Lorazepam

6Node page

what any key link opens

psx:agent/human/founder

no derivations recorded for this key

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1Provenance card

the boundary, as counts

Sources

3815 with DOI

16 strong · 17 moderate · 5 weak

Compilations

12026-05-09T12:23:15.751Z

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

Decisions

41last ruled 2026-10-02

1 awaiting a ruling

Issued documents

42026-10-02T13:09:09.604Z

notice · info card · emergency

Searches

200 with no results

queries and counts on the build

Claims checked

22414 supported

14 supported · 210 not

Correspondence

0received

consent field ships in Phase 4

Edges

563

derivations recorded for this entity

Complete over 38 sources, 1 compilation, and 41 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/lorazepam/archive

2Build

one panel per compilation run

generation run 2026-05-09

69 min completedmodel pipeline-v5plan not recordedrun/99c429a6…

Selection

results seen119

selected by the model41

consumed as sources38

Verification

claims checked224

supported10

partially supported4

not supported1

inconclusive209

record
seen / partial
working

The model's own caveats

taper_protocol_proposed
note
note

Reproduce

inputs: 38 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

20 searches for this run
#	source	query	seen	kept	rationale
1	PubMed	lorazepam pharmacology mechanism GABA receptor binding affinity	1	—	—
2	PubChem	lorazepam	1	1	Primary chemical identity verification
3	PubMed	lorazepam pharmacokinetics bioavailability half-life metabolism	10	1	PMID 6133404 directly reports lorazepam IV/IM pharmacokinetics: t1/2 14.1 hrs, Vd 1.24 L/kg, IM bioavailability 88.8%
4	PubMed	Greenblatt lorazepam pharmacokinetics plasma distribution elimination	7	6	Greenblatt series is definitive source for lorazepam pharmacokinetics in humans
5	OpenAlex	lorazepam benzodiazepine pharmacology clinical	10	2	PADIS guidelines and AES status epilepticus guidelines directly reference lorazepam clinical use
6	PubMed	lorazepam status epilepticus treatment efficacy	9	4	Evidence base for lorazepam in status epilepticus
7	PubMed	lorazepam GABA-A receptor binding affinity benzodiazepine site	9	2	Directly study lorazepam effects on GABA-A receptor chloride channel coupling during tolerance
8	PubMed	benzodiazepine tolerance dependence mechanism GABA receptor downregulation	7	3	Molecular mechanisms of BZD tolerance relevant to lorazepam dependence section
9	PubMed	lorazepam amnestic anterograde amnesia memory impairment cognitive effects	2	2	—
10	PubMed	lorazepam pregnancy teratogenicity fetal risk neonatal	1	1	—
11	WebSearch	lorazepam scheduling legal status UK US Canada Australia	10	2	—
12	PubChem REST API	—	1	1	—
13	PubMed	lorazepam GABAA subunit selectivity alpha1 alpha2	8	4	—
14	WebSearch	lorazepam history discovery synthesis Wyeth Laboratories approval FDA 1977	10	2	—
15	PubMed	lorazepam versus midazolam RAMPART prehospital status epilepticus	2	1	—
16	StatPearls/NCBI	—	1	1	—
17	PubMed	benzodiazepine withdrawal treatment diazepam taper discontinuation	8	1	—
18	PubMed	lorazepam alcohol withdrawal delirium treatment	8	3	—
19	PubMed	lorazepam propylene glycol toxicity ICU continuous infusion	4	2	—
20	ClinicalTrials.gov	lorazepam anxiety treatment	10	2	—

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

pharmacology56 · 2 ok

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Lorazepam is a positive allosteric modulator (PAM) of ionotropic gaba-a-receptor (gaba type A) receptorssupported
Reviews GABA-A receptor subunit pharmacology; α1 mediates sedation/amnesia, α2 mediates anxiolysis, α subunits involved in anticonvulsant activity; 1,4-BZDs like clonazepam compared to 1,5-BZD clobazam 11599020-000000000-00000
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Each α subunit mediates distinct pharmacological effects: α1 subunits contribute to sedation, hypnosis, anterograde amnesia, and anticonvulsant activity; α2 and α3 subunits mediate anxiolysis and muscle relaxation; α5 subunits modulate learning and memory.supported
α1 mediates sedation/amnesia, α2 mediates anxiolysis, α subunits involved in anticonvulsant activity 11599020-000000000-00000
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safety54 · 5 ok

