identified as common complication. 7854_2016_64
Xiang et al. state that 25E-NBOH "has caused several poisoning cases and even fatal cases", but provide no case details, numbers, circumstances, or clinical outcomessupported
Reports poisoning cases and fatalities involving 25B-NBOH and 25E-NBOH. j.jpba.2024.116020
Zawilska et al. confirm this adverse effects profile and report that NBOMe use has resulted in fatalitiessupported
Reports adverse effects: visual/auditory hallucinations, seizures, excited delirium, sympathomimetic signs, rhabdomyolysis, multiorgan failure. fnins.2020.00078
Isbister et al. describe severe toxicity from blotter paper hallucinogens in the NBOMe class.supported
Reports severe toxicity associated with NBOMe compounds found on blotting paper. pmid:26377297
Claim in safety — inconclusiveinconclusiveworking →
The serotonergic component (5-HT₂A/2B agonism) contributes additional cardiotoxicity risk through coronary vasoconstriction and potential valvulopathy with chronic exposure.supported
Notes that 5-HT2A/2B and 5-HT4 receptor agonism is relevant to cardiotoxicity. Reviews sympathomimetic effects in experimental and clinical studies. s43440-023-00539-4
25E-NBOH degrades to 2C-E under standard GC-MS conditionssupported
NBOH compounds are thermolabile and misidentified under GC-MS. c9an00062c
Claim in safety — inconclusiveinconclusiveworking →
The 2026 metabolic study confirms 2C-E as an actual N-debenzylation metabolitesupported
2C-E confirmed as a metabolite via N-debenzylation. j.jpba.2026.117417
Claim in safety — inconclusiveinconclusiveworking →
De la Fuente Revenga et al. demonstrated in mice that:supported
Repeated DOI induces progressive HTR decrease (tolerance). Cross-tolerance between psychedelic 5-HT2A agonists (DOI/LSD). DOI causes 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
No dependence liability studies (self-administration, conditioned place preference) have been conducted for 25E-NBOHsupported
Tests four 25X-NBOH compounds for locomotor effects in mice and discriminative stimulus effects in DOM-trained rats. fbp.0000000000000802
The structurally related compound 25C-NBF showed no rewarding effects in mice and no reinforcing effects in ratssupported
No rewarding or reinforcing effects in mice and rats. s41380-025-03341-1
Combination with monoamine oxidase inhibitors (MAOIs) — both reversible (moclobemide) and irreversible (phenelzine, tranylcypromine) — carries serious serotonin syndrome risk. 5-HT₂A agonist effects combined with elevated synaptic serotonin from MAO inhibition can precipitate potentially fatal serotonin toxicitysupported
Reviews serotonin toxicity risk from psychedelic substances with serotonergic mechanisms. Evaluates potential drug-drug interactions with SSRIs and MAOIs. s00213-021-05876-x
The interaction picture in combined serotonergic states is complex and incompletely characterized.supported
Reviews serotonin toxicity risk from psychedelic substances with serotonergic mechanisms. Evaluates potential drug-drug interactions with SSRIs and MAOIs. s00213-021-05876-x
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Seizure disorders (epilepsy): Seizure threshold reduction is documented at class level for NBOMe/NBOH compoundssupported
Reports adverse effects: visual/auditory hallucinations, seizures, excited delirium, sympathomimetic signs, rhabdomyolysis, multiorgan failure. fnins.2020.00078
Claim in safety — inconclusiveinconclusiveworking →
pharmacology12 · 9 ok
25E-NBOH exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptorssupported
25B-NBOH, 25C-NBOH, 25E-NBOH fully substituted for DOM (>=80%). fbp.0000000000000802
25E-NBOH exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptorssupported
NBOMes show subnanomolar 5-HT2A affinity. Addition of N-benzyl group markedly increases 5-HT2A binding affinity and hallucinogenic potency. 7854_2016_64
Claim in pharmacology — inconclusiveinconclusiveworking →
Recent cryo-EM structural work demonstrates that hallucinogenic effects of 5-HT₂A agonists require non-canonical Gᵢ signalling rather than the canonical Gq pathway, which mediates other downstream cellular actionssupported
Demonstrates that 5-HT2A-mediated non-canonical Gi signalling is essential for hallucinogenic effects of psychedelics. Cryo-EM structures of 5-HT2AR-Gi/Gq complexes. Identifies structural basis for signaling bias underlying hallucinogenic vs non-hallucinogenic effects. s41586-025-10061-7
Structure-activity studies on the closely related 25CN-NBOH demonstrate that interactions at residue Ser159(3×36) determine the balance between Gαq and β-arrestin-2 signalling, providing a structural framework applicable to 25E-NBOH.supported
