Skip to main content
Psychedex

25D-NBOMe

2-(2,5-dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine

Sources
26
3 strong · 15 moderate · 7 weak · 1 insufficient

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

Claims checked
82
57verified25inconclusive

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

Generated
May 9, 2026 · pipeline-v5
Values approved
170/170 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

sublingualtrace

FieldPublishedAI ProposedConfidence
Threshold300 µg300 µglow
Low300–800 µg300–800 µglow
Common800–1000 µg800–1000 µglow
Strong1000–1200 µg1000–1200 µglow
Heavy1200+ µg1200+ µglow
Editorial

All dose values are community consensus from PsychonautWiki and a single Erowid user report (1600 µg buccal). No controlled dose-escalation study exists for 25D-NBOMe. Values carried forward from existing DB seed data. The single user report at 1600 µg (above heavy threshold) described manageable but uncomfortable effects, broadly consistent with these ranges.

Reasoning

All dose values are community consensus from PsychonautWiki and a single Erowid user report (1600 µg buccal). No controlled dose-escalation study exists for 25D-NBOMe. Values carried forward from existing DB seed data. The single user report at 1600 µg (above heavy threshold) described manageable but uncomfortable effects, broadly consistent with these ranges.

Evidence basis: community_consensus_large

Duration

sublingual

FieldPublishedAI ProposedConfidence
Onsettrace20–40 minutes20–40 minuteslow
Editorial

DB seed data: 20-40 minutes sublingual. Single Erowid report showed ~10 min onset buccally at 1600 µg — likely faster due to higher dose and buccal vs sublingual route. Class data (Zawilska 2020) consistent with 20-40 min sublingual.

Reasoning

DB seed data: 20-40 minutes sublingual. Single Erowid report showed ~10 min onset buccally at 1600 µg — likely faster due to higher dose and buccal vs sublingual route. Class data (Zawilska 2020) consistent with 20-40 min sublingual.

Evidence basis: community_consensus_large

Come uptrace20–40 minutes20–40 minuteslow
Editorial

No direct data for 25D-NBOMe come_up phase. Proposed 20-40 minutes based on NBOMe class pharmacology and general 5-HT2A psychedelic come_up patterns. Structural analogy from 25I-NBOMe.

Reasoning

No direct data for 25D-NBOMe come_up phase. Proposed 20-40 minutes based on NBOMe class pharmacology and general 5-HT2A psychedelic come_up patterns. Structural analogy from 25I-NBOMe.

Evidence basis: structural_analogy

Peaktrace1–2 hours1–2 hourslow
Editorial

DB seed data: 1-2 hours. Erowid report peak at ~50 min (slightly faster, likely dose-dependent). Class data (Zawilska 2020) supports 1-2 hour peak for NBOMe sublingual.

Reasoning

DB seed data: 1-2 hours. Erowid report peak at ~50 min (slightly faster, likely dose-dependent). Class data (Zawilska 2020) supports 1-2 hour peak for NBOMe sublingual.

Evidence basis: community_consensus_large

Offsettrace1–2 hours1–2 hourslow
Editorial

DB seed data: 1-2 hours offset. Consistent with NBOMe class duration patterns. No substance-specific pharmacokinetic data.

Reasoning

DB seed data: 1-2 hours offset. Consistent with NBOMe class duration patterns. No substance-specific pharmacokinetic data.

Evidence basis: community_consensus_large

Totaltrace4–8 hours4–8 hourslow
Editorial

DB seed data listed 4-6 hours. Erowid report (1600 µg buccal) showed ~8 hours total including residual stimulation. Work-notes flag that total may extend to 6-8 hours at strong+ doses. Proposed 4-8 hours to capture dose-dependent range. Class data (Zawilska 2020) consistent.

Reasoning

DB seed data listed 4-6 hours. Erowid report (1600 µg buccal) showed ~8 hours total including residual stimulation. Work-notes flag that total may extend to 6-8 hours at strong+ doses. Proposed 4-8 hours to capture dose-dependent range. Class data (Zawilska 2020) consistent.

Evidence basis: community_consensus_large

After effectstrace1–4 hours1–4 hourslow
Editorial

Inferred from Erowid report showing insomnia and residual stimulation extending to ~8h total from a 4-6h subjective core. Proposed 1-4 hours aftereffects to account for residual stimulation and wakefulness beyond primary effects.

Reasoning

Inferred from Erowid report showing insomnia and residual stimulation extending to ~8h total from a 4-6h subjective core. Proposed 1-4 hours aftereffects to account for residual stimulation and wakefulness beyond primary effects.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutemoderatemoderatemedium
Chronicmoderatemoderatemedium
Organs Affectedcardiovascular, neurological, renalcardiovascular, neurological, renalmedium
Editorial

Acute 'moderate' supported by substance-specific hERG inhibition and QT prolongation in rats (Yoon 2019) plus class-level toxicity profile (seizures, rhabdomyolysis, hyperthermia — Halberstadt 2017). Chronic 'moderate' based on in vitro neurotoxicity (Gil-Martins 2024) and chronic dosing effects in rats (Wojtas 2024: genotoxicity markers, microglial activation). No human therapeutic index calculable. Cardiotoxicity data are animal/cell-line only — translation to human psychedelic doses unknown.

Reasoning

Acute 'moderate' supported by substance-specific hERG inhibition and QT prolongation in rats (Yoon 2019) plus class-level toxicity profile (seizures, rhabdomyolysis, hyperthermia — Halberstadt 2017). Chronic 'moderate' based on in vitro neurotoxicity (Gil-Martins 2024) and chronic dosing effects in rats (Wojtas 2024: genotoxicity markers, microglial activation). No human therapeutic index calculable. Cardiotoxicity data are animal/cell-line only — translation to human psychedelic doses unknown.

Evidence basis: animal_study

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalnegligiblenegligiblelow
Psychologicallowlowlow
Compulsive Redosinglowlowlow
Dose Escalationlowlowlow
Editorial

Dependence assessment relies entirely on animal data (Lee 2023 rodent IVSA/CPP). Physical dependence negligible per psychedelic class norms. Psychological dependence rated low due to confirmed dopaminergic reinforcement signal — unique among serotonergic psychedelics. No human dependence cases or withdrawal reports published for 25D-NBOMe or NBOMe class generally.

Reasoning

Dependence assessment relies entirely on animal data (Lee 2023 rodent IVSA/CPP). Physical dependence negligible per psychedelic class norms. Psychological dependence rated low due to confirmed dopaminergic reinforcement signal — unique among serotonergic psychedelics. No human dependence cases or withdrawal reports published for 25D-NBOMe or NBOMe class generally.

Evidence basis: animal_study

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitynonenonelow
Symptoms——low
FatalNoNolow
Medical SupervisionNot requiredNot requiredlow
Editorial

No withdrawal syndrome documented for 25D-NBOMe or NBOMe compounds generally. Consistent with serotonergic psychedelic class profile.

Reasoning

No withdrawal syndrome documented for 25D-NBOMe or NBOMe compounds generally. Consistent with serotonergic psychedelic class profile.

Evidence basis: animal_study

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidmedium
Half-life3 days3 daysmedium
Full Reset10 days10 daysmedium
Cross-tolerancesLSD, psilocybin, psilocin, mescaline, 2C-D, 2C-B, 2C-E, 2C-I, DOB, DOC, DOM, 25I-NBOMe, 25C-NBOMe, 25B-NBOMeLSD, psilocybin, psilocin, mescaline, 2C-D, 2C-B, 2C-E, 2C-I, DOB, DOC, DOM, 25I-NBOMe, 25C-NBOMe, 25B-NBOMemedium
Editorial

Rapid tolerance buildup confirmed in rodent models (Wojtas 2024 for NBOMe class). Half-life and reset values inferred from LSD/psilocybin 5-HT2A downregulation kinetics — no substance-specific human data. Cross-tolerance list based on shared 5-HT2A agonist mechanism across serotonergic psychedelic class.

Reasoning

Rapid tolerance buildup confirmed in rodent models (Wojtas 2024 for NBOMe class). Half-life and reset values inferred from LSD/psilocybin 5-HT2A downregulation kinetics — no substance-specific human data. Cross-tolerance list based on shared 5-HT2A agonist mechanism across serotonergic psychedelic class.

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
cardiovascular Pre-existing cardiac arrhythmia or prolonged QT intervaltraceabsoluteabsolutemedium
Editorial

Substance-specific hERG inhibition and QT prolongation confirmed in rats by Yoon et al. 2019. This is the only contraindication with direct substance-specific support.

Reasoning

Substance-specific hERG inhibition and QT prolongation confirmed in rats by Yoon et al. 2019. This is the only contraindication with direct substance-specific support.

cardiovascular Concurrent QT-prolonging medicationstraceabsoluteabsolutemedium
Editorial

25D-NBOMe's substance-specific hERG inhibition (Yoon 2019) combined with known QT-prolonging drugs creates pharmacologically predictable additive cardiac risk.

Reasoning

25D-NBOMe's substance-specific hERG inhibition (Yoon 2019) combined with known QT-prolonging drugs creates pharmacologically predictable additive cardiac risk.

neurological Seizure disorderstraceabsoluteabsolutemedium
Editorial

Class-level evidence from Halberstadt 2017 review of 51 NBOMe toxicity cases documenting seizures. No 25D-NBOMe-specific seizure data, but class mechanism applies.

Reasoning

Class-level evidence from Halberstadt 2017 review of 51 NBOMe toxicity cases documenting seizures. No 25D-NBOMe-specific seizure data, but class mechanism applies.

other Concurrent serotonergic medicationstraceabsoluteabsolutemedium
Editorial

Class-level pharmacological inference from potent 5-HT2A agonism. Tramadol additionally lowers seizure threshold, compounding risk. No substance-specific case reports but mechanism is well-established.

Reasoning

Class-level pharmacological inference from potent 5-HT2A agonism. Tramadol additionally lowers seizure threshold, compounding risk. No substance-specific case reports but mechanism is well-established.

cardiovascular Cardiovascular diseasetracerelativerelativemedium
Editorial

Class-level NBOMe sympathomimetic profile documented in Halberstadt 2017 and Zawilska 2020. Single user report confirms tachycardia and cardiovascular awareness.

Reasoning

Class-level NBOMe sympathomimetic profile documented in Halberstadt 2017 and Zawilska 2020. Single user report confirms tachycardia and cardiovascular awareness.

metabolic Hypokalemia or hypomagnesemiatracerelativerelativelow
Editorial

General pharmacological principle: electrolyte imbalances potentiate hERG-mediated arrhythmia risk. Applied to 25D-NBOMe given its confirmed hERG inhibition (Yoon 2019).

Reasoning

General pharmacological principle: electrolyte imbalances potentiate hERG-mediated arrhythmia risk. Applied to 25D-NBOMe given its confirmed hERG inhibition (Yoon 2019).

hepatic Hepatic impairmenttracerelativerelativelow
Editorial

Structural analogy from 25B/25C-NBOMe CYP enzyme assignments. No direct CYP profiling for 25D-NBOMe. Contraindication is entirely class-inferred.

Reasoning

Structural analogy from 25B/25C-NBOMe CYP enzyme assignments. No direct CYP profiling for 25D-NBOMe. Contraindication is entirely class-inferred.

psychiatric History of psychotic disorderstracerelativerelativemedium
Editorial

Class-level risk documented for NBOMe compounds in Halberstadt 2017 and Zawilska 2020. No 25D-NBOMe-specific psychiatric case reports.

Reasoning

Class-level risk documented for NBOMe compounds in Halberstadt 2017 and Zawilska 2020. No 25D-NBOMe-specific psychiatric case reports.

other Concurrent lithium usetraceabsoluteabsolutelow
Editorial

Class-level interaction documented for LSD + lithium. Applied to 25D-NBOMe as a potent serotonergic psychedelic. No substance-specific case data.

Reasoning

Class-level interaction documented for LSD + lithium. Applied to 25D-NBOMe as a potent serotonergic psychedelic. No substance-specific case data.

