generation run 2026-05-08
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15 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | OpenAlex | 25I-NBOH psychedelic phenethylamine | 10 | 5 | High-citation landmark papers relevant to 25I-NBOH class pharmacology |
| 2 | PubMed | 25I-NBOH pharmacology serotonin receptor | 5 | 5 | All directly relevant to 25I-NBOH pharmacology, metabolism, and toxicology |
| 3 | ClinicalTrials.gov · absence | 25I-NBOH NBOH psychedelic | 0 | — | No registered clinical trials; substance used only as research tool in preclinical studies |
| 4 | PubMed | 25I-NBOMe rhabdomyolysis seizure NBOMe toxicity | 1 | 1 | Definitive review of NBOMe class toxicology; applicable to NBOH analog |
| 5 | PubChem | 25I-NBOH | 1 | 1 | Sole PubChem entry for 25I-NBOH; confirms chemical identity and corrects seed data gaps |
| 6 | PubMed | 25I-NBOH blotter paper Brazil seized identification | 1 | 1 | First seizure report for 25I-NBOH specifically; critical for history and dose information |
| 7 | PubMed | Braden 2006 N-benzyl phenethylamine 5-HT2A receptor | 1 | 1 | Discovery/foundational paper for NBOMe/NBOH class |
| 8 | PubMed | 25I-NBOMe fatality death intoxication | 4 | 4 | Fatal cases involving structural analog 25I-NBOMe; directly informs NBOH risk profile |
| 9 | Erowid NBOMe Law page | 25I-NBOH legal status schedule | 1 | — | Only available source for jurisdiction-specific 25I-NBOH legal status |
| 10 | PubMed | NBOH compounds binding affinity 5-HT2A | 3 | 2 | SAR and pharmacological context for NBOH scaffold |
| 11 | DEA press release / Federal Register · absence | DEA scheduling NBOMe NBOH synthetic phenethylamine | 0 | — | Unable to access directly; using secondary source information |
| 12 | Erowid NBOMe Law page | 25I-NBOH legal status jurisdiction schedule | 1 | — | Best available source for jurisdiction-specific 25I-NBOH legal status; noted as incomplete |
| 13 | PubMed | tramadol serotonin syndrome mechanism opioid serotonergic | 6 | 2 | Mechanistic basis for 25I-NBOH + tramadol dangerous interaction |
| 14 | OpenAlex | NBOMe NBOH NBF 2C-I serotonin 5-HT2A binding comparison structure activity | 10 | 3 | Additional NBOH pharmacology, analytical, and preclinical characterization data |
| 15 | PsychonautWiki | 25I-NBOH dose legal history chemistry | 1 | — | Confirms seed dose data; no additional information beyond other sources |
78 claims by section — every cited sentence, checked against its source
safety23 · 16 ok
Kamiński et al. (2021) documented 51 non-fatal intoxications and 21 deaths in Europe attributable to 25I-NBOMesupported
51 non-fatal intoxications, 21 deaths in Europe. bkaa022
Postmortem data from 25I-NBOMe fatalities include peripheral blood concentrations of 405 pg/mL with brain concentrations of 2.54 ng/g in a 19-year-old, antemortem blood levels of 0.76 ng/mL in a 15-year-old who died of multi-system organ failure after combined 25I-NBOMe and psilocybin use, and postmortem heart blood concentrations of 19.8 ng/mL in two teenage male fatalities.supported
19-year-old man fatal intoxication. Peripheral blood 405 pg/mL, brain 2.54 ng/g. j.forsciint.2013.10.015
Postmortem data from 25I-NBOMe fatalities include peripheral blood concentrations of 405 pg/mL with brain concentrations of 2.54 ng/g in a 19-year-old, antemortem blood levels of 0.76 ng/mL in a 15-year-old who died of multi-system organ failure after combined 25I-NBOMe and psilocybin use, and postmortem heart blood concentrations of 19.8 ng/mL in two teenage male fatalities.supported
15-year-old male died of multi-system organ failure following 25I-NBOMe + psilocybin. Antemortem blood: 0.76 ng/mL 25I-NBOMe. bkv092
Postmortem data from 25I-NBOMe fatalities include peripheral blood concentrations of 405 pg/mL with brain concentrations of 2.54 ng/g in a 19-year-old, antemortem blood levels of 0.76 ng/mL in a 15-year-old who died of multi-system organ failure after combined 25I-NBOMe and psilocybin use, and postmortem heart blood concentrations of 19.8 ng/mL in two teenage male fatalities.supported
