generation run 2026-04-26
73 min completedmodel pipeline-v5plan not recordedrun/9c4f29e7…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- partial_efficacy_unverified
- no_human_data
Reproduce
- inputs
- 35 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
19 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov · absence | LSZ lysergamide psychedelic | 0 | — | — |
| 2 | PubChem · absence | LSZ lysergamide | 0 | — | — |
| 3 | PubMed | LSZ lysergic acid 2,4-dimethylazetidide psychedelic | 4 | 4 | — |
| 4 | OpenAlex | LSZ lysergamide psychedelic pharmacology | 24 | 3 | — |
| 5 | PubMed | Nichols lysergamide synthesis azetidide hallucinogen structure activity | 6 | 3 | — |
| 6 | PubChem | lysergic acid 2,4-dimethylazetidide | 1 | 1 | — |
| 7 | OpenAlex | Nichols lysergamide dimethylazetidine LSD structure activity 5-HT2A | 15 | 3 | — |
| 8 | PubMed | hallucinogen persisting perception disorder HPPD LSD | 2 | 1 | — |
| 9 | Erowid/WebSearch | LSZ lysergic acid 2,4-dimethylazetidide legal status scheduling UK US EU Australia | 10 | 7 | — |
| 10 | HandWiki | — | 1 | 5 | — |
| 11 | PubMed | LSD tolerance 5-HT2A downregulation cross-tolerance psychedelics | 1 | 1 | — |
| 12 | PubMed | serotonin syndrome tramadol opioid serotonergic drug interaction mechanism | 5 | 2 | — |
| 13 | PubMed | Holze LSD psilocybin direct comparison 2022 | 1 | 1 | — |
| 14 | WebSearch | LSD SSRI antidepressant interaction blunted effects study | 10 | 2 | — |
| 15 | WebSearch | LSD lithium interaction seizure case report | 10 | 2 | — |
| 16 | PMC | — | 1 | 3 | — |
| 17 | WebSearch | LSD cannabis interaction intensification psychedelic effects survey evidence | 10 | 1 | — |
| 18 | UNODC | — | 1 | 1 | — |
| 19 | PubMed | Holze LSD acute dose-dependent effects healthy subjects controlled 2021 | 1 | 1 | — |
94 claims by section — every cited sentence, checked against its source
safety34 · 19 ok
The closest class reference is a series of eight massive intranasal LSD overdoses reported by Klock et al., in which patients self-administered pure LSD tartrate powder at doses vastly exceeding recreational usesupported
Eight cases of massive intranasal LSD overdose: emesis, collapse, sympathetic overactivity, hyperthermia, coma, respiratory arrest, platelet dysfunction. pmid:4816396
All eight patients survived with supportive caresupported
All recovered with supportive care. pmid:4816396
At clinical doses of LSD (100–200 µg), moderate increases in blood pressure and heart rate are documentedsupported
Moderate BP and HR increase. s41386-020-00883-6
In direct comparison, LSD increases heart rate more than psilocybin at equivalent subjective doses, while psilocybin increases blood pressure moresupported
LSD increases HR more; psilocybin increases BP more. s41386-022-01297-2
Chronic 5-HT₂B agonism is the established mechanism underlying cardiac valvulopathy associated with ergot derivativessupported
LSD (unlike 2-Br-LSD) has 5-HT2B agonism linked to cardiac valvulopathy. j.celrep.2023.112203
Claim in safety — inconclusiveinconclusiveworking →
At LSD 200 µg — a dose roughly equivalent to the upper range of common LSZ doses — anxiety and ego dissolution increase significantly beyond the levels observed at 100 µgsupported
Ceiling for good effects at 100 ug; ego dissolution and anxiety increase at 200 ug. s41386-020-00883-6
At LSD 200 µg — a dose roughly equivalent to the upper range of common LSZ doses — anxiety and ego dissolution increase significantly beyond the levels observed at 100 µgsupported
LSD 200 ug higher ego dissolution, anxiety, impairments. s41386-022-01297-2
Hallucinogen persisting perception disorder (HPPD) is a documented rare adverse effect of hallucinogen usesupported
Review of HPPD plus survey of 20 Type-2 HPPD subjects. 7854_2016_457
Claim in safety — inconclusiveinconclusiveworking →
Tolerance to serotonergic psychedelics develops rapidly through 5-HT₂A receptor downregulation in the frontal cortexsupported
5-HT2AR downregulation in frontal cortex after repeated DOI. acschemneuro.2c00170
Tolerance to serotonergic psychedelics develops rapidly through 5-HT₂A receptor downregulation in the frontal cortexsupported
Tolerance to DOI mediated by selective 5-HT2A downregulation, not 5-HT2C. pmid:10435391
The mechanism is 5-HT₂A receptor-dependent but independent of β-arrestin-2supported
Tolerance mechanism independent of beta-arrestin-2. acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
Cross-tolerance was demonstrated between DOI and LSD in mice; no cross-tolerance was found with the non-psychedelic 5-HT₂A agonist lisuride, confirming the mechanism is specific to psychedelic-type agonism.supported
