generation run 2026-04-28
78 min completedmodel pipeline-v5plan not recordedrun/94ca8ca9…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 32 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
20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | 1B-LSD | 1 | 1 | — |
| 2 | OpenAlex | 1B-LSD butanoyl lysergamide psychedelic | 10 | 5 | — |
| 3 | PubMed | 1B-LSD 1-butanoyl-LSD lysergamide pharmacology | 2 | 2 | — |
| 4 | PubMed | LSD pharmacokinetics human plasma concentration half-life metabolism | 8 | 5 | — |
| 5 | Crossref | DOI 10.1016/j.cell.2016.12.033 | 1 | 1 | — |
| 6 | ClinicalTrials.gov · absence | 1B-LSD lysergamide | 0 | — | — |
| 7 | PubMed | LSD subjective effects controlled study human dose response psychedelic | 8 | 2 | — |
| 8 | OpenAlex | lysergamide acyl LSD prodrug structure activity relationship potency | 7 | 2 | — |
| 9 | PubMed | tramadol serotonin syndrome mechanism risk | 4 | 2 | — |
| 10 | PubMed | tolerance cross-tolerance psychedelic 5-HT2A | 1 | 1 | — |
| 11 | WebSearch | 1B-LSD 1-butanoyl-LSD research chemical first appearance market history | 10 | 2 | — |
| 12 | PMC | 1B-LSD Brandt 2019 full text | 1 | 2 | — |
| 13 | PubChem REST API | PubChem CID 145875086 properties | 1 | 2 | — |
| 14 | WebSearch | 1B-LSD legal status UK Germany US Australia Canada | 10 | 4 | — |
| 15 | PubMed | Holze LSD acute subjective effects randomized controlled | 5 | 2 | — |
| 16 | WebSearch | 1B-LSD NpSG Germany schedule 2019 | 10 | 2 | — |
| 17 | PubMed | CYP450 LSD metabolism nor-LSD 2-oxo-3-hydroxy-LSD | 1 | 1 | — |
| 18 | Research output writing | synthesis of all research into 01-research-output.md | 1 | 1 | — |
| 19 | PubChem REST API | 1B-LSD CID 145875086 SMILES and properties | 1 | 2 | — |
| 20 | PubMed multi-paper | LSD dose-response effects, CYP2D6 pharmacogenomics, metabolism pathway | 3 | 3 | — |
87 claims by section — every cited sentence, checked against its source
pharmacology26 · 20 ok
Cryo-EM structures of the LSD-bound 5-HT2A receptor in its active state confirm this binding mode and demonstrate G-protein couplingsupported
Cryo-EM structure of active-state 5-HT2A receptor bound to hallucinogen 25-CN-NBOH and Gaq heterotrimer; X-ray crystal structures with LSD. j.cell.2020.08.024
Direct demonstration of deacylation published for structural analogs ALD-52 and 1P-LSD with high LSD plasma levels detected in Sprague-Dawley rats following subcutaneous administrationsupported
High LSD plasma levels in rats after ALD-52 and 1P-LSD confirming prodrug status. j.neuropharm.2019.107856
The butanoyl group at the indole N1 position undergoes hydrolytic cleavage releasing the parent compound d-lysergic acid diethylamide in vivo via esterase activitysupported
High LSD plasma levels in rats after ALD-52 and 1P-LSD confirming prodrug status. j.neuropharm.2019.107856
The butanoyl group at the indole N1 position undergoes hydrolytic cleavage by plasma and tissue esterases releasing d-lysergic acid diethylamide in vivosupported
Proposed as LSD prodrug. dta.2613
Claim in pharmacology — inconclusiveinconclusiveworking →
Psychedelic effects are primarily 5-HT2A mediated as selective 5-HT2A antagonist ketanserin fully blocks all subjective effects of 200 ug LSD in healthy subjectssupported
Ketanserin blocked effects confirming 5-HT2A primary mediation. s41386-020-00883-6
LSD additionally engages 5-HT1A 5-HT2B 5-HT2C dopamine D1-D4 adrenergic alpha1 and alpha2 histamine H1 and trace amine receptorssupported
Comprehensive review of all aspects of LSD pharmacology and psychopharmacology. j.1755-5949.2008.00059.x
LSD is primarily a partial agonist at the serotonin 5-HT2A receptor on apical dendrites of neocortical pyramidal cells in layer Vsupported
psychedelics are agonists or partial agonists at brain 5-HT2A receptors, particularly neocortical pyramidal cells layer V. pr.115.011478
Despite detrimental effect on direct 5-HT2A binding and efficacy 1B-LSD induces head twitches in mice with high potency consistent with in vivo conversion to LSD as the active speciessupported
