Nicotine

6Node page

what any key link opens

psx:substance/nicotine/proposal/dosage/471029dd-1844-497e-b624-6f51eb5356fb

proposal2026-04-25recordapproved

derived from · upstream

none recorded

feeds · downstream

derived_fromvalue/dose/transdermal@1psx:substance/nicotine/value/dose/transdermal@1

psx:substance/nicotine/proposal/dosage/471029dd-1844-497e-b624-6f51eb5356fb
└─ derived_from  value/dose/transdermal@1

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

4332 with DOI

7 strong · 33 moderate · 3 weak

Compilations

22026-04-25T19:20:50.898Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

60last ruled 2026-06-04

1 awaiting a ruling

Issued documents

42026-10-19T20:33:19.402Z

notice · info card · emergency

Searches

190 with no results

queries and counts on the build

Claims checked

1983 supported

3 supported · 195 not

Correspondence

0received

consent field ships in Phase 4

Edges

530

derivations recorded for this entity

Complete over 43 sources, 2 compilations, and 60 decisions.Not here: the private journal (never); 1 proposal awaiting a ruling (listed as pending only).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/nicotine/archive

2Build

one panel per compilation run

generation run 2026-04-25

5 min failedmodel not recordedplan not recordedrun/0ba2510e…

research

no artifact

draft

no artifact

audit

no artifact

verify

no artifact

simplify

no artifact

publish

no artifact

Selection

results seen0

selected by the model0

consumed as sources43

Verification

claims checked0

supported0

partially supported0

not supported0

inconclusive0

record
seen / partial
working

The model's own caveats

none raised on this run

Reproduce

inputs: 43 source keys (listed under Sources)
plan: not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model: not recorded
streams: none — agent transcripts are persisted from 2026-09 onward

generation run 2026-04-25

60 min completedmodel pipeline-v5plan not recordedrun/90415aee…

Selection

results seen127

selected by the model35

consumed as sources43

Verification

claims checked198

supported2

partially supported1

not supported0

inconclusive195

record
seen / partial
working

The model's own caveats

none raised on this run

Reproduce

inputs: 43 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

19 searches — query, source, results, what was kept and why

19 searches for this run
#	source	query	seen	kept	rationale
1	PubChem	nicotine	1	1	Primary chemical identity verification for nicotine
2	PubMed	nicotine pharmacokinetics plasma half-life cotinine metabolism CYP2A6 human	7	4	Core pharmacokinetic papers on CYP2A6 metabolism of nicotine
3	OpenAlex	nicotine nicotinic acetylcholine receptor pharmacology	8	0	—
4	PubMed	nicotine pharmacology receptor binding mechanism action	12	0	—
5	PubMed	nicotine addiction dependence withdrawal dopamine reward mesolimbic	10	3	Key reviews on addiction neuroscience and dopamine/non-dopamine mechanisms
6	PubMed	nicotine pharmacokinetics bioavailability metabolism CYP human	2	0	—
7	PubMed	green tobacco sickness nicotine poisoning workers	8	3	Nicotine toxicity data via dermal absorption
8	PubMed	Benowitz nicotine clinical pharmacology review human	10	3	Comprehensive Benowitz-authored reviews covering nicotine pharmacology, toxicology, and addiction
9	ClinicalTrials.gov	nicotine pharmacology addiction treatment	10	3	Relevant completed trials on nicotine dependence pharmacotherapy
10	PubMed	Hukkanen nicotine metabolism pharmacokinetics review pharmacological	2	2	Landmark comprehensive pharmacokinetics reviews
11	WebSearch	nicotine isolation history 1828 Posselt Reimann discovery tobacco alkaloid	10	2	—
12	WebSearch	nicotine SMILES CAS 54-11-5 physical properties melting point boiling point	10	1	—
13	PubChem via WebFetch	Nicotine CID 89594	1	0	—
14	WebSearch	Mayer 2014 nicotine lethal dose LD50 re-evaluation Archives of Toxicology	10	1	—
15	DOI Verification	10.1007/s00204-013-1127-0	1	1	—
16	PubMed	PMID 40811135, 31663029, 15734728, 19184645, 32738308, 37832393	6	6	—
17	ClinicalTrials.gov	nicotine Parkinson disease cognitive neuroprotection	1	1	—
18	PubMed	tobacco smoke monoamine oxidase inhibition MAOI nicotine beta-carboline	8	3	—
19	WebSearch	nicotine legal status scheduling United States FDA regulated tobacco product	10	1	—

