generation run 2026-04-21
77 min completedmodel pipeline-v5plan not recordedrun/3bbbc1c5…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 25 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
16 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov | 2C-E phenethylamine psychedelic | 1 | 0 | No registered clinical trials for 2C-E identified |
| 2 | PubMed | 2C-E pharmacokinetics metabolism cytochrome P450 | 1 | 1 | Only available review covering 2C-E metabolic pathways and CYP enzymes |
| 3 | PubMed | 2C-E 2,5-dimethoxy-4-ethylphenethylamine pharmacology | 5 | 5 | All selected as directly relevant to 2C-E pharmacology and toxicology |
| 4 | PubMed | 2C-E psychedelic receptor binding serotonin | 2 | 1 | Rickli 2015 provides comparative binding affinity data for 2C-E |
| 5 | PubChem | 2C-E | 1 | 1 | Primary PubChem record for 2C-E confirms all chemical identity data |
| 6 | OpenAlex | 2C-E phenethylamine psychedelic pharmacology | 10 | 2 | Ray 2010 provides comprehensive receptor binding data; Dean 2013 is the key toxicology review for 2C class |
| 7 | ClinicalTrials.gov | 2C-E phenethylamine psychedelic | 1 | 0 | Confirms absence of registered clinical trials for 2C-E |
| 8 | Web/News | 2C-E Minnesota 2010 mass poisoning deaths teenagers | 10 | 1 | Key historical toxicological event for 2C-E |
| 9 | PubMed | tramadol serotonin syndrome monoamine oxidase interaction drug | 7 | 2 | Tramadol-2C-E interaction mechanism: both serotonergic agents, additive risk of serotonin syndrome |
| 10 | PubMed | hallucinogen cross-tolerance 5-HT2A downregulation | 1 | 1 | Mechanism for psychedelic cross-tolerance relevant to 2C-E tolerance profile |
| 11 | Erowid | 2C-E legal status by jurisdiction | 15 | 1 | Comprehensive jurisdiction-by-jurisdiction legal status |
| 12 | Web | 2C-E Shulgin PIHKAL synthesis history first report 1991 | 10 | 1 | Primary historical source information |
| 13 | Federal Register/PubMed | 2C-E DEA Schedule I SDAPA 2012 | 1 | 1 | Official US scheduling documentation |
| 14 | Crossref/DOI verification | DOI verification for key papers | 2 | 2 | Primary source verification |
| 15 | PubChem CID | CID 24729233 (2C-E) | 1 | 1 | Verification of all PubChem-available chemical identity data |
| 16 | PiHKAL / Web sources | 2C-E PIHKAL entry 24 magical half-dozen Shulgin | 5 | 1 | Historical synthesis and characterization data |
64 claims by section — every cited sentence, checked against its source
safety18 · 16 ok
A second mass poisoning (2019) involved middle-aged individuals in Europe who consumed both 2C-E and Bromo-DragonFlysupported
Case report of a mass poisoning event involving middle-aged individuals who consumed 2C-E combined with Bromo-DragonFly (BDF). s00414-018-1882-9
The clinical presentation of 2C-drug intoxication, reviewed comprehensively by Dean and colleagues (2013), includes hallucinations, agitation, aggression, hypertension, tachycardia, seizures, and hyperthermia. Excited delirium was the most consistent presentation among reported deaths from 2C-series compounds (at least five deaths attributed to the 2C class at the time of that review).supported
Documents at least 5 deaths; common presentations include hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
The clinical presentation of 2C-drug intoxication, reviewed comprehensively by Dean and colleagues (2013), includes hallucinations, agitation, aggression, hypertension, tachycardia, seizures, and hyperthermia. Excited delirium was the most consistent presentation among reported deaths from 2C-series compounds (at least five deaths attributed to the 2C class at the time of that review).supported
Documents at least 5 deaths; common presentations include hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
The toxidrome can resemble either a sympathomimetic presentation or serotonin toxicity, reflecting 2C-E's dual mechanism of 5-HT₂A agonism and mild monoamine reuptake inhibitionsupported