Cross-tolerance between DOI and LSD confirmed... No cross-tolerance with non-psychedelic 5-HT2AR agonist lisuride. acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The FDA issued a Drug Safety Communication warning of serotonin toxicity with opioid analgesics combined with serotonergic agents.supported
FDA Drug Safety Communication (2016) on entire class of opioids and serotonin toxicity. s00204-018-2244-6
Lithium co-administration with classical psychedelics is associated with seizures in 47% of analyzed reports (n = 62), with 39% requiring medical attentionsupported
47% of 62 lithium+psychedelic reports involved seizures, 39% required medical attention. a-1524-2794
A case report documented three generalized tonic-clonic seizures in a 15-year-old within 30 minutes of LSD ingestion while on low-dose lithium therapy; the patient had used LSD previously without incident before lithium initiation, and seizures occurred even at subtherapeutic lithium levelssupported
15-year-old with 3 generalized seizures within 30 minutes of LSD use while on low-dose lithium. Prior LSD use without seizures before lithium initiation. pmid:38986146
Lamotrigine (n = 34 reports) showed no such effectsupported
Lamotrigine (n=34): no seizures reported. a-1524-2794
Chronic SSRI use (fluoxetine, paroxetine, sertraline, trazodone; more than three weeks) decreased or eliminated LSD response in 88% of subjectssupported
88% of subjects chronically taking SSRIs (fluoxetine, paroxetine, sertraline, trazodone, >3 weeks) had decreased or eliminated LSD response. 0893-133x(95)00145-4
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 →
Concurrent tramadol use is contraindicated due to serotonin syndrome risk from dual serotonergic activation.supported
Tramadol inhibits SERT and causes serotonin syndrome. s00204-018-2244-6
Sympathomimetic effects including increased heart rate and blood pressure make LSZ inadvisable in severe uncontrolled hypertension, recent myocardial infarction, or conditions where acute hemodynamic stress poses risk.supported
Moderate BP and HR increase. s41386-020-00883-6
pharmacology17 · 13 ok
LSZ exerts its primary psychedelic effects through agonism at the serotonin 5-HT₂A receptorsupported
(S,S)-(+)-2,4-dimethylazetidine lysergamide has highest 5-HT2A affinity and functional potency. pmid:12213075
LSZ exerts its primary psychedelic effects through agonism at the serotonin 5-HT₂A receptorsupported
Both show LSD-like HTR in C57BL/6J mice via 5-HT2A mechanism. dta.1985
Claim in pharmacology — inconclusiveinconclusiveworking →
Second, among the three LSZ diastereomers, HTR potency correlates directly with 5-HT₂A binding affinity — the (S,S) isomer is potent; the (R,R) and cis isomers are notsupported
(S,S)-(+)-2,4-dimethylazetidine lysergamide has highest LSD-like behavioral and pharmacological activity among isomers; highest 5-HT2A affinity and functional potency. pmid:12213075
Third, class-level evidence from LSD confirms that the selective 5-HT₂A antagonist ketanserin almost fully blocks all acute subjective effects in humans.supported
Ketanserin given after LSD can reverse effects, confirming 5-HT2A dependence. pyac075
LSD and its close structural analogs bind D1 dopamine receptors (Ki ~25–50 nM) and D2 receptors with agonist-type profiles; D2 affinity is comparable to 5-HT₂A affinity, while D1 affinity is 2–3-fold lowersupported
LSD and analogs bind D2 with similar affinity to 5-HT2, D1 with 2-3 fold lower affinity. pmid:7568626
LSD and its close structural analogs bind D1 dopamine receptors (Ki ~25–50 nM) and D2 receptors with agonist-type profiles; D2 affinity is comparable to 5-HT₂A affinity, while D1 affinity is 2–3-fold lowersupported
LSD and analogs bind D2 with similar affinity to 5-HT2, D1 with 2-3 fold lower affinity. pmid:7568626
A comprehensive profiling study of 41 classical psychedelics against 318 human GPCRs demonstrated potent lysergamide actions at nearly every serotonin, dopamine, and adrenergic receptor subtypesupported
41 classical psychedelics profiled against 318 human GPCRs. Psychedelics have potent actions at nearly every serotonin, dopamine, and adrenergic receptor. j.neuron.2025.06.012
Claim in pharmacology — inconclusiveinconclusiveworking →
LSD also engages dopamine D2-like receptors in a temporally delayed second phase of action, potentially contributing to late-phase effects distinct from the initial serotonergic experiencesupported
Initial 5-HT2A effects (LSD-30) vs delayed D2 effects (LSD-90). j.neuropharm.2011.02.006
The following class-level reference values derive from controlled LSD studies: oral Tmax of approximately 1–2 hours, elimination half-life of 2.7 hours (range 1.5–6.2 hours) at microdoses with longer estimates of 3–5 hours at full doses, dose-proportional first-order elimination, and duration of subjective effects of 6.7–11 hours dose-dependently at 25–200 µg.supported
