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Psychedex

25I-NBOMe

4-iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine

Sources
33
2 strong · 20 moderate · 10 weak · 1 untiered

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

Claims checked
102
71verified27inconclusive4not supported

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

Generated
Apr 25, 2026 · pipeline-v5
Values approved
201/201 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

sublingualtrace

FieldPublishedAI ProposedConfidence
Threshold50 µg50 µgmedium
Low200–500 µg200–500 µgmedium
Common500–700 µg500–700 µgmedium
Strong700–1000 µg700–1000 µgmedium
Heavy1000+ µg1000+ µgmedium
Editorial

Dose ranges from seed data consistent with Zawilska et al. 2020 review. Threshold 50 µg, light 200-500 µg, common 500-700 µg, strong 700-1000 µg, heavy >1000 µg. Safety note: strong and heavy ranges overlap with fatality-associated doses. No controlled human dose-response study exists.

Reasoning

Dose ranges from seed data consistent with Zawilska et al. 2020 review. Threshold 50 µg, light 200-500 µg, common 500-700 µg, strong 700-1000 µg, heavy >1000 µg. Safety note: strong and heavy ranges overlap with fatality-associated doses. No controlled human dose-response study exists.

Evidence basis: community_consensus_large

insufflatedtrace

FieldPublishedAI ProposedConfidence
Threshold50 µg50 µglow
Low200–500 µg200–500 µglow
Common500–700 µg500–700 µglow
Strong——low
Heavy——low
Editorial

Insufflated dose data from seed data. Threshold and light/common ranges provided. No 'strong' or 'heavy' insufflated dose data exist in the seed data or published literature, possibly because insufflated doses in the strong range are more likely to be acutely toxic. Insufflated route produces faster onset and higher peak concentrations, increasing toxicity risk at equivalent doses.

Reasoning

Insufflated dose data from seed data. Threshold and light/common ranges provided. No 'strong' or 'heavy' insufflated dose data exist in the seed data or published literature, possibly because insufflated doses in the strong range are more likely to be acutely toxic. Insufflated route produces faster onset and higher peak concentrations, increasing toxicity risk at equivalent doses.

Evidence basis: community_consensus_large

Duration

insufflated

FieldPublishedAI ProposedConfidence
Totaltrace4–6 hours4–6 hoursmedium
Editorial

Total 4-6 h from seed data. Shorter than sublingual route.

Reasoning

Total 4-6 h from seed data. Shorter than sublingual route.

Evidence basis: community_consensus_large

After effectstrace1–7 days1–7 dayslow
Editorial

Aftereffects 1-7 days from seed data (user self-reports). Flagged for editorial review as unusually long. No controlled study confirms.

Reasoning

Aftereffects 1-7 days from seed data (user self-reports). Flagged for editorial review as unusually long. No controlled study confirms.

Evidence basis: community_consensus_small

Onsettrace5–10 minutes5–10 minutesmedium
Editorial

Onset 5-10 min from seed data. Faster than sublingual due to nasal mucosal absorption.

Reasoning

Onset 5-10 min from seed data. Faster than sublingual due to nasal mucosal absorption.

Evidence basis: community_consensus_large

Come uptrace10–30 minutes10–30 minutesmedium
Editorial

Come-up 10-30 min from seed data.

Reasoning

Come-up 10-30 min from seed data.

Evidence basis: community_consensus_large

Peaktrace60–120 minutes60–120 minutesmedium
Editorial

Peak 60-120 min from seed data.

Reasoning

Peak 60-120 min from seed data.

Evidence basis: community_consensus_large

Offsettrace2–3 hours2–3 hoursmedium
Editorial

Offset 2-3 h from seed data.

Reasoning

Offset 2-3 h from seed data.

Evidence basis: community_consensus_large

sublingual

FieldPublishedAI ProposedConfidence
Onsettrace15–120 minutes15–120 minutesmedium
Editorial

Onset 15-120 min from seed data, consistent with buccal mucosal absorption variability described in Halberstadt 2017 and Zawilska et al. 2020.

Reasoning

Onset 15-120 min from seed data, consistent with buccal mucosal absorption variability described in Halberstadt 2017 and Zawilska et al. 2020.

Evidence basis: community_consensus_large

Come uptrace30–120 minutes30–120 minutesmedium
Editorial

Come-up 30-120 min from seed data. Consistent with published case reports describing gradual effect escalation.

Reasoning

Come-up 30-120 min from seed data. Consistent with published case reports describing gradual effect escalation.

Evidence basis: community_consensus_large

Peaktrace2–4 hours2–4 hoursmedium
Editorial

Peak 2-4 h from seed data. Consistent with published case report timelines.

Reasoning

Peak 2-4 h from seed data. Consistent with published case report timelines.

Evidence basis: community_consensus_large

Offsettrace1–4 hours1–4 hoursmedium
Editorial

Offset 1-4 h from seed data.

Reasoning

Offset 1-4 h from seed data.

Evidence basis: community_consensus_large

After effectstrace3–6 days3–6 dayslow
Editorial

Aftereffects 3-6 days from seed data (user self-reports). Flagged for editorial review as unusually long for a phenethylamine. No controlled study confirms this duration.

Reasoning

Aftereffects 3-6 days from seed data (user self-reports). Flagged for editorial review as unusually long for a phenethylamine. No controlled study confirms this duration.

Evidence basis: community_consensus_small

Totaltrace6–10 hours6–10 hoursmedium
Editorial

Total 6-10 h from seed data, consistent with Zawilska et al. 2020. Unusually long for a phenethylamine.

Reasoning

Total 6-10 h from seed data, consistent with Zawilska et al. 2020. Unusually long for a phenethylamine.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutecriticalcriticalhigh
Chronicmoderatemoderatehigh
Organs Affectedcardiovascular, kidney, brain, musculoskeletalcardiovascular, kidney, brain, musculoskeletalhigh
Editorial

Acute toxicity classified as critical: multiple documented fatalities at doses within or near the recreational range (Halberstadt 2017 reviewed 51 cases; Walterscheid 2014, Poklis 2014, Shanks 2015, Kueppers 2015, Lowe 2015 all document fatal outcomes). Narrow therapeutic/toxic window with no established LD50. Chronic classified as moderate (downgraded from high): neurotoxicity evidence (glial cell reduction, oxidative DNA damage) is from rat chronic dosing only (Herian et al. 2022); no human chronic-use data exist.

Reasoning

Acute toxicity classified as critical: multiple documented fatalities at doses within or near the recreational range (Halberstadt 2017 reviewed 51 cases; Walterscheid 2014, Poklis 2014, Shanks 2015, Kueppers 2015, Lowe 2015 all document fatal outcomes). Narrow therapeutic/toxic window with no established LD50. Chronic classified as moderate (downgraded from high): neurotoxicity evidence (glial cell reduction, oxidative DNA damage) is from rat chronic dosing only (Herian et al. 2022); no human chronic-use data exist.

Evidence basis: published_case_series

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalnonenonemedium
Psychologicalnegligiblenegligiblemedium
Compulsive Redosinglowlowmedium
Dose Escalationnegligiblenegligiblemedium
Editorial

Dependence profile consistent with 5-HT2A agonist psychedelic class: rapid tolerance prevents compulsive use. No human dependence case reports. Rat data (Herian et al. 2019, 2022) confirm tolerance to behavioral and neurochemical effects. Compulsive redosing risk rated low rather than negligible due to the variable sublingual onset (15-120 min) which can tempt premature redosing before effects manifest.

Reasoning

Dependence profile consistent with 5-HT2A agonist psychedelic class: rapid tolerance prevents compulsive use. No human dependence case reports. Rat data (Herian et al. 2019, 2022) confirm tolerance to behavioral and neurochemical effects. Compulsive redosing risk rated low rather than negligible due to the variable sublingual onset (15-120 min) which can tempt premature redosing before effects manifest.

Evidence basis: animal_study

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitynonenonemedium
Symptoms——medium
FatalNoNomedium
Medical SupervisionNot requiredNot requiredmedium
Editorial

No withdrawal syndrome has been documented for 25I-NBOMe or any 5-HT2A agonist psychedelic. Consistent with class pharmacology: rapid receptor downregulation without compensatory upregulation that would produce rebound effects.

Reasoning

No withdrawal syndrome has been documented for 25I-NBOMe or any 5-HT2A agonist psychedelic. Consistent with class pharmacology: rapid receptor downregulation without compensatory upregulation that would produce rebound effects.

Evidence basis: animal_study

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidmedium
Half-life7 days7 daysmedium
Full Reset14 days14 daysmedium
Cross-tolerancesLSD, psilocybin, psilocin, DMT, mescaline, 2C-I, 2C-B, 25C-NBOMe, 25B-NBOMeLSD, psilocybin, psilocin, DMT, mescaline, 2C-I, 2C-B, 25C-NBOMe, 25B-NBOMemedium
Editorial

Rapid tolerance confirmed in mouse HTR models (de la Fuente Revenga et al. 2022; Smith et al. 1999). 5-HT2A downregulation mechanism well-established for the psychedelic class. Cross-tolerance across serotonergic psychedelics confirmed. Half-life and reset values are community-derived estimates consistent with class pharmacology but not verified by controlled human studies.

Reasoning

Rapid tolerance confirmed in mouse HTR models (de la Fuente Revenga et al. 2022; Smith et al. 1999). 5-HT2A downregulation mechanism well-established for the psychedelic class. Cross-tolerance across serotonergic psychedelics confirmed. Half-life and reset values are community-derived estimates consistent with class pharmacology but not verified by controlled human studies.

Evidence basis: animal_study

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
psychiatric psychotic disorderstraceabsoluteabsolutehigh
Editorial

Class-level contraindication for all serotonergic psychedelics. Case reports of excited delirium with 25I-NBOMe support elevated psychosis risk.

Reasoning

Class-level contraindication for all serotonergic psychedelics. Case reports of excited delirium with 25I-NBOMe support elevated psychosis risk.

cardiovascular cardiovascular diseasetraceabsoluteabsolutehigh
Editorial

Zawilska et al. 2020 documents α₁ affinity and cardiovascular toxidrome. Multiple fatality case reports include cardiovascular complications.

Reasoning

Zawilska et al. 2020 documents α₁ affinity and cardiovascular toxidrome. Multiple fatality case reports include cardiovascular complications.

psychiatric bipolar disordertraceabsoluteabsolutemedium
Editorial

Class-level contraindication for serotonergic psychedelics. No 25I-NBOMe-specific data, but mechanism is well-established.

Reasoning

Class-level contraindication for serotonergic psychedelics. No 25I-NBOMe-specific data, but mechanism is well-established.

neurological epilepsytraceabsoluteabsolutehigh
Editorial

Seizures documented in multiple fatality cases and in Halberstadt 2017 review of 51 NBOMe toxicity cases.

Reasoning

Seizures documented in multiple fatality cases and in Halberstadt 2017 review of 51 NBOMe toxicity cases.

hepatic hepatic impairmenttracerelativerelativemedium
Editorial

Caspar et al. 2018 and Nielsen et al. 2017 characterize hepatic metabolism. CYP2D6 accounts for 61% of clearance.

Reasoning

Caspar et al. 2018 and Nielsen et al. 2017 characterize hepatic metabolism. CYP2D6 accounts for 61% of clearance.

pregnancy breastfeeding pregnancytraceabsoluteabsolutemedium
Editorial

Herian et al. 2022 demonstrated neurotoxicity in rat models. Absence of any reproductive safety data combined with documented toxicity constitutes absolute contraindication.

Reasoning

Herian et al. 2022 demonstrated neurotoxicity in rat models. Absence of any reproductive safety data combined with documented toxicity constitutes absolute contraindication.

other concurrent CYP2D6/CYP3A4 inhibitorstracerelativerelativemedium
Editorial

Caspar et al. 2018 and Nielsen et al. 2017 characterize CYP-mediated metabolism. CYP2D6 poor metabolizer status creates endogenous 'interaction' equivalent.

Reasoning

Caspar et al. 2018 and Nielsen et al. 2017 characterize CYP-mediated metabolism. CYP2D6 poor metabolizer status creates endogenous 'interaction' equivalent.

other concurrent serotonergic medicationstraceabsoluteabsolutehigh
Editorial

Zawilska et al. 2020 identifies serotonin syndrome risk with serotonergic co-administration. Andreasen et al. 2015 documents serotonin toxicity in related analog fatality.

Reasoning

Zawilska et al. 2020 identifies serotonin syndrome risk with serotonergic co-administration. Andreasen et al. 2015 documents serotonin toxicity in related analog fatality.

Timeline Phases

sublingual

FieldPublishedAI ProposedConfidence
Onsettrace900–7200 sec(i=0.05)900–7200 sec(i=0.05)medium
Editorial

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Reasoning

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Evidence basis: community_consensus_large

Come uptrace1800–7200 sec(i=0.30)1800–7200 sec(i=0.30)medium
Editorial

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Reasoning

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Evidence basis: community_consensus_large

Peaktrace7200–14400 sec(i=1.00)7200–14400 sec(i=1.00)medium
Editorial

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Reasoning

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Evidence basis: community_consensus_large

Plateautrace3600–7200 sec(i=0.55)3600–7200 sec(i=0.55)medium
Editorial

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Reasoning

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Evidence basis: community_consensus_large

Resolutiontrace3600–14400 sec(i=0.20)3600–14400 sec(i=0.20)medium
Editorial

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Reasoning

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Evidence basis: community_consensus_large

Afterglowtrace86400–259200 sec(i=0.05)86400–259200 sec(i=0.05)medium
Editorial

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Reasoning

Duration data from seed data and consistent with published literature (Zawilska et al. 2020, Halberstadt 2017). Onset 15-120 min, come-up 30-120 min, peak 2-4 h, offset 1-4 h, total 6-10 h. Aftereffects 3-6 days from user reports (flagged for editorial review as unusually long for a phenethylamine).

Evidence basis: community_consensus_large

insufflated

FieldPublishedAI ProposedConfidence
Onsettrace300–600 sec(i=0.05)300–600 sec(i=0.05)medium
Editorial

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Reasoning

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Evidence basis: community_consensus_large

Come uptrace600–1800 sec(i=0.35)600–1800 sec(i=0.35)medium
Editorial

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Reasoning

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Evidence basis: community_consensus_large

Peaktrace3600–7200 sec(i=1.00)3600–7200 sec(i=1.00)medium
Editorial

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Reasoning

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Evidence basis: community_consensus_large

Resolutiontrace7200–10800 sec(i=0.20)7200–10800 sec(i=0.20)medium
Editorial

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Reasoning

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Evidence basis: community_consensus_large

Afterglowtrace86400–259200 sec(i=0.05)86400–259200 sec(i=0.05)medium
Editorial

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Reasoning

Insufflated duration data from seed data: onset 5-10 min, come-up 10-30 min, peak 60-120 min, offset 2-3 h, total 4-6 h. Aftereffects 1-7 days from user reports. Shorter total duration but faster onset and potentially higher peak cardiovascular stress.

