25B-NBOH

Claim in safety — inconclusiveinconclusiveworking →

Multiple fatalities have been attributed to the broader NBOMe/NBOH class, and Xiang et al. (2024) reference "several poisoning cases and even fatal cases" involving 25B-NBOHsupported

Cases of non-fatal and lethal intoxication. fnins.2020.00078

Claim in safety — inconclusiveinconclusiveworking →

The Ivory et al. (2022) poisoning cluster in Australia documents clinical toxicity — hallucinations, mydriasis, tachycardia, hypertension, agitation — from 25B-NBOH sold as LSD, but whether any cases were fatal cannot be determined from the available abstract.supported

First published report documenting clinical toxicity of NBOH derivatives. Cluster of poisonings from powder sold as LSD. 15563650.2022.2053150

Yoon et al. (2022) demonstrated that 25I-NBOH and 25C-NBOH (structural analogs) decrease viability of H9c2 cardiomyocytes on MTT assay, increase QT and RR intervals in rat ECG, and — in the case of 25I-NBOH — inhibit hERG potassium channels and downregulate PAK1 protein in cardiomyocytessupported

25I-NBOH and 25C-NBOH: decreased viability of H9c2 cardiomyocytes (MTT assay), increased QT and RR intervals in rat ECG, 25I-NBOH downregulated PAK1 protein, 25I-NBOH inhibited hERG potassium channels. j.toxlet.2021.11.016

Claim in safety — inconclusiveinconclusiveworking →

Seizures are a recognized complication of NBOMe/NBOH class toxicitysupported

Rhabdomyolysis is common in severe toxicity, linked to seizures, hyperthermia, vasoconstriction. 7854_2016_64

Claim in safety — inconclusiveinconclusiveworking →

Rhabdomyolysis has been documented in severe NBOMe poisoning cases, secondary to seizures, hyperthermia, and vasoconstrictionsupported

Rhabdomyolysis is common in severe toxicity, linked to seizures, hyperthermia, vasoconstriction. 7854_2016_64

Pelletier et al. (2024) documented serotonin syndrome in a case involving 25E-NBOH (structural analog) combined with MDPHPsupported

23-year-old male with serotonergic syndrome and loss of consciousness after consuming powder labeled as 25I-NBOH; actually contained 25E-NBOH + MDPHP. s00414-023-03151-6

Claim in safety — not_supportednot supportedworking →

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Seizure disorders. The NBOMe/NBOH class is associated with seizuressupported

Rhabdomyolysis is common in severe toxicity, linked to seizures, hyperthermia, vasoconstriction. 7854_2016_64

25B-NBOH's thermolability under GC conditions — degrading to 2C-B — means that clinical and forensic samples may be misidentified unless LC-MS/MS is employedsupported

Non-thermal method avoids thermal degradation misidentification. j.forsciint.2019.05.036

Recommended urinary biomarkers are metabolites B2-1, B2-2, and B6supported

Major metabolites for 25B-NBOH: B2-1 (56.61%), B2-2 (17.43%) and B6 (17.78%). j.jpba.2024.116020

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

De la Fuente Revenga et al. (2022) demonstrated that tolerance to 5-HT₂A agonist head-twitch response can develop after a single dose, mediated by receptor downregulation in the frontal cortex through a β-arrestin 2-independent mechanismsupported

Tolerance after single dose. DOI caused 5-HT2AR downregulation in frontal cortex. Mechanism independent of beta-arrestin-2. acschemneuro.2c00170

Eshleman et al. (2018) confirmed that NBOH compounds have low to mid-micromolar affinities at monoamine transporters (DAT, SERT, NET), indicating no significant dopaminergic reward pathway engagement at pharmacologically relevant dosessupported

Low micromolar potency at monoamine transporters. Results consistent with hallucinogenic activity, minimal psychostimulant activity. j.bcp.2018.09.024

The Pelletier et al. (2024) case of serotonin syndrome with 25E-NBOH + MDPHP provides the closest published clinical precedent for NBOH serotonin syndrome.supported

23-year-old male with serotonergic syndrome and loss of consciousness after consuming 25E-NBOH + MDPHP. Literature review of NBOH human exposure cases. s00414-023-03151-6

Prospective survey data from Barbut Siva et al. (2024) demonstrate reduced acute effects in SSRI users taking psychedelicssupported

SRI use during psychedelic experience associated with reduced acute subjective effects but similar post-experience improvements in well-being and depressive symptoms. 02698811231224217

