generation run 2026-04-26
44 min completedmodel pipeline-v5plan not recordedrun/b2904e59…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 17 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
18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | tryptamine sigma-1 receptor binding psychedelic | 9 | 3 | Establish sigma-1 receptor relevance for tryptamines; must note DET-specific data absent |
| 2 | PubChem | N,N-diethyltryptamine | 1 | 1 | Primary chemical identity confirmation |
| 3 | ClinicalTrials.gov | diethyltryptamine DET psychedelic | 1 | 1 | Only trial result - may not be DET-specific |
| 4 | PubMed | DET diethyltryptamine drug discrimination rat | 3 | 1 | Drug discrimination data relevant to hallucinogen potential |
| 5 | OpenAlex | N,N-diethyltryptamine psychedelic | 10 | 4 | High-citation review articles and primary pharmacology papers |
| 6 | PubMed | DET diethyltryptamine pharmacology receptor | 2 | 2 | Both directly test DET pharmacology |
| 7 | Erowid/TIHKAL | TIHKAL entry #3 DET | 1 | 1 | Shulgin primary data on DET dosing and effects |
| 8 | UNODC | tryptamines international control Convention Psychotropic Substances | 1 | 1 | Definitive international scheduling status |
| 9 | PubMed | hallucinogen head twitch response tryptamine HTR mouse 5-HT2A | 6 | 2 | Cross-species predictive data for tryptamine hallucinogenicity |
| 10 | PubMed | serotonin toxicity serotonergic psychedelics SSRI MAOI | 1 | 1 | Drug interaction and serotonin toxicity risk for tryptamines |
| 11 | Web | Szara 1956 1957 diethyltryptamine history hallucinogen | 10 | 2 | Key historical papers establishing DET's first human use |
| 12 | Web | DET diethyltryptamine legal USA Canada Australia DEA analog | 10 | 3 | Legal status by jurisdiction |
| 13 | Web/Erowid | DET TIHKAL Shulgin legal status scheduling | 10 | 2 | Primary sources for dosing and legal status |
| 14 | ClinicalTrials.gov | diethyltryptamine DET | 1 | 0 | Confirms no active or completed DET-specific clinical trials |
| 15 | ChemEurope | DET physical properties melting point SMILES CAS | 1 | 2 | Physical property data not returned by PubChem API |
| 16 | PubMed | tryptamine overdose death case poisoning toxicology | 6 | 1 | Confirms absence of DET-specific toxicology case reports; AMT noted for class context |
| 17 | Multiple · absence | DET seed data verification | 0 | 0 | Data verification for generation agent |
| 18 | Web | DET oral bioavailability no MAOI required steric bulk MAO-A | 10 | 1 | Key pharmacokinetic distinction from DMT |
60 claims by section — every cited sentence, checked against its source
safety18 · 7 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Alpha-methyltryptamine (AMT), a structurally related tryptamine with distinct pharmacology (monoamine-oxidase inhibitor activity that DET lacks), caused at least one documented fatality in the United States in 2003, with postmortem blood levels of 2.0 mg/Lsupported
First known AMT death in the US (Feb 2003, Miami-Dade). Postmortem blood AMT 2.0 mg/L… AMT described as antidepressant/stimulant/MAO inhibitor. pmid:16105268
tolerance to serotonergic psychedelics develops rapidly — effectively after a single dose — through 5-ht2a downregulation in the frontal cortexsupported
Tolerance after single dose. DOI caused 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Cross-tolerance between serotonergic psychedelics is established; doi–lsd cross-tolerance has been confirmed in micesupported
Cross-tolerance between DOI and LSD. acschemneuro.2c00170
These values are consistent with the class-level mechanistic data but have not been validated specifically for DET.supported
Repeated DOI induces progressive decrease in HTR. Cross-tolerance between DOI and LSD. acschemneuro.2c00170
Drug discrimination and self-administration studies in rodents have consistently failed to demonstrate reinforcement with classical 5-HT₂A agonist psychedelics.supported
Low abuse liability for DOM in rodents. jpet.111.179705
Malcolm evaluated serotonin-syndrome risk between serotonergic psychedelics and common psychiatric medications at the class level.supported
Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. s00213-021-05876-x
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
SSRIs present a dual risk: serotonin toxicity at the pharmacological level, and unpredictable modulation of the psychedelic experience — blunting or paradoxical intensification.supported
Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. s00213-021-05876-x
receptor-pharmacology14 · 2 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The sigma-1-receptor is established as a target for dmt, which acts as an endogenous sigma-1 agonist and inhibits voltage-gated sodium channelssupported
DMT bound to sigma-1 receptors and inhibited voltage-gated sodium channels. DMT is an endogenous sigma-1 receptor agonist. science.1166127
