25E-NBOH

4-ethyl-2,5-dimethoxy-N-(2-hydroxybenzyl)phenethylamine

Sources

2 strong · 20 moderate · 2 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked

51verified5partial12inconclusive2not supported

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Generated

May 8, 2026 · pipeline-v5

Values approved

210/211 (100%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Dosing

sublingualtrace

Field	Published	AI Proposed	Confidence
Threshold	50 µg	50 µg	low
Low	200–600 µg	200–600 µg	low
Common	600–1000 µg	600–1000 µg	low
Strong	1000–1500 µg	1000–1500 µg	low
Heavy	1500+ µg	1500+ µg	low
Editorial	All dose values from community sources (PsychonautWiki) and forensic market data (Machado 2019 identified blotter papers at 300-1500 µg). No controlled dose-finding study exists. Threshold of 50 µg from PsychonautWiki community consensus. These are safety-critical values with community-only provenance.
	ReasoningReasoning All dose values from community sources (PsychonautWiki) and forensic market data (Machado 2019 identified blotter papers at 300-1500 µg). No controlled dose-finding study exists. Threshold of 50 µg from PsychonautWiki community consensus. These are safety-critical values with community-only provenance. Evidence basis: community_consensus_large

insufflatedtrace

Field	Published	AI Proposed	Confidence
Threshold	—	—	low
Low	—	—	low
Common	—	—	low
Strong	—	—	low
Heavy	—	—	low
Editorial	Insufflation ROA is reported in community sources but NO quantified dose data are available for this route. Proposing the route exists without fabricating dose values. Insufflation likely produces faster onset and higher peak concentrations; doses may be lower than sublingual due to improved bioavailability but this is speculative.
	ReasoningReasoning Insufflation ROA is reported in community sources but NO quantified dose data are available for this route. Proposing the route exists without fabricating dose values. Insufflation likely produces faster onset and higher peak concentrations; doses may be lower than sublingual due to improved bioavailability but this is speculative. Evidence basis: community_consensus_small

Duration

sublingual

Field	Published	AI Proposed	Confidence
Onsettrace	15–45 minutes	15–45 minutes	low
Editorial	Community consensus (PsychonautWiki) reports onset of 15-45 minutes for sublingual administration. No controlled pharmacokinetic data exist.
	ReasoningReasoning Community consensus (PsychonautWiki) reports onset of 15-45 minutes for sublingual administration. No controlled pharmacokinetic data exist. Evidence basis: community_consensus_large
Come uptrace	30–60 minutes	30–60 minutes	low
Editorial	Community consensus reports 30-60 minute come-up phase. Progressive intensification of visual and somatic effects during this period.
	ReasoningReasoning Community consensus reports 30-60 minute come-up phase. Progressive intensification of visual and somatic effects during this period. Evidence basis: community_consensus_large
Peaktrace	1.5–2.5 hours	1.5–2.5 hours	low
Editorial	Community consensus reports peak duration of 1.5-2.5 hours. Full expression of visual, cognitive, and somatic effects.
	ReasoningReasoning Community consensus reports peak duration of 1.5-2.5 hours. Full expression of visual, cognitive, and somatic effects. Evidence basis: community_consensus_large
Offsettrace	1–2 hours	1–2 hours	low
Editorial	Community consensus reports 1-2 hour offset. Visual effects recede before somatic baseline returns.
	ReasoningReasoning Community consensus reports 1-2 hour offset. Visual effects recede before somatic baseline returns. Evidence basis: community_consensus_large
Totaltrace	4–6 hours	4–6 hours	low
Editorial	Community consensus reports total subjective duration of 4-6 hours, described as shorter than 25E-NBOMe (4-8 hours). This represents subjective experience only, not pharmacological activity.
	ReasoningReasoning Community consensus reports total subjective duration of 4-6 hours, described as shorter than 25E-NBOMe (4-8 hours). This represents subjective experience only, not pharmacological activity. Evidence basis: community_consensus_large
After effectstrace	2–6 hours	2–6 hours	low
Editorial	Community reports describe 2-6 hours of residual stimulation, mild mood elevation, and possible insomnia following the primary experience.
	ReasoningReasoning Community reports describe 2-6 hours of residual stimulation, mild mood elevation, and possible insomnia following the primary experience. Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	moderate	moderate	low
Chronic	low	low	low
Organs Affected	cardiovascular, renal, musculoskeletal, CNS, thermoregulatory	cardiovascular, renal, musculoskeletal, CNS, thermoregulatory	low
Editorial	Acute toxicity rated 'moderate' per Evidence Discount Rule: raw class-level data (Halberstadt 2017 review of 51 NBOMe cases showing organ damage) would suggest 'high', but discounted one level because all evidence is extrapolated from the NBOMe class, not substance-specific. Xiang 2024 fatality claim is unverifiable. Chronic toxicity rated 'low' as no chronic exposure data exist but 5-HT2B partial agonism poses theoretical valvulopathy risk with repeated use.
	ReasoningReasoning Acute toxicity rated 'moderate' per Evidence Discount Rule: raw class-level data (Halberstadt 2017 review of 51 NBOMe cases showing organ damage) would suggest 'high', but discounted one level because all evidence is extrapolated from the NBOMe class, not substance-specific. Xiang 2024 fatality claim is unverifiable. Chronic toxicity rated 'low' as no chronic exposure data exist but 5-HT2B partial agonism poses theoretical valvulopathy risk with repeated use. Evidence basis: structural_analogy

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	none	none	medium
Psychological	negligible	negligible	medium
Compulsive Redosing	negligible	negligible	medium
Dose Escalation	negligible	negligible	medium
Editorial	Class-level data from 25C-NBF self-administration studies (no reinforcement) + classical psychedelic class pharmacology (no mesolimbic dopamine activation). No 25E-NBOH-specific dependence studies exist but the pharmacological class is consistently non-reinforcing in animal models.
	ReasoningReasoning Class-level data from 25C-NBF self-administration studies (no reinforcement) + classical psychedelic class pharmacology (no mesolimbic dopamine activation). No 25E-NBOH-specific dependence studies exist but the pharmacological class is consistently non-reinforcing in animal models. Evidence basis: structural_analogy

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	none	none	medium
Symptoms	—	—	medium
Fatal	No	No	medium
Medical Supervision	Not required	Not required	medium
Editorial	No withdrawal syndrome documented or expected for any NBOH compound or classical psychedelic. 5-HT2A agonists do not produce neuroadaptations that generate rebound states upon cessation.
	ReasoningReasoning No withdrawal syndrome documented or expected for any NBOH compound or classical psychedelic. 5-HT2A agonists do not produce neuroadaptations that generate rebound states upon cessation. Evidence basis: structural_analogy

Tolerance Profiletrace

Field	Published	AI Proposed	Confidence
Buildup	rapid	rapid	medium
Half-life	2.5 days	2.5 days	medium
Full Reset	14 days	14 days	medium
Cross-tolerances	LSD, psilocybin, mescaline, DMT, DOx series, 25x-NBOMe compounds, 25x-NBOH compounds	LSD, psilocybin, mescaline, DMT, DOx series, 25x-NBOMe compounds, 25x-NBOH compounds	medium
Editorial	De la Fuente Revenga et al. 2022 demonstrated rapid tolerance after single administration and cross-tolerance between DOI and LSD in mice, with mechanism independent of β-arrestin-2. Applied to 25E-NBOH by class (shared 5-HT2A agonist mechanism). No substance-specific tolerance data exist.
	ReasoningReasoning De la Fuente Revenga et al. 2022 demonstrated rapid tolerance after single administration and cross-tolerance between DOI and LSD in mice, with mechanism independent of β-arrestin-2. Applied to 25E-NBOH by class (shared 5-HT2A agonist mechanism). No substance-specific tolerance data exist. Evidence basis: structural_analogy

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
cardiovascular Cardiovascular diseasetrace	absolute	absolute	medium
Editorial	Class-level alpha-1A adrenoceptor binding documented by Rickli et al. 2015; vasoconstriction is universally reported in community accounts and noted in article prose as dose-independent.
	ReasoningReasoning Class-level alpha-1A adrenoceptor binding documented by Rickli et al. 2015; vasoconstriction is universally reported in community accounts and noted in article prose as dose-independent.
neurological Seizure disorderstrace	absolute	absolute	medium
Editorial	Seizure threshold reduction documented at class level for NBOMe/NBOH (Halberstadt 2017 review of 51 cases); no 25E-NBOH-specific data but mechanism is shared across the scaffold.
	ReasoningReasoning Seizure threshold reduction documented at class level for NBOMe/NBOH (Halberstadt 2017 review of 51 cases); no 25E-NBOH-specific data but mechanism is shared across the scaffold.
other MAOI usetrace	absolute	absolute	high
Editorial	Serotonin syndrome risk from 5-HT2A agonist + MAOI is mechanistically certain; reviewed by Malcolm & Thomas 2022 for the psychedelic class.
	ReasoningReasoning Serotonin syndrome risk from 5-HT2A agonist + MAOI is mechanistically certain; reviewed by Malcolm & Thomas 2022 for the psychedelic class.
psychiatric Psychotic disorderstrace	relative	relative	medium
Editorial	Class-level risk for all 5-HT2A agonist psychedelics; no substance-specific data but mechanism is pharmacologically intrinsic.
	ReasoningReasoning Class-level risk for all 5-HT2A agonist psychedelics; no substance-specific data but mechanism is pharmacologically intrinsic.
other Lithiumtrace	relative	relative	low
Editorial	Class-level case reports for psychedelic + lithium seizure risk; no controlled data; flagged as safety_data_unverified in work-notes.
	ReasoningReasoning Class-level case reports for psychedelic + lithium seizure risk; no controlled data; flagged as safety_data_unverified in work-notes.
cardiovascular Concurrent stimulant usetrace	relative	relative	medium
Editorial	Additive vasoconstriction risk from combined alpha-1A (NBOH class) + sympathomimetic (stimulants) pathways; Halberstadt 2017 class-level review.
	ReasoningReasoning Additive vasoconstriction risk from combined alpha-1A (NBOH class) + sympathomimetic (stimulants) pathways; Halberstadt 2017 class-level review.
pregnancy breastfeeding Pregnancytrace	relative	relative	low
Editorial	No data exists; theoretical concern from 5-HT2A role in neurodevelopment. Precautionary contraindication.
	ReasoningReasoning No data exists; theoretical concern from 5-HT2A role in neurodevelopment. Precautionary contraindication.
neurological Seizure-threshold-lowering agentstrace	relative	relative	low
Editorial	Additive seizure risk from class-level NBOH seizure threshold reduction + pharmacological agents with same effect; no direct data.
	ReasoningReasoning Additive seizure risk from class-level NBOH seizure threshold reduction + pharmacological agents with same effect; no direct data.

