25B-NBOMe
4-bromo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine
Studies and references cited across this article, graded by evidence strength.
Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.
Data points an editor reviewed and accepted for publication.
Value Provenance
Dosing
sublingualtrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 50 µg | 50 µg | low |
| Low | 100–250 µg | 100–250 µg | low |
| Common | 250–500 µg | 250–500 µg | low |
| Strong | 500–750 µg | 500–750 µg | low |
| Heavy | 750+ µg | 750+ µg | low |
| Editorial | No controlled human dosing data exist for 25B-NBOMe. All dose values derive from community user reports (PsychonautWiki, Erowid, harm reduction forums). The research output explicitly flags that dose ranges are unverified against published controlled studies. Values are structurally plausible given Ki = 0.5 nM at 5-HT₂A (Rickli et al. 2015) indicating sub-milligram activity. Published fatal cases involved ingestion of multiple tablets/blotters but exact doses ingested were not quantified. | ||
ReasoningReasoningNo controlled human dosing data exist for 25B-NBOMe. All dose values derive from community user reports (PsychonautWiki, Erowid, harm reduction forums). The research output explicitly flags that dose ranges are unverified against published controlled studies. Values are structurally plausible given Ki = 0.5 nM at 5-HT₂A (Rickli et al. 2015) indicating sub-milligram activity. Published fatal cases involved ingestion of multiple tablets/blotters but exact doses ingested were not quantified. Evidence basis: community_consensus_small | |||
insufflatedtrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 25 µg | 25 µg | low |
| Low | 50–150 µg | 50–150 µg | low |
| Common | 150–300 µg | 150–300 µg | low |
| Strong | 300–500 µg | 300–500 µg | low |
| Heavy | 500+ µg | 500+ µg | low |
| Editorial | No controlled human dosing data exist. Insufflated doses inferred from community reports, expected to be lower than sublingual due to bypassing mucosal absorption barriers and first-pass metabolism. Research output notes insufflation causes rapid onset and unpredictable dose absorption with high overdose risk. Ranges widened to account for uncertainty. | ||
ReasoningReasoningNo controlled human dosing data exist. Insufflated doses inferred from community reports, expected to be lower than sublingual due to bypassing mucosal absorption barriers and first-pass metabolism. Research output notes insufflation causes rapid onset and unpredictable dose absorption with high overdose risk. Ranges widened to account for uncertainty. Evidence basis: community_consensus_small | |||
Duration
sublingual
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Come uptrace | 30–60 minutes | 30–60 minutes | low |
| Editorial | Community reports suggest 30–60 minute come-up following sublingual onset. No controlled data. | ||
ReasoningReasoningCommunity reports suggest 30–60 minute come-up following sublingual onset. No controlled data. Evidence basis: community_consensus_small | |||
| After effectstrace | 4–12 hours | 4–12 hours | low |
| Editorial | Residual effects (mood shifts, cognitive fatigue, sleep difficulty) reported for 4–12 hours after subjective effects resolve. Community sourced. | ||
ReasoningReasoningResidual effects (mood shifts, cognitive fatigue, sleep difficulty) reported for 4–12 hours after subjective effects resolve. Community sourced. Evidence basis: community_consensus_small | |||
| Onsettrace | 15–30 minutes | 15–30 minutes | low |
| Editorial | Community user reports indicate sublingual onset at 15–30 minutes. No controlled data. Consistent with sublingual absorption kinetics for phenethylamine compounds. | ||
ReasoningReasoningCommunity user reports indicate sublingual onset at 15–30 minutes. No controlled data. Consistent with sublingual absorption kinetics for phenethylamine compounds. Evidence basis: community_consensus_small | |||
| Peaktrace | 2–4 hours | 2–4 hours | low |
| Editorial | Community reports indicate 2–4 hour peak duration sublingually. Consistent with prolonged 5-HT₂A occupancy given Ki = 0.5 nM. | ||
ReasoningReasoningCommunity reports indicate 2–4 hour peak duration sublingually. Consistent with prolonged 5-HT₂A occupancy given Ki = 0.5 nM. Evidence basis: community_consensus_small | |||
| Offsettrace | 2–4 hours | 2–4 hours | low |
| Editorial | Community reports suggest gradual offset over 2–4 hours after peak. No controlled data. | ||
ReasoningReasoningCommunity reports suggest gradual offset over 2–4 hours after peak. No controlled data. Evidence basis: community_consensus_small | |||
| Totaltrace | 8–12 hours | 8–12 hours | low |
| Editorial | Research brief cites 8–12 hours total sublingual duration, consistent with published literature and community reports. Plausible given extremely high 5-HT₂A affinity. No controlled pharmacokinetic verification. | ||
ReasoningReasoningResearch brief cites 8–12 hours total sublingual duration, consistent with published literature and community reports. Plausible given extremely high 5-HT₂A affinity. No controlled pharmacokinetic verification. Evidence basis: community_consensus_large | |||
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 1–10 minutes | 1–10 minutes | low |
| Editorial | Insufflation produces rapid onset (1–10 minutes) per community reports. Research output confirms rapid onset and unpredictable dose absorption via this route. | ||
ReasoningReasoningInsufflation produces rapid onset (1–10 minutes) per community reports. Research output confirms rapid onset and unpredictable dose absorption via this route. Evidence basis: community_consensus_small | |||
| Come uptrace | 10–30 minutes | 10–30 minutes | low |
| Editorial | Community reports suggest compressed come-up of 10–30 minutes via insufflation. | ||
ReasoningReasoningCommunity reports suggest compressed come-up of 10–30 minutes via insufflation. Evidence basis: community_consensus_small | |||
| Peaktrace | 1.5–3 hours | 1.5–3 hours | low |
| Editorial | Insufflated peak estimated at 1.5–3 hours from community reports. Shorter than sublingual due to faster absorption. | ||
ReasoningReasoningInsufflated peak estimated at 1.5–3 hours from community reports. Shorter than sublingual due to faster absorption. Evidence basis: community_consensus_small | |||
| Offsettrace | 1–2 hours | 1–2 hours | low |
| Editorial | Community reports suggest 1–2 hour offset following insufflated peak. | ||
ReasoningReasoningCommunity reports suggest 1–2 hour offset following insufflated peak. Evidence basis: community_consensus_small | |||
| Totaltrace | 5–8 hours | 5–8 hours | low |
| Editorial | Insufflated total duration estimated at 5–8 hours from community reports. Shorter than sublingual (8–12 hours) consistent with faster absorption and elimination kinetics. | ||
ReasoningReasoningInsufflated total duration estimated at 5–8 hours from community reports. Shorter than sublingual (8–12 hours) consistent with faster absorption and elimination kinetics. Evidence basis: community_consensus_small | |||
| After effectstrace | 2–8 hours | 2–8 hours | low |
| Editorial | Residual effects 2–8 hours after insufflated experience ends. Community sourced. | ||
ReasoningReasoningResidual effects 2–8 hours after insufflated experience ends. Community sourced. Evidence basis: community_consensus_small | |||
Safety
Toxicity Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Acute | critical | critical | medium |
| Chronic | moderate | moderate | medium |
| Organs Affected | cardiovascular, kidney, skeletal_muscle, brain | cardiovascular, kidney, skeletal_muscle, brain | medium |
| Editorial | Acute toxicity classified as critical based on multiple published fatalities (Shanks 2015, Al-Imam 2018) at blood levels (1.59–3.14 ng/mL) overlapping with non-fatal cases (up to 10.1 ng/mL per Gee 2016), demonstrating no predictable safe threshold. Chronic toxicity classified as moderate (downgraded from high): genotoxicity evidence is from a single rat study (Wojtas 2021); no chronic human toxicity data exist. | ||
ReasoningReasoningAcute toxicity classified as critical based on multiple published fatalities (Shanks 2015, Al-Imam 2018) at blood levels (1.59–3.14 ng/mL) overlapping with non-fatal cases (up to 10.1 ng/mL per Gee 2016), demonstrating no predictable safe threshold. Chronic toxicity classified as moderate (downgraded from high): genotoxicity evidence is from a single rat study (Wojtas 2021); no chronic human toxicity data exist. Evidence basis: published_case_series | |||
Dependence Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Physical | none | none | low |
| Psychological | low | low | low |
| Compulsive Redosing | negligible | negligible | low |
| Dose Escalation | negligible | negligible | low |
| Editorial | WHO ECDD (2014) confirmed no human dependence studies exist. Psychological dependence rated low rather than negligible due to preclinical evidence of dopaminergic self-administration (Custodio et al. 2020), which is atypical for serotonergic psychedelics. Rapid tolerance development via 5-HT₂A downregulation limits compulsive redosing and dose escalation. | ||
ReasoningReasoningWHO ECDD (2014) confirmed no human dependence studies exist. Psychological dependence rated low rather than negligible due to preclinical evidence of dopaminergic self-administration (Custodio et al. 2020), which is atypical for serotonergic psychedelics. Rapid tolerance development via 5-HT₂A downregulation limits compulsive redosing and dose escalation. Evidence basis: animal_study | |||
Withdrawal Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Severity | none | none | low |
| Symptoms | — | — | low |
| Fatal | No | No | low |
| Medical Supervision | Not required | Not required | low |
| Editorial | No withdrawal syndrome has been reported or studied for 25B-NBOMe or for the serotonergic psychedelic class generally. Class-level inference: serotonergic psychedelics do not produce physical dependence or withdrawal. | ||
ReasoningReasoningNo withdrawal syndrome has been reported or studied for 25B-NBOMe or for the serotonergic psychedelic class generally. Class-level inference: serotonergic psychedelics do not produce physical dependence or withdrawal. Evidence basis: animal_study | |||
Tolerance Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Buildup | rapid | rapid | low |
| Half-life | 7 days | 7 days | low |
| Full Reset | 14 days | 14 days | low |
| Cross-tolerances | LSD, psilocybin, mescaline, DMT, 25I-NBOMe, 25C-NBOMe, 2C-B | LSD, psilocybin, mescaline, DMT, 25I-NBOMe, 25C-NBOMe, 2C-B | low |
| Editorial | Tolerance mechanism and cross-tolerance pattern inferred from serotonergic psychedelic class pharmacology. Zawilska et al. 2020 confirms cross-tolerance within the class. Specific kinetic values (7-day half-life, 14-day reset) from community consensus, not published studies. | ||
ReasoningReasoningTolerance mechanism and cross-tolerance pattern inferred from serotonergic psychedelic class pharmacology. Zawilska et al. 2020 confirms cross-tolerance within the class. Specific kinetic values (7-day half-life, 14-day reset) from community consensus, not published studies. Evidence basis: community_consensus_large | |||
Effects & Profile
Contraindications
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| cardiovascular cardiac arrhythmiastrace | absolute | absolute | high |
| Editorial | Published fatal case (Al-Imam 2018) documented death from cardiac arrest secondary to ventricular fibrillation. α₁-adrenergic binding confirmed by Rickli et al. 2015. | ||
ReasoningReasoningPublished fatal case (Al-Imam 2018) documented death from cardiac arrest secondary to ventricular fibrillation. α₁-adrenergic binding confirmed by Rickli et al. 2015. | |||
| cardiovascular long QT syndrometrace | absolute | absolute | medium |
| Editorial | Cardiac arrhythmia fatalities documented (Shanks 2015, Al-Imam 2018). Long QT syndrome increases arrhythmia susceptibility under sympathomimetic stress. | ||
ReasoningReasoningCardiac arrhythmia fatalities documented (Shanks 2015, Al-Imam 2018). Long QT syndrome increases arrhythmia susceptibility under sympathomimetic stress. | |||
| cardiovascular uncontrolled hypertensiontrace | absolute | absolute | medium |
| Editorial | Hypertension universal in Gee 2016 case series; α₁-adrenergic mechanism confirmed (Rickli 2015). | ||
ReasoningReasoningHypertension universal in Gee 2016 case series; α₁-adrenergic mechanism confirmed (Rickli 2015). | |||
| cardiovascular coronary artery diseasetrace | absolute | absolute | medium |
| Editorial | Cardiovascular toxicity profile from Rickli 2015 and clinical presentations in Gee 2016. | ||
ReasoningReasoningCardiovascular toxicity profile from Rickli 2015 and clinical presentations in Gee 2016. | |||
| psychiatric psychotic disorderstrace | absolute | absolute | medium |
| Editorial | Class-level contraindication for serotonergic psychedelic 5-HT₂A agonists. Mechanism well-established. | ||
ReasoningReasoningClass-level contraindication for serotonergic psychedelic 5-HT₂A agonists. Mechanism well-established. | |||
| psychiatric bipolar disordertrace | relative | relative | low |
| Editorial | Class-level contraindication reinforced by 25B-NBOMe's documented dopaminergic activity in preclinical models. | ||
ReasoningReasoningClass-level contraindication reinforced by 25B-NBOMe's documented dopaminergic activity in preclinical models. | |||
| neurological epilepsytrace | absolute | absolute | medium |
| Editorial | Seizures documented in clinical case series of NBOMe toxicity (Zawilska 2020, Gee 2016). | ||
ReasoningReasoningSeizures documented in clinical case series of NBOMe toxicity (Zawilska 2020, Gee 2016). | |||
| hepatic hepatic impairmenttrace | relative | relative | low |
| Editorial | CYP metabolism documented by Caspar et al. 2017. Pharmacokinetic reasoning. | ||
ReasoningReasoningCYP metabolism documented by Caspar et al. 2017. Pharmacokinetic reasoning. | |||
| renal renal impairmenttrace | relative | relative | medium |
| Editorial | Kidney injury documented in Gee 2016. Rhabdomyolysis common NBOMe complication (Zawilska 2020). | ||
ReasoningReasoningKidney injury documented in Gee 2016. Rhabdomyolysis common NBOMe complication (Zawilska 2020). | |||
| pregnancy breastfeeding pregnancy and breastfeedingtrace | absolute | absolute | medium |
| Editorial | Genotoxicity in rat comet assay (Wojtas 2021) combined with class-level serotonergic psychedelic contraindication in pregnancy. | ||
ReasoningReasoningGenotoxicity in rat comet assay (Wojtas 2021) combined with class-level serotonergic psychedelic contraindication in pregnancy. | |||
Timeline Phases
sublingual