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Third-trimester and peripartum use is associated with "floppy infant syndrome" (neonatal hypotonia, respiratory depression, reluctance to suck, apneic spells) and neonatal withdrawal symptoms persisting hours to months after birthsupported
late trimester use associated with floppy infant syndrome and neonatal withdrawal pmid:7881198
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Rebound anxiety and insomnia following discontinuation — even after short-term therapeutic use — are well-documented and contribute to the cycle of dependence.supported
management requires gradual tapering with long-acting BZD ijms27031430
Tolerance develops within days of continuous use for the anxiolytic, anticonvulsant, and sedative effects of lorazepampartially supported
prolonged use causes tolerance via GABA-A subunit downregulation and compensatory glutamatergic sensitization ijms27031430
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Standard management involves substitution with a long-acting benzodiazepine (typically Diazepam) and gradual dose tapersupported
management requires gradual tapering with long-acting BZD ijms27031430
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Pregnancy, especially first and third trimester (FDA Category D — fetal risk documented)partially supported
late trimester use associated with floppy infant syndrome and neonatal withdrawal pmid:7881198
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summary26 · 2 ok

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Level A evidence supports IV lorazepam as first-line treatment for convulsive status epilepticus, and the landmark PHTSE trial demonstrated superiority over placebo for prehospital seizure terminationsupported
IM midazolam, IV lorazepam, IV diazepam and IV phenobarbital established as efficacious for SE (Level A). 1535-7597-16.1.48
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Co-administration with opioids carries an FDA Black Box Warning: concurrent benzodiazepine–opioid use increases overdose mortality by 40–334%. tolerance to anxiolytic and anticonvulsant effects develops within days of continuous use, driven by GABA-A receptor uncoupling and compensatory glutamatergic sensitizationpartially supported
prolonged use causes tolerance via GABA-A subunit downregulation and compensatory glutamatergic sensitization ijms27031430
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neuroscience22 · 3 ok

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(5) Compensatory glutamatergic sensitization: As a homeostatic counterregulation to sustained GABAergic enhancement, excitatory glutamatergic systems are upregulated. This glutamatergic rebound-effect contributes to the hyperexcitability observed during withdrawal, including seizure susceptibility.supported
prolonged use causes tolerance via GABA-A subunit downregulation and compensatory glutamatergic sensitization ijms27031430
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(2) α1 subunit downregulation: Sustained benzodiazepine exposure activates L-type voltage-gated calcium channels, triggering a PKA/CREB-ICER signaling cascade that downregulates transcription of the GABA-A α1 subunit.partially supported
prolonged use causes tolerance via GABA-A subunit downregulation and compensatory glutamatergic sensitization ijms27031430
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(4) PLCδ/Ca²⁺/calcineurin-mediated receptor internalization: GABA-A receptors undergo calcineurin-dependent endocytosis and inhibitory synapse disassembly via the PLCδ/Ca²⁺ signaling pathway.supported
Prolonged diazepam exposure disrupts inhibitory GABAergic synapses via GABAR internalization through PLCδ/Ca2+/calcineurin pathway s41380-018-0100-y

clinical-evidence18 · 1 ok

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IV lorazepam holds Level A evidence as an established first-line treatment for adult convulsive status epilepticus (SE), per American Epilepsy Society guidelines.supported
IM midazolam, IV lorazepam, IV diazepam and IV phenobarbital established as efficacious for SE (Level A). 1535-7597-16.1.48
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pharmacokinetic-detail16 · 0 ok

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history10 · 1 ok

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The 2001 Prehospital Treatment of Status Epilepticus (PHTSE) trial, published in the New England Journal of Medicine, demonstrated that both lorazepam and diazepam were superior to placebo for prehospital seizure termination, establishing Level A evidence for IV lorazepam in this indicationsupported
IM midazolam, IV lorazepam, IV diazepam and IV phenobarbital established as efficacious for SE (Level A). 1535-7597-16.1.48

receptor-pharmacology10 · 0 ok

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comparative-pharmacology8 · 0 ok

