generation run 2026-04-26
57 min completedmodel pipeline-v5plan not recordedrun/f4f16e43…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 19 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
21 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | 2C or not 2C phenethylamine designer drug review | 1 | 1 | Key clinical toxicology review covering 2C drug adverse effects and treatment |
| 2 | PubMed | Monoamine receptor interaction profiles 4-thio-substituted phenethylamines 2C-T drugs | 1 | 1 | Most directly relevant pharmacological paper for 2C-T-2 receptor binding data |
| 3 | OpenAlex | 2C-T-2 phenethylamine psychedelic | 10 | 3 | Only 2C-T-2 specific papers selected; general psychedelic papers discarded |
| 4 | ClinicalTrials.gov · absence | 2C-T-2 psychedelic | 0 | 0 | No results — confirms no registered clinical trials |
| 5 | WebSearch | Luethi 2018 2C-T drugs monoamine receptor 2C-T-2 Ki EC50 binding affinity results | 10 | 1 | Key binding affinity data for 2C-T compound class including 2C-T-2 |
| 6 | PubMed | 2C-T-2 psychedelic phenethylamine pharmacology | 6 | 6 | All directly relevant to 2C-T-2 pharmacology, metabolism, or detection |
| 7 | PubMed | 2C-T-2 receptor binding serotonin 5-HT2A affinity Ki | 1 | 0 | Duplicate; already captured |
| 8 | WebSearch | Shulgin PiHKAL 2C-T-2 4-ethylthio synthesis discovery history | 10 | 2 | Primary source for discovery and synthesis history |
| 9 | WebSearch | 2C-T-2 legal status scheduling DEA controlled substance United States UK Australia | 10 | 3 | Legal status is required for the article |
| 10 | CrossRef/OpenAlex | DOI verification for key papers | 6 | 6 | DOI verification establishes api_verified status for these citations |
| 11 | PubChem | 2C-T-2 | 1 | 1 | Primary chemical identity verification for 2C-T-2 |
| 12 | PubMed | Nichols hallucinogenic phenethylamine structure activity relationships 5-HT2A | 8 | 2 | Nichols 2018 SAR review provides class-level context for 2C compounds; Hansen 2014 relevant to receptor binding mechanism |
| 13 | WebSearch | PiHKAL entry 40 2C-T-2 magical half-dozen Shulgin dosage effects | 10 | 1 | Primary source for discovery history |
| 14 | PubChem | CID 12074193 | 1 | 1 | Final chemical identity verification |
| 15 | CrossRef | Theobald 2007 DOI verification | 1 | 0 | DOI could not be verified; paper still valid via PMID 17067556 |
| 16 | WebSearch | EU Council Decision 2003/847/JHA 2C-T-2 2C-T-7 controlled substance | 10 | 1 | Primary legal source for EU scheduling of 2C-T-2 |
| 17 | WebSearch | 2C-T-2 MAO monoamine oxidase inhibition thioalkyl phenethylamine | 10 | 2 | Both papers directly address the MAO inhibitor claim in the seed data |
| 18 | WebSearch | Luethi 2018 2C-T drugs monoamine receptor 2C-T-2 Ki EC50 binding affinity | 10 | 1 | Provides class-level binding data from the key paper |
| 19 | PubMed · absence | 2C-T-2 2C-T-7 forensic toxicology death fatality postmortem | 0 | 0 | No results; general 2C death data came from Dean 2013 review instead |
| 20 | OpenAlex | Luethi Liechti in vitro predict human effective doses novel psychoactive | 5 | 2 | Key mechanistic papers for 2C-T-2 pharmacology and dose prediction |
| 21 | Grokipedia | 2C-T-2 receptor binding Ki EC50 legal status history | 1 | 3 | Web-retrieved data only; used for context but flagged appropriately; key specific values to be confirmed against primary sources |
74 claims by section — every cited sentence, checked against its source
safety19 · 15 ok
No confirmed fatal overdose attributed specifically to 2C-T-2 has been reported in the published literature.supported
At least 5 deaths. Excited delirium among fatalities. s13181-013-0295-x
Dean et al. (2013) reviewed clinical toxicology of the 2C drug class broadly, documenting the following presentation spectrum: hallucinations, agitation, aggression, violence, dysphoria, hypertension, tachycardia, seizures, and hyperthermiasupported
Clinical review of 2C drug pharmacology, toxicology, treatment. Hallucinations, agitation, tachycardia, seizures, hyperthermia. s13181-013-0295-x
At least five deaths have been attributed to 2C compounds collectively, with excited delirium the predominant fatal presentationsupported
At least 5 deaths. Excited delirium among fatalities. s13181-013-0295-x
Claim in safety — inconclusiveinconclusiveworking →