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 900–1800 sec(i=0.05) | 900–1800 sec(i=0.05) | low |
| Editorial | No controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | ||
ReasoningReasoningNo controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | |||
| Come uptrace | 1800–3600 sec(i=0.30) | 1800–3600 sec(i=0.30) | low |
| Editorial | No controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | ||
ReasoningReasoningNo controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | |||
| Peaktrace | 7200–14400 sec(i=1.00) | 7200–14400 sec(i=1.00) | low |
| Editorial | No controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | ||
ReasoningReasoningNo controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | |||
| Plateautrace | 5400–10800 sec(i=0.50) | 5400–10800 sec(i=0.50) | low |
| Editorial | No controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | ||
ReasoningReasoningNo controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | |||
| Resolutiontrace | 3600–7200 sec(i=0.20) | 3600–7200 sec(i=0.20) | low |
| Editorial | No controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | ||
ReasoningReasoningNo controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | |||
| Afterglowtrace | 14400–43200 sec(i=0.05) | 14400–43200 sec(i=0.05) | low |
| Editorial | No controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | ||
ReasoningReasoningNo controlled human pharmacokinetic or dosing data exist for 25B-NBOMe. Timeline estimates derive from community user reports (sublingual total duration 8–12 hours cited in research brief) and pharmacological class reasoning. The 8–12 hour total duration is consistent with the compound's extremely high 5-HT₂A affinity (Ki = 0.5 nM), suggesting prolonged receptor occupancy. | |||
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 60–600 sec(i=0.05) | 60–600 sec(i=0.05) | low |
| Editorial | No controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | ||
ReasoningReasoningNo controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | |||
| Come uptrace | 600–1800 sec(i=0.35) | 600–1800 sec(i=0.35) | low |
| Editorial | No controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | ||
ReasoningReasoningNo controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | |||
| Peaktrace | 5400–10800 sec(i=1.00) | 5400–10800 sec(i=1.00) | low |
| Editorial | No controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | ||
ReasoningReasoningNo controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | |||
| Plateautrace | 3600–7200 sec(i=0.50) | 3600–7200 sec(i=0.50) | low |
| Editorial | No controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | ||
ReasoningReasoningNo controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | |||
| Resolutiontrace | 1800–5400 sec(i=0.20) | 1800–5400 sec(i=0.20) | low |
| Editorial | No controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | ||
ReasoningReasoningNo controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | |||
| Afterglowtrace | 7200–28800 sec(i=0.05) | 7200–28800 sec(i=0.05) | low |
| Editorial | No controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | ||
ReasoningReasoningNo controlled human data exist for insufflated 25B-NBOMe pharmacokinetics. Timeline inferred from community user reports and pharmacological reasoning (insufflation bypasses first-pass metabolism, producing faster onset and shorter total duration compared to sublingual). Research output notes that insufflation causes rapid onset and unpredictable dose absorption. | |||
Dose Tier Summaries
At threshold doses, effects are subtle and may be difficult to distinguish from placebo: mild brightening of colors, slight enhancement of tactile and auditory perception, and a faint sense of altered awareness. Mood may shift slightly toward either euphoria or unease without clear cause. Physically, mild pupil dilation and a slight increase in heart rate may be noticeable. Body temperature regulation remains normal. These doses produce minimal functional impairment but signal that the compound is pharmacologically active.
No controlled human dosing data exist for 25B-NBOMe. Threshold descriptions inferred from community user reports and class-level serotonergic psychedelic phenomenology. Specific dose values derive from community sources only.
ReasoningReasoning
No controlled human dosing data exist for 25B-NBOMe. Threshold descriptions inferred from community user reports and class-level serotonergic psychedelic phenomenology. Specific dose values derive from community sources only.
Evidence basis: community_consensus_small
At light doses, recognizable psychedelic effects emerge: color enhancement and saturation, mild visual patterning on textured surfaces, subtle drifting of stationary objects, and increased pattern recognition. Thought connectivity increases and music sounds richer. Emotional sensitivity rises, with both positive and negative stimuli amplified. Physically, pupil dilation becomes apparent. Heart rate and blood pressure increase mildly. A stimulant body load — restlessness, jaw tension, mild peripheral vasoconstriction — becomes noticeable, reflecting the compound's α₁-adrenergic activity. Functional impairment is moderate. Sleep is unlikely for 6–8 hours after administration.
Descriptions inferred from community reports and case report clinical presentations. Physical effects (stimulation, vasoconstriction) supported by pharmacological profile documented in Rickli et al. 2015. No controlled dosing data.
ReasoningReasoning
Descriptions inferred from community reports and case report clinical presentations. Physical effects (stimulation, vasoconstriction) supported by pharmacological profile documented in Rickli et al. 2015. No controlled dosing data.
Evidence basis: community_consensus_small
At common doses, the full psychedelic experience manifests: pronounced open- and closed-eye visuals including geometric patterning, color shifting, object morphing and drifting, and enhanced pattern recognition. Time distortion becomes significant — minutes may feel like hours. Thought acceleration and increased conceptual connectivity produce novel associations. Emotional responses intensify substantially; empathy and introspection may alternate with anxiety or paranoia depending on set and setting. The sympathomimetic component becomes prominent: tachycardia, hypertension, mydriasis, increased body temperature, and peripheral vasoconstriction (cold extremities). Jaw clenching, muscle tension, and restlessness are common. Nausea may occur, particularly during the come-up. Sleep is impossible for 8–10 hours. The experience demands a full day's commitment and a controlled environment.
Descriptions synthesized from clinical case series presentations (Gee et al. 2016 documented sympathomimetic signs in all 10 patients at presumed common-to-strong doses) and community user reports. Specific dose ranges unverified.
ReasoningReasoning
Descriptions synthesized from clinical case series presentations (Gee et al. 2016 documented sympathomimetic signs in all 10 patients at presumed common-to-strong doses) and community user reports. Specific dose ranges unverified.
Evidence basis: community_consensus_small
At strong doses, visual effects become overwhelming and immersive: complete visual field distortion, complex fractal geometry, synesthesia, and difficulty distinguishing hallucination from reality. Ego dissolution may occur. Cognitive function is profoundly altered — thought loops, confusion, and disorientation are common. Anxiety and panic become significant risks, particularly in uncontrolled settings. Violent agitation — the predominant clinical presentation in published case series — may emerge. Sympathomimetic toxicity intensifies: marked tachycardia, hypertension, hyperthermia, profuse sweating, and significant vasoconstriction. Seizure risk increases. Rhabdomyolysis becomes possible with sustained physical agitation and hyperthermia. This dose range approaches documented clinical intoxication territory. The margin between strong effects and medical emergency is narrow and unpredictable.
Clinical case series (Gee et al. 2016) documented violent agitation, sympathomimetic toxidrome, hyperthermia, and rhabdomyolysis at presumed strong doses. Fatal and non-fatal blood levels overlap, making dose-toxicity prediction unreliable.
ReasoningReasoning
Clinical case series (Gee et al. 2016) documented violent agitation, sympathomimetic toxidrome, hyperthermia, and rhabdomyolysis at presumed strong doses. Fatal and non-fatal blood levels overlap, making dose-toxicity prediction unreliable.
Evidence basis: published_case_series
Heavy doses produce effects indistinguishable from severe clinical intoxication: complete dissociation from reality, uncontrollable hallucinations, total disorientation, and violent agitation. Cognitive function ceases to be coherent. The experience is overwhelmingly dysphoric in most documented cases at this intensity. Life-threatening complications dominate: severe hypertension, cardiac arrhythmia (including ventricular fibrillation), hyperthermia exceeding 40°C, seizures, rhabdomyolysis, disseminated intravascular coagulation, acute kidney injury, and metabolic acidosis. Published fatalities occurred at blood levels (1.59–3.14 ng/mL) that overlap with non-fatal presentations (up to 10.1 ng/mL), demonstrating that individual response is unpredictable. This dose range carries immediate risk of death. No safe upper limit has been established.
Published fatal cases (Shanks et al. 2015, Al-Imam 2018) and severe non-fatal case series (Gee et al. 2016) document the clinical presentation at heavy/overdose levels. Cardiac arrhythmia, multiorgan failure, and death are directly evidenced.
ReasoningReasoning
Published fatal cases (Shanks et al. 2015, Al-Imam 2018) and severe non-fatal case series (Gee et al. 2016) document the clinical presentation at heavy/overdose levels. Cardiac arrhythmia, multiorgan failure, and death are directly evidenced.
Evidence basis: published_case_series
History
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.
Sources
- [1]moderateReceptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME · 2015 · Neuropharmacology
- [2]moderateSerotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36.Ettrup A, da Cunha-Bang S, McMahon B, Lehel S, Dyssegaard A, Skibsted AW, et al. · 2014 · Journal of Cerebral Blood Flow and Metabolism
- [3]moderateNBOMes-Highly Potent and Toxic Alternatives of LSDZawilska JB, Kacela M, Adamowicz P · 2020 · Frontiers in Neuroscience
- [4]moderate25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential.Custodio RJP, Sayson LV, Botanas CJ, et al. · 2020 · Addiction Biology
- [5]weakCase series: toxicity from 25B-NBOMe--a cluster of N-bomb cases.Gee P, Schep LJ, Jensen BP, Moore G, Barrington S · 2016 · Clinical Toxicologydoi.org/10.3109/15563650.2015.1115056pubmed 2662134211 claims checked7 verified3 partial1 inconclusive
- [6]weakFatal Intoxications with 25B-NBOMe and 25I-NBOMe in Indiana During 2014.Shanks KG, Sozio T, Behonick GS · 2015 · Journal of Analytical Toxicology
- [7]weak25b-NBOMe: A Case Report of Sudden Death and Insightful View of Google Trends Data.Al-Imam A · 2018 · Iranian Journal of Psychiatry and Behavioral Sciencesdoi.org/10.5812/ijpbs.98706 claims checked5 verified1 partial
- [8]moderateExtensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands.Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, Marona-Lewicka D, Lill MA, Nichols DE · 2013 · ACS Chemical Neuroscience
- [9]moderateLegal highs: staying on top of the flood of novel psychoactive substancesBaumeister D, Tojo LM, Tracy DK · 2015 · Therapeutic Advances in Psychopharmacology
- [10]weak25B-NBOMe - Schedule I Placement (Temporary Scheduling, 25B/25I/25C-NBOMe)US Drug Enforcement Administration · 2013linkno claims checked
- [11]weakCritical Review of 25B-NBOMe (Expert Committee on Drug Dependence)WHO ECDD · 2014linkno claims checked
- [12]moderateRadiosynthesis 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
- [13]moderateAnalysis 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
- [14]weakTwo cases of severe intoxication associated with analytically confirmed use of the novel psychoactive substances 25B-NBOMe and 25C-NBOMe.Tang MH, Ching CK, Tsui MS, Chu FK, Mak TW · 2014 · Clinical Toxicology
- [15]weakSchedules of Controlled Substances: Permanent Placement of Three Synthetic Phenethylamines Into Schedule IUS Drug Enforcement Administration · 2015linkno claims checked
- [16]strongDesigner drugs: mechanism of action and adverse effectsLuethi D, Liechti ME · 2020 · Archives of Toxicology
- [17]moderateNeurochemical 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
- [18]moderateMetabolic fate and detectability of 25B-NBOMe and 25C-NBOMe in human and rat urine by GC-MS, LC-MSn, and LC-HR-MS/MS approaches.Caspar AT, Brandt SD, Stoever AE, Meyer MR, Maurer HH · 2017 · Journal of Pharmaceutical and Biomedical Analysis
- [19]moderateNeurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors.Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A · 2018 · Biochemical Pharmacology
- [20]moderateThe importance of small polar radiometabolites in molecular neuroimaging: A PET study with [11C]Cimbi-36 labeled in two positions.Johansen A, Hansen HD, Svarer C, Lehel S, Leth-Petersen S, et al. · 2017 · Journal of Cerebral Blood Flow and Metabolism
- [21]moderateHuman biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions.Johansen A, Holm S, Dall B, Keller S, Kristensen JL, Knudsen GM, Hansen HD · 2019 · EJNMMI Research
- [22]weakNCT01778686: Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A ReceptorsKnudsen GM (sponsor) · 2013linkno claims checked
- [23]weakNCT03289949: The Neurobiological Effect of 5-HT2AR ModulationKnudsen GM (sponsor) · 2017linkno claims checked
- [24]weakA fatal poisoning involving 25C-NBOMe.Andreasen MF, Telving R, Rosendal I, Eg MB, Hasselstrøm JB, Andersen LV · 2015 · Forensic Science International
- [25]weakDeath after 25C-NBOMe and 25H-NBOMe consumption.Morini L, Bernini M, Vezzoli S, Restori M, Moretti M, Crenna S, Papa P, Locatelli C, Osculati AMM, Vignali C, Groppi A · 2017 · Forensic Science International
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.
summary12 claims5verified5partial1inconclusive1not supported
partialWith a 5-HT₂A receptor affinity of Ki = 0.5 nM, it ranks among the most potent synthetic serotonergic psychedelics characterized, active at sub-milligram doses via sublingual and insufflated routes[1]model confidence 80%
Abstract confirms NBOMes are very potent 5-HT2A agonists with class EC50 0.04–0.5 µM, but does not state Ki = 0.5 nM specifically (only EC50 class range given). Sub-milligram dosing and specific routes (sublingual, insufflated) are not addressed.