Tmax ~1.1 h, half-life 2.7 h (range 1.5-6.2 h), dose-proportional. cpt.2057
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The following class-level reference values derive from controlled LSD studies: oral Tmax of approximately 1–2 hours, elimination half-life of 2.7 hours (range 1.5–6.2 hours) at microdoses with longer estimates of 3–5 hours at full doses, dose-proportional first-order elimination, and duration of subjective effects of 6.7–11 hours dose-dependently at 25–200 µg.supported
Duration of subjective effects 6.7-11 h (dose-dependent). s41386-020-00883-6
LSZ-specific metabolism data come from Wagmann et al., who studied the compound in pooled human liver S9 fractionssupported
LSZ metabolism via human liver S9 fractions. s00216-018-1558-9
Primary metabolic pathways are N-dealkylation and hydroxylation, catalyzed principally by CYP1A2 and CYP3A4supported
N-dealkylation and hydroxylation predominate, catalyzed primarily by CYP1A2 and CYP3A4. s00216-018-1558-9
The parent compound was not detectable in rat urine at expected recreational doses by standard urinalysis screening procedures, indicating that targeted metabolite detection methods are required for forensic identification.supported
Parent drug not detectable in rat urine at recreational doses by standard screening. s00216-018-1558-9
summary9 · 4 ok
In the mouse head-twitch response assay, LSZ is equipotent to LSD (ED₅₀ = 114.2 nmol/kg vs 132.8 nmol/kg), with a reported oral duration of 6–10 hours and an active dose range of approximately 100–300 µg.partially supported
LSZ ED50 = 114.2 nmol/kg, equipotent to LSD (ED50 = 132.8 nmol/kg) dta.1985
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Metabolism proceeds via N-dealkylation and hydroxylation catalyzed by CYP1A2 and CYP3A4supported
N-dealkylation and hydroxylation predominate, catalyzed primarily by CYP1A2 and CYP3A4. s00216-018-1558-9
No LD₅₀ or toxic dose has been established for LSZ; the closest class reference is a series of eight massive LSD overdoses, all survived with supportive caresupported
Eight cases of massive intranasal LSD overdose... All recovered with supportive care. pmid:4816396
Claim in summary — inconclusiveinconclusiveworking →
Tolerance develops rapidly through 5-HT₂A receptor downregulation in the frontal cortex, with full cross-tolerance to other serotonergic psychedelicssupported
5-HT2AR downregulation in frontal cortex after repeated DOI. Cross-tolerance between DOI and LSD confirmed. acschemneuro.2c00170
Claim in summary — inconclusiveinconclusiveworking →
comparative-pharmacology7 · 5 ok
Both compounds showed an inverted-U dose-response curve with maximal HTR at 200 µg/kgsupported
Maximal HTR at 200 ug/kg. dta.1985
Community-reported LSZ duration (6–10 hours total) appears shorter than LSD at doses producing comparable subjective intensity (LSD: 6.7–11 hours dose-dependently at 25–200 µg)supported
Duration of subjective effects 6.7-11 h (dose-dependent). s41386-020-00883-6
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Brandt et al. directly compared LSZ and LSD in the mouse head-twitch response (HTR) paradigm:supported
LSZ ED50 = 114.2 nmol/kg, equipotent to LSD (ED50 = 132.8 nmol/kg). dta.1985
LSZ is equipotent to LSD in this assay, with overlapping confidence intervalssupported
LSZ ED50 = 114.2 nmol/kg, equipotent to LSD (ED50 = 132.8 nmol/kg). dta.1985
Halberstadt et al. established a strong positive correlation (r = 0.9448) between mouse HTR potency and reported hallucinogenic potency in humans across 36 compounds, validating cautious extrapolation of HTR data to human dosing estimates.supported
Strong positive correlation (r=0.9448) between HTR potencies in mice and hallucinogenic potencies in humans (n=36). j.neuropharm.2019.107933
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
chemistry6 · 3 ok
Claim in chemistry — inconclusiveinconclusiveworking →
This conformational restriction was the design rationale: by limiting rotational freedom, Nichols et al. could map which spatial orientation of the diethylamide is required for potent 5-HT₂A binding.supported
Provides structural insight into amide conformation for 5-HT2A binding. pmid:12213075
Claim in chemistry — inconclusiveinconclusiveworking →
ECPLA also produces LSD-like head-twitch responses in mice.supported
Pharmacological characterization of ECPLA (LSZ isomer) via receptor binding, HTR in mice. s00213-018-5055-9
Of the three diastereomers synthesized by Nichols et al. — (S,S)-(+), (R,R)-(−), and cis — only the (S,S) isomer exhibited potent 5-HT₂A binding and LSD-like behavioral activitysupported