2C-T-2 showed lower cytotoxicity than its corresponding NBOMe analog (25T2-NBOMe), consistent with lower lipophilicitysupported
NBOMes more cytotoxic than 2C counterparts. jox14020044
Cardiovascular disease: 2C-class intoxication presents with hypertension and tachycardia; pre-existing cardiovascular conditions increase risk of adverse events.supported
Hallucinations, agitation, tachycardia, seizures, hyperthermia. s13181-013-0295-x
Dean et al. (2013) noted agitation, aggression, and violence as clinical presentations of 2C drug intoxication, consistent with a serotonergic sympathomimetic profile.supported
Clinical review of 2C drug pharmacology, toxicology, treatment. Hallucinations, agitation, tachycardia, seizures, hyperthermia. s13181-013-0295-x
De la Fuente Revenga et al. (2022) demonstrated this mechanism with DOI (a structurally related phenylisopropylamine psychedelic): repeated administration caused progressive HTR reduction and measurable 5-HT₂A receptor density decrease in mouse frontal cortex, independent of β-arrestin2.supported
DOI caused 5-HT2AR downregulation in frontal cortex. Tolerance independent of beta-arrestin-2. Repeated psychedelic administration causes progressive HTR decrease. acschemneuro.2c00170
Cross-tolerance is established between serotonergic psychedelics: DOI and LSD show bidirectional cross-tolerance, extending to the 2C class by mechanistic similaritysupported
Cross-tolerance between DOI and LSD. acschemneuro.2c00170
The absence of DAT interaction (Ki > 10,000 nM) is consistent with negligible engagement of dopaminergic reward circuits.supported
no monoamine transporter activity (Ki > 4000 nM) j.neuropharm.2017.07.012
Because MAO-A and MAO-B are the primary metabolic enzymes for 2C-T-2, co-administration with irreversible MAOIs (phenelzine, tranylcypromine), reversible MAOIs (moclobemide), or MAO-B inhibitors (selegiline at higher doses) will substantially reduce clearancesupported
MAO-A and MAO-B are major enzymes in deamination metabolism. 2C compounds are MAO substrates susceptible to drug interactions with MAO inhibitors. j.bcp.2006.09.033
Claim in safety — inconclusiveinconclusiveworking →
SSRIs and SNRIs (fluoxetine, sertraline, venlafaxine, duloxetine) create pharmacodynamic serotonergic synergy when combined with 5-HT₂A agonists, elevating serotonin syndrome risksupported
Serotonergic drugs associated with acute serotonin syndrome, hyperthermia, seizures. s00204-020-02693-7
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Concurrent MAO inhibitor therapy: Any irreversible or reversible MAOI, including dietary supplements containing harmine/harmaline (ayahuasca components). 2C-T-2's primary metabolism by MAO-A/B makes this interaction potentially lethal.supported
MAO-A and MAO-B are major enzymes in deamination metabolism. 2C compounds are MAO substrates susceptible to drug interactions with MAO inhibitors. j.bcp.2006.09.033
Epilepsy or seizure history: Seizures are documented in 2C class intoxication.supported
Hallucinations, agitation, tachycardia, seizures, hyperthermia. s13181-013-0295-x
CYP2D6 poor metabolizer status: Minor pathway, but combined with other clearance-reducing factors (SSRI co-administration), could contribute to elevated exposure.supported
CYP2D6 minor role for 2C-T-2. j.bcp.2006.09.033
In cases of suspected 2C-T-2 intoxication, treatment is primarily supportive: * Benzodiazepines for agitation and seizures * Active cooling for hyperthermia * Cyproheptadine (5-HT antagonist) for serotonin syndrome features * Avoid physical restraint in excited delirium presentations (worsens hyperthermia) * Do not administer haloperidol (lowers seizure threshold; cardiovascular risk)supported
Clinical review of 2C drug pharmacology, toxicology, treatment. Hallucinations, agitation, tachycardia, seizures, hyperthermia. Excited delirium among fatalities. s13181-013-0295-x
pharmacology15 · 10 ok
This mechanism is established by convergent evidence from in vitro receptor binding assays, functional activation studies, and in vivo head-twitch response (HTR) data in the 2C-T thioalkyl series.supported
SAR study using HTR behavioral assay confirms 2C-T compounds including 2C-T-2 as psychedelic drugs. s00213-022-06279-2
This mechanism is established by convergent evidence from in vitro receptor binding assays, functional activation studies, and in vivo head-twitch response (HTR) data in the 2C-T thioalkyl series.supported
