generation run 2026-05-09
81 min completedmodel pipeline-v5plan not recordedrun/cc9b6495…Selection
Verification
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The model's own caveats
11 further caveats recorded as free text — readable on the working page
Reproduce
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- 28 source keys (listed under Sources)
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21 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed · absence | 1Fe-LSD fluoroethyl lysergamide | 0 | — | — |
| 2 | PubChem · absence | 1Fe-LSD | 0 | 0 | — |
| 3 | OpenAlex · absence | 1Fe-LSD fluoroethyl LSD lysergamide | 0 | — | — |
| 4 | PubMed | lysergamide new psychoactive substance receptor binding pharmacology | 1 | 1 | — |
| 5 | Google Patents | — | 1 | — | — |
| 6 | hhcfriends.eu | — | 1 | — | — |
| 7 | PubMed + OpenAlex | 1P-LSD 1cP-LSD lysergamide prodrug psychedelic pharmacology | 7 | 3 | — |
| 8 | Bluelight.org forum | — | 1 | — | — |
| 9 | OpenAlex | novel lysergamide designer drugs forensic analysis | 54 | 2 | — |
| 10 | WebSearch | 1Fe-LSD ferrocenecarbonyl LSD IUPAC molecular formula SMILES PubChem CID 2024 2025 | 10 | 5 | — |
| 11 | PubMed | LSD pharmacokinetics Holze Dolder Liechti | 4 | 3 | — |
| 12 | PubMed | brain iron ferrocene-loaded rat dopamine Ward | 1 | 1 | — |
| 13 | PubMed | LSD crystal structure serotonin receptor Wacker | 1 | 1 | — |
| 14 | WebSearch | 1Fe-LSD ferrocene BBB iron oxidative stress Fenton chemistry safety 2025 | 10 | — | — |
| 15 | lsd-legal.de | — | 1 | — | — |
| 16 | PubMed | serotonin syndrome psychedelic MAOI | 1 | 1 | — |
| 17 | ClinicalTrials.gov | LSD lysergic acid diethylamide | 10 | — | — |
| 18 | PubMed | tolerance cross-tolerance 5-HT2A psychedelic de la Fuente Revenga | 1 | — | — |
| 19 | PubMed | hallucinogen persisting perception disorder HPPD LSD | 8 | 2 | — |
| 20 | WebSearch | 1Fe-LSD legal status US UK EU scheduling 2025 2026 | 10 | — | — |
| 21 | grokipedia.com | — | 1 | — | — |
63 claims by section — every cited sentence, checked against its source
safety16 · 10 ok
Ward and colleagues administered the ferrocene derivative 3,5,5-trimethylhexanoyl ferrocene to rats for four weeks and observed up to 50% increases in iron content in the substantia nigra, cerebellum, and cerebral cortexsupported
After 4 weeks administration of ferrocene derivative (3,5,5-trimethyl hexanoyl ferrocene) to rats, substantia nigra, cerebellum, and cerebral cortex showed up to 50% increase in iron content. pmid:7598744
Dopamine metabolism was significantly altered, with changes in homovanillic acid levels and dopamine turnover ratessupported
Dopamine metabolism significantly altered (HVA and dopamine turnover). pmid:7598744
Deaths directly attributable to LSD alone are exceedingly rare; most LSD-attributed fatalities have involved adulterants — particularly 25I-NBOMe sold as LSDsupported
Deaths attributed to LSD alone are rare. One likely caused by 25I-NBOMe substituted for LSD. j.forsciint.2018.01.006
For N1-acyl LSD analogs specifically, multi-platform in silico toxicity analysis of five compounds (ALD-52, 1P-LSD, 1B-LSD, 1V-LSD, 1cP-LSD) yielded predicted rat LD₅₀ values of 49–85 mg/kg, with elevated cardiotoxicity and genotoxicity alerts for 1cP-LSD specificallypartially supported
Predicted LD50 in rats: 49-85 mg/kg. Elevated pulmonary toxicity risk for 1cP-LSD (81%). Genotoxicity alerts. Cardiotoxicity assessment. s00204-025-04255-1
Acute anxiety, panic, and confusion are dose-dependent effects of LSD, becoming prominent at doses of 200 µg and abovesupported
Ego dissolution and anxiety greater at 200 µg. s41386-020-00883-6
Hallucinogen persisting perception disorder (HPPD) — a condition characterized by recurrent, involuntary re-experiencing of perceptual disturbances originally experienced during intoxication — is a recognized risk of LSD usesupported
Review of 45 papers on HPPD. brainsci8030047
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
LSD produces rapid tolerance (tachyphylaxis) mediated by 5-HT₂A receptor downregulation in the frontal cortexsupported
5-HT2AR downregulation in frontal cortex after DOI. Cross-tolerance between DOI and LSD. acschemneuro.2c00170
The tolerance mechanism is independent of β-arrestin-2 signalingsupported
Tolerance mechanism independent of beta-arrestin-2. acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) may substantially increase LSD exposure after 1Fe-LSD hydrolysis, as CYP2D6 is the primary enzyme metabolizing LSDsupported