198 claims by section — every cited sentence, checked against its source

safety62 · 2 ok

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Tobacco smoke contains multiple monoamine-oxidase inhibitors — β-carbolines (harman, norharman, harmaline), hydroquinones, and polyunsaturated fatty acids — that potentiate dopaminergic effects of nicotine by reducing dopamine degradation and stimulating dopamine-transporter-mediated dopamine releasesupported
Harmaline inhibits MAO-A and significantly attenuates DAT activity and dopamine uptake; also promotes dopamine release in synaptosomes. acschemneuro.4c00789
A review of 219 publications found that nicotine can be used with careful monitoring in patients taking pharmaceutical MAOIs; the interaction does not carry serotonin-syndrome risk but requires monitoring for cardiovascular effects (blood pressure and heart rate augmentation)partially supported
Narrative review investigating MAOI use in patients who use psychoactive substances. Suspected cases of serotonin toxicity reported for MAOIs in combination with DXM. Hypertensive urgency/emergency reported for MAOIs with multiple substances. s40263-025-01256-7
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pharmacology48 · 1 ok

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An important pharmacological distinction: β-carboline monoamine-oxidase inhibitors (harman, norharman, harmaline) present in tobacco smoke potentiate dopaminergic effects by reducing dopamine degradation and stimulating dopamine-transporter-mediated dopamine releasesupported
Harmaline inhibits MAO-A and significantly attenuates DAT activity and dopamine uptake; also promotes dopamine release in synaptosomes. acschemneuro.4c00789
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neuroscience28 · 0 ok

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summary18 · 0 ok

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pharmacokinetic-detail12 · 0 ok

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receptor-pharmacology10 · 0 ok

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comparative-pharmacology8 · 0 ok