Characterized monoamine receptor and transporter interaction profiles. j.neuropharm.2017.07.012
This mechanism is established by convergent evidence from in vitro receptor binding assays, functional activation studies, and in vivo head-twitch response (HTR) data in the 2C-T thioalkyl series.supported
In vitro receptor binding and function data for 2C-T-2 and related phenethylamines. s00213-013-3303-6
Class-level data for the 2C-T series show 5-HT₂A Ki values ranging 1–54 nM and 5-HT₂C Ki values ranging 40–350 nM, with partial agonism at 5-HT₂A and 5-HT₂B.supported
5-HT2A Ki 1-54 nM, 5-HT2C 40-350 nM, rat TAAR1 5-68 nM; partial agonists at 5-HT2A/2B j.neuropharm.2017.07.012
Compounds that preferentially activate Gq at 5-HT₂A produce psychedelic-like HTR in rodent models, while β-arrestin-biased agonists do notsupported
5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response. Beta-arrestin-biased ligands block psychedelic effects. s41467-023-44016-1
HTR structure-activity relationship data for 2C-T-2 and related thio-substituted phenylalkylamines closely parallel known 5-HT₂A SAR, confirming classification as a serotonergic psychedelic.supported
Close parallels between HTR data and known SAR at 5-HT2A. SAR study confirms 2C-T compounds including 2C-T-2 as psychedelic drugs. s00213-022-06279-2
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Published evidence establishes that MAO-A and MAO-B are the primary enzymes responsible for 2C-T-2 deaminationsupported
MAO-A and MAO-B are major enzymes in deamination metabolism. j.bcp.2006.09.033
Claim in pharmacology — not_supportednot supportedworking →
MAO-A and MAO-B are the major enzymes responsible for oxidative deamination of 2C-T-2, established using cDNA-expressed human CYPs and MAOs with GC-MS quantificationsupported
MAO-A and MAO-B are major enzymes in deamination metabolism. CYP2D6 minor role for 2C-T-2. j.bcp.2006.09.033
CYP2D6 plays a minor role in metabolismsupported
CYP2D6 minor role for 2C-T-2. j.bcp.2006.09.033
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
In rat models, the major urinary metabolites of 2C-T-2 are the N-acetylated-sulfoxide and S-methylated-N-acetylated-sulfoxidesupported
For 2C-T-2, major metabolites are the N-acetylated-sulfoxide and S-methylated-N-acetylated-sulfoxide. bpb.b15-00953
comparative-pharmacology9 · 6 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Luethi et al. (2018) characterized multiple 2C-T analogs and reported 5-HT₂A Ki values ranging from 1–54 nM across the series. 2C-T-2's Ki of ~12.5 nM places it in the moderate-affinity range within this seriessupported
5-HT2A Ki 1-54 nM j.neuropharm.2017.07.012
All 2C-T compounds tested showed partial agonism at 5-HT₂A and 5-HT₂B with no significant monoamine transporter activity.supported
partial agonists at 5-HT2A/2B; no monoamine transporter activity (Ki > 4000 nM) j.neuropharm.2017.07.012
Halberstadt et al. (2023) confirmed that HTR SAR data for thio-substituted phenylalkylamines parallels known 5-HT₂A SAR, with the chain length and branching of the thioalkyl group modulating potency.supported
SAR study using HTR behavioral assay confirms 2C-T compounds including 2C-T-2 as psychedelic drugs. Close parallels between HTR data and known SAR at 5-HT2A. s00213-022-06279-2
Rickli et al. (2015) provided comparative receptor interaction profiles for 2C drugs versus their NBOMe analogssupported
Receptor binding profiles of NBOMe drugs vs 2C drugs. Comparative binding affinity data across serotonin receptor subtypes and monoamine transporters. j.neuropharm.2015.08.034
Gil-Martins et al. (2024) demonstrated that 2C-T-2 shows lower cytotoxicity than its corresponding NBOMe analog (25T2-NBOMe) in neuronal cell cultures, consistent with the lower lipophilicity of the parent 2C compoundsupported
NBOMes more cytotoxic than 2C counterparts. jox14020044
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
The 2C-T series activates rat TAAR1 with Ki values in the 5–68 nM range — a notable interaction given emerging interest in TAAR1 pharmacology for schizophrenia and addiction therapeuticssupported
rat TAAR1 5-68 nM j.neuropharm.2017.07.012
pharmacokinetic-detail8 · 6 ok
In vitro receptor binding data for the 2C class predict reported human effective doses with reasonable accuracy — compounds with higher 5-HT₂A affinity tend to be active at lower dosessupported
