generation run 2026-04-28
53 min completedmodel pipeline-v5plan not recordedrun/3b361720…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 27 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
17 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | OpenAlex | 25C-NBOMe NBOMe serotonin receptor psychedelic | 93 | 5 | Selected highly-cited NBOMe-specific reviews and pharmacology papers; discarded NPS stimulant/cannabinoid reviews not specific to NBOMes. |
| 2 | PubChem | 25C-NBOMe | 1 | 1 | Only result; confirmed chemical identity. |
| 3 | PubMed | 25C-NBOMe toxicology overdose case report | 1 | 1 | First quantitative toxicological data from a fatal case; critical safety data. |
| 4 | PubMed | 25C-NBOMe pharmacology receptor binding | 1 | 1 | Core pharmacology paper with in vitro and in vivo data for 25C-NBOMe specifically. |
| 5 | ClinicalTrials.gov · absence | 25C-NBOMe | 0 | — | No results to select. |
| 6 | PubMed | NBOMe phenethylamine metabolism in vitro liver microsomes | 6 | 4 | Selected papers directly relevant to NBOMe class metabolism; discarded 1cP-LSD/4-AcO-DET paper as unrelated to NBOMe. |
| 7 | PubMed | NBOMe phenethylamine 5-HT2A binding affinity Ki structure activity | 1 | 1 | Core in vitro receptor binding profile data for 25C-NBOMe including comparison with parent 2C-C. |
| 8 | PubMed | 25I-NBOMe 25C-NBOMe schedule I DEA controlled substance 2013 | 1 | 1 | Primary US legal scheduling document; confirms legal status and Cimbi-82 alias. |
| 9 | PubMed | 25I-NBOMe 25B-NBOMe intoxication clinical toxicology emergency | 1 | 1 | Directly includes 25C-NBOMe case; important clinical data. |
| 10 | WebSearch | 25C-NBOMe Australia scheduling TGA | 10 | 0 | Could not confirm specific Australian scheduling date; noted as gap. |
| 11 | WebSearch | 25C-NBOMe CIMBI-82 first synthesized 2003 Knudsen Copenhagen radioligand | 10 | 1 | Establishes discovery history; noted discrepancy in dates between 2003 and 2009 for 25C-NBOMe specifically. |
| 12 | PubMed | NBOMe toxicities hallucinogens review literature | 3 | 2 | Comprehensive class-level toxicity reviews covering 25C-NBOMe cases. |
| 13 | Erowid | 25C-NBOMe 2C-C-NBOMe legal status jurisdictions | 1 | 6 | Selected confirmed jurisdictions with dates; noted Australia as gap. |
| 14 | OpenAlex | Braden Nichols N-benzyl 2C phenethylamine 5-HT2A SAR | 8 | 2 | Key SAR paper and CIMBI radioligand paper relevant to discovery and pharmacology of 25C-NBOMe. |
| 15 | PubMed | NBOMe adverse effects hospitalization clinical features case series | 2 | 1 | Gee 2016 is most detailed case series with management recommendations; applicable to 25C-NBOMe class. |
| 16 | Multiple sources | Cross-referencing all gathered data against brief seed data for 25C-NBOMe | 26 | 1 | Final cross-reference pass to ensure consistency between seed data and published literature. |
| 17 | WebSearch | 25C-NBOMe Ralf Heim 2003 synthesis discovery | 10 | 1 | Best available evidence for discovery history; flagged as unverifiable. |
88 claims by section — every cited sentence, checked against its source
safety26 · 16 ok
The margin between common recreational doses (300–700 µg sublingual) and doses associated with fatal outcomes is unknown and presumed narrowsupported
Young male hospitalized after recreational use died ~12h after ingestion with signs of serotonin toxicity. j.forsciint.2015.03.012
The first fatal 25C-NBOMe poisoning with quantitative confirmation was reported by Andreasen et al.: a young male died approximately 12 hours after recreational ingestion, with preceding signs of serotonin toxicity; cause of death was attributed to 25C-NBOMe in combination with amphetamine (ante-mortem blood 0.81 µg/kg; post-mortem peripheral blood 0.60 µg/kg)partially supported
Young male hospitalized after recreational use died ~12h after ingestion with signs of serotonin toxicity... Quantified in peripheral whole blood (0.60 µg/kg)... Cause of death: fatal overdose of 25C-NBOMe in combination with amphetamine. j.forsciint.2015.03.012
Claim in safety — inconclusiveinconclusiveworking →
The NBOMe class toxidrome, directly applicable to 25C-NBOMe, comprises:supported
Comprehensive review of NBOMe pharmacology, pattern of use, metabolism, desired and adverse effects; includes non-fatal and lethal intoxication cases fnins.2020.00078
