generation run 2026-05-11
70 min completedmodel pipeline-v5plan not recordedrun/98054f39…Selection
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The model's own caveats
4 further caveats recorded as free text — readable on the working page
Reproduce
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- 19 source keys (listed under Sources)
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28 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed · absence | LAE-32 lysergic acid ethylamide pharmacology | 0 | — | Needed to broaden search terms |
| 2 | NCATS Inxight | Lysergic acid ethylamide chemical identity | 1 | 2 | Authoritative chemical identity confirmation from FDA database |
| 3 | PubChem | LAE-32 | 1 | 2 | Both CIDs represent LAE-32; stereospecific CID 12304966 matches CAS 478-99-9 and NCATS entry |
| 4 | WebSearch | LAE-32 clinical study Giberti psychopathological effects history 1958 | 10 | 2 | Historical primary sources directly concerning LAE-32 clinical use |
| 5 | PubMed | LSD metabolism metabolites lysergic acid ethylamide nor-LSD human pharmacokinetics | 3 | 3 | All three relevant for metabolite context and class pharmacokinetics |
| 6 | OpenAlex | LAE-32 lysergic acid ethylamide psychedelic | 7 | 1 | Only directly relevant pharmacology paper found |
| 7 | WebSearch | LAE-32 lysergic acid ethylamide psychedelic compound | 10 | 3 | Historical PubMed articles are primary sources; NCATS provides CAS and stereochemical data |
| 8 | PubMed | lysergamide serotonin receptor binding affinity 5-HT2A ergoline pharmacology | 3 | 3 | All three describe lysergamide binding at 5-HT2A and 5-HT1A — directly applicable to class pharmacology for LAE-32 |
| 9 | PubMed | PMID 11817305 | 1 | 1 | Class metabolite reference; LAE-32 likely shares similar metabolic pathway |
| 10 | PubChem | CID 101704 LAE-32 racemic | 1 | 1 | Racemic form of LAE-32 — confirmed chemical identity |
| 11 | PubMed | PMID 13251531 | 1 | 1 | Earliest indexed clinical paper on LAE-32 psychological effects |
| 12 | PubMed | PMID 37596682 | 1 | 1 | Supplemental class PK reference |
| 13 | PubMed | Tolerance cross-tolerance psychedelic 5-HT2A receptor downregulation mechanism | 1 | 1 | Best available reference for psychedelic tolerance mechanism applicable to LAE-32 |
| 14 | PubMed | PMID 31756337 | 1 | 1 | Class pharmacology context; kept for indirect reference |
| 15 | PubMed | PMID 13659105 | 1 | 1 | Primary preclinical study directly on LAE-32; earliest animal study found |
| 16 | PubChem | CID 12304966 LAE-32 stereospecific | 1 | 1 | Stereospecific (6aR,9R) active form — preferred for pharmacological characterization |
| 17 | UK Home Office / GOV.UK | Circular 001/2015 LSD-related compounds Misuse of Drugs Act | 1 | 1 | Confirms LAE-32 not explicitly scheduled under MDA but covered by PSA 2016 |
| 18 | ClinicalTrials.gov · absence | LAE-32 lysergic acid ethylamide | 0 | 0 | Absence confirmed: no registered trials |
| 19 | PubMed | Nichols hallucinogens pharmacology serotonin review 2004 | 1 | 1 | Foundational class pharmacology reference |
| 20 | PubMed | ergoline serotonin 5-HT2A dopamine D2 receptor agonist partial mechanism psychedelic | 1 | 1 | Best available mechanistic review for LSD-class ergoline pharmacology |
| 21 | WebSearch | LAE-32 MKULTRA CIA psychedelic research | 10 | 0 | MKULTRA connection for LAE-32 specifically not confirmed from primary sources |
| 22 | PubMed | PMID 13580425 | 1 | 1 | Key primary source: first comparative clinical study of LAE-32 vs LSD-25 in human subjects |
| 23 | PubMed | PMID 20126400 Ray psychedelics human receptorome | 1 | 1 | Broad receptor profile reference for psychedelic class |
| 24 | PubMed | PMID 13466954 | 1 | 1 | Describes combined use; comparative clinical observations |
