generation run 2026-05-08
64 min completedmodel pipeline-v5plan not recordedrun/c784964a…Selection
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Reproduce
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19 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | NBOMe phenethylamine psychedelic binding affinity serotonin receptor | 8 | 5 | Selected papers with direct relevance to NBOMe class pharmacology and toxicology |
| 2 | PubChem | 25E-NBOMe | 1 | 1 | Primary chemical identity source for 25E-NBOMe |
| 3 | PubMed | 25E-NBOMe pharmacology toxicology | 1 | 1 | Only direct 25E-NBOMe pharmacology study found - highly relevant |
| 4 | PubMed | NBOMe metabolism analytical forensic detection urine blood | 4 | 4 | Metabolism and analytical detection papers for 25E-NBOMe class |
| 5 | OpenAlex | 25E-NBOMe pharmacology receptor binding | 10 | 3 | High-citation reviews and direct 25E-NBOMe metabolism study selected |
| 6 | PubMed | NBOMe 25I 25C 25B seizure rhabdomyolysis hyperthermia clinical toxicology | 2 | 1 | Important clinical case series for NBOMe toxicology and management |
| 7 | DEA/Federal Register/Erowid | 25E-NBOMe legal status scheduling DEA United Kingdom analog act | 10 | 3 | Establishes legal status for major jurisdictions |
| 8 | PubMed | head twitch response NBOMe hallucinogenic potency dose response mice | 2 | 2 | HTR assay validates NBOMe hallucinogenic potency and supports translational relevance |
| 9 | Wikipedia/web | 25E-NBOMe dose range duration effects history discovery | 5 | 2 | Background on dosing and history not available in academic databases |
| 10 | ClinicalTrials.gov · absence | 25E-NBOMe NBOMe psychedelic | 0 | — | Confirms absence of registered clinical trials |
| 11 | Crossref DOI verification | Verify key DOIs | 5 | 5 | DOI verification confirms api_verified status |
| 12 | PubMed | 5-HT2A receptor tolerance cross-tolerance psychedelic DOI LSD downregulation | 1 | 1 | Primary study on 5-HT2A-mediated tolerance mechanism applicable to 25E-NBOMe |
| 13 | PubMed | NBOMe blotter paper analytical characterization mass spectrometry forensic seized | 2 | 2 | Key analytical characterization papers - Zuba 2013 is first published description of seized 25E-NBOMe |
| 14 | OpenAlex | NBOMe 25I rhabdomyolysis hyperthermia seizure fatal toxicity case report | 8 | 3 | Major NPS review papers relevant to NBOMe class toxicity |
| 15 | PubMed | NBOMe Europe EMCDDA monitoring prevalence use 2013 2014 | 1 | 1 | Directly names 25E-NBOMe; reviews epidemiology and toxicity |
| 16 | Web/DEA | NBOMe 25I 25C 25B DEA emergency schedule 2013 Federal Register | 10 | 2 | Establishes US legal status for NBOMe class with specific dates |
| 17 | Erowid | NBOMe legal status all jurisdictions | 1 | 1 | Comprehensive international legal status source for NBOMe class |
| 18 | Crossref DOI verification | Verify remaining key DOIs | 3 | 3 | DOI verification for key substance-specific citations |
| 19 | Compiled from all sources | 25E-NBOMe final synthesis of pharmacology, metabolism, dosing, legal status | 30 | 2 | Final data extraction and handoff file creation |
84 claims by section — every cited sentence, checked against its source
safety28 · 15 ok
Fatal intoxications involving 25B-NBOMe (postmortem blood concentration: 1.59 ng/mL) and 25I-NBOMe (19.8 ng/mL) have been confirmedsupported
Two teenage deaths: 25B-NBOMe at 1.59 ng/mL postmortem blood; 25I-NBOMe at 19.8 ng/mL. bkv058
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Heterogeneous distribution of NBOMe compounds on blotter paper — demonstrated through multimodal imaging (microXRF, LA-ICP-OES, MALDI-MS) — creates an inherent risk of inadvertent overdose, as individual blotter units may contain doses far exceeding the intended amountsupported
Blotter papers analyzed by microXRF, LA-ICP-OES, MALDI-MS, LC-MS. Heterogeneous distribution on blotter paper implies inherent overdose risk for consumers. dta.2751
Preclinical toxicology studies specific to 25E-NBOMe are limited to the Kim et al. rodent studysupported
First direct psychopharmacological study of 25E-NBOMe. s12272-024-01491-4
Broader class data show 25X-NBOMes cause developmental impairments, cytotoxicity, cardiovascular toxicity, and behavioral changes in animal modelssupported