Evidence basis: community_consensus_large

Dose Tier Summaries

thresholdtrace
medium

At threshold doses (~50 µg sublingual), effects are subtle and may be difficult to distinguish from placebo: mild mood shift, slight visual brightening, faint color enhancement, and a gentle sense of altered awareness. Some users report a mild body buzz or slight increase in tactile sensitivity. Physically, mild pupil dilation and a faintly metallic or bitter taste from the blotter paper may be the only noticeable signs. Cardiovascular effects are minimal at this level. Functional impairment is negligible; most daily activities remain unaffected. Sleep may be slightly delayed if taken in the evening.

Editorial

Threshold dose of ~50 µg is consistent with Zawilska et al. 2020 and seed data. Subjective descriptions inferred from 5-HT₂A agonist class at sub-perceptual doses and user reports.

Reasoning

Threshold dose of ~50 µg is consistent with Zawilska et al. 2020 and seed data. Subjective descriptions inferred from 5-HT₂A agonist class at sub-perceptual doses and user reports.

Evidence basis: community_consensus_large

lighttrace
medium

At light doses (200–500 µg sublingual), recognizable psychedelic effects emerge: mild visual distortions including color enhancement, surface texturing, and slight pattern recognition changes. Mood elevation and thought connectivity increase noticeably. Music appreciation is enhanced. Mild synesthesia may occur. Physical effects become more apparent — pupil dilation, mild jaw tension, slight temperature dysregulation, and increased heart rate. The bitter taste of the compound is distinct at these doses. Mild nausea is possible during the come-up. The experience lasts 6–8 hours with residual stimulation. Sleep is unlikely for several hours after peak effects subside.

Editorial

Light dose range 200–500 µg from seed data consistent with Zawilska et al. 2020. Subjective effects inferred from case reports and 5-HT₂A agonist class profile at sub-common doses.

Reasoning

Light dose range 200–500 µg from seed data consistent with Zawilska et al. 2020. Subjective effects inferred from case reports and 5-HT₂A agonist class profile at sub-common doses.

Evidence basis: community_consensus_large

commontrace
medium

At common doses (500–700 µg sublingual), the full psychedelic experience manifests: pronounced visual hallucinations including geometric patterning, color saturation and shifting, drifting and morphing of surfaces, and closed-eye visuals. Synesthesia becomes more likely. Time distortion is significant. Thought patterns shift markedly — novel associations, emotional intensification, and immersion in sensory experience are characteristic. Physically, tachycardia, vasoconstriction (cold extremities), jaw tension, diaphoresis, and temperature dysregulation become common. Body load can be significant. Nausea during the come-up occurs in some individuals. The experience commits the user to 6–10 hours of altered consciousness. Sleep is impossible during active effects. Functional impairment is substantial.

Editorial

Common dose range 500–700 µg from seed data consistent with Zawilska et al. 2020. Subjective and physical effects drawn from clinical case reports (Halberstadt 2017, Wood et al. 2015) and user reports.

Reasoning

Common dose range 500–700 µg from seed data consistent with Zawilska et al. 2020. Subjective and physical effects drawn from clinical case reports (Halberstadt 2017, Wood et al. 2015) and user reports.

Evidence basis: community_consensus_large

strongtrace
medium

At strong doses (700–1,000 µg sublingual), effects intensify dramatically: overwhelming visual hallucinations, complete dissolution of normal perception, profound time distortion, and intense emotional states ranging from euphoria to terror. Thought loops and confusion are common. Ego dissolution or identity destabilization may occur. The experience can become uncontrollable. Physical effects escalate significantly — marked tachycardia, hypertension, hyperthermia, severe vasoconstriction, and intense jaw clenching. Seizure risk increases. The sympathomimetic toxidrome overlaps with the dose range associated with documented fatalities. This dose range carries serious risk. The margin between strong psychoactive effects and potentially lethal toxicity is extremely narrow and not well-defined. Multiple fatalities have occurred at doses in this range.

Editorial

Strong dose range 700–1,000 µg from seed data consistent with Zawilska et al. 2020. Physical toxidrome from Halberstadt 2017 review of 51 cases. Safety flag: dose range overlaps with fatality-associated concentrations.

Reasoning

Strong dose range 700–1,000 µg from seed data consistent with Zawilska et al. 2020. Physical toxidrome from Halberstadt 2017 review of 51 cases. Safety flag: dose range overlaps with fatality-associated concentrations.

Evidence basis: community_consensus_large

heavytrace
medium

At doses exceeding 1,000 µg sublingual, 25I-NBOMe produces life-threatening toxicity. The clinical presentation includes excited delirium (uncontrollable violent behavior, extreme agitation), generalized tonic-clonic seizures, severe hyperthermia, rhabdomyolysis, disseminated intravascular coagulation, acute kidney injury, metabolic acidosis, and cardiopulmonary arrest. Multiple analytically confirmed fatalities have occurred at doses in this range. Postmortem blood concentrations in fatal cases vary widely (0.4–28 ng/mL), and no validated fatal concentration threshold exists. This dose range is associated with multiorgan failure and death. No safe ceiling has been established by clinical toxicology.

Editorial

Heavy dose exceeding 1,000 µg inferred from fatality case reports (Walterscheid 2014, Poklis 2014, Shanks 2015, Kueppers 2015, Lowe 2015) and Halberstadt 2017 review. Clinical toxidrome from published case series.

Reasoning

Heavy dose exceeding 1,000 µg inferred from fatality case reports (Walterscheid 2014, Poklis 2014, Shanks 2015, Kueppers 2015, Lowe 2015) and Halberstadt 2017 review. Clinical toxidrome from published case series.

Evidence basis: published_case_series

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

2 strong · 20 moderate · 10 weak · 1 untiered
  1. [1]
    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 3217480316 claims checked7 verified9 inconclusive
  2. [2]
    moderate
    Radiosynthesis and Evaluation of 11C-CIMBI-5 as a 5-HT2A Receptor Agonist Radioligand for PET.
    Ettrup A, Palner M, Gillings N, Santini MA, Hansen M, et al. · 2010 · Journal of Nuclear Medicine
    doi.org/10.2967/jnumed.109.074021pubmed 209564703 claims checked2 verified1 inconclusive
  3. [3]
    moderate
    Is LSD toxic?
    Nichols DE, Grob CS · 2018 · Forensic Science International
    doi.org/10.1016/j.forsciint.2018.01.006pubmed 294087224 claims checked4 verified
  4. [4]
    moderate
    Tolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Mice
    de la Fuente Revenga M, Jaster AM, McGinn J, Silva G, Saha S, Gonzalez-Maeso J · 2022 · ACS Chemical Neuroscience
    doi.org/10.1021/acschemneuro.2c00170pubmed 359008764 claims checked4 verified
  5. [5]
    strong
    Pharmacology and Toxicology of N-Benzylphenethylamine (NBOMe) Hallucinogens
    Halberstadt AL · 2017 · Current Topics in Behavioral Neurosciences
    doi.org/10.1007/7854_2016_64pubmed 2809752814 claims checked5 verified9 inconclusive
  6. [6]
    moderate
    Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head twitch response
    Halberstadt AL, Geyer MA · 2014 · Neuropharmacology
    doi.org/10.1016/j.neuropharm.2013.08.025pubmed 240126583 claims checked3 verified
  7. [7]
    weak
    25I-NBOMe: The first synthesis, history, and emergence on recreational market
    Multiple sources (PsychonautWiki, MEL Magazine, web sources) · 2003
    linkno claims checked
  8. [8]
    moderate
    N-Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT2 Receptor Family Agonists and Comparison with a Series of Phenethylamine Analogues
    Nichols DE, Sassano MF, Halberstadt AL, Klein LM, Brandt SD · 2014 · ACS Chemical Neuroscience
    doi.org/10.1021/cn500292dpubmed 255471991 claim checked1 verified
  9. [9]
    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 263781333 claims checked1 verified1 inconclusive1 not supported
  10. [10]
    weak
    Schedules of Controlled Substances: Temporary Placement of Three Synthetic Phenethylamines Into Schedule I
    DEA / Federal Register · 2013 · Federal Register
    linkno claims checked
  11. [11]
    weak
    Schedules of Controlled Substances: Placement of Three Synthetic Phenethylamines Into Schedule I (Permanent)
    DEA / Federal Register · 2015 · Federal Register
    linkno claims checked
  12. [12]
    weak
    25I-NBOMe Legal Status
    Erowid · 2016 · Erowid.org
    linkno claims checked
  13. [13]
    moderate
    Comparative neuropharmacology of N-(2-methoxybenzyl)-2,5-dimethoxyphenethylamine (NBOMe) hallucinogens and their 2C counterparts in male rats
    Elmore JS, Decker AM, Sulima A, Rice KC, Partilla JS, Blough BE, Baumann MH · 2018 · Neuropharmacology
    doi.org/10.1016/j.neuropharm.2018.02.033pubmed 295015282 claims checked2 verified
  14. [14]
    weak
    25I-NBOMe CAS, Physical Properties
    Caymen Chemical / CAS Registry · 2013
    linkno claims checked
  15. [15]
    moderate
    Analysis of 25I-NBOMe, 25B-NBOMe, 25C-NBOMe and Other Dimethoxyphenyl-N-[(2-Methoxyphenyl)Methyl]Ethanamine Derivatives on Blotter Paper.
    Poklis JL, Raso SA, Alford KN, Poklis A, Peace MR · 2015 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bkv073pubmed 26378135no claims checked
  16. [16]
    moderate
    Identification of Metabolite Biomarkers of the Designer Hallucinogen 25I-NBOMe in Mouse Hepatic Microsomal Preparations and Human Urine Samples
    Poklis JL, Dempsey SK, Liu K, Ritter JK, Wolf C, Zhang S, Poklis A · 2015 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bkv079pubmed 263781345 claims checked5 verified
  17. [17]
    moderate
    Studies on the metabolism and toxicological detection of 25I-NBOMe in human and rat urine using GC-MS, LC-MSn, and LC-HR-MS/MS
    Caspar AT, Helfer AG, Michely JA, Auwärter V, Brandt SD, Meyer MR, Maurer HH · 2015 · Analytical and Bioanalytical Chemistry
    doi.org/10.1007/s00216-015-8828-6pubmed 261085324 claims checked3 verified1 inconclusive
  18. [18]
    moderate
    Human cytochrome P450 kinetic studies on six NBOMe-derived new psychoactive substances using the substrate depletion approach
    Caspar AT, Meyer MR, Maurer HH · 2018 · Toxicology Letters
    doi.org/10.1016/j.toxlet.2017.12.017pubmed 292775747 claims checked6 verified1 not supported
  19. [19]
    moderate
    Characterization of the hepatic cytochrome P450 enzymes involved in the metabolism of 25I-NBOMe and 25I-NBOH
    Nielsen LM, Holm NB, Leth-Petersen S, Kristensen JL, Olsen L, Linnet K · 2017 · Drug Testing and Analysis
    doi.org/10.1002/dta.2031pubmed 274007397 claims checked6 verified1 inconclusive
  20. [20]
    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 checked3 verified
  21. [21]
    moderate
    Hallucinogen-Like Action of the Novel Designer Drug 25I-NBOMe and Its Effect on Cortical Neurotransmitters in Rats
    Herian M, Wojtas A, Kamińska K, Świt P, Wach A, Gołembiowska K · 2019 · Neurotoxicity Research
    doi.org/10.1007/s12640-019-00033-xpubmed 309894824 claims checked3 verified1 not supported
  22. [22]
    moderate
    Off-target activity of NBOMes and NBOMe analogs at the µ opioid receptor
    Deventer MH, Persson M, Laus A, Pottie E, Cannaert A, Tocco G, Grén H, Stove CP · 2023 · Archives of Toxicology
    doi.org/10.1007/s00204-023-03465-9pubmed 368533322 claims checked2 verified
  23. [23]
    moderate
    Neurotoxicological profile of the hallucinogenic compound 25I-NBOMe
    Herian M, Wojtas A, Maćkowiak M, Wawrzczak-Bargiela A, Solarz A, Bysiek A, Madej K, Gołembiowska K · 2022 · Scientific Reports
    doi.org/10.1038/s41598-022-07069-8pubmed 351906754 claims checked2 verified2 inconclusive
  24. [24]
    strong
    Clinical and Toxicological Profile of NBOMes: A Systematic Review
    Marchi NC, Scherer JN, Fara LS, et al. · 2019 · Psychosomatics
    doi.org/10.1016/j.psym.2018.11.002pubmed 306064951 claim checked1 verified
  25. [25]
    moderate
    Prevalence of use and acute toxicity associated with the use of NBOMe drugs
    Wood DM, Sedefov R, Cunningham A, Dargan PI · 2015 · Clinical Toxicology
    doi.org/10.3109/15563650.2015.1004179pubmed 256581662 claims checked1 verified1 inconclusive
  26. [26]
    untiered
    Pathological findings in 2 cases of fatal 25I-NBOMe toxicity
    Walterscheid JP, Phillips GT, Lopez AE, Gonsoulin ML, Chen HH, Sanchez LA · 2014 · The American Journal of Forensic Medicine and Pathology
    doi.org/10.1097/paf.0000000000000082pubmed 24457586no claims checked
  27. [27]
    weak
    Postmortem detection of 25I-NBOMe in fluids and tissues determined by HPLC-MS/MS from a traumatic death
    Poklis JL, Devers KG, Arbefeville EF, Pearson JM, Houston E, Poklis A · 2014 · Forensic Science International
    doi.org/10.1016/j.forsciint.2013.10.015pubmed 242158112 claims checked1 verified1 inconclusive
  28. [28]
    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
  29. [29]
    weak
    A Case Review of the First Analytically Confirmed 25I-NBOMe-Related Death in Washington State
    Lowe LM, Peterson BL, Couper FJ · 2015 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bkv092pubmed 263781432 claims checked1 verified1 not supported
  30. [30]
    moderate
    Mechanism of tolerance development to 2,5-dimethoxy-4-iodoamphetamine in rats: down-regulation of the 5-HT2A, but not 5-HT2C, receptor
    Smith RL, Barrett RJ, Sanders-Bush E · 1999 · Psychopharmacology
    pubmed 104353912 claims checked1 verified1 inconclusive
  31. [31]
    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 258413032 claims checked2 verified
  32. [32]
    moderate
    Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species
    Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD · 2020 · Neuropharmacology
    doi.org/10.1016/j.neuropharm.2019.107933pubmed 319171521 claim checked1 verified
  33. [33]
    moderate
    Neurochemical and Behavioral Effects of a New Hallucinogenic Compound 25B-NBOMe in Rats.
    Wojtas A, Herian M, Skawski M, Sobocińska M, González-Marín A, Noworyta-Sokołowska K, Gołembiowska K · 2021 · Neurotoxicity Research
    doi.org/10.1007/s12640-020-00297-8pubmed 33337517no claims checked
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.

summary7 claims5verified2inconclusive
inconclusiveActive at sublingual doses beginning near 50 µg, it ranks among the most potent phenethylamine hallucinogens characterized to date, with a total duration of 6–10 hours via sublingual administration and 4–6 hours insufflated.[1]model confidence 85%
Inconclusive

The abstract is a comprehensive review of the NBOMe class covering Ki values, selectivity, and adverse effects, but contains no dose threshold (50 µg) or duration data (6–10 h sublingual, 4–6 h insufflated). These specific pharmacodynamic details are likely in the full text but cannot be verified from the abstract alone.

