generation run 2026-04-26
53 min completedmodel pipeline-v5plan not recordedrun/74644b8f…Selection
Verification
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- seen / partial
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The model's own caveats
none raised on this run
Reproduce
- inputs
- 19 source keys (listed under Sources)
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- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
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- none — agent transcripts are persisted from 2026-09 onward
24 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | Coney 2017 LSD analogs comparative study user profile human psychopharmacology | 1 | 1 | Only published human survey data directly comparing ETH-LAD effects to LSD |
| 2 | PubMed | ETH-LAD lysergamide pharmacology | 3 | 3 | All directly relevant to ETH-LAD chemistry, pharmacology, and metabolism |
| 3 | WebSearch | ETH-LAD TIHKAL Shulgin discovery synthesis history | 10 | 3 | Discovery history and early pharmacology; Shulgin's human use documentation |
| 4 | PubMed | return lysergamides AL-LAD LSZ Brandt Halberstadt | 2 | 3 | Complete series context for ETH-LAD research methodology and comparative potency |
| 5 | PubChem | ETH-LAD | 1 | 4 | Complete chemical identity data verified against brief seed data |
| 6 | WebSearch | ETH-LAD legal status scheduling UK US analog act controlled substance | 10 | 3 | Key legal status data for major jurisdictions |
| 7 | Crossref via verify_doi | 10.1021/jm00147a022 | 1 | 1 | This is the original ETH-LAD synthesis paper; DOI confirmed valid |
| 8 | OpenAlex | ETH-LAD 6-ethyl-6-nor-lysergic acid diethylamide | 17 | 4 | Papers in same series providing comparative lysergamide pharmacology context |
| 9 | ClinicalTrials.gov · absence | ETH-LAD lysergamide | 0 | 0 | Absence of clinical trials is a notable gap to document |
| 10 | Erowid/TiHKAL | ETH-LAD TiHKAL entry | 1 | 4 | Primary source for human phenomenology; Shulgin's personal account is foundational reference |
| 11 | PubMed | lysergamide receptor binding affinity 5-HT2A serotonin LSD analogs | 3 | 2 | ECPLA paper contains receptor binding methodology; Nichols 2002 provides SAR context |
| 12 | PubMed | LSD mechanism psychosis 5-HT2A 5-HT1A dopamine D2 | 1 | 1 | Comprehensive receptor profile applicable to ETH-LAD |
| 13 | WebSearch | Coney 2017 ETH-LAD effects comparison LSD survey Global Drug Survey results | 10 | 1 | Direct user survey data for ETH-LAD comparative effects |
| 14 | PubMed | serotonergic hallucinogen tolerance cross-tolerance 5-HT2A downregulation | 1 | 1 | Mechanism of tolerance development directly applicable to ETH-LAD class |
| 15 | UNODC/UK Home Office | UK scheduling ETH-LAD 2015 | 1 | 2 | Primary legal status source for UK |
| 16 | PubMed | Niwaguchi 1976 norlysergic acid amide synthesis | 1 | 1 | Earliest published synthesis paper for N6-substituted norlysergamides series including ETH-LAD |
| 17 | WebSearch | ETH-LAD receptor binding Ki 5-HT2A D2 serotonin affinity PDSP pharmacology | 10 | 2 | Ki values from commercial database, not verified against primary source; flagged as unverified |
| 18 | OpenAlex | LSD lysergic acid pharmacokinetics half-life human plasma controlled trial Liechti | 8 | 3 | Pharmacokinetic reference data for LSD class applicable to ETH-LAD by structural analogy |
| 19 | PubMed | lysergamide receptor binding affinity 5-HT2A serotonin LSD analogs | 3 | 2 | Comparative binding methodology; no ETH-LAD specific Ki values in PubMed |
| 20 | WebSearch | ETH-LAD seizure adverse event overdose case report safety concern | 10 | 0 | Absence of published case reports documented; anecdotal data noted |