The NBOMe class toxidrome, directly applicable to 25C-NBOMe, comprises:supported
Features: hallucinations, violent agitation, mydriasis, tachycardia, hypertension, hyperthermia... Clinical features similar to 25I-NBOMe and 25C-NBOMe. 15563650.2015.1115056
Claim in safety — inconclusiveinconclusiveworking →
Serious complications: rhabdomyolysis (linked to seizures, hyperthermia, and vasoconstriction), disseminated intravascular coagulation, metabolic acidosis, hypoglycemia, multiorgan failuresupported
Based on review of 51 NBOMe toxicity cases, rhabdomyolysis is a relatively common complication. 7854_2016_64
Serious complications: rhabdomyolysis (linked to seizures, hyperthermia, and vasoconstriction), disseminated intravascular coagulation, metabolic acidosis, hypoglycemia, multiorgan failuresupported
Comprehensive review of NBOMe pharmacology, pattern of use, metabolism, desired and adverse effects; includes non-fatal and lethal intoxication cases fnins.2020.00078
Claim in safety — not_supportednot supportedworking →
Based on published case series and reviews:supported
10 patients with adverse effects from 25B-NBOMe. 15563650.2015.1115056
Based on published case series and reviews:supported
Comprehensive review of NBOMe pharmacology, pattern of use, metabolism, desired and adverse effects fnins.2020.00078
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Acute psychological distress — including severe panic, paranoia, and psychotic-spectrum symptoms — is documented across the NBOMe classsupported
Comprehensive review of NBOMe pharmacology, pattern of use, metabolism, desired and adverse effects; includes non-fatal and lethal intoxication cases fnins.2020.00078
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — not_supportednot supportedworking →
The mechanism is 5-HT₂A receptor downregulation, which is activation-dependent and β-arrestin2-independentsupported
DOI causes 5-HT2AR downregulation in frontal cortex. Mechanism independent of beta-arrestin-2. acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
Full cross-tolerance exists with all 5-HT₂A agonist psychedelics, including LSD, psilocybin, DMT, mescaline, and all other NBOMe compoundspartially supported
Cross-tolerance between DOI and LSD but not with nonpsychedelic lisuride. acschemneuro.2c00170
No cross-tolerance develops with non-psychedelic 5-HT₂A partial agonists such as lisuride.supported
Cross-tolerance between DOI and LSD but not with nonpsychedelic lisuride. acschemneuro.2c00170
Classical serotonergic psychedelics lack the dopaminergic reward pathway activation associated with compulsive use and physical dependence.supported
Comprehensive review of designer drug pharmacology and adverse effects; covers NBOMes as serotonergic psychedelics acting via 5-HT2A agonism. s00204-020-02693-7
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Polydrug use involving NBOMes with other serotonergic substances is documented as increasing risk of severe adverse outcomessupported
Comprehensive review of designer drug pharmacology and adverse effects; covers NBOMes as serotonergic psychedelics acting via 5-HT2A agonism. s00204-020-02693-7
The fatal case reported by Andreasen et al. involved co-ingestion of amphetamine.supported
Cause of death: fatal overdose of 25C-NBOMe in combination with amphetamine. j.forsciint.2015.03.012
Seizure disorders — NBOMe compounds lower seizure threshold; seizures are a documented feature of acute toxicitysupported
Comprehensive review of NBOMe pharmacology, pattern of use, metabolism, desired and adverse effects; includes non-fatal and lethal intoxication cases fnins.2020.00078
pharmacology18 · 12 ok
25C-NBOMe is a potent agonist at serotonin 5-HT₂A and 5-HT₂C receptorssupported
Ki values in low nanomolar range for 5-HT2A and 5-HT2C receptors fnins.2020.00078
25C-NBOMe is a potent agonist at serotonin 5-HT₂A and 5-HT₂C receptorssupported
2,5-Dimethoxyphenethylamines (2C compounds) are 5-HT2A/2C receptor agonists... Findings show NBOMes are highly potent 5-HT2A agonists in rats. j.neuropharm.2018.02.033