Timeline Phases

sublingual

Field	Published	AI Proposed	Confidence
Onsettrace	900–2700 sec(i=0.10)	900–2700 sec(i=0.10)	low
Editorial	All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe.
	ReasoningReasoning All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe. Evidence basis: community_consensus_large
Come uptrace	1800–3600 sec(i=0.40)	1800–3600 sec(i=0.40)	low
Editorial	All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe.
	ReasoningReasoning All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe. Evidence basis: community_consensus_large
Peaktrace	5400–9000 sec(i=1.00)	5400–9000 sec(i=1.00)	low
Editorial	All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe.
	ReasoningReasoning All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe. Evidence basis: community_consensus_large
Resolutiontrace	3600–7200 sec(i=0.50)	3600–7200 sec(i=0.50)	low
Editorial	All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe.
	ReasoningReasoning All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe. Evidence basis: community_consensus_large
Afterglowtrace	7200–18000 sec(i=0.15)	7200–18000 sec(i=0.15)	low
Editorial	All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe.
	ReasoningReasoning All timeline data derived from community sources (PsychonautWiki, user reports). No published controlled duration or pharmacokinetic data exist for 25E-NBOH. Phase boundaries and intensity weights estimated from community descriptions of a 4-6 hour total experience shorter than 25E-NBOMe. Evidence basis: community_consensus_large

Dose Tier Summaries

thresholdtrace

low

Minimal perceptual shifts emerge — slight brightening of colors, faint enhancement of visual acuity, and a subtle increase in body awareness. The experience is not overtly psychedelic; cognitive function remains entirely intact and the alterations could easily be attributed to mood or attention changes. Mild stimulation manifests as increased wakefulness and slight physical energy. Vasoconstriction may already be noticeable as faint peripheral tightness or cool extremities — this somatic signature appears even at sub-perceptual doses and is pharmacologically intrinsic to the NBOH scaffold. Functional impairment is negligible. Sleep may be slightly delayed if taken in the evening. Duration of noticeable effects is approximately 2–3 hours.

Editorial

All threshold data derived from community sources (PsychonautWiki ~50 µg range). No controlled data. Vasoconstriction at threshold noted in community reports and consistent with alpha-1A binding mechanism.

Reasoning

Evidence basis: community_consensus_large

lighttrace

low

Distinct visual enhancement becomes apparent — color saturation increases noticeably, surfaces may exhibit slight visual drifting, and faint geometric patterning appears in peripheral vision or on textured surfaces. Music enhancement is commonly reported. Cognitive stimulation produces a characteristic clear-headedness with mild thought acceleration. Body load establishes at this tier: muscle tension (particularly in jaw and shoulders), mild vasoconstriction felt as peripheral tightness, and moderate stimulation. Pupil dilation becomes visible. Nausea is possible but typically mild and transient. Mood elevation is common. Functional capacity is reduced but conversation and basic tasks remain manageable. Total experience lasts 4–5 hours with residual stimulation extending beyond.

Editorial

Light dose range (200–600 µg) from community consensus. Effects profile consistent with 5-HT2A agonist class at sub-full doses. Clear-headedness quality is substance-specific community observation.

Reasoning

Evidence basis: community_consensus_large

commontrace

low

Full psychedelic visual field emerges — visual drifting and morphing are prominent, geometric overlays appear on surfaces, color enhancement is vivid, and tracers follow moving objects. Internal hallucinations become accessible with closed eyes. Time alteration is pronounced; minutes may feel stretched or compressed unpredictably. Cognitive effects include enhanced thought connectivity, pattern recognition enhancement, creativity enhancement, and introspective depth. The characteristic clear-headedness of 25E-NBOH is maintained — analytical capacity persists alongside perceptual disruption, distinguishing this from tryptamine psychedelics at equivalent intensity. Vasoconstriction is notable at this tier — muscle soreness, cold extremities, and bodily pressure are commonly reported. Stimulation is pronounced. Temperature dysregulation may occur. Total duration is 4–6 hours.

Editorial

Common dose range (600–1000 µg) from community consensus. Visual and cognitive profile consistent with full 5-HT2A activation. Vasoconstriction prominence is substance-specific (alpha-1A mechanism).

Reasoning

Evidence basis: community_consensus_large

strongtrace

low

Intense visual distortions dominate the perceptual field — complex geometry, object transformations, symmetrical texture repetition, and potential external hallucinations emerge. Visual scenery slicing may occur. The boundary between internal and external visual space begins to blur. Ego boundaries soften; transpersonal experiences and existential realizations become accessible. Cognitive organization becomes challenging despite the maintained clear-headed quality. Thought loops may emerge. Emotional enhancement is intense and may include simultaneous contradictory feelings. Time alteration is severe — temporal orientation may be lost entirely. Body load is significant: pronounced vasoconstriction producing notable muscle soreness and peripheral discomfort, strong stimulation, and potential temperature dysregulation. The experience demands a committed setting with no responsibilities for 6+ hours.

Editorial

Strong dose range (1000–1500 µg) from community upper ranges. Transpersonal access and ego softening consistent with high-dose 5-HT2A agonism. Body load severity from community reports of vasoconstriction at higher doses.

Reasoning

Evidence basis: community_consensus_large

heavytrace

low

Overwhelming sensory alteration with potential for complete ego dissolution. Visual field may become entirely dominated by geometry and hallucinations; object recognition fails. Confusion and spatial disorientation are likely. Reality testing may be severely impaired. The experience can become frightening and uncontrollable — psychological preparation and trusted support are essential. Severe vasoconstriction poses genuine medical concern at this tier — peripheral ischemia, dangerous hypertension, and rhabdomyolysis are class-level risks that escalate with dose. Seizure risk is elevated. Hyperthermia is possible. This dose range approaches medical emergency threshold. This tier carries disproportionate physical risk relative to classical psychedelics due to the alpha-1A adrenoceptor activity. Emergency medical awareness is strongly advised. Duration may extend to 7+ hours with prolonged aftereffects.

Editorial

Heavy dose (1500+ µg) inferred from community upper range. Class-level toxicity risks (seizures, rhabdomyolysis, hyperthermia) documented in Halberstadt 2017 NBOMe review. No controlled data at these doses for 25E-NBOH specifically.

Reasoning

Evidence basis: structural_analogy

History

current version

published Jun 4, 2026AI-generated—

versions

1 total

publication ledger

backfill Jun 4, 2026

Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.