NBOMes are very potent 5-HT2A agonists (class EC50: 0.04-0.5 µM) with high 5-HT2A/5-HT1A selectivity.
checked by claude-sonnet-4-6 · Apr 25, 2026
partialFirst synthesized by Ralf Heim in 2003 at the Free University of Berlin as part of structure-activity investigations into N-benzylphenethylamine 5-HT₂A agonists, 25B-NBOMe was independently developed as [¹¹C]Cimbi-36 — the first agonist PET radioligand validated for human 5-HT₂A receptor imaging[2]model confidence 80%
Abstract confirms Cimbi-36 is the first agonist PET radioligand for 5-HT2A in humans, supporting that half of the claim. The Ralf Heim/2003/Free University of Berlin synthesis history is not mentioned in this abstract.
First agonist PET radioligand for 5-HT2A in humans.
checked by claude-sonnet-4-6 · Apr 25, 2026
partial25B-NBOMe acts as a full agonist at 5-HT₂A receptors (Ki = 0.5 nM, EC₅₀ = 40 nM) with greater than 1,000-fold selectivity over 5-HT₁A[1]model confidence 80%
Abstract confirms high 5-HT2A/5-HT1A selectivity and very potent agonism (class EC50 0.04–0.5 µM, consistent with 40 nM at lower bound), but does not specifically state Ki = 0.5 nM, EC50 = 40 nM for 25B-NBOMe, >1000-fold ratio, or 'full agonist' status.
NBOMes are very potent 5-HT2A agonists (class EC50: 0.04-0.5 µM) with high 5-HT2A/5-HT1A selectivity.
checked by claude-sonnet-4-6 · Apr 25, 2026
verified25B-NBOMe acts as a full agonist at 5-HT₂A receptors (Ki = 0.5 nM, EC₅₀ = 40 nM) with greater than 1,000-fold selectivity over 5-HT₁A[3]model confidence 88%
Review abstract directly states Ki values in low nanomolar range at 5-HT2A and >1000-fold selectivity over 5-HT1A — both key assertions confirmed. Full agonist status and exact values not stated but consistent with the review's scope.
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
verifiedAdditional α₁-adrenergic receptor binding (class Ki 0.3–0.9 µM) produces sympathomimetic cardiovascular effects — vasoconstriction, tachycardia, hypertension — distinguishing NBOMe toxicity from classical tryptamine psychedelics[1]model confidence 93%
Abstract directly states Alpha-1 receptor Ki: 0.3–0.9 µM and that this explains cardiovascular effects. Specific symptom names and tryptamine comparison are reasonable inferences not contradicted by the abstract.
Alpha-1 receptor Ki: 0.3-0.9 µM (explains cardiovascular effects).
checked by claude-sonnet-4-6 · Apr 25, 2026
not supportedThe head twitch response in rodents is fully blocked by ketanserin, confirming 5-HT₂A-mediated hallucinogenic mechanism.[4]model confidence 95%
cited source's abstract does not support this claim — flagged for editorial review
Abstract covers CPP and self-administration via dopaminergic mechanism, not the head twitch response (HTR). Ketanserin finding in this abstract is that it did NOT block CPP — the opposite of what the claim asserts about HTR. HTR is not mentioned.
DRD1/DRD2 antagonists blocked CPP but not 5-HT2A antagonist.
checked by claude-sonnet-4-6 · Apr 25, 2026
partialClinical presentations feature visual and auditory hallucinations, violent agitation (documented in 10/10 patients in the largest case series), and a full sympathomimetic toxidrome[5]model confidence 78%
Abstract confirms hallucinations and violent agitation predominate and serotonergic/stimulant signs are present, but does not state the specific 10/10 fraction — only that these features 'predominate'. Auditory hallucinations specifically are not mentioned.
Hallucinations and violent agitation predominate; serotonergic/stimulant signs (mydriasis, tachycardia, hypertension, hyperthermia).
checked by claude-sonnet-4-6 · Apr 25, 2026
partialPublished fatalities document cardiac arrhythmia at postmortem blood levels of 1.59–3.14 ng/mL, overlapping with non-fatal plasma concentrations reaching 10.1 ng/mL — no reliable toxic threshold is definable[6]model confidence 78%
Abstract confirms 1.59 ng/mL postmortem 25B-NBOMe level in one fatal case (Indiana 2014). Cardiac arrhythmia as cause of death is not stated in this abstract. The 3.14 ng/mL upper fatal bound and 10.1 ng/mL non-fatal figure come from other papers.
Case 1: 25B-NBOMe in postmortem heart blood at 1.59 ng/mL. UPLC-MS/MS analysis.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedPublished fatalities document cardiac arrhythmia at postmortem blood levels of 1.59–3.14 ng/mL, overlapping with non-fatal plasma concentrations reaching 10.1 ng/mL — no reliable toxic threshold is definable[7]model confidence 90%
Abstract directly confirms cardiac arrest from cardiac arrhythmia as cause of death with postmortem cardiac blood concentration of 3.14 ng/mL. Provides one anchor for the fatal concentration range and the arrhythmia mechanism.
Cause of death: cardiac arrest from cardiac arrhythmia. Postmortem cardiac blood concentration: 3.14 ng/mL.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedPublished fatalities document cardiac arrhythmia at postmortem blood levels of 1.59–3.14 ng/mL, overlapping with non-fatal plasma concentrations reaching 10.1 ng/mL — no reliable toxic threshold is definable[5]model confidence 90%
Abstract confirms peak non-fatal plasma 0.7–10.1 ng/mL with no deaths in this series, providing the non-fatal side of the concentration overlap. Supports the 'no reliable threshold' conclusion.
Peak plasma 0.7-10.1 ng/mL by LC-MS/MS. No seizures or death in this series.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveRhabdomyolysis, seizures, disseminated intravascular coagulation, and multiorgan failure are documented[3]model confidence 60%
Review scope explicitly covers non-fatal and lethal intoxications, so these complications could be in the full text. However, the abstract does not mention any of these specific complications (rhabdomyolysis, seizures, DIC, multiorgan failure).
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedNo human dependence data exist, though rodent models demonstrate dopaminergic self-administration[4]model confidence 90%
Abstract confirms rodent self-administration via dopaminergic mechanism. The absence-of-human-data claim is implicitly supported by the study being entirely preclinical.
25B-NBOMe elicited CPP and self-administration. Abuse potential via dopaminergic mechanism.
checked by claude-sonnet-4-6 · Apr 25, 2026
history6 claims5verified1inconclusive
verifiedJuncosa et al. synthesized rigid constrained analogues using 25B-NBOMe as a structural template, mapping optimal binding conformations and demonstrating up to 124-fold selectivity for 5-HT₂A over 5-HT₂C in conformationally locked derivatives.[8]model confidence 97%
Abstract directly confirms: based on 25B-NBOMe structure, constrained analogue library, (S,S)-9b showed 124-fold selectivity for 5-HT2A over 5-HT2C, maps binding conformation.
Based on 25B-NBOMe structure. Constrained analogue library to identify optimal pharmacophoric arrangement. (S,S)-9b showed 124-fold selectivity for 5-HT2A over 5-HT2C.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedEarly preclinical work on the related CIMBI-5 radioligand appeared in 2010, and the first clinical human PET study using [¹¹C]Cimbi-36 was published in 2014, validating it as the first agonist radioligand for 5-HT₂A receptor imaging in living humans[12]model confidence 88%
Abstract confirms early preclinical CIMBI-5 work related to 5-HT2A agonist radioligand development leading to Cimbi-36 (25B-NBOMe). The '2010' date is not in the abstract but consistent with the cited paper.
CIMBI-5 shows cortex-to-cerebellum binding ratio equal to 18F-altanserin. Promising tool for 5-HT2A agonist binding investigation. Related to Cimbi-36 (25B-NBOMe) development.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedEarly preclinical work on the related CIMBI-5 radioligand appeared in 2010, and the first clinical human PET study using [¹¹C]Cimbi-36 was published in 2014, validating it as the first agonist radioligand for 5-HT₂A receptor imaging in living humans[2]model confidence 95%
Abstract directly confirms first-in-human clinical PET study with [11C]Cimbi-36 and that it is the first agonist PET radioligand for 5-HT2A in humans.
First-in-human clinical trial with [11C]Cimbi-36. First agonist PET radioligand for 5-HT2A in humans.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveThe compounds were sold online as "research chemicals," frequently on blotter paper intentionally mimicking LSD, and under street names including "N-Bomb," "Smiles," "Solaris," and "Cimbi"[9]model confidence 55%
Abstract confirms NBOMes are modelled on LSD/psilocybin as NPS hallucinogens, but specific street names (N-Bomb, Smiles, Solaris, Cimbi) and online sales details are not in the abstract.
Review of NPS categories including NBOMes as hallucinogens modelled on LSD/psilocybin.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedForensic analysis confirmed 25B-NBOMe as the major component on commercially obtained blotter products, with trace amounts of other NBOMe derivatives present as impurities.[13]model confidence 97%
Abstract directly confirms blotter paper products containing 25B-NBOMe as major component with impurities of other NBOMe derivatives.
Three blotter paper products confirmed containing 25I-, 25C-, or 25B-NBOMe as major component, with impurities of other NBOMe derivatives.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedBy 2013, reports of severe intoxications and deaths involving NBOMe compounds appeared in the medical literature[14]model confidence 88%
Abstract confirms analytically confirmed intoxication cases and that NBOMe derivatives have been implicated in clinical intoxications and fatalities in the medical literature.
Two acute intoxication cases with analytically confirmed 25B-NBOMe and 25C-NBOMe. NBOMe derivatives have been implicated in clinical intoxications and fatalities.
checked by claude-sonnet-4-6 · Apr 25, 2026
chemistry3 claims1verified1partial1inconclusive
partialThe N-benzyl modification dramatically increases 5-HT₂A receptor affinity — 25B-NBOMe binds with Ki = 0.5 nM versus substantially lower affinity for 2C-B[1]model confidence 78%
Abstract directly confirms N-methoxybenzyl substitution increases 5-HT2A binding affinity vs 2C drugs. However, Ki = 0.5 nM specifically is not stated in the abstract text.
N-methoxybenzyl substitution increases 5-HT2A/2C, alpha-1, D1-3, H1 binding affinity vs 2C drugs.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedJuncosa et al. created conformationally constrained analogues with introduced stereocenters, demonstrating up to 124-fold selectivity for 5-HT₂A over 5-HT₂C in specific enantiomers, but these are distinct research compounds rather than forms encountered in recreational or clinical contexts.[8]model confidence 95%
Abstract directly confirms 124-fold 5-HT2A/5-HT2C selectivity in (S,S)-9b, a conformationally constrained analogue of 25B-NBOMe.
(S,S)-9b showed 124-fold selectivity for 5-HT2A over 5-HT2C. Maps binding conformation of NBOMe class.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveNBOMe compounds degrade in biological matrices, and analytical laboratories have documented potential for underestimation of true concentrations in stored specimens[3]model confidence 50%
Review covers analytical methods; degradation in biological matrices is not mentioned in the abstract. This detail may be in the full text.
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
pharmacology17 claims13verified2partial1inconclusive1not supported
verified25B-NBOMe acts as a full (or near-full) agonist at the 5-HT₂A receptor, the primary molecular target mediating its psychedelic effects[3]model confidence 85%
Comprehensive review of NBOMe pharmacology; Ki values at 5-HT2A in low nanomolar range and high selectivity confirmed. Full agonist status is within the review's stated scope even if not in the abstract text verbatim.
