generation run 2026-04-26
52 min completedmodel pipeline-v5plan not recordedrun/84b9cafc…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 18 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
15 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | 2C-I | 1 | 1 | Confirms all key chemical identity data; fills gaps from brief (no CID, formula, weight, InChIKey given) |
| 2 | OpenAlex | 2C-I iodophenethylamine psychedelic serotonin receptor | 10 | 3 | Nichols 2014 provides 2C-I comparative SAR data; Wallach 2023 covers 5-HT2A Gq signaling mechanism; Zawilska 2020 covers NBOMe context where 2C-I is parent |
| 3 | WebSearch | 2C-I Wikipedia synthesis history Shulgin 1991 pharmacology | 10 | 2 | Historical/synthesis data not available via PubMed; PiHKAL is primary source for discovery narrative |
| 4 | PubMed | 2C-I 2,5-dimethoxy-4-iodophenethylamine pharmacology receptor binding | 4 | 4 | All directly relevant to 2C-I receptor pharmacology |
| 5 | WebSearch | 2C-I DEA Schedule I controlled substance; 2C-I legal status UK Germany Canada Australia | 10 | 3 | Web-retrieved legal status data; no primary regulatory PDFs retrieved |
| 6 | ClinicalTrials.gov | 2C-I phenethylamine psychedelic | 1 | 0 | No clinical trials for 2C-I found; 2C-B trial is not relevant to 2C-I article |
| 7 | PubMed | 2,5-dimethoxy-4-iodophenethylamine forensic analysis GC-MS detection | 3 | 3 | Drees 2009 is only direct 2C-I toxicity case report found; Karlsen 2014 relevant for forensic detection; Brandt 2015 for analytical chemistry |
| 8 | PubMed | PMID 24012658 | 1 | 1 | Primary in vivo pharmacology data specifically for 2C-I |
| 9 | PubMed | 2C-I metabolism toxicological detection rat urine gas chromatography designer drug | 1 | 1 | Only published 2C-I metabolism study; critical for pharmacokinetics section |
| 10 | WebSearch | 2C-I DEA Schedule I emergency scheduling 2012 federal register Synthetic Drug Abuse Prevention Act | 10 | 2 | Confirms US scheduling date and mechanism; DEA official source for legal status |
| 11 | PubMed | PMID 23494844, 39867514, 29501528, 26318099, 20126400, 32128596, 16810648 | 7 | 1 | API verification of all key citations for citation registry |
| 12 | PubMed | 25I-NBOMe 2C-I neuropharmacology receptor binding comparison rats | 8 | 5 | All directly relevant to 2C-I pharmacology and toxicology |
| 13 | PubMed | 2C or not 2C phenethylamine designer drug review medical toxicology | 3 | 2 | Dean 2013 is the key clinical toxicology review for 2C drugs; Hondebrink 2018 provides NPS effect fingerprinting context |
| 14 | PubChem + PubMed + WebSearch | Cross-reference all seed data against primary sources | 25 | 5 | Comprehensive cross-reference completed; discrepancies and gaps documented in research output |
| 15 | WebSearch | DEA 2C-I factsheet deadiversion.usdoj.gov | 1 | 1 | Government regulatory primary source for US scheduling information |
63 claims by section — every cited sentence, checked against its source
safety16 · 12 ok
Claim in safety — inconclusiveinconclusiveworking →
The sole peer-reviewed case report documenting 2C-I-associated morbidity describes a 39-year-old woman who presented with rapidly diminishing mental status, hypertension, and vasoconstrictionpartially supported
Case report: 39-year-old woman suffered hemorrhagic stroke after ingestion of cocaine, MDMA, and 2C-I. j.1556-4029.2009.01199.x
Claim in safety — inconclusiveinconclusiveworking →
Sympathomimetic effects — hypertension, tachycardia, and vasoconstriction — are documented in both the clinical case report and class-level clinical reviews of 2C drug intoxicationsupported
Common features: hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
Sympathomimetic effects — hypertension, tachycardia, and vasoconstriction — are documented in both the clinical case report and class-level clinical reviews of 2C drug intoxicationsupported
Comprehensive review of psychedelic pathways of 2C and NBOMe designer drugs; serotonergic interactions, cardiovascular complications, neurotoxicity, abuse potential. j.toxrep.2025.101890
The mechanism involves 5-HT₂A receptor-mediated vasoconstriction with possible additional contribution from adrenergic receptor activity.supported