Timeline Phases

sublingual

FieldPublishedAI ProposedConfidence
Onsettrace600–1200 sec(i=0.10)600–1200 sec(i=0.10)low
Editorial

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Reasoning

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Evidence basis: community_consensus_large

Come uptrace1200–2700 sec(i=0.50)1200–2700 sec(i=0.50)low
Editorial

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Reasoning

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Evidence basis: community_consensus_large

Peaktrace3600–5400 sec(i=1.00)3600–5400 sec(i=1.00)low
Editorial

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Reasoning

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Evidence basis: community_consensus_large

Resolutiontrace3600–7200 sec(i=0.35)3600–7200 sec(i=0.35)low
Editorial

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Reasoning

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Evidence basis: community_consensus_large

Afterglowtrace5400–12600 sec(i=0.15)5400–12600 sec(i=0.15)low
Editorial

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Reasoning

Timeline derived from single Erowid 25D-NBOMe user report (1600 µg buccal: onset ~10 min, peak ~50 min, total ~8h), DB seed data (onset 20-40 min, peak 1-2h, offset 1-2h, total 4-6h), and NBOMe class pharmacology (Zawilska 2020, Halberstadt 2017). No controlled pharmacokinetic data exist. Buccal report showed faster onset and longer total than sublingual class norm, likely dose-dependent. Phase durations represent the middle ~80% of expected experiences at common doses.

Evidence basis: community_consensus_large

Dose Tier Summaries

lighttrace
low

Discernible color enhancement and surface texturing become apparent — colors appear more saturated, surfaces gain a subtle breathing quality. Visual drifting may be faintly present. Cognitive effects are mild: a slight increase in associative thinking and novelty enhancement without significant impairment. Mild body stimulation emerges, with possible awareness of elevated heart rate. Appetite suppression is common. Pupil dilation becomes noticeable. The bitter sublingual taste persists as a defining feature of the experience. Duration is typically shorter than at common doses. Sleep may be delayed by 4–6 hours post-administration due to residual stimulation.

Editorial

Extrapolated from 25I-NBOMe light-dose reports and the single 25D-NBOMe Erowid report (which used a dose above this range). Community consensus from PsychonautWiki dose tables. No controlled data.

Reasoning

Extrapolated from 25I-NBOMe light-dose reports and the single 25D-NBOMe Erowid report (which used a dose above this range). Community consensus from PsychonautWiki dose tables. No controlled data.

Evidence basis: community_consensus_large

thresholdtrace
low

Subtle shifts in visual brightness and color saturation emerge without formed geometry. The world may appear slightly more vivid or textured, but effects can be difficult to distinguish from placebo. A mild undercurrent of stimulation — slight alertness, faint bodily awareness — may be present. Physical effects are minimal. The characteristic bitter, numbing taste on sublingual contact is noticeable and distinguishes the compound from LSD immediately. Body load is negligible at this level. Functional impairment is unlikely. Duration may be shorter than at higher doses, resolving within 3–4 hours. Sleep is generally unaffected.

Editorial

No controlled dose-response data exist for 25D-NBOMe. Threshold description inferred from 25I-NBOMe analog profile and general NBOMe class pharmacology. Single Erowid user report used a dose well above threshold. All values are community consensus.

Reasoning

No controlled dose-response data exist for 25D-NBOMe. Threshold description inferred from 25I-NBOMe analog profile and general NBOMe class pharmacology. Single Erowid user report used a dose well above threshold. All values are community consensus.

Evidence basis: community_consensus_large

commontrace
low

A clear psychedelic state with visual breathing, color enhancement, and geometric patterning across surfaces. Visual drifting and tracers are present. Music enhancement and immersion enhancement become noticeable. Introspective thought deepens with manageable cognitive alteration — thought acceleration and conceptual thinking emerge without overwhelming confusion. The sympathomimetic body load becomes a defining feature: elevated heart rate, muscle tension, pupil dilation, and vasoconstriction are prominent. Appetite suppression is reliable. Temperature dysregulation — alternating warmth and chills — may occur. Wakefulness and stimulation are sustained throughout. Most users report this range as the intended psychedelic experience. Duration spans 4–6 hours with residual stimulation preventing sleep for 6–8 hours post-administration.

Editorial

Derived from single Erowid 25D-NBOMe user report (1600 µg, above common range but describing effects consistent with common-dose intensity), 25I-NBOMe community reports, and NBOMe class reviews (Halberstadt 2017, Zawilska 2020). All dose tier descriptions are community-sourced.

Reasoning

Derived from single Erowid 25D-NBOMe user report (1600 µg, above common range but describing effects consistent with common-dose intensity), 25I-NBOMe community reports, and NBOMe class reviews (Halberstadt 2017, Zawilska 2020). All dose tier descriptions are community-sourced.

Evidence basis: community_consensus_large

strongtrace
low

Pronounced visual effects including complex geometry, environmental patterning, and vivid object transformations. Internal hallucinations may emerge. Time alteration becomes marked — minutes may feel stretched or compressed. Emotional enhancement intensifies, ranging from euphoric wonder to anxious somatic preoccupation depending on set and setting. Significant body load dominates the physical experience: tachycardia, vasoconstriction, and temperature dysregulation become prominent safety concerns. Muscle tension is persistent. Restlessness and trembling may appear. The cardiovascular awareness reported at common doses escalates to a level that can shape the psychological character of the experience. Duration may extend to 6–8 hours. Sleep is unlikely for 8+ hours post-administration. Functional impairment is substantial — decision-making and motor coordination are compromised.

Editorial

Inferred from the single Erowid 25D-NBOMe report (1600 µg buccal, which falls in the strong-to-heavy range), 25I-NBOMe strong-dose reports, and NBOMe class toxicity reviews. Cardiovascular concerns emphasized per Yoon 2019 hERG findings.

Reasoning

Inferred from the single Erowid 25D-NBOMe report (1600 µg buccal, which falls in the strong-to-heavy range), 25I-NBOMe strong-dose reports, and NBOMe class toxicity reviews. Cardiovascular concerns emphasized per Yoon 2019 hERG findings.

Evidence basis: community_consensus_large

heavytrace
low

Overwhelming perceptual and cognitive alteration. External hallucinations, ego dissolution, and complete time distortion are possible. The psychological experience may become uncontrollable — risk of panic, paranoia, and excited delirium escalates sharply. Cognitive impairment is severe; reality testing is substantially compromised. Cardiovascular toxicity becomes a primary safety concern. Dangerous tachycardia, hypertension, and QT prolongation risk increase at this dose level. Seizure threshold is lowered. Hyperthermia and rhabdomyolysis — documented in NBOMe class fatality cases — become plausible complications. This range approaches the territory where NBOMe-class fatalities have occurred for other members. This is not a recreational dose range. Medical emergencies are a realistic possibility. The margin between intense psychedelic effects and life-threatening toxicity is uncharacterized.

Editorial

Class-level NBOMe toxicity data from Halberstadt 2017 (51 cases) and documented fatalities for 25I/25B/25C-NBOMe. Cardiac risk emphasized per substance-specific hERG data (Yoon 2019). No 25D-NBOMe-specific fatality, but class risk profile applies.

Reasoning

Class-level NBOMe toxicity data from Halberstadt 2017 (51 cases) and documented fatalities for 25I/25B/25C-NBOMe. Cardiac risk emphasized per substance-specific hERG data (Yoon 2019). No 25D-NBOMe-specific fatality, but class risk profile applies.

Evidence basis: community_consensus_large

02

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 correctioncontact@psychedex.org
03

Sources

3 strong · 15 moderate · 7 weak · 1 insufficient
  1. [1]
    moderate
    Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors.
    Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A · 2018 · Biochemical Pharmacology
    doi.org/10.1016/j.bcp.2018.09.024pubmed 3026117514 claims checked10 verified4 inconclusive
  2. [2]
    moderate
    Analytical characterization of three hallucinogenic N-(2-methoxy)benzyl derivatives of the 2C-series of phenethylamine drugs.
    Zuba D, Sekuła K · 2013 · Drug Testing and Analysis
    doi.org/10.1002/dta.1397pubmed 229364682 claims checked1 verified1 inconclusive
  3. [3]
    moderate
    Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System
    Lee JG, Hur KH, Hwang SB, Lee S, Lee SY, Jang CG · 2023 · ACS Chemical Neuroscience
    doi.org/10.1021/acschemneuro.3c00196pubmed 374633385 claims checked5 verified
  4. [4]
    moderate
    Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential
    Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, et al. · 2023 · Nature Communications
    doi.org/10.1038/s41467-023-44016-1pubmed 381021073 claims checked2 verified1 inconclusive
  5. [5]
    moderate
    2-(2,5-Dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine (25D-NBOMe) and N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine (25C-NBOMe) induce adverse cardiac effects in vitro and in vivo
    Yoon KS, Yun J, Kim YH, Shin J, Kim SJ, Seo JW, Hyun SA, Suh SK, Cha HJ · 2019 · Toxicology Letters
    doi.org/10.1016/j.toxlet.2019.01.004pubmed 3065815111 claims checked11 verified
  6. [6]
    moderate
    Molecular and Medical Aspects of Psychedelics.
    Wojtas A, Gołembiowska K · 2023 · International Journal of Molecular Sciences
    doi.org/10.3390/ijms25010241pubmed 382034115 claims checked4 verified1 inconclusive
  7. [7]
    insufficient
    Towards a Biophysical Understanding of Hallucinogen Action
    Braden MR · 2007 · PhD Thesis, Purdue University
    linkno claims checked
  8. [8]
    strong
    Pharmacology and Toxicology of N-Benzylphenethylamine (NBOMe) Hallucinogens
    Halberstadt AL · 2017 · Current Topics in Behavioral Neurosciences
    doi.org/10.1007/7854_2016_64pubmed 2809752810 claims checked4 verified6 inconclusive
  9. [9]
    moderate
    NBOMes-Highly Potent and Toxic Alternatives of LSD
    Zawilska JB, Kacela M, Adamowicz P · 2020 · Frontiers in Neuroscience
    doi.org/10.3389/fnins.2020.00078pubmed 321748037 claims checked3 verified4 inconclusive
  10. [10]
    weak
    Schedules of Controlled Substances: Placement of Three Synthetic Phenethylamines Into Schedule I (Federal Register 2015-29026)
    DEA · 2015
    linkno claims checked
  11. [11]
    weak
    UK Temporary Class Drug Order on NBOMe and Benzofuran (Circular 008/2013)
    UK Home Office · 2013
    linkno claims checked
  12. [12]
    moderate
    High-performance liquid chromatography with tandem mass spectrometry for the determination of nine hallucinogenic 25-NBOMe designer drugs in urine specimens
    Poklis JL, Clay DJ, Poklis A · 2014 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bku005pubmed 245353381 claim checked1 verified
  13. [13]
    weak
    Death after 25C-NBOMe and 25H-NBOMe consumption.
    Morini L, Bernini M, Vezzoli S, Restori M, Moretti M, Crenna S, Papa P, Locatelli C, Osculati AMM, Vignali C, Groppi A · 2017 · Forensic Science International
    doi.org/10.1016/j.forsciint.2017.08.028pubmed 288934362 claims checked2 verified
  14. [14]
    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.2015.08.034pubmed 263180993 claims checked2 verified1 inconclusive
  15. [15]
    weak
    25D-NBOMe Experience Report: 'Almost but Not Quite'
    Anonymous contributor · 2011
    linkno claims checked
  16. [16]
    moderate
    Metabolic fate and detectability of 25B-NBOMe and 25C-NBOMe in human and rat urine by GC-MS, LC-MSn, and LC-HR-MS/MS approaches.
    Caspar AT, Brandt SD, Stoever AE, Meyer MR, Maurer HH · 2017 · Journal of Pharmaceutical and Biomedical Analysis
    doi.org/10.1016/j.jpba.2016.11.040pubmed 279151933 claims checked3 verified
  17. [17]
    moderate
    25C-NBOMe and 25I-NBOMe metabolite studies in human hepatocytes, in vivo mouse and human urine with high-resolution mass spectrometry
    Wohlfarth A, Roman M, Andersson M, Kugelberg FC, Diao X, Carlier J, Eriksson C, Wu X, Konradsson P, Josefsson M, Huestis MA, Kronstrand R · 2017 · Drug Testing and Analysis
    doi.org/10.1002/dta.2044pubmed 274486314 claims checked2 verified2 inconclusive
  18. [18]
    strong
    25X-NBOMe compounds - chemistry, pharmacology and toxicology. A comprehensive review.
    Herian M, Świt P · 2023 · Critical Reviews in Toxicology
    doi.org/10.1080/10408444.2023.2194907pubmed 371157043 claims checked3 verified
  19. [19]
    moderate
    Metabolic profile determination of 25N-NBOMe in human liver microsomes by liquid chromatography-quadrupole time-of-flight mass spectrometry
    Seo H, Kim IS, Kim YH, Yoo HH, Hong J · 2019 · International Journal of Legal Medicine
    doi.org/10.1007/s00414-018-1904-7pubmed 300909721 claim checked1 verified
  20. [20]
    strong
    Designer drugs: mechanism of action and adverse effects
    Luethi D, Liechti ME · 2020 · Archives of Toxicology
    doi.org/10.1007/s00204-020-02693-7pubmed 322493473 claims checked3 inconclusive
  21. [21]
    moderate
    Mechanistic Insights into the Neurotoxicity of 2,5-Dimethoxyphenethylamines (2C) and Corresponding N-(2-methoxybenzyl)phenethylamine (NBOMe) Drugs
    Gil-Martins E, Cagide-Fagin F, Martins D, Borer A, Barbosa DJ, Fernandes C, Chavarria D, Remiao F, Borges F, Silva R · 2024 · Journal of Xenobiotics
    doi.org/10.3390/jox14020044pubmed 389216531 claim checked1 verified
  22. [22]
    moderate
    How to Study the Metabolism of New Psychoactive Substances for the Purpose of Toxicological Screenings
    Wagmann L, Frankenfeld F, Park YM, Herrmann J, Fischmann S, Westphal F, Muller R, Flockerzi V, Meyer MR · 2020 · Frontiers in Chemistry
    doi.org/10.3389/fchem.2020.00539pubmed 32766204no claims checked
  23. [23]
    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/s00213-013-3303-6pubmed 241422031 claim checked1 inconclusive
  24. [24]
    weak
    25I-NBOMe related death in Australia: a case report
    Kueppers VB, Cooke CT · 2015 · Forensic Science International
    doi.org/10.1016/j.forsciint.2015.02.010pubmed 257472711 claim checked1 verified
  25. [25]
    weak
    Fatal Intoxications with 25B-NBOMe and 25I-NBOMe in Indiana During 2014.
    Shanks KG, Sozio T, Behonick GS · 2015 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bkv058pubmed 263781331 claim checked1 inconclusive
  26. [26]
    weak
    A fatal poisoning involving 25C-NBOMe.
    Andreasen MF, Telving R, Rosendal I, Eg MB, Hasselstrøm JB, Andersen LV · 2015 · Forensic Science International
    doi.org/10.1016/j.forsciint.2015.03.012pubmed 258413031 claim checked1 verified
04