This Gq-dependent pathway — rather than β-arrestin2 recruitment — correlates with head-twitch response magnitude in rodent models and is considered the primary effector of psychedelic phenomenology.supported
5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential (HTR). Threshold Gq activation required for psychedelic-like effects. s41467-023-44016-1
This modification increases binding affinity by orders of magnitude relative to the parent phenethylamine 2C-Csupported
N-methoxybenzylation of 2C compounds markedly increases their affinity for 5-HT2A receptors. j.neuropharm.2018.02.033
This modification increases binding affinity by orders of magnitude relative to the parent phenethylamine 2C-Csupported
Ki values in low nanomolar range for 5-HT2A and 5-HT2C receptors fnins.2020.00078
Despite this high affinity, functional assays (calcium mobilization) demonstrate that 25C-NBOMe and other NBOMes exhibit substantially lower agonist efficacy than their binding affinity would predict, consistent with partial agonist character at the 5-HT₂A receptor.supported
NBOMes displayed higher affinity for 5-HT2A receptors than their 2C counterparts but were substantially weaker in functional assays. j.neuropharm.2018.02.033
Claim in pharmacology — inconclusiveinconclusiveworking →
The primary route of administration is sublingual/buccal, typically via blotter papersupported
Comprehensive review of NBOMe pharmacology, pattern of use, metabolism, desired and adverse effects fnins.2020.00078
The primary route of administration is sublingual/buccal, typically via blotter papersupported
The major drug present on each of the three blotter products was different: 25I-NBOMe, 25C-NBOMe or 25B-NBOMe. bkv073
The only published human blood concentration data come from a fatal case: ante-mortem whole blood concentration was 0.81 µg/kg at 2–4 hours post-ingestion; post-mortem peripheral blood 0.60 µg/kg; urine 2.93 µg/kg; vitreous humor 0.33 µg/kg; liver 0.82 µg/kgpartially supported
Quantified in peripheral whole blood (0.60 µg/kg), urine (2.93 µg/kg), vitreous humor (0.33 µg/kg), liver (0.82 µg/kg). j.forsciint.2015.03.012
Brain penetration data from the structural analog 2C-B-Fly-NBOMe in rats show peak serum concentration at 30 minutes and peak brain tissue concentration at 60 minutes following subcutaneous administration, with detectable brain levels persisting at 8 hourssupported
2C-B-Fly-NBOMe: peak serum 30 min, peak brain tissue 60 min post s.c. Still present in brain at 8h. fphar.2023.1120419
The only published in vivo human metabolite data specific to 25C-NBOMe come from the fatal case reported by Andreasen et al., who identified a demethylated and glucuronidated metabolite in urine and blood using UPLC-HRTOF-MS.supported
25C-NBOMe and a demethylated and glucuronidated metabolite identified in urine and blood by UPLC-HRTOF-MS. j.forsciint.2015.03.012
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Confirmatory detection requires LC-MS/MS or UPLC-HRTOF-MS.supported
screened using DART-AccuTOF MS and HPLC-MS/MS bkv073
summary10 · 9 ok
This structural modification confers low-nanomolar binding affinity at the serotonin 5-HT₂A receptor — a >1000-fold increase over 2C-C — placing 25C-NBOMe among the most potent phenethylamine hallucinogens knownpartially supported
Ki values in low nanomolar range for 5-HT2A and 5-HT2C receptors; more than 1000-fold selectivity for 5-HT2A vs 5-HT1A fnins.2020.00078
The NBOMe series was first synthesized by Ralf Heim in a 2003 doctoral dissertation at the Free University of Berlin, as part of a program to develop high-affinity 5-HT₂A radioligand candidates. 25C-NBOMe carries the research designation Cimbi-82, assigned by the Copenhagen neuroimaging group that developed NBOMes as PET tracerspartially supported
DEA temporary Schedule I placement of 25I-NBOMe (Cimbi-5), 25C-NBOMe (Cimbi-82), and 25B-NBOMe (Cimbi-36) pmid:24236337
Claim in summary — inconclusiveinconclusiveworking →
The compound entered recreational drug markets around 2010–2011, frequently misrepresented as LSD on blotter paper, and has been associated with fatalities.supported
Cause of death: fatal overdose of 25C-NBOMe in combination with amphetamine. j.forsciint.2015.03.012
25C-NBOMe acts as a potent agonist at 5-HT₂A and 5-HT₂C receptors, with psychedelic effects mediated primarily through 5-HT₂A–Gq/11 coupling and downstream phospholipase C signalingsupported