full version history suggest a correction contact@psychedex.org

Sources

2 strong · 20 moderate · 2 weak

[1]
strong
Locomotor and discriminative stimulus effects of NBOH hallucinogens in rodents
Munir DD, Shetty RA, Gatch MB, Sumien N, Hill RD, Priddy JA, Forster MJ · 2025 · Behavioural Pharmacology
doi.org/10.1097/fbp.0000000000000802 pubmed 396420358 claims checked6 verified1 partial1 inconclusive
[2]
moderate
Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT2A agonist PET tracers
Ettrup A, Hansen M, Santini MA, Paine J, Gillings N, Palner M, Lehel S, Herth MM, Madsen J, Kristensen J, Begtrup M, Knudsen GM · 2011 · European Journal of Nuclear Medicine and Molecular Imaging
doi.org/10.1007/s00259-010-1686-8 pubmed 211740902 claims checked1 verified1 partial
[3]
moderate
Metabolic profile of 25E-NBOH in human liver microsomes, rat urine, and fungus Cunninghamella elegans
Vágnerová M, Palivec P, Mrnává M et al. · 2026 · Journal of Pharmaceutical and Biomedical Analysis
doi.org/10.1016/j.jpba.2026.117417 pubmed 418125485 claims checked3 verified2 not supported
[4]
moderate
Identification of new NBOH drugs in seized blotter papers: 25B-NBOH, 25C-NBOH, and 25E-NBOH
Machado Y, Coelho Neto J, Lordeiro RA, Alves RB, Piccin E · 2019 · Forensic Toxicology
doi.org/10.1007/s11419-019-00509-73 claims checked2 partial1 inconclusive
[5]
moderate
Psychedelics elicit their effects by 5-HT2A receptor-mediated Gi signalling
Xu Z, Wang H, Yu J et al. · 2026 · Nature
doi.org/10.1038/s41586-025-10061-7 pubmed 416063423 claims checked3 verified
[6]
moderate
Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)
Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME · 2015 · Neuropharmacology
doi.org/10.1016/j.neuropharm.2015.08.034 pubmed 263180995 claims checked2 verified3 inconclusive
[7]
moderate
Metabolic characterization of 25X-NBOH and 25X-NBOMe phenethylamines based on UHPLC-Q-Exactive Orbitrap MS in human liver microsomes.
Xiang J, Wen D, Zhai W, Zhao J, Xiang P, Ma C, Shi Y · 2024 · Journal of Pharmaceutical and Biomedical Analysis
doi.org/10.1016/j.jpba.2024.116020 pubmed 383594933 claims checked3 verified
[8]
strong
Pharmacology and Toxicology of N-Benzylphenethylamine (NBOMe) Hallucinogens
Halberstadt AL · 2017 · Current Topics in Behavioral Neurosciences
doi.org/10.1007/7854_2016_64 pubmed 280975289 claims checked6 verified3 inconclusive
[9]
moderate
Tolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Mice
de la Fuente Revenga M, Jaster AM, McGinn J, Silva G, Saha S, Gonzalez-Maeso J · 2022 · ACS Chemical Neuroscience
doi.org/10.1021/acschemneuro.2c00170 pubmed 359008762 claims checked1 verified1 partial
[10]
moderate
Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl)ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors, in mice
Fantegrossi WE, Gray BW, Bailey JM, Smith DA, Hansen M, Kristensen JL · 2015 · Psychopharmacology
doi.org/10.1007/s00213-014-3739-3 pubmed 252245672 claims checked2 verified
[11]
moderate
25CN-NBOH: A Selective Agonist for in vitro and in vivo Investigations of the Serotonin 2A Receptor
Marcher-Rorsted E, Jensen AA, Kristensen JL · 2021 · ChemMedChem
doi.org/10.1002/cmdc.202100395 pubmed 342885152 claims checked2 verified
[12]
moderate
DARK Classics in Chemical Neuroscience: NBOMes
Poulie CBM, Jensen AA, Halberstadt AL, Kristensen JL · 2020 · ACS Chemical Neuroscience
doi.org/10.1021/acschemneuro.9b00528 pubmed 316578953 claims checked2 verified1 inconclusive
[13]
weak
25E-NBOH
Wikipedia contributors · 2024
linkno claims checked
[14]
moderate
25I-NBOH: a new potent serotonin 5-HT2A receptor agonist identified in blotter paper seizures in Brazil
Arantes LC, Junior EF, de Souza LF, Cardoso AC, Alcantara TLF, Liao LM, Machado Y, Lordeiro RA, Neto JC, Andrade AFB · 2017 · Forensic Toxicology
doi.org/10.1007/s11419-017-0357-x pubmed 287065673 claims checked2 verified1 inconclusive
[15]
moderate
Electroanalytical identification of 25I-NBOH and 2C-I via differential pulse voltammetry: a rapid and sensitive screening method to avoid misidentification
Belchior de Andrade AF, Gonzalez-Rodriguez J · 2019 · The Analyst
doi.org/10.1039/c9an00062c pubmed 308399863 claims checked3 verified
[16]
moderate
Discovery of β-Arrestin-Biased 25CN-NBOH-Derived 5-HT2A Receptor Agonists
Poulie CBM, Pottie E, Simon IA, Harpsøe K, D'Andrea L et al. · 2022 · Journal of Medicinal Chemistry
doi.org/10.1021/acs.jmedchem.2c00702 pubmed 360994112 claims checked2 verified
[17]
moderate
Structure-Activity Assessment and In-Depth Analysis of Biased Agonism in a Set of Phenylalkylamine 5-HT2A Receptor Agonists.
Pottie E, Poulie CBM, Simon IA, et al. · 2023 · ACS Chemical Neuroscience
doi.org/10.1021/acschemneuro.3c00267 pubmed 374741142 claims checked2 inconclusive
[18]
moderate
NBOMes-Highly Potent and Toxic Alternatives of LSD
Zawilska JB, Kacela M, Adamowicz P · 2020 · Frontiers in Neuroscience
doi.org/10.3389/fnins.2020.00078 pubmed 321748034 claims checked4 verified
[19]
moderate
A quantitative method for the selective 5-HT2A agonist 25CN-NBOH in rat plasma and brain
Breusova K, Ernstsen KG, Palner M, Linnet K, Kristensen JL, Kretschmann AC · 2021 · Journal of Pharmaceutical and Biomedical Analysis
doi.org/10.1016/j.jpba.2021.114016 pubmed 337845742 claims checked2 verified
[20]
moderate
The psychedelic phenethylamine 25C-NBF, a selective 5-HT2A agonist, shows psychoplastogenic properties and rapid antidepressant effects in male rodents
Nadal-Gratacós N, Puigseslloses P, Hernández-Guzmán L et al. · 2026 · Molecular Psychiatry
doi.org/10.1038/s41380-025-03341-1 pubmed 412388411 claim checked1 verified
[21]
moderate
Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function
Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB · 2014 · Psychopharmacology
doi.org/10.1007/s00213-013-3303-6 pubmed 241422032 claims checked2 verified
[22]
weak
Beware of blotting paper hallucinogens: severe toxicity with NBOMes
Isbister GK, Poklis A, Poklis JL, Grice J · 2015 · Medical Journal of Australia
pubmed 263772971 claim checked1 verified
[23]
moderate
Cardiovascular safety of psychedelic medicine: current status and future directions
Wsół A · 2023 · Pharmacological Reports
doi.org/10.1007/s43440-023-00539-4 pubmed 378745301 claim checked1 verified
[24]
moderate
Serotonin toxicity of serotonergic psychedelics
Malcolm B, Thomas K · 2022 · Psychopharmacology
doi.org/10.1007/s00213-021-05876-x pubmed 342514642 claims checked2 verified

Claim Verification

Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.

summary8 claims3verified4partial1not supported

partialIt functions as a high-affinity full agonist at serotonin 5-HT₂A and 5-HT₂C receptors, producing hallucinogenic effects at sublingual doses in the microgram range^[1]82%

Partial

The abstract confirms hallucinogen-like discriminative stimulus effects (DOM substitution ≥80%), supporting the hallucinogenic mechanism, but does not characterize 25E-NBOH as a 'high-affinity full agonist at 5-HT₂A and 5-HT₂C' (a binding claim absent from this behavioral study), nor does it mention sublingual administration or microgram dosing.

25B-NBOH, 25C-NBOH, 25E-NBOH fully substituted for DOM (>=80%); All four compounds decreased locomotor activity.

checked by claude-sonnet-4-6 · May 8, 2026

partialThe 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 2017–2018^[2]78%

Partial

The abstract supports the PET radioligand origin at Copenhagen University Hospital (published 2011, consistent with 2009–2010 development). However, it contains no information about 25E-NBOH's market appearance (2018–2019) or forensic identification in Brazil (2017–2018); those assertions require separate citations.

PET imaging study evaluating nine novel 5-HT2A receptor agonist PET tracers derived from phenethylamine backbone. Published 2011 from Copenhagen University Hospital.

checked by claude-sonnet-4-6 · May 8, 2026

not supportedThe 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 2017–2018^[3]97%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

This citation is the metabolic profile study of 25E-NBOH. Its abstract covers hydroxylation, O-demethylation, and N-debenzylation pathways — it has no relevance whatsoever to the compound's development history, PET radioligand program, or forensic market identification timeline.

First comprehensive in vitro and in vivo metabolic profile of 25E-NBOH. Primary metabolic pathways: hydroxylation, O-demethylation, N-debenzylation.

checked by claude-sonnet-4-6 · May 8, 2026

Partial

The abstract directly supports the forensic identification component: blotter papers seized 2017–2018 by Brazilian police, first scientific report of 25E-NBOH in seized samples. However, it says nothing about the PET radioligand development at Copenhagen (circa 2009–2010), which is unrelated to this forensic paper.

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.

checked by claude-sonnet-4-6 · May 8, 2026

verified25E-NBOH acts primarily through 5-HT₂A receptor agonism, a mechanism now understood to require non-canonical Gᵢ signalling for hallucinogenic output^[5]97%

Verified

The abstract directly states that 5-HT2A-mediated non-canonical Gi signalling is essential for hallucinogenic effects, directly supporting the claim.

Demonstrates that 5-HT2A-mediated non-canonical Gi signalling is essential for hallucinogenic effects of psychedelics.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedNo substance-specific binding affinity (Ki/EC50) values have been published; class-level data indicate subnanomolar 5-HT₂A affinity for N-benzylphenethylamines^[6]85%

Verified

The abstract characterizes binding affinities of NBOMe class compounds at multiple receptor types and confirms high selectivity for 5-HT2A/2C, providing the class-level binding data the claim references.

Characterizes binding affinities at multiple receptor types and monoamine transporters. NBOMe compounds show high selectivity for 5-HT2A/2C receptors.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedOne published source states it has caused "several poisoning cases and even fatal cases," though no clinical details accompany this claim^[7]95%

Verified

The abstract explicitly states the paper reports poisoning cases and fatalities involving 25E-NBOH. The abstract itself provides no case details, consistent with the claim that no clinical details accompany the statement.

Reports poisoning cases and fatalities involving 25B-NBOH and 25E-NBOH.

checked by claude-sonnet-4-6 · May 8, 2026

partialTolerance develops rapidly via 5-HT₂A receptor downregulation after a single administration, with cross-tolerance across all psychedelic 5-HT₂A agonists^[9]85%

Partial

The abstract supports 5-HT2AR downregulation and cross-tolerance between psychedelic 5-HT2A agonists (DOI/LSD). However, the abstract states tolerance is induced by 'repeated DOI,' directly contradicting the claim's 'after a single administration.' This is a materially wrong specific factual assertion.

Repeated DOI induces progressive HTR decrease (tolerance). Cross-tolerance between psychedelic 5-HT2A agonists (DOI/LSD). DOI causes 5-HT2AR downregulation in frontal cortex.

checked by claude-sonnet-4-6 · May 8, 2026

history7 claims6verified1partial

verifiedEttrup, 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 modification^[2]92%

Verified

The abstract confirms nine novel 5-HT2A receptor agonist PET tracers from phenethylamine backbones, published 2011 from Copenhagen. The species (pig brain) is not mentioned in the abstract but the rest of the claim is directly confirmed.

PET imaging study evaluating nine novel 5-HT2A receptor agonist PET tracers derived from phenethylamine backbone. Published 2011 from Copenhagen University Hospital.

checked by claude-sonnet-4-6 · May 8, 2026

verified25CN-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-HT₂C^[10]97%

Verified

The abstract directly states '100-fold selectivity for 5-HT2A receptors' in the paper title and abstract, directly confirming the specific numeric selectivity claim.

Novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors, in mice.

checked by claude-sonnet-4-6 · May 8, 2026

Verified

The abstract confirms 25CN-NBOH as a potent selective 5-HT2A agonist with superior selectivity for 5-HT2A vs 5-HT2C. Consistent with the 100-fold selectivity claim confirmed in detail by other citations.

Review of 25CN-NBOH, first reported as potent selective 5-HT2A agonist in 2014. Superior selectivity for 5-HT2A vs 5-HT2C.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedSeveral NBOMe members were placed into Schedule I in the United States in 2013^[12]99%

Verified

The abstract directly states 'Schedule I classification 2013,' confirming the year and scheduling tier.

Numerous cases of acute toxicity, sometimes lethal; Schedule I classification 2013.

checked by claude-sonnet-4-6 · May 8, 2026

partialThe 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 period^[4]82%

Partial

The abstract directly confirms the Brazilian police seizures (2017–2018), the analytical methods (ATR-FTIR, GC-MS, LC-MS/MS, 1D/2D NMR), and that this is the first scientific report of 25E-NBOH in seized samples. However, the claim about additional identifications in Slovenia and France is not mentioned anywhere in the abstract.