HTR studies confirm LSD-like in vivo activity. High LSD plasma levels in rats after ALD-52 and 1P-LSD confirming prodrug status. j.neuropharm.2019.107856
In calcium mobilization functional assays 1B-LSD displayed weak efficacy or antagonist activity at 5-HT2 receptor subtypes in contrast to LSD full agonist profilesupported
ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+-mobilization assays. j.neuropharm.2019.107856
Competitive radioligand binding studies demonstrate N1-acyl substitution reduces affinity by 1-2 orders of magnitude relative to parent LSD across most monoamine receptor targets including the 5-HT2A sitesupported
1-Acyl-substitution reduced the affinity of LSD for most monoamine receptors, including 5-HT2A sites, by one to two orders of magnitude. j.neuropharm.2019.107856
Claim in pharmacology — inconclusiveinconclusiveworking →
Close structural analog 1CP-LSD was shown to release LSD upon incubation with human serum and ALD-52 the prototype N1-acylated derivative has been confirmed as a prodrug with hydrolysis to LSD responsible for its activitysupported
Prodrug for LSD via serum hydrolysis. dta.2789
CYP2D6 is the dominant enzyme in LSD metabolism in vivo per pharmacogenomic pooled analysissupported
CYP2D6 primary metabolizing enzyme confirmed. s41598-021-90343-y
Claim in pharmacology — inconclusiveinconclusiveworking →
Peak plasma concentrations Tmax occur at approximately 1.1 to 1.5 hours after oral administrationsupported
LSD plasma PK: mean half-life 2.7h, Tmax 1.1h. cpt.2057
Claim in pharmacology — inconclusiveinconclusiveworking →
The elimination half-life ranges from 2.7 to 5.1 hours across studies per microdose PKsupported
LSD plasma PK: mean half-life 2.7h. cpt.2057
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
LSD is metabolized primarily by CYP2D6 to nor-LSD and by CYP1A2 CYP2C9 CYP2E1 and CYP3A4 to 2-oxo-3-hydroxy-LSD or O-H-LSDsupported
CYP2D6, 2E1, 3A4 form nor-LSD; CYP1A2, 2C9, 2E1, 3A4 form O-H-LSD. j.bcp.2019.04.013
CYP2D6 is the dominant enzyme in LSD metabolism in vivo per paroxetine drug interaction studysupported
Strong evidence for CYP2D6 involvement in LSD metabolism. cpt.3618
Nor-LSD retains pharmacological activity with similar affinity at 5-HT1A 5-HT2A 5-HT2B and 5-HT2C receptors whereas O-H-LSD is inactivesupported
Nor-LSD pharmacologically active; O-H-LSD inactive. j.bcp.2019.04.013
Hepatic microsomal conversion accounts for less than 1% of LSD elimination over 4 hours indicating hepatic metabolism is not the primary elimination pathwaysupported
Minor metabolism (<1% over 4h) in human liver microsomes. j.bcp.2019.04.013
CYP2D6 poor metabolizers exhibit approximately 75% higher LSD exposure AUC prolonged elimination half-life and greater and longer subjective effectssupported
CYP2D6 poor metabolizers: ~75% higher LSD/O-H-LSD AUC, longer half-lives, greater mind alteration, longer effect duration. s41598-021-90343-y
Paroxetine a strong CYP2D6 inhibitor increased LSD Cmax by 1.4-fold and AUC by 1.5-foldsupported
Paroxetine (CYP2D6 inhibitor) increased LSD Cmax by 1.4x and AUC by 1.5x. cpt.3618
safety18 · 12 ok
Claim in safety — inconclusiveinconclusiveworking →
Multi-platform in silico toxicity predictions for five LSD analogs including 1B-LSD estimated a rat oral LD50 of 49-85 mg/kgsupported
Multi-platform in silico toxicity for five 1-acyl LSD derivatives. Predicted LD50 (rats): 49-85 mg/kg. s00204-025-04255-1
Same study predicted 75% hematotoxicity probability for 1B-LSD among the highest of the analogs tested while dermal and ocular irritation risks were predicted as uniformly lowsupported
1B-LSD predicted hematotoxicity 75%. s00204-025-04255-1
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
LSD the active moiety is generally considered physiologically safesupported
Generally considered physiologically safe, do not lead to dependence or addiction. pr.115.011478
Claim in safety — inconclusiveinconclusiveworking →
Combination of tramadol serotonin reuptake inhibition with direct 5-HT2A agonism creates multi-mechanism serotonergic load associated with life-threatening serotonin toxicitysupported