Ki values in low nanomolar range for 5-HT2A and 5-HT2C receptors fnins.2020.00078
25C-NBOMe acts as a potent agonist at 5-HT₂A and 5-HT₂C receptors, with psychedelic effects mediated primarily through 5-HT₂A–Gq/11 coupling and downstream phospholipase C signalingsupported
NBOMes displayed higher affinity for 5-HT2A receptors than their 2C counterparts... Findings show NBOMes are highly potent 5-HT2A agonists in rats. j.neuropharm.2018.02.033
Despite high binding affinity, functional assays show substantially lower agonist efficacy than affinity alone would predict, consistent with partial agonist character in calcium mobilization studiessupported
NBOMes displayed higher affinity for 5-HT2A receptors than their 2C counterparts but were substantially weaker in functional assays. j.neuropharm.2018.02.033
25C-NBOMe presents a critical acute safety profile: the margin between common recreational doses (300–700 µg sublingual) and doses associated with fatal outcomes is unknown and presumed narrowsupported
Young male hospitalized after recreational use died ~12h after ingestion with signs of serotonin toxicity. j.forsciint.2015.03.012
Severe toxicity features rhabdomyolysis, seizures, hyperthermia, and multiorgan failuresupported
Comprehensive review of NBOMe pharmacology, pattern of use, metabolism, desired and adverse effects; includes non-fatal and lethal intoxication cases fnins.2020.00078
Tolerance develops rapidly through 5-HT₂A receptor downregulation, with full cross-tolerance to all serotonergic psychedelics and an estimated 14-day reset periodpartially supported
Cross-tolerance between DOI and LSD but not with nonpsychedelic lisuride. DOI causes 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
receptor-pharmacology8 · 4 ok
25C-NBOMe binds with low nanomolar affinity at the 5-HT₂A receptor, with >1000-fold selectivity over 5-HT₁Asupported
Ki values in low nanomolar range for 5-HT2A and 5-HT2C receptors; more than 1000-fold selectivity for 5-HT2A vs 5-HT1A fnins.2020.00078
Affinity at 5-HT₂C is also in the low nanomolar range, while 5-HT₂B affinity, potency, and efficacy are markedly lower.partially supported
Ki values in low nanomolar range for 5-HT2A and 5-HT2C receptors fnins.2020.00078
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Specific Ki and EC₅₀ values for 25C-NBOMe at individual receptor targets are published in the data tables of Rickli et al. and Elmore et al. but were not extractable from abstract-only access during research.supported
2,5-Dimethoxyphenethylamines (2C compounds) are 5-HT2A/2C receptor agonists... NBOMes displayed higher affinity for 5-HT2A receptors j.neuropharm.2018.02.033
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The psychedelic behavioral response (head-twitch response in rodents) is predicted by Gq efficacy rather than β-arrestin2 recruitment.supported
5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential (HTR). s41467-023-44016-1
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
history7 · 5 ok
Claim in history — inconclusiveinconclusiveworking →
The compound was subsequently taken up by the Neurobiology Research Unit at Rigshospitalet, Copenhagen, under the CIMBI (Copenhagen Image of Neurobiological Indicators of Mood) research program directed by Gitte Moos Knudsen. 25C-NBOMe received the designation Cimbi-82partially supported
25C-NBOMe (Cimbi-82) pmid:24236337
The related compound 25I-NBOMe (CIMBI-5) was radiolabeled with carbon-11 and validated as a 5-HT₂A agonist PET tracer.supported
11C-CIMBI-5 (radiolabeled 25I-NBOMe) shows cortex-to-cerebellum binding ratio equivalent to 18F-altanserin... Promising 5-HT2A agonist PET tracer. jnumed.109.074021
NBOMe compounds appeared on online research chemical markets between approximately 2010 and 2011partially supported
25C-NBOMe consumption represents an emerging phenomenon... use is increased by its online availability at low costs. 734749
Claim in history — inconclusiveinconclusiveworking →
Analytical testing of seized blotter samples confirmed the presence of 25C-NBOMe alongside 25I-NBOMe and 25B-NBOMe, with trace amounts of multiple NBOMe analogs sometimes found on a single piece of blottersupported