Two teenage male deaths. 25I-NBOMe detected in postmortem heart blood at 19.8 ng/mL. bkv058
The toxidrome associated with severe N-benzylphenethylamine intoxication includes rhabdomyolysis — a relatively common complication linked mechanistically to seizure activity, hyperthermia, and vasoconstriction — along with disseminated intravascular coagulation (DIC), metabolic acidosis, hypoglycemia, acute kidney injury, and multiorgan failurepartially supported
Rhabdomyolysis common complication linked to seizures, hyperthermia, vasoconstriction. 7854_2016_64
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Bilel et al. (2025) demonstrated that 25I-NBOMe in mice disrupts prepulse inhibition, increases dopamine release in the nucleus accumbens shell, and prevents long-term potentiation (LTP) in the medial prefrontal cortex — with the LTP blockade not reversed by the selective 5-HT₂A antagonist MDL100907supported
25I-NBOMe affects DA transmission in NAc shell; disrupts PPI; prevents LTP in mPFC (not reversed by MDL100907). ijms26062815
25I-NBOH's thermal lability causes systematic misidentification as 2C-I in forensic laboratories relying on GC-MSsupported
Thermolabile - fragments to 2C-I under GC. s11419-017-0357-x
25I-NBOH's thermal lability causes systematic misidentification as 2C-I in forensic laboratories relying on GC-MSsupported
NBOH compounds are thermolabile and degrade to their 2C counterparts under GC-MS analysis. dta.3648
Conversely, products sold as 25I-NBOH may contain other substances: Pelletier et al. (2024) documented a case in which powder labeled as "25I-NBOH" contained 25E-NBOH and the synthetic cathinone MDPHP, with 25I-NBOH absent from the sample.supported
Case of serotonin syndrome and loss of consciousness in 23-year-old after powder labelled as 25I-NBOH (actual: 25E-NBOH + MDPHP). s00414-023-03151-6
The only published human case involving a product labeled as 25I-NBOH resulted in serotonin syndrome and loss of consciousness — toxicological analysis confirmed 25E-NBOH (2.3 ng/mL plasma) and MDPHP (3.4 ng/mL plasma) as the causative agents.partially supported
Case of serotonin syndrome and loss of consciousness in 23-year-old after powder labelled as 25I-NBOH (actual: 25E-NBOH + MDPHP). s00414-023-03151-6
Acute psychological distress, including panic attacks and overwhelming fear, is documented in clinical intoxication presentations involving structurally related compoundssupported
Analytically confirmed 25I-NBOMe intoxication; documents adverse effects in clinical setting. 15563650.2017.1319572
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Tramadol carries dual risk: it inhibits the serotonin reuptake transporter (SERT), potentiating serotonergic toxicity when combined with a 5-HT₂A agonist, and independently lowers the seizure threshold — compounding the seizure risk associated with high-dose N-benzylphenethylamine usepartially supported
Tramadol inhibits SERT (serotonin reuptake inhibitor), increasing intrasynaptic serotonin. Combined with 5-HT2A agonists, can precipitate serotonin syndrome. s00204-018-2244-6
Claim in safety — inconclusiveinconclusiveworking →
The FDA issued a Drug Safety Communication in March 2016 specifically warning about opioid-serotonin toxicity interactionssupported
FDA 2016 warning on opioid-serotonin toxicity. s00204-018-2244-6
Because 25I-NBOH is primarily metabolized by CYP2D6, co-administration with strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) may substantially increase drug exposurepartially supported
Major CYP enzymes for 25I-NBOH: CYP2D6 (primary). dta.2031
Claim in safety — inconclusiveinconclusiveworking →
Seizures are a documented complication of severe N-benzylphenethylamine intoxication, and any pre-existing reduction in seizure threshold substantially increases this risk.supported