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
N,N-Dialkyltryptamines including DMT, dpt, mipt, and dipt act as substrates — not blockers — at the serotonin-transporter (SERT) and vmat2 (VMAT2), with high binding-to-uptake ratios supporting transporter substrate behavior rather than reuptake-inhibitorsupported
High binding-to-uptake ratios indicate substrate (not blocker) behavior at both SERT and VMAT2. s00702-009-0308-8
pharmacology8 · 4 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
In PC12 cells stably expressing the rat 5-ht2a receptor, DET stimulates Gq-mediated phosphoinositide (PI) hydrolysis in a concentration-dependent mannersupported
DET causes concentration-dependent phosphoinositide hydrolysis via 5-HT2A in PC12 cells. pmid:11900766
The Gq-coupled signaling pathway — rather than β-arrestin2 recruitment — is the determinant of psychedelic potential: Wallach et al. demonstrated in mice that a threshold level of 5-HT₂A-Gq activation is required to produce the head-twitch response (HTR), the primary animal model of hallucinogenic activity, whereas β-arrestin2 recruitment efficacy has no predictive value.supported
5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. s41467-023-44016-1
Repeated 5-HT₂A activation induces downregulation and tolerance, a mechanism shared across classical psychedelics and mediated by G-protein-coupled receptor desensitization and internalization rather than β-arrestin2-dependent pathways.supported
DOI caused 5-HT2AR downregulation in frontal cortex. Tolerance mechanism independent of beta-arrestin-2. Cross-tolerance between DOI and LSD. acschemneuro.2c00170
Szára's early research identified 6-hydroxy-DET as a metabolite with minor psychoactive activity — in contrast to 6-hydroxy-DMT, which was found inactive. cyp2d6 mediates oxygenated metabolite formation for DMT in vitro, and this pathway may apply to DET, but no published DET-specific CYP enzyme mapping existssupported
DMT rapidly metabolized by CYP2D6 via hydroxylation on the indole core. 00498254.2023.2278488
comparative-pharmacology6 · 1 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Mouse head-twitch response (HTR) potency correlates strongly with human hallucinogenic potency across tryptamines and phenethylamines (r = 0.9448)supported
Strong positive correlation (r=0.9448) between HTR potencies in mice and reported hallucinogenic potencies in humans (n=36). j.neuropharm.2019.107933
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
neuroscience4 · 1 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Wallach et al. demonstrated that Gq efficacy at 5-HT₂A — not β-arrestin2 recruitment — is the molecular determinant of psychedelic-like behavioral responses in mice.supported
5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. s41467-023-44016-1
summary4 · 2 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
DET acts as an agonist at the serotonin 5-ht2a receptor, stimulating Gq-mediated phosphoinositide hydrolysissupported
DET causes concentration-dependent phosphoinositide hydrolysis via 5-HT2A in PC12 cells. pmid:11900766
No LD₅₀ data exist for any species, and no human fatalities attributable to DET have been reported — though this likely reflects low prevalence rather than established safety. tolerance develops rapidly through 5-HT₂A downregulation in the frontal cortex, a β-arrestin2-independent desensitization mechanism shared across classical psychedelicssupported
DOI caused 5-HT2AR downregulation in frontal cortex. Tolerance mechanism independent of beta-arrestin-2. acschemneuro.2c00170
chemistry2 · 1 ok
Claim in chemistry — inconclusiveinconclusiveworking →
Structure-activity relationship studies within the hallucinogenic tryptamine series have established that the N,N-dialkyl substitution pattern is critical for serotonin 2A receptor agonist activity and psychedelic potential.supported
Reviews SAR for classic serotonergic hallucinogens (tryptamines, ergolines, phenethylamines). 5-HT2A as principal target. Key structural features for each class. 7854_2017_475
history2 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
DET's early clinical use occurred within the broader mid-twentieth-century era of psycholytic therapy, during which numerous tryptamine and lysergamide compounds were explored in European psychiatric settingssupported
Comprehensive review of psycholytic therapy 1949-1970s, led by Hanscarl Leuner in Germany. Used at 30 European clinical centers. Various substances including tryptamines employed. fpsyt.2022.1020505
pharmacokinetic-detail2 · 1 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
For the structural parent DMT, cyp2d6 mediates formation of oxygenated metabolites in vitro, but DET-specific CYP isoform mapping has not been published.supported
DMT rapidly metabolized by CYP2D6 via hydroxylation on the indole core. 00498254.2023.2278488