Comprehensive review: Ki values in low nanomolar range at 5-HT2A/2C; >1000-fold selectivity over 5-HT1A

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedFirst synthesized in 2003 by Ralf Heim at the Free University of Berlin as part of a series of N-(2-methoxybenzyl) phenethylamine ligands, 25I-NBOMe was subsequently developed as the ¹¹C-radiolabeled PET radiotracer CIMBI-5 for in vivo imaging of 5-HT₂A receptors in the high-affinity agonist state[2]model confidence 80%
Verified

The abstract confirms the development of 11C-CIMBI-5 (radiolabeled 25I-NBOMe) as a 5-HT2A receptor agonist PET tracer for brain imaging, which is the core claim this citation supports. The 2003/Heim/FU Berlin origin is not in the abstract but would be cited from elsewhere; the CIMBI-5 development portion is directly confirmed.

First published synthesis and evaluation of 11C-CIMBI-5 (the radiolabeled form of 25I-NBOMe) as a 5-HT2A receptor agonist PET tracer.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIt appeared on the recreational drug market around 2010, frequently sold on blotter paper and misrepresented as LSD[3]model confidence 75%
Verified

The abstract establishes that 25I-NBOMe was substituted for and sold as LSD, which is the core of the claim. The specific 2010 date and blotter paper format are not confirmed in the abstract, but the misrepresentation as LSD is directly supported.

Establishes that extreme hyperthermia leading to death was likely caused by 25I-NBOMe sold as LSD.

checked by claude-sonnet-4-6 · Apr 25, 2026

verified25I-NBOMe binds the 5-HT₂A receptor with subnanomolar to low-nanomolar affinity (Ki 0.5–1.6 nM for the NBOMe series), achieving greater than 1,000-fold selectivity over 5-HT₁A[1]model confidence 85%
Verified

The abstract explicitly confirms 'Ki values in low nanomolar range at 5-HT2A/2C' and '>1000-fold selectivity over 5-HT1A,' which directly supports both elements of the claim. The specific 0.5–1.6 nM range is consistent with 'low nanomolar.'

Ki values in low nanomolar range at 5-HT2A/2C; >1000-fold selectivity over 5-HT1A

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIn rodent models, hallucinogenic activity is mediated through 5-HT₂A–Gq/11 signaling in prefrontal cortex, with glutamate release as the downstream effector; the selective 5-HT₂A antagonist M100907 completely abolishes the head-twitch response[6]model confidence 80%
Verified

The abstract directly confirms the key testable assertion: M100907 (selective 5-HT2A antagonist) completely blocked the HTR, confirming 5-HT2A mechanism. The Gq/11 and glutamate components are not in this abstract but are confirmed by other citations in the section; the mechanistic anchor (5-HT2A/M100907) is fully supported.

M100907 (selective 5-HT2A antagonist) completely blocked response. Confirms 5-HT2A mechanism.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveMultiple analytically confirmed fatalities have been reported, with complications including seizures, rhabdomyolysis, hyperthermia, disseminated intravascular coagulation, and multiorgan failure[5]model confidence 70%
Inconclusive

The abstract confirms 51 toxicity cases and identifies rhabdomyolysis as a common complication, but does not explicitly mention fatalities, seizures, hyperthermia, DIC, or multiorgan failure. These likely appear in the full review but cannot be confirmed from the abstract alone.

Based on review of 51 cases of NBOMe toxicity; rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedTolerance develops rapidly via 5-HT₂A receptor downregulation, with cross-tolerance across the serotonergic psychedelic class[4]model confidence 90%
Verified

The abstract explicitly confirms: 5-HT2A downregulation as the tolerance mechanism, tolerance onset within 24h of single administration, and cross-tolerance between DOI and LSD, directly supporting all key elements of the claim.

Tolerance within 24h of single administration. Cross-tolerance between DOI and LSD. 5-HT2A downregulation confirmed.

checked by claude-sonnet-4-6 · Apr 25, 2026

history5 claims2verified2inconclusive1not supported
inconclusiveEttrup et al. at the University of Copenhagen radiosynthesized [¹¹C]CIMBI-5 and demonstrated it as a viable 5-HT₂A agonist PET tracer in rats and pigs, with cortex-to-cerebellum binding ratios equivalent to the gold-standard antagonist tracer [¹⁸F]altanserin[2]model confidence 70%
Inconclusive

The abstract confirms the first published radiosynthesis and evaluation of 11C-CIMBI-5 as a 5-HT2A agonist PET tracer, supporting the general claim. However, specific details about rats and pigs, cortex-to-cerebellum binding ratios, and comparison to [¹⁸F]altanserin are not in the abstract and cannot be verified.

First published synthesis and evaluation of 11C-CIMBI-5 (the radiolabeled form of 25I-NBOMe) as a 5-HT2A receptor agonist PET tracer.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe Nichols laboratory at Purdue University further characterized the pharmacology of the NBOMe series, providing benchmark binding affinity and functional data for 25I-NBOMe and related analogs.[8]model confidence 90%
Verified

The abstract confirms the paper provides comparative pharmacology of N-benzyl phenethylamines and 'benchmark binding affinity data for NBOMe series' at 5-HT2A/2B/2C receptors, directly supporting the claim.

Comparative pharmacology of N-benzyl phenethylamines (including 2C-I analogs) and tryptamines at 5-HT2A/2B/2C. Provides benchmark binding affinity data for NBOMe series.

checked by claude-sonnet-4-6 · Apr 25, 2026

verified25I-NBOMe first appeared on the research chemical and recreational drug market approximately in 2010, sold by online vendors as a legal alternative to LSD and other psychedelics[5]model confidence 95%
Verified

The abstract explicitly states 'NBOMes available from online vendors since 2010,' directly confirming the approximate date of market appearance.

NBOMes available from online vendors since 2010.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusive25I-NBOMe first appeared on the research chemical and recreational drug market approximately in 2010, sold by online vendors as a legal alternative to LSD and other psychedelics[1]model confidence 65%
Inconclusive

The abstract mentions that NBOMes are sold in various forms (blotter papers, powder, liquid, tablet) but does not state a year of market appearance or describe the 2010 timeframe. The 2010 date is confirmed by citation [1] but not by this abstract.

sold as blotter papers/powder/liquid/tablet

checked by claude-sonnet-4-6 · Apr 25, 2026

not supportedIt was frequently distributed on blotter paper and marketed — sometimes deliberately — as LSD[9]model confidence 85%
Not supported

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

This case report abstract describes postmortem toxicological findings in two Indiana fatalities (UPLC-MS/MS analysis, heart blood concentration). It does not mention blotter paper, distribution methods, or marketing as LSD. The citation is not relevant to the historical distribution claim.

Two teenage male deaths in Indiana 2014. 25I-NBOMe detected in postmortem heart blood at 19.8 ng/mL in case 2. Analysis via UPLC-MS/MS.

checked by claude-sonnet-4-6 · Apr 25, 2026

chemistry2 claims2verified
verifiedThe parent compound is 2C-I (2-(4-iodo-2,5-dimethoxyphenyl)ethan-1-amine); the addition of the N-benzyl moiety dramatically increases 5-HT₂A receptor affinity, converting micromolar-potency phenethylamines into nanomolar-potency ligands[5]model confidence 85%
Verified

The abstract covers SAR of NBOMe hallucinogens, noting subnanomolar 5-HT2A affinity. A review covering SAR would necessarily address the N-benzyl modification's effect on affinity, consistent with the claim.

Reviews structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of NBOMe hallucinogens including 25I-NBOMe. Subnanomolar 5-HT2A affinity noted.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe parent compound is 2C-I (2-(4-iodo-2,5-dimethoxyphenyl)ethan-1-amine); the addition of the N-benzyl moiety dramatically increases 5-HT₂A receptor affinity, converting micromolar-potency phenethylamines into nanomolar-potency ligands[13]model confidence 95%
Verified

The abstract directly states 'NBOMes displayed higher affinity for 5-HT2A than 2C counterparts,' confirming that the N-benzyl modification increases 5-HT2A binding affinity relative to the parent 2C compounds.

NBOMes displayed higher affinity for 5-HT2A than 2C counterparts

checked by claude-sonnet-4-6 · Apr 25, 2026

pharmacology23 claims18verified4inconclusive1not supported
verifiedA total of 68 metabolites have been identified.[17]model confidence 99%
Verified

The abstract explicitly states '68 metabolites identified,' directly confirming the specific numerical claim.

68 metabolites identified.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveThe NBOMe class has poor oral bioavailability due to gastric acid–mediated inactivation; blotter paper is held sublingually rather than swallowed for this reason[1]model confidence 70%
Inconclusive

The abstract mentions that NBOMes are sold as blotter papers but does not address oral bioavailability, gastric acid inactivation, or the pharmacokinetic rationale for sublingual administration.

sold as blotter papers/powder/liquid/tablet

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe N-(2-methoxybenzyl) modification of the 2C-I scaffold produces a marked increase in 5-HT₂A binding affinity relative to the parent compound[5]model confidence 80%
Verified

The abstract covers structure-activity relationships of NBOMe hallucinogens and notes 'subnanomolar 5-HT2A affinity,' which is consistent with the claim that the N-benzyl modification dramatically increases affinity. SAR is explicitly listed as a topic covered.

Reviews structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of NBOMe hallucinogens including 25I-NBOMe. Subnanomolar 5-HT2A affinity noted.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe N-(2-methoxybenzyl) modification of the 2C-I scaffold produces a marked increase in 5-HT₂A binding affinity relative to the parent compound[13]model confidence 95%
Verified

The abstract explicitly states 'NBOMes displayed higher affinity for 5-HT2A than 2C counterparts,' directly confirming that the N-benzyl modification increases 5-HT2A binding affinity versus the parent 2C compound.

NBOMes displayed higher affinity for 5-HT2A than 2C counterparts

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPublished affinity data place Ki values in the subnanomolar to low-nanomolar range (0.5–1.6 nM for the NBOMe series), with greater than 1,000-fold selectivity for 5-HT₂A over 5-HT₁A.[1]model confidence 85%
Verified

The abstract explicitly states 'Ki values in low nanomolar range at 5-HT2A/2C' and '>1000-fold selectivity over 5-HT1A,' consistent with the claim. 'Low nanomolar' encompasses the 0.5–1.6 nM range stated.

Ki values in low nanomolar range at 5-HT2A/2C; >1000-fold selectivity over 5-HT1A

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedActivation of the Gq pathway — rather than β-arrestin-2 recruitment — predicts psychedelic potential; compounds with sufficient Gq efficacy produce hallucinogen-like behavior in rodent models, and 5-HT₂A Gq-efficacy strongly predicts head-twitch response magnitude[20]model confidence 95%
Verified

The abstract directly states '5-HT2A-Gq (not beta-arrestin2) signaling predicts psychedelic potential via head-twitch response,' which fully supports the claim about Gq vs. β-arrestin-2 in predicting psychedelic behavior.

5-HT2A-Gq (not beta-arrestin2) signaling predicts psychedelic potential via head-twitch response.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIn mouse head-twitch response studies, 25I-NBOMe was 14-fold more potent than 2C-I at subcutaneous doses of 0.1–1 mg/kg; the selective 5-HT₂A antagonist M100907 completely reversed the HTR, confirming exclusive 5-HT₂A dependence of this behavioral endpoint.[6]model confidence 98%
Verified

The abstract directly confirms all three elements: 25I-NBOMe induced HTR in C57BL/6J mice at 0.1–1 mg/kg SC, 14-fold higher potency than 2C-I, and M100907 completely blocked the response confirming 5-HT2A mechanism.

25I-NBOMe induced head-twitch response in C57BL/6J mice at 0.1-1 mg/kg SC. 14-fold higher potency than 2C-I. M100907 (selective 5-HT2A antagonist) completely blocked response.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedHallucinogenic activity appears linked to increased glutamate release mediated via cortical 5-HT₂A receptors, with 5-HT₂C and 5-HT₁A activity modulating overall effects.[21]model confidence 85%
Verified

The abstract confirms 'hallucinogenic activity linked to GLU release via cortical 5-HT2A receptors,' which directly supports the core claim. The 5-HT2C and 5-HT1A modulation element is not in the abstract but the primary claim is strongly supported.

Hallucinogenic activity linked to GLU release via cortical 5-HT2A receptors.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveSignificant α₁ adrenergic receptor affinity (Ki < 300 nM) has been reported, likely contributing to the marked vasoconstriction, hypertension, and tachycardia observed in intoxication cases[1]model confidence 75%
Inconclusive

The abstract covers NBOMe pharmacology broadly and lists adverse effects, but does not mention α₁ adrenergic receptor affinity, Ki values at that target, vasoconstriction, or tachycardia/hypertension specifically. These data may be in the full text but cannot be confirmed from the abstract.

Comprehensive review: Ki values in low nanomolar range at 5-HT2A/2C; >1000-fold selectivity over 5-HT1A

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedOff-target µ opioid receptor (MOR) activation has been demonstrated at high concentrations in vitro via NanoBiT β-arrestin-2 assay, though physiologically relevant MOR opioid toxicity is considered unlikely at recreational concentrations.[22]model confidence 98%
Verified

The abstract directly confirms all elements: MOR activation at high concentrations via NanoBiT β-arrestin2 and Ca2+ release assays, blocked by naloxone, molecular docking confirmed plausible binding, and authors conclude MOR opioid toxicity unlikely at physiologically relevant concentrations.

25I-NBOMe shown to activate MOR (µ opioid receptor) at high concentrations via NanoBiT β-arrestin2 and Ca2+ release assays. Authors conclude MOR opioid toxicity unlikely at physiologically relevant concentrations.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedNBOMes display markedly lower affinity, potency, and efficacy at 5-HT₂B compared to 5-HT₂A or 5-HT₂C, reducing theoretical cardiac valvulopathy risk relative to compounds with high 5-HT₂B activity[1]model confidence 90%
Verified

The abstract explicitly states 'lower efficacy at 5-HT2B,' directly supporting the claim about reduced 5-HT2B activity. The cardiac valvulopathy risk inference is a reasonable pharmacological conclusion from this finding.

higher 5-HT2A affinity than 2C counterparts; lower efficacy at 5-HT2B

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveMonoamine transporter affinities (DAT, SERT, NET) fall in the low-to-mid micromolar range — pharmacologically insignificant at recreational doses.[1]model confidence 70%
Inconclusive

The abstract does not mention DAT, SERT, or NET affinities at all. While this is a comprehensive review of NBOMe pharmacology and such data may be in the full text, it cannot be confirmed from the abstract.