Rhabdomyolysis common complication linked to seizures, hyperthermia, vasoconstriction. 7854_2016_64
Claim in safety — inconclusiveinconclusiveworking →
Individuals with non-functional CYP2D6 alleles may experience substantially elevated and prolonged drug exposure.supported
CYP2D6 polymorphism may be partly offset by direct glucuronidation. dta.2031
pharmacology14 · 12 ok
Activity at 5-HT₂B is markedly lower in affinity, potency, and efficacy, while 5-HT₁A demonstrates minimal agonist activitypartially supported
Low efficacy at 5-HT1A. j.bcp.2018.09.024
Functional potency at 5-HT₂A falls in the subnanomolar to low nanomolar range in inositol-phosphate accumulation assays, comparable to LSDsupported
Subnanomolar to low nanomolar potency in functional assays comparable to LSD. j.bcp.2018.09.024
At 5-HT₂C, affinity and efficacy are similarly high, comparable to both LSD and serotonin itselfpartially supported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency in functional assays comparable to LSD. j.bcp.2018.09.024
Binding at monoamine transporters (DAT, SERT, NET) occurs only at low to mid-micromolar concentrations, consistent with negligible psychostimulant contribution.supported
Low-to-mid micromolar at monoamine transporters. Consistent with hallucinogenic activity, little psychostimulant activity. j.bcp.2018.09.024
Wallach et al. (2023) demonstrated across a large panel of 5-HT₂A agonists that Gq efficacy — not β-arrestin2 recruitment — correlates with psychedelic potential as measured by the mouse head-twitch response (HTR); β-arrestin-biased agonists at 5-HT₂A block rather than produce psychedelic effects. 25I-NBOH also recruits β-arrestin2 at the 5-HT₂A receptor, though the quantitative Gq-versus-β-arrestin2 bias has not been characterized as precisely as for the closely related tool compound 25CN-NBOH.supported
5-HT2A-Gq efficacy (not beta-arrestin2) predicts psychedelic potential. Beta-arrestin-biased ligands block psychedelic effects. s41467-023-44016-1
Claim in pharmacology — inconclusiveinconclusiveworking →
Wallach et al. (2023) demonstrated across a large panel of 5-HT₂A agonists that Gq efficacy — not β-arrestin2 recruitment — correlates with psychedelic potential as measured by the mouse head-twitch response (HTR); β-arrestin-biased agonists at 5-HT₂A block rather than produce psychedelic effects. 25I-NBOH also recruits β-arrestin2 at the 5-HT₂A receptor, though the quantitative Gq-versus-β-arrestin2 bias has not been characterized as precisely as for the closely related tool compound 25CN-NBOH.supported
Biased agonism analysis of phenylalkylamine 5-HT2A agonists including NBOH series compounds; beta-arrestin2 vs miniGaq recruitment characterized for multiple compounds. acschemneuro.3c00267
Claim in pharmacology — inconclusiveinconclusiveworking →
Wallach et al. (2023) demonstrated across a large panel of 5-HT₂A agonists that Gq efficacy — not β-arrestin2 recruitment — correlates with psychedelic potential as measured by the mouse head-twitch response (HTR); β-arrestin-biased agonists at 5-HT₂A block rather than produce psychedelic effects. 25I-NBOH also recruits β-arrestin2 at the 5-HT₂A receptor, though the quantitative Gq-versus-β-arrestin2 bias has not been characterized as precisely as for the closely related tool compound 25CN-NBOH.supported
Beta-arrestin2-biased 5-HT2AR agonists derived from 25CN-NBOH scaffold; biased agonism of NBOH series characterized. acs.jmedchem.2c00702
Removal of either the 2- or 5-methoxy group markedly reduces HTR activity in mice — more than would be predicted from in vitro receptor binding data — indicating these groups contribute to receptor signaling efficacy beyond simple binding affinity.supported
2,5-dimethoxy motif important for in vivo potency of phenethylamine 5-HT2AR agonists; elimination of 2- or 5-methoxy group reduces binding and HTR activity more than expected from in vitro data. acschemneuro.0c00129