CYP2D6 inhibitors. By analogy with 25I-NBOH (where CYP2D6 is the primary metabolic enzyme), pharmacokinetic interactions with CYP2D6 inhibitors — including paroxetine, fluoxetine, bupropion, and quinidine — may increase 25B-NBOH plasma concentrations and prolong exposure, elevating cardiovascular and neurological toxicity risksupported

Major CYP enzymes for 25I-NBOH: CYP2D6. Intrinsic clearance for 25I-NBOH: 118.7 mL/min/kg. dta.2031

Cannabis used concomitantly with psychedelics dose-dependently increases mystical experience, visual alterations, and ego dissolution scores while also increasing challenging experience scorespartially supported

Cannabis used concomitantly with psychedelics (n=321) associated with dose-dependent increases in mystical experience, visual alterations, and ego dissolution scores. Quadratic relationship for challenging experience. s00213-021-05999-1

Pre-existing cardiac conditions. hERG potassium channel inhibition and QT prolongation demonstrated for NBOH structural analogs make 25B-NBOH contraindicated in individuals with congenital or acquired long QT syndrome, structural heart disease, or concurrent use of QT-prolonging medications.supported

25I-NBOH inhibited hERG potassium channels. Increased QT and RR intervals in rat ECG. j.toxlet.2021.11.016

Claim in safety — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

The compound appeared in European forensic seizures around June 2016 and became a predominant hallucinogen on blotter papers in parts of Brazil through 2019partially supported

NBOH substances have become the main hallucinogenic drug in the region. Not under UN Conventions control as of 2019. s11419-019-00509-7

The published evidence base comprises one direct in vivo behavioral study, one clinical poisoning cluster, and in vitro binding and metabolism data.supported

25B-NBOH, 25C-NBOH, 25E-NBOH, and 25I-NBOH tested in mice (locomotor) and DOM-trained rats (discriminative stimulus). fbp.0000000000000802

The published evidence base comprises one direct in vivo behavioral study, one clinical poisoning cluster, and in vitro binding and metabolism data.supported

First published report documenting clinical toxicity of NBOH derivatives. Cluster of poisonings from powder sold as LSD. 15563650.2022.2053150

Claim in summary — inconclusiveinconclusiveworking →

In DOM-trained rats, 25B-NBOH fully substitutes for DOM's discriminative stimulus (≥80% drug-appropriate responding) with potency exceeding DOM and several NBOMe analogssupported

25B-NBOH, 25C-NBOH, and 25E-NBOH fully substituted for DOM (>=80%). Discriminative stimulus effects more potent than DOM and 25X-NBOMe compounds. fbp.0000000000000802

Monoamine transporter affinity is negligible at pharmacologically relevant concentrations.supported

Low micromolar potency at monoamine transporters. Results consistent with hallucinogenic activity, minimal psychostimulant activity. j.bcp.2018.09.024

Claim in summary — inconclusiveinconclusiveworking →

Structural analogs 25I-NBOH and 25C-NBOH inhibit hERG potassium channels and reduce cardiomyocyte viability in preclinical models, and multiple NBOMe/NBOH-class fatalities are documented, though no confirmed 25B-NBOH-specific death has been publishedsupported

25I-NBOH and 25C-NBOH: decreased viability of H9c2 cardiomyocytes (MTT assay), increased QT and RR intervals in rat ECG, 25I-NBOH downregulated PAK1 protein, 25I-NBOH inhibited hERG potassium channels. j.toxlet.2021.11.016

Structural analogs 25I-NBOH and 25C-NBOH inhibit hERG potassium channels and reduce cardiomyocyte viability in preclinical models, and multiple NBOMe/NBOH-class fatalities are documented, though no confirmed 25B-NBOH-specific death has been publishedsupported

Comprehensive review of NBOMe compounds including pharmacological properties, pattern of use, metabolism, desired effects, and cases of non-fatal and lethal intoxication. fnins.2020.00078

Claim in summary — inconclusiveinconclusiveworking →

The compound does not engage dopaminergic reward pathways and is not habit-formingsupported

Low micromolar potency at monoamine transporters. Results consistent with hallucinogenic activity, minimal psychostimulant activity. j.bcp.2018.09.024

Tolerance develops rapidly via 5-HT₂A receptor downregulation, with cross-tolerance across serotonergic psychedelicssupported

Repeated DOI induces progressive decrease in HTR; tolerance after single dose. Cross-tolerance between DOI and LSD. DOI caused 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170

The NBOMe class has a substantially more extensive toxicological record, with multiple confirmed fatalities documented in case reports and reviewssupported