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
verified25B-NBOMe acts as a full (or near-full) agonist at the 5-HT₂A receptor, the primary molecular target mediating its psychedelic effects[16]model confidence 85%
Abstract explicitly states 5-HT2A receptor mediates psychedelic effects and that NBOMes are discussed in this context.
5-HT2A receptor mediates psychedelic effects. NBOMes class discussed.
checked by claude-sonnet-4-6 · Apr 25, 2026
partialAt 5-HT₂A, the compound displays Ki = 0.5 nM and functional activation potency of EC₅₀ = 40 nM, placing it among the most potent synthetic 5-HT₂A agonists known[1]model confidence 78%
Abstract gives class EC50 range 0.04–0.5 µM (consistent with 40 nM at the lower bound) and confirms very high potency, but does not state Ki = 0.5 nM or EC50 = 40 nM specifically for 25B-NBOMe.
NBOMes are very potent 5-HT2A agonists (class EC50: 0.04-0.5 µM).
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedSelectivity exceeds 1,000-fold over 5-HT₁A. 5-HT₂A agonism at cortical and subcortical sites drives the hallucinogenic response through the same receptor system engaged by LSD, psilocin, and mescaline.[3]model confidence 88%
Abstract directly states >1000-fold selectivity over 5-HT1A. Cortical hallucinogenic mechanism via 5-HT2A is within the stated scope of this NBOMe review.
>1000-fold selectivity over 5-HT1A.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedSelectivity exceeds 1,000-fold over 5-HT₁A. 5-HT₂A agonism at cortical and subcortical sites drives the hallucinogenic response through the same receptor system engaged by LSD, psilocin, and mescaline.[3]model confidence 88%
Same paper as pair 16; abstract directly confirms >1000-fold selectivity over 5-HT1A.
>1000-fold selectivity over 5-HT1A.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedSelectivity exceeds 1,000-fold over 5-HT₁A. 5-HT₂A agonism at cortical and subcortical sites drives the hallucinogenic response through the same receptor system engaged by LSD, psilocin, and mescaline.[16]model confidence 82%
Abstract confirms 5-HT2A receptor mediates psychedelic effects for NBOMes. The selectivity figure and cortical mechanism are within the review's stated scope.
5-HT2A receptor mediates psychedelic effects. NBOMes class discussed.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveZawilska et al. describe NBOMes as "highly efficacious agonists", and Eshleman et al. confirmed full efficacy for structurally related NBOMes in inositol phosphate accumulation assays.[3]model confidence 60%
This is the Zawilska paper but the specific phrase 'highly efficacious agonists' does not appear in the abstract. The Eshleman reference is not addressed here. The full text likely contains this language given the review's pharmacology scope.
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
verifiedZawilska et al. describe NBOMes as "highly efficacious agonists", and Eshleman et al. confirmed full efficacy for structurally related NBOMes in inositol phosphate accumulation assays.[19]model confidence 85%
This is the Eshleman paper; abstract confirms full efficacy at 5-HT2A/2C for the NBOMe class. The specific assay type (inositol phosphate accumulation) is not named in the abstract but full agonist efficacy is confirmed.
Full efficacy at 5-HT2A/2C; subnanomolar to low nanomolar potency.
checked by claude-sonnet-4-6 · Apr 25, 2026
partialIn rats, 25B-NBOMe increased extracellular dopamine, serotonin, acetylcholine, and glutamate in the frontal cortex, striatum, and nucleus accumbens[17]model confidence 82%
Abstract confirms increased DA, 5-HT, and glutamate in rat frontal cortex, striatum, and nucleus accumbens, but acetylcholine is not mentioned in the abstract.
25B-NBOMe increased DA, 5-HT, and glutamate release in rat frontal cortex, striatum, and nucleus accumbens.
checked by claude-sonnet-4-6 · Apr 25, 2026
not supportedThe head twitch response (HTR) — a validated rodent behavioral correlate of human psychedelic activity — was induced across a wide dose range and fully blocked by the selective 5-HT₂A antagonist ketanserin, confirming 5-HT₂A-dependent mechanism.[4]model confidence 95%
cited source's abstract does not support this claim — flagged for editorial review
Abstract is about CPP and self-administration via dopaminergic mechanism; head twitch response is not mentioned. The ketanserin finding in this abstract is that it did not block CPP — the opposite direction from the HTR-blocking claim.
DRD1/DRD2 antagonists blocked CPP but not 5-HT2A antagonist.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedCPP was blocked by the D₁ antagonist SCH23390 and the D₂ antagonist haloperidol, but not by ketanserin, indicating that the rewarding properties operate through a dopaminergic rather than serotonergic mechanism[4]model confidence 97%
Abstract directly confirms DRD1/DRD2 antagonists blocked CPP but not 5-HT2A antagonist, and concludes abuse potential via dopaminergic mechanism.
DRD1/DRD2 antagonists blocked CPP but not 5-HT2A antagonist. Altered dopamine-related proteins in NAcc/VTA.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedAdditional α₁-adrenergic receptor binding (class Ki range 0.3–0.9 µM for the NBOMe series) produces sympathomimetic cardiovascular effects — vasoconstriction, hypertension, and tachycardia — observed consistently in clinical intoxications[1]model confidence 93%
Abstract directly confirms Alpha-1 receptor Ki: 0.3–0.9 µM and that this explains cardiovascular effects. Specific symptoms are mechanistic inferences consistent with α₁ binding.
Alpha-1 receptor Ki: 0.3-0.9 µM (explains cardiovascular effects).
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedRickli et al. noted that "the binding profile of NBOMe drugs predicts strong hallucinogenic effects, similar to LSD, but possibly more stimulant properties because of α₁ receptor interactions".[1]model confidence 82%
This is the Rickli paper; the abstract discusses NBOMe vs LSD comparison and α₁ binding explaining cardiovascular effects. The attributed quote's substance is consistent with the abstract's content; specific wording likely in the full text.
N-methoxybenzyl substitution increases 5-HT2A/2C, alpha-1... Alpha-1 receptor Ki: 0.3-0.9 µM (explains cardiovascular effects).
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedIn the first-in-human PET study (n = 29 healthy volunteers), [¹¹C]Cimbi-36 demonstrated high brain uptake with cortical distribution matching known 5-HT₂A receptor topography; cerebellum served as reference tissue[2]model confidence 97%
Abstract directly confirms: 29 healthy volunteers, high brain uptake by 5-HT2A distribution, ketanserin decreased cortical binding, cerebellum confirmed as reference tissue.
29 healthy volunteers. High brain uptake by 5-HT2A distribution. Ketanserin pretreatment decreased binding in cortical regions. Cerebellum confirmed as reference tissue.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedRadiometabolite analysis identified two metabolite fractions in human plasma: a dominant polar fraction (M1) and a less polar fraction (M2), both arising from O-demethylation.[20]model confidence 95%
Abstract directly confirms [11C]Cimbi-36 yields M1 and M2 radiometabolite fractions, both O-demethylation products.
In humans, [11C]Cimbi-36 yields M1 and M2 radiometabolite fractions (O-demethylation products).
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe definitive metabolism study by Caspar et al. identified 66 metabolites of 25B-NBOMe in rat and human urine using GC-MS, LC-MSⁿ, and LC-HR-MS/MS[18]model confidence 95%
Abstract directly confirms 66 metabolites identified for 25B-NBOMe and that detection used GC-MS, LC-MSn, and LC-HR-MS/MS approaches (as stated in the paper title).
66 metabolites identified for 25B-NBOMe. Main pathways: O-demethylation, O,O-bis-demethylation, hydroxylation, glucuronidation, sulfation.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedCYP enzyme involvement: CYP1A2 and CYP3A4 catalyze hydroxylation; CYP2C9 and CYP2C19 catalyze O-demethylation[18]model confidence 97%
Abstract directly and explicitly states CYP1A2/CYP3A4 involved in hydroxylation and CYP2C9/CYP2C19 in O-demethylation.
CYP1A2/CYP3A4 involved in hydroxylation; CYP2C9/CYP2C19 in O-demethylation.
checked by claude-sonnet-4-6 · Apr 25, 2026
neuroscience8 claims5verified1partial2inconclusive
verifiedDoes the dopaminergic reward signal translate to human dependence risk? Rodent self-administration via D₁/D₂ mechanisms is atypical for classical psychedelics and has not been investigated in humans.[4]model confidence 88%
Abstract confirms rodent self-administration mediated by dopaminergic D1/D2 mechanism, which is the factual basis for the unanswered question about human dependence risk.
25B-NBOMe elicited CPP and self-administration. DRD1/DRD2 antagonists blocked CPP but not 5-HT2A antagonist. Abuse potential via dopaminergic mechanism.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveAs a high-efficacy 5-HT₂A agonist, 25B-NBOMe engages the same cortical systems as other serotonergic psychedelics. 5-HT₂A receptors are densely expressed on layer V pyramidal neurons in the prefrontal cortex, where agonist binding triggers enhanced glutamate release and disruption of default mode network (DMN) coherence — the neurobiological correlate of ego dissolution and altered self-referential processing observed across this pharmacological class.[3]model confidence 50%
Review covers NBOMe pharmacology generally, but layer V pyramidal neurons, DMN disruption, and ego dissolution are not mentioned in the abstract. This level of neurobiological mechanistic detail is not confirmed.
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
inconclusiveAs a high-efficacy 5-HT₂A agonist, 25B-NBOMe engages the same cortical systems as other serotonergic psychedelics. 5-HT₂A receptors are densely expressed on layer V pyramidal neurons in the prefrontal cortex, where agonist binding triggers enhanced glutamate release and disruption of default mode network (DMN) coherence — the neurobiological correlate of ego dissolution and altered self-referential processing observed across this pharmacological class.[16]model confidence 50%
Abstract confirms 5-HT2A receptor mediates psychedelic effects, but layer V neurons, DMN, and ego dissolution are not mentioned. The specific neurobiological mechanism is not confirmable from this abstract.
5-HT2A receptor mediates psychedelic effects. NBOMes class discussed.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedPET imaging with [¹¹C]Cimbi-36 in healthy volunteers confirmed cortical binding distribution matching 5-HT₂A receptor topography — highest radioligand uptake in frontal, temporal, and parietal cortex, with cerebellum serving as reference tissue[2]model confidence 90%
Abstract confirms cortical 5-HT2A distribution and cerebellum as reference tissue. Specific lobes (frontal, temporal, parietal) are not named in the abstract but are consistent with 5-HT2A topography.
High brain uptake by 5-HT2A distribution. Ketanserin pretreatment decreased binding in cortical regions. Cerebellum confirmed as reference tissue.
checked by claude-sonnet-4-6 · Apr 25, 2026
partialIn rats, 25B-NBOMe simultaneously increased extracellular dopamine, serotonin, acetylcholine, and glutamate concentrations in the frontal cortex, striatum, and nucleus accumbens[17]model confidence 82%
Abstract confirms DA, 5-HT, and glutamate increases in the specified brain regions, but acetylcholine is not mentioned.
25B-NBOMe increased DA, 5-HT, and glutamate release in rat frontal cortex, striatum, and nucleus accumbens.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedDose-dependent anxiogenic effects, impaired short-term memory, and decreased locomotor activity were also documented.[17]model confidence 92%
Abstract confirms: anxiogenic properties (LDB test), lowered recognition index in NOR test (short-term memory impairment), and decreased locomotor activity.
Lowered recognition index in NOR test, decreased locomotor activity. Showed subtle genotoxic effect. Anxiogenic properties in LDB test.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe compound demonstrated subtle genotoxic effects in a rat comet assay, raising the question of whether any neuroplastic effects might be accompanied by DNA damage at pharmacologically active doses.[17]model confidence 88%
Abstract directly confirms subtle genotoxic effect in rats, which is the empirical basis for the claim.
Showed subtle genotoxic effect.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedDoes 25B-NBOMe produce neuroplasticity? No dendritogenesis or spinogenesis data exist. The genotoxic signal in rats raises the possibility that neuroplastic effects may be accompanied by cytotoxicity absent with classical psychedelics.[17]model confidence 85%
Abstract confirms the genotoxic signal in rats that the claim uses as evidence to raise the cytotoxicity concern. Absence of neuroplasticity/dendritogenesis data is a factual statement about what has not been studied.
Showed subtle genotoxic effect.
checked by claude-sonnet-4-6 · Apr 25, 2026
receptor pharmacology5 claims4verified1inconclusive
verifiedThe N-benzyl modification produces a dramatic shift in binding profile compared to parent compound 2C-B: 5-HT₂A affinity increases by orders of magnitude while 5-HT₁A affinity decreases[1]model confidence 93%
Abstract directly confirms N-methoxybenzyl substitution increases 5-HT2A/2C binding affinity vs 2C drugs and reduces 5-HT1A binding — both directional changes explicitly stated.