Nielsen et al. (2017) established that CYP2D6 is the primary cytochrome P450 enzyme responsible for 25I-NBOH metabolism — a notable distinction from 25I-NBOMe, which is primarily metabolized by CYP3A4partially supported
Major CYP enzymes for 25I-NBOH: CYP2D6 (primary). dta.2031
The intrinsic hepatic clearance (CLint) is 118.7 mL/min/kg, approximately 1.7-fold higher than that of 25I-NBOMe (70.1 mL/min/kg).partially supported
CLint 118.7 mL/min/kg. dta.2031
Metabolic pathways include hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, and combinations thereof, along with direct glucuronidation as a phase II conjugation pathwaysupported
Biotransformations: hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, direct glucuronidation. dta.2031
The CYP2D6 dependence carries clinical implications: strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) may substantially increase 25I-NBOH plasma levels, and CYP2D6 poor metabolizers may experience elevated and prolonged exposure.partially supported
Major CYP enzymes for 25I-NBOH: CYP2D6 (primary). CYP2D6 polymorphism may be partly offset by direct glucuronidation. dta.2031
summary8 · 8 ok
It functions as a full agonist at the 5-HT₂A receptor with subnanomolar to low nanomolar functional potency comparable to LSD, producing effects lasting 5–8 hours via sublingual administration — the only documented route.partially supported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency in functional assays comparable to LSD. j.bcp.2018.09.024
The N-benzyl phenethylamine scaffold was first characterized by Braden, Parrish, Naylor, and Nichols at Purdue University in 2006, when the addition of an N-arylmethyl group to 2C-class phenethylamines was shown to increase 5-HT₂A binding affinity by up to 300-fold. 25I-NBOH — the ortho-hydroxybenzyl analog of 25I-NBOMe — appeared on research chemical markets between approximately 2010 and 2015 and was first identified in seized blotter papers from Brazil in 2017supported
First characterization of N-benzyl phenethylamines as 5-HT2A agonists. N-arylmethyl substitution increases affinity up to 300-fold over N-alkyl homologs. pmid:17000863
The N-benzyl phenethylamine scaffold was first characterized by Braden, Parrish, Naylor, and Nichols at Purdue University in 2006, when the addition of an N-arylmethyl group to 2C-class phenethylamines was shown to increase 5-HT₂A binding affinity by up to 300-fold. 25I-NBOH — the ortho-hydroxybenzyl analog of 25I-NBOMe — appeared on research chemical markets between approximately 2010 and 2015 and was first identified in seized blotter papers from Brazil in 2017supported
First scientific report of 25I-NBOH identified in actual seizures (Brazil). s11419-017-0357-x
25I-NBOH exerts its psychedelic effects through Gq-protein-coupled signaling at cortical 5-HT₂A receptors, where Gq efficacy — not β-arrestin2 recruitment — correlates with psychedelic potentialsupported
5-HT2A-Gq efficacy (not beta-arrestin2) predicts psychedelic potential. Beta-arrestin-biased ligands block psychedelic effects. s41467-023-44016-1
It demonstrates full efficacy at both 5-HT₂A and 5-HT₂C with negligible activity at monoamine transporterssupported
Full efficacy at 5-HT2A/2C; Low-to-mid micromolar at monoamine transporters. Consistent with hallucinogenic activity, little psychostimulant activity. j.bcp.2018.09.024
Hepatic metabolism proceeds primarily through CYP2D6, with an intrinsic clearance of 118.7 mL/min/kg — substantially higher than its NBOMe counterpart.partially supported
Major CYP enzymes for 25I-NBOH: CYP2D6 (primary). CLint 118.7 mL/min/kg. dta.2031
The mouse head-twitch response — the canonical behavioral proxy for psychedelic potential — correlates strongly with human hallucinogenic potency across 36 compounds (r = 0.9448), and 25I-NBOH reliably induces this responsepartially supported
Strong correlation (r=0.9448) between mouse HTR potency and human hallucinogenic potency. j.neuropharm.2019.107933