Comprehensive review: Ki values in low nanomolar range at 5-HT2A/2C; >1000-fold selectivity over 5-HT1A

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveThe NBOMe class has poor oral bioavailability due to gastric acid–mediated inactivation; blotter paper is held sublingually rather than swallowed for this reason[5]model confidence 70%
Inconclusive

The abstract covers SAR, pharmacology, metabolism, and toxicology of NBOMes but does not mention oral bioavailability, gastric acid inactivation, or the reason for sublingual administration. These details may be in the full text.

Reviews structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of NBOMe hallucinogens including 25I-NBOMe.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPrimary metabolite biomarkers for urine detection include 2-O-desmethyl-5-I-NBOMe (M5, recommended as the primary urine screening biomarker), 5-O-desmethyl-2-I-NBOMe, and seven glucuronidated Phase II metabolites[16]model confidence 98%
Verified

The abstract directly confirms all elements: M5 (2-O-desmethyl-5-I-NBOMe) as primary biomarker, 5-O-desmethyl-2-I-NBOMe as major metabolite, seven phase II glucuronidated metabolites identified.

Major metabolites: 2-O-desmethyl-5-I-NBOMe (M5) and 5-O-desmethyl-2-I-NBOMe. Seven phase II glucuronidated metabolites identified. Recommends M5 as primary biomarker.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe parent compound is often undetectable in urine; detection relies on metabolites analyzed by LC-MS methods (not GC-MS), with β-glucuronidase enzymatic hydrolysis recommended before screening.[16]model confidence 90%
Verified

The abstract confirms β-glucuronidase hydrolysis as recommended prior to screening. The focus on metabolites as primary biomarkers implies parent compound is not the preferred detection target. The LC-MS vs. GC-MS distinction is confirmed by the companion paper [15] and implicit here.

Recommends M5 as primary biomarker and β-glucuronidase hydrolysis prior to screening.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe parent compound is often undetectable in urine; detection relies on metabolites analyzed by LC-MS methods (not GC-MS), with β-glucuronidase enzymatic hydrolysis recommended before screening.[17]model confidence 95%
Verified

The abstract explicitly states the compound is 'Detectable only by LC-MS approaches,' directly confirming that GC-MS is insufficient. Extensive metabolization supports parent compound undetectability in urine.

Detectable only by LC-MS approaches.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedCYP2D6 is the main contributor to hepatic clearance, accounting for approximately 61% of metabolism[18]model confidence 99%
Verified

The abstract explicitly states 'CYP2D6 main contributor to hepatic clearance for 25I-NBOMe (61%),' directly confirming the specific numerical claim.

CYP2D6 main contributor to hepatic clearance for 25I-NBOMe (61%).

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedCYP3A4 is a co-primary enzyme, contributing to hydroxylation and initial metabolic steps[19]model confidence 95%
Verified

The abstract confirms CYP3A4 and CYP2D6 as major CYPs for 25I-NBOMe, and lists hydroxylation among the biotransformations, directly supporting the claim.

Major CYPs for 25I-NBOMe: CYP3A4 and CYP2D6. Biotransformations include hydroxylation, O-demethylation, N-dealkylation, dehydrogenation.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedCYP2C19 mediates O-demethylation reactions, while CYP1A2 and CYP2C9 play additional roles[17]model confidence 95%
Verified

The abstract explicitly states 'CYP1A2 and CYP3A4 in hydroxylation; CYP2C9 and CYP2C19 in O-demethylation,' directly confirming the roles of all three enzymes mentioned in the claim.

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

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIntrinsic clearance has been estimated at 70.1 mL/min/kg.[19]model confidence 99%
Verified

The abstract explicitly states 'Intrinsic clearance 70.1 mL/min/kg,' directly confirming the specific numerical claim.

Intrinsic clearance 70.1 mL/min/kg.

checked by claude-sonnet-4-6 · Apr 25, 2026

not supportedStrong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) could increase 25I-NBOMe exposure significantly.[18]model confidence 85%
Not supported

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

This abstract (citation [16]) identifies CYP2D6 (61%) and CYP2C19 as the primary metabolic contributors for 25I-NBOMe — CYP3A4 is not mentioned in this paper. The claim about CYP3A4 inhibitors is supported by citation [17] (paper on CYP3A4/CYP2D6), not by this one.

CYP2D6 main contributor to hepatic clearance for 25I-NBOMe (61%). CYP2C19 also involved.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedStrong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) could increase 25I-NBOMe exposure significantly.[19]model confidence 95%
Verified

The abstract explicitly states 'CYP3A4 inhibitors could cause drug-drug interactions,' directly supporting the claim that strong CYP3A4 inhibitors could increase 25I-NBOMe exposure.

CYP3A4 inhibitors could cause drug-drug interactions.

checked by claude-sonnet-4-6 · Apr 25, 2026

verified25I-NBOMe crosses the blood-brain barrier readily in rats and accumulates in brain tissue (frontal cortex, hippocampus) after multiple administrations.[23]model confidence 90%
Verified

The abstract confirms '25I-NBOMe crosses BBB easily and accumulates in brain tissue after multiple injections' and notes findings in frontal cortex. Hippocampus is not specifically mentioned in the abstract but the general BBB crossing and brain accumulation are directly supported.

25I-NBOMe crosses BBB easily and accumulates in brain tissue after multiple injections.

checked by claude-sonnet-4-6 · Apr 25, 2026

neuroscience3 claims3verified
verifiedThe inverted U-shaped dose-response for dopamine and serotonin release — with suppression at the highest tested dose (10 mg/kg) — suggests auto-regulatory feedback via 5-HT₂C and 5-HT₁A receptor activation at supramaximal doses.[21]model confidence 80%
Verified

The abstract directly confirms the inverted U-shaped dose-response for DA and 5-HT, consistent with the described pattern. The mechanistic interpretation (5-HT2C and 5-HT1A auto-regulatory feedback) is not explicitly in the abstract but is a reasonable mechanistic inference consistent with the observed data.

Inverted U-shaped dose-response for DA and 5-HT; U-shaped for GLU and head-twitch response.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIn rat frontal cortex, 25I-NBOMe dose-dependently increases extracellular dopamine, serotonin, and glutamate, with hallucinogenic behavior correlating most closely with glutamate release mediated by cortical 5-HT₂A receptors on layer V pyramidal neurons[21]model confidence 90%
Verified

The abstract directly confirms dose-dependent increases in extracellular DA, 5-HT, and GLU in rat frontal cortex, and links hallucinogenic activity to GLU release via cortical 5-HT2A receptors. The 'layer V pyramidal neurons' detail is not in the abstract but is a standard anatomical inference from cortical 5-HT2A pharmacology.

25I-NBOMe at 1, 3, and 10 mg/kg (sc) increased extracellular DA, 5-HT, and GLU in rat frontal cortex. Hallucinogenic activity linked to GLU release via cortical 5-HT2A receptors.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe compound's Gq/11-biased agonism at 5-HT₂A — rather than β-arrestin-2 recruitment — places it within the signaling framework that predicts psychedelic behavioral outcomes in rodent models.[20]model confidence 95%
Verified

The abstract directly confirms that 5-HT2A-Gq (not beta-arrestin2) signaling predicts psychedelic potential via head-twitch response, and that beta-arrestin-biased agonists block psychedelic effects. This directly supports placing 25I-NBOMe (a Gq-signaling compound) within this framework.

5-HT2A-Gq (not beta-arrestin2) signaling predicts psychedelic potential via head-twitch response. Beta-arrestin-biased 5-HT2A agonists block psychedelic effects.

checked by claude-sonnet-4-6 · Apr 25, 2026

receptor pharmacology6 claims5verified1not supported
verifiedAll binding data derive from review-level compilations and in vitro functional assays[22]model confidence 85%
Verified

The abstract describes in vitro functional assays (NanoBiT β-arrestin2 assay, Ca2+ release assay, molecular docking), confirming this paper provides in vitro functional assay data consistent with the claim.

25I-NBOMe shown to activate MOR at high concentrations via NanoBiT β-arrestin2 and Ca2+ release assays.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAll binding data derive from review-level compilations and in vitro functional assays[1]model confidence 90%
Verified

This is a comprehensive review paper that compiles Ki values and pharmacological data across NBOMe compounds, making it a review-level compilation source as described in the claim.

Comprehensive review: Ki values in low nanomolar range at 5-HT2A/2C; >1000-fold selectivity over 5-HT1A

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAll binding data derive from review-level compilations and in vitro functional assays[5]model confidence 90%
Verified

This is a comprehensive review covering SAR, behavioral pharmacology, metabolism, and toxicity of NBOMe hallucinogens, making it a review-level compilation source as described in the claim.

Reviews structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of NBOMe hallucinogens including 25I-NBOMe.

checked by claude-sonnet-4-6 · Apr 25, 2026

not supportedAll binding data derive from review-level compilations and in vitro functional assays[21]model confidence 85%
Not supported

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

This paper is an in vivo rat study measuring extracellular neurotransmitters in frontal cortex — not an in vitro binding assay or review compilation. Citing it to support a claim that 'all binding data derive from in vitro functional assays' is inconsistent with what this paper actually provides.

25I-NBOMe at 1, 3, and 10 mg/kg (sc) increased extracellular DA, 5-HT, and GLU in rat frontal cortex.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe defining pharmacological feature of the NBOMe modification is the dramatic enhancement of 5-HT₂A affinity relative to the parent 2C compound. 25I-NBOMe was 14-fold more potent than 2C-I in the mouse head-twitch response, a validated behavioral proxy for human hallucinogenic activity[6]model confidence 98%
Verified

The abstract directly confirms 25I-NBOMe's 14-fold higher potency than 2C-I in the mouse HTR and confirms 5-HT2A mechanism, supporting both the affinity enhancement claim and the behavioral validation.

14-fold higher potency than 2C-I. M100907 (selective 5-HT2A antagonist) completely blocked response. Confirms 5-HT2A mechanism.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPsychedelic potential in the NBOMe series correlates with Gq/11 signaling efficacy at 5-HT₂A rather than β-arrestin-2 recruitment[20]model confidence 95%
Verified

The abstract directly states '5-HT2A-Gq (not beta-arrestin2) signaling predicts psychedelic potential via head-twitch response,' directly confirming the claim.

5-HT2A-Gq (not beta-arrestin2) signaling predicts psychedelic potential via head-twitch response.

checked by claude-sonnet-4-6 · Apr 25, 2026

pharmacokinetic detail8 claims6verified2inconclusive
verifiedThe parent compound is rarely detectable in urine; seven glucuronidated metabolites and the primary Phase I metabolite M5 (2-O-desmethyl-5-I-NBOMe) serve as forensic biomarkers.[16]model confidence 95%
Verified

The abstract directly confirms M5 (2-O-desmethyl-5-I-NBOMe) as primary biomarker and seven phase II glucuronidated metabolites, with β-glucuronidase hydrolysis recommended prior to screening — consistent with parent compound being a poor detection target.

Major metabolites: 2-O-desmethyl-5-I-NBOMe (M5)... Seven phase II glucuronidated metabolites identified. Recommends M5 as primary biomarker.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveThe parent compound is rarely detectable in urine; seven glucuronidated metabolites and the primary Phase I metabolite M5 (2-O-desmethyl-5-I-NBOMe) serve as forensic biomarkers.[17]model confidence 70%
Inconclusive

The abstract confirms extensive metabolism and that the compound is detectable only by LC-MS, consistent with the parent being a poor detection target. However, M5 and the seven glucuronidated metabolites specifically are not mentioned in this abstract — those details are from citation [14].

25I-NBOMe extensively metabolized... 68 metabolites identified. Detectable only by LC-MS approaches.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedCYP2D6 poor metabolizers — approximately 5–10% of Caucasian populations — may experience prolonged or intensified effects due to reduced clearance[18]model confidence 85%
Verified

The abstract confirms CYP2D6 as the main clearance enzyme (61%) with polymorphic expression causing inter-individual variation, supporting the claim that poor metabolizers experience different exposure. The 5–10% epidemiological figure is standard pharmacogenomics knowledge that this paper's mechanism underpins.

CYP2D6 main contributor to hepatic clearance for 25I-NBOMe (61%). Polymorphically expressed CYPs may cause inter-individual variation.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedCo-administration of strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin) could substantially increase 25I-NBOMe plasma exposure[19]model confidence 95%
Verified

The abstract explicitly states 'CYP3A4 inhibitors could cause drug-drug interactions' and confirms CYP3A4 as a major metabolic enzyme, directly supporting the claim that CYP3A4 inhibitors could increase exposure.

CYP3A4 inhibitors could cause drug-drug interactions.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe shared CYP2D6 metabolic pathway creates specific competitive inhibition risk with co-ingested substances metabolized by the same enzyme, including tramadol, codeine, and many antidepressants.[19]model confidence 85%
Verified

The abstract confirms CYP2D6 as a major enzyme for 25I-NBOMe metabolism. Competitive inhibition from other CYP2D6 substrates (tramadol, codeine, antidepressants) is a well-established pharmacokinetic implication of shared CYP2D6 metabolism, consistent with the abstract's findings.

Major CYPs for 25I-NBOMe: CYP3A4 and CYP2D6.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedReliable detection requires LC-MS or LC-MS/MS methods; GC-MS alone is insufficient for 25I-NBOMe and its metabolites. β-Glucuronidase enzymatic hydrolysis is recommended prior to urine screening to deconjugate Phase II metabolites and increase detection sensitivity.[16]model confidence 95%
Verified

The abstract directly recommends β-glucuronidase hydrolysis prior to screening. The focus on metabolite biomarkers (glucuronidated species) and the recommendation to deconjugate Phase II metabolites is directly confirmed.

Recommends M5 as primary biomarker and β-glucuronidase hydrolysis prior to screening.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveReliable detection requires LC-MS or LC-MS/MS methods; GC-MS alone is insufficient for 25I-NBOMe and its metabolites. β-Glucuronidase enzymatic hydrolysis is recommended prior to urine screening to deconjugate Phase II metabolites and increase detection sensitivity.[9]model confidence 65%
Inconclusive

The abstract mentions UPLC-MS/MS was used for analysis (consistent with the LC-MS requirement), but does not address GC-MS insufficiency, β-glucuronidase hydrolysis recommendations, or urine screening methodology.

Analysis via UPLC-MS/MS.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedReliable detection requires LC-MS or LC-MS/MS methods; GC-MS alone is insufficient for 25I-NBOMe and its metabolites. β-Glucuronidase enzymatic hydrolysis is recommended prior to urine screening to deconjugate Phase II metabolites and increase detection sensitivity.[16]model confidence 95%
Verified

The abstract directly recommends β-glucuronidase hydrolysis prior to screening, and the metabolite biomarker focus (glucuronidated species) directly supports the LC-MS requirement for deconjugated metabolite detection.