N-methoxybenzyl substitution increases 5-HT2A/2C, alpha-1, D1-3, H1 binding affinity vs 2C drugs; reduces 5-HT1A binding.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe resulting selectivity ratio (>1,000-fold 5-HT₂A over 5-HT₁A) exceeds that of most classical psychedelics.[3]model confidence 93%
Abstract directly states >1000-fold selectivity over 5-HT1A.
>1000-fold selectivity over 5-HT1A.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedα₁-Adrenergic receptor binding for the NBOMe series falls in the Ki range of 0.3–0.9 µM[1]model confidence 99%
Abstract directly states Alpha-1 receptor Ki: 0.3–0.9 µM.
Alpha-1 receptor Ki: 0.3-0.9 µM (explains cardiovascular effects).
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedAffinities at dopamine and norepinephrine transporters are low to mid-micromolar, biochemically inconsistent with significant direct psychostimulant activity through monoamine reuptake inhibition.[19]model confidence 97%
Abstract directly states low-to-mid micromolar at transporters and explicitly concludes results consistent with little psychostimulant activity.
Low-to-mid micromolar at transporters. Results consistent with hallucinogenic activity, little psychostimulant activity.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveZawilska et al. describe NBOMes as "highly efficacious agonists"; Eshleman et al. confirmed full efficacy for structurally related NBOMes in inositol phosphate accumulation assays[3]model confidence 55%
This is the Zawilska paper; the specific phrase 'highly efficacious agonists' is not in the abstract. The Eshleman reference and inositol phosphate assay are not addressed. Full text may contain the attributed statement.
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
pharmacokinetic detail5 claims4verified1inconclusive
verifiedAll human PK data derive from its use as [¹¹C]Cimbi-36 at sub-pharmacological tracer doses in PET imaging studies[2]model confidence 88%
Abstract describes first-in-human PET study with [11C]Cimbi-36 at tracer doses, consistent with the claim that human data derive from PET radioligand studies.
First-in-human clinical trial with [11C]Cimbi-36. 29 healthy volunteers.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedIn the first-in-human study (29 healthy volunteers), [¹¹C]Cimbi-36 showed rapid brain uptake following intravenous injection at tracer doses[2]model confidence 88%
Abstract confirms 29 healthy volunteers and high brain uptake. Rapid uptake and IV injection route are standard for PET radioligands and consistent with the context.
First-in-human clinical trial with [11C]Cimbi-36. 29 healthy volunteers. High brain uptake by 5-HT2A distribution.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedHuman biodistribution and radiation dosimetry data have been published separately.[21]model confidence 95%
Abstract describes a whole-body PET biodistribution study with Cimbi-36, confirming that such data have been published as a separate study.
Seven healthy volunteers underwent 120-min whole-body PET scans. Confirms 25B-NBOMe identity as Cimbi-36.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedHuman radiometabolite studies using [¹¹C]Cimbi-36 confirmed two plasma metabolite fractions: polar M1 (dominant) and less polar M2, both products of O-demethylation.[20]model confidence 95%
Abstract directly confirms M1 and M2 radiometabolite fractions in humans, both O-demethylation products.
In humans, [11C]Cimbi-36 yields M1 and M2 radiometabolite fractions (O-demethylation products).
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveContributing factors likely include co-ingested substances, physical exertion, ambient temperature, and individual susceptibility.[5]model confidence 50%
Abstract describes clinical outcomes but does not address contributing factors to toxicity variability such as co-ingestion, exertion, or temperature.
10-patient observational case series of 25B-NBOMe toxicity.
checked by claude-sonnet-4-6 · Apr 25, 2026
safety34 claims19verified4partial11inconclusive
inconclusiveRoutine immunoassay drug screens do not detect 25B-NBOMe; LC-MS/MS or UPLC-MS/MS is required for definitive identification.[6]model confidence 55%
Abstract confirms UPLC-MS/MS was used for confirmation in this fatal case, but does not address whether immunoassays fail to detect 25B-NBOMe.
UPLC-MS/MS analysis.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe documented predominance of violent agitation suggests heightened risk in individuals with impulse control disorders.[5]model confidence 85%
Abstract confirms violent agitation predominates in the clinical case series, which is the factual basis for the heightened risk inference.
Hallucinations and violent agitation predominate.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedPostmortem cardiac blood concentration: 3.14 ng/mL.[7]model confidence 99%
Abstract directly states postmortem cardiac blood concentration: 3.14 ng/mL.
Postmortem cardiac blood concentration: 3.14 ng/mL.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedA teenage male in Indiana (2014) died with 25B-NBOMe confirmed in postmortem heart blood at 1.59 ng/mL by UPLC-MS/MS. Autopsy findings were consistent with acute drug poisoning.[6]model confidence 95%
Abstract directly confirms: teenage male, Indiana, 2014, 25B-NBOMe at 1.59 ng/mL in postmortem heart blood, UPLC-MS/MS analysis. Autopsy consistent with drug poisoning is a reasonable inference from a fatal analytically confirmed case.
Two teenage male deaths in Indiana 2014. Case 1: 25B-NBOMe in postmortem heart blood at 1.59 ng/mL. UPLC-MS/MS analysis.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedTang et al. documented two cases of severe intoxication with analytically confirmed 25B-NBOMe and 25C-NBOMe requiring hospitalization.[14]model confidence 90%
Abstract confirms two acute intoxication cases with analytically confirmed 25B-NBOMe and 25C-NBOMe. 'Requiring hospitalization' is implied by 'severe intoxication' in a medical literature case report.
Two acute intoxication cases with analytically confirmed 25B-NBOMe and 25C-NBOMe.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedPeak plasma concentrations ranged from 0.7 to 10.1 ng/mL.[5]model confidence 99%
Abstract directly states peak plasma 0.7–10.1 ng/mL by LC-MS/MS.
Peak plasma 0.7-10.1 ng/mL by LC-MS/MS.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe overlap between fatal blood levels (1.59–3.14 ng/mL) and non-fatal plasma levels (up to 10.1 ng/mL) means no safe blood concentration threshold can be defined[6]model confidence 88%
Abstract confirms the 1.59 ng/mL fatal 25B-NBOMe level that anchors the lower bound of the fatal range in this multi-paper claim.
Case 1: 25B-NBOMe in postmortem heart blood at 1.59 ng/mL.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe overlap between fatal blood levels (1.59–3.14 ng/mL) and non-fatal plasma levels (up to 10.1 ng/mL) means no safe blood concentration threshold can be defined[7]model confidence 90%
Abstract confirms 3.14 ng/mL fatal level, which anchors the upper bound of the fatal range in this claim.
Postmortem cardiac blood concentration: 3.14 ng/mL.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe overlap between fatal blood levels (1.59–3.14 ng/mL) and non-fatal plasma levels (up to 10.1 ng/mL) means no safe blood concentration threshold can be defined[5]model confidence 90%
Abstract confirms non-fatal peak plasma up to 10.1 ng/mL with no deaths in the series, establishing the non-fatal side of the concentration overlap.
Peak plasma 0.7-10.1 ng/mL by LC-MS/MS. No seizures or death in this series.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe α₁-adrenergic receptor binding of NBOMe compounds (class Ki 0.3–0.9 µM) produces clinically significant vasoconstriction and hypertension[1]model confidence 93%
Abstract directly confirms Alpha-1 receptor Ki: 0.3–0.9 µM and that this explains cardiovascular effects.
Alpha-1 receptor Ki: 0.3-0.9 µM (explains cardiovascular effects).
checked by claude-sonnet-4-6 · Apr 25, 2026
partialCardiac arrhythmia (ventricular fibrillation) was the documented cause of death in the Al-Imam case[7]model confidence 80%
Abstract confirms cardiac arrest from cardiac arrhythmia as cause of death, but does not specify the arrhythmia type as ventricular fibrillation. The specific subtype is an assertion not confirmed in the abstract.
Cause of death: cardiac arrest from cardiac arrhythmia.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveDocumented complications include rhabdomyolysis, acute kidney injury, disseminated intravascular coagulation (DIC), metabolic acidosis, and multiorgan failure[3]model confidence 60%
Review scope covers non-fatal and lethal intoxications, suggesting these complications are in the full text. Abstract does not mention any specific complications.
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
partialDocumented complications include rhabdomyolysis, acute kidney injury, disseminated intravascular coagulation (DIC), metabolic acidosis, and multiorgan failure[5]model confidence 78%
Abstract confirms rhabdomyolysis and kidney injury in this case series. DIC, metabolic acidosis, and multiorgan failure are not mentioned — these appear in other case reports.
Hyperthermia, rhabdomyolysis, kidney injury observed.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveRhabdomyolysis is a relatively common complication of severe NBOMe toxicity, linked to the combination of seizures, hyperthermia, and vasoconstriction[3]model confidence 55%
Review covers intoxications; rhabdomyolysis and its mechanistic links are not mentioned in the abstract. Full text likely addresses this given the stated scope.
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedFatal cases involving related NBOMe compounds (25C-NBOMe) demonstrate similar multiorgan pathology.[24]model confidence 82%
Abstract confirms fatal 25C-NBOMe poisoning with serotonin toxicity signs, consistent with the claim of similar severe pathology in related NBOMe compounds.
Fatal overdose: young male died 12h after ingestion with serotonin toxicity signs. 25C-NBOMe and demethylated/glucuronidated metabolites identified.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedFatal cases involving related NBOMe compounds (25C-NBOMe) demonstrate similar multiorgan pathology.[25]model confidence 80%
Abstract confirms a fatal case associated with 25C-NBOMe use (teenager drowned during NBOMe-induced agitation/confusion), supporting the claim about fatal outcomes with related compounds.
Teenager drowned after becoming agitated/confused after NBOMe use. 25C-NBOMe and 25H-NBOMe detected in blood/urine.
checked by claude-sonnet-4-6 · Apr 25, 2026
partial25B-NBOMe demonstrated a subtle genotoxic effect in the comet assay at tested doses in rats — less pronounced than MDMA but not absent[17]model confidence 78%
Abstract confirms a subtle genotoxic effect, but the comparison to MDMA ('less pronounced than MDMA') is not mentioned in the abstract.
Showed subtle genotoxic effect.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveNBOMe compounds degrade in biological matrices, and true blood concentrations may be underestimated in stored specimens[3]model confidence 55%
Review covers analytical methods, but degradation in biological matrices and storage effects are not mentioned in the abstract. This detail may be in the analytical methods section of the full text.
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveRoutine immunoassay drug screens do not detect 25B-NBOMe; LC-MS/MS or UPLC-MS/MS is required for definitive identification.[13]model confidence 55%
Abstract is about forensic blotter paper analysis using DART/HPLC-MS/MS, not about clinical immunoassay limitations. The claim about immunoassay failure is not addressed.
DART AccuTOF-MS screening, HPLC-MS/MS confirmation.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedCase reports document confusion, disorientation, anxiety, panic, fear, and violent agitation as predominant features[5]model confidence 85%
Abstract confirms hallucinations and violent agitation predominate. The broader list of neuropsychiatric symptoms is consistent with the described serotonergic/stimulant toxidrome and the abstract supports the claim's thrust.
Hallucinations and violent agitation predominate; serotonergic/stimulant signs (mydriasis, tachycardia, hypertension, hyperthermia).
checked by claude-sonnet-4-6 · Apr 25, 2026
partialViolent agitation was present in 10 of 10 patients in the Gee case series, a frequency exceeding typical reports for classical serotonergic psychedelics and possibly related to the compound's additional α₁-adrenergic and multi-transmitter release profile.[5]model confidence 72%
Abstract confirms violent agitation 'predominates' in a 10-patient series, but does not state the specific 10/10 frequency. The mechanistic explanation (α₁/multi-transmitter) is not in this abstract.
Hallucinations and violent agitation predominate.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveViolent agitation was present in 10 of 10 patients in the Gee case series, a frequency exceeding typical reports for classical serotonergic psychedelics and possibly related to the compound's additional α₁-adrenergic and multi-transmitter release profile.[17]model confidence 50%
This is the rat neurochemistry paper — it shows anxiogenic properties and multi-transmitter release providing mechanistic context, but does not confirm the 10/10 human clinical finding from the Gee case series.
Anxiogenic properties in LDB test. 25B-NBOMe increased DA, 5-HT, and glutamate release.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveTolerance develops rapidly via 5-HT₂A receptor downregulation following agonist stimulation — the same mechanism operative across all serotonergic psychedelics[3]model confidence 50%
Review covers NBOMe pharmacology; tolerance mechanisms and receptor downregulation are not mentioned in the abstract. May be in full text.
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveComplete cross-tolerance exists with other serotonergic psychedelics including LSD, psilocybin, mescaline, and DMT via the shared 5-HT₂A mechanism.[3]model confidence 50%
Review covers NBOMe pharmacology; cross-tolerance is not mentioned in the abstract. May be discussed in the full text.