Preclinical: developmental impairments, cytotoxicity, cardiovascular toxicity, behavioral changes. 10408444.2023.2194907
A subtle genotoxic effect was observed for 25B-NBOMe in the comet assay; whether this generalizes to 25E-NBOMe is unknown.supported
Subtle genotoxicity (comet assay). Close structural analog to 25E-NBOMe. s12640-020-00297-8
25E-NBOMe is not detectable by standard immunoassay drug screenssupported
Undetected by routine drug screening. s00204-020-02693-7
Confirmation in clinical or forensic settings requires LC-MS/MS or GC-MS with appropriate reference standards.supported
Validated GC-MS method for 23 NPS including 25E-NBOMe in blood and urine. Successfully quantified NBOMe compounds in 75% of reanalyzed blood samples. bky109
Confirmation in clinical or forensic settings requires LC-MS/MS or GC-MS with appropriate reference standards.supported
GC-EI-MS, LC-ESI-QTOF-MS, FTIR, NMR used. Confirms molecular formula and structure. dta.1397
In a 25B-NBOMe toxicity series, 7 of 10 patients required benzodiazepine sedation.{{/Warning}}supported
10 patients with 25B-NBOMe adverse effects. 7/10 required benzodiazepines. 15563650.2015.1115056
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
By class pharmacology, rapid tolerance (tachyphylaxis) is expected via 5-HT₂A receptor downregulation in the frontal cortex following repeated administrationsupported
Tolerance after single dose. 5-HT2AR downregulated in frontal cortex. acschemneuro.2c00170
Cross-tolerance exists between psychedelic 5-HT₂A agonists (demonstrated between DOI and LSD) but not with nonpsychedelic 5-HT₂A agonistssupported
Cross-tolerance between DOI and LSD. Non-psychedelic 5-HT2AR agonist lisuride does not produce cross-tolerance. acschemneuro.2c00170
Kim et al. demonstrated conditioned place preference and self-administration in male rodents, providing preclinical evidence of reinforcement potentialsupported
25E-NBOMe induces conditioned place preference via D1DR signaling in NAc. s12272-024-01491-4
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Seizure disorders: NBOMe compounds lower the seizure threshold; epilepsy or any seizure predisposition constitutes a contraindication.supported
Adverse effects: hallucinations, seizures, hyperthermia, rhabdomyolysis, DIC. fnins.2020.00078
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Hepatic impairment: Given that 25E-NBOMe undergoes extensive hepatic Phase I metabolism, impaired liver function could reduce clearance and increase toxicity risksupported
26 metabolites of 25E-NBOMe identified in pooled human liver microsomes. Main pathways: oxidative deamination, N-dealkylation, O-demethylation, hydroxylation. dta.2446
Pregnancy: Preclinical data showing developmental impairments from 25X-NBOMe exposure make pregnancy a contraindication.supported
Preclinical: developmental impairments, cytotoxicity, cardiovascular toxicity, behavioral changes. 10408444.2023.2194907
pharmacology15 · 12 ok
25E-NBOMe acts as a full agonist at serotonin 5-HT₂A receptors, the primary molecular target mediating its hallucinogenic propertiessupported
Full efficacy at 5-HT2A/2C. Results consistent with hallucinogenic activity, little psychostimulant activity. j.bcp.2018.09.024
In inositol-phosphate accumulation assays using cells heterologously expressing human receptors, 25E-NBOMe displayed subnanomolar-to-low-nanomolar EC₅₀ at 5-HT₂A with full efficacy comparable to LSDsupported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency. j.bcp.2018.09.024
The compound also exhibits very high potency and full efficacy at 5-HT₂C receptors, lower affinity and efficacy at 5-HT₂B, and very low potency at 5-HT₁Asupported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency. Low efficacy at 5-HT1A. j.bcp.2018.09.024
Affinity at monoamine transporters (DAT, SERT, NET) falls in the low-to-mid micromolar range — a profile characterized as "consistent with hallucinogenic activity, with little psychostimulant activity".supported
Low-to-mid micromolar at transporters. Results consistent with hallucinogenic activity, little psychostimulant activity. j.bcp.2018.09.024
Activation of 5-HT₂A receptors on layer V pyramidal neurons in the prefrontal cortex increases extracellular glutamate release, proposed as the proximal mechanism underlying hallucinogenic perceptionsupported