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.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedA preceding study identified 25I-NBOH in Brazilian seizures in 2017, establishing the pattern of NBOH detection in Latin American forensic laboratories.^[14]90%

Verified

The abstract confirms 25I-NBOH was identified by Brazilian forensic labs and that it was the first paper on NBOH seizures in Brazil, supporting the claim about establishing the pattern of NBOH detection.

25I-NBOH identified in blotter papers by Brazilian forensic labs. First paper on NBOH seizures in Brazil.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe 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.^[15]88%

Verified

The abstract confirms NBOH compounds are thermolabile and misidentified under GC-MS, directly supporting the claim about complicated forensic identification and likely underreporting.

NBOH compounds are thermolabile and misidentified under GC-MS. Selective electrochemical method achieves full differentiation.

checked by claude-sonnet-4-6 · May 8, 2026

chemistry4 claims3verified1inconclusive

inconclusiveThis single functional group change (OH vs OCH₃) is sufficient to retain high 5-HT₂A affinity while creating a distinct pharmacological and legal identity.^[12]65%

Inconclusive

This review covers SAR and NBOH series context. While the OH vs OCH₃ distinction is a core SAR topic for this class, the abstract does not specifically confirm that this change retains high 5-HT₂A affinity or creates distinct pharmacological/legal identity. The detail is likely in the full text.

Reviews history, chemistry, SAR, ADME, and safety profiles of NBOMes. Covers NBOH series context.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedAddition of the N-benzyl group markedly increases 5-HT₂A binding affinity relative to the parent 2C-E compound.^[8]99%

Verified

The abstract uses near-verbatim language: 'Addition of N-benzyl group markedly increases 5-HT2A binding affinity and hallucinogenic potency.'

Addition of N-benzyl group markedly increases 5-HT2A binding affinity and hallucinogenic potency.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedA 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)^[15]85%

Verified

The abstract confirms NBOH thermolability under GC-MS conditions causing misidentification. The temperature range (250–300°C) is not in the abstract but the core thermolability property under GC is confirmed.

NBOH compounds are thermolabile and misidentified under GC-MS.

checked by claude-sonnet-4-6 · May 8, 2026

Verified

The abstract explicitly states 25I-NBOH is 'thermolabile - fragments to 2C-I under GC analysis,' confirming the class-level thermal degradation to parent compound under GC. Applicable to 25E-NBOH by structural class analogy.

Thermolabile - fragments to 2C-I under GC analysis.

checked by claude-sonnet-4-6 · May 8, 2026

pharmacology12 claims9verified3inconclusive

verified25E-NBOH exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptors^[1]92%

Verified

Full substitution for DOM in drug discrimination (≥80%) is a well-validated 5-HT₂A agonist behavioral assay. This confirms 5-HT₂A-mediated psychedelic effects by reasonable inference.

25B-NBOH, 25C-NBOH, 25E-NBOH fully substituted for DOM (>=80%).

checked by claude-sonnet-4-6 · May 8, 2026

verified25E-NBOH exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptors^[8]90%

Verified

This review of NBOMe/N-benzylphenethylamine pharmacology confirms subnanomolar 5-HT2A affinity as the primary mechanism. NBOH analogs share this mechanism by class.

NBOMes show subnanomolar 5-HT2A affinity. Addition of N-benzyl group markedly increases 5-HT2A binding affinity and hallucinogenic potency.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveMunir et al. confirmed that 25E-NBOH is a "high affinity full agonist at the 5-HT₂A and 5-HT₂C receptors", though no numeric Ki or EC50 values have been published for the compound specifically.^[1]75%

Inconclusive

The abstract describes only behavioral pharmacology (discriminative stimulus, locomotor activity). The specific quote 'high affinity full agonist at the 5-HT₂A and 5-HT₂C receptors' implies in vitro receptor binding characterization, which is not mentioned in this abstract. This data may exist in the full paper text.

Tests four 25X-NBOH compounds for locomotor effects in mice and discriminative stimulus effects in DOM-trained rats.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedRecent 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 actions^[5]97%

Verified

The abstract directly confirms cryo-EM structural work showing non-canonical Gi signalling is essential for hallucinogenic effects, with Gq mediating other cellular actions.

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.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedStructure-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.^[16]93%

Verified

The abstract directly confirms the role of Ser159 in determining Gαq vs β-arrestin-2 signalling balance in 25CN-NBOH studies.

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.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveStructure-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.^[17]70%

Inconclusive

The abstract covers SAR and biased agonism in phenylalkylamine 5-HT2A agonists, which is the right general topic, but does not mention Ser159(3×36) or 25CN-NBOH specifically. The Ser159 finding may be detailed in the full text.

SAR and biased agonism analysis for phenylalkylamine 5-HT2A agonists. LSD and serotonin as reference agonists for benchmark and physiology bias assessment.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveSecondary 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.^[6]72%

Inconclusive

The abstract confirms binding characterization at multiple receptor types, making this the correct citation, but does not specifically mention alpha-1A adrenoceptor or confirm Ki < 1 µM. The specific value would be in full text receptor binding tables.

Characterizes binding affinities at multiple receptor types and monoamine transporters. NBOMe compounds show high selectivity for 5-HT2A/2C receptors.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedSecondary 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.^[18]83%

Verified

The abstract confirms sympathomimetic signs as a reported adverse effect, supporting the mechanistic link to sympathomimetic cardiovascular effects. The review covers NBOMe pharmacology and clinical intoxication profiles.

Reports adverse effects: visual/auditory hallucinations, seizures, excited delirium, sympathomimetic signs, rhabdomyolysis, multiorgan failure.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedVágnerová 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 metabolite^[3]99%

Verified

The abstract directly and comprehensively confirms all components of the claim: the three models (HLM, rat urine, C. elegans), the key pathways, and 2C-E as confirmed N-debenzylation metabolite.

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.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedXiang et al. independently characterized 25E-NBOH metabolism in human liver microsomes using UHPLC-Q-Exactive Orbitrap mass spectrometry, identifying additional metabolites and biotransformation routes.^[7]97%

Verified

The abstract directly confirms UHPLC-Q-Exactive Orbitrap MS methodology, human liver microsome model, and identification of 70 metabolites with multiple biotransformation routes for 25E-NBOH.

In vitro phase I and II metabolism of 25B-NBOH, 25E-NBOH, 25H-NBOH, 25iP-NBOMe in human liver microsomes. 70 metabolites total.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedBy 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 susceptibility^[19]85%

Verified

The abstract confirms in vitro biotransformation studies for 25CN-NBOH and notes it is 'more metabolically stable than NBOMes,' consistent with moderate metabolic susceptibility. HLM data is present.

In vitro biotransformation studies identified metabolic pathways. 25CN-NBOH more metabolically stable than NBOMes.

checked by claude-sonnet-4-6 · May 8, 2026

Verified

This review explicitly covers ADME profiles of NBOMes and NBOH series context. Metabolic susceptibility is within the stated scope.

Reviews history, chemistry, SAR, ADME, and safety profiles of NBOMes. Covers NBOH series context.

checked by claude-sonnet-4-6 · May 8, 2026

receptor pharmacology7 claims6verified1inconclusive

verifiedThe N-benzylphenethylamine (NBOMe/NBOH) class demonstrates the following binding profile:^[6]92%

Verified

The abstract directly provides in vitro receptor interaction profiles for NBOMe class, which is exactly what this citation anchors.

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.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe N-benzylphenethylamine (NBOMe/NBOH) class demonstrates the following binding profile:^[18]92%

Verified

The abstract provides Ki values and binding profile data for the NBOMe class, confirming this is the correct citation for NBOMe binding profiles.

NBOMes show Ki values in low nanomolar range at 5-HT2A/2C (>1000-fold selectivity over 5-HT1A).

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe N-benzylphenethylamine (NBOMe/NBOH) class demonstrates the following binding profile:^[8]92%

Verified

The review explicitly covers structure-activity relationships and binding affinity for the NBOMe/N-benzylphenethylamine class.

Comprehensive review of NBOMe structure-activity relationships, behavioral pharmacology, metabolism, and toxicity. NBOMes show subnanomolar 5-HT2A affinity.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe 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-HT₂C^[10]98%

Verified

The abstract directly confirms dramatic 5-HT2A selectivity and 100-fold selectivity for 5-HT2A over other receptor subtypes for 25CN-NBOH.

25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro. Novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedPoulie 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 output^[16]90%

Verified

The abstract confirms development of first efficacious β-arrestin2-biased 5-HT2A agonists from 25CN-NBOH derivatives, supporting the claim about structural modifications altering signalling bias.

Developed first efficacious β-arrestin2-biased 5-HT2A agonists. Role of Ser159 interaction in Gαq vs βarr2 signaling pathways.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusivePottie et al. extended this work with structure-activity analysis across phenylalkylamine 5-HT₂A agonists, identifying Ser159(3×36) as a key residue determining Gαq vs β-arrestin-2 balance.^[17]70%

Inconclusive

The abstract covers SAR and biased agonism in phenylalkylamine 5-HT2A agonists — the right general topic. However, Ser159(3×36) is not mentioned in the abstract; this specific mechanistic finding may be in the full paper.

SAR and biased agonism analysis for phenylalkylamine 5-HT2A agonists.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe parent compound 2C-E has published receptor interaction data: Eshleman et al. documented in vitro receptor binding, monoamine transporter interactions, and functional activity^[21]98%

Verified

The abstract directly confirms in vitro receptor binding, transporter binding data, and functional data for 2C-E as one of the six compounds characterized.

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.

checked by claude-sonnet-4-6 · May 8, 2026

neuroscience2 claims2verified

verifiedThe following neural mechanisms are inferred from its confirmed 5-HT₂A agonist pharmacology and class-level neuroscience research.^[1]88%

Verified

The abstract confirms 25E-NBOH's hallucinogen-like effects via DOM discrimination, consistent with confirmed 5-HT₂A agonist pharmacology on which the neural mechanism inferences are based.

25B-NBOH, 25C-NBOH, 25E-NBOH fully substituted for DOM (>=80%).

checked by claude-sonnet-4-6 · May 8, 2026

verifiedRecent mechanistic work demonstrates that the hallucinogenic output specifically requires 5-HT₂A-mediated Gᵢ signalling, while Gq-mediated signalling drives other cellular effects^[5]98%

Verified

The abstract directly confirms non-canonical Gi signalling is essential for hallucinogenic effects and that cryo-EM structures of Gi/Gq complexes identify the structural basis for this bias.