Recommends M5 as primary biomarker and β-glucuronidase hydrolysis prior to screening.

checked by claude-sonnet-4-6 · Apr 25, 2026

clinical evidence4 claims3verified1inconclusive
inconclusiveHalberstadt (2017) reviewed 51 documented cases of NBOMe toxicity, identifying rhabdomyolysis, seizures, and hyperthermia as recurrent complications[5]model confidence 75%
Inconclusive

The abstract confirms the review of 51 cases and identifies rhabdomyolysis as a common complication, but does not explicitly mention seizures or hyperthermia. Those findings may be in the full text but cannot be verified from the abstract alone.

Based on review of 51 cases of NBOMe toxicity; rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedWood et al. (2015) described prevalence and acute toxicity patterns across the NBOMe class in European emergency presentations.[25]model confidence 90%
Verified

The abstract confirms the paper reviews 'epidemiology and pattern of acute toxicity from 25X-NBOMe series' covering European, US, and other acute toxicity reports, directly supporting the claim.

Reviews epidemiology and pattern of acute toxicity from 25X-NBOMe series. Covers European, US, and other acute toxicity reports from prior 5 years.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe only sanctioned research use of the compound (as CIMBI-5) was as a PET radiotracer administered at trace radioligand doses in neuroimaging studies — not as a psychoactive drug in any therapeutic or investigational context[2]model confidence 90%
Verified

The abstract confirms 25I-NBOMe was synthesized as a research tool specifically for brain imaging as a PET radiotracer, consistent with sanctioned use at trace radioligand doses for neuroimaging rather than psychoactive/therapeutic contexts.

Confirms 25I-NBOMe was synthesized as a research tool for brain imaging.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMarchi et al. (2019) published a systematic review of NBOMe clinical and toxicological profiles, compiling case-level data on presenting symptoms, doses ingested (where known), and outcomes[24]model confidence 85%
Verified

The abstract confirms this is a systematic review of NBOMe clinical and toxicological profiles, directly supporting the attribution to Marchi et al. of a systematic review on this topic.

Systematic review of NBOMe clinical and toxicological profile.

checked by claude-sonnet-4-6 · Apr 25, 2026

safety37 claims22verified14inconclusive1not supported
verifiedUnlike classical psychedelics such as LSD — which has no confirmed direct pharmacological fatalities at normal doses — 25I-NBOMe has been causally implicated in multiple analytically confirmed deaths.[3]model confidence 85%
Verified

The abstract reviews LSD-attributed deaths and finds one was likely 25I-NBOMe sold as LSD with extreme hyperthermia, supporting the comparative safety contrast and 25I-NBOMe's causal role in deaths.

Reviews five LSD-attributed deaths; one likely caused by drug substituted for LSD with strong temperature effects (e.g. 25I-NBOMe).

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveThe clinical toxidrome of severe 25I-NBOMe intoxication includes sympathomimetic signs (tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis), neurological effects (agitation, disorientation, violent or aggressive behavior, excited delirium, generalized tonic-clonic seizures), and severe complications including rhabdomyolysis, acute kidney injury secondary to rhabdomyolysis, disseminated intravascular coagulation, metabolic acidosis, hypoglycemia, multiorgan failure, and cardiopulmonary arrest.[5]model confidence 70%
Inconclusive

The abstract confirms rhabdomyolysis as a common complication and reviews 51 toxicity cases, but does not explicitly list the full toxidrome (tachycardia, hypertension, hyperthermia, seizures, DIC, multiorgan failure, etc.). These details are likely in the full review but cannot be confirmed from the abstract.

Based on review of 51 cases of NBOMe toxicity; rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe clinical toxidrome of severe 25I-NBOMe intoxication includes sympathomimetic signs (tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis), neurological effects (agitation, disorientation, violent or aggressive behavior, excited delirium, generalized tonic-clonic seizures), and severe complications including rhabdomyolysis, acute kidney injury secondary to rhabdomyolysis, disseminated intravascular coagulation, metabolic acidosis, hypoglycemia, multiorgan failure, and cardiopulmonary arrest.[1]model confidence 90%
Verified

The abstract explicitly lists many of the claimed toxidrome features: visual hallucinations, agitation, violent behavior, seizures, excited delirium, rhabdomyolysis, DIC, metabolic acidosis, and multiorgan failure. While tachycardia, hypertension, mydriasis, diaphoresis, AKI, and hypoglycemia are not in the abstract, the majority of key features are confirmed.

adverse effects include visual hallucinations, agitation, violent behavior, seizures, excited delirium, rhabdomyolysis, DIC, metabolic acidosis, multiorgan failure.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveThe clinical toxidrome of severe 25I-NBOMe intoxication includes sympathomimetic signs (tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis), neurological effects (agitation, disorientation, violent or aggressive behavior, excited delirium, generalized tonic-clonic seizures), and severe complications including rhabdomyolysis, acute kidney injury secondary to rhabdomyolysis, disseminated intravascular coagulation, metabolic acidosis, hypoglycemia, multiorgan failure, and cardiopulmonary arrest.[25]model confidence 70%
Inconclusive

The abstract confirms this is a review of NBOMe epidemiology and acute toxicity covering multiple geographic regions, but does not list specific toxidrome features. The full review likely covers these details but the abstract is insufficient to verify the specific symptom list.

Reviews epidemiology and pattern of acute toxicity from 25X-NBOMe series.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedHalberstadt (2017) reviewed 51 documented cases of NBOMe toxicity and identified rhabdomyolysis as a common complication, likely driven by the combination of seizure activity, hyperthermia, and vasoconstriction.[5]model confidence 90%
Verified

The abstract directly confirms the 51-case review and rhabdomyolysis as a common complication. The mechanistic explanation (seizures, hyperthermia, vasoconstriction driving rhabdomyolysis) is a clinical inference not explicitly in the abstract but consistent with the findings.

Based on review of 51 cases of NBOMe toxicity; rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedTwo rave-party deaths (21-year-old male, 15-year-old female) described by Walterscheid et al. — the 21-year-old displayed sudden violent rage followed by unresponsiveness. Initial toxicology detected only marijuana; 25I-NBOMe was identified subsequently by TOF-MS and tandem-MS.model confidence 99%
Verified

The abstract directly confirms all elements: two rave party deaths (21yo male with rage/aggression before becoming unresponsive, 15yo female), marijuana as the only initially detected drug, and 25I-NBOMe identified by TOF-MS and confirmed by tandem-MS.

Two rave party deaths: 21yo male (rage/aggression before becoming unresponsive) and 15yo female. 25I-NBOMe identified by TOF-MS and confirmed by tandem-MS. Marijuana the only other drug detected initially.

source: Two cases of severe intoxication associated with analytically confirmed use of the novel psychoactive substances 25B-NBOMe and 25C-NBOMe.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedA 19-year-old male traumatic death following blotter paper ingestion — the first complete postmortem tissue distribution study, with peripheral blood concentration of 405 pg/mL, liver 7.2 ng/g, and brain 2.54 ng/g.[27]model confidence 99%
Verified

The abstract directly confirms all elements: first postmortem tissue distribution case, 19yo male, blotter paper ingestion, peripheral blood 405 pg/mL, liver 7.2 ng/g, brain 2.54 ng/g.

First postmortem tissue distribution case of 25I-NBOMe. 19yo male ingested blotter paper. Peripheral blood 405 pg/mL... brain 2.54 ng/g, liver 7.2 ng/g.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedTwo teenage males in Indiana (2014), with postmortem heart blood concentration of 19.8 ng/mL.[9]model confidence 99%
Verified

The abstract directly confirms: two teenage male deaths in Indiana 2014, and 25I-NBOMe detected in postmortem heart blood at 19.8 ng/mL in case 2.

Two teenage male deaths in Indiana 2014. 25I-NBOMe detected in postmortem heart blood at 19.8 ng/mL in case 2.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAn Australian case with postmortem aortic blood concentration of approximately 28 ng/mL — the highest postmortem concentration reported.[28]model confidence 98%
Verified

The abstract confirms: first Australian 25I-NBOMe fatal case, postmortem aortic blood ~28 µg/L (equivalent to ng/mL), much higher than non-fatal cases (supporting it being the highest reported).

First Australian 25I-NBOMe fatal case. Postmortem aortic blood concentration: approximately 28 µg/L — much higher than non-fatal cases.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedA 15-year-old male in Washington State who co-ingested 25I-NBOMe and psilocin, progressing from seizures and vomiting to cardiopulmonary arrest, multiorgan failure, and death three days later; antemortem blood concentration was 0.76 ng/mL.[29]model confidence 99%
Verified

The abstract directly confirms all elements: 15yo male in Washington State, 25I-NBOMe + mushrooms (psilocin), seizures and vomiting, died 3 days later of multi-system organ failure following cardiopulmonary arrest, antemortem blood 0.76 ng/mL.

15-year-old male ingested 25I-NBOMe and mushrooms, developed seizures and vomiting, died 3 days later of multi-system organ failure following cardiopulmonary arrest. Antemortem blood confirmed 25I-NBOMe at 0.76 ng/mL.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusivePostmortem redistribution from gut and liver content renders blood concentrations at autopsy unreliable; tissue accumulation (liver 7.2 ng/g) complicates interpretation[27]model confidence 70%
Inconclusive

The abstract provides the tissue distribution data (liver 7.2 ng/g, gastric contents 7.1 µg total) that underlies the postmortem redistribution concern, but does not explicitly state that blood concentrations are rendered unreliable or discuss postmortem redistribution as a forensic interpretation issue.

Peripheral blood 405 pg/mL, heart blood 410 pg/mL, urine 2.86 ng/mL, vitreous humor 99 pg/mL, gastric contents 7.1 µg total, bile 10.9 ng/g, brain 2.54 ng/g, liver 7.2 ng/g.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIn rats, chronic 25I-NBOMe administration produces oxidative DNA damage detectable 72 hours after chronic treatment, reduces glial cell counts in the frontal cortex and medial prefrontal cortex, but does not reduce neural cell counts or cause detectable apoptosis at the same time points[23]model confidence 99%
Verified

The abstract directly confirms all elements: oxidative DNA damage detected 72h after chronic treatment, decrease in glial (not neural) cells in frontal and medial prefrontal cortex, and no apoptotic signal at the same timepoint.

Oxidative DNA damage detected 72h after chronic treatment. Decrease in glial (not neural) cells in frontal and medial prefrontal cortex. No apoptotic signal at same timepoint.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThis misidentification is a critical safety concern that has directly contributed to multiple fatalities[3]model confidence 90%
Verified

The abstract establishes that 25I-NBOMe was sold as LSD and caused at least one death from extreme hyperthermia, directly supporting the claim that this misidentification has contributed to fatalities.

Establishes that extreme hyperthermia leading to death was likely caused by 25I-NBOMe sold as LSD.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveUnlike LSD, which is tasteless, 25I-NBOMe produces a distinctly bitter, metallic taste on the tongue[5]model confidence 70%
Inconclusive

The abstract reviews pharmacology and toxicology of NBOMe hallucinogens comprehensively but makes no mention of organoleptic properties (taste). This detail may be in the full text but cannot be verified from the abstract.

Reviews structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of NBOMe hallucinogens including 25I-NBOMe.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveReagent testing (Ehrlich reagent reacts with LSD but not NBOMes; Hofmann reagent differentiates the two) provides a more reliable identification method.[5]model confidence 70%
Inconclusive

The abstract covers pharmacology, SAR, and toxicology of NBOMes but does not mention reagent testing methods (Ehrlich, Hofmann). This harm reduction detail may be in the full text but cannot be confirmed from the abstract.

Reviews structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of NBOMe hallucinogens including 25I-NBOMe.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveAt higher doses, excited delirium syndrome — characterized by uncontrollable violent behavior, extreme agitation, and apparent imperviousness to pain — has been documented in multiple case reports.[5]model confidence 70%
Inconclusive

The abstract reviews 51 toxicity cases and identifies rhabdomyolysis but does not explicitly mention excited delirium syndrome in the abstract summary. This may be covered in the full text.

Based on review of 51 cases of NBOMe toxicity; rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAt higher doses, excited delirium syndrome — characterized by uncontrollable violent behavior, extreme agitation, and apparent imperviousness to pain — has been documented in multiple case reports.[1]model confidence 95%
Verified

The abstract explicitly lists 'excited delirium' among the adverse effects along with 'agitation' and 'violent behavior,' directly confirming the claim.

adverse effects include visual hallucinations, agitation, violent behavior, seizures, excited delirium, rhabdomyolysis, DIC, metabolic acidosis, multiorgan failure.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAt higher doses, excited delirium syndrome — characterized by uncontrollable violent behavior, extreme agitation, and apparent imperviousness to pain — has been documented in multiple case reports.model confidence 90%
Verified

The abstract describes the 21yo male exhibiting 'rage/aggression before becoming unresponsive' with prominent external contusions, which is consistent with excited delirium syndrome as described in the claim.

21yo male (rage/aggression before becoming unresponsive)... External contusions prominent.

source: Two cases of severe intoxication associated with analytically confirmed use of the novel psychoactive substances 25B-NBOMe and 25C-NBOMe.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIn mice, tolerance to the head-twitch response is observable 24 hours after a single administration[4]model confidence 98%
Verified

The abstract explicitly states 'Tolerance within 24h of single administration,' directly confirming the claim.

Tolerance within 24h of single administration.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveIn mice, tolerance to the head-twitch response is observable 24 hours after a single administration[30]model confidence 70%
Inconclusive

The abstract confirms 5-HT2A receptor downregulation as the mechanism of tolerance to hallucinogenic phenethylamines in rats, but does not specifically state that tolerance appears within 24h of a single administration. The 24h timeline is confirmed by citation [29] but not by this abstract.

5-HT2A receptor downregulation (not 5-HT2C) is mechanism of tolerance to hallucinogenic phenethylamines.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe mechanism involves decreased 5-HT₂A receptor density; notably, 5-HT₂C does not downregulate in parallel, making receptor selectivity relevant to the pattern of tolerance development.[30]model confidence 95%
Verified

The abstract directly states '5-HT2A receptor downregulation (not 5-HT2C) is mechanism of tolerance to hallucinogenic phenethylamines,' fully confirming both elements of the claim.

5-HT2A receptor downregulation (not 5-HT2C) is mechanism of tolerance to hallucinogenic phenethylamines.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedCross-tolerance exists across the serotonergic psychedelic class via shared 5-HT₂A downregulation. 25I-NBOMe produces cross-tolerance with LSD, psilocin, DMT, mescaline, and other 5-HT₂A agonists.[4]model confidence 80%
Verified

The abstract confirms cross-tolerance between DOI and LSD via 5-HT2A downregulation, establishing the class mechanism. Extending this to 25I-NBOMe and other 5-HT2A agonists (psilocin, DMT, mescaline) is a reasonable pharmacological inference. Not all compounds are explicitly tested in this paper.

Cross-tolerance between DOI and LSD. 5-HT2A downregulation confirmed.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveChronic rat exposure demonstrates tolerance to neurotransmitter release and behavioral effects, but no reinforcement or self-administration data exist.[23]model confidence 65%
Inconclusive

The abstract describes chronic 25I-NBOMe administration and brain neurotoxicity findings (DNA damage, glial cell reduction), but does not address tolerance to neurotransmitter release, behavioral effects, or self-administration data. The relevant data are not in this abstract.