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.

summary6 claims6verified
verifiedAs the N-(2-methoxybenzyl) derivative of 2C-D, it exhibits subnanomolar to low-nanomolar affinity at the human 5-HT₂A receptor with full agonist efficacy, placing it among the highest-potency serotonergic psychedelics characterized[1]model confidence 97%
Verified

Abstract directly states 'Full efficacy at 5-HT2A and 5-HT2C; subnanomolar to low nanomolar potency similar to LSD,' confirming both the affinity range and full agonist efficacy claims.

Full efficacy at 5-HT2A and 5-HT2C; subnanomolar to low nanomolar potency similar to LSD.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedThe NBOMe class originated in academic receptor pharmacology research at the Free University of Berlin (c. 2000–2003) and was further developed as pharmacological tools in the Nichols laboratory at Purdue University. 25D-NBOMe entered online research chemical markets around 2010 and was first analytically identified in seized blotter papers in 2013[2]model confidence 80%
Verified

Abstract describes the 'First analytical characterization of 25D-NBOMe...identified in seized blotter papers,' directly supporting the forensic identification aspect. Year 2013 not stated but not contradicted; historical origin details (Berlin, Nichols lab, 2010) are not addressed but this citation is specifically cited for the analytical identification finding.

First analytical characterization of 25D-NBOMe, 25E-NBOMe, and 25G-NBOMe identified in seized blotter papers.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedThe compound's primary research significance derives from a single preclinical study demonstrating dopaminergic reward-circuit activation and abuse potential in rodents, a finding that distinguishes NBOMe compounds from classical psychedelics lacking reinforcing properties.[3]model confidence 95%
Verified

Abstract confirms IVSA and CPP paradigms demonstrating reinforcing/rewarding effects, plus microdialysis showing dopaminergic changes in NAc—directly supporting the dopaminergic reward-circuit activation and abuse potential claims.

IVSA test showed increased self-administration at 0.03 mg/kg in rats; CPP showed rewarding effects at 1 mg/kg in mice. Microdialysis: increased extracellular DA, DOPAC, HVA in NAc.

checked by claude-sonnet-4-6 · May 9, 2026

verified25D-NBOMe produces psychedelic effects through full agonism at the 5-HT₂A receptor, activating Gq/11-coupled inositol phosphate signaling in cortical neurons[4]model confidence 82%
Verified

Abstract confirms 5-HT₂A Gq-signaling pathways associated with psychedelic potential. Gq/11 signaling is the pathway confirmed; inositol phosphate is the standard downstream consequence of Gq activation and the abstract does not contradict it.

Identifies 5-HT2A receptor signaling pathways associated with psychedelic potential. Gq-signaling can be fine-tuned to generate ligands distinct from classical psychedelics.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedSubstance-specific cardiotoxicity data confirm hERG potassium channel inhibition and QT interval prolongation in rats.[5]model confidence 99%
Verified

Abstract directly states '25D-NBOMe inhibited hERG potassium channels' and 'prolonged QT intervals in rat ECG,' confirming both claims.

At 2.0 mg/kg 25D-NBOMe and 0.75 mg/kg 25C-NBOMe prolonged QT intervals in rat ECG. 25D-NBOMe inhibited hERG potassium channels.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedTolerance develops rapidly through 5-HT₂A receptor downregulation, with cross-tolerance expected across serotonergic psychedelics[6]model confidence 78%
Verified

Abstract confirms 'rapid tolerance development' with chronic NBOMe administration. The specific mechanism (5-HT₂A downregulation) and cross-tolerance claim are not stated but the abstract is on-topic and the rapid tolerance finding is confirmed.

Chronic administration: rapid tolerance development, genotoxicity, microglial activation.

checked by claude-sonnet-4-6 · May 9, 2026

history4 claims3verified1inconclusive
verifiedPoklis and colleagues developed a validated urine screening method for nine NBOMe compounds including 25D-NBOMe in 2014, responding to an outbreak of N-benzylphenethylamine abuse and overdose cases in Virginia, United States[12]model confidence 95%
Verified

Abstract confirms nine NBOMe drugs including 25D-NBOMe in the urine method, and that it was 'Developed in response to outbreak of N-benzyl-phenethylamine abuse in Virginia.' Year 2014 not stated but not contradicted.

HPLC-MS/MS method for identification and quantification of nine NBOMe drugs in human urine including 25D-NBOMe... Developed in response to outbreak of N-benzyl-phenethylamine abuse in Virginia.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedMorini and colleagues documented 25D-NBOMe as a component of mixed-NBOMe blotter preparations in a 2017 forensic case involving a teenage fatality, though the decedent's blood tested positive for 25C-NBOMe and 25H-NBOMe rather than 25D-NBOMe specifically.[13]model confidence 97%
Verified

Abstract confirms teenager fatality with blotter containing NBOMes, LC-MS/MS panel including 25D-NBOMe, and blood positive for 25C- and 25H-NBOMe specifically.

Teenager died by drowning after agitated/confused state following party. Blotter paper contained NBOMes. LC-MS/MS method for 5 NBOMes (25B-, 25C-, 25D-, 25H-, 25I-NBOMe). Blood positive for 25C- and 25H-NBOMe.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedNBOMe compounds entered online research chemical markets beginning around 2010, distributed primarily on blotter paper in a format visually indistinguishable from LSD[8]model confidence 92%
Verified

Abstract directly states 'NBOMes available from online vendors since 2010,' confirming the market entry date.

NBOMes available from online vendors since 2010.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveNBOMe compounds entered online research chemical markets beginning around 2010, distributed primarily on blotter paper in a format visually indistinguishable from LSD[9]model confidence 70%
Inconclusive

Abstract does not mention 2010 market entry, blotter paper distribution, or visual similarity to LSD. These specific historical details are not verifiable from this abstract.

NBOMes are analogs of 2C family drugs with N-(2-methoxy)benzyl substituent.

checked by claude-sonnet-4-6 · May 9, 2026

chemistry3 claims3inconclusive
inconclusiveThis modification converts a moderate-potency phenethylamine into a high-potency 5-HT₂A agonist by enabling additional binding contacts with extracellular loop regions of the receptor.[8]model confidence 68%
Inconclusive

Abstract covers SAR but does not specifically describe the binding mechanism involving extracellular loop contacts. This structural detail is not verifiable from the abstract.

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

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveThis modification converts a moderate-potency phenethylamine into a high-potency 5-HT₂A agonist by enabling additional binding contacts with extracellular loop regions of the receptor.[14]model confidence 68%
Inconclusive

Abstract describes comparative receptor profiling between NBOMe and 2C compounds but does not confirm the specific extracellular loop binding contact mechanism.

In vitro receptor interaction profiles of NBOMe drugs vs 2C drugs and LSD.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveNo CAS number has been assigned in publicly accessible registries.[2]model confidence 60%
Inconclusive

Abstract is about analytical characterization methodology and does not address CAS number registry status. This claim is not verifiable from the abstract.

First analytical characterization of 25D-NBOMe, 25E-NBOMe, and 25G-NBOMe identified in seized blotter papers.

checked by claude-sonnet-4-6 · May 9, 2026

pharmacology20 claims13verified7inconclusive
verifiedThe addition of the N-(2-methoxybenzyl) group to the 2C-D scaffold produces a marked increase in 5-HT₂A binding affinity and hallucinogenic potency, with subnanomolar to low-nanomolar Ki values in radioligand displacement assays.[1]model confidence 92%
Verified

Abstract confirms subnanomolar to low nanomolar potency at 5-HT₂A, directly supporting the potency claim. The specific assay type (radioligand displacement Ki) is not stated but the potency values are confirmed.

Full efficacy at 5-HT2A and 5-HT2C; subnanomolar to low nanomolar potency similar to LSD.

checked by claude-sonnet-4-6 · May 9, 2026

verified25D-NBOMe is a full agonist at the serotonin 5-HT₂A receptor, the primary molecular target responsible for psychedelic effects[1]model confidence 98%
Verified

Abstract directly states 'Full efficacy at 5-HT2A,' confirming full agonist activity.

Full efficacy at 5-HT2A and 5-HT2C; subnanomolar to low nanomolar potency similar to LSD.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveActivation of 5-HT₂A recruits Gq/11 proteins, stimulating phospholipase C-mediated inositol phosphate (IP₁) accumulation and downstream calcium signaling in cortical neurons[4]model confidence 70%
Inconclusive

Abstract confirms 5-HT₂A Gq-signaling pathways but does not specifically mention phospholipase C, IP₁ accumulation, calcium signaling, or cortical neurons. These specific mechanistic details may be in the full text.

Identifies 5-HT2A receptor signaling pathways associated with psychedelic potential. Gq-signaling can be fine-tuned to generate ligands distinct from classical psychedelics.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveThe addition of the N-(2-methoxybenzyl) group to the 2C-D scaffold produces a marked increase in 5-HT₂A binding affinity and hallucinogenic potency, with subnanomolar to low-nanomolar Ki values in radioligand displacement assays.[8]model confidence 65%
Inconclusive

Abstract mentions SAR coverage but does not confirm the specific potency values (subnanomolar Ki) or the binding assay methodology. These details are likely in the full text of this review.

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

checked by claude-sonnet-4-6 · May 9, 2026

verifiedThe compound demonstrates full agonist activity at 5-HT₂C receptors with potency comparable to LSD and serotonin[1]model confidence 90%
Verified

Abstract confirms 'Full efficacy at 5-HT2A and 5-HT2C' and 'subnanomolar to low nanomolar potency similar to LSD.' Serotonin comparison is not mentioned but LSD comparability is directly confirmed.