2C-E acts as partial agonist of 5-HT2A, 5-HT2B, and 5-HT2C; inhibits NE and 5-HT reuptake. Induced perceptual alterations, hallucinations, euphoric mood, physiological stimulation. fphar.2020.00233
The toxidrome can resemble either a sympathomimetic presentation or serotonin toxicity, reflecting 2C-E's dual mechanism of 5-HT₂A agonism and mild monoamine reuptake inhibitionsupported
common presentations include hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
Claim in safety — not_supportednot supportedworking →
In the only controlled human observation (n=10, oral 6.5–25 mg), elevated blood pressure and heart rate were documented, with no serious adverse events at these dosessupported
Observational study of 10 recreational psychedelic users self-administering oral 2C-E (6.5–25 mg). Induced perceptual alterations, hallucinations, euphoric mood, physiological stimulation. fphar.2020.00233
Claim in safety — inconclusiveinconclusiveworking →
The mechanism involves 5-HT₂A receptor downregulation in frontal cortex, demonstrated for psychedelic 5-HT₂A agonists in mouse modelssupported
Repeated DOI causes progressive HTR decrease and 5-HT2AR downregulation. Cross-tolerance between psychedelic 5-HT2A agonists (DOI, LSD). acschemneuro.2c00170
Cross-tolerance with other classical psychedelics — LSD, psilocybin, mescaline, DMT, and other 2C compounds — is established for the classpartially supported
Cross-tolerance between psychedelic 5-HT2A agonists (DOI, LSD) but not with non-psychedelic lisuride. acschemneuro.2c00170
This cross-tolerance is specific to psychedelic 5-HT₂A agonists and does not extend to non-psychedelic 5-HT₂A agonists such as lisuride.supported
Cross-tolerance between psychedelic 5-HT2A agonists (DOI, LSD) but not with non-psychedelic lisuride. acschemneuro.2c00170
The principal interaction risk for 2C-E derives from its serotonergic activity — partial agonism at 5-HT₂A/2B/2C receptors combined with weak serotonin and norepinephrine reuptake inhibition.supported
2C-E acts as partial agonist of 5-HT2A, 5-HT2B, and 5-HT2C; inhibits NE and 5-HT reuptake. fphar.2020.00233
Tramadol inhibits the serotonin transporter (SERT) in human SERT-transfected HEK293 cells and is associated with serotonin syndrome when combined with other serotonergic agentssupported
Tramadol inhibits human SERT in HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome. s00204-018-2244-6
Tramadol inhibits the serotonin transporter (SERT) in human SERT-transfected HEK293 cells and is associated with serotonin syndrome when combined with other serotonergic agentssupported
Tramadol inhibits SERT and has serotonergic effects. Warning exists for all serotonergic antidepressants combined with tramadol. 0897190013504957
The combination of 5-HT₂A agonism (2C-E) with SERT inhibition (tramadol) substantially increases synaptic serotonin activity — a recognised mechanism for serotonin syndromesupported
Tramadol inhibits human SERT in HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome. s00204-018-2244-6
Bromo-DragonFly was documented in a mass poisoning event when combined with 2C-E; the specific mechanism of the combined toxicity has not been characterised.supported
Case report of a mass poisoning event involving middle-aged individuals who consumed 2C-E combined with Bromo-DragonFly (BDF). s00414-018-1882-9
Cardiovascular conditions — 2C-E produces elevated blood pressure and heart ratesupported
Induced perceptual alterations, hallucinations, euphoric mood, physiological stimulation. fphar.2020.00233
Epilepsy and seizure disorders — seizures are a documented feature of 2C-class intoxication, indicating that 2C-E may lower the seizure threshold.supported
common presentations include hallucinations, agitation, hypertension, tachycardia, seizures, hyperthermia, excited delirium. s13181-013-0295-x
pharmacology10 · 9 ok