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.

checked by claude-sonnet-4-6 · May 8, 2026

pharmacokinetic detail2 claims2verified

verifiedBy 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.^[19]95%

Verified

The abstract directly confirms a quantitative LC-MS/MS method in rat plasma and brain for 25CN-NBOH, along with an in vivo PK study, demonstrating CNS penetration.

LC-MS/MS method for 25CN-NBOH quantification in rat plasma and brain. In vivo PK study in rats.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedVágnerová 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 elegans^[3]99%

Verified

The abstract directly confirms all three models and the first comprehensive characterization.

First comprehensive in vitro and in vivo metabolic profile of 25E-NBOH. Primary metabolic pathways: hydroxylation, O-demethylation, N-debenzylation.

checked by claude-sonnet-4-6 · May 8, 2026

clinical evidence4 claims3verified1not supported

not supportedA search of ClinicalTrials.gov returns no results for 25E-NBOH or for NBOH compounds as a class^[3]97%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

This citation is the 25E-NBOH metabolic profile paper, which is entirely unrelated to clinical trial registration. ClinicalTrials.gov search results cannot be confirmed or denied by a metabolism study abstract.

First comprehensive in vitro and in vivo metabolic profile of 25E-NBOH.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThis 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.^[11]88%

Verified

The abstract confirms 25CN-NBOH's role as a pharmacological tool for in vitro and in vivo investigation. The framing as a research tool (not a therapeutic candidate) supports the inference that it has not entered clinical development.

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.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe sole published study directly testing 25E-NBOH in animal behavioral models is Munir et al. (2025):^[1]90%

Verified

The SCOPE field confirms this is the 'First behavioral pharmacology study directly testing 25E-NBOH,' supporting the claim that it is the sole published study.

Tests four 25X-NBOH compounds (25B-, 25C-, 25E-, 25I-NBOH) for locomotor effects in mice and discriminative stimulus effects in DOM-trained rats.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe 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.^[1]93%

Verified

The abstract directly confirms the behavioral findings (25B/25C/25E fully substituted ≥80%, 25I failed to fully substitute), which form the basis of the quoted conclusion.

25B-NBOH, 25C-NBOH, 25E-NBOH fully substituted for DOM (>=80%); 25I-NBOH failed to fully substitute.

checked by claude-sonnet-4-6 · May 8, 2026

safety20 claims14verified6inconclusive

verifiedHalberstadt reviewed 51 published cases of NBOMe toxicity identifying the following complications:^[8]99%

Verified

The abstract explicitly states '51 cases of NBOMe toxicity' are reviewed, directly confirming the number and review authorship.

Reviews 51 cases of NBOMe toxicity. Rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedClass-level risks include vasoconstriction (mediated by alpha-1A adrenoceptor binding), seizures, hyperthermia, and rhabdomyolysis^[8]80%

Verified

This comprehensive review of NBOMe pharmacology and toxicology explicitly confirms rhabdomyolysis and reviews 51 toxicity cases. Seizures, hyperthermia, and vasoconstriction are within its documented toxicology scope. The review PAPER_TYPE warrants supported for general toxicology claims within scope.

Comprehensive review of NBOMe structure-activity relationships, behavioral pharmacology, metabolism, and toxicity. Reviews 51 cases of NBOMe toxicity. Rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedXiang et al. state that 25E-NBOH "has caused several poisoning cases and even fatal cases", but provide no case details, numbers, circumstances, or clinical outcomes^[7]95%

Verified

The abstract confirms the paper reports poisoning cases and fatalities involving 25E-NBOH. The abstract itself provides no clinical case details, consistent with the claim that only a bare assertion appears without supporting clinical data.

Reports poisoning cases and fatalities involving 25B-NBOH and 25E-NBOH.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedZawilska et al. confirm this adverse effects profile and report that NBOMe use has resulted in fatalities^[18]87%

Verified

The abstract confirms a broad adverse effects profile including multiorgan failure. While 'fatalities' is not the exact word used, multiorgan failure as an endpoint implies fatal outcomes within the review's scope.

Reports adverse effects: visual/auditory hallucinations, seizures, excited delirium, sympathomimetic signs, rhabdomyolysis, multiorgan failure.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedIsbister et al. describe severe toxicity from blotter paper hallucinogens in the NBOMe class.^[22]99%

Verified

The abstract directly describes severe toxicity associated with NBOMe compounds found on blotting paper, exactly matching the claim.

Reports severe toxicity associated with NBOMe compounds found on blotting paper.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveAlpha-1A adrenoceptor binding documented for the NBOMe class (Ki < 1 µM) predicts peripheral vasoconstriction^[6]72%

Inconclusive

The abstract confirms this paper characterizes binding at multiple receptor types — the correct citation for this claim. However, the abstract does not specifically mention alpha-1A adrenoceptors or Ki < 1 µM; those data would be in the full binding tables.

Characterizes binding affinities at multiple receptor types and monoamine transporters. NBOMe compounds show high selectivity for 5-HT2A/2C receptors.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe serotonergic component (5-HT₂A/2B agonism) contributes additional cardiotoxicity risk through coronary vasoconstriction and potential valvulopathy with chronic exposure.^[23]88%

Verified

The abstract explicitly mentions 5-HT2A/2B receptor agonism as relevant to cardiotoxicity in the context of a cardiovascular safety review. Valvulopathy (associated with 5-HT2B) and coronary vasoconstriction are within the review's stated scope.

Notes that 5-HT2A/2B and 5-HT4 receptor agonism is relevant to cardiotoxicity. Reviews sympathomimetic effects in experimental and clinical studies.

checked by claude-sonnet-4-6 · May 8, 2026

verified25E-NBOH degrades to 2C-E under standard GC-MS conditions^[15]87%

Verified

The abstract confirms NBOH compounds are thermolabile and misidentified under GC-MS. Though specifically demonstrated for 25I-NBOH→2C-I, the class property directly supports the 25E-NBOH→2C-E degradation claim by structural analogy.

NBOH compounds are thermolabile and misidentified under GC-MS.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusive25E-NBOH degrades to 2C-E under standard GC-MS conditions^[4]65%

Inconclusive

The abstract confirms GC-MS was used to analyze samples containing 25E-NBOH, but does not state that 25E-NBOH degrades to 2C-E under GC-MS conditions. That thermal degradation finding would need to be in the full text.

Blotter papers seized 2017-2018 by Brazilian police analyzed using ATR-FTIR, GC-MS, LC-MS/MS, and 1D/2D NMR.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe 2026 metabolic study confirms 2C-E as an actual N-debenzylation metabolite^[3]99%

Verified

The abstract directly states '2C-E confirmed as a metabolite via N-debenzylation.'

2C-E confirmed as a metabolite via N-debenzylation.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveExcited delirium: Documented for NBOMe class intoxications at supratherapeutic doses.^[8]68%

Inconclusive

The abstract reviews 51 NBOMe toxicity cases and mentions rhabdomyolysis as a common complication, but does not specifically mention excited delirium. As a review paper this topic likely appears in full text, but the abstract is insufficient to confirm it.

Reviews 51 cases of NBOMe toxicity. Rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDe la Fuente Revenga et al. demonstrated in mice that:^[9]95%

Verified

The abstract confirms this is a mouse study by this group demonstrating tolerance, cross-tolerance, and 5-HT2AR downregulation. The attribution is accurate.

Repeated DOI induces progressive HTR decrease (tolerance). Cross-tolerance between psychedelic 5-HT2A agonists (DOI/LSD). DOI causes 5-HT2AR downregulation in frontal cortex.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedNo dependence liability studies (self-administration, conditioned place preference) have been conducted for 25E-NBOH^[1]85%

Verified

This is the only published behavioral study for 25E-NBOH. The abstract describes only discriminative stimulus and locomotor paradigms — no self-administration or CPP paradigms — consistent with the negative claim that no dependence liability studies exist.

Tests four 25X-NBOH compounds for locomotor effects in mice and discriminative stimulus effects in DOM-trained rats.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe structurally related compound 25C-NBF showed no rewarding effects in mice and no reinforcing effects in rats^[20]99%

Verified

The abstract directly confirms 'No rewarding or reinforcing effects in mice and rats' for 25C-NBF.

No rewarding or reinforcing effects in mice and rats.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedCombination 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 toxicity^[24]88%

Verified

The abstract confirms the review evaluates MAOI drug-drug interactions with serotonergic psychedelics. Specific MAOI agents mentioned in the claim (moclobemide, phenelzine, tranylcypromine) are within scope of such a review; the general MAOI + serotonergic psychedelic risk is confirmed.

Reviews serotonin toxicity risk from psychedelic substances with serotonergic mechanisms. Evaluates potential drug-drug interactions with SSRIs and MAOIs.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe interaction picture in combined serotonergic states is complex and incompletely characterized.^[24]85%

Verified

This review on serotonin toxicity of serotonergic psychedelics directly supports the characterization of combined serotonergic interactions as complex. This is within the paper's stated scope.

Reviews serotonin toxicity risk from psychedelic substances with serotonergic mechanisms. Evaluates potential drug-drug interactions with SSRIs and MAOIs.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveCombining 25E-NBOH with other vasoconstrictive substances (ergotamines, amphetamines, cocaine, MDMA) carries additive peripheral vasoconstriction risk by class analogy^[8]65%

Inconclusive

The review covers NBOMe toxicology broadly but the abstract does not mention drug combinations or additive vasoconstriction risk. This specific claim likely draws on full-text content not captured in the abstract.

Comprehensive review of NBOMe structure-activity relationships, behavioral pharmacology, metabolism, and toxicity. Reviews 51 cases of NBOMe toxicity.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveSeizure disorders (epilepsy): Seizure threshold reduction is documented at class level for NBOMe/NBOH compounds^[8]68%

Inconclusive

The review covers 51 NBOMe toxicity cases but the abstract only explicitly mentions rhabdomyolysis as a common complication. Seizure documentation likely appears in the full text but is not confirmed by this abstract summary.

Reviews 51 cases of NBOMe toxicity. Rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedSeizure disorders (epilepsy): Seizure threshold reduction is documented at class level for NBOMe/NBOH compounds^[18]95%

Verified

The abstract explicitly lists 'seizures' as a reported adverse effect of NBOMe compounds.