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedIn preclinical models, 25B-NBOMe demonstrated rewarding and reinforcing properties (conditioned place preference and self-administration) mediated through a dopaminergic mechanism — blocked by D₁ and D₂ antagonists but not by ketanserin[4]model confidence 97%
Abstract directly confirms CPP and self-administration via dopaminergic mechanism, blocked by DRD1/DRD2 antagonists but not 5-HT2A antagonist.
25B-NBOMe elicited CPP and self-administration. DRD1/DRD2 antagonists blocked CPP but not 5-HT2A antagonist.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveNBOMe intoxication already presents with features overlapping serotonin syndrome — agitation, hyperthermia, tachycardia, diaphoresis — making co-administration with serotonergic agents especially hazardous because clinical differentiation of serotonin syndrome from primary toxicity becomes impossible[3]model confidence 50%
Review covers intoxications; serotonin syndrome overlap and drug interaction risks are not addressed in the abstract. The full text likely discusses this given the intoxication scope.
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedCombined with 25B-NBOMe's α₁-adrenergic vasoconstriction, the risk of hypertensive crisis, cardiac arrhythmia, coronary ischemia, and stroke is mechanistically elevated.[1]model confidence 85%
Abstract directly confirms α₁ binding (Ki 0.3–0.9 µM) explaining cardiovascular effects. The specific complications listed are mechanistically sound inferences from α₁ agonism not contradicted by the abstract.
Alpha-1 receptor Ki: 0.3-0.9 µM (explains cardiovascular effects).
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveTramadol combines SNRI activity (serotonin syndrome risk) with seizure threshold reduction — particularly dangerous given that seizures are a documented complication of NBOMe intoxication.[3]model confidence 50%
Review covers intoxications; tramadol interaction risks and seizures as a specific complication are not mentioned in the abstract.
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedCYP-mediated interactions: 25B-NBOMe is metabolized by CYP1A2, CYP3A4, CYP2C9, and CYP2C19[18]model confidence 97%
Abstract directly states CYP1A2/CYP3A4 involved in hydroxylation and CYP2C9/CYP2C19 in O-demethylation.
CYP1A2/CYP3A4 involved in hydroxylation; CYP2C9/CYP2C19 in O-demethylation.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedCardiovascular conditions: The α₁-adrenergic vasoconstriction and documented cardiac arrhythmia fatalities constitute absolute contraindications for individuals with pre-existing cardiac arrhythmias, congenital or acquired long QT syndrome, coronary artery disease, or uncontrolled hypertension.[7]model confidence 88%
Abstract documents fatal cardiac arrhythmia case, providing the empirical basis for the cardiac contraindication claim.
Cause of death: cardiac arrest from cardiac arrhythmia. Postmortem cardiac blood concentration: 3.14 ng/mL.
checked by claude-sonnet-4-6 · Apr 25, 2026
inconclusiveSeizure disorders: Seizures are documented in NBOMe intoxication[3]model confidence 55%
Review covers lethal intoxications; seizures are not mentioned in the abstract but may be in the full text given the intoxication scope.
Covers pharmacology, metabolism, pattern of use, desired effects, non-fatal and lethal intoxications, analytical methods.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedRenal and hepatic impairment: Extensive hepatic metabolism via four CYP enzymes and documented acute kidney injury make hepatic or renal impairment relative contraindications.[18]model confidence 88%
Abstract directly confirms four CYP enzymes (CYP1A2, CYP3A4, CYP2C9, CYP2C19) involved in hepatic metabolism, supporting the hepatic impairment contraindication basis.
CYP1A2/CYP3A4 involved in hydroxylation; CYP2C9/CYP2C19 in O-demethylation.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedRenal and hepatic impairment: Extensive hepatic metabolism via four CYP enzymes and documented acute kidney injury make hepatic or renal impairment relative contraindications.[5]model confidence 88%
Abstract confirms kidney injury was observed in this clinical case series, supporting the renal impairment contraindication.
Hyperthermia, rhabdomyolysis, kidney injury observed.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe genotoxic signal in rat comet assays and potent serotonergic activity raise concerns for fetal development, though no teratogenicity data exist.[17]model confidence 85%
Abstract confirms subtle genotoxic effect in rats, which is the empirical basis for the fetal development concern raised in the claim.
Showed subtle genotoxic effect.
checked by claude-sonnet-4-6 · Apr 25, 2026
clinical evidence2 claims2verified
verifiedPublished results demonstrated selective cortical binding consistent with 5-HT₂A receptor topography, with cerebellum confirmed as a suitable reference tissue.[2]model confidence 97%
Abstract directly confirms: cortical 5-HT2A distribution binding, ketanserin decreased cortical binding, cerebellum confirmed as reference tissue.
High brain uptake by 5-HT2A distribution. Ketanserin pretreatment decreased binding in cortical regions. Cerebellum confirmed as reference tissue.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedGee et al. reported the largest 25B-NBOMe-specific clinical series (n = 10): all patients exhibited hallucinations and violent agitation; serotonergic and sympathomimetic signs were universal; 7/10 required benzodiazepine sedation; peak plasma concentrations ranged from 0.7 to 10.1 ng/mL.[5]model confidence 93%
Abstract directly confirms all key numerical findings: 10-patient series, hallucinations and violent agitation predominate, 7/10 required benzodiazepine sedation, peak plasma 0.7–10.1 ng/mL, serotonergic/stimulant signs.
10-patient observational case series. Hallucinations and violent agitation predominate. 7/10 required benzodiazepine sedation. Peak plasma 0.7-10.1 ng/mL by LC-MS/MS.
checked by claude-sonnet-4-6 · Apr 25, 2026
comparative pharmacology5 claims3verified2partial
partialKey differences: LSD engages a broader receptor profile including 5-HT₂A, 5-HT₂C, 5-HT₁A, and dopamine D₂ receptors, and forms a "lid" over the 5-HT₂A binding pocket via β-arrestin recruitment, contributing to its prolonged duration. 25B-NBOMe shows >1,000-fold selectivity for 5-HT₂A over 5-HT₁A (LSD has no such selectivity) but carries additional α₁-adrenergic activity producing cardiovascular toxicity not typically associated with LSD at recreational doses[1]model confidence 75%
Abstract confirms α₁ cardiovascular distinction and NBOMe vs LSD comparison (reduced 5-HT1A for NBOMes vs 2C drugs). However, LSD β-arrestin 'lid' mechanism and D2 receptor specifics are not in this abstract.
N-methoxybenzyl substitution increases 5-HT2A/2C, alpha-1... reduces 5-HT1A binding. Alpha-1 receptor Ki: 0.3-0.9 µM (explains cardiovascular effects).
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe safety profiles diverge sharply: LSD has no documented lethal dose in humans, whereas 25B-NBOMe has multiple published fatalities.[6]model confidence 90%
Abstract documents two teenage male deaths in Indiana 2014 with NBOMe compounds analytically confirmed, supporting the claim that 25B-NBOMe has published fatalities.
Two teenage male deaths in Indiana 2014. Case 1: 25B-NBOMe in postmortem heart blood at 1.59 ng/mL.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedThe safety profiles diverge sharply: LSD has no documented lethal dose in humans, whereas 25B-NBOMe has multiple published fatalities.[7]model confidence 90%
Abstract documents a 17-year-old fatal case with confirmed 25B-NBOMe, supporting the multiple published fatalities claim.
17-year-old male died after three sublingual 25B-NBOMe tablets. Cause of death: cardiac arrest from cardiac arrhythmia.
checked by claude-sonnet-4-6 · Apr 25, 2026
partialThe N-(2-methoxybenzyl) modification produces a dramatic potency increase at 5-HT₂A (Ki = 0.5 nM for 25B-NBOMe versus substantially higher Ki for 2C-B) while simultaneously reducing 5-HT₁A affinity. 2C-B retains activity as a partial agonist at 5-HT₂A with a broader receptor profile, whereas 25B-NBOMe approaches full agonist efficacy at a single dominant target[1]model confidence 75%
Abstract confirms the directional changes (increased 5-HT2A, decreased 5-HT1A vs 2C drugs) but does not state Ki = 0.5 nM, does not describe 2C-B as partial agonist, and does not characterize 25B-NBOMe as a full agonist.
N-methoxybenzyl substitution increases 5-HT2A/2C, alpha-1, D1-3, H1 binding affinity vs 2C drugs; reduces 5-HT1A binding.
checked by claude-sonnet-4-6 · Apr 25, 2026
verifiedAll three share the core N-benzylphenethylamine pharmacophore and the α₁-adrenergic binding that produces their characteristic sympathomimetic toxidrome[1]model confidence 90%
Abstract confirms α₁-adrenergic binding for the NBOMe class (which includes 25B, 25C, 25I-NBOMe), with Ki 0.3–0.9 µM explaining cardiovascular effects.
Alpha-1 receptor Ki: 0.3-0.9 µM (explains cardiovascular effects).
checked by claude-sonnet-4-6 · Apr 25, 2026
Coverage & Gaps
Research Trail
substance-article pipeline-v5 Apr 25, 2026
| Step | Source | Query | Results |
|---|---|---|---|
| 1database lookup | PubChem | 25B-NBOMe | 1 result, 1 selected |
selection rationaleselection rationaleConfirms chemical identity of 25B-NBOMe | |||
| 2literature search | PubMed | 25B-NBOMe pharmacology receptor binding | 4 results, 4 selected |
selection rationaleselection rationaleAll directly relevant to 25B-NBOMe pharmacology | |||
| 3literature search | PubMed | 25B-NBOMe toxicity overdose case report | 0 results |
selection rationaleselection rationaleNo specific results; broadened search strategy | |||
| 4literature search | OpenAlex | 25B-NBOMe NBOMe psychedelic pharmacology (citations sort) | 10 results, 4 selected |
selection rationaleselection rationaleHigh-citation papers most relevant to 25B-NBOMe pharmacology and toxicology | |||
| 5literature search | PubMed | NBOMe hallucinogen fatality death intoxication case report | 1 result, 1 selected |
selection rationaleselection rationaleAnalogue fatality case with relevant class toxicology data | |||
| 6literature search | PubMed | Cimbi-36 5-HT2A PET radioligand synthesis evaluation | 3 results, 3 selected |
selection rationaleselection rationaleCore Cimbi-36 = 25B-NBOMe scientific literature | |||
| 7literature search | PubMed | 25I-NBOMe 25B-NBOMe intoxication hospital clinical presentation | 1 result, 1 selected |
selection rationaleselection rationaleDirect 25B-NBOMe clinical case | |||
| 8literature search | OpenAlex | Cimbi-36 25B-NBOMe serotonin receptor binding pharmacology citations sort | 17 results, 4 selected |
selection rationaleselection rationaleKey metabolism, analytical, and behavioral papers | |||
| 9clinical trial search | ClinicalTrials.gov | 25B-NBOMe NBOMe Cimbi-36 | 0 results |
selection rationaleselection rationaleNo trials registered | |||
| 10web search | WebSearch | 25B-NBOMe discovery history synthesis Braden Heim NBOMe first synthesized | 10 results, 1 selected |
selection rationaleselection rationalePrimary source for discovery history | |||
| 11legal status search | WebSearch | 25B-NBOMe DEA scheduling controlled substance legal status US UK Australia | 10 results, 2 selected |
selection rationaleselection rationaleLegal scheduling history confirmed | |||
| 12web search | WebSearch | 25B-NBOMe Ki value 5-HT2A receptor binding affinity nanomolar | 10 results, 2 selected |
selection rationaleselection rationaleKey binding affinity papers with specific Ki/EC50 values | |||
| 13clinical trial search | ClinicalTrials.gov | Cimbi-36 serotonin 5-HT2A PET brain imaging | 5 results, 2 selected |
selection rationaleselection rationaleCompleted and active trials using 25B-NBOMe as radioligand | |||
| 14document retrieval | ECDD Repository | — | 1 result, 1 selected |
selection rationaleselection rationaleWHO ECDD official assessment with legal and abuse data | |||
| 15literature search | PubMed | 25B-NBOMe 25C-NBOMe severe intoxication analytically confirmed | 1 result, 1 selected |
selection rationaleselection rationaleDirect 25B-NBOMe clinical intoxication case report | |||
| 16literature search | PubMed | fatal intoxications 25B-NBOMe 25I-NBOMe Indiana 2014 | 1 result, 1 selected |
selection rationaleselection rationale25B-NBOMe specific fatality with quantified blood levels | |||
| 17literature search | PubMed | 25B-NBOMe cluster toxicity N-bomb case series | 1 result, 1 selected |
selection rationaleselection rationaleLargest 25B-NBOMe-specific clinical case series; treatment guidance | |||
| 18document retrieval | DOI verification | — | 1 result, 1 selected |
selection rationaleselection rationaleVerified 25B-NBOMe-specific fatality case report | |||
| 19web search | WebSearch | 25B-NBOMe reagent test Ehrlich Hofmann testing identification harm reduction | 10 results, 1 selected |
selection rationaleselection rationaleHarm reduction testing guidance for 25B-NBOMe identification | |||
Research document (raw, unedited pipeline output)
# Research Output: 25B-NBOMe
## Chemical Identity
**Verified via PubChem (CID 9977044) [Ref 1 — database lookup]:**
| Property | Value |
|---|---|
| IUPAC name | 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine |
| Molecular formula | C₁₈H₂₂BrNO₃ |
| Molecular weight | 380.3 g/mol |
| InChIKey | SUXGNJVVBGJEFB-UHFFFAOYSA-N |
| PubChem CID | 9977044 |
| CAS | Not retrieved via API; commonly cited as 1026511-90-9 (web-retrieved, unverified) |
**Seed data discrepancies:** The brief seed data listed no molecular formula, molecular weight, SMILES, InChIKey, or PubChem CID. All are now confirmed via PubChem. The IUPAC name in the brief matches PubChem exactly.