The acute risk profile is inferred from 25I-NBOMe, whose class has been linked to 21 deaths and 51 non-fatal intoxications in Europesupported
51 non-fatal intoxications, 21 deaths in Europe. bkaa022
comparative-pharmacology7 · 7 ok
No classical psychedelic has accumulated a comparable fatality record: 25I-NBOMe alone accounts for 21 deaths in Europe, whereas published fatality data attributable solely to LSD or psilocybin are essentially absent.partially supported
51 non-fatal intoxications, 21 deaths in Europe. bkaa022
Both compounds demonstrate ultra-high 5-HT₂A affinity and full agonist efficacy.supported
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency in functional assays comparable to LSD. j.bcp.2018.09.024
The metabolic divergence — CYP2D6 versus CYP3A4 — is the most pharmacologically consequential distinction between the two compoundssupported
Major CYP enzymes for 25I-NBOH: CYP2D6 (primary). CLint 118.7 mL/min/kg. dta.2031
Both compounds are thermolabile and degrade to 2C-I under GC conditions, though the NBOH series has been characterized as somewhat more prone to this degradation in some analytical studies.partially supported
NBOH compounds are thermolabile and degrade to their 2C counterparts under GC-MS analysis. dta.3648
Within the NBOH series, the cyano analog 25CN-NBOH has been developed as the most selective 5-HT₂A agonist tool compound, with superior receptor selectivity for 5-HT₂A over 5-HT₂C compared to 25I-NBOH. 25CN-NBOH has been the scaffold of choice for biased agonism studies and electrophysiological investigations of 5-HT₂A-mediated cortical effectssupported
25CN-NBOH KD ~1 nM at 5-HT2AR with selectivity over 5-HT2B/2C. j.bcp.2020.113979
Within the NBOH series, the cyano analog 25CN-NBOH has been developed as the most selective 5-HT₂A agonist tool compound, with superior receptor selectivity for 5-HT₂A over 5-HT₂C compared to 25I-NBOH. 25CN-NBOH has been the scaffold of choice for biased agonism studies and electrophysiological investigations of 5-HT₂A-mediated cortical effectssupported
Beta-arrestin2-biased 5-HT2AR agonists derived from 25CN-NBOH scaffold; biased agonism of NBOH series characterized. acs.jmedchem.2c00702
Compared to classical serotonergic psychedelics (LSD, psilocybin, mescaline), the N-benzylphenethylamine compounds including 25I-NBOH demonstrate substantially higher binding affinity at 5-HT₂A — achieving subnanomolar potency where classical tryptamines typically bind in the low-to-high nanomolar rangepartially supported
Subnanomolar to low nanomolar potency in functional assays comparable to LSD. j.bcp.2018.09.024
history6 · 6 ok
The study revealed a critical analytical complication: 25I-NBOH is thermolabile and fragments to its parent phenethylamine 2C-I under standard gas chromatography conditions, indicating the compound was likely present in earlier seizures but systematically misidentified.supported
NBOH compounds are thermolabile and degrade to their 2C counterparts under GC-MS analysis. dta.3648
The structural foundation for 25I-NBOH was established in 2006, when Braden, Parrish, Naylor, and Nichols at Purdue University published the first systematic characterization of N-benzyl phenethylamine agonists at the 5-HT₂A receptorsupported
First characterization of N-benzyl phenethylamines as 5-HT2A agonists. Foundational SAR paper for NBOMe/NBOH class. pmid:17000863
Subsequent structure-activity work confirmed that ortho substitution on the benzyl ring (the hydroxyl group in NBOH, the methoxy group in NBOMe) further enhances this affinity, while para substitution diminishes it.supported
Ortho or meta substitution on benzyl enhances affinity; para substitution reduces affinity. cn500292d
The study revealed a critical analytical complication: 25I-NBOH is thermolabile and fragments to its parent phenethylamine 2C-I under standard gas chromatography conditions, indicating the compound was likely present in earlier seizures but systematically misidentified.supported