2C-E is a partial agonist at serotonin 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors and a weak inhibitor of norepinephrine and serotonin reuptakesupported
2C-E acts as partial agonist of 5-HT2A, 5-HT2B, and 5-HT2C; inhibits NE and 5-HT reuptake. fphar.2020.00233
The 5-HT₂A receptor is the primary mediator of psychedelic effects: agonism at this receptor on neocortical layer V pyramidal cells enhances non-synchronous glutamatergic excitatory postsynaptic potentials, with downstream effects on thalamocortical connectivity and prefrontal cortical metabolism.supported
Novel 5-HT2A-mediated enhancement of glutamatergic EPSPs at cortical pyramidal cell dendrites proposed as mechanism for cognitive/perceptual distortions. pmid:10432484
The 5-HT₂A receptor is the primary mediator of psychedelic effects: agonism at this receptor on neocortical layer V pyramidal cells enhances non-synchronous glutamatergic excitatory postsynaptic potentials, with downstream effects on thalamocortical connectivity and prefrontal cortical metabolism.supported
Comprehensive review: hallucinogens stimulate 5-HT2A receptors on neocortical pyramidal cells; activation leads to increased cortical glutamate via thalamic afferents. pmid:14761703
As a phenethylamine of the 2C series, 2C-E has lower intrinsic activity at 5-HT₂A than phenylisopropylamine analogues of the DO series (e.g., DOET, DOM), reflecting the established structure-activity relationship whereby the alpha-methyl group of the amphetamine side chain increases both potency and efficacy at serotonergic targetssupported
(R)-phenylisopropylamines have higher intrinsic activity than phenethylamine counterparts. Relevant to 2C-E vs DO-series comparison. pmid:16277614
At monoamine transporters, 2C-E exerts weak effects on dopamine, serotonin, and norepinephrine reuptake compared to classical stimulants — the compound's primary activity is receptor-mediated rather than transporter-mediated.supported
2C-E slightly influenced monoamine reuptake/release vs stimulants; primary activity at serotonin receptors confirmed. pmid:17223101
In rat brain membrane preparations, 2C-E stimulated [³⁵S]GTPγS binding at serotonin receptors in cortical membranes, confirming functional receptor activation.supported
2C-E stimulated G protein binding in cortical membranes. Demonstrates 2C-E acts at serotonin receptors in rat brain. pmid:18057721
The only published human pharmacokinetic data derive from an observational study conducted in Spain with 10 recreational psychedelic users who self-administered 2C-E orally at doses of 6.5, 8, 10, 15, or 25 mg.supported
Observational study of 10 recreational psychedelic users self-administering oral 2C-E (6.5–25 mg). fphar.2020.00233
The primary metabolic pathways for 2C-E, reviewed for the 2C class generally, are O-demethylation at the 2- and 5-methoxy positions, hydroxylation of the ethyl side chain at position 4, deamination of the ethylamine moiety, and phase II conjugation (glucuronidation, sulphation) of hydroxylated metabolites.supported
Reviews metabolic pathways of 2C compounds including 2C-E. Covers in vivo/in vitro metabolites and CYP enzyme-dependent metabolism for phenethylamine-type designer drugs. pmid:20540700
Claim in pharmacology — inconclusiveinconclusiveworking →
2C-E has been confirmed as a metabolite of 25E-NBOH via N-debenzylation, with identity verified using a commercial reference standardsupported
2C-E confirmed as a metabolite of 25E-NBOH via N-debenzylation using commercial reference standard. j.jpba.2026.117417
comparative-pharmacology9 · 9 ok
Observational studies of both compounds were conducted in recreational users using identical methodology: 2C-B at 10–20 mg oral (2018) and 2C-E at 6.5–25 mg oral (2020).supported
Observational study of 16 healthy experienced users taking oral 2C-B (10-20 mg). Comparison study to 2C-E. fphar.2018.00206
Observational studies of both compounds were conducted in recreational users using identical methodology: 2C-B at 10–20 mg oral (2018) and 2C-E at 6.5–25 mg oral (2020).supported
