generation run 2026-04-24
57 min completedmodel pipeline-v5plan not recordedrun/25b05ecb…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 33 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
22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | LSD pharmacokinetics human plasma half-life metabolism | 7 | 4 | LSD PK data relevant as 1P-LSD prodrug |
| 2 | PubChem | 1P-LSD | 1 | 1 | Primary chemical identity source |
| 3 | OpenAlex | 1P-LSD 1-propionyl lysergamide psychedelic | 32 | 4 | Landmark papers on 1P-LSD pharmacology |
| 4 | ClinicalTrials.gov | LSD lysergic acid diethylamide treatment | 10 | 3 | Background LSD clinical context only |
| 5 | PubMed | PMID 30617391 | 1 | 1 | Metabolism and CYP enzyme data |
| 6 | ClinicalTrials.gov · absence | 1P-LSD lysergamide psychedelic | 0 | 0 | No 1P-LSD trials exist |
| 7 | PubMed | PMID 31756337 | 1 | 1 | Key prodrug mechanism study |
| 8 | PubMed | 1P-LSD 1-propionyl-LSD lysergamide pharmacology | 2 | 2 | Direct 1P-LSD metabolism data |
| 9 | PubMed | psychedelic tolerance cross-tolerance 5-HT2A downregulation | 1 | 1 | Cross-tolerance mechanism data |
| 10 | PubMed | PMID 26456305 | 1 | 1 | Foundational first characterization paper |
| 11 | Crossref | 10.1016/j.cell.2016.12.033 | 1 | 1 | Structural basis for LSD binding mechanism relevant to 1P-LSD prodrug |
| 12 | PubMed | hallucinogen persisting perception disorder HPPD LSD treatment mechanism | 4 | 4 | HPPD as known adverse effect of LSD-class substances |
| 13 | PubMed | LSD lysergic acid diethylamide dopamine receptor binding D2 pharmacology | 8 | 2 | LSD dopaminergic pharmacology relevant to 1P-LSD as prodrug |
| 14 | PubMed | Nichols psychedelics review 2016 pharmacology serotonin hallucinogens | 2 | 2 | Foundational pharmacology review for LSD/psychedelics |
| 15 | OpenAlex | 1CP-LSD 1V-LSD lysergamide new psychoactive prodrug analytical characterization | 5 | 2 | Comparative prodrug data strengthens 1P-LSD mechanism |
| 16 | PubMed | LSD psychotherapy anxiety treatment clinical trial randomized | 8 | 3 | LSD clinical context as primary active substance for 1P-LSD prodrug |
| 17 | WebSearch | 1P-LSD legal status Germany UK Canada Australia scheduling 2023 2024 | 10 | 5 | Legal status by major jurisdiction |
| 18 | PubMed | tramadol serotonin reuptake SERT inhibition mechanism | 6 | 2 | Mechanism for dangerous tramadol-1P-LSD interaction |
| 19 | PubMed | 1P-LSD human self-experiment psychoactive effects report blotter | 1 | 1 | Only human self-report data on 1P-LSD effects |
| 20 | WebSearch/WebFetch | 1P-LSD first appeared market research chemical 2015 2014 ALD-52 history | 10 | 2 | Historical context for discovery/origin section |
| 21 | Crossref | 10.1002/hup.2599 | 1 | 1 | Verification of user survey citation |
| 22 | PubMed | Grumann 1P-LSD pharmacokinetics subjective effects humans oral intravenous | 1 | 1 | Only published human study of 1P-LSD - most critical citation in corpus |
88 claims by section — every cited sentence, checked against its source
safety24 · 1 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 →
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 →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Hepatic impairment — 1P-LSD requires hepatic CYP-mediated deacylation; impaired liver function may alter prodrug conversion kinetics and LSD exposuresupported
For 1P-LSD: deacylation to LSD observed; CYP1A2 and CYP3A4 are primary metabolizing enzymes. s00216-018-1558-9
summary12 · 6 ok
Administered orally at 75–150 µg, it undergoes near-complete first-pass deacylation to LSD, producing an indistinguishable psychedelic experience lasting approximately 8–12 hourspartially supported
Oral 1P-LSD (100 µg): only LSD detected in serum/urine; biphasic LSD elimination t1/2=6.4h. Bioavailability of LSD from oral 1P-LSD ~100%. Psychosensory effects comparable to LSD. dta.2821
1P-LSD first appeared on the research chemical market in early 2015 with no prior description in the scientific literaturesupported
1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a research chemical. First published characterization using GC-MS, NMR, IR. dta.1884
The only published controlled human study (n = 2) confirmed complete oral prodrug conversion and characterized basic pharmacokineticssupported
Oral 1P-LSD (100 µg): only LSD detected in serum/urine; biphasic LSD elimination t1/2=6.4h. Bioavailability of LSD from oral 1P-LSD ~100%. dta.2821