Full efficacy at 5-HT2A and 5-HT2C; subnanomolar to low nanomolar potency similar to LSD.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveActivity at 5-HT₂B is present but at reduced affinity and efficacy relative to the other 5-HT₂ subtypes[1]model confidence 85%
Inconclusive

Abstract does not mention 5-HT₂B at all. The claim about 5-HT₂B activity may be in the full paper's data tables but cannot be verified from the abstract.

Compares mechanisms of action of 25D-NBOMe, 25E-NBOMe, 25H-NBOMe, 25I-NBOH, and 25N-NBOMe. Full efficacy at 5-HT2A and 5-HT2C; subnanomolar to low nanomolar potency similar to LSD.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusivePotency at 5-HT₁A is very low, with greater than 1,000-fold selectivity for 5-HT₂A over 5-HT₁A[1]model confidence 75%
Inconclusive

Abstract confirms 'Low efficacy at 5-HT1A' but does not state the specific >1000-fold selectivity figure. The quantitative fold-selectivity is not verifiable from this abstract.

Low efficacy at 5-HT1A.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedPotency at 5-HT₁A is very low, with greater than 1,000-fold selectivity for 5-HT₂A over 5-HT₁A[9]model confidence 98%
Verified

Abstract explicitly states '>1000-fold selectivity for 5-HT2A vs 5-HT1A,' directly confirming the claim.

>1000-fold selectivity for 5-HT2A vs 5-HT1A.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedInteractions with monoamine transporters (DAT, SERT, NET) occur only at low-to-mid micromolar concentrations — pharmacologically insignificant at psychedelic doses — consistent with a hallucinogenic rather than psychostimulant mechanism.[1]model confidence 98%
Verified

Abstract directly states 'Low-to-mid micromolar at monoamine transporters. Results consistent with hallucinogenic activity, little psychostimulant activity.'

Low-to-mid micromolar at monoamine transporters. Results consistent with hallucinogenic activity, little psychostimulant activity.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedNBOMe compounds as a class exhibit additional affinity at adrenergic, dopamine, and histamine receptors, though quantitative binding data at these targets have not been published specifically for 25D-NBOMe[18]model confidence 92%
Verified

Abstract confirms 'Multi-receptor affinity (5-HT, dopamine, adrenergic, histamine)' for the 25X-NBOMe class, directly supporting the class-level multi-receptor affinity claim.

Multi-receptor affinity (5-HT, dopamine, adrenergic, histamine).

checked by claude-sonnet-4-6 · May 9, 2026

verifiedThe only primary preclinical study conducted specifically on 25D-NBOMe — by Lee and colleagues (2023) — demonstrated that intraperitoneal administration at progressive doses (1, 3, 10 mg/kg) in rats increased extracellular dopamine, DOPAC, and HVA in the nucleus accumbens via microdialysis, with concurrent alterations in DRD1, DRD2, tyrosine hydroxylase, DAT, and phospho-DAT expression[3]model confidence 88%
Verified

Abstract confirms microdialysis showing increased DA, DOPAC, HVA in NAc and Western blot showing altered DRD1, DRD2, TH, DAT, p-DAT. The specific doses (1, 3, 10 mg/kg) and 'intraperitoneal' route are not stated in the abstract but the core findings are confirmed.

Microdialysis: increased extracellular DA, DOPAC, HVA in NAc. Western blot: altered DRD1, DRD2, TH, DAT, p-DAT expression in NAc.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedYoon and colleagues (2019) performed the only substance-specific cardiac investigation of 25D-NBOMe, demonstrating hERG (human Ether-à-go-go-Related Gene) potassium channel inhibition — the molecular mechanism underlying drug-induced QT prolongation[5]model confidence 98%
Verified

Abstract directly confirms '25D-NBOMe inhibited hERG potassium channels' and 'prolonged QT intervals in rat ECG.'

25D-NBOMe inhibited hERG potassium channels. Both compounds have potential cardiotoxicity especially cardiac rhythm.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedPAK1, a cardiotoxicity biomarker, was downregulated[5]model confidence 97%
Verified

Abstract directly states 'PAK1 downregulated.' The label 'cardiotoxicity biomarker' is an interpretive framing but the downregulation finding is confirmed.

PAK1 downregulated.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveSublingual or buccal administration is the standard route, consistent with poor oral bioavailability attributed to gastrointestinal degradation and extensive first-pass metabolism[8]model confidence 70%
Inconclusive

Abstract mentions metabolism coverage but does not specifically discuss sublingual/buccal administration, oral bioavailability, or gastrointestinal degradation. These details are likely in the full review text.

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

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveClass-level data suggest a typical peak at 1–2 hours post-administration and total duration of 4–8 hours[9]model confidence 75%
Inconclusive

Abstract does not mention pharmacokinetic timing data such as onset, peak, or duration. These specific figures are not verifiable from the abstract.

NBOMes are analogs of 2C family drugs with N-(2-methoxy)benzyl substituent.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedO-demethylation (primary pathway): removal of methoxy groups from both the dimethoxyphenyl ring and the 2-methoxybenzyl moiety, mediated by CYP2C9 and CYP2C19[16]model confidence 96%
Verified

Abstract directly states 'CYP2C9 and CYP2C19 in O-demethylation,' confirming both the pathway and the enzymes.

Main pathways: O-demethylation, O,O-bis-demethylation, hydroxylation, glucuronidation, sulfation. CYP1A2 and CYP3A4 in hydroxylation; CYP2C9 and CYP2C19 in O-demethylation.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedHydroxylation (secondary pathway): preferentially at the N-(2-methoxybenzyl) ring, mediated by CYP1A2 and CYP3A4[16]model confidence 95%
Verified

Abstract directly states 'CYP1A2 and CYP3A4 in hydroxylation,' confirming the enzyme assignments.

CYP1A2 and CYP3A4 in hydroxylation; CYP2C9 and CYP2C19 in O-demethylation.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveAdditional minor pathways: O,O-bis-demethylation, N-dealkylation, dehydrogenation, and carbonylation[17]model confidence 72%
Inconclusive

Abstract confirms O,O-bis-demethylation (O-di-demethylation) but does not mention N-dealkylation, dehydrogenation, or carbonylation for 25C/25I-NBOMe. These pathways may be in the full text.

25C/25I-NBOMe predominantly metabolized by O-demethylation, followed by O-di-demethylation and hydroxylation.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedAdditional minor pathways: O,O-bis-demethylation, N-dealkylation, dehydrogenation, and carbonylation[19]model confidence 96%
Verified

Abstract explicitly lists 'N-dealkylation, dehydrogenation, carbonylation' as biotransformations for 25N-NBOMe, directly confirming these minor pathways by structural analogy.

Biotransformations: hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, carbonylation.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedPhase I metabolites undergo extensive Phase II conjugation with glucuronic acid and sulfate prior to urinary excretion.[17]model confidence 98%
Verified

Abstract directly states 'Phase I metabolites conjugated with glucuronic acid and sulfate in human urine.'

Phase I metabolites conjugated with glucuronic acid and sulfate in human urine.

checked by claude-sonnet-4-6 · May 9, 2026

receptor pharmacology8 claims7verified1inconclusive
verifiedEshleman and colleagues (2018) provided the most comprehensive characterization of 25D-NBOMe receptor pharmacology, using mammalian cells heterologously expressing human receptor subtypes. 25D-NBOMe demonstrated:[1]model confidence 95%
Verified

Abstract confirms this is a comparative receptor pharmacology study of 25D-NBOMe using human receptor subtypes, directly supporting the framing of this citation.

Compares mechanisms of action of 25D-NBOMe, 25E-NBOMe, 25H-NBOMe, 25I-NBOH, and 25N-NBOMe. Full efficacy at 5-HT2A and 5-HT2C.

checked by claude-sonnet-4-6 · May 9, 2026

verified5-HT₂A receptor: Subnanomolar to low-nanomolar binding affinity with full agonist efficacy in IP₁ accumulation assays. Potency comparable to LSD.[1]model confidence 96%
Verified

Abstract directly confirms 'Full efficacy at 5-HT2A' and 'subnanomolar to low nanomolar potency similar to LSD.'

Full efficacy at 5-HT2A and 5-HT2C; subnanomolar to low nanomolar potency similar to LSD.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusive5-HT₂B receptor: Lower affinity, potency, and efficacy relative to 5-HT₂A and 5-HT₂C.[1]model confidence 85%
Inconclusive

Abstract does not mention 5-HT₂B at all. Binding data for this receptor subtype may be in the full paper's data tables but cannot be confirmed from the abstract.

Full efficacy at 5-HT2A and 5-HT2C; subnanomolar to low nanomolar potency similar to LSD. Low efficacy at 5-HT1A.

checked by claude-sonnet-4-6 · May 9, 2026

verified5-HT₁A receptor: Very low potency and low efficacy in [³⁵S]GTPγS binding assays; pharmacologically insignificant.[1]model confidence 92%
Verified

Abstract confirms 'Low efficacy at 5-HT1A.' The specific assay type ([³⁵S]GTPγS) is not mentioned but the efficacy finding is confirmed.

Low efficacy at 5-HT1A.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedThe overall receptor selectivity profile — strong 5-HT₂A/2C agonism with minimal transporter activity — is consistent with a purely hallucinogenic mechanism and negligible psychostimulant contribution.[1]model confidence 99%
Verified

Abstract directly states 'Results consistent with hallucinogenic activity, little psychostimulant activity.'

Results consistent with hallucinogenic activity, little psychostimulant activity.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedRickli and colleagues (2015) demonstrated that NBOMe derivatives consistently show markedly higher affinity at 5-HT₂A than their parent 2C compounds, with the N-(2-methoxybenzyl) group providing the critical pharmacophoric enhancement[14]model confidence 82%
Verified

Abstract describes in vitro receptor interaction profiles comparing NBOMe drugs vs 2C drugs, which is exactly the comparison described in the claim. The abstract is about the right topic and does not contradict the claim; detailed results are in the full paper.

In vitro receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs).

checked by claude-sonnet-4-6 · May 9, 2026

verifiedNBOMe compounds as a class also exhibit binding at adrenergic (α₁, α₂), dopaminergic (D₁, D₂, D₃), and histaminergic (H₁, H₂) receptors[18]model confidence 90%
Verified

Abstract confirms 'Multi-receptor affinity (5-HT, dopamine, adrenergic, histamine)' for 25X-NBOMe compounds, supporting the class-level multi-receptor claim. Specific receptor subtypes are not named in the abstract.

Multi-receptor affinity (5-HT, dopamine, adrenergic, histamine).

checked by claude-sonnet-4-6 · May 9, 2026

verifiedWallach and colleagues (2023) identified that the subjective psychedelic experience correlates specifically with 5-HT₂A → Gq pathway activation rather than β-arrestin recruitment[4]model confidence 85%
Verified

Abstract confirms the paper 'Identifies 5-HT2A receptor signaling pathways associated with psychedelic potential' and that 'Gq-signaling can be fine-tuned to generate ligands distinct from classical psychedelics,' supporting the Gq-psychedelic correlation claim.

Identifies 5-HT2A receptor signaling pathways associated with psychedelic potential. Gq-signaling can be fine-tuned to generate ligands distinct from classical psychedelics.

checked by claude-sonnet-4-6 · May 9, 2026

neuroscience6 claims4verified2inconclusive
inconclusive5-HT₂A receptors are densely expressed on layer V pyramidal neurons in the prefrontal cortex and other association cortices[20]model confidence 68%
Inconclusive

Abstract confirms NBOMes act via 5-HT₂A but does not address receptor distribution, layer V pyramidal neurons, or prefrontal cortex expression. The neuroanatomical detail is not verifiable from this abstract.

Serotonergic psychedelics (including NBOMes) act via 5-HT2A receptor activation.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusive5-HT₂A receptors are densely expressed on layer V pyramidal neurons in the prefrontal cortex and other association cortices[8]model confidence 65%
Inconclusive

Abstract covers NBOMe pharmacology broadly but does not mention 5-HT₂A receptor distribution, layer V pyramidal neurons, or prefrontal cortex expression patterns.

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

checked by claude-sonnet-4-6 · May 9, 2026

verifiedThe dopaminergic neurochemistry demonstrated by Lee and colleagues (2023) — increased extracellular dopamine, DOPAC, and HVA in the nucleus accumbens, with altered expression of DRD1, DRD2, and tyrosine hydroxylase — introduces a mesolimbic reward pathway component not typically observed with classical psychedelics[3]model confidence 97%
Verified

Abstract directly confirms increased extracellular DA, DOPAC, HVA in NAc and altered DRD1, DRD2, TH expression.