Cases of non-fatal and lethal intoxication. fnins.2020.00078

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

The N-benzyl modification elevates 5-HT₂A affinity from moderate (2C-B) to low nanomolar (25B-NBOH, Ki ≈ 5 nM).supported

Examines how 5-HT2A/2C affinity is influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) derivatives. Includes compounds with N-(2-hydroxybenzyl) substitution (25B-NBOH). j.bmc.2014.12.011

Mallaroni et al. (2023) found that subjective effects of 2C-B (oral) largely resolve within 6 hourssupported

Duration of 2C-B largely resolved within 6 hours. cpt.2958

Metabolically, 2C-B is cleared by MAO-A, MAO-B, cytosolic enzymes, and CYP2D6, while 25B-NBOH's dominant CYP enzyme is inferred to be CYP2D6 based on 25I-NBOH datasupported

Key metabolic enzymes: MAO-A, MAO-B, cytosolic enzymes, CYP2D6. j.dmd.2025.100086

A significant pharmacokinetic divergence exists in CYP enzyme involvement. 25B-NBOMe metabolism is dominated by CYP1A2 and CYP3A4 (hydroxylation) and CYP2C9 and CYP2C19 (O-demethylation), whereas the NBOH series likely relies primarily on CYP2D6supported

CYP1A2/CYP3A4 involved in hydroxylation; CYP2C9/CYP2C19 in O-demethylation. j.jpba.2016.11.040

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

Both compounds are thermolabile under GC conditions, degrading to their shared parent phenethylamine 2C-B.supported

Non-thermal method avoids thermal degradation misidentification. Simultaneous identification of 25-NBOH compounds and their 2C counterparts. j.forsciint.2019.05.036

In contrast, 25B-NBOH may function as a partial agonist at 5-HT₂A based on the Hansen et al. (2015) observation of reduced efficacy in the bromo-substituted series.supported

Generally found to be less efficacious partial agonists vs. previously reported N-benzyl phenethylamines. j.bmc.2014.12.011

Yoon et al. (2022) demonstrated that 25I-NBOH inhibits hERG potassium channels, decreases cardiomyocyte viability, and prolongs QT and RR intervals in rat ECGsupported

25I-NBOH inhibited hERG potassium channels. Decreased viability of H9c2 cardiomyocytes (MTT assay). Increased QT and RR intervals in rat ECG. j.toxlet.2021.11.016

25B-NBOH is a potent agonist at serotonin 5-HT₂A and 5-HT₂C receptors, with psychoactive effects mediated primarily through 5-HT₂A activation — consistent with the broader N-benzylphenethylamine classsupported

Reviews NBOMe structure-activity relationships, behavioral pharmacology, metabolism, and toxicity. 7854_2016_64

25B-NBOH is a potent agonist at serotonin 5-HT₂A and 5-HT₂C receptors, with psychoactive effects mediated primarily through 5-HT₂A activation — consistent with the broader N-benzylphenethylamine classsupported

Ki values in low nanomolar range at 5-HT2A/2C with >1000-fold selectivity over 5-HT1A. fnins.2020.00078

Claim in pharmacology — inconclusiveinconclusiveworking →

The notably higher affinity at 5-HT₂C relative to 5-HT₂A is unusual within the class and may indicate partial agonism at 5-HT₂A, as the original study noted that compounds in this series "were generally found to be less efficacious agonists than previously reported N-benzyl phenethylamines".supported

Generally found to be less efficacious partial agonists vs. previously reported N-benzyl phenethylamines. j.bmc.2014.12.011

At the class level, NBOH compounds exhibit subnanomolar to low nanomolar functional potencies at 5-HT₂A and 5-HT₂C, comparable to LSDsupported

Full efficacy at 5-HT2A/2C with subnanomolar to low nanomolar potency. j.bcp.2018.09.024

Affinity at other targets is substantially lower: 5-HT₁A shows very low potency and low efficacy; 5-HT₂B shows reduced affinity relative to 5-HT₂A/₂C; and monoamine transporters (DAT, SERT, NET) bind only at low to mid-micromolar concentrations, indicating minimal psychostimulant contribution.supported

Low efficacy at 5-HT1A. Low micromolar potency at monoamine transporters. Results consistent with hallucinogenic activity, minimal psychostimulant activity. j.bcp.2018.09.024

Claim in pharmacology — inconclusiveinconclusiveworking →

Claim in pharmacology — inconclusiveinconclusiveworking →

Three metabolites — designated B2-1 (56.61% peak area ratio), B2-2 (17.43%), and B6 (17.78%) — were identified as recommended biomarkers for forensic detection.supported