The 1-propionyl substitution reduces direct 5-HT₂A receptor affinity by one to two orders of magnitude relative to LSDsupported
1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude. j.neuropharm.2019.107856
Hepatic deacylation — catalyzed primarily by CYP1A2 and CYP3A4 — liberates LSD, which acts as a partial agonist at 5-HT₂A receptors on layer V cortical pyramidal neuronssupported
For 1P-LSD: deacylation to LSD observed; CYP1A2 and CYP3A4 are primary metabolizing enzymes. s00216-018-1558-9
Claim in summary — inconclusiveinconclusiveworking →
Oral administration yields approximately 100% bioavailability of LSD, with a terminal elimination half-life of ~6.4 hours.supported
Bioavailability of LSD from oral 1P-LSD ~100%. Biphasic LSD elimination t1/2=6.4h. dta.2821
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
pharmacology11 · 7 ok
The 1-propionyl substitution reduces affinity for 5-HT₂A and other monoamine receptors by one to two orders of magnitude compared to LSD; in calcium mobilization assays, 1P-LSD and related N1-acyl lysergamides show weak efficacy or antagonist activity at 5-HT₂ subtypes.supported
1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude. ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+ assays. j.neuropharm.2019.107856
In vitro: Pooled human liver S9 fraction incubation confirms deacylation of 1P-LSD to LSD, catalyzed primarily by CYP1A2 and CYP3A4.supported
Human liver S9 fraction metabolism of nine LSD derivatives. For 1P-LSD: deacylation to LSD observed; CYP1A2 and CYP3A4 are primary metabolizing enzymes. s00216-018-1558-9
In vivo (animal): Subcutaneous administration of 1P-LSD to Sprague-Dawley rats produced high plasma concentrations of LSD, demonstrating rapid and efficient systemic deacylation.supported
High LSD plasma levels detected in rats after 1P-LSD, confirming prodrug status. j.neuropharm.2019.107856
In vivo (human): Oral ingestion of 100 µg 1P-LSD hemitartrate (n = 2) produced no detectable 1P-LSD in serum or urine — only LSD was found, with biphasic elimination and a terminal half-life of approximately 6.4 hours. LSD bioavailability from oral 1P-LSD approached 100%.supported
Oral 1P-LSD (100 µg): only LSD detected in serum/urine; biphasic LSD elimination t1/2=6.4h. Bioavailability of LSD from oral 1P-LSD ~100%. dta.2821
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
In mice, 1P-LSD induces the head-twitch response (HTR) — a validated 5-HT₂A-mediated behavioral proxy for psychedelic activity — with an ED₅₀ of 349.6 nmol/kg, approximately 38% of LSD's potency (ED₅₀ = 132.8 nmol/kg)supported
Head-twitch response ED50=349.6 nmol/kg (~38% potency of LSD). Abolished by M100907 (5-HT2A antagonist). dta.1884
Oral 1P-LSD undergoes near-complete first-pass conversion; intravenous 1P-LSD is detectable in serum for up to 4.16 hours before being fully convertedsupported
Oral 1P-LSD (100 µg): only LSD detected in serum/urine. IV 1P-LSD: detectable up to 4.16h serum. dta.2821
LSD metabolism involves CYP1A2, CYP3A4, and CYP2D6; inhibition of CYP2D6 by paroxetine increased LSD C_max by 1.4× and AUC by 1.5×partially supported
For 1P-LSD: deacylation to LSD observed; CYP1A2 and CYP3A4 are primary metabolizing enzymes. s00216-018-1558-9
Claim in pharmacology — inconclusiveinconclusiveworking →
comparative-pharmacology8 · 2 ok
In humans, where conversion has hours to proceed, the potency gap narrows substantially: 100 µg oral 1P-LSD produces effects comparable to 100 µg LSD.supported
Oral 1P-LSD (100 µg): only LSD detected in serum/urine. Bioavailability of LSD from oral 1P-LSD ~100%. Psychosensory effects comparable to LSD. dta.2821
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
In the acute HTR assay, 1P-LSD achieves 38% of LSD's potency — a function of incomplete conversion within the assay window, not intrinsic pharmacological differencessupported
Head-twitch response ED50=349.6 nmol/kg (~38% potency of LSD). Abolished by M100907 (5-HT2A antagonist). dta.1884
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
neuroscience7 · 3 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
The psychoplastogenic properties of LSD are mediated in part through direct binding to TrkB receptors, promoting BDNF signaling and synaptic plasticity independently of 5-HT₂A activationsupported
LSD directly binds TrkB. Plasticity and antidepressant effects depend on TrkB binding and BDNF signaling but independent of 5-HT2A activation. s41593-023-01316-5