Hallucinogenic phenethylamines activate 5-HT2 receptors; additional targets include dopamine, adrenergic, GABA-A receptors. j.pharmthera.2017.10.022
Dean et al. reviewed the 2C drug class and documented at least five deaths attributed to 2C drug intoxicationsupported
At least 5 deaths reported. s13181-013-0295-x
Claim in safety — inconclusiveinconclusiveworking →
Clinical toxicology presentations of 2C drug intoxication include agitation, aggression, and dysphoria.partially supported
Common features: hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
Wallach et al. demonstrated that β-arrestin-biased 5-HT₂A agonists induce receptor internalization and tachyphylaxis; classical Gq-biased psychedelics including 2C-I produce tolerance through analogous downregulation pathwayspartially supported
Beta-arrestin-biased agonists block psychedelic effects and cause tachyphylaxis. s41467-023-44016-1
Claim in safety — inconclusiveinconclusiveworking →
Additionally, tramadol lowers the seizure threshold, compounding the seizure risk documented in excited delirium presentations of 2C drug intoxicationsupported
Common features: hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
The case of hemorrhagic stroke in a patient with Moyamoya disease following 2C-I co-ingestion demonstrates that 2C-I-induced hypertension and vasoconstriction can precipitate catastrophic cerebrovascular events in predisposed individuals.partially supported
Case report: 39-year-old woman suffered hemorrhagic stroke after ingestion of cocaine, MDMA, and 2C-I. Underlying Moyamoya cerebrovascular abnormality. j.1556-4029.2009.01199.x
Cardiovascular disease — including uncontrolled hypertension, structural heart disease, and conditions predisposing to arrhythmia — constitutes a contraindication given the documented sympathomimetic effects (hypertension, tachycardia, vasoconstriction).supported
Common features: hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
Cardiovascular disease — including uncontrolled hypertension, structural heart disease, and conditions predisposing to arrhythmia — constitutes a contraindication given the documented sympathomimetic effects (hypertension, tachycardia, vasoconstriction).supported
Comprehensive review of psychedelic pathways of 2C and NBOMe designer drugs; serotonergic interactions, cardiovascular complications, neurotoxicity, abuse potential. j.toxrep.2025.101890
Epilepsy or lowered seizure threshold represents a relative contraindication, as seizures are documented in severe 2C drug intoxication.supported
Common features: hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
summary10 · 8 ok
The evidence base comprises one rat metabolism study, one clinical case report, and animal pharmacology demonstrating 5-HT₂A-mediated head-twitch responses in mice. 2C-I was permanently placed in Schedule I in the United States in 2012.partially supported
GC/MS STA procedure detects intake at common dose in rat urine. pmid:16810648
The evidence base comprises one rat metabolism study, one clinical case report, and animal pharmacology demonstrating 5-HT₂A-mediated head-twitch responses in mice. 2C-I was permanently placed in Schedule I in the United States in 2012.partially supported
Case report: 39-year-old woman suffered hemorrhagic stroke after ingestion of cocaine, MDMA, and 2C-I. LC-MS/MS confirmed 2C-I in urine. j.1556-4029.2009.01199.x
The evidence base comprises one rat metabolism study, one clinical case report, and animal pharmacology demonstrating 5-HT₂A-mediated head-twitch responses in mice. 2C-I was permanently placed in Schedule I in the United States in 2012.partially supported
2C-I (1-10 mg/kg SC) and N-benzyl derivatives (25I-NBOMe, 25I-NBMD) induce head twitch response via 5-HT2A activation in C57BL/6J mice. j.neuropharm.2013.08.025
2C-I acts as a serotonin 5-HT₂A receptor agonist with reported Ki ≈ 0.73 nM at that site , signaling through Gq-coupled pathways that underlie its psychedelic activitypartially supported
2C-I (1-10 mg/kg SC) and N-benzyl derivatives induce head twitch response via 5-HT2A activation in C57BL/6J mice. M100907 completely blocked HTR. j.neuropharm.2013.08.025
2C-I acts as a serotonin 5-HT₂A receptor agonist with reported Ki ≈ 0.73 nM at that site , signaling through Gq-coupled pathways that underlie its psychedelic activitypartially supported
