generation run 2026-04-26
50 min completedmodel pipeline-v5plan not recordedrun/e3ad5c8f…Selection
Verification
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- 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
17 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | OpenAlex | 2C-D psychedelic phenethylamine receptor binding | 342 | 1 | Only MAO inhibition paper directly relevant to 2C-D |
| 2 | PubChem | 2C-D | 1 | 1 | Only match; confirms seed data chemical identity |
| 3 | PubMed | 2C-D 2,5-dimethoxy-4-methylphenethylamine pharmacology | 1 | 1 | Direct study on 2C-D pharmacology; receptor binding and drug discrimination data |
| 4 | PubMed | 2C phenethylamine series 5-HT2A receptor binding Ki hallucinogen discrimination | 1 | 1 | Relevant SAR context for 2C series |
| 5 | ClinicalTrials.gov · absence | 2C-D phenethylamine psychedelic | 0 | 0 | No relevant results |
| 6 | OpenAlex | 2C-D 2,5-dimethoxy-4-methylphenethylamine Shulgin | 13 | 3 | All directly relevant to 2C series pharmacology context |
| 7 | PubMed | 2C-D serotonin receptor 5-HT2A binding affinity 2,5-dimethoxy-4-methylphenethylamine | 1 | 0 | No new papers found |
| 8 | PMC | 2C-D specific dosage pharmacokinetics | 1 | 3 | Direct article text with 2C-D specific data |
| 9 | Web Search | 2C-D PIHKAL Shulgin 1991 synthesis first described history | 10 | 3 | Key historical provenance data |
| 10 | Erowid | 2C-D PIHKAL entry dosage effects history | 1 | 5 | Primary source for 2C-D human bioassay and synthesis history |
| 11 | Web Search | 2C-D legal status scheduling DEA US controlled substance | 10 | 3 | Key legal status data by jurisdiction |
| 12 | Cayman Chemical | 2C-D chemical identifiers | 1 | 1 | Confirms CAS registry number |
| 13 | PubMed | psychedelic cross-tolerance serotonin 5-HT2A receptor downregulation LSD | 1 | 1 | Directly supports tolerance mechanism section |
| 14 | Web Search | 2C-D UK Misuse of Drugs Act Class A schedule legal status Europe Australia | 10 | 3 | Legal status by jurisdiction |
| 15 | PubMed | 4-alkyl chain 2,5-dimethoxyamphetamine serotonin receptor psychedelic Molecular Psychiatry | 1 | 1 | DOM is the amphetamine analog of 2C-D; provides closest published in vitro data for the 4-methyl 2,5-dimethoxy scaffold |
| 16 | PubMed | 2,5-dimethoxy-amphetamine phenethylamine biological matrices forensic toxicology | 1 | 1 | Relevant to analytical detection and metabolic pathways for 2C-x series |
| 17 | Multiple | Comparing seed data duration vs PIHKAL data | 2 | 2 | Identified discrepancy requiring editorial flag |
48 claims by section — every cited sentence, checked against its source
safety17 · 14 ok
No human toxic dose has been establishedsupported
2C-D dose range 20-60mg, duration 4-6h. s13181-013-0295-x
The Dean et al. clinical toxicology review documented at least five deaths in the 2C drug literature overall, but these involved other 2C compounds — primarily 2c-e and 2c-i — and no 2C-D-specific fatalities were reported.partially supported
At least 5 deaths reported; excited delirium common. No specific 2C-D deaths documented. s13181-013-0295-x
For the 2C-series class, acute adverse presentations include:supported
Sympathomimetic and serotonin toxicity presentations. s13181-013-0295-x
2C-D's demonstrated MAO inhibitory potential represents an additional toxicological mechanism: MAO inhibition elevates synaptic monoamine concentrations, which can contribute to cardiovascular stress, agitation, and serotonin toxicity, particularly when 2C-D is combined with other serotonergic or sympathomimetic substances.supported
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. IC50 values ranged from 10–125 μM for MAO-A and 1.7–180 μM for MAO-B. dta.2494
Claim in safety — inconclusiveinconclusiveworking →
This tolerance is mediated by 5-HT₂A receptor downregulation in the frontal cortex and is independent of β-arrestin-2supported
Tolerance develops after single and repeated DOI administration via 5-HT2AR downregulation in frontal cortex. Mechanism independent of beta-arrestin-2. acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
The combination of 2C-D with other serotonergic substances carries risk of serotonin toxicity. 2C-D contributes to this risk through two mechanisms: direct 5-HT₂A agonism and MAO inhibitionsupported
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
Tramadol inhibits the serotonin transporter (SERT), elevating synaptic serotoninsupported
Reviews serotonin toxicity from opioids, particularly tramadol via SERT inhibition. Tramadol implicated in serotonin toxicity through multiple mechanisms. s00204-018-2244-6
Combined with 2C-D's 5-HT₂A agonism and MAO inhibitory potential, this creates convergent serotonergic stimulationsupported
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
Tramadol fatalities in combination with MAOIs are documentedsupported
tramadol + MAOI fatalities documented. s40263-025-01256-7