Thermolabile - fragments to 2C-I under GC. s11419-017-0357-x
Brazil added the compound to its controlled substances list around the same periodsupported
Not scheduled by UNODC; only Sweden and Brazil controlled it at time of publication. s11419-017-0357-x
The publication of Eshleman et al.'s neurochemical pharmacology data in 2018 and Nielsen et al.'s metabolism study in 2017 established the first formal pharmacological characterization of the compound, transitioning it from an analytically identified market substance to a scientifically profiled tool compound.supported
25I-NBOH among compounds studied. Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency in functional assays comparable to LSD. j.bcp.2018.09.024
neuroscience5 · 5 ok
Preclinical data from the structural analog 25I-NBOMe reveal disruption of prepulse inhibition (an index of sensorimotor gating), increased dopamine release in the nucleus accumbens shell (at 1 mg/kg i.p.), and prevention of long-term potentiation (LTP) in the medial prefrontal cortexsupported
25I-NBOMe affects DA transmission in NAc shell; disrupts PPI; prevents LTP in mPFC (not reversed by MDL100907). ijms26062815
Electrophysiological studies using the close analog 25CN-NBOH in mouse medial prefrontal cortex reveal a dual cellular action: acute increases in spontaneous excitatory postsynaptic current (sEPSC) frequency via 5-HT₂A receptor activation, alongside paradoxical suppression of neuronal firing rate through M-current (Kv7) channels — a mechanism independent of 5-HT₂Asupported
25CN-NBOH increases sEPSC frequency via 5-HT2AR in mPFC pyramidal neurons; paradoxically suppresses firing rate via M-current channels (independent of 5-HT2AR). syn.70014
Nicotine pretreatment attenuates the head-twitch response and associated Phase 2 EEG waveform while prolonging behavioral arrest, indicating nicotinic cholinergic modulation of 5-HT₂A-mediated cortical processing.partially supported
Nicotine attenuates HTR and Phase 2 waveforms. s41598-021-81552-6
The dual excitatory-inhibitory cellular action observed with 25CN-NBOH maps onto this framework: simultaneous cortical excitation (increased sEPSCs) and firing-rate suppression (M-current activation) could represent the cellular substrate of "relaxed" cortical hierarchies.supported
Dual excitatory/inhibitory cellular actions. syn.70014
The LTP-blocking effect of 25I-NBOMe not reversed by 5-HT₂A antagonism — does 25I-NBOH share this off-target mechanism, and what receptor mediates it?supported
Prevents LTP in mPFC (not reversed by MDL100907). ijms26062815
receptor-pharmacology5 · 5 ok
Eshleman et al. (2018) provided the most comprehensive receptor-level pharmacological characterization of 25I-NBOH, profiling the compound across serotonin receptor subtypes and monoamine transporters.supported
25I-NBOH among compounds studied. Full efficacy at 5-HT2A/2C; Low efficacy at 5-HT1A. Low-to-mid micromolar at monoamine transporters. j.bcp.2018.09.024
The ultra-high 5-HT₂A affinity of the NBOH scaffold reflects the molecular interaction first elucidated by Braden et al. (2006), in which the N-benzyl moiety engages receptor residue Phe339⁽⁶·⁵¹⁾ within the 5-HT₂A orthosteric binding pocket. Ortho substitution on the benzyl ring — the hydroxyl group in NBOH, the methoxy group in NBOMe — further enhances this interaction, while para substitution diminishes it.supported
Ortho or meta substitution on benzyl enhances affinity; para substitution reduces affinity. cn500292d
25I-NBOH activates both Gq-protein and β-arrestin2 signaling pathways at the 5-HT₂A receptorsupported
Biased agonism analysis of phenylalkylamine 5-HT2A agonists including NBOH series compounds; beta-arrestin2 vs miniGaq recruitment characterized for multiple compounds. acschemneuro.3c00267