5-HT2A Gq efficacy predicts psychedelic potential. s41467-023-44016-1
The selective 5-HT₂A antagonist M100907 completely abolishes 2C-I-induced head-twitch responses in mice, confirming 5-HT₂A as the primary mechanistic targetsupported
M100907 completely blocked HTR. j.neuropharm.2013.08.025
Claim in summary — inconclusiveinconclusiveworking →
Acute cardiovascular stress — hypertension, tachycardia, and vasoconstriction — is documented in clinical presentationssupported
Common features: hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
Tolerance develops rapidly through 5-HT₂A receptor downregulation following repeated agonist activation; no physical dependence or withdrawal syndrome has been documentedpartially supported
Beta-arrestin-biased agonists block psychedelic effects and cause tachyphylaxis. s41467-023-44016-1
Claim in summary — inconclusiveinconclusiveworking →
pharmacology9 · 9 ok
Wallach et al. demonstrated that 5-HT₂A Gq efficacy — rather than β-arrestin2 recruitment — is the key predictor of psychedelic potential in the head-twitch response (HTR) model. 2C-I fits this mechanistic framework as a full-efficacy Gq agonist at 5-HT₂Asupported
5-HT2A Gq efficacy predicts psychedelic potential. Beta-arrestin-biased agonists block psychedelic effects and cause tachyphylaxis. s41467-023-44016-1
Halberstadt and Geyer confirmed that 2C-I (1–10 mg/kg subcutaneous) induces the HTR in C57BL/6J mice through 5-HT₂A activation: the selective 5-HT₂A antagonist M100907 completely abolished the responsesupported
2C-I (1-10 mg/kg SC) and N-benzyl derivatives (25I-NBOMe, 25I-NBMD) induce head twitch response via 5-HT2A activation in C57BL/6J mice. 25I-NBOMe is 14-fold more potent than 2C-I. M100907 completely blocked HTR. j.neuropharm.2013.08.025
Nonaka et al. independently confirmed that 2C-I stimulates G protein activation ([³⁵S]GTPγS binding) in rat cortical membranes, directly demonstrating receptor-coupled signal transduction.supported
2C-I among phenethylamines stimulating G protein binding in rat brain cortical membranes. pmid:18057721
Beyond 5-HT₂A, 2C-I acts at 5-HT₂C receptors — activity conferred by the 2,5-dimethoxy phenethylamine scaffold common to all 2C compoundssupported
Elimination of 2- or 5-methoxy group from 2C-B/DOB leads to modest drop in binding affinity/potency at 5-HT2A and 5-HT2C. acschemneuro.0c00129
The broader receptor profile extends well beyond the 5-HT₂ family: Ray's comprehensive NIMH-PDSP screening of 25 psychedelics across 51 receptor sites established that phenethylamine hallucinogens interact with 42 of 49 broadly assayed targetssupported
NIMH-PDSP data for 25 psychedelic drugs at 51 receptors, transporters, and ion channels. Phenylalkylamines interact with 42 of 49 sites. journal.pone.0009019
At concentrations reached during human recreational use, additional targets include α₂-adrenergic receptors, dopamine receptors, GABA-A receptors, and acetylcholine receptors.partially supported
Hallucinogenic phenethylamines activate 5-HT2 receptors; additional targets include dopamine, adrenergic, GABA-A receptors. j.pharmthera.2017.10.022
The sole metabolism study, conducted in a rat model by Theobald et al., characterized urinary metabolites via GC/MS and CE/MS. Identified metabolic pathways include:supported
2C-I metabolized by O-demethylation at positions 2 and 5, followed by N-acetylation or deamination with subsequent oxidation/reduction. Beta-hydroxylation also identified. pmid:16810648
2C-I is detectable in human urine by LC-MS/MS and in rat urine by GC/MS following acid hydrolysis, liquid-liquid extraction, and microwave-assisted acetylation — a procedure sensitive enough to detect metabolites following a common recreational dose.supported
LC-MS/MS confirmed 2C-I in urine. j.1556-4029.2009.01199.x
2C-I is detectable in human urine by LC-MS/MS and in rat urine by GC/MS following acid hydrolysis, liquid-liquid extraction, and microwave-assisted acetylation — a procedure sensitive enough to detect metabolites following a common recreational dose.supported
GC/MS STA procedure detects intake at common dose in rat urine. pmid:16810648