| 25 | PubMed | PMID 39440803 tramadol pharmacology | 1 | 1 | Confirms tramadol's serotonergic mechanism, supporting dangerous interaction with serotonergic psychedelics |
| 26 | PubMed | PMID 26108222 | 1 | 1 | Best available class pharmacokinetic reference for oral lysergamides |
| 27 | WebSearch | LAE-32 Australia psychoactive substances blanket ban | 10 | 0 | Establishes broad legal picture for major jurisdictions |
| 28 | WebSearch | LAE-32 DEA Schedule I United States Analog Act | 10 | 0 | Absence of explicit scheduling confirmed; analog act applicability noted as uncertain |
56 claims by section — every cited sentence, checked against its source
summary11 · 5 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Its psychedelic activity is presumed to arise from partial agonism at the serotonin 5-HT₂A receptor, the canonical mechanism for classical psychedelics of the ergoline classsupported
Hallucinogens stimulate 5-HT2A receptors especially on neocortical pyramidal cells. pmid:14761703
The reduced steric bulk of the monoethyl amide relative to LSD's diethyl group alters binding geometry at 5-HT₂A, consistent with the observed potency reductionsupported
Conformationally constrained LSD analogues evaluated for 5-HT2A receptor affinity and LSD-like behavioral activity in rat drug discrimination. pmid:12213075
Secondary activity at 5-HT₁A and dopamine D₂ receptors is expected from class pharmacologysupported
LSD mechanism is pleiotropic: 5-HT2A partial agonist, 5-HT1A agonist, dopamine D2 agonist at higher doses, TAAR1 stimulation. ijms17111834
Claim in summary — inconclusiveinconclusiveworking →
Ergoline psychedelics as a class demonstrate high physiological safety at psychoactive doses and do not produce physical dependencesupported
Considered physiologically safe; do not produce dependence. pmid:14761703
Rapid functional tolerance is expected via 5-HT₂A receptor downregulation, with cross-tolerance to other classical psychedelicssupported
5-HT2AR downregulation in frontal cortex. Cross-tolerance between DOI and LSD. acschemneuro.2c00170
pharmacology9 · 6 ok
Activation of cortical 5-HT₂A receptors increases glutamate release, likely via presynaptic receptor-mediated release from thalamocortical afferentssupported
Activation leads to increased cortical glutamate levels via presynaptic receptor-mediated release from thalamic afferents. pmid:14761703
De Gregorio et al. (2016) documented activity at 5-HT₁A receptors (modulating raphe-cortical circuits), dopamine D₂ receptors (contributing to stimulant and perceptual effects at higher doses), and Trace Amine-Associated Receptor 1 (TAAR₁), with modulation of glutamatergic neurotransmission as a downstream consequencesupported
LSD mechanism is pleiotropic: 5-HT2A partial agonist, 5-HT1A agonist, dopamine D2 agonist at higher doses, TAAR1 stimulation. Glutamatergic involvement. Dorsal raphe and VTA modulation. ijms17111834
Claim in pharmacology — inconclusiveinconclusiveworking →
Nichols et al. (2002) demonstrated that the precise orientation and geometry of the diethylamide moiety is critical for optimal 5-HT₂A binding in lysergamides, and the loss of one ethyl group in LAE-32 would diminish the hydrophobic interactions required for high-affinity receptor engagement.supported
Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD) pmid:12213075
Claim in pharmacology — inconclusiveinconclusiveworking →
Monte et al. (1995) confirmed that stereoselective (6aR,9R) configuration is required for optimal activity at both 5-HT₂A and 5-HT₁A receptors in d-lysergic acid amides, establishing the critical role of absolute stereochemistry across the seriessupported
(R)-lysergamides consistently more potent than (S)-amides at 5-HT2A and 5-HT1A receptors. Stereoselective agonist activity at 5-HT2A receptor (phosphoinositide hydrolysis). pmid:7699712