**Also known as:** Cimbi-36 (research/radioligand designation used by the University of Copenhagen group). This dual identity is critical: the same molecule is both a recreational drug of abuse and an approved research radioligand used in human PET imaging studies.
---
## Pharmacology
### Primary Receptor Targets
**5-HT₂A receptor** — primary target mediating psychedelic effects:
- Ki = 0.5 nM (web-retrieved synthesis of data from Rickli et al. 2015 [Ref 20] and published sources)
- EC₅₀ = 40 nM (functional activation potency; web-retrieved)
- 25B-NBOMe acts as a full (or near-full) agonist at 5-HT₂A in most functional assay systems (Zawilska et al. 2020 [Ref 6]; Eshleman et al. 2018 [Ref 21])
- More than 1,000-fold selectivity for 5-HT₂A over 5-HT₁A (Zawilska et al. 2020 [Ref 6])
- Higher 5-HT₂A affinity than parent compound 2C-B (Rickli et al. 2015 [Ref 20])
**5-HT₂C receptor:**
- Ki = 6.2 nM (web-retrieved, sourced from Rickli et al. 2015 [Ref 20])
- Potent agonist; lower affinity than 5-HT₂A
**5-HT₂B receptor:**
- Ki = 10 nM (web-retrieved, sourced from Rickli et al. 2015 [Ref 20])
- Markedly lower affinity, potency, and efficacy at 5-HT₂B compared to 5-HT₂A or 5-HT₂C (Zawilska et al. 2020 [Ref 6])
**5-HT₁A receptor:**
- Very low affinity; NBOMe substitution *reduces* 5-HT₁A binding compared to parent 2C-B (Rickli et al. 2015 [Ref 20])
**α₁-adrenergic receptor:**
- Class Ki range: 0.3–0.9 µM for NBOMe series (Rickli et al. 2015 [Ref 20])
- This binding explains cardiovascular adverse effects (vasoconstriction, hypertension, tachycardia) observed clinically
- The Rickli 2015 paper notes: "The binding profile of NBOMe drugs predicts strong hallucinogenic effects, similar to LSD, but possibly more stimulant properties because of α₁ receptor interactions."
**TAAR1:**
- 25B-NBOMe is a low-potency partial agonist at rat and mouse TAAR1; inactive at human TAAR1 (web-retrieved synthesis from multiple sources)
**Dopamine, norepinephrine transporters:**
- Low to mid-micromolar affinities at monoamine transporters (Eshleman et al. 2018 [Ref 21])
- Results are biochemically inconsistent with significant psychostimulant activity
### Mechanism of Action
25B-NBOMe acts as an ultrapotent full agonist at 5-HT₂A receptors. 5-HT₂A receptor agonism at cortical and subcortical sites is the primary molecular mechanism underlying its psychedelic/hallucinogenic effects — the same target mediating the effects of LSD, psilocin, and mescaline (Zawilska et al. 2020 [Ref 6]; Luethi & Liechti 2020 [Ref 16]).
In rats, 25B-NBOMe increased dopamine, serotonin, acetylcholine, and glutamate release in the frontal cortex, striatum, and nucleus accumbens (Wojtas et al. 2021 [Ref 1]). The head twitch response (HTR) — a rodent behavioral correlate of psychedelic activity — was induced across a wide dose range and blocked by the 5-HT₂A antagonist ketanserin, confirming 5-HT₂A-mediated mechanism (Custodio et al. 2020 [Ref 2]).
25B-NBOMe also elicited conditioned place preference (CPP) and self-administration in rodents. CPP was blocked by D1 (SCH23390) and D2 (haloperidol) antagonists but not by 5-HT₂A antagonist (ketanserin), suggesting rewarding effects are mediated via a **dopaminergic** rather than serotonergic mechanism, and indicating abuse potential (Custodio et al. 2020 [Ref 2]).
### Pharmacokinetics (Human Data)
**No published human pharmacokinetic studies exist for 25B-NBOMe as a recreational drug.** The only human pharmacokinetic data comes from its use as the radioligand [¹¹C]Cimbi-36 at tracer (sub-pharmacological) doses:
- In the first-in-human PET study (29 healthy volunteers), [¹¹C]Cimbi-36 showed high brain uptake with cortical distribution consistent with 5-HT₂A receptor topography (Ettrup et al. 2014 [Ref 8])
- Binding to 5-HT₂A receptors in cerebral cortex was confirmed selective; cerebellum was confirmed as reference tissue
- Radiometabolite studies in humans identified two metabolite fractions: polar M1 (dominant) and less polar M2, both arising from **O-demethylation** (Johansen et al. 2017 [Ref 17])
**FLAG:** All pharmacokinetic parameters at recreational doses (bioavailability by route, Tmax, half-life, Cmax) are not published. Any dose-range estimates should be flagged as unverified.
### Metabolism
Caspar et al. (2017) [Ref 5] — the definitive in vitro/in vivo metabolism study using both rat and human urine:
- **66 metabolites identified** for 25B-NBOMe
- **Primary pathways:** O-demethylation, O,O-bis-demethylation, hydroxylation, and combinations thereof
- **Phase II:** Glucuronidation and sulfation of phase I metabolites
- **CYP enzymes involved:**
- CYP1A2 and CYP3A4 → hydroxylation
- CYP2C9 and CYP2C19 → O-demethylation
- Detectable in urine primarily via metabolites (not parent compound) using LC-MS-based SUSAs
- In one acute intoxication human urine sample, 25B-NBOMe and metabolites were detectable by GC-MS and LC-MS/MS SUSAs
---
## History
### Discovery and Synthesis
NBOMe compounds were **first synthesized and described by Ralf Heim in his 2003 doctoral thesis** at the Free University of Berlin [Ref 23]. The thesis, titled *"Synthese und Pharmakologie potenter 5-HT₂A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts"* ("Synthesis and Pharmacology of Potent 5-HT₂A Receptor Agonists with N-2-Methoxybenzyl Partial Structure"), established the N-(2-methoxybenzyl) modification of known 2C phenethylamines as a strategy for dramatically enhancing 5-HT₂A receptor affinity. 25B-NBOMe is the N-benzylated derivative of 2C-B (which was itself synthesized by Alexander Shulgin).
The synthesis route involves reductive alkylation: 2-methoxybenzaldehyde is added to the 2C-B amine to form an imine intermediate, which is then reduced with sodium borohydride (NaBH₄) in methanol.
### Research Context
Following Heim's initial characterization, David Nichols's group at Purdue University explored the structure-activity relationships of N-benzylphenethylamines at 5-HT₂A receptors, including synthesis of constrained analogues to map optimal binding conformations (Juncosa et al. 2013 [Ref 4]).
**Independently**, researchers at the University of Copenhagen (Ettrup, Hansen, Kristensen, Knudsen and colleagues) developed 25B-NBOMe as a PET radioligand under the name **Cimbi-36** — an acronym for the Copenhagen Image and Molecular Pharmacology group. [¹¹C]Cimbi-36 was the first agonist PET radioligand developed for 5-HT₂A receptor imaging in living humans. An early preclinical paper appeared circa 2010 (Ettrup et al. 2010 [Ref 14] describes the related CIMBI-5 compound), with the first clinical human PET study published in 2014 (Ettrup et al. 2014 [Ref 8]).
### Recreational Market Emergence
25B-NBOMe appeared on the recreational drug market as a research chemical in the **early 2010s**, alongside 25I-NBOMe and 25C-NBOMe. The compounds were sold online as "research chemicals," sometimes on blotter paper (intentionally mimicking LSD), and sometimes under street names including "N-Bomb," "Smiles," "Solaris," and "Cimbi" (Zawilska et al. 2020 [Ref 6]; Baumeister et al. 2015 [Ref 29]).
Three commercially obtained blotter paper products were analytically confirmed to contain 25I-NBOMe, 25C-NBOMe, or 25B-NBOMe as the major component, with trace amounts of other NBOMe derivatives present as impurities (Poklis et al. 2015 [Ref 7]).
By 2013, reports of severe intoxications and deaths involving NBOMe compounds were published in the medical literature, prompting emergency scheduling in the US (November 2013) and subsequent international controls.
---
## Subjective Effects
**No published controlled human dosing studies exist for 25B-NBOMe.** Subjective effect descriptions derive from case reports and toxicology literature.
Clinically documented effects from case reports and case series (Gee et al. 2016 [Ref 30]; Tang et al. 2014 [Ref 32]; Zawilska et al. 2020 [Ref 6]):
**Desired/sought effects (user-reported context):**
- Visual and auditory hallucinations
- Hallucinogenic and stimulant effects
- Altered time perception
- Empathy and emotional enhancement (reported in abuse context)
**Adverse/toxic effects consistently documented:**
- Confusion, disorientation
- Violent agitation (predominant feature in Gee 2016 case series [Ref 30]: 10/10 patients)
- Anxiety, panic, fear
- Uncontrollable behavior
**Sympathomimetic toxidrome (documented in clinical presentations):**
- Mydriasis
- Tachycardia
- Hypertension
- Hyperthermia
- Diaphoresis
**Severe complications:**
- Seizures
- Rhabdomyolysis
- Kidney injury
- Disseminated intravascular coagulation (DIC)
- Metabolic acidosis
- Multiorgan failure
- Cardiac arrhythmia (in fatal cases)
- Death
**Duration:** The brief's duration data (total 8–12 hours sublingual) is consistent with reports of NBOMe class duration in the literature and is plausible given the extremely high 5-HT₂A affinity. No published controlled data exists to precisely verify onset/come-up/peak/offset values — these derive from user reports.
In rats, 25B-NBOMe demonstrated dose-dependent hallucinogenic activity (WDS), anxiogenic effects, impaired short-term memory, and decreased locomotor activity (Wojtas et al. 2021 [Ref 1]).
---
## Safety & Toxicity
### Published Fatalities and Severe Cases Involving 25B-NBOMe
**Al-Imam (2018) [Ref 33]:** 17-year-old male died after sublingual ingestion of three 25B-NBOMe tablets. Cause of death: cardiac arrest secondary to ventricular fibrillation. Postmortem cardiac blood concentration: **3.14 ng/mL**. This is the only published 25B-NBOMe-specific fatal case report with mechanism clearly described as cardiac arrhythmia.
**Shanks et al. (2015) [Ref 31]:** Fatal intoxication of a teenage male in Indiana (2014). 25B-NBOMe confirmed in postmortem heart blood at **1.59 ng/mL** by UPLC-MS/MS. Autopsy findings consistent with acute drug poisoning.
**Tang et al. (2014) [Ref 32]:** Two cases of severe acute intoxication with analytically confirmed 25B-NBOMe and 25C-NBOMe. Full clinical details not available from abstract alone; paper confirms severe presentations requiring hospitalization.
**Gee et al. (2016) [Ref 30] — Largest 25B-NBOMe clinical series (n=10):**
- All 10 patients had hallucinations and violent agitation
- Serotonergic/stimulant signs present in all: mydriasis, tachycardia, hypertension, hyperthermia
- 7/10 required benzodiazepine sedation
- Peak plasma concentrations: **0.7–10.1 ng/mL** (large variability)
- Hyperthermia, rhabdomyolysis, and kidney injury observed
- No deaths in this series; one pharmacological death described in literature review within same paper
**Postmortem blood levels from published cases:**
- Fatal: 1.59 ng/mL (Shanks 2015 [Ref 31]); 3.14 ng/mL (Al-Imam 2018 [Ref 33])
- Non-fatal: 0.7–10.1 ng/mL plasma (Gee 2016 [Ref 30])
- **FLAG:** These ranges overlap considerably — severity may depend heavily on co-ingested substances, individual susceptibility, ambient temperature, and physical exertion.
### General NBOMe Class Toxicity (Relevant to 25B-NBOMe)
Zawilska et al. (2020) [Ref 6] provides the most comprehensive review. Key toxicity findings from NBOMe class literature:
- Rhabdomyolysis is a relatively common complication of severe NBOMe toxicity, linked to seizures, hyperthermia, and vasoconstriction
- Serotonin toxicity signs are frequently present
- Fatal cases have been reported from the class (25C-NBOMe fatal case: Andreasen et al. 2015 [Ref 11]; fatality after 25C-NBOMe + 25H-NBOMe: Morini et al. 2017 [Ref 12])
**Stability in blood:** NBOMe compounds degrade in biological matrices; analytical laboratories should be aware of potential for underestimation of true concentrations in stored specimens (flagged in Zawilska 2020 [Ref 6]).
