generation run 2026-05-11
71 min completedmodel pipeline-v5plan not recordedrun/52ba62fa…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
7 further caveats recorded as free text — readable on the working page
Reproduce
- inputs
- 28 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
18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | 1-cyclopropanoyl LSD analog acyl lysergamide designer drug | 1 | 1 | Key paper on 1-cyclopropanoyl LSD class, establishes prodrug mechanism |
| 2 | PubMed | 1cP-MiPLA lysergamide psychedelic | 1 | 1 | Only paper directly describing 1cP-MiPLA; forensic first report |
| 3 | OpenAlex | 1cP-MiPLA lysergamide cyclopropanoyl designer drug | 4 | 3 | Sister compounds with structurally analogous 1cP acyl group; prodrug class context |
| 4 | ClinicalTrials.gov · absence | 1cP-MiPLA lysergamide psychedelic | 0 | — | — |
| 5 | PubChem · absence | 1cP-MiPLA | 0 | — | — |
| 6 | PubMed | Return lysergamides 1P-LSD prodrug designer drug Brandt Halberstadt | 2 | 1 | Establishes 1-acyl prodrug mechanism across lysergamide class |
| 7 | PubMed | MiPLA N-methyl-N-isopropyl lysergamide pharmacology | 3 | 3 | All directly relevant to parent compound MIPLA pharmacology |
| 8 | PubMed | lysergamide AL-LAD 1P-LSD return new psychoactive substance analytical characterization | 1 | 2 | 1P-LSD is closest characterized 1-acyl lysergamide for comparison |
| 9 | PubMed | tramadol serotonin reuptake inhibition serotonergic toxicity case report interaction | 2 | 1 | Tramadol serotonin reuptake inhibition creates SS risk with serotonergic drugs |
| 10 | OpenAlex | LSD receptor pharmacology binding affinity serotonin dopamine ergoline Nichols | 10 | 2 | Core receptor pharmacology data for LSD applicable to MIPLA/1cP-MiPLA class |
| 11 | PubMed | lysergamide return series Parts V, VII, 1B-LSD, 1V-LSD analytical behavioral | 10 | 3 | Systematic HTR data showing 1-acyl substitution reduces potency 3-7x; consistent class mechanism |
| 12 | PubMed | hallucinogen persisting perception disorder HPPD LSD flashbacks visual disturbance | 4 | 2 | HPPD is known risk of LSD-class psychedelics; relevant to safety section for 1cP-MiPLA |
| 13 | PubMed | Holze LSD pharmacokinetics subjective effects healthy subjects randomized controlled trial | 9 | 4 | LSD PK/PD data provides framework for estimating 1cP-MiPLA properties as prodrug |
| 14 | WebSearch | 1cP-MiPLA legal status scheduling controlled substance 2024 2025 | 10 | 3 | — |
| 15 | PubChem | CID 170763684 | 1 | 1 | Confirmed molecular identity; InChIKey matches systematic name in brief |
| 16 | PsychonautWiki | — | 1 | 1 | — |
| 17 | WebSearch | MIPLA lysergamide legal status | 10 | 3 | — |
| 18 | PubMed | LSD overdoses case reports toxicity Nichols Grob | 2 | 2 | Core LSD class toxicity data for safety section |
76 claims by section — every cited sentence, checked against its source
safety19 · 18 ok
LSD has no known organotoxicity at any dose studied in humanssupported
LSD has no known organotoxicity. j.forsciint.2018.01.006
The human LD₅₀ is unknown and cannot be ethically determined; the animal LD₅₀ is approximately 0.3 mg/kg intravenous in rabbits (among the most sensitive species)supported
Human LD50 unknown; animal LD50 only in rabbits (~0.3 mg/kg IV). j.forsciint.2018.01.006
Five deaths have historically been attributed to LSD; Nichols and Grob (2018) found none credibly attributable to direct pharmacotoxicitysupported
Critical review of 5 LSD-attributed deaths; most attributable to drug substitution (25I-NBOMe), physical restraint, or extreme overdose. j.forsciint.2018.01.006
One documented case of accidental ingestion of approximately 55 mg (550× a standard dose) resulted in severe vomiting and prolonged altered consciousness but complete recovery without organ sequelae.supported
One subject accidentally ingested ~550x normal dose (55 mg) with severe vomiting but no lasting sequelae. pmid:32048609
LSD has not been associated with chronic organ damage in epidemiological or clinical datasupported
LSD has no known organotoxicity. j.forsciint.2018.01.006
Acute psychological distress — anxiety, paranoia, thought-loops, and panic — can occur at any dose of a classical psychedelic, particularly in unsupportive settings or in individuals with pre-existing psychiatric vulnerability. ego-dissolution at high doses, while therapeutically significant in clinical contexts, can be profoundly distressing without preparation and support.supported
Ceiling for good effects at 100 µg; ego dissolution/anxiety at 200 µg. s41386-020-00883-6
Hallucinogen persisting perception disorder (HPPD) is a rare condition characterized by persistent visual disturbances — after-images, peripheral movement, halos, and visual snow — following psychedelic usesupported
Rare condition. Clinical features: persistent visual disturbances (after-images, peripheral movement, halos). brainsci8030047
Pharmacological management includes lamotrigine, clonidine, and benzodiazepinessupported
Treatment: lamotrigine, clonidine, benzodiazepines. brainsci8030047
Classical serotonergic psychedelics develop rapid, near-complete tolerance to their psychedelic effects after a single dosepartially supported
Daily LSD (130 ug/kg IP x 5 days) decreased 5-HT2 binding in cortex at 24h. Decrease evident within 3 days. Parallels behavioral tolerance. pmid:1969270
Classical serotonergic psychedelics develop rapid, near-complete tolerance to their psychedelic effects after a single dosesupported
Psychedelic 5-HT2A agonists (DOI, LSD) show rapid tolerance and cross-tolerance via 5-HT2A receptor downregulation. acschemneuro.2c00170
The mechanism involves downregulation of cortical 5-HT₂A receptor density: in mice, tolerance to the 5-HT₂A-mediated head-twitch response is observable within 24 hours of a single dose and proceeds independently of β-arrestin-2.supported
Rapid tolerance and cross-tolerance via 5-HT2A receptor downregulation. Beta-arrestin-2 independent. acschemneuro.2c00170
Full cross-tolerance exists between LSD and other classical psychedelics (psilocybin, DOI) via the shared 5-HT₂A receptor mechanismsupported
Psychedelic 5-HT2A agonists (DOI, LSD) show rapid tolerance and cross-tolerance via 5-HT2A receptor downregulation. acschemneuro.2c00170
Full cross-tolerance exists between LSD and other classical psychedelics (psilocybin, DOI) via the shared 5-HT₂A receptor mechanismsupported
Cross-tolerance among classical psychedelics. 5-HT2A receptor as primary target. j.bbr.2014.07.016
Claim in safety — inconclusiveinconclusiveworking →
Co-administration with serotonergic psychedelics creates a risk of serotonin syndrome — characterized by neuromuscular abnormalities (tremor, clonus, hyperreflexia), altered mental status, and autonomic hyperactivity (tachycardia, fever, hypertension)supported
Serotonin syndrome (tremor, hyperreflexia, diarrhea, tachycardia, hypertension, fever). cureus.76968
Fatalities from tramadol combined with serotonergic agents have been reportedsupported
Fatalities reported for MAOIs combined with tramadol (in overdose) and 5-MeO-DMT, MDMA. s40263-025-01256-7
The combination of MAOIs with serotonergic substances and tramadol has produced fatalities.supported
Fatalities reported for MAOIs combined with tramadol (in overdose) and 5-MeO-DMT, MDMA. s40263-025-01256-7
Concurrent tramadol use (absolute): Serotonin syndrome risk via combined serotonergic mechanisms.supported
Case report: venlafaxine + tramadol combination causing serotonin syndrome (tremor, hyperreflexia, diarrhea, tachycardia, hypertension, fever). cureus.76968
Concurrent MAOI use (absolute): Serotonin syndrome risk.supported
Serotonin toxicity cases documented for MAOIs + tramadol, MDMA, meperidine. s40263-025-01256-7
pharmacology15 · 13 ok
For LSD administered orally in controlled human studies: T_max is approximately 1.1 hours, oral bioavailability is 80%, and elimination half-life ranges from 2.7 hours at microdoses to approximately 3.5 hours at standard dosespartially supported
LSD 5-20 µg: Tmax ~1.1h; t1/2 ~2.7h (1.5-6.2h range). cpt.2057
The 1-acyl modification at the indole nitrogen reduces receptor affinity by 1–2 orders of magnitude, rendering the intact prodrug pharmacologically inactive at serotonin receptorssupported
1-acyl substitution reduced receptor affinity by 1-2 orders of magnitude at monoamine receptors. Key finding: N1-acyl group blocks receptor binding, prodrug must hydrolyze to active LSD. j.neuropharm.2019.107856
1cP-LSD → LSD (confirmed in human serum at 37°C)supported
Incubation with human serum produces LSD, confirming prodrug mechanism. dta.2789
Claim in pharmacology — inconclusiveinconclusiveworking →
1P-ETH-LAD → ETH-LAD (confirmed in human serum)supported
1P-ETH-LAD incubated with human serum at 37C produces ETH-LAD, demonstrating 1-acyl prodrug mechanism across lysergamide class. dta.2196
1P-AL-LAD → AL-LAD (confirmed in pooled human liver microsomes, N1-deacylation as predominant pathway)supported
1P-AL-LAD converts to AL-LAD in pooled human liver microsomes. N1-deacylation confirmed. dta.3281
1V-LSD → LSD (behavioral confirmation)supported
1V-LSD HTR ED50=373 nmol/kg (~1/3 LSD potency). Likely prodrug for LSD. dta.3205
Tanaka et al. (2023) explicitly stated that the metabolic pathways and biological activities of 1cP-MiPLA have not been reported, but the consistency of the prodrug mechanism across the entire characterized 1-acyl lysergamide class provides strong structural-analog support for this inference.supported
Metabolic pathways and biological activities not reported. s11419-023-00661-1
In controlled human LSD studies, the selective 5-HT₂A antagonist ketanserin completely abolishes all subjective effectssupported
Ketanserin (5-HT2A antagonist) blocked effects. Primary mediation by 5-HT2A. s41386-020-00883-6
The full mechanism of LSD-class compounds additionally involves 5-HT₁A partial agonism, 5-HT₂C agonism, and modulation of dopaminergic and glutamatergic neurotransmission.supported
Pleiotropic mechanism involving serotonergic (5-HT2A, 5-HT1A, 5-HT2C), dopaminergic, and glutamatergic neurotransmission. ijms17111834
For LSD administered orally in controlled human studies: T_max is approximately 1.1 hours, oral bioavailability is 80%, and elimination half-life ranges from 2.7 hours at microdoses to approximately 3.5 hours at standard dosespartially supported
LSD 5-20 µg: Tmax ~1.1h; t1/2 ~2.7h (1.5-6.2h range). cpt.2057
For LSD administered orally in controlled human studies: T_max is approximately 1.1 hours, oral bioavailability is 80%, and elimination half-life ranges from 2.7 hours at microdoses to approximately 3.5 hours at standard dosespartially supported
LSD oral bioavailability = 80%; all oral formulations bioequivalent. cpt.3726
The primary metabolizing enzyme is CYP2D6; poor CYP2D6 metabolizers exhibit approximately 75% higher plasma AUC and prolonged eliminationsupported
CYP2D6 poor metabolizers: 75% higher LSD AUC, longer t1/2, greater subjective effects. CYP2D6 is primary metabolic enzyme for LSD in vivo. s41598-021-90343-y
CYP1A2 and CYP2C9 contribute to LSD metabolism in vitro, though their in vivo significance has not been confirmed.partially supported
CYP1A2, CYP2C9, CYP2C19, CYP2B6 showed no significant effect. s41598-021-90343-y
Claim in pharmacology — inconclusiveinconclusiveworking →
summary11 · 9 ok
It is distributed on blotter sheets and tablets, with community-reported total durations of 4–6 hours at oral doses in the 100–250 µg range — notably shorter than LSD, consistent with the reduced serotonin receptor affinity of its presumed active metabolite, MiPLA.supported
4-5x lower affinity at [3H]ketanserin 5-HT2 sites pmid:8208787
MiPLA was first synthesized and pharmacologically characterized by Huang, Marona-Lewicka, Pfaff, and Nichols at Purdue University in 1994. 1cP-MiPLA itself first appeared on online research chemical markets circa 2020 and was formally identified by Tanaka and colleagues at Japan's National Institute of Health Sciences in 2023 using GC-MS, LC-Q-TOF-MS, and NMR spectroscopypartially supported
MIPLA (N-methyl-N-isopropyl LSD) evaluated for LSD-like activity pmid:8208787
MiPLA was first synthesized and pharmacologically characterized by Huang, Marona-Lewicka, Pfaff, and Nichols at Purdue University in 1994. 1cP-MiPLA itself first appeared on online research chemical markets circa 2020 and was formally identified by Tanaka and colleagues at Japan's National Institute of Health Sciences in 2023 using GC-MS, LC-Q-TOF-MS, and NMR spectroscopysupported
First forensic identification of 1cP-MiPLA in Japanese sheet products s11419-023-00661-1
No formal pharmacological characterization of 1cP-MiPLA has been published; the metabolic pathways and biological activities of the compound remain uncharacterized in controlled settings.supported
Metabolic pathways and biological activities not reported s11419-023-00661-1
1cP-MiPLA is presumed to act as a prodrug for MiPLA via enzymatic hydrolysis of the N1-acyl bond, a mechanism confirmed across five other 1-acyl lysergamides including 1cP-LSD and 1P-LSDsupported
Incubation with human serum produces LSD, confirming prodrug mechanism. Acts as LSD prodrug via N1-acyl hydrolysis. dta.2789
Claim in summary — inconclusiveinconclusiveworking →
The released MiPLA acts as an agonist at 5-HT₂A and 5-HT₁A receptors, with 4–5× lower affinity than LSD at cortical 5-HT₂ sitessupported
Displaces [125I]DOI (5-HT2) and [3H]8-OH-DPAT (5-HT1A) with Ki similar to LSD, but 4-5x lower affinity at [3H]ketanserin 5-HT2 sites pmid:8208787
By class extrapolation from LSD — which has no known organotoxicity and an estimated lethal dose exceeding 14,000 µg in humans — acute physiological toxicity is expected to be negligiblepartially supported
Human LD50 unknown; animal LD50 only in rabbits (~0.3 mg/kg IV). LSD has no known organotoxicity. j.forsciint.2018.01.006
Claim in summary — inconclusiveinconclusiveworking →
Tolerance develops rapidly via 5-HT₂A receptor downregulation and cross-generalizes to other psychedelicssupported
Psychedelic 5-HT2A agonists (DOI, LSD) show rapid tolerance and cross-tolerance via 5-HT2A receptor downregulation. acschemneuro.2c00170
Principal risks are psychological: acute anxiety, paranoia, thought-loops, and rare cases of hallucinogen persisting perception disorder (HPPD)supported
Rare condition; more common in prior psychological issues. LSD and LSD-like substances most common triggers. brainsci8030047
comparative-pharmacology10 · 9 ok
Sources: 1P-LSD, 1cP-LSD, 1V-LSD, 1H-LSD, 1B-LSD.supported
1B-LSD HTR ED50=976.7 nmol/kg (~14% LSD potency). dta.2613
Sources: 1P-LSD, 1cP-LSD, 1V-LSD, 1H-LSD, 1B-LSD.supported
1CP-LSD characterized analytically. Mouse HTR ED50 = 430.0 nmol/kg. dta.2789
Sources: 1P-LSD, 1cP-LSD, 1V-LSD, 1H-LSD, 1B-LSD.supported
1V-LSD HTR ED50=373 nmol/kg (~1/3 LSD potency). dta.3205
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
All other published entries — 1P-LSD, 1cP-LSD, 1B-LSD, 1V-LSD, 1H-LSD, and 1DD-LSD — produce LSD as their active metabolite. 1cP-MiPLA's presumed metabolite, MiPLA, has a distinct pharmacological profile from LSD: 4–5× lower 5-HT₂ affinity at [³H]ketanserin sites, with preserved 5-HT₁A and functional 5-HT₂ binding.supported
Acts as LSD prodrug via N1-acyl hydrolysis. dta.2789
All other published entries — 1P-LSD, 1cP-LSD, 1B-LSD, 1V-LSD, 1H-LSD, and 1DD-LSD — produce LSD as their active metabolite. 1cP-MiPLA's presumed metabolite, MiPLA, has a distinct pharmacological profile from LSD: 4–5× lower 5-HT₂ affinity at [³H]ketanserin sites, with preserved 5-HT₁A and functional 5-HT₂ binding.partially supported
1B-LSD HTR ED50=976.7 nmol/kg (~14% LSD potency). LSD-like behavioral profile. Prodrug hypothesis. dta.2613
All other published entries — 1P-LSD, 1cP-LSD, 1B-LSD, 1V-LSD, 1H-LSD, and 1DD-LSD — produce LSD as their active metabolite. 1cP-MiPLA's presumed metabolite, MiPLA, has a distinct pharmacological profile from LSD: 4–5× lower 5-HT₂ affinity at [³H]ketanserin sites, with preserved 5-HT₁A and functional 5-HT₂ binding.partially supported
1-acylated analog anticipated to hydrolyze to LSD in vivo. dta.3767
All other published entries — 1P-LSD, 1cP-LSD, 1B-LSD, 1V-LSD, 1H-LSD, and 1DD-LSD — produce LSD as their active metabolite. 1cP-MiPLA's presumed metabolite, MiPLA, has a distinct pharmacological profile from LSD: 4–5× lower 5-HT₂ affinity at [³H]ketanserin sites, with preserved 5-HT₁A and functional 5-HT₂ binding.partially supported
1DD-LSD HTR ED50 = 3.60 umol/kg. Higher lipophilicity may reduce bioavailability of prodrug conversion. dta.3691
Sources: 1P-LSD, 1cP-LSD, 1V-LSD, 1H-LSD, 1B-LSD.supported
First published characterization of 1P-LSD. Mouse HTR ED50=349.6 nmol/kg. dta.1884
For 1cP-MiPLA, the additional factor of MiPLA's intrinsically lower 5-HT₂ affinity (2–3× less potent than LSD in drug discrimination) would compound this effect, potentially placing 1cP-MiPLA's behavioral potency well below the 1-acyl LSD series.supported
Drug discrimination: ED50 2-3x greater than LSD. pmid:8208787
history7 · 4 ok
The parent compound MiPLA (N-methyl-N-isopropyllysergamide) was first synthesized and characterized by Huang, Marona-Lewicka, Pfaff, and Nichols at Purdue University in 1994 as part of a systematic investigation of N-isopropyl lysergamide derivativessupported
MIPLA (N-methyl-N-isopropyl LSD) evaluated for LSD-like activity. Drug discrimination and receptor binding studies of N-isopropyl lysergamide derivatives. pmid:8208787
Claim in history — inconclusiveinconclusiveworking →
The broader class of 1-acyl LSD analogs began appearing on research chemical markets from approximately 2015 onward. 1P-LSD was the first member to receive detailed analytical and behavioral characterization, published by Brandt and colleagues in the inaugural Return of the Lysergamides seriessupported
First published characterization of 1P-LSD. dta.1884
Subsequent entries — ALD-52, 1B-LSD, 1V-LSD, and 1cP-LSD — each demonstrated the same prodrug mechanism: enzymatic hydrolysis of the N1-acyl bond releasing LSD as the active compound. 1cP-MiPLA represents an extension of this strategy to a non-LSD lysergamide parent, combining the established 1-acyl prodrug approach with an alternative carboxamide.partially supported
1B-LSD HTR ED50=976.7 nmol/kg (~14% LSD potency). LSD-like behavioral profile. Prodrug hypothesis. dta.2613
Subsequent entries — ALD-52, 1B-LSD, 1V-LSD, and 1cP-LSD — each demonstrated the same prodrug mechanism: enzymatic hydrolysis of the N1-acyl bond releasing LSD as the active compound. 1cP-MiPLA represents an extension of this strategy to a non-LSD lysergamide parent, combining the established 1-acyl prodrug approach with an alternative carboxamide.supported
Acts as LSD prodrug via N1-acyl hydrolysis. dta.2789
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
chemistry4 · 4 ok
It is a dual-modified derivative of LSD: the N1-indole nitrogen bears a cyclopropanecarbonyl (cyclopropanoyl) acyl group (the same modification present in 1cP-LSD), while the C-8 carboxamide carries an N-methyl-N-isopropyl substituent rather than the N,N-diethyl group of LSD (the same amide modification defining MiPLA)supported
Modifications at N1 (cyclopropanoyl) and N18 (N-methyl-N-isopropyl) compared to LSD. s11419-023-00661-1
Nichols and colleagues demonstrated that increasing alkyl chain length or branching at this position progressively reduces 5-HT₂A affinity, with the N,N-diisopropyl analog (DIPLA) exhibiting approximately 8× lower potency than LSD in drug discriminationsupported
DIPLA has 8x lower potency. pmid:8208787
MiPLA's mixed N-methyl-N-isopropyl substituent occupies an intermediate position — retaining full LSD substitution with a 2–3× reduction in potency.supported
Drug discrimination: ED50 2-3x greater than LSD. pmid:8208787
Nichols et al. (1996) demonstrated stereoselective preferences for lysergic acid amides with chiral 2-aminoalkane substituents, with the R configuration at the amide nitrogen yielding the highest potency at both 5-HT₂A and 5-HT₁A receptorssupported
Chiral lysergic acid amides show stereoselective preference at 5-HT2A and 5-HT1A for R configuration alkyl groups. pmid:8788487
receptor-pharmacology4 · 3 ok
The N,N-diisopropyl analog (DIPLA) showed approximately 8× lower potency than LSD in drug discrimination, indicating that increasing N-alkyl bulk beyond the N-methyl-N-isopropyl configuration further degrades receptor complementarity.supported
DIPLA has 8x lower potency. pmid:8208787
The only published receptor binding data relevant to 1cP-MiPLA's active metabolite come from Huang et al. (1994), who characterized MiPLA alongside several N-isopropyl lysergamide derivatives:supported
MIPLA (N-methyl-N-isopropyl LSD) evaluated for LSD-like activity. Displaces [125I]DOI (5-HT2) and [3H]8-OH-DPAT (5-HT1A) with Ki similar to LSD pmid:8208787
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The crystal structure of LSD bound to the human 5-HT₂B receptor (Wacker et al. 2017) revealed that an extracellular loop 2 (EL2) "lid" structure closes over the bound ligand, producing an exceptionally slow dissociation rate (k_off)supported
Crystal structure of LSD complexed with 5-HT2B receptor. EL2 lid mechanism explains LSD's unusually slow dissociation kinetics. j.cell.2016.12.033
neuroscience3 · 1 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
LSD also engages 5-HT₁A partial agonism, which modulates the 5-HT₂A-mediated response and contributes to anxiolytic-like effects in animal modelssupported
5-HT1A and 5-HT2A interact in mediating LSD effects. j.neuropharm.2011.01.017
pharmacokinetic-detail2 · 2 ok
For the structural sister compound 1cP-LSD, conversion to LSD in human serum at 37°C has been confirmed, though precise hydrolysis rate constants have not been publishedsupported
Incubation with human serum produces LSD, confirming prodrug mechanism. dta.2789
In pooled human liver microsomes, the 1-acyl lysergamide 1P-AL-LAD produces AL-LAD as the principal metabolite via N1-deacylation, confirming that hepatic metabolism also contributes to prodrug activation.supported
1P-AL-LAD converts to AL-LAD in pooled human liver microsomes. N1-deacylation confirmed. dta.3281
clinical-evidence1 · 1 ok
LSD at 100–200 µg produces dose-dependent increases in subjective drug effects, mystical-type experience scores, and acute anxiety, with all effects abolished by pre-treatment with the 5-HT₂A antagonist ketanserinsupported
Ceiling for good effects at 100 µg; ego dissolution/anxiety at 200 µg. Ketanserin (5-HT2A antagonist) blocked effects. s41386-020-00883-6