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chemistry4 · 0 ok

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3Sources

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

Sources 1 to 30
year	source	tier	status	feeds
2026	Benzodiazepine Dependence: Clinical and Molecular Aspects, Preventive Strategies and Therapeutic Approaches.Navarrete F, Marín-Mayor M, Martínez-Hostyn L, Rubio G, Manzanares J · International journal of molecular sciencesdoi:10.3390/ijms27031430	moderate	consumed	3 sections
2026	The Enduring Impact of Ghostwriting on the Treatment of Alcohol WithdrawalWeintraub SJ · Journal of general internal medicinedoi:10.1007/s11606-025-10025-7	moderate	consumed	3 sections
2024	Clinical Outcomes of Benzodiazepine Prescribing for People Receiving Opioid Agonist Treatment: A Systematic ReviewMatheson C, Vucic C, Dumbrell J, Robertson R, et al. · Pharmacy (Basel, Switzerland)doi:10.3390/pharmacy12050152	strong	consumed	2 sections
2024	Lorazepam - Chemical Properties (PubChem CID 3958 REST API)PubChemurl:de89389c1fd88c84	weak	consumed	cited only
2024	Lorazepam - PubChem Compound CID 3958PubChem · PubChempmid:3958	moderate	consumed	1 section
2024	Lorazepam - StatPearlsGhiasi N, Bhansali RK, Marwaha R · StatPearls [Internet]url:df9d4ba508cef4cc	weak	consumed	cited only
2024	Lorazepam - WikipediaWikipedia contributorsurl:e573c4005a76a816	weak	consumed	cited only
2022	Management of Alcohol Withdrawal Syndrome in Patients with Alcoholic Liver DiseaseChand PK, Panda U, Mahadevan J, Murthy P · Journal of clinical and experimental hepatologydoi:10.1016/j.jceh.2022.03.003	moderate	consumed	3 sections
2022	Termination of seizures in the paediatric age group, best benzodiazepine and route of administration: A network meta-analysisHasan SU, Pervez A, Bhatty S, Shamim S, et al. · The European journal of neurosciencedoi:10.1111/ejn.15732	strong	consumed	1 section
2020	Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic MedicationsCosci F, Chouinard G · Psychotherapy and Psychosomaticsdoi:10.1159/000506868	strong	consumed	3 sections
2020	Comparison of diazepam and lorazepam for the emergency treatment of adult status epilepticus: a systemic review and meta-analysisKobata H, Hifumi T, Hoshiyama E, Yamakawa K, Nakamura K, Soh M, Kondo Y, Yokobori S · Acute medicine & surgerydoi:10.1002/ams2.582	strong	consumed	cited only
2018	Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS 2018)Devlin JW, Skrobik Y, Gélinas C, et al. · Critical Care Medicinedoi:10.1097/ccm.0000000000003299	strong	consumed	cited only
2018	Diazepam-induced loss of inhibitory synapses mediated by PLCδ/Ca2+/calcineurin signalling downstream of GABAA receptors.Nicholson MW, Sweeney A, Pekle E, et al. · Molecular psychiatrydoi:10.1038/s41380-018-0100-y	moderate	consumed	1 section
2016	Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and AdultsGlauser TA, Shinnar S, Gloss D, Alldredge BK, Arya R · Epilepsy currentsdoi:10.5698/1535-7597-16.1.48	strong	consumed	4 sections
2015	The effects of the nonselective benzodiazepine lorazepam and the α2/α3 subunit-selective GABAA receptor modulators AZD7325 and AZD6280 on plasma prolactin levelsTe Beek ET, Chen X, Jacobs GE, Nahon KJ, de Kam ML, Lappalainen J, Cross AJ, van Gerven JM, Hay JL · Clinical pharmacology in drug developmentdoi:10.1002/cpdd.134	strong	consumed	cited only
2013	Reinforcing effects of compounds lacking intrinsic efficacy at α1 subunit-containing GABAA receptor subtypes in benzodiazepine-experienced monkeysShinday NM, Sawyer EK, Fischer BD, Platt DM, et al. · Neuropsychopharmacologydoi:10.1038/npp.2012.265	moderate	consumed	1 section