Classical MAOIs combined with 2C-D would produce dual MAO inhibition (exogenous MAOI plus 2C-D's own MAO inhibitory activity) alongside direct 5-HT₂A agonism — a high-risk combination for serotonin toxicity.supported
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
Classical MAOIs combined with 2C-D would produce dual MAO inhibition (exogenous MAOI plus 2C-D's own MAO inhibitory activity) alongside direct 5-HT₂A agonism — a high-risk combination for serotonin toxicity.supported
2C-B noted with agitation adverse events in MAOI combinations; MAOIs generally manageable with some classic hallucinogens with monitoring. s40263-025-01256-7
2C-series drugs including 2C-I have been specifically documented in serotonin syndrome case reports when combined with other serotonergic agents. 2C-D carries the same mechanistic risk.supported
Systematic review of serotonin toxicity from NPS. Psychedelic phenethylamines (2C-I, 25I-NBOMe) implicated. j.expneurol.2021.113638
Cardiovascular disease — sympathomimetic effects (hypertension, tachycardia) documented for the 2C-series class may be clinically significant in patients with pre-existing cardiovascular conditionssupported
Sympathomimetic and serotonin toxicity presentations. s13181-013-0295-x
Concurrent MAOI use — dual MAO inhibition plus 5-HT₂A agonism creates high risk for serotonin toxicitysupported
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
Claim in safety — inconclusiveinconclusiveworking →
pharmacology10 · 5 ok
2C-D exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptors, the principal molecular target for classical hallucinogenic phenethylamines and tryptamines. 5-HT₂A activation on layer V pyramidal neurons in the prefrontal cortex induces enhanced asynchronous glutamatergic excitatory postsynaptic currents (EPSCs), a mechanism proposed to underlie the perceptual distortions and cognitive alterations characteristic of psychedelic states. 2C-D also acts as an agonist at 5-HT₂C receptors, though the relative contribution of 5-HT₂C activation to its subjective effects has not been delineated.supported
5-HT2A as principal target. Discusses 2C series and the importance of 4-substituent size/lipophilicity on potency. 7854_2017_475
2C-D exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptors, the principal molecular target for classical hallucinogenic phenethylamines and tryptamines. 5-HT₂A activation on layer V pyramidal neurons in the prefrontal cortex induces enhanced asynchronous glutamatergic excitatory postsynaptic currents (EPSCs), a mechanism proposed to underlie the perceptual distortions and cognitive alterations characteristic of psychedelic states. 2C-D also acts as an agonist at 5-HT₂C receptors, though the relative contribution of 5-HT₂C activation to its subjective effects has not been delineated.supported
Convergent evidence that tryptamines and phenethylamines are partial agonists at 5-HT2A receptors. 5-HT2A-mediated enhancement of glutamatergic EPSPs in cortical layer V pyramidal cells proposed as mechanism for perceptual distortions. pmid:10432484
2C-D exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptors, the principal molecular target for classical hallucinogenic phenethylamines and tryptamines. 5-HT₂A activation on layer V pyramidal neurons in the prefrontal cortex induces enhanced asynchronous glutamatergic excitatory postsynaptic currents (EPSCs), a mechanism proposed to underlie the perceptual distortions and cognitive alterations characteristic of psychedelic states. 2C-D also acts as an agonist at 5-HT₂C receptors, though the relative contribution of 5-HT₂C activation to its subjective effects has not been delineated.supported
5-HT2A receptor activation induces asynchronous glutamate release in layer V pyramidal cells of prefrontal cortex; DOI (5-HT2A agonist) replicated these effects. pmid:10216183
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Wagmann et al. evaluated 17 psychoactive 2C-series drugs including 2C-D for inhibition of human monoamine oxidase A (MAO-A) and MAO-Bsupported
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
Compound-specific IC₅₀ values for 2C-D were reported in the full paper's tables but are not available from the published abstractsupported
IC50 values ranged from 10–125 μM for MAO-A and 1.7–180 μM for MAO-B. dta.2494
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
summary7 · 5 ok
2C-D acts as an agonist at 5-HT₂A and 5-HT₂C receptors, with psychedelic effects mediated through the canonical 5-HT₂A pathway in cortical layer V pyramidal neuronssupported
5-HT2A receptor activation induces asynchronous glutamate release in layer V pyramidal cells of prefrontal cortex; DOI (5-HT2A agonist) replicated these effects. pmid:10216183
2C-D acts as an agonist at 5-HT₂A and 5-HT₂C receptors, with psychedelic effects mediated through the canonical 5-HT₂A pathway in cortical layer V pyramidal neuronssupported