| 21 | OpenAlex | LSD lysergic acid pharmacokinetics half-life human plasma controlled trial Liechti | 8 | 3 | LSD PK as reference class for ETH-LAD; no specific ETH-LAD human PK data available |
| 22 | PubMed · absence | psychedelic contraindication personal history psychosis bipolar disorder risk | 0 | 0 | Safety gaps documented |
| 23 | ClinicalTrials.gov · absence | ETH-LAD lysergamide | 0 | 0 | Confirmed no clinical trials |
| 24 | WebSearch | ETH-LAD Switzerland Sweden Denmark controlled scheduled 2015 2016 | 10 | 2 | Additional legal status jurisdictions |
65 claims by section — every cited sentence, checked against its source
pharmacology17 · 15 ok
Its primary mechanism is agonism or partial agonism at the serotonin 5-HT₂A receptor, particularly on apical dendrites of neocortical pyramidal cells in cortical layer Vsupported
Psychedelics are agonists/partial agonists at brain 5-HT2A receptors. pr.115.011478
Its primary mechanism is agonism or partial agonism at the serotonin 5-HT₂A receptor, particularly on apical dendrites of neocortical pyramidal cells in cortical layer Vsupported
Highest density in cortical layer V. j.pharmr.2025.100059
The necessity and sufficiency of 5-HT₂A activation for the psychedelic behavioral signature has been established across the lysergamide class: the selective 5-HT₂A antagonist M100907 completely abolishes the head-twitch response (HTR) induced by 1P-LSD, AL-LAD, and LSZsupported
HTR ED50=349.6 nmol/kg. Abolished by M100907 (5-HT2A antagonist). dta.1884
The necessity and sufficiency of 5-HT₂A activation for the psychedelic behavioral signature has been established across the lysergamide class: the selective 5-HT₂A antagonist M100907 completely abolishes the head-twitch response (HTR) induced by 1P-LSD, AL-LAD, and LSZsupported
AL-LAD HTR ED50=174.9 nmol/kg; LSZ ED50=114.2 nmol/kg; LSD ED50=132.8 nmol/kg. 5-HT2A mechanism confirmed. dta.1985
In humans, the 5-HT₂A antagonist ketanserin fully blocks the subjective effects of 200 µg LSD.supported
5-HT2A mediates full psychedelic effects (blocked by ketanserin). s41386-020-00883-6
ETH-LAD's binding to the 5-HT₂A receptor is predicted to share LSD's extracellular loop 2 (EL2) lid mechanism, characterized crystallographically by Wacker et al. (2017): the EL2 domain closes over the bound ligand, creating exceptionally slow dissociation kinetics from both 5-HT₂A and 5-HT₂B receptors and contributing to the prolonged receptor occupancy that underlies the extended duration of action.supported
EL2 lid mechanism explains slow dissociation from 5-HT2A/2B. Structural basis for LSD's prolonged kinetics. j.cell.2016.12.033
By class-level structural analogy with LSD, the broader receptor profile is expected to include 5-HT₁A partial agonism, 5-HT₂A/2B/2C partial agonism, dopamine D₂ agonism (particularly at higher doses), trace amine-associated receptor 1 (TAAR₁) stimulation, and glutamatergic modulationsupported
LSD mechanism is pleiotropic: 5-HT2A partial agonist, 5-HT1A agonist, dopamine D2 agonist (at higher doses), TAAR1 stimulation. Glutamatergic involvement. ijms17111834
By class-level structural analogy with LSD, the broader receptor profile is expected to include 5-HT₁A partial agonism, 5-HT₂A/2B/2C partial agonism, dopamine D₂ agonism (particularly at higher doses), trace amine-associated receptor 1 (TAAR₁) stimulation, and glutamatergic modulationsupported
Psychedelics are agonists/partial agonists at brain 5-HT2A receptors. pr.115.011478
ETH-LAD functions as a partial agonist at 5-HT₁A receptors in the dorsal raphe nucleus by class inference from LSD, an activity that modulates serotonergic tone and may attenuate some 5-HT₂A-mediated effects.supported
5-HT1A agonist... Dorsal raphe and VTA modulation. ijms17111834