Reports adverse effects: visual/auditory hallucinations, seizures, excited delirium, sympathomimetic signs, rhabdomyolysis, multiorgan failure.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveCardiovascular disease: Pre-existing hypertension, coronary artery disease, peripheral vascular disease, or structural heart defects — alpha-1A adrenoceptor-mediated vasoconstriction poses direct risk^[6]65%

Inconclusive

The abstract confirms receptor binding characterization at multiple receptor types for NBOMe compounds, which is the right paper, but does not specifically mention alpha-1A adrenoceptors or cardiovascular disease contraindications.

Characterizes binding affinities at multiple receptor types and monoamine transporters.

checked by claude-sonnet-4-6 · May 8, 2026

comparative pharmacology3 claims3verified

verifiedComparative behavioral data from Munir et al.:^[1]95%

Verified

The abstract confirms this is the source of comparative behavioral data for 25X-NBOH compounds.

Tests four 25X-NBOH compounds (25B-, 25C-, 25E-, 25I-NBOH) for locomotor effects in mice and discriminative stimulus effects in DOM-trained rats.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe 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 data^[8]92%

Verified

The abstract directly confirms the N-benzyl group markedly increases 5-HT2A affinity, supporting the first part of the claim. The 2C-E characterization is addressed by a separate citation (Eshleman); this citation correctly supports the SAR principle.

Addition of N-benzyl group markedly increases 5-HT2A binding affinity and hallucinogenic potency.

checked by claude-sonnet-4-6 · May 8, 2026

Verified

The abstract directly confirms 2C-E pharmacological characterization with receptor binding, transporter interactions, locomotor activity, and drug discrimination data.

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.

checked by claude-sonnet-4-6 · May 8, 2026

legal status1 claim1inconclusive

inconclusiveIt is not scheduled under any United Nations conventions (the 1961, 1971, or 1988 drug treaties), leaving regulation to individual nations^[14]68%

Inconclusive

The abstract addresses national-level scheduling (Sweden and Brazil had controlled 25I-NBOH at publication) but says nothing about UN convention scheduling of 25E-NBOH. International treaty status cannot be confirmed from this abstract.

Only Sweden and Brazil controlled it at time of publication.

checked by claude-sonnet-4-6 · May 8, 2026

Coverage & Gaps

effect links

181 links · 180 approved · 43 audited0/181 with evidence basis

Research Trail

substance-article pipeline-v5 May 7, 2026

Step	Source	Query	Results
1database lookup	PubChem	25E-NBOH	1 result, 1 selected
selection rationaleselection rationale Only result; confirms chemical identity from brief discarded 0: no summary recorded
2literature search	PubMed	25E-NBOH phenethylamine NBOH psychedelic	2 results, 2 selected
selection rationaleselection rationale Both directly relevant - only published papers with 25E-NBOH-specific data
3literature search	OpenAlex	25x-NBOH psychedelic phenethylamine receptor	10 results, 4 selected
selection rationaleselection rationale High-citation papers with direct relevance to NBOH/NBOMe pharmacology
4literature search	PubMed	NBOMe NBOMes 5-HT2A agonist potent psychedelic binding	3 results, 3 selected
selection rationaleselection rationale Key pharmacological references for NBOMe/NBOH class
5literature search	PubMed	25CN-NBOH serotonin 5-HT2A selective agonist receptor	10 results, 3 selected
selection rationaleselection rationale 25CN-NBOH is closest well-studied structural analog to 25E-NBOH; relevant for class pharmacology context
6clinical trial search	ClinicalTrials.gov	25E-NBOH NBOH psychedelic phenethylamine	0 results
selection rationaleselection rationale Expected - 25E-NBOH is an emerging NPS with no clinical development
7literature search	PubMed	2C-E 2,5-dimethoxy-4-ethylphenethylamine hallucinogen psychedelic pharmacology	1 result, 1 selected
selection rationaleselection rationale 2C-E is the parent compound of 25E-NBOH; pharmacology data provides context
8web search	WebSearch	25E-NBOH legal status scheduling US UK EU controlled substance analog	10 results, 4 selected
selection rationaleselection rationale Legal status critical data; forensic paper is direct primary source for 25E-NBOH discarded 3: no summary recorded
9web search	WebSearch	NBOH series Martin Hansen University Copenhagen 2010 discovery	10 results, 1 selected
selection rationaleselection rationale Key historical paper establishing NBOH class origin
10document retrieval	PubMed	Locomotor and discriminative stimulus effects of NBOH hallucinogens	1 result, 1 selected
selection rationaleselection rationale Most important direct 25E-NBOH behavioral data
11document retrieval	PMC	25E-NBOH behavioral pharmacology data	1 result, 3 selected
selection rationaleselection rationale Full quantitative pharmacological data for 25E-NBOH
12web search	WebSearch	25E-NBOH dose range human experience	10 results, 1 selected
selection rationaleselection rationale Only available dose data; labeled as community reports
13document retrieval	PsychonautWiki	25E-NBOH dose duration effects safety	1 result, 3 selected
selection rationaleselection rationale Harm reduction dose reference; labeled as community data
14database lookup	PubChem	CID 135391539	1 result, 1 selected
selection rationaleselection rationale Verifies chemical identity
15literature search	PubMed	DARK classics NBOMe ACS chemical neuroscience 2020	1 result, 1 selected
selection rationaleselection rationale Major review of NBOMe/NBOH class covering all key aspects
16literature search	PubMed	NBOMe blotting paper severe toxicity beware	1 result, 1 selected
selection rationaleselection rationale Relevant clinical safety reference for NBOH class
17cross reference	PubChem + PubMed + OpenAlex	25E-NBOH data synthesis	31 results, 1 selected
selection rationaleselection rationale Final cross-reference confirming consistency across sources
18document retrieval	PsychonautWiki	dose duration effects safety 25E-NBOH	1 result, 2 selected
selection rationaleselection rationale Only quantitative dose data available; labeled as community-report source

Research document (raw, unedited pipeline output)

# Research Output: 25E-NBOH

---

## Chemical Identity

**PubChem CID:** 135391539 (api_verified via PubChem lookup)

**Molecular Formula:** C19H25NO3

**Molecular Weight:** 315.4 g/mol

**IUPAC Name:** 2-[[2-(4-ethyl-2,5-dimethoxyphenyl)ethylamino]methyl]phenol

**InChIKey:** SYBINTRPEZWFLZ-UHFFFAOYSA-N

**Common synonyms:** 2C-E-NBOH, NBOH-2CE, NBOH-2C-E

**Brief seed data discrepancies:**
- The brief listed SMILES, Molecular formula, Molecular weight, InChIKey, and PubChem CID all as empty. PubChem confirms CID 135391539, C19H25NO3, MW 315.4, and InChIKey SYBINTRPEZWFLZ-UHFFFAOYSA-N. The IUPAC name in the brief matches. **FLAG for generation agent: PubChem CID, formula, weight, and InChIKey should be populated in the database from this verified data.**
- SMILES: Not returned by the PubChem API tool used in this pipeline. SMILES can be retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/135391539. Based on structure, the canonical SMILES is derivable from 2C-E parent with N-(2-hydroxybenzyl) addition.

**Physical properties:** No published melting point, log P, aqueous solubility, or stability data specific to 25E-NBOH were found in the literature. The compound is thermolabile — it degrades to 2C-E under standard gas chromatography conditions (Belchior de Andrade & Gonzalez-Rodriguez 2019 [Ref 20]; Arantes et al. 2017 [Ref 18]; Machado et al. 2019 [Ref 14]). This thermolability is shared with 25I-NBOH and is a characteristic of the NBOH class.

---

## Pharmacology

### Receptor Binding

25E-NBOH is a potent agonist at serotonin 5-HT2A and 5-HT2C receptors [Ref 15]. No published Ki or EC50 values specific to 25E-NBOH have been identified in the literature. Available data are at the class level:

**NBOH/NBOMe class binding profile (by analogy):**
- The N-benzylphenethylamine (NBOMe) class shows subnanomolar affinity at 5-HT2A receptors and high selectivity over 5-HT1A receptors (Zawilska et al. 2020 [Ref 5]; Halberstadt 2017 [Ref 3]; Rickli et al. 2015 [Ref 4])
- NBOH compounds use a 2-hydroxybenzyl N-substituent (vs. 2-methoxybenzyl in NBOMes) and retain high 5-HT2A receptor affinity
- Addition of the N-benzyl group to 2C-E's phenethylamine scaffold markedly increases 5-HT2A binding affinity and hallucinogenic potency relative to 2C-E (Halberstadt 2017 [Ref 3]; Poulie et al. 2020 [Ref 21])
- NBOMe class drugs are partial agonists at 5-HT2A and 5-HT2B receptors with high selectivity for 5-HT2A/2C over 5-HT1A (Rickli et al. 2015 [Ref 4])
- Alpha-1A adrenoceptor binding (Ki < 1 µM) has been documented for NBOMe compounds, mechanistically linking the class to vasoconstriction and cardiovascular sympathomimetic effects (Rickli 2015 [Ref 4]; Zawilska et al. 2020 [Ref 5])

**25E-NBOH specifically:** Munir et al. (2025 [Ref 15]) confirm that 25E-NBOH "was found to be a high affinity full agonist at the 5-HT2A and 5-HT2C receptors." No numeric Ki or EC50 values for 25E-NBOH are provided in any published source.

**FLAG:** No substance-specific radioligand binding data (Ki, EC50) for 25E-NBOH exist in the published literature. All binding affinity claims for 25E-NBOH should be explicitly attributed to structural analogy with the NBOH/NBOMe class.

### Mechanism of Action

Psychedelic effects are mediated primarily through 5-HT2A receptor agonism (Xu et al. 2026 [Ref 12]; Halberstadt 2017 [Ref 3]). Recent cryo-EM structural data demonstrate that 5-HT2A-mediated non-canonical Gi signalling is essential for hallucinogenic effects, while Gq signalling mediates other downstream actions (Xu et al. 2026 [Ref 12]). Biased agonism studies on structurally related 25CN-NBOH show that interactions at Ser159(3×36) determine Gαq vs. β-arrestin-2 signalling balance (Poulie et al. 2022 [Ref 9]; Pottie et al. 2023 [Ref 10]). Whether 25E-NBOH has distinct signalling bias has not been investigated.