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clinical-evidence4 · 0 ok

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effects-overview4 · 0 ok

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chemistry2 · 0 ok

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history2 · 0 ok

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3Sources

43 consumed · sorted by year · feeds = sections resting on it

Sources 1 to 30
year	source	tier	status	feeds
2026	Global Burden of Green Tobacco Sickness in Farm Workers: A Systematic Review and Meta-Analysis.Jahromi HK et al. · Indian journal of occupational and environmental medicinedoi:10.4103/ijoem.ijoem_106_25	strong	consumed	1 section
2026	Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive SubstancesRached G, Campana A, Fiani D, et al. · CNS Drugsdoi:10.1007/s40263-025-01256-7	strong	consumed	1 section
2025	Caffeine, nicotine, cannabis, and psilocybin: Pharmacology, toxicology, and potential therapeutic uses of four naturally occurring psychoactive substances.Christen SE, Bekka E, Schmid Y, Benowitz NL, Liakoni E · Swiss medical weeklydoi:10.57187/s.4346	moderate	consumed	cited only
2025	FDA Tobacco Product Standard for Nicotine Yield: Proposed Rule 2025US FDAurl:4d14e05b62716b90	weak	consumed	cited only
2025	Monoamine Oxidase Inhibitors Present in Tobacco Modulate Dopamine Balance Via the Dopamine Transporter.Saro G, Johne S, Latino DARS et al. · ACS chemical neurosciencedoi:10.1021/acschemneuro.4c00789	moderate	consumed	2 sections
2024	Nicotine physical properties: CAS 54-11-5, melting point, boiling point, solubilityVarious chemical databasesurl:029aa0370391edd8	weak	consumed	cited only
2024	Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness.Ziska LH, Parks RM · Communications medicinedoi:10.1038/s43856-024-00584-x	moderate	consumed	1 section
2023	Age-dependent effects of tobacco smoke and nicotine on cognition and the brain: A systematic review of the human and animal literature comparing adolescents and adults.Colyer-Patel K, Kuhns L, Weidema A, Lesscher H, Cousijn J · Neuroscience and biobehavioral reviewsdoi:10.1016/j.neubiorev.2023.105038	strong	consumed	2 sections
2023	Cardiovascular and Pulmonary Responses to Acute Use of Electronic Nicotine Delivery Systems and Combustible Cigarettes in Long-Term Users.Tattersall MC, Hughey CM, Piasecki TM et al. · Chestdoi:10.1016/j.chest.2023.03.047	moderate	consumed	1 section
2023	Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation.Theodoulou A, Chepkin SC, Ye W et al. · The Cochrane database of systematic reviewsdoi:10.1002/14651858.cd013308.pub2	strong	consumed	cited only
2023	Impact of Prenatal Nicotine Exposure on Placental Function and Respiratory Neural Network Development.Beltran-Castillo S, Bravo K, Eugeniu J · Advances in experimental medicine and biologydoi:10.1007/978-3-031-32554-0_10	moderate	consumed	2 sections
2023	Nicotine addiction: More than just dopamine.Kim K, Picciotto MR · Current opinion in neurobiologydoi:10.1016/j.conb.2023.102797	moderate	consumed	5 sections
2022	A Review of Electronic Cigarettes and Liquid Nicotine Poisoning Exposure Cases in the United States.Ahmed A · Journal of pharmacy & pharmaceutical sciencesdoi:10.18433/jpps33141	moderate	consumed	1 section
2022	A review of monoamine oxidase (MAO) inhibitors in tobacco or tobacco smoke.Hong SW, Teesdale-Spittle P, Page R, Truman P · Neurotoxicologydoi:10.1016/j.neuro.2022.09.008	moderate	consumed	3 sections
2022	Physiologic Functions and Therapeutic Applications of alpha7 Nicotinic Acetylcholine Receptor in Brain Disorders.Lee CH, Hung SY · Pharmaceuticsdoi:10.3390/pharmaceutics15010031	moderate	consumed	2 sections
2022	Tobacco use disorder and cardiovascular health.Benowitz NL, Liakoni E · Addiction (Abingdon, England)doi:10.1111/add.15703	moderate	consumed	1 section
2020	Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction.Wittenberg RE, Wolfman SL, De Biasi M, Dani JA · Neuropharmacologydoi:10.1016/j.neuropharm.2020.108256	moderate	consumed	4 sections
2019	A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic profiles of cigarettes and e-cigarettes with nicotine salt formulations in US adult smokers.O'Connell G, Pritchard JD, Prue C et al. · Internal and emergency medicinedoi:10.1007/s11739-019-02025-3	strong	consumed	1 section
2019	Acute separate and combined effects of cannabinoid and nicotinic receptor agonists on MMN-indexed auditory deviance detection in healthy humans.de la Salle S, Inyang L, Impey D et al. · Pharmacology, biochemistry, and behaviordoi:10.1016/j.pbb.2019.172739	strong	consumed	2 sections
2019	Chronic Nicotine Exposure Alters the Neurophysiology of Habenulo-Interpeduncular Circuitry.Arvin MC, Jin XT, Yan Y et al. · The Journal of neurosciencedoi:10.1523/jneurosci.2816-18.2019	moderate	consumed	cited only
2019	Current advances in research in treatment and recovery: Nicotine addiction.Prochaska JJ, Benowitz NL · Science advancesdoi:10.1126/sciadv.aay9763	moderate	consumed	1 section
2019	Green tobacco sickness: mecamylamine, varenicline, and nicotine vaccine as clinical research tools and potential therapeutics.McMahon LR · Expert review of clinical pharmacologydoi:10.1080/17512433.2019.1570844	moderate	consumed	1 section
2019	Relationship between skin melanin index and nicotine pharmacokinetics in African American smokers.Liakoni E, St Helen G, Dempsey DA, Jacob P, Tyndale RF, Benowitz NL · Drug and alcohol dependencedoi:10.1016/j.drugalcdep.2019.04.039	moderate	consumed	1 section
2018	Cognitive Effects of Nicotine: Recent Progress.Valentine G, Sofuoglu M · Current neuropharmacologydoi:10.2174/1570159x15666171103152136	moderate	consumed	cited only
2018	Differential associations of combined vs. isolated cannabis and nicotine on brain resting state networks.Filbey FM, Gohel S, Prashad S, Biswal BB · Brain structure & functiondoi:10.1007/s00429-018-1690-5	moderate	consumed	1 section
2015	Nicotine and the Developing Human: A Neglected Element in the Electronic Cigarette Debate.England LJ, Bunnell RE, Pechacek TF, Tong VT, McAfee TA · American journal of preventive medicinedoi:10.1016/j.amepre.2015.01.015	moderate	consumed	1 section
2015	Smokeless tobacco, sport and the heart.Chague F, Guenancia C, Gudjoncik A et al. · Archives of cardiovascular diseasesdoi:10.1016/j.acvd.2014.10.003	moderate	consumed	1 section
2014	How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century.Mayer B · Archives of toxicologydoi:10.1007/s00204-013-1127-0	moderate	consumed	2 sections
2013	Psychiatric and psychological features of nicotine dependence.Miyasato K · Nihon rinsho. Japanese journal of clinical medicinepmid:23631239	moderate	consumed	2 sections
2012	Nicotine replacement therapy for smoking cessationStead LF, Perera R, Bullen C, Mant D, Hartmann-Boyce J · Cochrane Database of Systematic Reviewsdoi:10.1002/14651858.cd000146.pub4	strong	consumed	1 section