Hallucinogenic activity (HTR) mediated via GLU increase through 5-HT2A receptors. s12640-019-00033-x
Kim et al. confirmed that the head twitch response (HTR) induced by 25E-NBOMe in rodents is blocked by a selective 5-HT₂A antagonist, establishing 5-HT₂A dependence for its hallucinogenic-proxy behaviorsupported
Head twitch response mediated by 5-HT2A receptor activity. s12272-024-01491-4
The HTR correlates strongly (r = 0.9448) with reported hallucinogenic potency in humans across the psychedelic class.supported
Strong correlation (r=0.9448) between HTR potency in mice and human hallucinogenic potency (n=36 compounds). j.neuropharm.2019.107933
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
NBOMe compounds as a class are inactive by the oral route — a well-documented property, though the specific mechanism has not been formally elucidatedsupported
Routes of admin: sublingual/buccal, IV, insufflation, smoking. fnins.2020.00078
Active routes include sublingual/buccal, nasal insufflation, intravenous, and smokingsupported
Routes of admin: sublingual/buccal, IV, insufflation, smoking. fnins.2020.00078
Claim in pharmacology — inconclusiveinconclusiveworking →
Grafinger et al. identified 26 Phase I metabolites of 25E-NBOMe in pooled human liver microsomes (pHLM) and 11 in the microbial model Cunninghamella eleganssupported
26 metabolites of 25E-NBOMe identified in pooled human liver microsomes. 11 in C. elegans. dta.2446
N-oxide and hydroxylamine metabolites were identified for the first time for any NBOMe compound in this studysupported
First report of NBOMe N-oxide and hydroxylamine metabolites. dta.2446
Phase II metabolism has not been studied for 25E-NBOMe directly; O-desmethyl glucuronide and sulfonate conjugates detected in 25B-NBOMe cases are expected by class analogy.supported
Phase II glucuronide and sulfonate detected in biofluids. Methods applicable to 25E-NBOMe class. molecules30224450
summary10 · 9 ok
It is the N-(2-methoxybenzyl) derivative of 2C-E, bearing the structural modification that confers subnanomolar-to-low-nanomolar functional potency at the 5-HT₂A receptorsupported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency. j.bcp.2018.09.024
Claim in summary — inconclusiveinconclusiveworking →
The NBOMe scaffold was first synthesized by Ralf Heim in 2003 as a candidate PET radioligand for 5-HT₂A receptors. 25E-NBOMe appeared on illicit markets in the early 2010s and was first analytically confirmed from seized blotter papers in 2013supported
First analytical characterization of 25E-NBOMe, 25D-NBOMe, and 25G-NBOMe identified in seized blotter papers. GC-EI-MS, LC-ESI-QTOF-MS, FTIR, NMR used. dta.1397
The evidence base is exceptionally sparse: a single rodent study has directly investigated 25E-NBOMe pharmacology, one in vitro metabolism study has characterized its Phase I metabolic pathways, and no controlled human data of any kind exist.supported
First direct psychopharmacological study of 25E-NBOMe. s12272-024-01491-4
The evidence base is exceptionally sparse: a single rodent study has directly investigated 25E-NBOMe pharmacology, one in vitro metabolism study has characterized its Phase I metabolic pathways, and no controlled human data of any kind exist.supported
26 metabolites of 25E-NBOMe identified in pooled human liver microsomes. 11 in C. elegans. Main pathways: oxidative deamination, N-dealkylation, O-demethylation, hydroxylation. dta.2446
25E-NBOMe acts as a full agonist at 5-HT₂A and 5-HT₂C receptors with subnanomolar-to-low-nanomolar functional potency and negligible activity at monoamine transporters — a profile consistent with hallucinogenic activity without significant psychostimulant propertiessupported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency. Low-to-mid micromolar at transporters. Results consistent with hallucinogenic activity, little psychostimulant activity. j.bcp.2018.09.024
The NBOMe class carries a narrow margin of safety owing to microgram-range active doses and heterogeneous distribution on blotter papersupported
Heterogeneous distribution on blotter paper implies inherent overdose risk for consumers. dta.2751