Evaluates 25CN-NBOH and close analogues for biased signaling at 5-HT2A receptor. Developed first efficacious β-arrestin2-biased 5-HT2A agonists. Role of Ser159 interaction in Gαq vs βarr2 signaling pathways. acs.jmedchem.2c00702
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Secondary pharmacological actions likely include alpha-1A adrenoceptor binding (Ki < 1 µM documented for the NBOMe class), mechanistically linking the compound to vasoconstriction and cardiovascular sympathomimetic effects.supported
Reports adverse effects: visual/auditory hallucinations, seizures, excited delirium, sympathomimetic signs, rhabdomyolysis, multiorgan failure. fnins.2020.00078
Vágnerová et al. characterized the metabolic profile of 25E-NBOH in human liver microsomes, rat urine, and the fungus Cunninghamella elegans, identifying key biotransformation pathways and confirming 2C-E (the parent phenethylamine) as an N-debenzylation metabolitesupported
First comprehensive in vitro and in vivo metabolic profile of 25E-NBOH. Primary metabolic pathways: hydroxylation, O-demethylation, N-debenzylation. 2C-E confirmed as a metabolite via N-debenzylation. j.jpba.2026.117417
Xiang et al. independently characterized 25E-NBOH metabolism in human liver microsomes using UHPLC-Q-Exactive Orbitrap mass spectrometry, identifying additional metabolites and biotransformation routes.supported
In vitro phase I and II metabolism of 25B-NBOH, 25E-NBOH, 25H-NBOH, 25iP-NBOMe in human liver microsomes. 70 metabolites total. j.jpba.2024.116020
By class analogy with 25CN-NBOH: NBOH compounds are susceptible to first-pass hepatic metabolism, and metabolic stability studies in human liver microsomes suggest moderate metabolic susceptibilitysupported
In vitro biotransformation studies identified metabolic pathways. 25CN-NBOH more metabolically stable than NBOMes. j.jpba.2021.114016
By class analogy with 25CN-NBOH: NBOH compounds are susceptible to first-pass hepatic metabolism, and metabolic stability studies in human liver microsomes suggest moderate metabolic susceptibilitysupported
Reviews history, chemistry, SAR, ADME, and safety profiles of NBOMes. Covers NBOH series context. acschemneuro.9b00528
summary8 · 7 ok
It functions as a high-affinity full agonist at serotonin 5-HT₂A and 5-HT₂C receptors, producing hallucinogenic effects at sublingual doses in the microgram rangepartially supported
25B-NBOH, 25C-NBOH, 25E-NBOH fully substituted for DOM (>=80%); All four compounds decreased locomotor activity. fbp.0000000000000802
The NBOH scaffold was developed circa 2009–2010 by Martin Hansen and colleagues at the University of Copenhagen as part of a program to create agonist PET radioligands for the 5-HT₂A receptor. 25E-NBOH appeared on research chemical markets approximately 2018–2019 and was first forensically identified in seized blotter papers from Brazil in 2017–2018partially supported
PET imaging study evaluating nine novel 5-HT2A receptor agonist PET tracers derived from phenethylamine backbone. Published 2011 from Copenhagen University Hospital. s00259-010-1686-8
Claim in summary — not_supportednot supportedworking →
The NBOH scaffold was developed circa 2009–2010 by Martin Hansen and colleagues at the University of Copenhagen as part of a program to create agonist PET radioligands for the 5-HT₂A receptor. 25E-NBOH appeared on research chemical markets approximately 2018–2019 and was first forensically identified in seized blotter papers from Brazil in 2017–2018partially supported
Blotter papers seized 2017-2018 by Brazilian police analyzed using ATR-FTIR, GC-MS, LC-MS/MS, and 1D/2D NMR. First scientific report of 25E-NBOH in seized samples. s11419-019-00509-7
25E-NBOH acts primarily through 5-HT₂A receptor agonism, a mechanism now understood to require non-canonical Gᵢ signalling for hallucinogenic outputsupported
Demonstrates that 5-HT2A-mediated non-canonical Gi signalling is essential for hallucinogenic effects of psychedelics. s41586-025-10061-7
No substance-specific binding affinity (Ki/EC50) values have been published; class-level data indicate subnanomolar 5-HT₂A affinity for N-benzylphenethylaminessupported
Characterizes binding affinities at multiple receptor types and monoamine transporters. NBOMe compounds show high selectivity for 5-HT2A/2C receptors. j.neuropharm.2015.08.034
One published source states it has caused "several poisoning cases and even fatal cases," though no clinical details accompany this claimsupported
Reports poisoning cases and fatalities involving 25B-NBOH and 25E-NBOH. j.jpba.2024.116020
Tolerance develops rapidly via 5-HT₂A receptor downregulation after a single administration, with cross-tolerance across all psychedelic 5-HT₂A agonistspartially supported