Claim in neuroscience — inconclusiveinconclusiveworking →
LSD and other serotonergic psychedelics promote rapid and sustained structural neuroplasticity — increased dendritic branching, spine density, and synaptogenesis — effects now attributed in part to direct TrkB engagement rather than exclusively to 5-HT₂A signalingsupported
LSD directly binds TrkB. Plasticity and antidepressant effects depend on TrkB binding and BDNF signaling but independent of 5-HT2A activation. Head-twitching requires 5-HT2A but not TrkB. s41593-023-01316-5
Why higher bioavailability from the prodrug? Oral 1P-LSD yields ~100% LSD bioavailability versus ~80% from direct oral LSD. The mechanism — whether protection from acid degradation, enhanced absorption, or reduced presystemic metabolism — is unknown.supported
Bioavailability of LSD from oral 1P-LSD ~100%. dta.2821
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
pharmacokinetic-detail7 · 3 ok
The LSD terminal half-life measured after oral 1P-LSD (~6.4 h) exceeds values from studies using direct LSD administration: ~2.7 h at microdoses, ~3.5 h at 100 µg, and ~3.6 h in the Dolder et al. (2015) PK studysupported
Microdose LSD PK study: mean t1/2 2.7h, Tmax 1.1h. cpt.2057
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
The only published human pharmacokinetic study of 1P-LSD is the Grumann et al. (2020) controlled self-experiment (n = 2), which characterized both oral and intravenous routes.supported
Oral 1P-LSD (100 µg): only LSD detected in serum/urine; biphasic LSD elimination t1/2=6.4h. IV 1P-LSD: detectable up to 4.16h serum. dta.2821
1P-LSD deacylation to LSD is catalyzed by CYP1A2 and CYP3A4, as demonstrated in human liver S9 fractionsupported
For 1P-LSD: deacylation to LSD observed; CYP1A2 and CYP3A4 are primary metabolizing enzymes. s00216-018-1558-9
receptor-pharmacology7 · 2 ok
No direct receptor binding Ki values for 1P-LSD itself have been published; the N1-acyl substitution reduces 5-HT₂A affinity by 1–2 orders of magnitude relative to LSD, but specific numerical Ki values were not reported.supported
1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude. j.neuropharm.2019.107856
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 →
This interaction promotes BDNF signaling and neuroplasticity independently of 5-HT₂A activation and may contribute to antidepressant-like effects observed in preclinical models.supported
LSD directly binds TrkB. Plasticity and antidepressant effects depend on TrkB binding and BDNF signaling but independent of 5-HT2A activation. s41593-023-01316-5
clinical-evidence4 · 1 ok
The only controlled human data derive from Grumann et al. (2020), a self-experiment in which two volunteers received 100 µg 1P-LSD hemitartrate by oral and intravenous routes under controlled conditionssupported
Oral 1P-LSD (100 µg): only LSD detected in serum/urine; biphasic LSD elimination t1/2=6.4h. IV 1P-LSD: detectable up to 4.16h serum, LSD up to 24h serum/80h urine. dta.2821
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
effects-overview3 · 1 ok
Claim in effects-overview — inconclusiveinconclusiveworking →
The oral route — the only route with published human data — involves a prodrug conversion step that may slightly delay onset relative to direct LSD, though no controlled comparison exists.supported
Oral 1P-LSD (100 µg): only LSD detected in serum/urine. Psychosensory effects comparable to LSD. dta.2821
Claim in effects-overview — inconclusiveinconclusiveworking →
history3 · 2 ok
1P-LSD appeared on online research chemical markets in approximately January 2015, marketed in blotter and powder formpartially supported
1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a research chemical. dta.1884
The compound had no prior description in the published scientific literature — as Brandt and colleagues noted, 1P-LSD "has previously not been described in the published literature despite being closely related to 1-acetyl-LSD"supported
First published characterization using GC-MS, NMR, IR. dta.1884
Claim in history — inconclusiveinconclusiveworking →
chemistry2 · 1 ok
In practice, 100 µg oral 1P-LSD hemitartrate produces effects comparable to 100 µg LSD in published studies, suggesting functional dose equivalence at this scale.supported
Oral 1P-LSD (100 µg): only LSD detected in serum/urine... Psychosensory effects comparable to LSD. dta.2821
Claim in chemistry — inconclusiveinconclusiveworking →