Major metabolites for 25B-NBOH: B2-1 (56.61%), B2-2 (17.43%) and B6 (17.78%). j.jpba.2024.116020

Nielsen et al. (2017) identified CYP2D6 as the dominant enzyme for 25I-NBOH clearance (CLint = 118.7 mL/min/kg), with additional contributions from direct glucuronidation that may partially offset the impact of CYP2D6 genetic polymorphismsupported

Major CYP enzymes for 25I-NBOH: CYP2D6. Intrinsic clearance for 25I-NBOH: 118.7 mL/min/kg. 25I-NBOH also subject to direct glucuronidation, which may diminish impact of CYP2D6 genetic polymorphism. dta.2031

The parent compound 2C-B is metabolized by MAO-A, MAO-B, cytosolic enzymes, and CYP2D6, with primary metabolites that do not activate 5-HT₂A receptors.supported

Key metabolic enzymes: MAO-A, MAO-B, cytosolic enzymes, CYP2D6. Metabolites BDMPAA and B-2-HMPAA do not activate 5-HT2AR. j.dmd.2025.100086

The neural mechanisms described below are inferred from 25B-NBOH's confirmed 5-HT₂A agonism and from class-level neuroscience data for serotonergic psychedelics.supported

25B-NBOH fully substituted for DOM (>=80%). Discriminative stimulus effects more potent than DOM and 25X-NBOMe compounds. fbp.0000000000000802

Contreras et al. (2021) used 25I-NBOH as a selective 5-HT₂A agonist tool compound to characterize EEG and behavioral correlates of receptor activation, identifying behavioral arrest and a characteristic slow waveform as hallmark responses to selective 5-HT₂A engagementsupported

Behavioral arrest preceding HTR by precise interval; characteristic EEG waveforms (Phase 1: 3.5-4.5 Hz, Phase 2: 2.5-3.2 Hz). Suggests behavioral arrest and EEG waveforms are hallmarks of 5-HT2AR activation. s41598-021-81552-6

Xu et al. (2026) identified non-canonical Gi signaling through the 5-HT₂A receptor as essential for hallucinogenic effects, while Wallach et al. (2023) found that Gq efficacy predicts psychedelic potential in the head-twitch assaysupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response in mice. s41467-023-44016-1

Whether the compound's possible partial agonism at 5-HT₂A affects its neuroplastogenic potential relative to full agonists remains an open question.supported

Generally found to be less efficacious partial agonists vs. previously reported N-benzyl phenethylamines. j.bmc.2014.12.011

De la Fuente Revenga et al. (2022) demonstrated that tolerance to 5-HT₂A agonist head-twitch response can develop after a single dose, driven by receptor downregulation in the frontal cortex through a β-arrestin 2-independent mechanismsupported

Tolerance after single dose. DOI caused 5-HT2AR downregulation in frontal cortex. Mechanism independent of beta-arrestin-2. acschemneuro.2c00170

Claim in neuroscience — inconclusiveinconclusiveworking →

Nielsen et al. (2017) characterized 25I-NBOH metabolism and identified CYP2D6 as the dominant clearance enzyme with an intrinsic clearance (CLint) of 118.7 mL/min/kgsupported

Major CYP enzymes for 25I-NBOH: CYP2D6. Intrinsic clearance for 25I-NBOH: 118.7 mL/min/kg. dta.2031

The parent compound 2C-B, studied in humans at 30 mg oral by Thomann et al. (2025), is metabolized by MAO-A, MAO-B, cytosolic enzymes, and CYP2D6supported

First human plasma PK study of 2C-B (30 mg oral dose). Key metabolic enzymes: MAO-A, MAO-B, cytosolic enzymes, CYP2D6. j.dmd.2025.100086

Xiang et al. (2024) conducted the most comprehensive metabolism study for 25B-NBOH using human liver microsomes with UHPLC-Q-Exactive Orbitrap mass spectrometrysupported

Investigated phase I and II metabolism of 25B-NBOH in human liver microsomes. 70 metabolites total. UHPLC-Q-Exactive Orbitrap MS. j.jpba.2024.116020

Importantly, 25I-NBOH is also subject to direct glucuronidation — a phase II conjugation pathway that may partially offset the pharmacogenomic impact of CYP2D6 polymorphism by providing an alternative elimination route.supported

25I-NBOH also subject to direct glucuronidation, which may diminish impact of CYP2D6 genetic polymorphism. dta.2031