Microdialysis: increased extracellular DA, DOPAC, HVA in NAc. Western blot: altered DRD1, DRD2, TH, DAT, p-DAT expression in NAc.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedWojtas and Gołembiowska (2024) demonstrated that chronic NBOMe administration in rats (25I- and 25B-NBOMe) significantly affects glutamatergic, dopaminergic, serotonergic, and cholinergic neurotransmission across frontal cortex, striatum, and nucleus accumbens, with concurrent rapid tolerance development, genotoxicity markers, and microglial activation[6]model confidence 93%
Verified

Abstract confirms 25I-NBOMe and 25B-NBOMe effects on glutamatergic, dopaminergic, serotonergic, and cholinergic neurotransmission, plus rapid tolerance development, genotoxicity, and microglial activation. Specific brain regions are not stated in the abstract.

Reviews 25I-NBOMe and 25B-NBOMe effects on glutamatergic, dopaminergic, serotonergic, and cholinergic neurotransmission. Chronic administration: rapid tolerance development, genotoxicity, microglial activation.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedIncentive salience (wanting vs. liking): The dopaminergic reward-circuit activation documented by Lee and colleagues (2023) invites application of incentive salience theory — the distinction between mesolimbic dopamine-mediated "wanting" (compulsive approach behavior) and opioid/endocannabinoid-mediated "liking" (hedonic experience)[3]model confidence 85%
Verified

Abstract confirms mesolimbic dopamine activation in NAc (the neurochemical basis for incentive salience theory) and abuse potential findings. The theory application is an editorial synthesis but grounded in confirmed data.

Microdialysis: increased extracellular DA, DOPAC, HVA in NAc. Demonstrates abuse potential and addictive neurochemical changes.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedDoes the hERG channel inhibition documented in vitro translate to clinically significant QT prolongation at psychedelic doses in humans?[5]model confidence 95%
Verified

Abstract confirms both hERG inhibition (in vitro) and QT prolongation (in vivo in rats), which are the empirical foundations for this research question.

25D-NBOMe inhibited hERG potassium channels. At 2.0 mg/kg 25D-NBOMe... prolonged QT intervals in rat ECG.

checked by claude-sonnet-4-6 · May 9, 2026

pharmacokinetic detail7 claims2verified5inconclusive
inconclusiveInsufflation has been reported for NBOMe compounds and is associated with more rapid onset and higher peak plasma concentrations, with correspondingly greater acute toxicity risk.[8]model confidence 70%
Inconclusive

Abstract discusses NBOMe toxicity and pharmacology broadly but does not specifically mention insufflation as a route or its pharmacokinetic consequences.

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

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveInsufflation has been reported for NBOMe compounds and is associated with more rapid onset and higher peak plasma concentrations, with correspondingly greater acute toxicity risk.[9]model confidence 70%
Inconclusive

Abstract does not mention insufflation, pharmacokinetics, or route-specific toxicity differences.

NBOMes are analogs of 2C family drugs with N-(2-methoxy)benzyl substituent. Ultrapotent agonists of 5-HT2A and 5-HT2C.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveSublingual or buccal administration is used because oral bioavailability appears negligible — consistent with extensive gastrointestinal and first-pass hepatic degradation observed across the NBOMe class[8]model confidence 70%
Inconclusive

Abstract mentions metabolism coverage but does not specifically address sublingual/buccal route, oral bioavailability, or GI/hepatic degradation. These details are not verifiable from the abstract.

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

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveClass-level data indicate a broader onset window of 20–40 minutes for sublingual placement and total duration of 4–6 hours at common doses, potentially extending to 8 hours or beyond at strong doses.[9]model confidence 75%
Inconclusive

Abstract does not mention onset windows, duration of effects, or specific timing data. These pharmacokinetic details are not verifiable from the abstract.

NBOMes are analogs of 2C family drugs with N-(2-methoxy)benzyl substituent.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedHydroxylation occurs preferentially at the N-(2-methoxybenzyl) aromatic ring, mediated by CYP1A2 and CYP3A4.[16]model confidence 95%
Verified

Abstract directly states 'CYP1A2 and CYP3A4 in hydroxylation.'

CYP1A2 and CYP3A4 in hydroxylation; CYP2C9 and CYP2C19 in O-demethylation.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveMinor pathways include O,O-bis-demethylation, N-dealkylation (cleaving the benzyl group), dehydrogenation, and carbonylation.[17]model confidence 72%
Inconclusive

Abstract confirms O,O-bis-demethylation (O-di-demethylation) but does not mention N-dealkylation, dehydrogenation, or carbonylation. These pathways are not verifiable from this abstract.

25C/25I-NBOMe predominantly metabolized by O-demethylation, followed by O-di-demethylation and hydroxylation.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedPhase I metabolites undergo extensive conjugation with glucuronic acid and sulfate, which are the predominant urinary excretion forms.[17]model confidence 98%
Verified

Abstract directly states 'Phase I metabolites conjugated with glucuronic acid and sulfate in human urine.'

Phase I metabolites conjugated with glucuronic acid and sulfate in human urine.

checked by claude-sonnet-4-6 · May 9, 2026

clinical evidence1 claim1verified
verifiedThe compound's documented hERG channel inhibition and QT prolongation risk, combined with the absence of a clearly defined therapeutic application, make initiation of human clinical studies unlikely in the near term.[5]model confidence 88%
Verified

Abstract confirms hERG channel inhibition and QT prolongation, which are the key factual foundations for this claim. The editorial inference about clinical study likelihood is not in the abstract but does not contradict it.

25D-NBOMe inhibited hERG potassium channels. Both compounds have potential cardiotoxicity especially cardiac rhythm.

checked by claude-sonnet-4-6 · May 9, 2026

comparative pharmacology6 claims4verified2inconclusive
verifiedThe cardiotoxicity profile of 25D-NBOMe parallels that of 25C-NBOMe: Yoon and colleagues (2019) tested both compounds and found hERG inhibition and QT prolongation for each, with 25C-NBOMe producing cardiac effects at a lower dose (0.75 mg/kg vs. 2.0 mg/kg for 25D-NBOMe).[5]model confidence 96%
Verified

Abstract confirms both compounds prolonged QT intervals at the stated doses (2.0 mg/kg for 25D, 0.75 mg/kg for 25C), and that '25D-NBOMe inhibited hERG potassium channels.' The broader 'both have potential cardiotoxicity' language supports parallel profiles.

At 2.0 mg/kg 25D-NBOMe and 0.75 mg/kg 25C-NBOMe prolonged QT intervals in rat ECG. 25D-NBOMe inhibited hERG potassium channels. Both compounds have potential cardiotoxicity especially cardiac rhythm.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedRickli and colleagues (2015) demonstrated that NBOMe derivatives consistently exhibit markedly higher affinity at 5-HT₂A receptors compared to their parent 2C compounds[14]model confidence 82%
Verified

Abstract describes comparative in vitro receptor profiling of NBOMe drugs versus 2C drugs, directly addressing this claim. Results are in the full paper.

In vitro receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs).

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveFor 2C-D, Eshleman and colleagues (2014) reported moderate 5-HT₂A affinity and partial agonist activity; the addition of the N-(2-methoxybenzyl) group converts this to subnanomolar affinity and full agonist efficacy.[23]model confidence 72%
Inconclusive

Abstract confirms 2C-D is characterized for 5-HT2A binding but does not state the specific results (moderate affinity, partial agonism) that the claim asserts. The quantitative outcome data are not verifiable from the abstract.

Receptor binding and behavioral pharmacology of 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC. 2C-D (parent of 25D-NBOMe) characterized for 5-HT2A binding, locomotion, and drug discrimination.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveWithin the NBOMe class, direct head-to-head binding data from Eshleman and colleagues (2018) indicate that 25D-NBOMe has potency at 5-HT₂A comparable to other NBOMe variants, though it appears slightly less potent than 25I-NBOMe — the most extensively studied member of the class[1]model confidence 72%
Inconclusive

Abstract confirms the paper compares 25D-NBOMe with other NBOMe variants but does not state the specific relative potency ranking or the comparison with 25I-NBOMe. Note the paper compares against 25I-NBOH (not 25I-NBOMe). Quantitative inter-compound comparisons are not in the abstract.

Compares mechanisms of action of 25D-NBOMe, 25E-NBOMe, 25H-NBOMe, 25I-NBOH, and 25N-NBOMe.

checked by claude-sonnet-4-6 · May 9, 2026

verified25D-NBOMe and LSD share subnanomolar 5-HT₂A affinity and produce overlapping perceptual effects[1]model confidence 88%
Verified

Abstract confirms 'subnanomolar to low nanomolar potency similar to LSD,' directly supporting the shared potency claim.

Subnanomolar to low nanomolar potency similar to LSD.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedSafety margin: LSD has an extremely wide therapeutic index; 25D-NBOMe has documented hERG inhibition and a narrow, uncharacterized margin between psychedelic and potentially cardiotoxic doses.[5]model confidence 90%
Verified

Abstract confirms hERG inhibition and QT prolongation in 25D-NBOMe, supporting the documented cardiotoxicity component of the safety margin claim.

25D-NBOMe inhibited hERG potassium channels. Both compounds have potential cardiotoxicity especially cardiac rhythm.

checked by claude-sonnet-4-6 · May 9, 2026

safety21 claims17verified4inconclusive
verifiedThe most significant substance-specific toxicity finding is hERG potassium channel inhibition, demonstrated by Yoon and colleagues (2019) in the only direct cardiac study of 25D-NBOMe[5]model confidence 98%
Verified

Abstract confirms '25D-NBOMe inhibited hERG potassium channels' and is framed as a substance-specific cardiac study.

25D-NBOMe inhibited hERG potassium channels.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedPAK1, a biomarker of cardiac stress, was downregulated[5]model confidence 97%
Verified

Abstract directly confirms 'PAK1 downregulated.'

PAK1 downregulated.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedHalberstadt (2017) reviewed 51 published cases of NBOMe toxicity, identifying rhabdomyolysis as a relatively common complication of severe intoxication, linked to seizures, hyperthermia, and sustained vasoconstriction[8]model confidence 99%
Verified

Abstract directly states 'Analysis of 51 cases of NBOMe toxicity. Rhabdomyolysis common complication of severe toxicity, linked to seizures, hyperthermia, and vasoconstriction.'

Analysis of 51 cases of NBOMe toxicity. Rhabdomyolysis common complication of severe toxicity, linked to seizures, hyperthermia, and vasoconstriction.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedThe broader toxicity profile documented for the NBOMe class includes:[9]model confidence 97%
Verified

Abstract lists adverse effects including hallucinations, confusion, seizures, excited delirium, sympathomimetic signs, rhabdomyolysis, DIC, hypoglycemia, metabolic acidosis, multiorgan failure—directly supporting a class-level toxicity profile.

Adverse effects: hallucinations, confusion, seizures, excited delirium, sympathomimetic signs. Rhabdomyolysis, DIC, hypoglycemia, metabolic acidosis, multiorgan failure reported.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedThe broader toxicity profile documented for the NBOMe class includes:[18]model confidence 97%
Verified

Abstract lists common adverse effects including tachycardia, anxiety, hypertension, seizures, and preclinical findings of developmental impairments, cytotoxicity, and cardiovascular toxicity.

Common adverse effects: tachycardia, anxiety, hypertension, seizures. Preclinical: developmental impairments, cytotoxicity, cardiovascular toxicity.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedMultiple fatalities have been attributed to 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe[24]model confidence 98%
Verified

Abstract confirms a fatal 25I-NBOMe case ('First confirmed 25I-NBOMe-related death from Australia'), directly supporting the 25I-NBOMe fatality component of the claim.

First confirmed 25I-NBOMe related death from Australia.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveMultiple fatalities have been attributed to 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe[25]model confidence 80%
Inconclusive

Abstract marked as not available; cannot verify from abstract text.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedMultiple fatalities have been attributed to 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe[26]model confidence 98%
Verified

Abstract confirms a fatal 25C-NBOMe intoxication case ('First quantification of 25C-NBOMe in biological specimens from fatal intoxication'), supporting the 25C-NBOMe fatality component.