LSD demonstrates dose-proportional pharmacokinetics with first-order elimination, an average plasma half-life of approximately 2.4 hours, and a duration of subjective effects spanning 6.7–11 hours depending on dose (25–200 µg)supported
Dose-proportional pharmacokinetics, first-order elimination. Duration 6.7-11h depending on dose. s41386-020-00883-6
LSD demonstrates dose-proportional pharmacokinetics with first-order elimination, an average plasma half-life of approximately 2.4 hours, and a duration of subjective effects spanning 6.7–11 hours depending on dose (25–200 µg)supported
LSD duration clearly longer than psilocybin. Both dose-proportional pharmacokinetics. s41386-022-01297-2
Claim in pharmacology — inconclusiveinconclusiveworking →
The disparity between the short plasma half-life and prolonged subjective duration reflects the slow dissociation kinetics imposed by the EL2 lid mechanism at the 5-HT₂A receptor.supported
EL2 lid mechanism explains slow dissociation from 5-HT2A/2B. Structural basis for LSD's prolonged kinetics. j.cell.2016.12.033
Claim in pharmacology — inconclusiveinconclusiveworking →
Wagmann et al. (2019) established the in vitro metabolic fate of ETH-LAD using pooled human liver S9 fractionsupported
Human liver S9 fraction metabolism of nine LSD derivatives including ETH-LAD and 1P-ETH-LAD. s00216-018-1558-9
1-Propionyl ETH-LAD (1P-ETH-LAD) undergoes hydrolysis to ETH-LAD when incubated with human serum at 37°C over 1–6 hours, with ETH-LAD remaining detectable at 24 hourssupported
1P-ETH-LAD hydrolyzes to ETH-LAD in human serum at 37C suggesting prodrug status. dta.2196
This strongly supports 1P-ETH-LAD functioning as a prodrug in vivo, mirroring the established 1P-LSD → LSD prodrug relationship.supported
ALD-52, 1P-LSD, 1B-LSD act as prodrugs for LSD in vivo. High LSD plasma levels in rats after 1P-LSD. j.neuropharm.2019.107856
safety9 · 5 ok
Claim in safety — inconclusiveinconclusiveworking →
LSD-class compounds produce mild, dose-dependent increases in heart rate and blood pressuresupported
Weak autonomic stimulation. No complications in medical settings. npp.2017.86
Claim in safety — inconclusiveinconclusiveworking →
Classical psychedelics generally do not produce dependence or addictionsupported
Generally physiologically safe, no dependence. pr.115.011478
Rapid tolerance (tachyphylaxis) develops through 5-HT₂A receptor downregulation in the frontal cortex within 24 hours of a single dose and progresses with repeated dosing over 4 dayssupported
Repeated DOI induces progressive HTR decrease. Tolerance involves 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Complete cross-tolerance exists between serotonergic psychedelics acting at the 5-HT₂A receptor (e.g., LSD ↔ DOI), and ETH-LAD would be expected to show full cross-tolerance with LSD and partial cross-tolerance with psilocybin and other 5-HT₂A agonists.supported
Cross-tolerance between DOI and LSD. No cross-tolerance with non-psychedelic 5-HT2AR agonist lisuride. acschemneuro.2c00170
Given ETH-LAD's metabolism via CYP1A2 and CYP3A4, strong inhibitors of these enzymes (e.g., fluvoxamine for CYP1A2; ketoconazole, ritonavir, grapefruit juice for CYP3A4) could theoretically increase ETH-LAD plasma concentrationssupported
CYP1A2 and CYP3A4 identified as primary metabolizing enzymes via N-dealkylation and hydroxylation. s00216-018-1558-9
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
summary9 · 6 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
The compound entered the novel psychoactive substance (NPS) market in the 2010s and has been analytically characterized by Brandt et al., but formal pharmacological investigation beyond the original 1985 study remains absent.supported
Analytical characterization (GC-MS, NMR, HPLC, IR) of ETH-LAD and 1P-ETH-LAD. dta.2196