Repeated DOI induces progressive HTR decrease (tolerance). Cross-tolerance between psychedelic 5-HT2A agonists (DOI/LSD). DOI causes 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
history7 · 7 ok
Ettrup, Hansen et al. published the in vivo validation of nine novel 5-HT₂A receptor agonist PET tracers in pig brain in 2011, derived from phenethylamine backbones including the NBOH modificationsupported
PET imaging study evaluating nine novel 5-HT2A receptor agonist PET tracers derived from phenethylamine backbone. Published 2011 from Copenhagen University Hospital. s00259-010-1686-8
25CN-NBOH emerged as the most pharmacologically significant compound from this program, characterized as a highly selective 5-HT₂A agonist with approximately 100-fold selectivity over 5-HT₂Csupported
Novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors, in mice. s00213-014-3739-3
25CN-NBOH emerged as the most pharmacologically significant compound from this program, characterized as a highly selective 5-HT₂A agonist with approximately 100-fold selectivity over 5-HT₂Csupported
Review of 25CN-NBOH, first reported as potent selective 5-HT2A agonist in 2014. Superior selectivity for 5-HT2A vs 5-HT2C. cmdc.202100395
Several NBOMe members were placed into Schedule I in the United States in 2013supported
Numerous cases of acute toxicity, sometimes lethal; Schedule I classification 2013. acschemneuro.9b00528
The first academic forensic identification of 25E-NBOH in seized street samples was reported by Machado et al. in 2019: blotter papers seized in 2017–2018 by Brazilian police were characterized using ATR-FTIR, GC-MS, LC-MS/MS, and 1D/2D NMR spectroscopy. 25E-NBOH was also identified in seized samples from Slovenia and France during this periodpartially supported
First academic work to identify and characterize 25E-NBOH in authentic street-seized samples. Blotter papers seized 2017-2018 by Brazilian police analyzed using ATR-FTIR, GC-MS, LC-MS/MS, and 1D/2D NMR. s11419-019-00509-7
A preceding study identified 25I-NBOH in Brazilian seizures in 2017, establishing the pattern of NBOH detection in Latin American forensic laboratories.supported
25I-NBOH identified in blotter papers by Brazilian forensic labs. First paper on NBOH seizures in Brazil. s11419-017-0357-x
The thermolability of 25E-NBOH — its degradation to 2C-E under standard gas chromatography conditions — complicated early forensic identification and likely resulted in underreporting of its presence in seized materials.supported
NBOH compounds are thermolabile and misidentified under GC-MS. Selective electrochemical method achieves full differentiation. c9an00062c
receptor-pharmacology7 · 6 ok
The N-benzylphenethylamine (NBOMe/NBOH) class demonstrates the following binding profile:supported
In vitro receptor interaction profiles of NBOMe drugs vs 2C drugs (including 2C-B) and LSD. Characterizes binding affinities at multiple receptor types and monoamine transporters. j.neuropharm.2015.08.034
The N-benzylphenethylamine (NBOMe/NBOH) class demonstrates the following binding profile:supported
NBOMes show Ki values in low nanomolar range at 5-HT2A/2C (>1000-fold selectivity over 5-HT1A). fnins.2020.00078
The N-benzylphenethylamine (NBOMe/NBOH) class demonstrates the following binding profile:supported
Comprehensive review of NBOMe structure-activity relationships, behavioral pharmacology, metabolism, and toxicity. NBOMes show subnanomolar 5-HT2A affinity. 7854_2016_64
The NBOH modification (2-hydroxybenzyl vs 2-methoxybenzyl in NBOMes) retains high 5-HT₂A affinity. 25CN-NBOH — the best-characterized member of the NBOH class — demonstrates approximately 100-fold selectivity for 5-HT₂A over 5-HT₂Csupported
25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro. Novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors. s00213-014-3739-3
Poulie et al. identified 25CN-NBOH derivatives with β-arrestin-2 bias through modifications at the 2-hydroxybenzyl ring, demonstrating that subtle structural changes profoundly alter signalling outputsupported
Developed first efficacious β-arrestin2-biased 5-HT2A agonists. Role of Ser159 interaction in Gαq vs βarr2 signaling pathways. acs.jmedchem.2c00702
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The parent compound 2C-E has published receptor interaction data: Eshleman et al. documented in vitro receptor binding, monoamine transporter interactions, and functional activitysupported
In vitro receptor binding and function data for 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC. Includes mouse locomotion, rat drug discrimination, transporter binding data. 2C-E (the parent compound of 25E-NBOH) characterized pharmacologically. s00213-013-3303-6
chemistry4 · 3 ok
Claim in chemistry — inconclusiveinconclusiveworking →