Observational study of 10 recreational psychedelic users self-administering oral 2C-E (6.5–25 mg). fphar.2020.00233
Saliva Tmax was approximately 1 hour for 2C-B versus approximately 2 hours for 2C-E, suggesting slower absorption or distribution kinetics for 2C-E. 2C-E is consistently characterised — by Shulgin and in user reports — as more cognitively demanding, with greater introspective depth and more prominent body load than 2C-B at equipotent doses.supported
Saliva Tmax ~2 h post-administration. fphar.2020.00233
Saliva Tmax was approximately 1 hour for 2C-B versus approximately 2 hours for 2C-E, suggesting slower absorption or distribution kinetics for 2C-E. 2C-E is consistently characterised — by Shulgin and in user reports — as more cognitively demanding, with greater introspective depth and more prominent body load than 2C-B at equipotent doses.supported
Observational study of 16 healthy experienced users taking oral 2C-B (10-20 mg). Tmax ~1 h. fphar.2018.00206
The N-2-methoxybenzyl (NBOMe) derivatives of 2C compounds — including 25E-NBOMe, the direct NBOMe analogue of 2C-E — show dramatically higher 5-HT₂A binding affinity than their parent 2C compounds (low nanomolar Ki values versus the higher Ki values of the 2C series)supported
Characterizes receptor binding profiles of NBOMe drugs vs 2C drugs and LSD in vitro. Includes Ki values at multiple receptor subtypes and monoamine transporters. j.neuropharm.2015.08.034
This potency differential translates to substantially lower active doses for NBOMe compounds and a correspondingly narrower margin between active and toxic doses.supported
Ki values in low nanomolar range at 5-HT2A/2C (>1000-fold selectivity over 5-HT1A). Higher 5-HT2A affinity than 2C counterparts. fnins.2020.00078
This potency differential translates to substantially lower active doses for NBOMe compounds and a correspondingly narrower margin between active and toxic doses.supported
Review of NBOMe epidemiology and acute toxicity. Adverse effects include hallucinations, agitation, violent behavior, seizures, hyperthermia, excited delirium. 15563650.2015.1004179
2C-E has been confirmed as the N-debenzylation metabolite of 25E-NBOH, establishing a direct metabolic and structural relationship between these compound families.supported
2C-E confirmed as a metabolite of 25E-NBOH via N-debenzylation using commercial reference standard. j.jpba.2026.117417
The structural relationship between 2C-E (phenethylamine) and DOET (phenylisopropylamine) illustrates a key structure-activity principle: the alpha-methyl group of the amphetamine side chain increases both potency and intrinsic efficacy at 5-HT₂A, with DO-series compounds acting as more efficacious agonists than their 2C-series counterpartssupported
(R)-phenylisopropylamines have higher intrinsic activity than phenethylamine counterparts. Relevant to 2C-E vs DO-series comparison. pmid:16277614
pharmacokinetic-detail6 · 6 ok
The single human dataset provides only saliva concentration-time data following oral administration of 6.5–25 mg in 10 subjects.supported
Observational study of 10 recreational psychedelic users self-administering oral 2C-E (6.5–25 mg). Saliva Tmax ~2 h post-administration. fphar.2020.00233
Saliva Tmax of approximately 2 hours following oral dosing suggests peak absorption occurs within the first 2 hours post-ingestionsupported
Saliva Tmax ~2 h post-administration. fphar.2020.00233
The metabolic pathways characterised for the 2C class — O-demethylation, side-chain hydroxylation, deamination, and phase II conjugation — are reviewed in Meyer and Maurer (2010)supported
Reviews metabolic pathways of 2C compounds including 2C-E. Covers in vivo/in vitro metabolites and CYP enzyme-dependent metabolism for phenethylamine-type designer drugs. pmid:20540700
The compound's weak monoamine transporter inhibition suggests pharmacodynamic interactions are more likely clinically significant than pharmacokinetic interactions.supported