Claim in pharmacology — inconclusiveinconclusiveworking →
Holze et al. (2024) confirmed and extended these findings with comprehensive PK/PD modeling and urinary recovery datasupported
Comprehensive LSD PK/PD study; urinary recovery data; confirmatory study. bcp.15887
Metabolism (class inference): Canezin et al. (2001) identified the major urinary metabolite of LSD as 2-oxo-3-hydroxy-LSD (OH-LSD), with nor-LSD, nor-iso-LSD, and glucuronide conjugates also detectedsupported
OH-LSD (2-oxo-3-hydroxy-LSD) is the main urinary metabolite of LSD; nor-LSD, nor-iso-LSD, trioxylated-LSD, and glucuronide conjugates also detected. s1570-0232(01)00494-9
receptor-pharmacology7 · 6 ok
LAE-32 is presumed to act as a partial agonist, consistent with the mechanism established for LSD and other ergoline psychedelicssupported
Hallucinogens stimulate 5-HT2A receptors especially on neocortical pyramidal cells. pmid:14761703
The monoethyl amide substitution reduces binding affinity relative to the diethyl group of LSD, as predicted by the SAR data of Nichols et al. (2002)supported
Conformationally constrained LSD analogues evaluated for 5-HT2A receptor affinity... map the binding orientation of the diethylamide moiety. pmid:12213075
Halberstadt et al. (2019) confirmed that the structurally related N-ethyl-N-cyclopropyl lysergamide (ECPLA) retains 5-HT₂A agonist activity sufficient to produce head-twitch responses in mice — the standard behavioural correlate of 5-HT₂A activation.supported
5-HT2A mechanism confirmed via head-twitch response (HTR). s00213-018-5055-9
Monte et al. (1995) demonstrated 5-HT₁A binding for d-lysergic acid amides with the (6aR,9R) configuration. 5-HT₁A agonism may contribute to anxiolytic and mood-modulatory components of the subjective experience.supported
(R)-lysergamides consistently more potent than (S)-amides at 5-HT2A and 5-HT1A receptors. pmid:7699712
Dopamine D₂: Agonist activity expected at higher doses, consistent with the broader ergoline pharmacologysupported
LSD mechanism is pleiotropic: 5-HT2A partial agonist, 5-HT1A agonist, dopamine D2 agonist at higher doses, TAAR1 stimulation. ijms17111834
TAAR₁: LSD activates Trace Amine-Associated Receptor 1; similar activity is plausible for LAE-32 but unconfirmed.supported
LSD mechanism is pleiotropic: 5-HT2A partial agonist, 5-HT1A agonist, dopamine D2 agonist at higher doses, TAAR1 stimulation. ijms17111834
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
safety6 · 4 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Nichols (2004) stated that hallucinogens as a class "do not produce dependence or addiction".supported
Considered physiologically safe; do not produce dependence. pmid:14761703
De la Fuente Revenga et al. (2022) demonstrated that this tolerance is mediated by 5-HT₂A receptor downregulation in the frontal cortex, with cross-tolerance confirmed between DOI and LSD in murine modelssupported
Cross-tolerance between DOI and LSD. 5-HT2AR downregulation in frontal cortex. Tolerance mechanism independent of beta-arrestin-2. acschemneuro.2c00170
Cross-tolerance with other classical psychedelics — including LSD, psilocybin, and mescaline — is expected by shared mechanism of actionsupported
Cross-tolerance between DOI and LSD. No cross-tolerance with non-psychedelic 5-HT2AR agonist lisuride. acschemneuro.2c00170
Tramadol — a weak mu-opioid agonist that also acts as a serotonin and norepinephrine reuptake inhibitor — carries a dangerous interaction classificationsupported
Tramadol is a synthetic opioid acting as a weak mu-opioid agonist and as a norepinephrine and serotonin reuptake inhibitor. 15360288.2024.2411239
chemistry5 · 5 ok
This modification is the structural basis for its reduced potency at serotonin 5-HT₂A receptors.supported