Tramadol, meperidine, methadone and dextromethorphan are weak SRIs; dangerous in combination with MAOIs causing life-threatening serotonin toxicity. pmid:16051647
Tramadol a weak serotonin-norepinephrine reuptake inhibitor in addition to its opioid agonist activity poses a dangerous interaction risksupported
Tramadol has SRI properties. Review of tramadol-serotonergic antidepressant interaction for serotonin syndrome risk. 0897190013504957
VigiBase pharmacovigilance data have noted substance use disorder reports associated with LSD in real-world voluntary reporting though methodological limitations constrain interpretationsupported
LSD associated with substance use disorder reports. Exploratory study. j.psychres.2025.116929
Psychedelics are generally considered not to produce physical dependence or addictionsupported
do not lead to dependence or addiction. pr.115.011478
Pre-drug anxiety and mental state are significant predictors of adverse psychological outcomessupported
Pre-drug mental states (anxiety, well-being) also important. s41398-024-03074-9
At doses equivalent to 200 ug LSD and above significant anxiety and ego dissolution emerge as dose-limiting psychological effectssupported
200 ug: ego dissolution, significant anxiety. s41386-020-00883-6
Relative contraindications include CYP2D6 poor metabolizer status which substantially increases LSD exposure after prodrug conversion and may result in unexpectedly prolonged and intensified effectssupported
CYP2D6 poor metabolizers: ~75% higher LSD/O-H-LSD AUC, longer half-lives, greater mind alteration, longer effect duration. s41598-021-90343-y
CYP2D6 poor metabolizers experience approximately 75% higher LSD exposure with prolonged and intensified effectssupported
CYP2D6 poor metabolizers: ~75% higher LSD/O-H-LSD AUC, longer half-lives, greater mind alteration, longer effect duration. s41598-021-90343-y
Strong CYP2D6 inhibitors including fluoxetine paroxetine bupropion haloperidol increase LSD exposure by 1.4 to 1.5-foldsupported
Paroxetine (CYP2D6 inhibitor) increased LSD Cmax by 1.4x and AUC by 1.5x. cpt.3618
Claim in safety — inconclusiveinconclusiveworking →
summary8 · 5 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
LSD the active moiety is generally considered physiologically safe with no documented lethal dose in humans and no proarrhythmic signal on QTc monitoring - reviewpartially supported
Generally considered physiologically safe, do not lead to dependence or addiction. pr.115.011478
Claim in summary — inconclusiveinconclusiveworking →
Its analytical and behavioral pharmacology was characterized in the Return of the lysergamides series which established its mouse head-twitch response potency ED50 976.7 nmol/kg approximately 14% that of LSD and its compatibility with prodrug statussupported
HTR studies in C57BL/6J mice: ED50 = 976.7 nmol/kg (~14% potency of LSD, ED50=132.8 nmol/kg). Proposed as LSD prodrug. dta.2613
Analytical and behavioral pharmacology characterized in the lysergamides series establishing mouse HTR potency and prodrug status for 1B-LSDpartially supported
HTR studies confirm LSD-like in vivo activity. Receptorome screening performed with 1B-LSD. j.neuropharm.2019.107856
1B-LSD exerts psychoactive effects through in vivo deacylation to LSD which acts as partial agonist at 5-HT2A receptor on layer V cortical pyramidal neurons confirmed by complete blockade with ketanserin in controlled human studiessupported
Ketanserin blocked effects confirming 5-HT2A primary mediation. s41386-020-00883-6
The resulting experience encompasses visual distortions ego dissolution thought connectivity and emotional intensification with set and setting serving as significant non-pharmacological modulators of outcomesupported
Pre-drug mental states (anxiety, well-being) also important. Trait openness predicts mystical effects. s41398-024-03074-9
pharmacokinetic-detail7 · 7 ok
Disparity between 1B-LSD reduced mouse HTR potency 14% of LSD and community-reported human dose ranges comparable to LSD likely reflects species differences in deacylation efficiency bioavailability or pharmacokinetic routesupported