No LD₅₀ data, human lethal dose, or fatal cases specific to 25E-NBOMe have been published; however, fatalities involving the closely related 25I-NBOMe and 25B-NBOMe are well documentedsupported
Two teenage deaths: 25B-NBOMe at 1.59 ng/mL postmortem blood; 25I-NBOMe at 19.8 ng/mL. Reviews published NBOMe fatalities. bkv058
Class-typical severe complications include seizures, rhabdomyolysis, hyperthermia, and multiorgan failuresupported
Adverse effects: hallucinations, seizures, hyperthermia, rhabdomyolysis, DIC. fnins.2020.00078
Tolerance develops rapidly via 5-HT₂A receptor downregulation, with cross-tolerance expected across serotonergic psychedelicssupported
Tolerance after single dose. Cross-tolerance between DOI and LSD. 5-HT2AR downregulated in frontal cortex. acschemneuro.2c00170
receptor-pharmacology8 · 7 ok
Rickli et al. characterized receptor interaction profiles of NBOMe drugs versus 2C drugs and LSD in vitro, providing comparative data across the class.supported
In vitro receptor interaction profiles of NBOMe drugs vs 2C drugs (including 2C-B) and LSD. j.neuropharm.2015.08.034
Eshleman et al. characterized the functional pharmacology of 25E-NBOMe at human serotonin and dopamine receptors expressed in heterologous cell systems.supported
25D-NBOMe, 25E-NBOMe, 25H-NBOMe, 25I-NBOH, 25N-NBOMe studied. Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency. j.bcp.2018.09.024
5-HT₂A: Subnanomolar-to-low-nanomolar EC₅₀ in inositol-phosphate accumulation assays with full efficacy, comparable to LSD and placing 25E-NBOMe among the most potent compounds tested in the study.supported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency. j.bcp.2018.09.024
5-HT₂C: Very high potency (comparable to LSD and serotonin) with full efficacy.supported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency. j.bcp.2018.09.024
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
5-HT₁A: Very low potency and low efficacy.supported
Low efficacy at 5-HT1A. j.bcp.2018.09.024
Affinities and potencies at DAT, SERT, and NET fall in the low-to-mid micromolar range, indicating negligible transporter-mediated activity at pharmacologically relevant concentrations.supported
Low-to-mid micromolar at transporters. j.bcp.2018.09.024
The 25X-NBOMe class exhibits binding affinity at dopamine, adrenergic, and histamine receptors in addition to serotonin receptors — a multi-receptor profile contributing to the complex toxicology of the seriessupported
Multi-receptor affinity (5-HT, dopamine, adrenergic, histamine). Complex metabolism explains high toxicity. 10408444.2023.2194907
comparative-pharmacology5 · 5 ok
The N-(2-methoxybenzyl) substitution that distinguishes NBOMe compounds from their 2C-series parents markedly increases 5-HT₂A receptor affinitysupported
NBOMes higher 5-HT2A affinity than 2C counterparts. j.neuropharm.2018.02.033
In the head twitch response assay, 25I-NBOMe was 14-fold more potent than its parent 2C-Isupported
25I-NBOMe 14-fold more potent than 2C-I in HTR. j.neuropharm.2013.08.025
Eshleman et al. tested 25E-NBOMe alongside 25D-NBOMe, 25H-NBOMe, 25I-NBOH, and 25N-NBOMe under identical assay conditionssupported
25D-NBOMe, 25E-NBOMe, 25H-NBOMe, 25I-NBOH, 25N-NBOMe studied. j.bcp.2018.09.024
25E-NBOMe shares with LSD full agonism at both 5-HT₂A and 5-HT₂C receptors with comparable functional potencysupported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency. j.bcp.2018.09.024
The clinical consequence is that 25E-NBOMe produces a pharmacological profile "consistent with hallucinogenic activity, with little psychostimulant activity", whereas LSD's broader receptor engagement contributes additional sympathomimetic and dopaminergic components.supported
Results consistent with hallucinogenic activity, little psychostimulant activity. j.bcp.2018.09.024
history5 · 4 ok
Wood et al. named 25E-NBOMe among the 25X-NBOMe series members identified in reports of use and acute toxicity from Europe, the United States, and other regions over the period 2010–2015.supported
Review of the 25X-NBOMe series — explicitly lists 25E-NBOMe as a series member. Documents epidemiology of use and acute toxicity pattern from reports in Europe, US, and elsewhere 2010-2015. 15563650.2015.1004179
Claim in history — inconclusiveinconclusiveworking →