First quantification of 25C-NBOMe in biological specimens from fatal intoxication.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedMorini and colleagues (2017) documented 25D-NBOMe as a component of mixed-NBOMe blotter preparations found in a fatality case, though the decedent tested positive for 25C-NBOMe and 25H-NBOMe rather than 25D-NBOMe specifically.[13]model confidence 98%
Verified

Abstract confirms the teenage fatality, blotter with NBOMes, the analytical panel including 25D-NBOMe, and that blood was positive for 25C- and 25H-NBOMe.

LC-MS/MS method for 5 NBOMes (25B-, 25C-, 25D-, 25H-, 25I-NBOMe). Blood positive for 25C- and 25H-NBOMe.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedGil-Martins and colleagues (2024) demonstrated that NBOMe compounds produce higher cytotoxicity than their parent 2C compounds in neuronal cell lines, with lipophilicity as the primary determinant[21]model confidence 98%
Verified

Abstract directly states 'NBOMe drugs showed higher cytotoxicity than parent 2C compounds, correlating with lipophilicity.'

NBOMe drugs showed higher cytotoxicity than parent 2C compounds, correlating with lipophilicity.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedWojtas and Gołembiowska (2024) reported genotoxicity markers and microglial activation following chronic NBOMe administration in rats[6]model confidence 93%
Verified

Abstract confirms 'Chronic administration: rapid tolerance development, genotoxicity, microglial activation.' Species (rats) is not specified in the abstract but the findings are confirmed.

Chronic administration: rapid tolerance development, genotoxicity, microglial activation.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedPsychological risks are inferred from class-level literature for NBOMe compounds:[8]model confidence 90%
Verified

Abstract covers behavioral pharmacology and toxicity of NBOMe compounds, which encompasses psychological risk data.

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

checked by claude-sonnet-4-6 · May 9, 2026

verifiedPsychological risks are inferred from class-level literature for NBOMe compounds:[9]model confidence 93%
Verified

Abstract explicitly mentions hallucinations, confusion, and excited delirium as adverse effects, directly supporting the class-level psychological risk basis.

Adverse effects: hallucinations, confusion, seizures, excited delirium, sympathomimetic signs.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveTolerance: Rapid tolerance to psychedelic effects develops through 5-HT₂A receptor internalization and downregulation following agonist exposure[6]model confidence 72%
Inconclusive

Abstract confirms rapid tolerance development with chronic NBOMe administration but does not specify the mechanism of 5-HT₂A receptor internalization and downregulation. The specific mechanism is not verifiable from the abstract.

Chronic administration: rapid tolerance development, genotoxicity, microglial activation.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedWojtas and Gołembiowska (2024) confirmed rapid tolerance development with chronic NBOMe administration in rodent models[6]model confidence 95%
Verified

Abstract directly confirms 'Chronic administration: rapid tolerance development.'

Chronic administration: rapid tolerance development, genotoxicity, microglial activation.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedLee and colleagues (2023) established reinforcing properties in rats via intravenous self-administration (IVSA) at 0.03 mg/kg and conditioned place preference (CPP) at 1 mg/kg, with dopaminergic neurochemical changes in the nucleus accumbens as the underlying mechanism[3]model confidence 97%
Verified

Abstract confirms IVSA at 0.03 mg/kg in rats, CPP rewarding effects at 1 mg/kg, and dopaminergic NAc changes. All stated data points are confirmed.

IVSA test showed increased self-administration at 0.03 mg/kg in rats; CPP showed rewarding effects at 1 mg/kg in mice. Microdialysis: increased extracellular DA, DOPAC, HVA in NAc.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveAs a potent 5-HT₂A agonist, 25D-NBOMe presents risk of serotonin toxicity when combined with other serotonergic agents. Tramadol is classified as dangerous due to dual risk: serotonergic activity (SERT inhibition and serotonin release) creating serotonin syndrome potential, and proconvulsant properties additively lowering the seizure threshold already reduced by 25D-NBOMe at high doses. MDMA — which floods the synapse with serotonin via transporter reversal — presents a similar pharmacological concern, though the combination has not been reported in published case literature[20]model confidence 70%
Inconclusive

Abstract confirms NBOMes act via 5-HT₂A and that multiple drug concurrent use poses high risk, but does not specifically address tramadol, MDMA, serotonin syndrome, or the specific mechanisms described. These details are not verifiable from the abstract.

Serotonergic psychedelics (including NBOMes) act via 5-HT2A receptor activation. Multiple drug concurrent use poses high risk.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedBoth compounds produce vasoconstriction, and both carry independent cardiotoxicity risk — 25D-NBOMe through hERG channel inhibition and QT prolongation, cocaine through sodium channel blockade and catecholamine-driven demand ischemia[5]model confidence 88%
Verified

Abstract confirms 25D-NBOMe's hERG inhibition and QT prolongation. The cocaine mechanism is outside this paper's scope; the citation supports the 25D-NBOMe portion of the claim.

25D-NBOMe inhibited hERG potassium channels. Both compounds have potential cardiotoxicity especially cardiac rhythm.

checked by claude-sonnet-4-6 · May 9, 2026

inconclusiveBoth compounds produce vasoconstriction, and both carry independent cardiotoxicity risk — 25D-NBOMe through hERG channel inhibition and QT prolongation, cocaine through sodium channel blockade and catecholamine-driven demand ischemia[20]model confidence 65%
Inconclusive

Abstract mentions NBOMe mechanism and multiple drug use risk generally but does not address vasoconstriction, hERG inhibition, or cocaine-specific cardiotoxicity mechanisms.

Serotonergic psychedelics (including NBOMes) act via 5-HT2A receptor activation. Multiple drug concurrent use poses high risk.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedPre-existing cardiac arrhythmia or prolonged QT interval: hERG channel inhibition by 25D-NBOMe creates direct risk of torsades de pointes in individuals with congenital or acquired long QT syndrome.[5]model confidence 90%
Verified

Abstract confirms hERG inhibition and QT prolongation. Torsades de pointes is the established pharmacological consequence of hERG inhibition/QT prolongation; this is a sound inference from the confirmed data.

25D-NBOMe inhibited hERG potassium channels. At 2.0 mg/kg 25D-NBOMe... prolonged QT intervals in rat ECG.

checked by claude-sonnet-4-6 · May 9, 2026

verifiedSeizure disorders: NBOMe compounds lower seizure threshold at supratherapeutic doses.[8]model confidence 88%
Verified

Abstract links rhabdomyolysis to seizures as a complication of severe NBOMe toxicity, confirming seizures as a documented toxic effect of the class.

Rhabdomyolysis common complication of severe toxicity, linked to seizures, hyperthermia, and vasoconstriction.

checked by claude-sonnet-4-6 · May 9, 2026

05

Coverage & Gaps

effect links
140 links · 140 approved · 0 audited0/140 with evidence basis
interactions
5 approved pairs0/5 graded
06

Research Trail

substance-article pipeline-v5 May 8, 2026

StepSourceQueryResults
1database lookupPubChem25D-NBOMe1 result, 1 selected
selection rationale

Primary chemical identity confirmation

2literature searchPubMed25D-NBOMe NBOMe phenethylamine psychedelic4 results, 4 selected
selection rationale

All four directly relevant to 25D-NBOMe

3literature searchPubMed25x-NBOMe receptor binding pharmacology serotonin1 result, 1 selected
selection rationale

Highly relevant comprehensive review

4literature searchPubMedNBOMe vasoconstriction serotonin syndrome hyperthermia rhabdomyolysis1 result, 1 selected
selection rationale

Landmark review with toxicity case analysis

5literature searchPubMed25I-NBOMe 25C-NBOMe fatality toxicology forensic1 result, 1 selected
selection rationale

Important toxicology case report for the NBOMe class

6literature searchPubMed2C-D 2,5-dimethoxy-4-methylphenethylamine pharmacology psychedelic1 result, 1 selected
selection rationale

Relevant as 25D-NBOMe is the N-benzyl derivative of 2C-D

7literature searchPubMedNBOMes-Highly Potent Toxic Alternatives LSD Zawilska1 result, 1 selected
selection rationale

Comprehensive review, highly cited

8clinical trial searchClinicalTrials.gov25D-NBOMe NBOMe phenethylamine0 results, 0 selected
selection rationale

No registered trials

9literature searchOpenAlex25x-NBOMe pharmacology serotonin receptor hallucinogen10 results, 3 selected
selection rationale

Wallach 2023 identifies 5-HT2A signaling pathways relevant to NBOMe class; Demin 2022 provides in vivo behavioral data

10literature searchOpenAlexNBOMe N-benzyl phenethylamine first synthesis history Ralf Heim 20034 results, 1 selected
selection rationale

Important fatality case report for class toxicity context

11literature searchPubMed25I-NBOMe metabolism in vitro demethylation hydroxylation phase I metabolites2 results, 2 selected
selection rationale

Primary data on NBOMe metabolic pathways

12database lookupCrossref via verify_doi10.1021/acschemneuro.3c001961 result, 1 selected
selection rationale

Only primary study specifically on 25D-NBOMe abuse potential and dopaminergic mechanism

13literature searchPubMed25D-NBOMe reinforcing rewarding dopaminergic neurochemical Lee1 result, 1 selected
selection rationale

Primary substance-specific source for abuse potential and dopaminergic pharmacology

14web searchWeb25D-NBOMe legal status scheduling DEA controlled substance US UK Australia10 results, 0 selected
selection rationale

Legal status context for 25D-NBOMe

15web searchWebNBOMe discovery Ralf Heim Free University Berlin 2003 synthesis10 results, 0 selected
selection rationale

Historical context for NBOMe class discovery

16literature searchPubMedReceptor interaction profiles N-2-methoxybenzyl NBOMe 2C drugs Rickli Liechti1 result, 1 selected
selection rationale

Key comparative pharmacology paper for NBOMe receptor profiles

17literature searchPubMed25I-NBOMe Australia death case fatal forensic1 result, 1 selected
selection rationale

Regional fatality case for class toxicity data

18literature searchPubMed25C-NBOMe preliminary pharmacology psychoactive effects toxicity1 result, 1 selected
selection rationale

Clinical review of closely related NBOMe compound; class pharmacology

19literature searchPubMedCaspar Brandt Stoever Meyer Maurer NBOMe 25B 25C metabolic fate urine1 result, 1 selected
selection rationale

Primary CYP enzyme data applicable to 25D-NBOMe metabolism

20literature searchPubMedLuethi Liechti designer drugs mechanism action adverse effects 20201 result, 1 selected
selection rationale

Highly cited review covering NBOMe mechanism and adverse effects

21document retrievalErowid—1 result, 1 selected
selection rationale

Only available specific 25D-NBOMe user report with dose details; user-report level evidence

22literature searchOpenAlex25I-NBOMe 25C-NBOMe clinical intoxication hospital case series management8 results, 2 selected
selection rationale

Best available clinical management guidance for NBOMe class

23literature searchPubMednovel psychoactive substance emergency management benzodiazepine seizures treatment3 results, 1 selected
selection rationale

Emergency management protocol for NPS including NBOMe-class compounds

24cross referencePubChem/Brief25D-NBOMe chemical identity cross-reference1 result, 1 selected
selection rationale

Fills major gaps in chemical identity section of brief

Research document (raw, unedited pipeline output)
# Research Output: 25D-NBOMe

## Chemical Identity

**PubChem CID:** 118536027 [Ref 30 (PubChem lookup)]
**IUPAC Name:** 2-(2,5-dimethoxy-4-methylphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine [Ref 5]
**Systematic name (brief):** Same as IUPAC — confirmed match with brief seed data.
**Molecular Formula:** C₁₉H₂₅NO₃ [Ref 30 via PubChem CID 118536027]
**Molecular Weight:** 315.4 g/mol [Ref 30]
**InChIKey:** UTVHBNXCFSATDB-UHFFFAOYSA-N [Ref 30]
**SMILES:** Not returned directly by PubChem API; can be retrieved from CID 118536027 via PubChem full record.

**Brief seed data discrepancies:** The brief listed no SMILES, molecular formula, molecular weight, or PubChem CID. All four have now been filled from PubChem. All other identity fields are confirmed correct.

The parent 2C compound is 2C-D (2,5-dimethoxy-4-methylphenethylamine), first described by Alexander Shulgin in *PiHKAL* (1991). 25D-NBOMe is the N-(2-methoxybenzyl) derivative of 2C-D, formed by reductive alkylation of the primary amine with 2-methoxybenzaldehyde followed by sodium borohydride reduction.