HTR studies in C57BL/6J mice: ED50 = 976.7 nmol/kg (~14% potency of LSD, ED50=132.8 nmol/kg). Proposed as LSD prodrug. dta.2613
LSD is metabolized to nor-LSD by CYP2D6 CYP2E1 and CYP3A4 and to O-H-LSD by CYP1A2 CYP2C9 CYP2E1 and CYP3A4supported
CYP2D6, 2E1, 3A4 form nor-LSD; CYP1A2, 2C9, 2E1, 3A4 form O-H-LSD. j.bcp.2019.04.013
CYP2D6 is the dominant enzyme in vivo as demonstrated by pharmacogenomic analysis confirming primary metabolizing enzymesupported
CYP2D6 primary metabolizing enzyme confirmed. s41598-021-90343-y
CYP2D6 is the dominant enzyme in vivo as demonstrated by drug interaction study with paroxetinesupported
Strong evidence for CYP2D6 involvement in LSD metabolism. cpt.3618
Paroxetine pre-administration increased LSD Cmax by 1.4-fold and AUC by 1.5-fold though notably reduced bad drug effect anxiety and nauseasupported
Paroxetine (CYP2D6 inhibitor) increased LSD Cmax by 1.4x and AUC by 1.5x. LSD+SSRI appears well-tolerated. cpt.3618
Hepatic microsomal conversion accounts for less than 1% of LSD elimination over 4 hours indicating extrahepatic mechanisms play a significant role in overall clearancesupported
Minor metabolism (<1% over 4h) in human liver microsomes. j.bcp.2019.04.013
ALD-52 and 1P-LSD produce high LSD plasma levels in rats following subcutaneous administration and 1CP-LSD releases LSD upon incubation with human serum in vitrosupported
High LSD plasma levels in rats after ALD-52 and 1P-LSD confirming prodrug status. j.neuropharm.2019.107856
comparative-pharmacology6 · 5 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Heterocyclic acyl variants including furanyl 1F-LSD and thienyl 1T-LSD have been characterized confirming generality of N1-acyl prodrug mechanism across diverse substituent structuressupported
1F-LSD and 1T-LSD both induce HTR and are hydrolyzed to LSD in vivo. dta.3829
Increasing acyl chain length from acetyl C2 through propanoyl C3 to butanoyl C4 and beyond hexanoyl C6 and dodecanoyl C12 progressively reduces direct receptor affinity while maintaining in vivo activity through prodrug mechanismsupported
1DD-LSD ED50=2.17 mg/kg (27-fold less potent than LSD). Long-chain acyl groups reduce hydrolysis efficiency. dta.3691
Despite detrimental effect of N1-acyl substitution on 5-HT2A affinity and direct efficacy all N1-acylated LSD derivatives induce head twitches with high potency consistent with in vivo conversion to LSDsupported
HTR studies confirm LSD-like in vivo activity. High LSD plasma levels in rats after ALD-52 and 1P-LSD confirming prodrug status. j.neuropharm.2019.107856
Strong positive correlation r 0.9448 between HTR potencies in mice and reported hallucinogenic potencies in humans demonstrated across 36 compounds establishing HTR as robust predictor of human psychedelic potencysupported
Strong positive correlation (r=0.9448) between HTR potencies in mice and hallucinogenic potencies in humans (n=36 compounds). j.neuropharm.2019.107933
1B-LSD is approximately 14% as potent as LSD in the HTR assay ED50 976.7 nmol/kg vs 132.8 nmol/kgsupported
HTR studies in C57BL/6J mice: ED50 = 976.7 nmol/kg (~14% potency of LSD, ED50=132.8 nmol/kg). dta.2613
history6 · 3 ok
1B-LSD appeared August 2016 and was characterized as Part V of the Return of the lysergamides seriessupported
Return of the lysergamides. Part V: Analytical and behavioural characterization of 1-butanoyl-d-lysergic acid diethylamide (1B-LSD). dta.2613
1P-LSD appeared on the research chemical market circa 2013-2015 and was characterized as Part I of the Return of the lysergamides seriessupported
Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD). dta.1884
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
First analytical and behavioral characterization was published by Brandt and colleagues in 2019 as Part V of the Return of the lysergamides series in Drug Testing and Analysissupported
Return of the lysergamides. Part V: Analytical and behavioural characterization of 1-butanoyl-d-lysergic acid diethylamide (1B-LSD). dta.2613