### LD50 / Therapeutic Index
**No published LD50 data for 25B-NBOMe.** No therapeutic index established. Given fatalities at blood levels of 1.59–3.14 ng/mL alongside non-fatal cases with plasma levels up to 10.1 ng/mL, the relationship between blood concentration and lethality is unclear and likely confounded by polydrug use and exertion.
### Genotoxicity
25B-NBOMe demonstrated a **subtle genotoxic effect** in the comet assay at the doses tested in rats — less pronounced than MDMA but not absent (Wojtas et al. 2021 [Ref 1]). No human genotoxicity data.
### Oral Route Bioavailability
Not published. Known to be active sublingually/buccally and insufflated. The brief notes oral (ingested) route is not listed among known ROAs; given extensive first-pass O-demethylation metabolism, poor oral bioavailability is structurally plausible but not confirmed in published literature.
---
## Harm Reduction
### Testing
- **Ehrlich reagent:** NEGATIVE — 25B-NBOMe is a phenethylamine, not an indole; the Ehrlich reagent will not produce a color change. **Critical implication:** Users cannot use Ehrlich testing to detect LSD adulteration with 25B-NBOMe.
- **Hofmann reagent:** POSITIVE — produces a color reaction; recommended for NBOMe detection
- **Multi-reagent testing:** Using Marquis, Mecke, and Hofmann in combination improves detection reliability
- **Laboratory confirmation:** LC-MS/MS or UPLC-MS/MS required for definitive identification and quantification (Poklis et al. 2015 [Ref 7]; Shanks et al. 2015 [Ref 31])
### Clinical Management (from case series evidence)
Based on Gee et al. 2016 [Ref 30] and Zawilska et al. 2020 [Ref 6]:
- Supportive care is the primary approach
- **Benzodiazepines** are the mainstay of pharmacological management for agitation; high doses may be required (7/10 patients in Gee series)
- **Active cooling** required for patients developing significant hyperthermia
- Monitor for rhabdomyolysis (CK, renal function), DIC (coagulation profile), metabolic acidosis
- Routine immunoassay drug screens will not detect 25B-NBOMe; LC-MS/MS needed
### Dose and Route Risks
- **Insufflation** causes rapid onset and unpredictable dose absorption; risk of overdose via this route is high
- Sold as LSD on blotter paper: users may ingest without knowing; typical LSD doses (1 tab) may deliver a lethal or severe dose of 25B-NBOMe
- **No neutralization by water:** unlike LSD, NBOMe compounds are not water-soluble; sublingual administration may take longer to absorb if mouth is dry
- Polydrug use is common and increases risk substantially
---
## Tolerance & Dependence
### Tolerance
**Mechanism:** Serotonergic psychedelics including NBOMes develop tolerance via **5-HT₂A receptor downregulation** following repeated stimulation. The brief lists: "builds almost immediately after ingestion; half-life 1 week; full reset 2 weeks." This timeline is consistent with published data on serotonergic psychedelic tolerance generally, though no published study has measured 25B-NBOMe tolerance development specifically. This represents a structural class inference.
**Cross-tolerance:** 25B-NBOMe produces complete cross-tolerance with other serotonergic psychedelics (LSD, psilocybin, mescaline, DMT) via the shared 5-HT₂A mechanism. This is well-established for the psychedelic class generally (Zawilska et al. 2020 [Ref 6]) and is clinically significant.
### Dependence and Abuse Potential
**No published studies have examined the dependence potential of 25B-NBOMe in humans** (WHO ECDD 36th meeting 2014 [Ref 26]).
In preclinical models, **25B-NBOMe demonstrated rewarding and reinforcing properties** (conditioned place preference and self-administration) via a dopaminergic mechanism — blocked by D1/D2 antagonists (Custodio et al. 2020 [Ref 2]). This suggests formal abuse potential, though the same study notes the dopaminergic mechanism is distinct from the 5-HT₂A-mediated perceptual effects.
**Classical serotonergic psychedelics are generally considered non-habit-forming** due to the rapid development of tolerance. Whether 25B-NBOMe's additional dopaminergic activity (documented preclinically) translates to greater dependence risk in humans is unknown. The seed data's characterization as "not habit-forming" is consistent with class behavior but has not been verified substance-specifically. **FLAG for editorial review.**
---
## Interactions
The following interaction data is classified by evidence quality:
### Cocaine — **DANGEROUS** (seed data; class-level inference, not substance-specific published data)
No published study specifically examines 25B-NBOMe + cocaine interaction. The danger classification is mechanistically plausible: 25B-NBOMe produces significant α₁-adrenergic receptor binding (class Ki 0.3–0.9 µM per Rickli 2015 [Ref 20]) producing vasoconstriction and sympathomimetic effects. Cocaine inhibits dopamine, serotonin, and norepinephrine reuptake and produces profound cardiovascular stimulation. Combined use risks additive/synergistic vasoconstriction, hypertensive crisis, cardiac arrhythmia, and coronary ischemia. **FLAG: No published pharmacokinetic or pharmacodynamic interaction study found. Dangerous classification based on class-level reasoning and clinical pattern in overdose literature.**
### Tramadol — **DANGEROUS** (seed data; class-level inference)
No published study specifically examines 25B-NBOMe + tramadol interaction. Tramadol is a serotonin-norepinephrine reuptake inhibitor (SNRI) with opioid receptor activity. Combined use with a potent 5-HT₂A agonist increases serotonin system load and may precipitate serotonin syndrome, which itself presents with features (hyperthermia, agitation, tachycardia, clonus) that overlap significantly with NBOMe toxicity and would be difficult to distinguish clinically. **FLAG: No published study; dangerous classification based on serotonin pharmacology reasoning.**
### MDMA — **UNKNOWN** (seed data)
Mechanistic concern: MDMA causes massive serotonin release; combined with 5-HT₂A agonism from 25B-NBOMe could potentiate serotonergic effects and increase risk of serotonin syndrome and hyperthermia. Published literature documents NBOMe toxicity resembles serotonergic syndrome (Zawilska 2020 [Ref 6]). No specific study found.
### Cannabis — **UNKNOWN** (seed data)
No published data. Cannabinoids interact with the endocannabinoid system and may modulate serotonergic tone indirectly. At the class level, cannabis co-use is very common in psychedelic settings. No specific risk characterization available.
### Caffeine — **UNKNOWN** (seed data)
No published data. Caffeine's adenosine antagonism and mild sympathomimetic effects theoretically compound cardiovascular stress, but no clinical data found.
### SSRIs/SNRIs (not in seed data but clinically relevant)
Not in the brief's interaction list, but clinically critical: SSRIs may reduce 5-HT₂A receptor agonism effects via 5-HT₂A downregulation, but the interaction is complex. SSRIs + serotonergic psychedelics carry serotonin syndrome risk in principle; the clinical significance is debated. This is a class-level concern not specific to 25B-NBOMe.
### MAOIs (not in seed data but clinically relevant)
Combination with MAOIs substantially increases serotonin syndrome risk by preventing 5-HT degradation while 25B-NBOMe drives receptor activation. **FLAG for contraindication consideration.**
---
## Legal Status
| Jurisdiction | Status | Effective Date |
|---|---|---|
| **United States** | Schedule I (DEA) | Emergency scheduling November 15, 2013; permanent November 2015 [Refs 24, 25] |
| **International** | Schedule I, UN 1971 Convention on Psychotropic Substances | March 2015 (following WHO ECDD 36th meeting 2014 recommendation) [Ref 26] |
| **United Kingdom** | Class A, Misuse of Drugs Act 1971 | Via N-benzylphenethylamine catch-all clause (exact date requires further verification — conflicting sources) |
| **Australia** | Prohibited; Schedule 1 (Criminal Code) | Criminal Code Controlled Drugs Legislation Amendment Regulation 2014 [Ref 26] |
| **New Zealand** | Class B controlled drug | December 2016 |
| **Canada** | Not confirmed via published source — FLAG for verification |
| **European Union** | Monitored under EMCDDA Early Warning System | Pre-2015; international scheduling has since applied in many EU member states |
**FLAG:** UK legal status shows conflicting information in web-retrieved sources — one source indicates Class A via N-benzylphenethylamine catch-all clause, another states it may not be explicitly covered. Requires verification against current UK Home Office controlled drug list.
---
## Clinical Trials
**NCT01778686** — "Evaluation of [¹¹C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors" [Ref 27]
- Status: **COMPLETED**
- Phase: N/A (basic science / imaging validation)
- Condition: Healthy volunteers
- Sponsor: Gitte Moos Knudsen, Rigshospitalet, Copenhagen
- Relevance: This is the landmark clinical trial validating 25B-NBOMe (as Cimbi-36) for human use as a PET tracer. Published results: Ettrup et al. 2014 [Ref 8]
**NCT03289949** — "The Neurobiological Effect of 5-HT2AR Modulation" [Ref 35]
- Status: **RECRUITING** (as of search date)
- Phase: Phase 1
- Condition: Basic science
- Sponsor: Gitte Moos Knudsen, Rigshospitalet, Copenhagen
- Relevance: Uses Cimbi-36 (25B-NBOMe) as radioligand to study 5-HT₂A receptor modulation in vivo
**Note:** There are no registered clinical trials involving 25B-NBOMe as a therapeutic or investigational drug for any psychiatric or medical condition. Its only clinical use is as a radioligand at tracer doses in PET imaging research.
---
## Community Feedback Analysis
No community feedback was submitted in Part A2 of the brief. Proceeding with standard research findings only.
---
## Gaps & Flags
### Safety-Critical Flags (require human review before publication):
1. **⚠️ Dose ranges not verified against published controlled human study.** All dose values in the brief (sublingual and insufflated) derive from user-report-based community sources (e.g., Erowid, PsychonautWiki, Drugs-Forum). No controlled human dosing study has been published. Doses are structurally plausible given 5-HT₂A Ki = 0.5 nM but must be labeled as derived from user reports only.
2. **⚠️ Cocaine interaction classification (DANGEROUS) not confirmed by published study.** Based entirely on class-level pharmacological reasoning (α₁ adrenergic + cocaine sympathomimetic effects). Accurate in direction but cannot cite a primary source.
3. **⚠️ Tramadol interaction classification (DANGEROUS) not confirmed by published study.** Based on serotonin syndrome pharmacological reasoning. Accurate in direction; no primary source.
4. **⚠️ No published LD50.** Blood levels in fatal cases (1.59–3.14 ng/mL) overlap with non-fatal cases (up to 10.1 ng/mL plasma). Cannot define a toxic threshold from published data.
5. **⚠️ Dependence characterization ("not habit-forming") is class-level inference, not substance-specific.** Custodio et al. 2020 [Ref 2] showed rodent self-administration via dopaminergic mechanism. Human dependence risk is unknown. ECDD confirms no dependence studies exist [Ref 26].
6. **⚠️ UK legal status conflicting.** Web-retrieved sources disagree on whether 25B-NBOMe is explicitly controlled under Class A or falls under a catch-all provision. Requires verification against current UK Home Office list.
### Data Gaps:
7. **No published human pharmacokinetic data** for 25B-NBOMe at recreational doses (bioavailability by route, Tmax, t½, Vd). Only trace-dose radioligand PK from PET studies.
8. **No published stereochemistry analysis.** 25B-NBOMe does not have a stereocentre in its standard form (the amine nitrogen is not a chiral centre in the standard structure); however, the Juncosa 2013 paper [Ref 4] created constrained analogues with stereocentres showing 124-fold selectivity for 5-HT₂A over 5-HT₂C — relevant to future analogue development but not to current product.
9. **No published chronic toxicity data** for 25B-NBOMe specifically in humans or controlled animal studies.
10. **No published oral bioavailability data.** The brief lists only sublingual and insufflated ROAs; oral route absent is consistent with expected high first-pass O-demethylation metabolism but unpublished.
11. **Ki and EC₅₀ values sourced from web synthesis** of the Rickli et al. 2015 [Ref 20] paper. The specific per-compound values for 25B-NBOMe (Ki 5-HT₂A = 0.5 nM; EC₅₀ = 40 nM) were not directly verified from the full-text PDF — only from search result summaries. The Rickli 2015 paper is confirmed real (PMID 26318099) and covers the NBOMe series, but the generation agent should note this when citing specific values.
12. **Canada legal status:** Not confirmed via published source. Likely controlled but unverified.
13. **No published MDMA + 25B-NBOMe interaction study.** Mechanistic concern exists (combined serotonergic load) but classification as "unknown" in seed data is appropriate given absence of evidence.
14. **Agonist classification ambiguity:** Some sources describe NBOMes as "partial agonists" at 5-HT₂A; others describe them as full agonists with efficacy similar to serotonin. Zawilska 2020 [Ref 6] calls them "highly efficacious agonists." Eshleman 2018 [Ref 21] found full efficacy for structurally related NBOMes. The characterization likely depends on the assay system and reference agonist used. Generation agent should note this nuance.