CYP2D6 poor metabolizers have ~75% higher LSD and OH-LSD AUC, longer half-lives. s41598-021-90343-y
Claim in safety — inconclusiveinconclusiveworking →
Current MAOI use — Risk of unpredictable potentiation and serotonin toxicity.supported
Reviews drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs/MAOIs. Evaluates clinical evidence for serotonin syndrome risk. s00213-021-05876-x
Claim in safety — inconclusiveinconclusiveworking →
pharmacology15 · 14 ok
This prodrug mechanism is established across the N1-acyl LSD analog class: Halberstadt and colleagues demonstrated that ALD-52, 1p-lsd, and 1B-LSD undergo rapid deacylation in rat plasma to yield LSD, with psychedelic activity contingent on this conversionsupported
High levels of LSD detected in plasma of rats after subcutaneous ALD-52 and 1P-LSD, demonstrating rapid deacylation in vivo. Findings consistent with prediction that 1-acyl LSD derivatives serve as prodrugs for LSD. j.neuropharm.2019.107856
Brandt and colleagues confirmed the mechanism for 1cp-lsd using human serum incubation and later extended it to 1F-LSD (1-furan-2-carbonyl-LSD) and 1T-LSD (1-thiophene-2-carbonyl-LSD).partially supported
1CP-LSD incubation with human serum led to formation of LSD, indicating prodrug mechanism. dta.2789
Brandt and colleagues confirmed the mechanism for 1cp-lsd using human serum incubation and later extended it to 1F-LSD (1-furan-2-carbonyl-LSD) and 1T-LSD (1-thiophene-2-carbonyl-LSD).supported
1F-LSD and 1T-LSD also produce HTR and hydrolyze to LSD. dta.3829
N1-acyl substitution reduces direct 5-HT₂A binding affinity by 1–2 orders of magnitude relative to LSD, consistent with the silent prodrug model in which the intact compound is pharmacologically inert and requires in vivo deacylation for activity.supported
1-Acyl-substitution reduced affinity of LSD for monoamine receptors including 5-HT2A by 1-2 orders of magnitude... Findings consistent with prediction that 1-acyl LSD derivatives serve as prodrugs for LSD. j.neuropharm.2019.107856
Within the N1-acyl series, larger and more lipophilic substituents reduce hydrolysis efficiency: 1DD-LSD (1-dodecanoyl-LSD) shows 27-fold lower potency than LSD in the HTR assay, attributed to incomplete hydrolysis of the twelve-carbon acyl chainsupported
LSD has 27-fold higher potency. Increased lipophilicity may reduce efficiency of hydrolysis compared to shorter chain analogs. dta.3691
The liberated LSD acts as a partial agonist at multiple monoamine receptors, with 5-HT₂A as the primary mediator of psychedelic effectssupported
Ergolines including LSD as the primary ergoline psychedelic scaffold. j.pharmr.2025.100059
Claim in pharmacology — inconclusiveinconclusiveworking →
Oral LSD reaches peak plasma concentration (T_max) at approximately 1.1 hours in the 5–20 µg range, with dose-proportional kinetics confirmed from 5 to 200 µgpartially supported
Mean Tmax 1.1 h... Dose-proportional plasma concentrations. cpt.2057
Oral LSD reaches peak plasma concentration (T_max) at approximately 1.1 hours in the 5–20 µg range, with dose-proportional kinetics confirmed from 5 to 200 µgpartially supported
Mean Tmax 1.1 h... Dose-proportional plasma concentrations. cpt.2057
Oral LSD reaches peak plasma concentration (T_max) at approximately 1.1 hours in the 5–20 µg range, with dose-proportional kinetics confirmed from 5 to 200 µgpartially supported
LSD dose-proportional PK and dose-dependent subjective responses from 25 µg. s41386-020-00883-6
Mean elimination half-life is 2.7 hours (range 1.5–6.2 hours)supported
Mean elimination half-life 2.7 h (range 1.5-6.2 h). cpt.2057
CYP2D6 is the primary metabolizing enzyme; poor metabolizers exhibit approximately 75% higher AUC for LSD and its primary metabolite 2-oxo-3-hydroxy-LSD (OH-LSD) compared to extensive metabolizers, with prolonged half-livessupported
CYP2D6 poor metabolizers have ~75% higher LSD and OH-LSD AUC, longer half-lives. s41598-021-90343-y
OH-LSD is the primary urinary metabolite used in forensic detection.supported
LC-MS/MS validated for LSD, OH-LSD, and 9 LSD analogs in urine... Suitable for forensic surveillance of emerging LSD analogs. 1556-4029.15572
A hallmark of LSD pharmacology is the disparity between its short plasma half-life (~3 hours) and prolonged subjective effects (6.7 hours at 25 µg to 11 hours at 200 µg)supported
Duration 6.7-11 h at doses of 25-200 µg. s41386-020-00883-6
This discrepancy is explained by the EL2 "lid" mechanism: the crystal structure of LSD bound to 5-HT₂B revealed that extracellular loop 2 closes over the binding pocket after LSD enters, creating a kinetic trap responsible for the drug's exceptionally slow receptor dissociation ratesupported