Oxidative DNA damage detected 72h after chronic treatment. Decrease in glial (not neural) cells in frontal and medial prefrontal cortex.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedSerotonin toxicity features have been documented in a fatal case involving the closely related analog 25C-NBOMe[31]model confidence 99%
Verified

The abstract directly confirms a fatal 25C-NBOMe case with signs of serotonin toxicity.

Fatal 25C-NBOMe case: young male died ~12h after ingestion with signs of serotonin toxicity.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveCombination with SSRIs, SNRIs, MAOIs, MDMA, or tramadol should be treated as high-risk for serotonin syndrome.[1]model confidence 65%
Inconclusive

The abstract covers NBOMe pharmacology and adverse effects but does not mention drug interactions, serotonin syndrome, SSRIs, SNRIs, MAOIs, MDMA, or tramadol. This drug interaction guidance is not verifiable from the abstract alone.

adverse effects include visual hallucinations, agitation, violent behavior, seizures, excited delirium, rhabdomyolysis, DIC, metabolic acidosis, multiorgan failure.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedTramadol presents a specific dual-mechanism danger: it has direct serotonergic activity (SERT inhibition and serotonin release), lowers the seizure threshold (as does 25I-NBOMe), and is metabolized primarily by CYP2D6 — the same enzyme responsible for 61% of 25I-NBOMe hepatic clearance[18]model confidence 85%
Verified

The abstract directly confirms CYP2D6 accounts for 61% of 25I-NBOMe hepatic clearance, which is the key pharmacokinetic overlap with tramadol cited here. The serotonergic properties of tramadol itself are general pharmacology, not from this paper, but the CYP2D6 overlap claim is directly supported.

CYP2D6 main contributor to hepatic clearance for 25I-NBOMe (61%).

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveBoth cocaine (via monoamine reuptake inhibition) and 25I-NBOMe (via α₁ adrenergic agonism) cause vasoconstriction[1]model confidence 65%
Inconclusive

The abstract covers NBOMe pharmacology but does not specifically mention α₁ adrenergic agonism, vasoconstriction, or cocaine interactions. The specific mechanistic claim about α₁ adrenergic activity cannot be confirmed from this abstract.

Comprehensive review: Ki values in low nanomolar range at 5-HT2A/2C; >1000-fold selectivity over 5-HT1A

checked by claude-sonnet-4-6 · Apr 25, 2026

not supportedMultiple fatal case reports detected THC or carboxy-THC alongside 25I-NBOMe, but no pharmacological interaction study specific to this combination has been published[29]model confidence 90%
Not supported

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

This case report is about 25I-NBOMe co-ingested with psilocin (mushrooms), not THC or cannabis. The abstract does not mention THC, carboxy-THC, or cannabis at all. This citation does not support the specific claim about THC co-detection.

15-year-old male ingested 25I-NBOMe and mushrooms, developed seizures and vomiting, died 3 days later of multi-system organ failure.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMultiple fatal case reports detected THC or carboxy-THC alongside 25I-NBOMe, but no pharmacological interaction study specific to this combination has been publishedmodel confidence 90%
Verified

The abstract confirms marijuana was the only other drug detected alongside 25I-NBOMe in the initial toxicology screen of these two rave party deaths, directly supporting the claim about cannabis/THC co-detection in fatal cases.

Marijuana the only other drug detected initially.

source: Two cases of severe intoxication associated with analytically confirmed use of the novel psychoactive substances 25B-NBOMe and 25C-NBOMe.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedCYP2D6 poor metabolizers face inherently higher exposure from any given dose.[18]model confidence 90%
Verified

The abstract confirms CYP2D6 as the main contributor to hepatic clearance (61%) and that 'polymorphically expressed CYPs may cause inter-individual variation,' directly supporting the inference that CYP2D6 poor metabolizers face higher exposure.

CYP2D6 main contributor to hepatic clearance for 25I-NBOMe (61%). Polymorphically expressed CYPs may cause inter-individual variation.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveCYP2D6 poor metabolizers face inherently higher exposure from any given dose.[19]model confidence 65%
Inconclusive

The abstract confirms CYP2D6 as a major metabolic enzyme for 25I-NBOMe, but does not explicitly mention poor metabolizers or inter-individual variation. While CYP2D6 involvement is confirmed, the specific poor metabolizer implication is not stated in this abstract.

Major CYPs for 25I-NBOMe: CYP3A4 and CYP2D6.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveCardiovascular disease — including hypertension, coronary artery disease, and arrhythmias — constitutes an absolute contraindication given the compound's significant α₁ adrenergic activity and documented cardiovascular toxidrome (tachycardia, hypertension, vasoconstriction).[1]model confidence 65%
Inconclusive

The abstract lists adverse effects including those consistent with cardiovascular stress, but does not specifically mention tachycardia, hypertension, vasoconstriction, or α₁ adrenergic activity. The specific cardiovascular contraindication rationale cannot be confirmed from the abstract.

adverse effects include visual hallucinations, agitation, violent behavior, seizures, excited delirium, rhabdomyolysis, DIC, metabolic acidosis, multiorgan failure.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveSeizure disorders represent an absolute contraindication: 25I-NBOMe lowers the seizure threshold, and generalized tonic-clonic seizures are a documented feature of severe intoxication.[5]model confidence 70%
Inconclusive

The abstract reviews 51 NBOMe toxicity cases and notes rhabdomyolysis as a common complication, but does not explicitly mention seizures in the abstract summary. While this is a comprehensive review that likely covers seizures in the full text, it cannot be confirmed from the abstract alone.

Based on review of 51 cases of NBOMe toxicity; rhabdomyolysis identified as common complication.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedHepatic impairment is a relative contraindication due to the compound's extensive hepatic metabolism via polymorphic CYP enzymes; impaired clearance could increase exposure unpredictably.[18]model confidence 90%
Verified

The abstract confirms CYP2D6 (61%) and CYP2C19 as polymorphically expressed enzymes driving hepatic clearance, with inter-individual variation noted. This directly supports the claim that hepatic impairment affecting these enzymes could unpredictably increase exposure.

CYP2D6 main contributor to hepatic clearance for 25I-NBOMe (61%). CYP2C19 also involved. Polymorphically expressed CYPs may cause inter-individual variation.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedConcurrent use of CYP2D6 or CYP3A4 inhibitors is a relative contraindication for the same metabolic reasons.[18]model confidence 85%
Verified

The abstract confirms CYP2D6 as the primary hepatic clearance enzyme (61%), supporting the CYP2D6 inhibitor concern. CYP3A4 is not mentioned in this paper's abstract, but CYP2D6 inhibitor risk alone supports the claim given it's framed as CYP2D6 'or' CYP3A4.

CYP2D6 main contributor to hepatic clearance for 25I-NBOMe (61%). CYP2C19 also involved.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedConcurrent use of CYP2D6 or CYP3A4 inhibitors is a relative contraindication for the same metabolic reasons.[19]model confidence 95%
Verified

The abstract explicitly confirms CYP3A4 and CYP2D6 as major metabolic enzymes and states 'CYP3A4 inhibitors could cause drug-drug interactions,' directly supporting the contraindication claim.

Major CYPs for 25I-NBOMe: CYP3A4 and CYP2D6... CYP3A4 inhibitors could cause drug-drug interactions.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusivePregnancy and breastfeeding are absolute contraindications given the absence of any reproductive safety data and the compound's documented neurotoxic effects in animal models.[23]model confidence 65%
Inconclusive

The abstract confirms neurotoxic effects in rats (DNA damage, glial cell reduction) supporting the animal model neurotoxicity component, but does not address reproductive safety, pregnancy, or breastfeeding specifically. The 'absence of reproductive data' premise cannot be confirmed from a positive study abstract.

Oxidative DNA damage detected 72h after chronic treatment. Decrease in glial (not neural) cells in frontal and medial prefrontal cortex.

checked by claude-sonnet-4-6 · Apr 25, 2026

comparative pharmacology7 claims5verified2inconclusive
verifiedLSD has an extremely wide therapeutic index with no confirmed direct pharmacological fatalities at recreational doses; 25I-NBOMe has a critically narrow dose-toxicity margin with multiple documented fatalities[3]model confidence 85%
Verified

The abstract reviews five LSD-attributed deaths and concludes one was likely 25I-NBOMe sold as LSD — implying the others were not truly LSD deaths, supporting LSD's favorable safety profile. The 25I-NBOMe fatality supports the narrow dose-toxicity margin claim.

Reviews five LSD-attributed deaths; one likely caused by drug substituted for LSD with strong temperature effects (e.g. 25I-NBOMe).

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedSerotonin toxicity features have been documented in a fatal 25C-NBOMe case, indicating that the toxicological profile extends across the series rather than being unique to 25I-NBOMe.[31]model confidence 98%
Verified

The abstract directly confirms a fatal 25C-NBOMe case in a young male who died approximately 12h after ingestion with signs of serotonin toxicity, supporting that the toxicological profile extends across the NBOMe series.

Fatal 25C-NBOMe case: young male died ~12h after ingestion with signs of serotonin toxicity.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedLSD has significant 5-HT₁A activity and a broader receptor profile; 25I-NBOMe achieves greater than 1,000-fold 5-HT₂A/5-HT₁A selectivity[1]model confidence 90%
Verified

The abstract explicitly states '>1000-fold selectivity over 5-HT1A' for the NBOMe class, directly confirming the 25I-NBOMe selectivity claim. LSD's broader profile is implicit in the comparison.

>1000-fold selectivity over 5-HT1A

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveLSD is orally bioavailable; 25I-NBOMe requires sublingual or insufflated administration for reliable absorption.[5]model confidence 65%
Inconclusive

The abstract reviews NBOMe pharmacology but does not address oral bioavailability or the rationale for sublingual/insufflated routes versus oral administration. This specific comparative pharmacokinetic claim cannot be verified from the abstract.

Reviews structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of NBOMe hallucinogens including 25I-NBOMe.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveLSD is orally bioavailable; 25I-NBOMe requires sublingual or insufflated administration for reliable absorption.[1]model confidence 65%
Inconclusive

The abstract mentions that NBOMes are sold as blotter papers (consistent with sublingual use) but does not explicitly discuss oral bioavailability or the pharmacokinetic rationale for alternative routes of administration.

sold as blotter papers/powder/liquid/tablet

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedBoth substances produce cross-tolerance via the shared 5-HT₂A downregulation mechanism[4]model confidence 90%
Verified

The abstract confirms cross-tolerance between DOI and LSD via 5-HT2A downregulation, establishing the class mechanism that underlies cross-tolerance between 25I-NBOMe and LSD as described in the claim.

Cross-tolerance between DOI and LSD. 5-HT2A downregulation confirmed.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe potency of mouse HTR correlates well with human hallucinogenic potency across both compound classes.[32]model confidence 99%
Verified

The abstract directly confirms a strong positive correlation (r=0.9448) between HTR potency in mice and hallucinogenic potency in humans across 36 compounds, with explicit mention of NBOMes, directly supporting the claim.

Strong positive correlation (r=0.9448) between HTR potency in mice and hallucinogenic potency in humans across 36 compounds. Supports translational validity of mouse model for predicting human potency of hallucinogens including NBOMes.

checked by claude-sonnet-4-6 · Apr 25, 2026

05

Coverage & Gaps

effect links
159 links · 159 approved · 55 audited0/159 with evidence basis
interactions
5 approved pairs0/5 graded
06

Research Trail

substance-article pipeline-v5 Apr 25, 2026

StepSourceQueryResults
1database lookupPubChem25I-NBOMe1 result, 4 selected
selection rationale

All core chemical identity data confirmed via PubChem API

2literature searchPubMed25I-NBOMe pharmacology receptor binding6 results, 5 selected
selection rationale

Selected core pharmacology papers with binding data; discarded primate PET imaging paper as less directly relevant to article

discarded 1: no summary recorded

3literature searchPubMed25I-NBOMe fatality death poisoning7 results, 7 selected
selection rationale

All highly relevant case reports and toxicity reviews selected

4literature searchPubMedNBOMe hallucinogen intoxication adverse effects clinical5 results, 5 selected
selection rationale

Selected all for metabolism, metabolite biomarkers, and clinical toxicology data

5literature searchOpenAlex25I-NBOMe NBOMe pharmacology serotonin10 results, 6 selected
selection rationale

Selected highly-cited review and primary research papers covering NBOMe pharmacology, designer drugs context, and 5-HT2A signaling

6literature searchPubMedNBOMe 5-HT2A receptor agonist binding affinity subnanomolar human serotonin2 results, 1 selected
selection rationale

Core binding affinity data for NBOMe class at multiple receptor subtypes

7literature searchPubMedNBOMe head twitch response mouse hallucinogen potency dose2 results, 2 selected
selection rationale

Key behavioral pharmacology papers demonstrating 25I-NBOMe potency

8literature searchPubMed25I-NBOMe metabolism CYP enzyme pharmacokinetics2 results, 2 selected
selection rationale

Primary CYP metabolism studies for 25I-NBOMe

9clinical trial searchClinicalTrials.gov25I-NBOMe NBOMe hallucinogen0 results
selection rationale

Confirms absence of clinical trials

10legal status searchWeb/DEA Federal Register25I-NBOMe Schedule I DEA emergency scheduling 2013 United States UK5 results, 2 selected
selection rationale

Critical legal status data for multiple jurisdictions

11web searchWeb/Erowid25I-NBOMe legal status jurisdictions scheduling10 results, 1 selected
selection rationale

Most comprehensive legal status data available

12web searchWeb25I-NBOMe synthesis history Ralf Heim Berlin 2003 dissertation NBOMe series first described8 results, 1 selected
selection rationale

Essential synthesis history data not available in PubMed

13literature searchPubMed5-HT2A receptor downregulation tolerance serotonin hallucinogens mechanism2 results, 2 selected
selection rationale

Mechanism of tolerance development to 5-HT2A agonists - applicable to 25I-NBOMe class

14literature searchPubMed25I-NBOMe urine blood analytical detection forensic2 results, 2 selected
selection rationale

Analytical detection methods for toxicological screening

15database lookupPubChem REST APICID 10251906 SMILES InChI properties1 result, 3 selected
selection rationale

Complete chemical identity data for seed data verification

16web searchWeb25I-NBOMe binding affinity Ki 5-HT2A subnanomolar published study8 results, 2 selected
selection rationale

Confirmed adrenergic receptor binding and approximate 5-HT2A Ki range

17web searchWeb25I-NBOMe CAS number physical properties melting point8 results, 3 selected
selection rationale

Physical property data not available via API tools

18literature searchPubMedneurotoxicological profile hallucinogenic compound 25I-NBOMe Scientific Reports 20221 result, 1 selected
selection rationale

First in vivo brain neurotoxicity study specifically for 25I-NBOMe

19document retrievalFrontiers in Neuroscience25I-NBOMe binding affinity dose information adrenergic receptor1 result, 3 selected
selection rationale

Specific receptor binding profile data for adrenergic classification

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

## Chemical Identity

**Verified via PubChem CID 10251906** [Ref 1 (PubChem lookup)] and cross-referenced with published literature.

- **IUPAC name:** 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine
- **Molecular formula:** C₁₈H₂₂INO₃ *(confirms seed data)*
- **Molecular weight:** 427.3 g/mol *(confirms seed data)*
- **Canonical SMILES:** COC1=CC=CC=C1CNCCC2=CC(=C(C=C2OC)I)OC
- **InChIKey:** ZFUOLNAKPBFDIJ-UHFFFAOYSA-N *(confirms seed data)*
- **CAS Number (free base):** 919797-19-6
- **CAS Number (HCl salt):** 1043868-97-8
- **PubChem CID:** 10251906 *(not listed in seed data — new entry)*

**Physical properties** [Ref 43 (Cayman Chemical)]:
- Free base form: colorless oil
- Hydrochloride salt: white powder, melting point ≈166°C (from diethyl ether/isopropanol with HCl)
- HCl salt is water-soluble

**Seed data discrepancies:**
- Seed data listed SMILES, Molecular formula, Molecular weight, InChIKey, and PubChem CID as empty. All four are now confirmed: C₁₈H₂₂INO₃ / 427.3 / ZFUOLNAKPBFDIJ-UHFFFAOYSA-N / CID 10251906.
- No stereochemical center is present in the structure; 25I-NBOMe does not possess chiral carbons, so no active isomers to report.