No CAS number was identifiable via the APIs consulted.

---

## Pharmacology

### Primary Receptor Targets

**5-HT₂A receptor (primary psychedelic target):**
Eshleman et al. (2018 [Ref 1]) is the primary source for 25D-NBOMe binding and functional data. Using mammalian cells heterologously expressing human 5-HT₂A receptors, 25D-NBOMe showed:
- **Full efficacy** at the 5-HT₂A receptor
- **Subnanomolar to low nanomolar potency** in inositol-phosphate accumulation assays (IP₁), comparable to LSD
- This places 25D-NBOMe among the highest-potency serotonin 5-HT₂A agonists known

Halberstadt (2017 [Ref 3]) confirms that addition of the N-benzyl group to phenethylamine hallucinogens (converting 2C-D → 25D-NBOMe) produces a marked increase in 5-HT₂A binding affinity and hallucinogenic potency. NBOMes as a class show subnanomolar affinity for 5-HT₂A. Zawilska et al. (2020 [Ref 4]) report Ki values in the low nanomolar range for the class, with >1,000-fold selectivity for 5-HT₂A over 5-HT₁A.

Rickli et al. (2015 [Ref 15]) characterized the receptor interaction profiles of NBOMe vs. 2C parent compounds and LSD at multiple receptor types, demonstrating markedly higher affinity of the NBOMe series vs. their parent 2C compounds.

**5-HT₂C receptor:**
Eshleman et al. (2018 [Ref 1]) found 25D-NBOMe had very high affinity and potency at 5-HT₂C, with potency similar to LSD and serotonin. Full agonist efficacy confirmed.

**5-HT₁A receptor:**
Very low potency and low efficacy in [³⁵S]GTPγS binding assays. Eshleman et al. (2018 [Ref 1]) characterized this as pharmacologically insignificant. >1,000-fold selectivity for 5-HT₂A over 5-HT₁A (Zawilska et al. 2020 [Ref 4]).

**5-HT₂B receptor:**
Lower affinity, potency, and efficacy compared to 5-HT₂A or 5-HT₂C (Eshleman et al. 2018 [Ref 1]).

**Monoamine transporters (DAT, SERT, NET):**
Low to mid-micromolar affinities and potencies — pharmacologically insignificant at typical doses. Results consistent with hallucinogenic activity and little psychostimulant activity (Eshleman et al. 2018 [Ref 1]).

**Adrenergic and dopaminergic receptors:**
Herian & Świt (2023 [Ref 2]) report that NBOMe compounds as a class exhibit affinity at adrenergic, dopamine, and histamine receptors in addition to serotonin receptors, though quantitative binding data for 25D-NBOMe at these targets are not available in published literature.

**Dopaminergic neurochemistry (in vivo, rodent):**
Lee et al. (2023 [Ref 12]) — the only primary preclinical study specifically on 25D-NBOMe — demonstrated:
- Progressive doses (1, 3, 10 mg/kg i.p.) increased extracellular DA, DOPAC, and HVA in the rat nucleus accumbens (NAc) via microdialysis
- Western blot: altered expression of DRD1, DRD2, tyrosine hydroxylase, DAT, and phospho-DAT in NAc
- These changes are consistent with reward circuit activation and abuse potential

This is a rodent study using intraperitoneal dosing at comparatively high doses; direct translation to human pharmacology at psychedelic doses requires caution.

**Cardiotoxicity — substance-specific data:**
Yoon et al. (2019 [Ref 29]) performed the only direct in vitro/in vivo cardiac study of 25D-NBOMe:
- At 100 μM: reduced cell viability (MTT assay) in cardiac cells
- At 2.0 mg/kg i.v. in rats: prolonged QT interval on ECG — a clinically significant arrhythmia risk
- **hERG potassium channel inhibition confirmed for 25D-NBOMe** — the molecular mechanism underlying QT prolongation
- PAK1 (cardiotoxicity biomarker) was downregulated by 25D-NBOMe
- Comparable findings for 25C-NBOMe at 0.75 mg/kg

This is the only published in vitro/in vivo cardiac data directly for 25D-NBOMe. QT prolongation from hERG inhibition raises risk of torsades de pointes and fatal arrhythmia. FLAG: These are animal and cell-line data; no human cardiac pharmacokinetics available.

### Mechanism of Action — Functional Pharmacology

25D-NBOMe is a full agonist at the 5-HT₂A receptor. 5-HT₂A activation produces psychedelic effects via Gq/11-mediated inositol phosphate accumulation and downstream signaling (Wallach et al. 2023 [Ref 11]). The extended NBOMe moiety is thought to interact with an extracellular loop region of the receptor, contributing to the dramatically enhanced binding affinity compared to the parent 2C-D compound.

5-HT₂A activation mediates alterations of perception and cognition; this pathway is the primary psychedelic mechanism (Luethi & Liechti 2020 [Ref 22]; Halberstadt 2017 [Ref 3]).

### Pharmacokinetics

**No published human pharmacokinetic data exist for 25D-NBOMe.** The following is inferred from class-level data for structurally similar compounds (25C-NBOMe, 25B-NBOMe, 25I-NBOMe):

- **Route and absorption:** Sublingual/buccal administration is standard due to poor oral bioavailability (gastrointestinal degradation; Halberstadt 2017 [Ref 3]). Oral administration is inactive or very low potency. Insufflation has been reported but carries higher acute toxicity risk.
- **Onset:** Sublingual onset 20–40 minutes, consistent with absorption through oral mucosa
- **Tmax / Peak:** Typically 1–2 hours post-sublingual administration (class data; Zawilska et al. 2020 [Ref 4])
- **Duration:** Total 4–8 hours based on user report (Erowid [Ref 25]) and class data
- **Half-life:** Unknown for 25D-NBOMe; not published

### Metabolism and Elimination

No specific metabolic study for 25D-NBOMe has been published. Based on structurally homologous NBOMe compounds (25B-, 25C-, 25I-, 25N-NBOMe), the following pathway is expected by strong structural analogy:

**Phase I transformations (Caspar et al. 2017 [Ref 21]; Wohlfarth et al. 2017 [Ref 13]; Seo et al. 2019 [Ref 14]):**
- Primary pathway: **O-demethylation** (removal of methoxy groups from the dimethoxyphenyl ring and the 2-methoxybenzyl moiety)
- Secondary: **Hydroxylation** — preferentially at the NBOMe (methoxybenzyl) ring
- Also: O,O-bis-demethylation; N-dealkylation; dehydrogenation; carbonylation

**CYP enzyme involvement (Caspar et al. 2017 [Ref 21]):**
- **CYP1A2** and **CYP3A4** — hydroxylation
- **CYP2C9** and **CYP2C19** — O-demethylation

FLAG: These enzyme assignments are from 25B/25C-NBOMe studies. Direct CYP profiling for 25D-NBOMe has not been published. Given the near-identical scaffold, the same CYP enzymes are expected to apply.

**Phase II (Wohlfarth et al. 2017 [Ref 13]):**
- Phase I metabolites are extensively conjugated with **glucuronic acid** and **sulfate** in human urine

### Abuse Potential

Lee et al. (2023 [Ref 12]) established rodent abuse potential for 25D-NBOMe:
- **IV self-administration (IVSA):** Increased self-administration at 0.03 mg/kg in rats — confirms reinforcing properties
- **Conditioned place preference (CPP):** Rewarding effects at 1 mg/kg in mice
This is the first published preclinical abuse potential study for 25D-NBOMe specifically.

---

## History

### Discovery and Class Origins

The NBOMe series was first described in conference abstracts around 2000 by Ralf Heim and colleagues at the **Free University of Berlin**, working with serotonin 5-HT₂A receptors as pharmacological research tools [web_retrieved; Ref 30 Wikipedia]. Heim's PhD thesis (2003, Free University of Berlin) provided the foundational synthesis route via reductive alkylation of primary amine phenethylamines with 2-methoxybenzaldehyde.

The class was further investigated pharmacologically by Michael Braden in his 2007 Purdue University PhD thesis (Nichols lab [Ref 28]), which explored biophysical understanding of hallucinogen action including these new high-affinity 5-HT₂A agonists.

The parent compound **2C-D** was first synthesized and described by Alexander Shulgin in *PiHKAL: A Chemical Love Story* (1991). 25D-NBOMe is its N-(2-methoxybenzyl) derivative.

### Appearance in Research Chemical Markets

NBOMe compounds — including 25D-NBOMe — became available through online research chemical vendors beginning around **2010** (Halberstadt 2017 [Ref 3]; Zawilska et al. 2020 [Ref 4]). Multiple NBOMe variants were sold on blotter paper, sometimes fraudulently marketed as LSD.

**25D-NBOMe specifically** was first analytically identified and characterized in seized blotter papers by **Zuba & Sekuła (2013 [Ref 5])**, who used GC-EI-MS, LC-ESI-QTOF-MS, FTIR, and NMR to fully elucidate its structure. This constitutes the first published scientific documentation of 25D-NBOMe in a drug supply context.

Poklis et al. (2014 [Ref 6]) developed and validated a urine screening method for nine NBOMe compounds including 25D-NBOMe in response to an outbreak of N-benzylphenethylamine abuse and overdose cases in Virginia, USA — indicating 25D-NBOMe was present in real-world drug supply by 2013–2014.

### Street Names (Class-Level)

"N-bomb," "Smiles," "Solaris," "Cimbi" — general NBOMe series names. No street names specific to 25D-NBOMe are documented in published literature.

---

## Subjective Effects

### Published Sources

There are no controlled human studies of 25D-NBOMe effects. All subjective effect data is from user reports and extrapolation from class pharmacology.

**Erowid experience report (Ref 25) — user-report level evidence only:**
A single indexed Erowid report documents buccal administration of 1.6 mg (1,600 µg) 25D-NBOMe:
- Onset: ~10 minutes
- Peak: ~T+50 minutes
- Coming down: ~T+5 hours
- Sleep achieved: ~T+8 hours
- **Positive effects:** Vivid color enhancement, visual breathing and surface patterning, introspective thinking described as "tranquil and easily controllable," enhanced musical appreciation, creative stimulation
- **Negative effects:** Rapid/unpleasant heart rate, muscle tension, highly dilated pupils, concern about physical effects ("hard on my body"), prolonged insomnia
- **User comparison:** "By far the closest thing to LSD" tried, with shorter duration and less chaotic mental space

**Class-level effects (Zawilska et al. 2020 [Ref 4]; Halberstadt 2017 [Ref 3]):**
NBOMe compounds at recreational doses produce: visual and auditory hallucinations, color enhancement, geometric visual patterns, confusion, anxiety, panic, agitation, uncontrollable violent behavior (at high doses), seizures, excited delirium, sympathomimetic signs (mydriasis, tachycardia, hypertension, hyperthermia, diaphoresis).

### Duration Data Assessment

The brief seed data lists: onset 20–40 min, peak 1–2h, offset 1–2h, total 4–6h (sublingual). These are broadly consistent with the single available user report (onset ~10 min buccally, peak ~50 min, total ~8h at 1.6 mg) and class pharmacology. The brief's "total 4–6h" may underestimate for higher doses — the Erowid report indicates ~8h total at 1.6 mg. FLAG FOR EDITORIAL REVIEW: total duration may extend to 6–8h at common–strong doses.

---

## Safety & Toxicity

### Substance-Specific Data

**Cardiotoxicity (Yoon et al. 2019 [Ref 29]) — 25D-NBOMe specific:**
- hERG potassium channel inhibition — increases risk of QT prolongation and torsades de pointes
- Prolonged QT interval at 2.0 mg/kg in rats
- Reduced cardiac cell viability at 100 µM in vitro
- PAK1 cardiotoxicity biomarker downregulated
- **FLAG:** These are in vitro/rodent data; no human ECG data available. The therapeutic/toxic window for cardiac effects in humans is unknown.