Crystal structure of LSD bound to 5-HT2B receptor. EL2 'lid' mechanism explains LSD's exceptionally slow dissociation from both 5-HT2B and 5-HT2A receptors. j.cell.2016.12.033
neuroscience12 · 6 ok
LSD disrupts the default mode network (DMN) — a set of cortical midline structures (medial prefrontal cortex, posterior cingulate cortex, precuneus) whose coherent activity supports self-referential processing, mind-wandering, and the narrative sense of selfsupported
Psychedelics disrupt DMN connectivity while enhancing global integration. Ego dissolution associated with these network effects. j.neubiorev.2025.106529
Under LSD, DMN functional integrity decreases while connectivity between normally segregated brain networks increases, a state characterized by elevated neural entropy and global functional connectivitysupported
Psychedelics disrupt DMN connectivity while enhancing global integration. j.neubiorev.2025.106529
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
These effects — including increased dendritic spine density and enhanced synaptic connectivity — persist beyond the acute psychedelic experience and are hypothesized to mediate the therapeutic effects observed in clinical depression trials.supported
Narrative review of 5-HT2A receptor role in neuroplasticity and antidepressant effects of serotonergic psychedelics including LSD. Reviews evidence for and against 5-HT2A necessity for neuroplastic effects vs. hallucinogenic effects. s41380-025-03169-9
Claim in neuroscience — inconclusiveinconclusiveworking →
Ketanserin blockade at this receptor completely abolishes all subjective effects, confirming that 5-HT₂A activation on these neurons is the necessary cellular event.supported
Ketanserin prevented 200 µg LSD response. Full psychedelic effects primarily mediated by 5-HT2A. s41386-020-00883-6
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Does 1Fe-LSD alter brain iron homeostasis? Ferrocene derivatives increase brain iron content by up to 50% in rats with consequent alterations in dopamine metabolism. Whether 1Fe-LSD at recreational doses and frequencies produces equivalent, lesser, or negligible effects on human brain iron homeostasis is unknown.supported
substantia nigra, cerebellum, and cerebral cortex showed up to 50% increase in iron content. Dopamine metabolism significantly altered (HVA and dopamine turnover). pmid:7598744
Is 1Fe-LSD a true silent prodrug? The principle that N1-acyl LSD analogs are pharmacologically silent at 5-HT₂A has been demonstrated for small acyl substituents but has not been tested for the sterically unusual ferrocene group.supported
1-Acyl-substitution reduced affinity of LSD for monoamine receptors including 5-HT2A by 1-2 orders of magnitude. ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists. j.neuropharm.2019.107856
receptor-pharmacology7 · 6 ok
5-HT₂A receptor — Primary psychedelic target. LSD binds as a high-affinity partial agonist. The 5-HT₂A antagonist ketanserin completely abolishes all subjective effects of LSD at doses up to 200 µg, confirming 5-HT₂A as the necessary and sufficient receptor for the psychedelic experience.supported
Ketanserin prevented 200 µg LSD response. Full psychedelic effects primarily mediated by 5-HT2A. s41386-020-00883-6
The intact N1-acylated compound is expected to have markedly reduced 5-HT₂A affinity relative to LSD — reductions of 1–2 orders of magnitude are typical across the N1-acyl series — consistent with the silent prodrug model.supported
1-Acyl-substitution reduced affinity of LSD for monoamine receptors including 5-HT2A by 1-2 orders of magnitude. j.neuropharm.2019.107856
The pharmacological profile of the presumed active moiety, LSD, encompasses multiple receptor systems:supported
Ergolines including LSD as the primary ergoline psychedelic scaffold. j.pharmr.2025.100059
Wacker and colleagues solved the crystal structure of LSD bound to the human 5-HT₂B receptor, revealing that extracellular loop 2 (EL2) forms a "lid" over the binding pocket after ligand entrysupported
Crystal structure of LSD bound to 5-HT2B receptor. EL2 'lid' mechanism explains LSD's exceptionally slow dissociation. j.cell.2016.12.033
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Tolerance to the psychedelic effects of the serotonergic class develops through 5-HT₂A receptor downregulation in the frontal cortex, independently of β-arrestin-2 signalingsupported
5-HT2AR downregulation in frontal cortex after DOI. Tolerance mechanism independent of beta-arrestin-2. acschemneuro.2c00170