Show all 43 sources — 13 more

Sources 31 to 43
year	source	tier	status	feeds
2011	Expression of water-soluble, ligand-binding concatameric extracellular domains of the human neuronal nicotinic receptor alpha4 and beta2 subunits.Stergiou C, Zisimopoulou P, Tzartos SJ · The Journal of biological chemistrydoi:10.1074/jbc.m110.171645	moderate	consumed	cited only
2010	Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area alpha6beta2* Receptors.Gotti C, Guiducci S, Tedesco V et al. · Journal of Neurosciencedoi:10.1523/jneurosci.5095-09.2010	moderate	consumed	4 sections
2009	Nicotine chemistry, metabolism, kinetics and biomarkers.Benowitz NL, Hukkanen J, Jacob P · Handbook of experimental pharmacologydoi:10.1007/978-3-540-69248-5_2	moderate	consumed	4 sections
2009	The neuronal pathways mediating the behavioral and addictive properties of nicotine.Balfour DJ · Handbook of experimental pharmacologydoi:10.1007/978-3-540-69248-5_8	moderate	consumed	2 sections
2007	Population pharmacokinetics of nicotine and its metabolites I. Model development.Levi M, Dempsey DA, Benowitz NL, Sheiner LB · Journal of pharmacokinetics and pharmacodynamicspmid:17206524	moderate	consumed	2 sections
2006	CYP2A6 genotype and the metabolism and disposition kinetics of nicotine.Benowitz NL, Swan GE, Jacob P, Lessov-Schlaggar CN, Tyndale RF · Clinical pharmacology and therapeuticspmid:17112802	moderate	consumed	2 sections
2006	Human Tobacco Smokers in Early Abstinence Have Higher Levels of beta2* Nicotinic Acetylcholine Receptors than Nonsmokers.Staley JK, Krishnan-Sarin S, Cosgrove K et al. · Journal of Neurosciencedoi:10.1523/jneurosci.0546-06.2006	moderate	consumed	2 sections
2005	Metabolism and disposition kinetics of nicotine.Hukkanen J, Jacob P, Benowitz NL · Pharmacological reviewspmid:15734728	moderate	consumed	4 sections
2004	The comparative pharmacology and up-regulation of rat neuronal nicotinic receptor subtype binding sites stably expressed in transfected mammalian cells.Xiao Y, Kellar KJ · The Journal of pharmacology and experimental therapeuticspmid:15016836	moderate	consumed	2 sections
2003	Subtype-selective up-regulation by chronic nicotine of high-affinity nicotinic receptors in rat brain demonstrated by receptor autoradiography.Nguyen HN, Rasmussen BA, Perry DC · The Journal of pharmacology and experimental therapeuticspmid:14560040	moderate	consumed	4 sections
1998	Agonist-induced up-regulation of alpha4beta2 nicotinic acetylcholine receptors in M10 cells: pharmacological and spatial definition.Whiteaker P, Sharples CG, Wonnacott S · Molecular pharmacologypmid:9584223	moderate	consumed	2 sections
1997	Nicotine and sympathetic neurotransmission.Haass M, Kubler W · Cardiovascular drugs and therapypmid:9110108	moderate	consumed	3 sections
1828	Nicotine isolation history: Posselt and Reimann 1828Variousurl:0fb287fd7f7fa51a	weak	consumed	cited only