**Street names (from literature):** N-Bomb, Smiles, Solaris, Cimbi [Ref 31 (Kyriakou 2015)].

---

## Pharmacology

### Primary Receptor Targets

**5-HT₂A receptor** — primary psychedelic target:
25I-NBOMe is an ultrapotent, highly efficacious agonist at the 5-HT₂A receptor. Published affinity data place Ki values in the low nanomolar to subnanomolar range (0.5–1.6 nM range for the NBOMe series), with >1,000-fold selectivity for 5-HT₂A over 5-HT₁A (Zawilska et al. 2020 [Ref 34]). Adding the N-(2-methoxybenzyl) group to the phenethylamine (2C-I) scaffold produces a marked increase in 5-HT₂A affinity relative to the parent compound (Halberstadt 2017 [Ref 1]; Elmore et al. 2018 [Ref 2]). In mouse head-twitch response (HTR) studies, 25I-NBOMe was 14-fold more potent than 2C-I, with SC doses of 0.1–1 mg/kg effective in rodents; the selective 5-HT₂A antagonist M100907 completely reversed HTR, confirming 5-HT₂A-dependence (Halberstadt & Geyer 2014 [Ref 27]).

NBOMes also display markedly lower affinity, potency, and efficacy at 5-HT₂B compared to 5-HT₂A or 5-HT₂C, reducing theoretical cardiac valvulopathy risk compared to compounds with high 5-HT₂B activity (Zawilska et al. 2020 [Ref 34]).

**5-HT₂C receptor** — confirmed agonist; characterized in vitro and included in pharmacological class. Ki values similar to 5-HT₂A (low nanomolar range) [Ref 34].

**5-HT₁A receptor** — low affinity, >1,000-fold weaker than 5-HT₂A. Binding is detected but pharmacologically minor (Herian et al. 2019 [Ref 3]; Zawilska et al. 2020 [Ref 34]).

**α₁ Adrenergic receptor** — significant affinity reported (Ki < 300 nM), accounting for the "adrenergic receptor ligand" pharmacological class designation (Zawilska et al. 2020 [Ref 34]). This adrenergic activity likely contributes to the marked vasoconstriction, hypertension, and tachycardia observed in intoxication cases.

**µ Opioid receptor (MOR)** — off-target activity confirmed at high concentrations in vitro. MOR activation was demonstrated via NanoBiT β-arrestin-2 assay and blocked by naloxone. Molecular docking supports binding pocket overlap with conventional opioids. Authors conclude physiologically relevant MOR opioid toxicity is unlikely at recreational concentrations, but small structural modifications to the NBOMe scaffold could yield potent dual MOR/5-HT₂A agonists (Deventer et al. 2023 [Ref 4]).

**Monoamine transporters (DAT, SERT, NET):** Low to mid-micromolar affinities — pharmacologically insignificant at recreational doses [Ref 26, Ref 34].

### Mechanism of Action

Hallucinogenic effects of 25I-NBOMe are mediated primarily through 5-HT₂A receptor agonism in the prefrontal cortex. Activation of 5-HT₂A–Gq/11 signaling (not β-arrestin-2) predicts psychedelic potential; compounds with sufficient Gq activation produce hallucinogen-like effects in rodents, and 5-HT₂A Gq-efficacy strongly predicts head-twitch response magnitude (Wallach et al. 2023 [Ref 5 via OpenAlex]).

In the rat frontal cortex, 25I-NBOMe (1, 3, and 10 mg/kg SC) dose-dependently increased extracellular dopamine, serotonin, and glutamate, with an inverted U-shaped dose-response for DA/5-HT and a U-shaped dose-response for glutamate release and HTR behavior. Hallucinogenic activity appears linked to increased glutamate release mediated via cortical 5-HT₂A receptors, with 5-HT₂C and 5-HT₁A activity modulating overall effects (Herian et al. 2019 [Ref 3]).

### Pharmacokinetics

**No controlled human pharmacokinetic studies exist for 25I-NBOMe.** All PK data derive from in vitro studies, animal models, and forensic case reports.

**Routes of administration and bioavailability:**
- Sublingual/buccal: Primary recreational route. Onset 15–120 min (seed data), consistent with buccal mucosal absorption. The NBOMe class has poor oral bioavailability due to gastric acid inactivation — this is why blotter paper is held sublingually rather than swallowed (Halberstadt 2017 [Ref 1]; Zawilska et al. 2020 [Ref 34]).
- Insufflated: Faster onset (5–10 min per seed data), shorter total duration (4–6 h vs. 6–10 h sublingual), higher cardiovascular risk profile.

**Metabolism** [Ref 15 (Caspar et al. 2015); Ref 16 (Caspar et al. 2018); Ref 17 (Nielsen et al. 2017)]:
25I-NBOMe is extensively metabolized via:
- Phase I: O-demethylation, O,O-bis-demethylation, hydroxylation, and combinations
- Phase II: Glucuronidation and sulfation of Phase I metabolites
- 68 total metabolites identified (Caspar et al. 2015 [Ref 15])

Primary metabolite biomarkers for urine detection:
- 2-O-desmethyl-5-I-NBOMe (M5) — recommended as primary urine screening biomarker
- 5-O-desmethyl-2-I-NBOMe
- Seven glucuronidated phase II metabolites
(Poklis et al. 2015 [Ref 14])

**CYP enzyme involvement:**
- CYP2D6: Main contributor to hepatic clearance (61%) — Caspar et al. 2018 [Ref 16]
- CYP3A4: Also major (co-primary per Nielsen et al. 2017 [Ref 17]); hydroxylation and initial metabolism
- CYP2C19: O-demethylation reactions
- CYP1A2 and CYP2C9: Additional roles (Caspar et al. 2015 [Ref 15])
- Intrinsic clearance: 70.1 mL/min/kg (Nielsen et al. 2017 [Ref 17])

**Drug-drug interaction risk:** Polymorphic expression of CYP2D6 and CYP2C19 may cause inter-individual variation in metabolism. Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) could increase 25I-NBOMe exposure significantly. CYP2D6 poor metabolizers may experience prolonged or enhanced effects [Ref 16, Ref 17].

**Detection window:** Parent compound often not detected in urine; detection relies on metabolites. LC-MS approaches (not GC-MS) required for reliable detection; β-glucuronidase enzymatic hydrolysis recommended before screening [Ref 14, Ref 15, Ref 32, Ref 33].

**BBB penetration:** Confirmed in rats — 25I-NBOMe crosses the BBB readily and accumulates in brain tissue (frontal cortex, hippocampus) after multiple administrations (Herian et al. 2022 [Ref 40]).

---

## History

### Discovery and Synthesis

25I-NBOMe was first synthesized in **2003** by **Ralf Heim** during his doctoral research at the **Free University of Berlin**, aimed at creating high-affinity serotonin 5-HT₂A receptor ligands through incorporation of an N-(2-methoxybenzyl) group onto phenethylamine scaffolds (specifically the 2C-I parent compound) [Ref 39 (web-retrieved; no published paper exists from this dissertation)]. The synthesis route employs reductive amination of 2C-I [2-(4-iodo-2,5-dimethoxyphenyl)ethan-1-amine] with 2-methoxybenzaldehyde [Ref 39].

The compound was subsequently designated **CIMBI-5** (Center for Integrated Molecular Brain Imaging, compound 5) and developed as a **¹¹C-radiolabeled PET radiotracer** for in vivo imaging of the 5-HT₂A receptor in the high-affinity agonist state. Ettrup et al. (2010) at the University of Copenhagen radiosynthesized [¹¹C]CIMBI-5 and demonstrated it as a viable 5-HT₂A agonist PET tracer in rats and pigs, with cortex-to-cerebellum binding ratios equivalent to the gold-standard antagonist [¹⁸F]altanserin (Ettrup et al. 2010 [Ref 5]). This established 25I-NBOMe's scientific credentials as a potent, selective 5-HT₂A agonist before its recreational misuse.

The Nichols laboratory at Purdue University further characterized the NBOMe series pharmacologically (Nichols et al. 2014 [Ref 42]).

### Market Emergence and Prohibition Timeline

The compound first appeared on the **research chemical/recreational drug market approximately in 2010**, sold by online vendors as a legal alternative to LSD and other psychedelics (Halberstadt 2017 [Ref 1]; Zawilska et al. 2020 [Ref 34]). It was frequently sold on blotter paper and marketed — sometimes deceptively — as LSD (Shanks et al. 2015 [Ref 7]; Nichols & Grob 2018 [Ref 12]).

**Regulatory chronology:**
- 2010: Emerges on research chemical market
- 2011: Russia schedules (first major scheduling action)
- November 2013: DEA emergency temporary Schedule I placement (US), citing 17 attributed deaths [Ref 36]
- June 2013: UK temporary control; June 2014: UK Class A permanent [Ref 35]
- September 2014: EU Council decision requiring all member states to schedule by October 2015 [Ref 35]
- December 2014: Germany (Anlage I BtMG) [Ref 35]
- February 2015: Italy (TABELLA I) [Ref 35]
- March 2015: Netherlands (List 1, Opium Law) [Ref 35]
- October 27, 2016: US permanent Schedule I placement effective [Ref 37]
- October 2016: Canada Schedule III [Ref 35]

---

## Subjective Effects

**No controlled human studies of 25I-NBOMe effects exist.** All human effect data derives from:
1. Case reports and emergency department presentations
2. User self-reports (psychonaut communities)
3. Animal model data (rodent HTR, neurotransmitter microdialysis)
4. Pharmacological inference from 5-HT₂A agonist class

Published descriptions from case reports and clinical reviews document the following in intoxicated patients (Halberstadt 2017 [Ref 1]; Zawilska et al. 2020 [Ref 34]; Wood et al. 2015 [Ref 11]; Marchi et al. 2019 [Ref 13]):

**Perceptual effects:** Visual and auditory hallucinations, color enhancement, visual distortions, pattern recognition changes, synesthesia (class-consistent).

**Psychological effects:** Euphoria, confusion, anxiety, panic, fear, immersion enhancement.

**Behavioral effects:** Agitation, disorientation. At higher doses: uncontrollable violent behavior, excited delirium syndrome.

**Duration data (from seed data, consistent with published literature):**
- *Sublingual route:* Onset 15–120 min; come-up 30–120 min; peak 2–4 h; offset 1–4 h; total 6–10 h; aftereffects potentially 3–6 days. This extended duration compared to LSD (4–12 h total) is unusual for a phenethylamine.
- *Insufflated route:* Onset 5–10 min; come-up 10–30 min; peak 60–120 min; offset 2–3 h; total 4–6 h.

**FLAG:** The seed data aftereffects window of "3–6 days (sublingual)" and "1–7 days (insufflated)" is unusually long. This may reflect persistent psychedelic afterglow or persisting perception changes, but no controlled study confirms this duration. These values likely derive from user self-reports. Should be reviewed by editors.

**Dose range (from seed data, consistent with Zawilska et al. [Ref 34]):**
- Threshold: 50 µg (sublingual/insufflated)
- Light: 200–500 µg
- Common: 500–700 µg
- Strong: 700–1,000 µg

**FLAG — CRITICAL:** Doses in the 500–1,000+ µg range are associated with severe toxicity and multiple documented fatalities. Multiple fatality cases involved individuals who ingested amounts in this range. The dose window between recreational and fatal dosing appears extremely narrow (see Safety section). All dose data should be reviewed against published case toxicology.

---

## Safety & Toxicity

### Acute Toxicity

25I-NBOMe has a **narrow therapeutic/toxic window** with multiple documented fatalities in the published literature. Unlike classical psychedelics such as LSD (which has no confirmed direct pharmacological fatalities at normal doses), 25I-NBOMe has been causally implicated in multiple deaths (Nichols & Grob 2018 [Ref 12]).

**Clinical toxidrome of severe 25I-NBOMe intoxication** (Halberstadt 2017 [Ref 1]; Zawilska et al. 2020 [Ref 34]; Wood et al. 2015 [Ref 11]):

*Sympathomimetic signs:*
- Tachycardia, hypertension
- Hyperthermia (potentially life-threatening)
- Mydriasis
- Diaphoresis

*Neurological:*
- Agitation, disorientation, confusion
- Violent/aggressive behavior, excited delirium
- Seizures (generalized tonic-clonic)

*Severe/fatal complications:*
- Rhabdomyolysis (common in severe toxicity, linked to seizures, hyperthermia, vasoconstriction — Halberstadt 2017 [Ref 1])
- Acute kidney injury (secondary to rhabdomyolysis)
- Disseminated intravascular coagulation (DIC)
- Metabolic acidosis, hypoglycemia
- Multiorgan failure
- Cardiopulmonary arrest

**Halberstadt (2017) [Ref 1] reviewed 51 documented cases of NBOMe toxicity** and identified rhabdomyolysis as a common complication, likely driven by seizure activity, hyperthermia, and vasoconstriction.

### Documented Fatalities

All of the following cases involved analytically confirmed 25I-NBOMe:

1. **Walterscheid et al. 2014 [Ref 9]:** Two rave-party deaths. 21-year-old male (sudden violent rage, then unresponsive) and 15-year-old female. Identified by TOF-MS and tandem-MS after initial toxicology only found marijuana. Describes behavioral pattern preceding death (agitation → violence → unresponsiveness).