Conformationally constrained LSD analogues evaluated for 5-HT2A receptor affinity and LSD-like behavioral activity... map the binding orientation of the diethylamide moiety. pmid:12213075
Nichols et al. (2002) demonstrated that the orientation and geometry of the amide substituents in lysergamides are critical determinants of 5-HT₂A binding affinitysupported
Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD). Conformationally constrained LSD analogues evaluated for 5-HT2A receptor affinity. pmid:12213075
Halberstadt et al. (2019) confirmed that N-monoalkyl lysergamides retain 5-HT₂A activity, characterizing the closely related N-ethyl-N-cyclopropyl lysergamide (ECPLA)supported
Pharmacological characterization of ECPLA, a close LSD analog sold as a research chemical. 5-HT2A mechanism confirmed via head-twitch response (HTR). s00213-018-5055-9
Monte et al. (1995) established that the (6aR,9R) stereoconfiguration is required for optimal activity at both 5-HT₂A and 5-HT₁A receptors across the d-lysergic acid amide series.supported
(R)-lysergamides consistently more potent than (S)-amides at 5-HT2A and 5-HT1A receptors. Stereoselective agonist activity at 5-HT2A receptor (phosphoinositide hydrolysis). pmid:7699712
Monte et al. (1995) confirmed that this stereoconfiguration is essential for activity at serotonin receptors across the lysergic acid amide series; the corresponding (6aS,9S) (iso-lysergic acid) configuration is pharmacologically inactive or substantially less active.supported
(R)-lysergamides consistently more potent than (S)-amides at 5-HT2A and 5-HT1A receptors. pmid:7699712
comparative-pharmacology5 · 3 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Nichols et al. (2002) demonstrated that the diethylamide geometry of LSD provides optimal hydrophobic contact with the 5-HT₂A binding pocketsupported
Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD). pmid:12213075
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Halberstadt et al. (2019) characterised ECPLA (N-ethyl-N-cyclopropyl lysergamide), the closest modern pharmacological comparison available for an N-monoalkyl lysergamidesupported
Pharmacological characterization of ECPLA, a close LSD analog sold as a research chemical. Receptor binding data for lysergamides. s00213-018-5055-9
Halberstadt et al. (2020) further examined 1-acyl-substituted LSD derivatives, demonstrating that structural modifications to the lysergamide scaffold produce systematic changes in receptor binding and behavioural potencysupported
1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude. j.neuropharm.2019.107856
clinical-evidence4 · 0 ok
history4 · 0 ok
pharmacokinetic-detail3 · 3 ok
Dolder et al. (2015) characterised oral LSD pharmacokinetics in healthy volunteers:supported
First modern pharmacokinetic characterization of oral LSD in humans. Dose-proportional pharmacokinetics and concentration-effect relationship confirmed. pyv072
Holze et al. (2024) confirmed dose-proportional kinetics and provided urinary recovery data, demonstrating that metabolites account for the majority of excreted dose.supported
Comprehensive LSD PK/PD study; urinary recovery data; confirmatory study. bcp.15887
By analogy with LSD metabolism:supported
OH-LSD (2-oxo-3-hydroxy-LSD) is the main urinary metabolite of LSD; nor-LSD, nor-iso-LSD, trioxylated-LSD, and glucuronide conjugates also detected. s1570-0232(01)00494-9
neuroscience2 · 1 ok
Thalamocortical gating disruption: 5-HT₂A activation on cortical pyramidal neurons disrupts the thalamic filter that normally gates sensory information entering consciousnesssupported
Hallucinogens stimulate 5-HT2A receptors especially on neocortical pyramidal cells. Activation leads to increased cortical glutamate levels via presynaptic receptor-mediated release from thalamic afferents. pmid:14761703
Claim in neuroscience — inconclusiveinconclusiveworking →