5-HT2A and 5-HT2C receptor affinity correlates with human effective doses for psychedelics. pyy047
MAO-A and MAO-B are the major enzymes responsible for oxidative deamination; CYP2D6 contributes a minor metabolic rolesupported
MAO-A and MAO-B are major enzymes in deamination metabolism. CYP2D6 minor role for 2C-T-2. j.bcp.2006.09.033
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
In rat urine, the major metabolites of 2C-T-2 are the N-acetylated-sulfoxide and S-methylated-N-acetylated-sulfoxidesupported
For 2C-T-2, major metabolites are the N-acetylated-sulfoxide and S-methylated-N-acetylated-sulfoxide. bpb.b15-00953
2C-T-2 can be detected in urine by gas chromatography-mass spectrometry (GC-MS) after solid-phase extraction, with validated methods reporting a limit of detection (LOD) of 2–10 ng/mL and limit of quantification (LOQ) of approximately 10 ng/mLsupported
GC/MS method for 10 psychedelic phenethylamines including 2C-T-2 in urine. LOD 2-10 ng/mL, LOQ 10 ng/mL. pmid:21871155
Earlier methods validated detection in human blood plasma by GC-MSsupported
GC/MS method for 2C series drugs including 2C-T-2 in human blood plasma. jms.859
A comprehensive review of analytical methods for 2,5-dimethoxyphenethylamines in biological matrices is available.supported
Review of analytical methods for quantification of DOx and 2C-x compounds in biological matrices including 2C-T-2. s11419-022-00638-6
receptor-pharmacology7 · 6 ok
Specific Ki and EC₅₀ values were compiled from the Luethi et al. 2018 pharmacological characterization of 2C-T drugs as reported via a secondary compilation, supplemented by data from Eshleman et al. 2014 and Rickli et al. 2015.supported
4-Thio-substituted phenethylamines (2C-T drugs) are potent psychedelics. Characterized monoamine receptor and transporter interaction profiles. j.neuropharm.2017.07.012
Specific Ki and EC₅₀ values were compiled from the Luethi et al. 2018 pharmacological characterization of 2C-T drugs as reported via a secondary compilation, supplemented by data from Eshleman et al. 2014 and Rickli et al. 2015.supported
In vitro receptor binding and function data for 2C-T-2 and related phenethylamines. s00213-013-3303-6
Specific Ki and EC₅₀ values were compiled from the Luethi et al. 2018 pharmacological characterization of 2C-T drugs as reported via a secondary compilation, supplemented by data from Eshleman et al. 2014 and Rickli et al. 2015.supported
Receptor binding profiles of NBOMe drugs vs 2C drugs. Comparative binding affinity data across serotonin receptor subtypes and monoamine transporters. j.neuropharm.2015.08.034
Psychedelic effects are selectively associated with the Gq pathway: compounds that activate Gq at 5-HT₂A produce HTR in rodents, while β-arrestin2-biased agonists (e.g., lisuride) do not generate psychedelic-like behavioral signatures. 2C-T-2's high efficacy (~87%) at 5-HT₂A–Gq is consistent with its full psychedelic activity.supported
5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response. Beta-arrestin-biased ligands block psychedelic effects. s41467-023-44016-1
β-Arrestin-biased 5-HT₂A agonists can still induce receptor downregulation and tachyphylaxis, indicating that tolerance and psychedelic effects are dissociable at the signaling pathway level.supported
Beta-arrestin-biased ligands block psychedelic effects and induce tachyphylaxis. s41467-023-44016-1
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Comparative receptor interaction profiles for the 2C series versus their NBOMe derivatives show that N-benzylation dramatically increases 5-HT₂A affinity while widening the selectivity gap over 5-HT₂C, contextualizing 2C-T-2's moderate but balanced binding profile.supported
Receptor binding profiles of NBOMe drugs vs 2C drugs. Comparative binding affinity data across serotonin receptor subtypes and monoamine transporters. j.neuropharm.2015.08.034
summary6 · 6 ok
The compound shows no dopaminergic transporter activity and no evidence of dependence liabilitysupported
no monoamine transporter activity (Ki > 4000 nM) j.neuropharm.2017.07.012
2C-T-2 binds the 5-HT₂A receptor with Ki ≈ 12.5 nM and the 5-HT₂C receptor with Ki ≈ 14.2 nM, functioning as a high-efficacy agonist at both targets (~87% and ~93% efficacy relative to serotonin, respectively)partially supported