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

The foundational structure-activity work establishing the NBOH scaffold was published in 2014 by Hansen and colleagues at the University of Copenhagen, who synthesized a series of 48 N-benzyl phenethylamine derivatives and demonstrated that N-benzyl substitution of 2,5-dimethoxy-substituted phenethylamines dramatically increased 5-HT₂A binding affinitysupported

48-compound SAR study using 2C-B phenethylamine scaffold. N-benzyl substitution produces dramatic increase in binding affinity and functional activity at 5-HT2A receptor. cn400216u

The specific pharmacological characterization of 25B-NBOH — employing the 4-bromo-2,5-dimethoxyphenethylamine backbone with an ortho-hydroxybenzyl N-substituent — followed in 2015.supported

Examines how 5-HT2A/2C affinity is influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) derivatives. Includes compounds with N-(2-hydroxybenzyl) substitution (25B-NBOH). j.bmc.2014.12.011

The same Brazilian forensic team subsequently identified 25B-NBOH in seized blotter papers between 2017 and 2018, alongside 25C-NBOH and 25E-NBOHsupported

First forensic identification and detailed characterization of 25B-NBOH, 25C-NBOH, and 25E-NBOH in seized blotter papers (Brazil, 2017-2018). s11419-019-00509-7

A significant public health event occurred in Australia in 2022, when a cluster of 25B-NBOH poisonings resulted from powder sold as LSD, underscoring the compound's role as an adulterant and the critical importance of drug checking services.supported

Cluster of poisonings from powder sold as LSD. 15563650.2022.2053150

Compound-specific binding data for 25B-NBOH derive from Hansen et al. (2015), who characterized a series of N-benzyl substituted 4-bromo-2,5-dimethoxyphenethylamines:supported

Examines how 5-HT2A/2C affinity is influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) derivatives. Includes compounds with N-(2-hydroxybenzyl) substitution (25B-NBOH). j.bmc.2014.12.011

Hansen et al. noted that compounds in this series were generally less efficacious agonists than previously characterized N-benzyl phenethylamines, raising the possibility that 25B-NBOH functions as a partial agonist at 5-HT₂Asupported

Generally found to be less efficacious partial agonists vs. previously reported N-benzyl phenethylamines. j.bmc.2014.12.011

Wallach et al. (2023) identified 5-HT₂A–Gq efficacy — rather than β-arrestin2 recruitment — as the primary predictor of psychedelic potential as measured by head-twitch response in micesupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response in mice. s41467-023-44016-1

Pottie et al. (2020) showed that NBOH compounds — specifically 25H-NBOH and structurally related analogs — exhibit statistically significant β-arrestin 2 preference over miniGαq relative to LSDsupported

25H-NBOH shows statistically significant β-arrestin 2 bias over miniGαq at 5-HT2AR compared to LSD. j.bcp.2020.114251

This N-benzyl substitution converts the moderate-potency parent phenethylamine into a high-potency 5-HT₂A receptor agonist active in the microgram rangesupported

N-benzyl substitution produces dramatic increase in binding affinity and functional activity at 5-HT2A receptor. Highest affinity at 0.29 nM. cn400216u

A critical analytical property is thermolability: 25B-NBOH degrades to its parent phenethylamine 2C-B under standard gas chromatography conditionssupported

Non-thermal method avoids thermal degradation misidentification. LC-MS/MS method for simultaneous identification of 25-NBOH compounds including 25B-NBOH, 25C-NBOH, 25I-NBOH, their 2C counterparts. j.forsciint.2019.05.036

A related case report by Pelletier et al. (2024) documented severe intoxication with 25E-NBOH (a structural analog) combined with MDPHP, presenting with serotonin syndrome and loss of consciousnesssupported

23-year-old male with serotonergic syndrome and loss of consciousness after consuming powder labeled as 25I-NBOH; actually contained 25E-NBOH + MDPHP. s00414-023-03151-6

Ivory et al. (2022) reported a cluster of poisonings in Australia resulting from powder sold as LSD that was subsequently identified as 25B-NBOHsupported

Cluster of poisonings from powder sold as LSD. 25B-NBOH is a synthetic hallucinogen closely related to the NBOMe family. 15563650.2022.2053150

Claim in effects-overview — inconclusiveinconclusiveworking →

The compound is not controlled under United Nations drug conventions as of the most recent assessment, though the UNODC maintains a substance database entrysupported

Not under UN Conventions control as of 2019. s11419-019-00509-7