As a lysergamide, ETH-LAD is presumed to act primarily through agonism at the serotonin 5-HT₂A receptor on cortical layer V pyramidal neurons, with additional partial agonism at 5-HT₁A and dopamine D₂ receptors by class analogysupported
Psychedelics are agonists/partial agonists at brain 5-HT2A receptors. pr.115.011478
As a lysergamide, ETH-LAD is presumed to act primarily through agonism at the serotonin 5-HT₂A receptor on cortical layer V pyramidal neurons, with additional partial agonism at 5-HT₁A and dopamine D₂ receptors by class analogysupported
Highest density in cortical layer V. Three agonist scaffolds: tryptamines, ergolines, phenylalkylamines. j.pharmr.2025.100059
As a lysergamide, ETH-LAD is presumed to act primarily through agonism at the serotonin 5-HT₂A receptor on cortical layer V pyramidal neurons, with additional partial agonism at 5-HT₁A and dopamine D₂ receptors by class analogysupported
LSD mechanism is pleiotropic: 5-HT2A partial agonist, 5-HT1A agonist, dopamine D2 agonist (at higher doses), TAAR1 stimulation. ijms17111834
Tolerance develops rapidly through 5-HT₂A receptor downregulation in the frontal cortex, with complete cross-tolerance to other serotonergic psychedelics; this rapid tachyphylaxis functionally prevents compulsive use, and ETH-LAD is not considered habit-formingsupported
Cross-tolerance between DOI and LSD. Tolerance involves 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Tolerance develops rapidly through 5-HT₂A receptor downregulation in the frontal cortex, with complete cross-tolerance to other serotonergic psychedelics; this rapid tachyphylaxis functionally prevents compulsive use, and ETH-LAD is not considered habit-formingsupported
Generally physiologically safe, no dependence. pr.115.011478
comparative-pharmacology7 · 4 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
In the Global Drug Survey, LSD analogues collectively received lower ratings than LSD across multiple domains (pleasurable high, strength of effect, comedown, urge for more, perceived risk), though this comparison is confounded by potential dose non-equivalence.supported
Survey study of self-reported patterns of use and effects of LSD analogues (AL-LAD, 1P-LSD, ETH-LAD) and characteristics of users. hup.2599
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
AL-LAD has been more extensively characterized in HTR assays (ED₅₀ published by Brandt et al.), while ETH-LAD lacks published HTR ED₅₀ datasupported
AL-LAD HTR ED50=174.9 nmol/kg; LSZ ED50=114.2 nmol/kg; LSD ED50=132.8 nmol/kg. dta.1985
1P-ETH-LAD serves as a prodrug of ETH-LAD, undergoing serum hydrolysis to the parent compoundsupported
1P-ETH-LAD hydrolyzes to ETH-LAD in human serum at 37C suggesting prodrug status. dta.2196
This parallels the 1P-LSD → LSD and 1B-LSD prodrug relationships characterized in the same research seriessupported
ALD-52, 1P-LSD, 1B-LSD act as prodrugs for LSD in vivo. j.neuropharm.2019.107856
chemistry5 · 4 ok
Claim in chemistry — inconclusiveinconclusiveworking →
The acylated derivative 1-propionyl ETH-LAD (1P-ETH-LAD) functions as a prodrug, undergoing hydrolysis to ETH-LAD in human serum, mirroring the 1P-LSD → LSD prodrug relationship.supported
1P-ETH-LAD hydrolyzes to ETH-LAD in human serum at 37C suggesting prodrug status. dta.2196
The acylated derivative 1-propionyl ETH-LAD (1P-ETH-LAD) functions as a prodrug, undergoing hydrolysis to ETH-LAD in human serum, mirroring the 1P-LSD → LSD prodrug relationship.supported
ALD-52, 1P-LSD, 1B-LSD act as prodrugs for LSD in vivo. j.neuropharm.2019.107856
Brandt et al. (2017) provided GC-MS, HPLC, ¹H-NMR, and GC solid-state IR data for analytical identification but did not report bulk physical properties.supported
Analytical characterization (GC-MS, NMR, HPLC, IR) of ETH-LAD and 1P-ETH-LAD. dta.2196