5-HT2A Ki 1-54 nM, 5-HT2C 40-350 nM; partial agonists at 5-HT2A/2B j.neuropharm.2017.07.012
Psychedelic effects are transduced through 5-HT₂A–Gq signaling rather than β-arrestin2 recruitmentsupported
5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response. s41467-023-44016-1
In vitro studies demonstrate concentration-dependent mitochondrial dysfunction in neuronal cell lines at concentrations far exceeding pharmacologically relevant exposure. 2C-T-2 is metabolized primarily by MAO-A and MAO-B, making co-administration with MAO inhibitors a potentially lethal contraindication via impaired clearance and serotonin syndrome riskpartially supported
In vitro neurotoxicity of 2C-T-2 in SH-SY5Y cells: mitochondrial dysfunction, ATP depletion, GSH reduction. jox14020044
In vitro studies demonstrate concentration-dependent mitochondrial dysfunction in neuronal cell lines at concentrations far exceeding pharmacologically relevant exposure. 2C-T-2 is metabolized primarily by MAO-A and MAO-B, making co-administration with MAO inhibitors a potentially lethal contraindication via impaired clearance and serotonin syndrome riskpartially supported
MAO-A and MAO-B are major enzymes in deamination metabolism. 2C compounds are MAO substrates susceptible to drug interactions with MAO inhibitors. j.bcp.2006.09.033
Tolerance develops rapidly through 5-HT₂A receptor downregulation in the frontal cortex, with cross-tolerance extending to other serotonergic psychedelicssupported
DOI caused 5-HT2AR downregulation in frontal cortex. Cross-tolerance between DOI and LSD. acschemneuro.2c00170
clinical-evidence4 · 4 ok
At least five deaths were attributed to the 2C drug class, with excited delirium as the presentation consistent among fatalitiessupported
At least 5 deaths. Excited delirium among fatalities. s13181-013-0295-x
Clinical presentations of 2C intoxication may resemble sympathomimetic toxidrome or serotonin toxicity.supported
Hallucinations, agitation, tachycardia, seizures, hyperthermia. s13181-013-0295-x
Clinical presentations of 2C intoxication may resemble sympathomimetic toxidrome or serotonin toxicity.supported
Serotonergic drugs associated with acute serotonin syndrome, hyperthermia, seizures. s00204-020-02693-7
Dean et al. (2013) reviewed clinical presentations of 2C drug class intoxication, documenting hallucinations, agitation, aggression, dysphoria, hypertension, tachycardia, seizures, and hyperthermia as common featuressupported
Hallucinations, agitation, tachycardia, seizures, hyperthermia. s13181-013-0295-x
chemistry2 · 1 ok
Claim in chemistry — inconclusiveinconclusiveworking →
As a primary amine with two methoxy groups and a thioether, the compound is expected to be moderately lipophilic, with the thioether contributing to higher lipophilicity than the corresponding bromo or iodo analogs — consistent with the observation that 2C-T-2 shows lower cytotoxicity than its NBOMe derivative (25T2-NBOMe), a difference attributed in part to differential lipophilicity.supported
NBOMes more cytotoxic than 2C counterparts. jox14020044
history2 · 2 ok
The compound has attracted pharmacological research interest primarily as a member of the 2C-T thioalkyl series, providing structure-activity relationship data for phenethylamine psychedelicssupported
SAR study using HTR behavioral assay confirms 2C-T compounds including 2C-T-2 as psychedelic drugs. s00213-022-06279-2
The compound has attracted pharmacological research interest primarily as a member of the 2C-T thioalkyl series, providing structure-activity relationship data for phenethylamine psychedelicssupported
4-Thio-substituted phenethylamines (2C-T drugs) are potent psychedelics. Characterized monoamine receptor and transporter interaction profiles. j.neuropharm.2017.07.012
neuroscience2 · 1 ok
Activation of these receptors by serotonergic psychedelics enhances glutamatergic excitatory postsynaptic currents (EPSCs) at layer V pyramidal cell dendrites via an asynchronous mode of glutamate release — a mechanism first characterized by Aghajanian and Marek and proposed as the neurophysiological basis for hallucinogenic perceptual distortionssupported
5-HT2A-mediated enhancement of glutamatergic EPSPs at cortical pyramidal cell dendrites proposed as mechanism for cognitive/perceptual distortions. pmid:10432484
Claim in neuroscience — inconclusiveinconclusiveworking →