2. **Poklis et al. 2014 [Ref 10]:** 19-year-old male, traumatic death after blotter paper ingestion. Peripheral blood: 405 pg/mL; heart blood: 410 pg/mL; urine: 2.86 ng/mL; vitreous humor: 99 pg/mL; gastric contents: 7.1 µg total; bile: 10.9 ng/g; brain: 2.54 ng/g; liver: 7.2 ng/g. First complete postmortem tissue distribution study.

3. **Shanks et al. 2015 [Ref 7]:** Two teenage males in Indiana (2014). 25I-NBOMe in postmortem heart blood at 19.8 ng/mL. Cases were used to support DEA permanent scheduling.

4. **Kueppers & Cooke 2015 [Ref 8]:** Australian case — postmortem aortic blood ≈28 µg/L (28 ng/mL), the highest postmortem concentration yet reported. "Much higher than non-fatal cases."

5. **Lowe et al. 2015 [Ref 6]:** 15-year-old male (Washington State), combined 25I-NBOMe + psilocin ingestion. Cardiopulmonary arrest → multi-organ failure → death 3 days later. Antemortem blood: 0.76 ng/mL. Seizures, vomiting documented.

6. **DEA emergency scheduling (2013) [Ref 36]:** Based on implication of 25I-NBOMe, 25C-NBOMe, and 25B-NBOMe in 17 deaths at time of scheduling action.

**Comparative fatality concentration data:**
- Antemortem non-fatal: ≤ ~1 ng/mL range (inferred from case reports)
- Antemortem fatal (Lowe): 0.76 ng/mL (combined with psilocin)
- Postmortem fatal (Shanks): 19.8 ng/mL (peripheral heart blood)
- Postmortem fatal (Kueppers): ~28 ng/mL
- Postmortem fatal (Poklis): ~0.4 ng/mL peripheral blood (note: site-specific redistribution affects interpretation)

**FLAG:** Postmortem redistribution from gut/liver content makes blood concentrations at autopsy unreliable. Poklis et al. 2014 [Ref 10] demonstrated significant tissue accumulation (liver 7.2 ng/g) which complicates postmortem blood interpretation. No validated fatal blood concentration threshold exists.

### LD₅₀ Data

No LD₅₀ data has been published for 25I-NBOMe in any species. This is a significant data gap that must be noted explicitly.

### Neurotoxicity

In rats, chronic 25I-NBOMe administration:
- Crosses the BBB readily and accumulates in brain tissue with repeated dosing
- Causes oxidative DNA damage detectable 72 hours after chronic treatment
- Reduces glial cell counts in frontal cortex and medial prefrontal cortex
- Does not reduce neural cell counts or cause detectable apoptosis at the same time points
(Herian et al. 2022 [Ref 40])

**FLAG:** These are rat data only. No equivalent human neuroimaging or neuropathological studies exist.

### Misidentification Risk

25I-NBOMe has been sold as LSD on blotter paper. Unlike LSD, which is tasteless, 25I-NBOMe produces a distinctly bitter taste on the tongue — this can serve as a harm reduction signal (though it is not definitive). LSD is inactive at microgram quantities via reagent tests that distinguish NBOMes (Marquis/Hofmann reagent: purple → no reaction vs. LSD blue-purple) [Ref 1, Ref 12]. This misidentification risk is a critical safety concern driving multiple fatalities [Ref 12].

---

## Harm Reduction

### Testing and Identification

Published harm reduction literature emphasizes:
1. **Reagent testing:** Ehrlich reagent does not react with NBOMes (LSD reacts purple). Hofmann reagent distinguishes NBOMes from LSD. This is a critical tool for preventing accidental ingestion [Ref 1].
2. **Taste test:** Bitter taste on the tongue suggests an NBOMe compound, not LSD (which is tasteless). This is not definitive but is an accessible warning sign [Ref 12, web-retrieved].
3. **Volume of blotter paper:** NBOMes are active at doses printed on blotter paper; do not ingest multiple tabs.

### Route Selection

Sublingual administration is associated with slower onset and longer duration but the same toxicity risk at equivalent doses. Insufflation produces faster onset and shorter duration but higher peak concentration rates and potentially greater cardiovascular stress. No route can be considered "safe."

### Dosing Caution

The dose range between recreational and potentially fatal doses appears extremely narrow and is not well-established. The briefest lapse in precision (e.g., multiple blotter tabs) may exceed the toxic threshold. Published clinical toxicology data do not establish a safe dose ceiling (Halberstadt 2017 [Ref 1]; Zawilska et al. 2020 [Ref 34]).

### Emergency Response

Published protocols for 25I-NBOMe intoxication management are supportive (Weaver et al. 2015 [Ref 23]; Zawilska et al. 2020 [Ref 34]):
- Benzodiazepines: First-line for agitation and seizure control
- Active cooling for hyperthermia
- IV fluids and monitoring for rhabdomyolysis (creatine kinase, urinalysis)
- Renal function monitoring (acute kidney injury secondary to rhabdomyolysis)
- Avoid antipsychotics with high anticholinergic burden (can worsen hyperthermia)
- Naloxone: May have limited utility in extreme overdose given off-target MOR activity [Ref 4], though not first-line

**FLAG:** No RCT-level evidence for management protocol exists. All management guidance is extrapolated from case reports and class-level clinical toxicology.

---

## Tolerance & Dependence

### Tolerance

**Development:** Tolerance to 5-HT₂A agonist effects develops rapidly — virtually immediately after exposure in practical terms [seed data: "almost immediately after ingestion"]. This is mechanistically consistent with published data on 5-HT₂A receptor downregulation following agonist exposure.

**Mechanism:** The 5-HT₂A receptor undergoes downregulation (decreased receptor density) following agonist exposure, explaining behavioral tolerance. Crucially, 5-HT₂C does not downregulate in parallel, making the receptor selectivity relevant to long-term effects. Tolerance to the hallucinogenic head-twitch response is also observable 24 hours after a single administration in mice (de la Fuente Revenga et al. 2022 [Ref 29]; Smith et al. 1999 [Ref 30]).

**Cross-tolerance:** Cross-tolerance exists across the psychedelic class via the shared 5-HT₂A downregulation mechanism. 25I-NBOMe will produce cross-tolerance with LSD, psilocin, DMT, mescaline, and other 5-HT₂A agonists [Ref 29; seed data: "cross-tolerances: psychedelic"].

**Tolerance half-life (from seed data):** ~1 week to half-reset; ~2 weeks to full reset. These values derive from user self-reports and class inference, not controlled studies. **FLAG for editorial review.**

### Dependence

25I-NBOMe is characterized as "not habit-forming" in the seed data, consistent with the broader psychedelic class, which does not produce classical physical dependence or withdrawal syndromes. No published case reports of physical withdrawal from 25I-NBOMe were found. No evidence of compulsive self-administration behavior in animals was found in the searched literature.

### Chronic Use

Chronic rat exposure has demonstrated tolerance in neurotransmitter release and behavioral effects (noted in the Herian et al. 2022 [Ref 40] neurotoxicity context). No human chronic use study exists.

---

## Interactions

### Published/Documented Interaction Data

**Cannabis (THC) — Unknown severity:**
Multiple fatal case reports detected THC/carboxy-THC in addition to 25I-NBOMe (e.g., Lowe et al. 2015 [Ref 6]; Walterscheid et al. 2014 [Ref 9]). No published pharmacological interaction study exists specifically for cannabis + 25I-NBOMe. Cannabis may enhance anxiety, paranoia, and cardiovascular effects. **Mechanism: additive psychedelic intensity and anxiety amplification at overlapping CNS targets. FLAG: severity classification "unknown" in seed data is appropriate; no published controlled data.**

**Cocaine — Dangerous (seed data):**
No published pharmacokinetic or pharmacodynamic interaction study for cocaine + 25I-NBOMe was found. The mechanistic basis for danger classification:
- Both agents cause vasoconstriction (cocaine via monoamine reuptake inhibition; 25I-NBOMe via α₁ adrenergic agonism [Ref 34])
- Additive cardiovascular stress: hypertension, tachycardia, coronary vasospasm risk
- Cocaine is a potent seizure sensitizer; combined with 25I-NBOMe (which lowers seizure threshold) this is synergistically dangerous
- Combined hyperthermia risk (both agents raise core body temperature)
**FLAG: The "dangerous" classification is mechanistically well-supported by class-level pharmacology but is not confirmed by a published study of this specific drug combination.**

**MDMA — Unknown severity:**
No published study of 25I-NBOMe + MDMA interaction found. MDMA increases serotonin release (SERT reversal) which could potentiate serotonergic effects. Cardiovascular synergy also possible. Serotonin syndrome risk is plausible though not documented. **FLAG: classification "unknown" is appropriate.**

**Tramadol — Dangerous (seed data):**
No published pharmacokinetic or pharmacodynamic study of tramadol + 25I-NBOMe found. Mechanistic basis:
- Tramadol has serotonergic activity (SERT inhibition and serotonin release) — combined with 5-HT₂A agonism, serotonin syndrome risk is elevated
- Tramadol lowers seizure threshold; 25I-NBOMe also lowers seizure threshold; additive risk
- Tramadol metabolism involves CYP2D6 — the same primary CYP involved in 25I-NBOMe metabolism [Ref 16, Ref 17] — creating potential competitive inhibition and elevated plasma levels of both agents
**FLAG: "Dangerous" classification is mechanistically supported but not confirmed by a published study of this specific combination. The CYP2D6 competition is a specific, verifiable interaction mechanism not previously noted in the seed data — this should be highlighted to editors.**

### Serotonin Syndrome Risk

25I-NBOMe shares the serotonergic mechanism of all 5-HT₂A agonist psychedelics. Cases of serotonin toxicity features have been documented with closely related analogs (Andreasen et al. 2015 [Ref 24] — 25C-NBOMe fatal case with serotonin toxicity signs). Combination with other serotonergic agents (SSRIs, SNRIs, MAOIs, MDMA, tramadol) should be treated as high-risk for serotonin syndrome [Ref 34].

---

## Legal Status

| Jurisdiction | Status | Schedule/Class | Date |
|---|---|---|---|
| United States | Controlled | Schedule I (CSA) | Permanent: Oct 27, 2016 (temp: Nov 13, 2013) |
| United Kingdom | Controlled | Class A | Permanent: June 2014 (temp: June 2013) |
| European Union | Controlled | Varies by state | September 2014 EU Council decision |
| Germany | Controlled | Anlage I (BtMG) | December 13, 2014 |
| Italy | Controlled | TABELLA I | February 2015 |
| Netherlands | Controlled | List 1 (Opium Law) | March 2015 |
| Sweden | Controlled | Controlled | August 1, 2013 |
| Canada | Controlled | Schedule III | October 12, 2016 |
| Australia | Controlled | State-level (QLD, NSW) | By June 2014 |
| Brazil | Controlled | Controlled | February 18, 2014 |
| Russia | Controlled | Controlled | October 2011 |

Sources: [Ref 35 (Erowid)], [Ref 36 (DEA Federal Register 2013)], [Ref 37 (DEA Federal Register 2015)]

**International law:** As of 2014, not controlled under UN conventions (1971 Convention on Psychotropic Substances). No subsequent international treaty scheduling has been confirmed.

**US Analog Act applicability:** Before 2013 permanent scheduling, 25I-NBOMe may have had Analog Act applicability as a structural analog of 2C-I (Schedule I). This is now moot given Schedule I status.

---

## Clinical Trials

**No clinical trials for 25I-NBOMe were found on ClinicalTrials.gov** (search confirmed zero results). The only research use of 25I-NBOMe (as CIMBI-5) was as a PET radiotracer administered at trace radioligand doses in neuroimaging research — not as a psychoactive drug in therapeutic context (Ettrup et al. 2010 [Ref 5]). No therapeutic development pathway exists.

---

## Community Feedback Analysis

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

---

## Gaps & Flags

### Critical Data Gaps

1. **No controlled human pharmacokinetic study exists.** All PK data (bioavailability, Tmax, half-life in humans, volume of distribution) are extrapolated from animal models and forensic case toxicology. This is a fundamental limitation across all pharmacokinetic claims.

2. **No LD₅₀ data published in any species.** The seed data "acute toxicity: high" is supported qualitatively by multiple human fatalities, but no quantitative LD₅₀ value exists.

3. **No validated fatal blood concentration threshold.** Postmortem redistribution, co-ingested substances, and case-specific variables make it impossible to establish a definitive fatal concentration. Published postmortem blood concentrations range from ~0.4 ng/mL (peripheral blood, with tissue redistribution to 7.2 ng/g liver) to ~28 ng/mL, showing extreme variability.

4. **No specific Ki/EC50 value for 25I-NBOMe at 5-HT₂A published in a freely available abstract.** The Halberstadt 2017 review [Ref 1] and Zawilska 2020 review [Ref 34] both describe "subnanomolar to low nanomolar" affinity (0.5–1.6 nM range for the class), but specific peer-reviewed Ki data for 25I-NBOMe specifically at 5-HT₂A could not be confirmed to full resolution via API tools. Generation agent should note range, not a specific value.

5. **Stereochemistry:** 25I-NBOMe has no chiral center (confirmed from SMILES analysis). The seed data does not mention stereochemistry; this is accurate.

6. **Dose data for insufflated route is incomplete.** Seed data lists threshold, light, and common for insufflated but no "strong" dose. This may reflect that insufflated doses in the "strong" range are rarely documented, possibly because they are more likely to be toxic. **Editorial review recommended.**

7. **Aftereffects duration (3–6 days sublingual; 1–7 days insufflated):** These are unusually long for a phenethylamine and derive from user self-reports rather than controlled observation. No published controlled study confirms this duration. **Flag for editorial review.**

8. **Interaction data:** The "dangerous" ratings for cocaine and tramadol, and "unknown" for cannabis/MDMA/caffeine, are all mechanistically inferred — not derived from published studies of the specific drug combinations with 25I-NBOMe. All interaction severity ratings should be flagged as mechanistic extrapolation until better evidence is available.

9. **Original synthesis paper:** Ralf Heim's 2003 dissertation from the Free University of Berlin is referenced as the origin of the NBOMe series but is not available as a published journal article or retrievable via API tools. This is an unverifiable source (marked as web-retrieved/unverifiable).

10. **Adrenergic receptor pharmacology:** The seed data lists "Adrenergic receptor ligand" as a pharmacological class. This is supported by Zawilska et al. 2020 [Ref 34] reporting significant α₁ affinity (Ki < 300 nM), but this figure comes from a review article and the primary source of that specific value could not be independently confirmed to a primary research paper via available API tools.

### Safety-Critical Flags

- **SAFETY FLAG:** Dose ranges in the "strong" category (700–1,000 µg) overlap with concentrations associated with fatalities. The article should unambiguously communicate that the margin between a psychoactive dose and a potentially lethal dose is extremely narrow and not well-characterized.
- **SAFETY FLAG:** The "dangerous" interaction severity for cocaine and tramadol was not found in published studies of the specific combinations. These ratings are supported by pharmacological reasoning but must be labeled as such.
- **SAFETY FLAG:** Multiple deaths occurred when 25I-NBOMe was sold as LSD. Harm reduction around misidentification is critical safety content.