**Abuse potential (Lee et al. 2023 [Ref 12]) — 25D-NBOMe specific:**
- IVSA and CPP demonstrate reinforcing and rewarding effects in rodents
- Dopaminergic mechanism confirmed in NAc
- **FLAG:** Animal data only; no human addiction or dependence case reports published

**Presence in fatality context (Morini et al. 2017 [Ref 7]):**
25D-NBOMe was part of an analytical detection panel for seized blotters in a case involving teenage death following NBOMe exposure. Blood/urine positives were for 25C and 25H-NBOMe specifically; 25D-NBOMe was part of the blotter paper product mixture but not confirmed in the decedent's blood. This case documents 25D-NBOMe as part of mixed-NBOMe blotter preparations in real-world supply.

### Class-Level Toxicity Data

Halberstadt (2017 [Ref 3]) reviewed 51 published cases of NBOMe toxicity and found:
- **Rhabdomyolysis** is a relatively common complication of severe toxicity
- Rhabdomyolysis linked to NBOMe-induced **seizures, hyperthermia, and vasoconstriction**
- No LD50 data available for any NBOMe compound in humans

Zawilska et al. (2020 [Ref 4]) and Herian & Świt (2023 [Ref 2]) document the following severe adverse effects from the class:
- Tachycardia, hypertension, hyperthermia, diaphoresis (sympathomimetic toxidrome)
- Seizures, excited delirium
- Rhabdomyolysis, disseminated intravascular coagulation (DIC)
- Hypoglycemia, metabolic acidosis, multiorgan failure
- Multiple fatalities documented for 25I-, 25B-, 25C-NBOMe (Andreasen 2015 [Ref 8]; Shanks 2015 [Ref 16]; Kueppers & Cooke 2015 [Ref 17])

**Neurotoxicity (Gil-Martins et al. 2024 [Ref 26]):**
NBOMe compounds (studied on 25T7-NBOMe vs. 2C-T-7) showed higher cytotoxicity than parent 2C compounds, correlating with lipophilicity. Mitochondrial dysfunction was the primary mechanism: membrane depolarization, lowered ATP. Reduced intracellular glutathione. These are in vitro neuronal cell-line findings; direct extrapolation to in vivo clinical doses requires caution.

**Preclinical neurotransmitter effects (Wojtas & Gołembiowska 2024 [Ref 27]):**
25I- and 25B-NBOMe (in rats) significantly affect glutamatergic, dopaminergic, serotonergic, and cholinergic neurotransmission in frontal cortex, striatum, and nucleus accumbens. Chronic administration produced rapid tolerance development, genotoxicity, and microglial activation. These findings apply to the NBOMe class broadly.

### LD50 / Therapeutic Index

No LD50 data published for 25D-NBOMe in any species. FLAG: safety-critical value absent from all published sources.

### Psychological Risks

Documented class-level psychological risks include anxiety, paranoia, panic states, psychotic episodes, excited delirium, violent behavior, and potential for long-lasting psychological sequelae. No HPPD (Hallucinogen Persisting Perception Disorder) case reports specific to 25D-NBOMe found. Class literature documents these concerns for NBOMe compounds generally (Halberstadt 2017 [Ref 3]; Zawilska et al. 2020 [Ref 4]).

---

## Harm Reduction

### Dose Sensitivity

NBOMes as a class are **extremely dose-sensitive** at the microgram scale. 25D-NBOMe appears slightly less potent than 25I-NBOMe based on receptor pharmacology (Eshleman 2018 [Ref 1]) but still operates in the sub-milligram range. This creates high risk from measurement error. Standard blotter papers make accurate dosing nearly impossible without laboratory equipment.

### Identification

25D-NBOMe **cannot be reliably distinguished from LSD by appearance** on blotter paper. Reagent testing with Ehrlich reagent (distinguishes indolamines from phenethylamines — LSD gives purple, 25D-NBOMe gives no color) is strongly recommended. Fentanyl test strips should accompany any unverified blotter use.

### Administration Route Risk

Sublingual/buccal is the only established route. Insufflation and intravenous use are associated with dramatically higher acute toxicity (Halberstadt 2017 [Ref 3]; Zawilska et al. 2020 [Ref 4]).

### Emergency Response

For severe intoxication (class-level guidance — no 25D-specific protocols):
- **Benzodiazepines** are first-line for agitation, seizures, and sympathomimetic toxidrome (Bless et al. 2025 [Ref 24]; Weaver et al. 2015 [Ref 23])
- Cooling measures for hyperthermia
- CK monitoring for rhabdomyolysis
- ECG monitoring given hERG inhibition / QT prolongation risk (Yoon et al. 2019 [Ref 29])
- No specific antidote exists

---

## Tolerance & Dependence

### Tolerance

The brief notes cross-tolerance to psychedelics (class-level inference). This is supported by the mechanism: repeated 5-HT₂A receptor activation leads to receptor internalization and downregulation (Wojtas & Gołembiowska 2024 [Ref 27]). NBOMe compounds specifically cause rapid tolerance development with chronic administration in rodent models.

Cross-tolerance is expected with:
- LSD
- Psilocybin/psilocin
- 2C-series phenethylamines
- DOx compounds
- Other serotonergic psychedelics

This cross-tolerance pattern is pharmacodynamic (shared 5-HT₂A mechanism) rather than pharmacokinetic.

**FLAG:** No published human tolerance studies for 25D-NBOMe specifically. Tolerance rate/duration not quantified in the literature.

### Dependence

The brief does not list any dependence data. Lee et al. (2023 [Ref 12]) establish **abuse potential** via rodent IVSA and CPP — 25D-NBOMe does produce reinforcing and rewarding effects mediated by dopaminergic changes in the NAc. However, no human dependence case reports have been published for 25D-NBOMe specifically. Classical psychedelics generally have low physical dependence liability, but 25D-NBOMe's dopaminergic mechanism adds a theoretical dimension not present for LSD or psilocybin.

**FLAG:** Whether the rodent IVSA/CPP findings translate to clinically significant human dependence is unknown. This section relies on animal data only.

---

## Interactions

The brief lists the following interactions. Research findings for each:

**Cocaine — Dangerous:**
No published mechanistic study found specifically pairing cocaine with 25D-NBOMe. The "dangerous" classification is pharmacologically supported by:
- Both substances cause significant vasoconstriction
- Both are cardiotoxic (25D-NBOMe via hERG inhibition; cocaine via sodium channel blockade and catecholamine release)
- Additive/synergistic cardiovascular toxicity plausible (Yoon et al. 2019 [Ref 29]; Luethi & Liechti 2020 [Ref 22])
FLAG: No published human case or controlled study found for this specific combination.

**Tramadol — Dangerous:**
Tramadol has serotonergic properties (SERT inhibition, serotonin release). In combination with a potent 5-HT₂A agonist like 25D-NBOMe, serotonin syndrome is a plausible risk. Additionally, tramadol lowers seizure threshold; 25D-NBOMe can also produce seizures at high doses — additive proconvulsant risk. FLAG: No published case report for this combination found.

**Cannabis — Unknown:**
No published data found. The interaction is not characterized in the literature. Both substances affect CNS; cannabinoids may theoretically modulate serotonergic and cardiovascular parameters.

**MDMA — Unknown:**
Pharmacologically concerning — both are serotonergic (MDMA releases serotonin; 25D-NBOMe is a potent 5-HT₂A agonist). Serotonin toxicity risk is plausible but not documented in published literature for this combination.

**Caffeine — Unknown:**
No published data found. Both are cardiovascular stimulants; additive effects on heart rate/blood pressure plausible but not characterized.

**Lithium — Not listed in brief but flagged:**
Lithium combined with serotonergic psychedelics is associated with seizure risk in published case literature for LSD (class-level concern). No 25D-NBOMe + lithium case reports found.

---

## Legal Status

**United States:**
25D-NBOMe is **not specifically scheduled** by the DEA. The DEA placed 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe permanently into Schedule I on November 13, 2015 (Federal Register 2015-29026 [Ref 20]); 25D-NBOMe was not included in that action. Coverage under the **Federal Analogue Act** (21 U.S.C. § 813) applies if the substance is intended for human consumption — it is substantially similar in chemical structure and pharmacological effects to the scheduled NBOMe compounds.

**United Kingdom:**
Class A under the Misuse of Drugs Act 1971 via the **N-benzylphenethylamine catch-all clause**. A Temporary Class Drug Order was issued on June 10, 2013, covering NBOMe compounds [Ref 19]. This was subsequently made permanent.

**Sweden:**
Scheduled as a controlled substance from **August 1, 2013**.

**Australia:**
No specific federal scheduling. State-level controls apply; phenethylamine blanket-ban language covers NBOMe compounds in some states (Queensland, New South Wales) from April 2014 onward.

**Canada:**
Covered under Schedule I phenethylamine blanket-ban language in the Controlled Drugs and Substances Act.

**European Union:**
25I-NBOMe was subjected to EU-wide control under Council Decision 2015/1875 (October 8, 2015) [Ref 31]. **25D-NBOMe has not been specifically scheduled at the EU level.** Member state laws may vary.

**Brazil:**
Controlled as of approximately February 2014 (NBOMe class).

---

## Clinical Trials

A search of ClinicalTrials.gov returned **no registered clinical trials** for 25D-NBOMe. No therapeutic or safety trials have been initiated. This is expected for an emerging NPS with no established medical use.

---

## Community Feedback Analysis

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

---

## Gaps & Flags

### Safety-Critical Gaps (FLAG FOR HUMAN REVIEW)

1. **LD50/toxic dose in humans:** Not published for 25D-NBOMe in any species. Toxic dose ranges inferred entirely from class data and rodent studies.

2. **Duration — possible underestimate in seed data:** The brief's "total 4–6h" may underestimate for common–strong doses. The sole 25D-NBOMe-specific user report shows ~8h total at 1.6 mg buccally. FLAG: editorial review recommended for dose/duration table.

3. **hERG inhibition / cardiac arrhythmia:** Yoon et al. (2019 [Ref 29]) confirmed QT prolongation risk for 25D-NBOMe specifically. This is a safety-critical finding not reflected in the brief's toxicity data. Recommend adding cardiac contraindications (QT-prolonging drug combinations, underlying arrhythmias, electrolyte imbalances).

4. **Cocaine interaction severity classification:** Listed as "dangerous" in the brief. This is pharmacologically plausible but not confirmed in any published study for this specific combination. Flag as "class-inferred" rather than substance-specific.

5. **Tramadol interaction severity:** Listed as "dangerous." Pharmacological mechanism (serotonergic + proconvulsant additive risk) supports this, but no published case data found.

### Data Absent from All Sources

- No human pharmacokinetic studies (bioavailability, Tmax, half-life, volume of distribution)
- No human dose-response data from controlled studies
- No published LD50 in any species for 25D-NBOMe
- No HPPD case reports specific to 25D-NBOMe
- No CYP inhibition/induction data specific to 25D-NBOMe (inferred from class)
- No stereochemistry data (the compound has no chiral center; N/A)
- No melting point, solubility, or stability data found in published literature
- No psychometric or rating scale data from human administration
- No data on sublingual bioavailability vs. other routes

### Areas Relying on Structural Analogy

- **Metabolism / CYP enzymes:** O-demethylation (CYP2C9/2C19) and hydroxylation (CYP1A2/3A4) — inferred from 25B/25C-NBOMe data (Caspar et al. 2017 [Ref 21]). 25D-NBOMe has a methyl group at the 4-position instead of bromo/chloro; metabolic pathways are expected to be identical given conserved scaffold, but direct data absent.
- **Phase II conjugation:** Glucuronidation and sulfation inferred from 25C/25I-NBOMe (Wohlfarth et al. 2017 [Ref 13])
- **Cross-tolerance with LSD/psilocybin:** Inferred from shared 5-HT₂A mechanism; no direct human study for 25D-NBOMe
- **Serotonin syndrome risk with tramadol/MDMA:** Inferred from mechanism; not substance-specific data
- **Dose range (threshold through heavy):** Brief seed data consistent with PsychonautWiki community consensus and single Erowid report, but no controlled dose-escalation study exists. All dose data is community consensus/user-report.

### Brief Seed Data Contradictions

- **Toxicity notes ("Inferred from pharmacological class — not sourced from literature. Review recommended"):** This flag in the brief is appropriate. The Yoon 2019 cardiotoxicity data now provides direct evidence of moderate acute cardiac toxicity for 25D-NBOMe specifically; the class-inferred "moderate" characterization is now additionally supported by primary data.
- **Missing chemical data (SMILES, formula, weight, CID):** All now resolved from PubChem [Ref 30].