Claim in history — inconclusiveinconclusiveworking →
receptor-pharmacology6 · 4 ok
5-HT2A primary target for psychedelic effects partial agonist confirmed by full blockade with ketanserin in humanssupported
Ketanserin blocked effects confirming 5-HT2A primary mediation. s41386-020-00883-6
In calcium mobilization functional assays at 5-HT2 receptor subtypes LSD acts as a full agonist while 1B-LSD alongside ALD-52 and 1P-LSD displayed weak efficacy or outright antagonist activitysupported
ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+-mobilization assays. j.neuropharm.2019.107856
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Receptorome screening of 1B-LSD was performed by Halberstadt and colleagues providing broad receptor binding profile across monoamine targetssupported
Receptorome screening performed with 1B-LSD. j.neuropharm.2019.107856
Principal finding is that N1-acyl substitution uniformly reduces affinity at monoamine receptors by 1-2 log units relative to LSDsupported
1-Acyl-substitution reduced the affinity of LSD for most monoamine receptors, including 5-HT2A sites, by one to two orders of magnitude. j.neuropharm.2019.107856
chemistry4 · 4 ok
Systematic elongation of the N1-acyl chain from acetyl through propanoyl butanoyl and hexanoyl to dodecanoyl has provided a structure-activity framework for studying acyl substituent size hydrolysis rate and in vivo potencysupported
1H-LSD (6-carbon acyl chain) HTR ED50 = 387 nmol/kg; roughly equipotent to ALD-52. Expected to hydrolyze to LSD in vivo as prodrug. dta.3767
Distinguishing structural feature is a butanoyl four-carbon acyl group attached to the indole nitrogen at N1 position differentiating it from propanoyl of 1P-LSD acetyl of ALD-52 and cyclopropanoyl of 1CP-LSDsupported
Comprehensive analytical characterization of 1B-LSD: NMR, mass spectrometry, GC, LC, IR. dta.2613
Systematic elongation of N1-acyl chain from acetyl through propanoyl butanoyl hexanoyl to dodecanoyl has provided SAR framework for acyl substituent size hydrolysis rate and potency per 1DD-LSD studysupported
1DD-LSD ED50=2.17 mg/kg (27-fold less potent than LSD). Long-chain acyl groups reduce hydrolysis efficiency. dta.3691
1B-LSD is a constitutional isomer of 1-propanoyl-6-ethyl-6-nor-lysergic acid diethylamide 1P-ETH-LAD sharing the molecular formula C24H31N3O2 but differing in substituent modificationssupported
Constitutional isomer of 1P-ETH-LAD. dta.2613
clinical-evidence3 · 3 ok
Holze and colleagues characterized dose-dependent LSD effects in double-blind placebo-controlled study of 16 healthy subjects across four oral doses 25 50 100 and 200 ugsupported
LSD 25-200 ug dose-response, n=16 healthy subjects (8M/8F), placebo-controlled crossover. s41386-020-00883-6
Selective 5-HT2A antagonist ketanserin 40 mg fully blocked all subjective effects confirming 5-HT2A mediationsupported
Ketanserin blocked effects confirming 5-HT2A primary mediation. s41386-020-00883-6
In a pooled analysis of 213 healthy subjects from 9 controlled LSD studies dose was the strongest predictor of subjective effects followed by pre-drug anxiety and trait opennesssupported
N=213 healthy subjects from 9 studies. LSD dose most important predictor. Pre-drug mental states (anxiety, well-being) also important. Trait openness predicts mystical effects. s41398-024-03074-9
neuroscience2 · 1 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Cellular trigger for psychedelic effects is 5-HT2A receptor activation on apical dendrites of layer V pyramidal neurons in neocortexsupported
psychedelics are agonists or partial agonists at brain 5-HT2A receptors, particularly neocortical pyramidal cells layer V. pr.115.011478
effects-overview1 · 1 ok
Set and setting exert powerful influence across the entire dose range with same dose producing experiences ranging from serene contemplation to acute distress depending on psychological environment and user mental statesupported
Pre-drug mental states (anxiety, well-being) also important. LSD dose most important predictor. s41398-024-03074-9