### In Vivo Behavioral Pharmacology

Munir et al. (2025 [Ref 15]) is the only published study directly testing 25E-NBOH in animal models:

- **Drug discrimination (rat, DOM-trained):** 25E-NBOH fully substituted for DOM (≥80% drug-lever responding). Discriminative stimulus ED50: **0.072 ± 0.19 mg/kg** (i.p., rat), approximately 3.5-fold more potent than DOM (ED50 0.25 mg/kg). The discriminative stimulus effects of 25E-NBOH were **more potent than both DOM and the 25X-NBOMe compounds** tested previously.
- **Locomotor activity (mouse):** All four NBOH compounds tested produced time-dependent and dose-dependent depression of locomotor activity. Locomotor ED50 for 25E-NBOH: **10.7 ± 0.027 mg/kg** (i.p., mouse). This is approximately 2-fold less potent than DOM (ED50 4.8 mg/kg) and less potent than 25X-NBOMe compounds in previous reports. Maximal locomotor depressant effects appeared within 10 minutes and lasted approximately 3 hours.
- **Conclusion:** 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" (Munir et al. 2025 [Ref 15]). 25I-NBOH failed to fully substitute for DOM and may have lower recreational hallucinogen liability.

The zebrafish model study on N-benzyl-2-phenylethylamine (NBPEA) derivatives (Demin et al. 2022 [Ref 7]) — though not testing 25E-NBOH specifically — demonstrated anxiogenic/hallucinogenic-like behavioral effects for several NBPEA compounds and confirmed 5-HT2A receptor overlap with conventional serotonergic hallucinogens by AI-based behavioral analysis and in silico functional modeling.

### Parent Compound (2C-E) Pharmacology

The parent compound 2,5-dimethoxy-4-ethylphenethylamine (2C-E) has its own published pharmacological characterization: Eshleman et al. (2014 [Ref 6]) documented in vitro receptor binding, monoamine transporter interactions, mouse locomotor activity, and rat drug discrimination data for 2C-E. The N-benzyl modification in 25E-NBOH produces markedly increased 5-HT2A affinity compared to 2C-E, as documented for the class (Halberstadt 2017 [Ref 3]).

### Pharmacokinetics

No published human pharmacokinetic data exist for 25E-NBOH. By class analogy with 25CN-NBOH (Breusova et al. 2021 [Ref 25]):
- NBOH compounds are susceptible to first-pass metabolism
- Metabolic stability of 25CN-NBOH in human liver microsomes and rat in vivo suggests moderate metabolic susceptibility
- Similar class-level ADME patterns are expected for 25E-NBOH based on Poulie et al. 2020 [Ref 21]

---

## History

### Origin of the Parent Compound (2C-E)

2C-E (2,5-dimethoxy-4-ethylphenethylamine) was first synthesized and described by Alexander Shulgin and published in *PiHKAL: A Chemical Love Story* (Shulgin & Shulgin 1991; unverifiable book reference). 2C-E belongs to the 2C-x series of substituted phenethylamines derived structurally from mescaline.

### Development of the NBOH Series

The NBOH compound class was developed by Martin Hansen and colleagues at the Neurobiology Research Unit, Copenhagen University Hospital, as part of the Center for Integrated Molecular Brain Imaging (Cimbi) program, seeking to develop agonist PET radioligands for the serotonin 5-HT2A receptor. Ettrup, Hansen et al. (2011 [Ref 17]) published the in vivo validation of nine novel 5-HT2A receptor agonist PET tracers in the pig brain, derived from phenethylamine backbones including the NBOH scaffold. The paper was received August 2010, placing development of the series around 2009-2010.

25CN-NBOH emerged as the most pharmacologically important compound from this program, described as a highly selective 5-HT2A agonist with 100-fold selectivity over 5-HT2C (Fantegrossi et al. 2015 [Ref 16]; Märcher-Rørsted et al. 2021 [Ref 8]). The DARK Classics review (Poulie et al. 2020 [Ref 21]) documents that NBOMes (the 2-methoxybenzyl analogs) were introduced as new psychoactive substances in 2010, followed by scheduling of several members as Schedule I in 2013. The NBOH series followed a parallel trajectory as a research chemical market alternative.

### Market Appearance of 25E-NBOH

Per Vágnerová et al. (2026 [Ref 1]): "25E-NBOH has been on the market for the last seven years" (counting from 2026 publication date → market appearance approximately 2018-2019). This aligns with Wikipedia's statement that 25E-NBOH was first developed as a brain imaging agent in 2010 but subsequently sold as a designer drug [Ref 23].

### First Forensic Identification

The first academic forensic identification of 25E-NBOH in seized street samples was reported by Machado et al. (2019 [Ref 14]): blotter papers seized 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** in this period [Ref 14, Ref 23]. A preceding study identified 25I-NBOH in Brazilian seizures in 2017 (Arantes et al. 2017 [Ref 18]), establishing the pattern of NBOH detection in Latin American forensic labs.

---

## Subjective Effects

No controlled human studies or even case reports with confirmed 25E-NBOH administration and documented subjective effects have been published. All subjective effect data comes from community sources (user reports, harm reduction wikis).

### Published/Community Descriptions

From community sources [Refs 23, 27, 28] (labeled as user-report-only; no controlled study data):
- 25E-NBOH is described as a "clear-headed, dose-sensitive psychedelic" capable of producing strong visual distortions
- **Visual effects:** Open- and closed-eye visuals, color enhancement, geometry, visual drifting, tracers, after-images
- **Body load:** Significant vasoconstriction described as making muscles very sore; dehydration sensation; stimulation; muscle tension. Users report some take niacin supplements to counteract vasoconstriction.
- **Cognitive effects:** Time distortion, enhanced introspection, creativity enhancement, pattern recognition enhancement
- **Transpersonal:** Ego dissolution possible at higher doses
- **Character:** Described as sharing most properties with 25E-NBOMe but with "moderately reduced potency and a shorter duration" [Ref 23]

### Effects Taxonomy (Basis for Seed Effect Profile)

The 44 seed effects listed in the brief (all lacking intensity/frequency values) are consistent with the NBOH class profile inferred from: Zawilska et al. 2020 [Ref 5] (NBOMe adverse effects), Munir et al. 2025 [Ref 15] (behavioral effects in animals), and community reports [Refs 27, 28]. Specific effects requiring editorial attention and evidence-grading:
- **Vasoconstriction** [body]: Class-level documented (alpha-1A adrenoceptor binding) [Ref 4]; should be high intensity/high frequency
- **Stimulation** [body]: Common for 5-HT2A agonists; class-level
- **Seizure threshold reduction** [body]: Documented for NBOMe class [Refs 3, 5]; frequency likely rare
- **Temperature dysregulation** [body]: Documented for NBOMe class (hyperthermia) [Ref 5]
- **Pupil dilation** [body]: Class-level documented for 5-HT2A agonists; should be high frequency

**FLAG:** All effect intensities and frequencies in the seed data are null/null. Every proposed value for the 44 effects must be flagged as community_consensus or analog_inference — no controlled study data exist to assign values.

---

## Safety & Toxicology

### Published Toxicity References

**Case reports involving 25E-NBOH specifically:** Xiang et al. (2024 [Ref 2]) state: "25B-NBOH, 25E-NBOH, 25H-NBOH, and 25iP-NBOMe have begun to flow into the black market and **have caused several poisoning cases and even fatal cases**." No case details are provided in this metabolic characterization paper. **FLAG: Safety-critical. This is the only published statement about 25E-NBOH fatalities; details are absent and unverifiable from this source alone.**

**NBOMe/NBOH class toxicology (by structural analogy):**
Halberstadt (2017 [Ref 3]) reviewed 51 published cases of NBOMe toxicity and identified:
- Rhabdomyolysis as a relatively common complication, likely linked to seizures, hyperthermia, and vasoconstriction
- Excited delirium, agitation, violent behavior
- Sympathomimetic signs: mydriasis, tachycardia, hypertension, hyperthermia, diaphoresis
- Seizures
- DIC, hypoglycemia, metabolic acidosis, multiorgan failure

Zawilska et al. (2020 [Ref 5]) confirm this adverse effects profile and report that NBOMe use has led to fatalities. Isbister et al. (2015 [Ref 22]) describe severe toxicity from blotter paper hallucinogens (NBOMes).

### Thermolability and Misidentification Risk

25E-NBOH is thermolabile and degrades to 2C-E under GC-MS analysis conditions (Belchior de Andrade & Gonzalez-Rodriguez 2019 [Ref 20]; Machado et al. 2019 [Ref 14]). This means:
1. Standard GC-MS screening may misidentify 25E-NBOH as 2C-E (the parent compound)
2. Analytical confirmation requires LC-MS/MS, NMR, or FTIR
3. Clinical and forensic diagnosis of 25E-NBOH intoxication is complicated; cases may be misattributed

The 2026 metabolic study (Vágnerová et al. [Ref 1]) also confirms 2C-E as an actual N-debenzylation metabolite, further complicating GC-MS-based diagnosis.

### LD50

No LD50 data for 25E-NBOH in any species have been published.

### Organ Toxicity

No organ toxicity data specific to 25E-NBOH have been published. By class analogy: rhabdomyolysis-induced acute kidney injury, hepatic injury from hyperthermia, cardiac arrhythmias from sympathomimetic effects (Halberstadt 2017 [Ref 3]; Zawilska et al. 2020 [Ref 5]).

### Cardiovascular Risk

Alpha-1A adrenoceptor binding in the NBOMe class (Rickli et al. 2015 [Ref 4]) predicts vasoconstriction. Class cardiovascular risks: hypertension, tachycardia, peripheral ischemia. Wsół (2023 [Ref cited in text]) reviews cardiovascular safety of psychedelics, noting serotonergic agonism at 5-HT2A/2B and 5-HT4 receptors as relevant to cardiotoxicity.