NBOMe compounds appeared on the illicit drug market in the early 2010s, with online research chemical vendors offering the series from approximately 2010 onward. 25E-NBOMe was first analytically confirmed from seized blotter papers by Zuba and Sekulą in 2013, who characterized samples from the Polish drug market using GC-EI-MS, LC-ESI-QTOF-MS, FTIR, and NMRsupported
Online vendor availability since 2010. 7854_2016_64
NBOMe compounds appeared on the illicit drug market in the early 2010s, with online research chemical vendors offering the series from approximately 2010 onward. 25E-NBOMe was first analytically confirmed from seized blotter papers by Zuba and Sekulą in 2013, who characterized samples from the Polish drug market using GC-EI-MS, LC-ESI-QTOF-MS, FTIR, and NMRsupported
First analytical characterization of 25E-NBOMe, 25D-NBOMe, and 25G-NBOMe identified in seized blotter papers. GC-EI-MS, LC-ESI-QTOF-MS, FTIR, NMR used. dta.1397
Throughout this period, NBOMe compounds were commonly sold as LSD on blotter paper, exploiting their microgram-range potency and blotter-compatible form factorsupported
Both sold as/substituted for LSD. bkv058
neuroscience5 · 4 ok
Does the unique di-O-demethylation metabolic pathway identified by Grafinger et al. produce pharmacologically active or toxic metabolites?supported
Oxidative di-O-demethylation unique to 25E-NBOMe. dta.2446
Herian et al. found that 25I-NBOMe administration in rats increased extracellular dopamine, serotonin, and glutamate in the prefrontal cortex, with the head twitch response — the behavioral correlate of hallucinogenic activity — selectively correlated with increased extracellular glutamatesupported
25I-NBOMe increases extracellular DA, 5-HT, GLU in frontal cortex. Hallucinogenic activity (HTR) mediated via GLU increase through 5-HT2A receptors. s12640-019-00033-x
Kim et al. demonstrated that 25E-NBOMe modulates the mesolimbic dopamine system in rodents, reducing NAc dopamine levels while upregulating D1 receptors and dopamine transporters — a pattern consistent with compensatory plasticity following acute exposuresupported
NAc dopamine levels reduced after 25E-NBOMe. DAT and D1R expression enhanced. s12272-024-01491-4
Claim in neuroscience — inconclusiveinconclusiveworking →
Is the D1-dependent reinforcement pathway identified in rodents by Kim et al. clinically relevant to human abuse liability, or an artifact of the rodent behavioral paradigm?supported
25E-NBOMe induces conditioned place preference via D1DR signaling in NAc. D1DR blockade attenuated CPP. s12272-024-01491-4
pharmacokinetic-detail4 · 3 ok
N-oxidation — N-oxide and hydroxylamine metabolites identified for the first time for any NBOMe compoundsupported
First report of NBOMe N-oxide and hydroxylamine metabolites. dta.2446
Grafinger et al. conducted the definitive metabolism study using pooled human liver microsomes (pHLM) and the fungal model Cunninghamella eleganssupported
26 metabolites of 25E-NBOMe identified in pooled human liver microsomes. 11 in C. elegans. dta.2446
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
In 25B-NBOMe cases, O-desmethyl glucuronide and sulfonate conjugates have been detectedsupported
Phase II glucuronide and sulfonate detected in biofluids. molecules30224450
chemistry3 · 2 ok
The compound is derived from 2C-E (2,5-dimethoxy-4-ethylphenethylamine) by N-alkylation with a 2-methoxybenzyl group, a modification that markedly increases 5-HT₂A receptor affinity relative to the parent 2C compoundsupported
NBOMes higher 5-HT2A affinity than 2C counterparts but weaker in functional assays. j.neuropharm.2018.02.033
Dominant GC-EI-MS fragment ions appear at m/z 150, 121, and 91 — ions shared with 25D-NBOMe and 25G-NBOMe, necessitating LC-MS/MS or NMR for definitive identification.supported
Dominant GC-MS ions at m/z 150, 121, 91. dta.1397
Claim in chemistry — inconclusiveinconclusiveworking →
clinical-evidence1 · 1 ok
The sole published experimental study directly investigating 25E-NBOMe pharmacology is the rodent behavioral study by Kim et al., which examined conditioned place preference, self-administration, and head twitch responsesupported
25E-NBOMe induces conditioned place preference via D1DR signaling. Head twitch response mediated by 5-HT2A receptor activity. First direct psychopharmacological study of 25E-NBOMe. s12272-024-01491-4