receptor-pharmacology8 · 7 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Eshleman et al. studied 2C-I among six phenethylamines with in vitro receptor binding and transporter assays, and Rickli et al. provided comparative receptor interaction profiles for the 2C drug class versus NBOMe derivatives; full Ki tables from both papers require access to the complete manuscripts for verification.supported
In vitro receptor binding and function data for 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC. s00213-013-3303-6
Eshleman et al. studied 2C-I among six phenethylamines with in vitro receptor binding and transporter assays, and Rickli et al. provided comparative receptor interaction profiles for the 2C drug class versus NBOMe derivatives; full Ki tables from both papers require access to the complete manuscripts for verification.supported
In vitro receptor interaction profiles of NBOMe drugs vs 2C drugs and LSD. Characterizes binding affinities at multiple receptor types and monoamine transporters. j.neuropharm.2015.08.034
2C-I activates 5-HT₂C receptors, consistent with the 2,5-dimethoxy pharmacophore shared by all 2C compoundssupported
Elimination of 2- or 5-methoxy group from 2C-B/DOB leads to modest drop in binding affinity/potency at 5-HT2A and 5-HT2C. In vivo reduction is more pronounced. 2C-I referenced throughout. acschemneuro.0c00129
The NIMH Psychoactive Drug Screening Program (PDSP) dataset demonstrates that phenethylamine psychedelics are not selective for 5-HT₂A/2C — they interact with the majority of assayed receptor sites (42 of 49)supported
NIMH-PDSP data for 25 psychedelic drugs at 51 receptors, transporters, and ion channels. Phenylalkylamines interact with 42 of 49 sites. journal.pone.0009019
Relevant secondary targets at human brain concentrations include α₂-adrenergic, dopaminergic, GABAergic, and cholinergic receptors.partially supported
Hallucinogenic phenethylamines activate 5-HT2 receptors; additional targets include dopamine, adrenergic, GABA-A receptors. j.pharmthera.2017.10.022
Wallach et al. established that Gq efficacy, not β-arrestin2 recruitment, predicts psychedelic potentialsupported
5-HT2A Gq efficacy predicts psychedelic potential. Beta-arrestin-biased agonists block psychedelic effects and cause tachyphylaxis. s41467-023-44016-1
Nonaka et al. confirmed G protein activation by 2C-I using [³⁵S]GTPγS binding in rat cortical membranessupported
2C-I among phenethylamines stimulating G protein binding in rat brain cortical membranes. pmid:18057721
comparative-pharmacology7 · 5 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
This modification produces a dramatic increase in 5-HT₂A affinity and in vivo potency: 25I-NBOMe is approximately 14-fold more potent than 2C-I in the mouse HTR assaysupported
25I-NBOMe is 14-fold more potent than 2C-I. j.neuropharm.2013.08.025
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Ray's PDSP screening demonstrated that phenethylamine psychedelics as a class are not selective for 5-HT₂ receptors, interacting with 42 of 49 broadly assayed binding sitessupported
Phenylalkylamines interact with 42 of 49 sites. journal.pone.0009019
Hondebrink et al. confirmed that at concentrations achieved during recreational use, phenethylamine NPS engage adrenergic, dopaminergic, GABAergic, and cholinergic targetspartially supported
Hallucinogenic phenethylamines activate 5-HT2 receptors; additional targets include dopamine, adrenergic, GABA-A receptors. j.pharmthera.2017.10.022
Comparative binding profiles for 2C-I alongside other phenethylamine hallucinogens have been characterized by Eshleman et al. and Rickli et al., though complete quantitative comparison requires access to full-text binding tables.supported
In vitro receptor binding and function data for 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC. s00213-013-3303-6
Comparative binding profiles for 2C-I alongside other phenethylamine hallucinogens have been characterized by Eshleman et al. and Rickli et al., though complete quantitative comparison requires access to full-text binding tables.supported
In vitro receptor interaction profiles of NBOMe drugs vs 2C drugs and LSD. Characterizes binding affinities at multiple receptor types and monoamine transporters. j.neuropharm.2015.08.034
pharmacokinetic-detail5 · 5 ok