4Docket

one filing per activity — decisions, correspondence, reports

awaiting ruling — 1

dependence · tapercited2026-07-03

0012026-04-25revisionRevision 1
Initial LLM generation (v5 pipeline, wiki)
psx:substance/nicotine/version/1
0022026-06-04proposal57 value proposals approved together
one review action inferred from a shared reviewer and instant — the graph records one activity per proposal
57 items in this filing
- dose_tier · light
- dose_tier · common
- dose_tier · strong
- dose_tier · heavy
- timeline · smoked · onset
- timeline · smoked · come_up
- timeline · smoked · peak
- timeline · smoked · plateau
- timeline · smoked · resolution
- timeline · smoked · afterglow
- timeline · buccal · onset
- timeline · buccal · come_up
- timeline · buccal · peak
- timeline · buccal · plateau
- timeline · buccal · resolution
- timeline · buccal · afterglow
- timeline · oral · onset
- timeline · oral · come_up
- timeline · oral · peak
- timeline · oral · plateau
- timeline · oral · resolution
- timeline · oral · afterglow
- toxicity
- dependence · full
- withdrawal
- tolerance
- dosage · smoked
- dosage · buccal
- dosage · transdermal
- duration · smoked · onset
- duration · smoked · come_up
- duration · smoked · peak
- duration · smoked · offset
- duration · smoked · total
- duration · smoked · aftereffects
- duration · buccal · onset
- duration · buccal · come_up
- duration · buccal · peak
- duration · buccal · offset
- duration · buccal · total
- duration · buccal · aftereffects
- duration · oral · onset
- duration · oral · come_up
- duration · oral · peak
- duration · oral · offset
- duration · oral · total
- duration · oral · aftereffects
- contraindication · pregnancy_breastfeeding
- contraindication · pregnancy_breastfeeding
- contraindication · cardiovascular
- contraindication · cardiovascular
- contraindication · cardiovascular
- contraindication · cardiovascular
- contraindication · metabolic
- contraindication · other
- contraindication · age
psx:substance/nicotine/proposal/dose_tier/963922ab-2697-4fb8-890d-eb9c6bc8d467
0032026-06-04publicationPublication — backfill
psx:substance/nicotine/pub/5ed3ce14-df05-46ad-8a40-2864d5f94da1

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
document	content hash	issued	from version	superseded
info_card	0620683a29b02ddcb25c21d7…	2026-10-19 20:33	Revision 1	current
emergency	777b5863d801327b008f5610…	2026-09-04 04:31	Revision 1	current
info_card	1eec9c7c323c4e1aceb7f4fd…	2026-09-04 04:31	Revision 1	superseded2026-10-19
notice	f8bfb1cb8b0a2f3da7fc6a2c…	2026-09-04 04:31	Revision 1	current

Nicotine

6Node page

derived from · upstream

feeds · downstream

1Provenance card

2Build

generation run 2026-04-25

research→

draft→

audit→

verify→

simplify→

publish

Selection

Verification

The model's own caveats

Reproduce

generation run 2026-04-25

research→

draft→

audit→

verify→

simplify→

publish

Selection

Verification

The model's own caveats

Reproduce

3Sources

4Docket

awaiting ruling — 1

5Issued documents

research

draft

audit

verify

simplify

research

draft

audit

verify

simplify