Cross-tolerance develops between LSD and other 5-HT₂A agonist psychedelics but not with non-psychedelic 5-HT₂A agonists such as lisuride, suggesting psychedelic-specific signaling cascades — potentially involving biased agonism — underlie the tolerance mechanism.supported
Cross-tolerance between DOI and LSD. No cross-tolerance with non-psychedelic 5-HT2A agonist lisuride. acschemneuro.2c00170
summary5 · 4 ok
Expected duration is 8–12 hours based on LSD class data.partially supported
Duration 6.7-11 h at doses of 25-200 µg. s41386-020-00883-6
As an N1-acyl LSD analog, 1Fe-LSD is presumed to undergo metabolic hydrolysis of its ferrocenecarbonyl bond, releasing LSD and ferrocenecarboxylic acidsupported
High levels of LSD detected in plasma of rats after subcutaneous ALD-52 and 1P-LSD, demonstrating rapid deacylation in vivo. Findings consistent with prediction that 1-acyl LSD derivatives serve as prodrugs for LSD. j.neuropharm.2019.107856
Claim in summary — inconclusiveinconclusiveworking →
The ferrocene moiety introduces a safety concern absent from prior lysergamide analogs: ferrocene derivatives administered to rats produced up to 50% increases in brain iron content with altered dopamine metabolismsupported
substantia nigra, cerebellum, and cerebral cortex showed up to 50% increase in iron content... Dopamine metabolism significantly altered (HVA and dopamine turnover). pmid:7598744
Tolerance develops rapidly via 5-HT₂A downregulation, and no physical dependence is expected. The safety profile of 1Fe-LSD cannot be assumed equivalent to prior N1-acyl LSD analogs until ferrocene-specific toxicological questions are empirically resolved.supported
5-HT2AR downregulation in frontal cortex after DOI. Tolerance mechanism independent of beta-arrestin-2. acschemneuro.2c00170
comparative-pharmacology4 · 3 ok
All members share the LSD core scaffold with differing acyl substituents at the indole N-1 position and are presumed to act through the same prodrug mechanism — in vivo hydrolysis yielding LSD as the common active moiety.supported
Findings consistent with prediction that 1-acyl LSD derivatives serve as prodrugs for LSD. j.neuropharm.2019.107856
For small acyl groups (acetyl through cyclopropanoyl), hydrolysis is rapid and essentially complete, yielding HTR potencies equivalent to LSDsupported
High levels of LSD detected in plasma of rats after subcutaneous ALD-52 and 1P-LSD, demonstrating rapid deacylation in vivo. j.neuropharm.2019.107856
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
The 27-fold potency reduction observed with 1DD-LSD establishes that a threshold exists beyond which increasing lipophilicity and steric bulk of the N1 group impairs hydrolysis sufficiently to reduce apparent activity.supported
LSD has 27-fold higher potency. Increased lipophilicity may reduce efficiency of hydrolysis compared to shorter chain analogs. dta.3691
pharmacokinetic-detail3 · 3 ok
In a pooled analysis of controlled studies, poor metabolizers exhibited approximately 75% higher AUC for both LSD and OH-LSD compared to extensive metabolizers, with correspondingly prolonged half-lives and greater subjective effect intensitysupported
CYP2D6 poor metabolizers have ~75% higher LSD and OH-LSD AUC, longer half-lives, greater mind alteration, and longer subjective effect durations. s41598-021-90343-y
CYP1A2 and CYP2C9 are also implicated in LSD metabolism but produce no significant phenotypic effect in vivo.supported
No significant effect of CYP1A2, 2C9, 2C19, 2B6. s41598-021-90343-y
Increasing lipophilicity and steric bulk of the N1 substituent correlate with reduced hydrolysis efficiency. 1DD-LSD, bearing a twelve-carbon aliphatic acyl chain, exhibits 27-fold lower potency than LSD in the mouse HTR assay, attributed primarily to reduced hydrolysis rate rather than intrinsic receptor activity of the intact prodrug.supported
LSD has 27-fold higher potency. Increased lipophilicity may reduce efficiency of hydrolysis compared to shorter chain analogs. dta.3691
chemistry1 · 1 ok
Within this family, it is a member of the N1-acyl LSD prodrug series, in which the indole nitrogen at the N-1 position of the lsd scaffold carries an acyl substituent that is cleaved in vivo to liberate the parent compound.supported
High levels of LSD detected in plasma of rats after subcutaneous ALD-52 and 1P-LSD, demonstrating rapid deacylation in vivo. Findings consistent with prediction that 1-acyl LSD derivatives serve as prodrugs for LSD. j.neuropharm.2019.107856