Convergent evidence that tryptamines and phenethylamines are partial agonists at 5-HT2A receptors. 5-HT2A-mediated enhancement of glutamatergic EPSPs in cortical layer V pyramidal cells proposed as mechanism for perceptual distortions. pmid:10432484
Claim in summary — not_supportednot supportedworking →
No LD₅₀ or toxic dose data have been published for 2C-D, and no fatalities attributable to 2C-D alone appear in the clinical literaturesupported
No specific 2C-D deaths documented. s13181-013-0295-x
Tolerance develops rapidly via 5-HT₂A receptor downregulation in the frontal cortex, a class-wide mechanism confirmed in mouse models. 2C-D demonstrates MAO inhibitory potential, elevating the risk of serotonin toxicity in combination with serotonergic agentspartially supported
Tolerance develops after single and repeated DOI administration via 5-HT2AR downregulation in frontal cortex. Cross-tolerance between DOI and LSD confirmed. Mechanism independent of beta-arrestin-2. acschemneuro.2c00170
Tolerance develops rapidly via 5-HT₂A receptor downregulation in the frontal cortex, a class-wide mechanism confirmed in mouse models. 2C-D demonstrates MAO inhibitory potential, elevating the risk of serotonin toxicity in combination with serotonergic agentspartially supported
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
Claim in summary — inconclusiveinconclusiveworking →
pharmacokinetic-detail4 · 0 ok
receptor-pharmacology4 · 3 ok
Eshleman et al. conducted in vitro receptor binding and functional studies on six substituted phenethylamines including 2C-D, measuring binding affinities at multiple receptor targets and monoamine transporters (DAT, NET, SERT) alongside behavioral data in rodent modelssupported
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
The Eshleman et al. paper appears to include transporter binding data for 2C-D, but values were not accessible from the abstractsupported
Includes transporter binding, mouse locomotion, and rat drug discrimination data. s00213-013-3303-6
The 4-methyl group of 2C-D is the smallest common substituent, resulting in lower receptor affinity than 2c-b (4-bromo), 2c-i (4-iodo), or 2c-e (4-ethyl)supported
Discusses 2C series and the importance of 4-substituent size/lipophilicity on potency. 7854_2017_475
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
chemistry2 · 2 ok
The "2C" designation refers to the two carbon atoms in the ethylamine side chain, distinguishing this series from their α-methylated amphetamine analogs (the DOx series). 2C-D bears a 4-methyl group, making it the structural phenethylamine counterpart of dom (2,5-dimethoxy-4-methylamphetamine)supported
Discusses relationship between 4-methyl (DOM/2C-D) and 4-iodo (DOI/2C-I) substitution. acsptsci.4c00157
The 4-methyl substituent is the smallest commonly encountered in the 2C-x family, a structural feature directly responsible for 2C-D's relatively low potency.supported
Discusses 2C series and the importance of 4-substituent size/lipophilicity on potency. 7854_2017_475
comparative-pharmacology2 · 2 ok
The 4-methyl substituent produces lower 5-HT₂A affinity than the 4-bromo (2c-b), 4-iodo (2c-i), or 4-ethyl (2c-e) analogssupported
Discusses 2C series and the importance of 4-substituent size/lipophilicity on potency. 7854_2017_475
Luethi et al. demonstrated that DOM was the most efficacious compound in the head-twitch response (HTR) assay among the 4-alkyl 2,5-dimethoxyamphetamine series, with in vitro 5-HT₂A activities across the series ranging from 2–56 nMsupported
DOM (4-methyl 2,5-dimethoxyamphetamine; closest known amphetamine analog of 2C-D) was most efficacious in head-twitch response assay. 5-HT2 subtypes primary targets; in vitro 5-HT2A activities 2-56 nM across alkyl chain length series. s41380-025-03325-1
neuroscience2 · 2 ok
As a 5-HT₂A receptor agonist, 2C-D is expected to engage the same cortical circuits characterized for other serotonergic psychedelics. 5-HT₂A receptors are densely expressed on layer V pyramidal neurons in the prefrontal cortex, where agonist binding increases glutamatergic transmission through an asynchronous release mechanismsupported
5-HT2A receptor activation induces asynchronous glutamate release in layer V pyramidal cells of prefrontal cortex; DOI (5-HT2A agonist) replicated these effects. pmid:10216183
As a 5-HT₂A receptor agonist, 2C-D is expected to engage the same cortical circuits characterized for other serotonergic psychedelics. 5-HT₂A receptors are densely expressed on layer V pyramidal neurons in the prefrontal cortex, where agonist binding increases glutamatergic transmission through an asynchronous release mechanismsupported
Convergent evidence that tryptamines and phenethylamines are partial agonists at 5-HT2A receptors. 5-HT2A-mediated enhancement of glutamatergic EPSPs in cortical layer V pyramidal cells proposed as mechanism for perceptual distortions. pmid:10432484