The major drug present on each of the three blotter products was different: 25I-NBOMe, 25C-NBOMe or 25B-NBOMe. Papers also contained minute amounts of NBOMe derivative impurities. bkv073
Drug Enforcement Administration placed 25C-NBOMe, 25I-NBOMe, and 25B-NBOMe into Schedule I of the Controlled Substances Act on November 15, 2013, under temporary scheduling authoritypartially supported
DEA temporary Schedule I placement of 25I-NBOMe (Cimbi-5), 25C-NBOMe (Cimbi-82), and 25B-NBOMe (Cimbi-36) under 21 U.S.C. 811(h). pmid:24236337
comparative-pharmacology6 · 4 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Both compounds are 5-HT₂A agonists active at microgram doses, but they differ in several critical respects: LSD acts across a broader receptor profile (including dopamine D₂, 5-HT₁A, 5-HT₂B, and adrenergic receptors), has a well-characterized safety profile with no confirmed human fatalities from pharmacological toxicity alone, and possesses a far wider therapeutic index. 25C-NBOMe and other NBOMes, by contrast, have documented fatal outcomes at recreational doses and produce a pronounced sympathomimetic toxidrome largely absent from LSD intoxicationsupported
Comprehensive review of NBOMe pharmacology, pattern of use, metabolism, desired and adverse effects; includes non-fatal and lethal intoxication cases fnins.2020.00078
This modification increases 5-HT₂A binding affinity from the micromolar range (2C-C) to the low nanomolar range (25C-NBOMe) — an enhancement exceeding 1000-foldpartially supported
Ki values in low nanomolar range for 5-HT2A and 5-HT2C receptors; more than 1000-fold selectivity for 5-HT2A vs 5-HT1A fnins.2020.00078
This modification increases 5-HT₂A binding affinity from the micromolar range (2C-C) to the low nanomolar range (25C-NBOMe) — an enhancement exceeding 1000-foldsupported
N-methoxybenzylation of 2C compounds markedly increases their affinity for 5-HT2A receptors. NBOMes displayed higher affinity for 5-HT2A receptors than their 2C counterparts j.neuropharm.2018.02.033
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
All NBOMe compounds share the class-level toxidrome: sympathomimetic crisis, seizures, rhabdomyolysis, and hyperthermiasupported
Comprehensive review of NBOMe pharmacology, pattern of use, metabolism, desired and adverse effects; includes non-fatal and lethal intoxication cases fnins.2020.00078
pharmacokinetic-detail5 · 1 ok
The only published human concentration data derive from a single fatal case:supported
Quantified in peripheral whole blood (0.60 µg/kg), urine (2.93 µg/kg), vitreous humor (0.33 µg/kg), liver (0.82 µg/kg). j.forsciint.2015.03.012
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
chemistry4 · 2 ok
Claim in chemistry — inconclusiveinconclusiveworking →
The defining structural feature of the NBOMe class is the N-(2-methoxybenzyl) substituent on the amine nitrogen of the 2C scaffold — an addition that dramatically increases 5-HT₂A receptor binding affinity relative to the unsubstituted parent.supported
N-methoxybenzylation of 2C compounds markedly increases their affinity for 5-HT2A receptors. j.neuropharm.2018.02.033
Claim in chemistry — inconclusiveinconclusiveworking →
These methoxy groups serve as sites for metabolic O-demethylation.supported
25C-NBOMe and a demethylated and glucuronidated metabolite identified in urine and blood by UPLC-HRTOF-MS. j.forsciint.2015.03.012
clinical-evidence2 · 1 ok
Cause of death was determined to be fatal overdose of 25C-NBOMe in combination with amphetamine.supported
Cause of death: fatal overdose of 25C-NBOMe in combination with amphetamine. j.forsciint.2015.03.012
Claim in clinical-evidence — inconclusiveinconclusiveworking →
neuroscience2 · 1 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
The partial agonist character of 25C-NBOMe at 5-HT₂A (demonstrated in calcium mobilization assays) may modulate the magnitude or quality of these downstream neural effects compared to full agonists, though this has not been empirically tested for NBOMe compounds.supported
NBOMes displayed higher affinity for 5-HT2A receptors than their 2C counterparts but were substantially weaker in functional assays. j.neuropharm.2018.02.033