(S,S)-(+)-2,4-dimethylazetidine lysergamide has highest LSD-like behavioral and pharmacological activity among isomers; highest 5-HT2A affinity and functional potency. pmid:12213075
Claim in chemistry — inconclusiveinconclusiveworking →
history6 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Pharmacological evaluation revealed that only the (S,S)-(+) isomer — designated LSZ — exhibited binding affinity and behavioral potency closely matching LSD, while the (R,R) and cis isomers were significantly less active in all assayssupported
(S,S)-(+)-2,4-dimethylazetidine lysergamide has highest LSD-like behavioral and pharmacological activity among isomers; highest 5-HT2A affinity and functional potency. pmid:12213075
Claim in history — inconclusiveinconclusiveworking →
clinical-evidence5 · 5 ok
In vitro receptor binding and metabolism studiessupported
(S,S)-(+)-2,4-dimethylazetidine lysergamide... highest 5-HT2A affinity and functional potency. pmid:12213075
In vitro receptor binding and metabolism studiessupported
LSZ metabolism via human liver S9 fractions. s00216-018-1558-9
Animal behavioral pharmacology (mouse head-twitch response, rat drug discrimination)supported
Both show LSD-like HTR in C57BL/6J mice via 5-HT2A mechanism. dta.1985
Animal behavioral pharmacology (mouse head-twitch response, rat drug discrimination)supported
Drug discrimination study in rats. pmid:12213075
Analytical characterization of NPS market samplessupported
Full analytical characterization (NMR, GC-MS, HPLC, IR). dta.1985
receptor-pharmacology5 · 4 ok
Receptor binding affinities for LSZ are attributed to Nichols et al. 2002 via secondary compilationsupported
(S,S)-(+)-2,4-dimethylazetidine lysergamide... highest 5-HT2A affinity and functional potency. pmid:12213075
Jain et al. profiled 41 classical psychedelics — including multiple lysergamides — against 318 human GPCRs and found potent actions at nearly every serotonin, dopamine, and adrenergic receptor subtypesupported
41 classical psychedelics profiled against 318 human GPCRs. Psychedelics have potent actions at nearly every serotonin, dopamine, and adrenergic receptor. j.neuron.2025.06.012
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The dopaminergic component of lysergamide pharmacology was characterized by Watts et al., who found D1 (Ki ~25–50 nM) and D2 receptor binding with agonist-type profiles across LSD and structural analogssupported
LSD and lysergamide analogs compete for D1 and D2 dopamine receptors with agonist profiles. pmid:7568626
By structural analogy, LSZ likely shares this dopaminergic engagement, which may contribute to a temporally distinct second phase of action as documented for chronic LSD administration.supported
Initial 5-HT2A effects (LSD-30) vs delayed D2 effects (LSD-90). j.neuropharm.2011.02.006
pharmacokinetic-detail3 · 3 ok
Wagmann et al. studied LSZ metabolism in pooled human liver S9 fractions and identified N-dealkylation and hydroxylation as the primary metabolic pathways, catalyzed principally by CYP1A2 and CYP3A4supported
LSZ metabolism via human liver S9 fractions. N-dealkylation and hydroxylation predominate, catalyzed primarily by CYP1A2 and CYP3A4. s00216-018-1558-9
The parent compound was undetectable in rat urine at expected recreational doses using standard urinalysis screening procedures, with forensic implications for clinical and workplace drug testing: targeted metabolite detection methods are required for LSZ identification.supported
Parent drug not detectable in rat urine at recreational doses by standard screening. s00216-018-1558-9
These interactions have not been studied for LSZ specifically but are predictable from its established metabolic pathway.supported
N-dealkylation and hydroxylation predominate, catalyzed primarily by CYP1A2 and CYP3A4. s00216-018-1558-9
neuroscience2 · 2 ok
LSD directly binds the TrkB receptor (BDNF receptor) with approximately 1000-fold higher affinity than classical antidepressants, promoting structural neuroplasticity through BDNF/TrkB signaling independently of 5-HT₂A activationsupported
LSD and psilocin bind TrkB with 1000-fold higher affinity than other antidepressants. Effects on neuroplasticity and antidepressant behavior depend on TrkB. LSD head twitching is 5-HT2A-dependent and TrkB-independent. s41593-023-01316-5
The psychoplastogen hypothesis frames classical psychedelics as compounds that promote rapid structural and functional neural plasticity, potentially resetting maladaptive neural circuitssupported
Effects on neuroplasticity and antidepressant behavior depend on TrkB. s41593-023-01316-5