---

## Harm Reduction

### Analytical Testing
- Standard GC-MS **cannot reliably identify** 25E-NBOH due to thermolability → degradation to 2C-E (Machado 2019 [Ref 14]; Belchior de Andrade 2019 [Ref 20])
- LC-MS/MS, ATR-FTIR, or NMR required for definitive identification
- Reagent colorimetric tests (Ehrlich, Hofmann): The Hofmann/Simon's reagent is not selective for NBOHs
- Drug checking services using advanced LC-MS/MS should be used when feasible

### Route of Administration
- Typically sublingual via blotter paper; sometimes insufflated
- Insufflation carries higher adverse event risk (faster onset, difficult dose titration)
- Intravenous use of NBOMe/NBOH class has been associated with severe toxicity (Zawilska et al. 2020 [Ref 5])

### Dose Sensitivity
- 25E-NBOH is described as "dose-sensitive" in community sources [Ref 27]
- Wide variation in blotter paper dosing (300-1500 µg per unit [Ref 23]) means a single blotter contains highly variable active doses
- Individual sensitivity variation is high and unpredictable

### Medical Emergency
- Class-level emergency signs: agitation, seizures, hyperthermia, tachycardia, hypertension, loss of consciousness
- Rhabdomyolysis risk with severe presentations (Halberstadt 2017 [Ref 3])
- No specific antidote; supportive care

---

## Tolerance & Dependence

### Tolerance

No published tolerance data for 25E-NBOH specifically.

By class (5-HT2A agonist mechanism, de la Fuente Revenga et al. 2022 [Ref 19]):
- Rapid tolerance develops to psychedelic effects via 5-HT2A receptor downregulation in the frontal cortex
- Tolerance is detectable after a **single administration** (24h post-dose)
- Repeated dosing over 4 days produces progressive decrease in behavioral effects
- **Cross-tolerance** exists bidirectionally among psychedelic 5-HT2A agonists (DOI ↔ LSD); does not occur with non-psychedelic 5-HT2A agonists (lisuride)
- Tolerance mechanism is independent of β-arrestin-2 signalling

This implies 25E-NBOH would show cross-tolerance with LSD, psilocybin, DMT, mescaline, and other psychedelic 5-HT2A agonists. The standard caution of waiting at least 2 weeks between psychedelic sessions to minimize tolerance applies by class analogy.

### Dependence

No published dependence liability data for 25E-NBOH. Classic psychedelics as a class have very low reinforcing potential in animal self-administration models. 25C-NBF (a structurally related NBF analog) showed no rewarding effects in mice and no reinforcing effects in rats (Nadal-Gratacós et al. 2026 [PMID 41238841]). No evidence of compulsive use or physical dependence for the NBOH class.

### Withdrawal

No published withdrawal data. Classical psychedelics produce no clinically significant physical withdrawal syndrome.

---

## Interactions

### Serotonergic Interactions

**MAOIs:** Combination with monoamine oxidase inhibitors (both reversible and irreversible) carries serotonin syndrome risk. 5-HT2A agonists combined with elevated synaptic serotonin from MAOI-mediated inhibition can precipitate serotonin toxicity. Malcolm & Thomas (2022 [Ref 11]) review this risk for serotonergic psychedelics.

**SSRIs/SNRIs:** Chronic SSRI use causes 5-HT2A receptor downregulation, potentially attenuating psychedelic effects. Acute combination may theoretically increase serotonergic tone. The interaction in clinical psychedelic settings is complex and under investigation (Malcolm & Thomas 2022 [Ref 11]).

**Lithium:** Lithium combined with psychedelic 5-HT2A agonists has been reported to increase seizure risk in case reports involving serotonergic psychedelics. Mechanism unclear but may involve altered intracellular signaling cascade downstream of 5-HT2A. **FLAG: Safety-critical. No controlled data; based on class-level case reports.**

### Cardiovascular/Vasoconstriction Interactions

Combining 25E-NBOH with other vasoconstrictive substances (ergotamines, stimulants such as amphetamine, cocaine, MDMA) is expected to carry additive peripheral vasoconstriction risk by class analogy with NBOMe compounds (Halberstadt 2017 [Ref 3]).

### Pharmacological Contraindications

- MAOIs (absolute)
- Cardiovascular disease (vasoconstriction risk)
- Epilepsy/seizure disorders (seizure threshold reduction)
- Psychiatric disorders with psychosis susceptibility

---

## Legal Status

**United Kingdom:** Class A controlled substance under the Misuse of Drugs Act 1971, by virtue of the N-benzylphenethylamine catch-all clause [Ref 23]. This makes 25E-NBOH possession and supply a serious criminal offense.

**Brazil:** Explicitly scheduled since approximately December 2018 (per Arantes et al. 2017 [Ref 18] context and Wikipedia [Ref 23]). Brazil was among the first countries to control NBOH compounds.

**Canada:** Controlled substance under phenethylamine blanket-ban language in the Controlled Drugs and Substances Act [web-retrieved].

**United States:** Not an explicitly scheduled substance. May be subject to prosecution under the Federal Analogue Act (21 USC §813) as a compound structurally similar to Schedule I substances. **FLAG: US legal status not directly confirmed via DEA scheduling database; relies on analog act analysis and secondary sources.**

**Australia:** Not specifically verified. Australia's Standard for the Uniform Scheduling of Medicines and Poisons may cover this compound under generic phenethylamine language; verification against TGA schedules was not possible via available tools.

**European Union:** Individual member states vary. Germany, Sweden, and others have scheduled specific NBOH compounds; comprehensive EU-wide scheduling data not confirmed in this research.

**International:** NBOH compounds are not scheduled under any UN Conventions (1961, 1971, 1988 drug treaties) [Ref 18, Ref 23].

---

## Clinical Trials

**None found.** A search of ClinicalTrials.gov returned no studies for 25E-NBOH or NBOH compounds generally. As an emerging NPS with a market history of ~7 years (Vágnerová et al. 2026 [Ref 1]), 25E-NBOH has no clinical development history. This contrasts with 25CN-NBOH, which has been used extensively as a pharmacological research tool (Märcher-Rørsted et al. 2021 [Ref 8]).

---

## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief.

---

## Gaps & Flags

### 🔴 Safety-Critical Flags

1. **Fatality reference without case data:** Xiang et al. 2024 [Ref 2] states 25E-NBOH "has caused several poisoning cases and even fatal cases." No case details, numbers, circumstances, or outcomes are provided in this metabolic paper. The generation agent should note these fatalities exist but cannot characterize them further without additional sources.

2. **Dose ranges are community-report only:** The PsychonautWiki dose range (Threshold: 50 µg; Light: 200-600 µg; Common: 600-1000 µg) [Ref 27] and the blotter paper dose range (300-1500 µg per unit) [Ref 14, Ref 23] are entirely derived from community sources and forensic market data. No controlled dose-finding study exists. **These values should be presented in the article with explicit community-report labeling.**

3. **Lithium interaction warning:** Class-level only, no 25E-NBOH-specific data.

4. **US legal status:** Not confirmed via DEA scheduling database; analog act applicability is inferential.

### 🟡 Data Gaps

5. **No substance-specific Ki/EC50 values:** All receptor binding data for 25E-NBOH are inferred from NBOH and NBOMe class data (25CN-NBOH, 25I-NBOMe, 25C-NBOMe, etc.). The generation agent must clearly flag all binding affinity values as class-level analogy, not substance-specific measurements.

6. **SMILES string not recovered:** PubChem API did not return SMILES. Should be populated from PubChem website (CID 135391539).

7. **No human pharmacokinetic data:** Bioavailability, Tmax, half-life, and CYP enzyme involvement are entirely unknown for 25E-NBOH in humans. Metabolic pathway data (Vágnerová 2026 [Ref 1]; Xiang 2024 [Ref 2]) is in vitro/animal only.

8. **Duration data is community-report only:** Reported as shorter than 25E-NBOMe, which is 4-8 hours; no published controlled duration data.

9. **No melting point, solubility, or physical property data:** These are unpublished for 25E-NBOH.

10. **No stereochemistry/chiral center analysis:** 25E-NBOH appears to lack chiral centers based on its structure (confirmed by InChIKey analysis); no published sterochemistry analysis found.

11. **Effect intensity/frequency values (all 44 seed effects):** All null/null in the brief. Without controlled human studies, all proposed values must be derived from structural analog inference (NBOH class) and community consensus. The generation agent should assign values based on the evidence hierarchy while clearly flagging the provenance as analog_inference.

12. **Australia legal status:** Unverified.

13. **No abuse liability or dependence animal studies specific to 25E-NBOH:** The Munir 2025 [Ref 15] paper covers locomotor and discriminative stimulus effects only, not self-administration or conditioned place preference.

### Summary of Basis for Structured Data Proposals

| Data Point | Evidence Level | Source(s) |
|---|---|---|
| Chemical identity | High — API verified | PubChem [Ref 17 context] |
| 5-HT2A/2C agonist mechanism | High — direct behavioral confirmation | Munir 2025 [Ref 15] |
| Discriminative stimulus ED50 (0.072 mg/kg, rat) | Moderate — single animal study | Munir 2025 [Ref 15] |
| Locomotor depression ED50 (10.7 mg/kg, mouse) | Moderate — single animal study | Munir 2025 [Ref 15] |
| Metabolic pathways | Moderate — in vitro/animal only | Vágnerová 2026 [Ref 1], Xiang 2024 [Ref 2] |
| 2C-E as metabolite | High — confirmed by reference standard | Vágnerová 2026 [Ref 1] |
| Dose ranges | Low — community/market data only | PsychonautWiki [Ref 27], Machado 2019 [Ref 14] |
| Duration | Low — community data only | Wikipedia [Ref 23], PsychonautWiki [Ref 27] |
| Vasoconstriction | Moderate — class-level mechanism | Rickli 2015 [Ref 4], community reports |
| Fatalities | Low — stated without detail | Xiang 2024 [Ref 2] |
| Tolerance mechanism | Moderate — class-level animal data | de la Fuente Revenga 2022 [Ref 19] |
| UK legal status | High | MDA 1971 catch-all clause [Ref 23] |
| Brazil scheduling | High | Arantes 2017 [Ref 18] + Wikipedia [Ref 23] |
| Canada | Moderate | Web-retrieved |
| US | Low — inferential only | Federal Analog Act |

25E-NBOH

Value Provenance

Dosing

sublingualtrace →

insufflatedtrace →

Duration

sublingual

Safety

Toxicity Profiletrace →

Dependence Profiletrace →

Withdrawal Profiletrace →

Tolerance Profiletrace →

Effects & Profile

Contraindications

Timeline Phases

sublingual

Dose Tier Summaries

History

Sources

Claim Verification

Coverage & Gaps

Research Trail

sublingualtrace

insufflatedtrace

Toxicity Profiletrace

Dependence Profiletrace

Withdrawal Profiletrace

Tolerance Profiletrace