2012	GABA(A) receptor physiology and its relationship to the mechanism of action of the 1,5-benzodiazepine clobazam.Sankar R · CNS drugsdoi:10.2165/11599020-000000000-00000	moderate	consumed	4 sections
2011	RAMPART: a double-blind randomized clinical trial of IM midazolam versus IV lorazepam for prehospital status epilepticusSilbergleit R, Lowenstein D, Durkalski V, Conwit R · Epilepsiadoi:10.1111/j.1528-1167.2011.03235.x	strong	consumed	2 sections
2009	Propylene glycol accumulation in critically ill patients receiving continuous intravenous lorazepam infusionsHorinek EL, Kiser TH, Fish DN, MacLaren R · The Annals of pharmacotherapydoi:10.1345/aph.1m313	moderate	consumed	cited only
2006	Dose-dependent retrograde facilitation of verbal memory in healthy elderly after acute oral lorazepam administrationPomara N, Facelle TM, Roth AE, Willoughby LM, Greenblatt DJ, Sidtis JJ · Psychopharmacologypmid:16525857	strong	consumed	1 section
2006	GABAA receptor subtype specific enhancement of inhibition in human motor cortexDi Lazzaro V, Pilato F, Dileone M, Ranieri F, Ricci V, Profice P, Bria P, Tonali PA, Ziemann U · The Journal of physiologypmid:16809358	strong	consumed	3 sections
2006	Osmol gap as a surrogate marker for serum propylene glycol concentrations in patients receiving lorazepam for sedationBarnes BJ, Gerst C, Smith JR, Terrell AR, Mullins ME · Pharmacotherapypmid:16422667	moderate	consumed	2 sections
2005	Sedation in PACU: the role of benzodiazepinesArcangeli A, Antonelli M, Mignani V, Sandroni C · Current drug targetspmid:16305452	moderate	consumed	1 section
2002	RWJ-51204, a new nonbenzodiazepine anxiolytic (comparison with lorazepam as full agonist)Dubinsky B, Vaidya AH, et al. · The Journal of pharmacology and experimental therapeuticspmid:12388665	moderate	consumed	3 sections
2001	A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticusAlldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, et al. · The New England journal of medicinepmid:11547716	strong	consumed	2 sections
1999	Effects of tiapride on electroencephalograms and cognitive functions in the elderlyPatat A, Alberini H, Bonhomme D, Soubrane C, Allain H, Gandon JM · International clinical psychopharmacologypmid:10468312	strong	consumed	2 sections
1999	Prolonged sedation requiring mechanical ventilation after routine doses of clorazepam - lorazepam preferred in hepatic impairmentGuglielminotti J, Maury E, et al. · Intensive care medicinepmid:10660854	weak	consumed	2 sections
1994	The effects of benzodiazepine use during pregnancy and lactation.McElhatton PR · Reproductive toxicologypmid:7881198	moderate	consumed	1 section
1992	Effects of lorazepam tolerance and withdrawal on GABAA receptor operated chloride channels in mice selected for differences in ethanol withdrawal severityAllan AM, Baier LD, Zhang X · Life sciencespmid:1381457	moderate	consumed	2 sections
1992	Effects of lorazepam tolerance and withdrawal on GABAA receptor-operated chloride channelsAllan AM, Baier LD, Zhang X · The Journal of pharmacology and experimental therapeuticspmid:1374467	moderate	consumed	3 sections

Show all 38 sources — 8 more

Sources 31 to 38
year	source	tier	status	feeds
1989	Kinetic and dynamic study of intravenous lorazepam: comparison with intravenous diazepamGreenblatt DJ, Ehrenberg BL, Gunderman J, Scavone JM, Tai NT, Harmatz JS, Shader RI · The Journal of pharmacology and experimental therapeuticspmid:2746493	strong	consumed	4 sections
1987	Lorazepam and FG 7142 induce tolerance to the DMCM antagonistic effect of benzodiazepine receptor ligandsPetersen EN, