generation run 2026-04-20
60 min completedmodel pipeline-v5plan not recordedrun/3685b523…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- taper_protocol_is_substitution_based
- post_abstinence_overdose_risk
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
27 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov | heroin diacetylmorphine opioid use disorder treatment | 10 | 3 | — |
| 2 | PubMed | heroin overdose respiratory depression naloxone treatment mortality | 10 | 3 | — |
| 3 | PubMed | heroin diacetylmorphine pharmacokinetics metabolism 6-monoacetylmorphine morphine human | 10 | 6 | — |
| 4 | PubMed · absence | heroin synthesis history Heinrich Dreser Bayer 1898 diacetylmorphine | 0 | — | Will search OpenAlex and web for history |
| 5 | OpenAlex | heroin diacetylmorphine history synthesis discovery 1898 Bayer | 8 | 1 | Useful historical timeline embedded in this review article |
| 6 | PubChem | heroin | 1 | 1 | All chemical identity data selected for verification of seed data |
| 7 | OpenAlex | heroin diacetylmorphine pharmacology opioid receptor | 10 | 2 | Selected landmark papers on heroin treatment and complications |
| 8 | PubMed | heroin diacetylmorphine pharmacology receptor binding opioid | 11 | 2 | — |
| 9 | PubMed | heroin needle exchange harm reduction supervised injection overdose prevention | 8 | 3 | — |
| 10 | OpenAlex | heroin Schedule I controlled substance legal status international drug policy prohibition | 8 | 2 | — |
| 11 | PubMed | NAOMI heroin assisted treatment randomized trial injectable diamorphine Canada | 4 | 2 | — |
| 12 | PubMed | heroin fentanyl contamination adulteration street drug supply overdose | 8 | 1 | — |
| 13 | PubMed | heroin toxicity LD50 lethal dose lethality pharmacology | 8 | 2 | — |
| 14 | OpenAlex | heroin diacetylmorphine opioid tolerance physical dependence withdrawal mechanism | 8 | 1 | — |
| 15 | WebSearch + DEA | heroin diacetylmorphine legal status Schedule I US UK Class A Controlled Substances Act scheduling | 10 | 3 | Key legal status data for all major jurisdictions |
| 16 | PubMed | diamorphine prescribed heroin randomized controlled trial outcomes response | 8 | 1 | — |
| 17 | WebSearch | heroin pharmacokinetics half-life 6-MAM IV intranasal bioavailability | 10 | 3 | Critical PK data for all ROAs |
| 18 | WebSearch | heroin diacetylmorphine CAS number 561-27-3 SMILES synthesis Alder Wright 1874 | 10 | 3 | Essential chemical identity and history data |
| 19 | EUDA Drug Profile | — | — | — | Official EU agency drug profile with verified pharmacological data |
| 20 | PubMed | heroin opioid use disorder epidemiology global prevalence burden disease | 8 | 1 | — |
| 21 | WebSearch - Australia/Canada/Germany | heroin legal status Australia Canada Germany Schedule classification 2024 | 15 | 3 | Multi-jurisdictional legal status coverage |
| 22 | PubMed | Oviedo-Joekes NAOMI diacetylmorphine versus methadone NEJM 2009 | 1 | 1 | Landmark RCT for heroin-assisted treatment |
| 23 | NIST WebBook | diacetylmorphine CAS 561-27-3 physical properties | 1 | — | Key physical property data for heroin article |
| 24 | Guide to Pharmacology IUPHAR/BPS | diamorphine binding affinity opioid receptor Ki | 1 | — | Confirms prodrug mechanism; no direct receptor affinity data available from this source |
| 25 | PubMed | leukoencephalopathy heroin inhalation toxic white matter brain MRI | 6 | 2 | — |
| 26 | PubMed | xylazine veterinary sedative illicit drug supply opioid combination wounds overdose 2023 | 1 | 1 | — |
| 27 | PubMed | heroin pregnancy fetal maternal opioid placenta neonatal abstinence | 5 | 2 | — |
73 claims by section — every cited sentence, checked against its source
safety19 · 3 ok
Claim in safety — inconclusiveinconclusiveworking →
Significant respiratory depression (elevated ETCO₂) occurs in the majority of patients at therapeutic doses — Jolley et al. (2015) observed clinically meaningful hypoventilation in 8 of 10 HAT patients within 30 minutes of supervised injectionsupported
Significant respiratory depression (increased ETCO2%) following IOT in 8/10 patients at 30 minutes. Hypoventilation reliably detected by capnography but not SpO2 alone. journal.pone.0140995
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Infective endocarditis: right-sided predominance, Staphylococcus aureus and Candida speciessupported
Landmark review of medical complications of heroin addiction including endocarditis, pulmonary edema, hepatitis, tetanus, and malaria from shared needles. 0003-4819-67-1-1
Claim in safety — inconclusiveinconclusiveworking →
Septicemia, skin and soft tissue abscesses, tetanussupported
Landmark review of medical complications of heroin addiction including endocarditis, pulmonary edema, hepatitis, tetanus, and malaria from shared needles. 0003-4819-67-1-1
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 →
pharmacology11 · 7 ok
At concentrations attainable shortly after IV injection, approximately 70% of heroin transforms to 6-MAM within 3 minutessupported
About 70% transformed to 6-MAM within 3 min after IV injection. bcpt.13926
Vitreous humor is the optimal postmortem matrix for confirming heroin usesupported
Vitreous humor best for detecting 6-MAM (100% of cases). dta.2492
Morphine is subsequently glucuronidated to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G).supported
Reviews pharmacokinetics and pharmacodynamics of heroin and metabolites (6-MAM, morphine, M6G). s41398-023-02406-5
Current evidence supports a more complex interplay: heroin itself may possess some direct CNS activity, and the sequential actions of heroin, 6-MAM, morphine, and M6G only partially overlap in time, producing the distinctive temporal pattern of heroin's effects that distinguishes it from equivalent doses of morphine.supported
arguing heroin is not merely a prodrug but has distinct pharmacological effects. s41398-023-02406-5
Claim in pharmacology — inconclusiveinconclusiveworking →
Both 6-MAM and heroin are substantially more lipid-soluble than morphine, enabling faster and more complete blood-brain barrier transit.supported
Reviews pharmacokinetics and pharmacodynamics of heroin and metabolites (6-MAM, morphine, M6G). s41398-023-02406-5
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Heroin plasma half-life: Highly concentration-dependent — 1.2–1.7 minutes at concentrations ≥25 μM, increasing to approximately 20 minutes at 1 μM concentrationssupported
Half-life of heroin in human blood was highly concentration dependent, ranging from 1.2–1.7 min for concentrations ≥25 μM to ~20 min for 1 μM. bcpt.13926
Co-present markers of illicit heroin include papaverine, noscapine, and codeine — opium alkaloid impurities carried through illicit manufacture.supported
Papaverine, noscapine, codeine as markers of illicit heroin use. dta.2492
history9 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
1924: The US Anti-Heroin Act banned heroin entirely, including for medical use — making the United States the first country to prohibit the substance outrightsupported
banned by federal government in 1924. aia.0000000000000270
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
clinical-evidence8 · 0 ok
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — not_supportednot supportedworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
summary8 · 3 ok
Alder Wright in 1874 and commercialized by Bayer in 1898 as a cough suppressant, heroin became the most widely studied substance of abuse in the 20th centurypartially supported
Mentions diacetylmorphine synthesized in 1897, marketed as heroin in 1898 by Bayer, banned by federal government in 1924. aia.0000000000000270
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Sequential deacetylation produces 6-monoacetylmorphine (6-MAM) — the primary mediator of rapid neural effects — followed by morphine and morphine-6-glucuronide (M6G)supported
Reviews pharmacokinetics and pharmacodynamics of heroin and metabolites (6-MAM, morphine, M6G), arguing heroin is not merely a prodrug but has distinct pharmacological effects. s41398-023-02406-5
The plasma half-life is concentration-dependent (1.2–1.7 minutes at concentrations ≥25 μM), with approximately 70% converting to 6-MAM within 3 minutes of intravenous injectionsupported
Half-life of heroin in human blood was highly concentration dependent, ranging from 1.2–1.7 min for concentrations ≥25 μM to ~20 min for 1 μM. About 70% transformed to 6-MAM within 3 min after IV injection. bcpt.13926
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
comparative-pharmacology5 · 2 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
6-MAM mediation: The rapid neural effects of IV heroin are attributable to 6-MAM, not morphine — morphine alone cannot replicate the characteristic rushsupported
demonstrates that 6-MAM (not morphine) mediates the rapid neural effects of IV heroin, including respiratory depression and cerebral vasodilation. acschemneuro.9b00305
Temporal cascade: Sequential metabolite formation produces a temporal effect profile distinct from equianalgesic morphinesupported
arguing heroin is not merely a prodrug but has distinct pharmacological effects. s41398-023-02406-5
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
pharmacokinetic-detail5 · 4 ok
Data sources: IV parameters from Bogen et al. 2023; intranasal bioavailability from Guessoum et al. 2025; BBB penetration from EUDA.supported
Half-life of heroin in human blood was highly concentration dependent... About 70% transformed to 6-MAM within 3 min after IV injection. bcpt.13926
Data sources: IV parameters from Bogen et al. 2023; intranasal bioavailability from Guessoum et al. 2025; BBB penetration from EUDA.supported
Characterizes PK/PD of therapeutically-relevant intranasal doses of diacetylmorphine and metabolites. s40263-025-01189-1
As concentrations fall to ~1 μM, the half-life extends to approximately 20 minutessupported
ranging from 1.2–1.7 min for concentrations ≥25 μM to ~20 min for 1 μM. bcpt.13926
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
The sequential metabolite formation follows overlapping time-concentration profiles:supported
Reviews pharmacokinetics and pharmacodynamics of heroin and metabolites (6-MAM, morphine, M6G). s41398-023-02406-5
receptor-pharmacology4 · 1 ok
Claim in receptor-pharmacology — not_supportednot supportedworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
This cascade model explains why heroin's subjective effects differ qualitatively from equianalgesic doses of morphine despite shared receptor targets.supported
arguing heroin is not merely a prodrug but has distinct pharmacological effects. s41398-023-02406-5
neuroscience3 · 2 ok
This biphasic pattern was absent with equimolar morphine, confirming 6-MAM as the critical mediator of heroin's rewarding onset.supported
Using oxygen sensors in nucleus accumbens, demonstrates that 6-MAM (not morphine) mediates the rapid neural effects of IV heroin. acschemneuro.9b00305
Jolley et al. (2015) documented significant increases in end-tidal CO₂ (ETCO₂) in 8 of 10 HAT patients within 30 minutes of supervised injection, indicating clinically meaningful hypoventilation that was reliably detected by capnography but not by pulse oximetry alone in early stages.supported
Significant respiratory depression (increased ETCO2%) following IOT in 8/10 patients at 30 minutes. Hypoventilation reliably detected by capnography but not SpO2 alone. journal.pone.0140995
Claim in neuroscience — inconclusiveinconclusiveworking →
legal-status1 · 0 ok
Claim in legal-status — inconclusiveinconclusiveworking →