The Gq-versus-β-arrestin2 bias of 25I-NBOH has not been quantitatively characterized to the same degree as the closely related cyano analog 25CN-NBOH, which serves as the primary NBOH scaffold tool compound in biased agonism studiessupported
25CN-NBOH KD ~1 nM at 5-HT2AR with selectivity over 5-HT2B/2C. NBOH scaffold SAR; ortho-OH vs ortho-OMe key for selectivity. j.bcp.2020.113979
Poulie et al. (2022) used 25CN-NBOH as a starting scaffold for designing β-arrestin-biased 5-HT₂A agonists, demonstrating that modifications to the NBOH benzyl group can shift the signaling balance between pathways.supported
Beta-arrestin2-biased 5-HT2AR agonists derived from 25CN-NBOH scaffold; biased agonism of NBOH series characterized. acs.jmedchem.2c00702
chemistry4 · 4 ok
The defining structural modification of the NBOH series is the addition of a 2-hydroxybenzyl (ortho-phenol) group to the amine nitrogen of the 2C backbone — a change that increases 5-HT₂A receptor binding affinity by up to 300-fold relative to the unsubstituted phenethylamine.supported
N-arylmethyl substitution increases affinity up to 300-fold over N-alkyl homologs. pmid:17000863
The 2,5-dimethoxy substitution pattern is essential for full in vivo psychedelic potency: removal of either methoxy group markedly reduces head-twitch response activity in mice to a degree exceeding what in vitro binding data predict.supported
Elimination of 2- or 5-methoxy group reduces binding and HTR activity more than expected from in vitro data. acschemneuro.0c00129
The defining physical characteristic relevant to both forensic science and harm reduction is thermal lability. 25I-NBOH degrades to its parent phenethylamine 2C-I under standard gas chromatography (GC) conditions, resulting in systematic misidentification in forensic laboratories relying on routine GC-MS screeningsupported
Non-thermal method prevents misidentification due to NBOH thermal lability. j.forsciint.2019.05.036
Reliable analytical identification requires liquid chromatography methods (LC-MS/MS or HPLC-HRMS) or chemical derivatization with trifluoroacetic anhydride prior to GC-MS.supported
Trifluoroacetyl derivatization or HPLC-HRMS needed for reliable identification. dta.3648
clinical-evidence3 · 2 ok
The only published human case involving a product labeled as 25I-NBOH resulted in serotonin syndrome and loss of consciousness, but toxicological analysis confirmed the active substances were 25E-NBOH (2.3 ng/mL plasma) and MDPHP (3.4 ng/mL plasma) — 25I-NBOH was absent from the samplepartially supported
Case of serotonin syndrome and loss of consciousness in 23-year-old after powder labelled as 25I-NBOH (actual: 25E-NBOH + MDPHP). s00414-023-03151-6
25I-NBOH appears in published preclinical studies as a selective 5-HT₂A/₂C receptor agonist tool compound — for example, as a positive control in head-twitch response assays and in microglial neuroimmune studies assessing the anti-inflammatory properties of 5-HT₂ receptor activationsupported
25I-NBOH used as selective 5-HT2AR agonist in mice. Behavioral arrest precedes HTR. s41598-021-81552-6
Claim in clinical-evidence — inconclusiveinconclusiveworking →
pharmacokinetic-detail2 · 2 ok
All pharmacokinetic data for 25I-NBOH derive from in vitro studies; no human pharmacokinetic parameters have been published.supported
Major CYP enzymes for 25I-NBOH: CYP2D6 (primary). CLint 118.7 mL/min/kg. Biotransformations: hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, direct glucuronidation. dta.2031
Direct glucuronidation (a CYP-independent phase II pathway) may partially compensate for reduced CYP2D6 activity, attenuating the magnitude of the pharmacogenomic effectsupported
CYP2D6 polymorphism may be partly offset by direct glucuronidation. dta.2031
legal-status1 · 1 ok
As of 2017, 25I-NBOH was not subject to control under United Nations international drug conventionssupported
Not scheduled by UNODC; only Sweden and Brazil controlled it at time of publication. s11419-017-0357-x