Theobald et al. administered 2C-I to Wistar rats and identified metabolites in urine by GC/MS and CE/MS. Two primary phase I pathways were characterized:supported
2C-I metabolized by O-demethylation at positions 2 and 5, followed by N-acetylation or deamination with subsequent oxidation/reduction. Beta-hydroxylation also identified. Most metabolites partially excreted in conjugated form. pmid:16810648
The systematic toxicological analysis (STA) procedure — full-scan GC/MS after acid hydrolysis, liquid-liquid extraction, and microwave-assisted acetylation — detected metabolites at doses corresponding to common recreational use.supported
GC/MS STA procedure detects intake at common dose in rat urine. pmid:16810648
2C-I and its metabolites are detectable in biological matrices by multiple validated methods: GC/MS with microwave-assisted acetylation in rat urine, LC-MS/MS in human urine, and isotope-dilution quantification using [¹³C₆]-labelled standardspartially supported
GC/MS STA procedure detects intake at common dose in rat urine. pmid:16810648
2C-I and its metabolites are detectable in biological matrices by multiple validated methods: GC/MS with microwave-assisted acetylation in rat urine, LC-MS/MS in human urine, and isotope-dilution quantification using [¹³C₆]-labelled standardssupported
LC-MS/MS confirmed 2C-I in urine. j.1556-4029.2009.01199.x
2C-I and its metabolites are detectable in biological matrices by multiple validated methods: GC/MS with microwave-assisted acetylation in rat urine, LC-MS/MS in human urine, and isotope-dilution quantification using [¹³C₆]-labelled standardssupported
Synthesis of 13C6-labelled internal standards including 2C-I for GC-MS/LC-MS/MS quantification in forensic analysis. jlcr.3193
chemistry3 · 3 ok
The compound is detectable and quantifiable in biological matrices by GC/MS and CE/MS.supported
GC/MS STA procedure detects intake at common dose in rat urine. pmid:16810648
The 2,5-dimethoxy groups are critical for serotonin 5-HT₂A and 5-HT₂C receptor activity; Marcher-Rørsted et al. demonstrated that this motif is essential for in vivo potency, though removal of either methoxy group causes only modest reduction in in vitro bindingsupported
Elimination of 2- or 5-methoxy group from 2C-B/DOB leads to modest drop in binding affinity/potency at 5-HT2A and 5-HT2C. In vivo reduction is more pronounced. acschemneuro.0c00129
This N-benzylation dramatically increases 5-HT₂A affinity and in vivo potency — 25I-NBOMe is approximately 14-fold more potent than 2C-I in the mouse head-twitch response assay.supported
25I-NBOMe is 14-fold more potent than 2C-I. j.neuropharm.2013.08.025
clinical-evidence3 · 3 ok
Dean et al. reviewed clinical presentations across the 2C drug class (including 2C-I, 2C-B, 2C-E, 2C-T-7, and others), documenting at least five deaths and a consistent pattern of sympathomimetic toxidrome, serotonin toxicity, and excited delirium in severe casessupported
At least 5 deaths reported. Common features: hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
The sole peer-reviewed human-level evidence consists of one clinical case report: Drees et al. documented a 39-year-old woman who presented with diminishing mental status, hypertension, and vasoconstriction after co-ingesting cocaine, MDA, and 2C-Ipartially supported
Case report: 39-year-old woman suffered hemorrhagic stroke after ingestion of cocaine, MDMA, and 2C-I. j.1556-4029.2009.01199.x
Gil-Martins et al. provided the most current review of 2C and NBOMe drug toxicodynamics, including discussion of abuse potentialsupported
Comprehensive review of psychedelic pathways of 2C and NBOMe designer drugs; serotonergic interactions, cardiovascular complications, neurotoxicity, abuse potential. j.toxrep.2025.101890
history2 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
This substitution pattern — where scheduling of one compound drives adoption of structurally related unscheduled analogs — is a recurring dynamic in the novel psychoactive substance (NPS) market. 2C-I was detected in forensic toxicology cases in the United States and across Europe during this period, establishing its presence in the recreational drug supply well before regulatory action.partially supported
LC-MS/MS confirmed 2C-I in urine. j.1556-4029.2009.01199.x