Addition of the N-benzyl group markedly increases 5-HT₂A binding affinity relative to the parent 2C-E compound.supported
Addition of N-benzyl group markedly increases 5-HT2A binding affinity and hallucinogenic potency. 7854_2016_64
A critical physical property is thermolability: 25E-NBOH degrades to its parent compound 2C-E under the thermal conditions of standard gas chromatography (inlet temperatures typically 250–300°C)supported
NBOH compounds are thermolabile and misidentified under GC-MS. c9an00062c
A critical physical property is thermolability: 25E-NBOH degrades to its parent compound 2C-E under the thermal conditions of standard gas chromatography (inlet temperatures typically 250–300°C)supported
Thermolabile - fragments to 2C-I under GC analysis. s11419-017-0357-x
clinical-evidence4 · 3 ok
Claim in clinical-evidence — not_supportednot supportedworking →
This contrasts with 25CN-NBOH, which has been used extensively as a pharmacological research tool for investigating 5-HT₂A receptor function in vitro and in vivo, though even 25CN-NBOH has not entered formal clinical development for any therapeutic indication.supported
Review of 25CN-NBOH, first reported as potent selective 5-HT2A agonist in 2014. Outlines discovery, pharmacological profile, and findings from studies using it as a pharmacological tool. cmdc.202100395
The sole published study directly testing 25E-NBOH in animal behavioral models is Munir et al. (2025):supported
Tests four 25X-NBOH compounds (25B-, 25C-, 25E-, 25I-NBOH) for locomotor effects in mice and discriminative stimulus effects in DOM-trained rats. fbp.0000000000000802
The authors concluded that 25B-NBOH, 25C-NBOH, and 25E-NBOH are hallucinogen-like compounds "most likely to be used as recreational hallucinogens in a similar manner to DOM and the 25X-NBOMe compounds," while 25I-NBOH failed to fully substitute for DOM and may have lower recreational hallucinogen liability.supported
25B-NBOH, 25C-NBOH, 25E-NBOH fully substituted for DOM (>=80%); 25I-NBOH failed to fully substitute. fbp.0000000000000802
comparative-pharmacology3 · 3 ok
Comparative behavioral data from Munir et al.:supported
Tests four 25X-NBOH compounds (25B-, 25C-, 25E-, 25I-NBOH) for locomotor effects in mice and discriminative stimulus effects in DOM-trained rats. fbp.0000000000000802
The N-benzyl modification converting 2C-E to 25E-NBOH produces a dramatic increase in 5-HT₂A binding affinity, consistent with class-level structure-activity relationships. 2C-E itself has been pharmacologically characterized with in vitro receptor binding, monoamine transporter interactions, mouse locomotor activity, and rat drug discrimination datasupported
Addition of N-benzyl group markedly increases 5-HT2A binding affinity and hallucinogenic potency. 7854_2016_64
The N-benzyl modification converting 2C-E to 25E-NBOH produces a dramatic increase in 5-HT₂A binding affinity, consistent with class-level structure-activity relationships. 2C-E itself has been pharmacologically characterized with in vitro receptor binding, monoamine transporter interactions, mouse locomotor activity, and rat drug discrimination datasupported
In vitro receptor binding and function data for 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC. Includes mouse locomotion, rat drug discrimination, transporter binding data. s00213-013-3303-6
neuroscience2 · 2 ok
The following neural mechanisms are inferred from its confirmed 5-HT₂A agonist pharmacology and class-level neuroscience research.supported
25B-NBOH, 25C-NBOH, 25E-NBOH fully substituted for DOM (>=80%). fbp.0000000000000802
Recent mechanistic work demonstrates that the hallucinogenic output specifically requires 5-HT₂A-mediated Gᵢ signalling, while Gq-mediated signalling drives other cellular effectssupported
Demonstrates that 5-HT2A-mediated non-canonical Gi signalling is essential for hallucinogenic effects of psychedelics. Cryo-EM structures of 5-HT2AR-Gi/Gq complexes. s41586-025-10061-7
pharmacokinetic-detail2 · 2 ok
By structural analogy with 25CN-NBOH — for which a quantitative LC-MS/MS method in rat plasma and brain has been developed — NBOH compounds do achieve CNS penetration sufficient for behavioral effects.supported
LC-MS/MS method for 25CN-NBOH quantification in rat plasma and brain. In vivo PK study in rats. j.jpba.2021.114016
Vágnerová et al. conducted the first comprehensive metabolic profile of 25E-NBOH using three complementary models: human liver microsomes (HLM), rat urine in vivo, and the fungal model organism Cunninghamella eleganssupported
First comprehensive in vitro and in vivo metabolic profile of 25E-NBOH. Primary metabolic pathways: hydroxylation, O-demethylation, N-debenzylation. j.jpba.2026.117417
legal-status1 · 0 ok
Claim in legal-status — inconclusiveinconclusiveworking →