N-Ethyl-N-isopropyllysergamide (EIPLA) is a constitutional isomer of ETH-LAD with identical molecular formula and mass but distinct mass spectral fragmentationsupported
EIPLA is an isomer of ETH-LAD. dta.3530
history5 · 2 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — not_supportednot supportedworking →
Brandt et al. (2017) provided the first comprehensive analytical characterization of ETH-LAD and 1P-ETH-LAD, noting that "limited analytical data for ETH-LAD were previously available" — confirming that the compound's presence on the NPS market predated adequate forensic characterization.supported
Analytical characterization (GC-MS, NMR, HPLC, IR) of ETH-LAD and 1P-ETH-LAD. dta.2196
Coney et al. (2017), using Global Drug Survey 2016 data (N = 96,894), documented significant user populations for ETH-LAD, AL-LAD, and 1P-LSD, particularly in the United Kingdom and United Statessupported
Survey study of self-reported patterns of use and effects of LSD analogues (AL-LAD, 1P-LSD, ETH-LAD) and characteristics of users. hup.2599
neuroscience5 · 3 ok
As a presumed 5-HT₂A agonist, ETH-LAD is expected to disrupt thalamocortical gating via activation of 5-HT₂A receptors on layer V pyramidal neurons in the prefrontal cortexsupported
Psychedelics are agonists/partial agonists at brain 5-HT2A receptors. pr.115.011478
As a presumed 5-HT₂A agonist, ETH-LAD is expected to disrupt thalamocortical gating via activation of 5-HT₂A receptors on layer V pyramidal neurons in the prefrontal cortexsupported
Highest density in cortical layer V. Three agonist scaffolds: tryptamines, ergolines, phenylalkylamines. j.pharmr.2025.100059
Claim in neuroscience — inconclusiveinconclusiveworking →
The REBUS (Relaxed Beliefs Under Psychedelics) model proposes that psychedelics relax the precision weighting of high-level prior beliefs in the cortical hierarchy, allowing bottom-up sensory signals to exert greater influence on conscious experiencesupported
Psychedelics relax precision of high-level priors, liberating bottom-up information flow. pr.118.017160
Claim in neuroscience — inconclusiveinconclusiveworking →
receptor-pharmacology5 · 4 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
LSD's characterized binding profile includes:supported
LSD mechanism is pleiotropic: 5-HT2A partial agonist, 5-HT1A agonist, dopamine D2 agonist (at higher doses), TAAR1 stimulation. ijms17111834
LSD's characterized binding profile includes:supported
Psychedelics are agonists/partial agonists at brain 5-HT2A receptors. pr.115.011478
The crystal structure of LSD bound to the 5-HT₂A receptor reveals that extracellular loop 2 (EL2) forms a lid over the binding pocket, dramatically slowing ligand dissociationpartially supported
Crystal structure of LSD in complex with human 5-HT2B. EL2 lid mechanism explains slow dissociation from 5-HT2A/2B. j.cell.2016.12.033
LSD shows pronounced β-arrestin bias at certain serotonin receptor subtypes, but the functional consequences of the N⁶-ethyl modification on signaling bias are unknown.supported
Structural basis for LSD's prolonged kinetics and beta-arrestin2 recruitment. j.cell.2016.12.033
pharmacokinetic-detail2 · 1 ok
Wagmann et al. (2019) characterized ETH-LAD metabolism in vitro using pooled human liver S9 fraction:supported
Human liver S9 fraction metabolism of nine LSD derivatives including ETH-LAD and 1P-ETH-LAD. s00216-018-1558-9
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
clinical-evidence1 · 1 ok
The only systematic human data derive from Coney et al. (2017), a cross-sectional analysis of the Global Drug Survey 2016 (N = 96,894)supported
Survey study of self-reported patterns of use and effects of LSD analogues (AL-LAD, 1P-LSD, ETH-LAD) and characteristics of users. hup.2599