2C-E acts as partial agonist of 5-HT2A, 5-HT2B, and 5-HT2C; inhibits NE and 5-HT reuptake. fphar.2020.00233
General screening methods applicable to 2C-E detection include GC-EI-MS and HPLC-electrospray-MSsupported
GC-MS and LC-MS method for designer phenethylamines including 2C series in blood and urine. pmid:15516287
A UPLC-MS/MS method for 75 phenethylamines and derivatives, including 2C-E, has been validated in hair matrices, providing a forensic detection window extending beyond the acute exposure period.supported
UPLC-MS/MS method for 75 phenethylamines including 2C-series in hair. LOD 0.5-10 pg/mg. Applied to forensic cases. j.jpba.2023.115367
summary6 · 6 ok
A single observational pharmacokinetic study (n=10, oral doses 6.5–25 mg) remains the only controlled human data. 2C-E was placed in Schedule I in the United States in 2012 under the Synthetic Drug Abuse Prevention Act, creating substantial regulatory barriers to further human research.supported
Observational study of 10 recreational psychedelic users self-administering oral 2C-E (6.5–25 mg). fphar.2020.00233
A single observational pharmacokinetic study (n=10, oral doses 6.5–25 mg) remains the only controlled human data. 2C-E was placed in Schedule I in the United States in 2012 under the Synthetic Drug Abuse Prevention Act, creating substantial regulatory barriers to further human research.supported
SDAPA signed July 9, 2012 placed 26 substances including 2C-E in Schedule I. pmid:23289157
2C-E acts as a partial agonist at serotonin 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with weak inhibition of serotonin and norepinephrine reuptakesupported
2C-E acts as partial agonist of 5-HT2A, 5-HT2B, and 5-HT2C; inhibits NE and 5-HT reuptake. fphar.2020.00233
Receptor screening across 42 of 49 tested sites confirms a broad interaction profile typical of phenylalkylamines, though the primary psychedelic effects are 5-HT₂A-mediatedpartially supported
Receptor affinity pharmacology (Ki values) of 25 psychedelic drugs including 2C-E at 51 receptors, transporters, and ion channels using NIMH-PDSP data. journal.pone.0009019
One confirmed fatality — a 19-year-old male following insufflation — and two mass poisoning events are documentedpartially supported
Case report of a mass poisoning event involving middle-aged individuals who consumed 2C-E combined with Bromo-DragonFly (BDF). s00414-018-1882-9
Tolerance develops rapidly via 5-HT₂A receptor downregulation in frontal cortex and cross-generalises to other classical psychedelicssupported
Repeated DOI causes progressive HTR decrease and 5-HT2AR downregulation. Cross-tolerance between psychedelic 5-HT2A agonists (DOI, LSD) but not with non-psychedelic lisuride. acschemneuro.2c00170
receptor-pharmacology4 · 4 ok
Ray (2010) screened 2C-E across 51 receptor, transporter, and ion channel targets through the NIMH Psychoactive Drug Screening Program (NIMH-PDSP). 2C-E demonstrated measurable affinity at 42 of 49 sites tested, consistent with the broad receptor interaction profile typical of phenylalkylamines.supported
Receptor affinity pharmacology (Ki values) of 25 psychedelic drugs including 2C-E at 51 receptors, transporters, and ion channels using NIMH-PDSP data. journal.pone.0009019
Rickli and colleagues (2015) compared the receptor profiles of 2C-series compounds (including 2C-E) against NBOMe derivatives and LSD at multiple serotonin receptor subtypes and monoamine transporters. 2C-E showed moderate affinity at 5-HT₂A and 5-HT₂C; by contrast, NBOMe derivatives demonstrated dramatically higher 5-HT₂A affinity (low nanomolar Ki values compared to the higher Ki values of parent 2C compounds).supported
Characterizes receptor binding profiles of NBOMe drugs vs 2C drugs and LSD in vitro. Includes Ki values at multiple receptor subtypes and monoamine transporters. j.neuropharm.2015.08.034
Eshleman and colleagues (2014) characterised in vitro receptor and transporter binding for 2C-E alongside 2C-C, 2C-D, 2C-I, 2C-T-2, and DOC, including functional transporter binding data.supported
In vitro receptor binding and function data for 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC. Includes transporter binding, mouse locomotion, and rat drug discrimination data. s00213-013-3303-6
While 5-HT₂A agonism is the established primary mechanism for psychedelic effects, contributions of secondary receptor targets — including 5-HT₂B, 5-HT₂C, adrenergic, and trace amine-associated receptors — to the overall pharmacological and subjective profile of 2C-E have not been systematically dissected.supported
Comprehensive review: hallucinogens stimulate 5-HT2A receptors on neocortical pyramidal cells; activation leads to increased cortical glutamate via thalamic afferents. pmid:14761703
chemistry3 · 3 ok
This structural difference accounts for 2C-E's lower intrinsic activity at 5-HT₂A compared to its DO-series counterpart.supported
(R)-phenylisopropylamines have higher intrinsic activity than phenethylamine counterparts. Relevant to 2C-E vs DO-series comparison. pmid:16277614
Forensic analytical methods for detection have been developed using GC-EI-MS and HPLC-electrospray-MS and UPLC-MS/MS in hair matrices.supported
GC-MS and LC-MS method for designer phenethylamines including 2C series in blood and urine. pmid:15516287
Forensic analytical methods for detection have been developed using GC-EI-MS and HPLC-electrospray-MS and UPLC-MS/MS in hair matrices.supported
UPLC-MS/MS method for 75 phenethylamines including 2C-series in hair. LOD 0.5-10 pg/mg. Applied to forensic cases. j.jpba.2023.115367
neuroscience3 · 3 ok
5-HT₂A agonism on layer V pyramidal neurons in the prefrontal cortex triggers enhanced glutamatergic excitatory postsynaptic potentials via a non-synchronous release mechanismsupported
Novel 5-HT2A-mediated enhancement of glutamatergic EPSPs at cortical pyramidal cell dendrites proposed as mechanism for cognitive/perceptual distortions. pmid:10432484
2C-E's classification as a partial agonist at 5-HT₂A — with lower intrinsic activity than DO-series compounds — suggests that its neural effects may represent a submaximal activation of the 5-HT₂A-mediated cortical disruption pathwaysupported
(R)-phenylisopropylamines have higher intrinsic activity than phenethylamine counterparts. Relevant to 2C-E vs DO-series comparison. pmid:16277614
How does 2C-E's broad receptor interaction profile (affinity at 42 of 49 tested targets) modulate the neural signature compared to more selective 5-HT₂A agonists?supported
Receptor affinity pharmacology (Ki values) of 25 psychedelic drugs including 2C-E at 51 receptors, transporters, and ion channels using NIMH-PDSP data. journal.pone.0009019
clinical-evidence2 · 1 ok
The sole published controlled human data come from an observational (non-interventional) study assessing acute effects in 10 recreational psychedelic users who self-administered oral doses of 6.5–25 mgsupported
Observational study of 10 recreational psychedelic users self-administering oral 2C-E (6.5–25 mg). fphar.2020.00233
Claim in clinical-evidence — inconclusiveinconclusiveworking →
history2 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
A second mass poisoning event, documented in 2019, involved middle-aged individuals in Europe who consumed a combination of 2C-E and Bromo-DragonFly, representing an unusual case both for the age profile of the consumers and the polydrug combination involved.supported
Case report of a mass poisoning event involving middle-aged individuals who consumed 2C-E combined with Bromo-DragonFly (BDF). s00414-018-1882-9
legal-status1 · 1 ok
In the United States, it was placed in Schedule I under the Synthetic Drug Abuse Prevention Act of 2012supported
SDAPA signed July 9, 2012 placed 26 substances including 2C-E in Schedule I. pmid:23289157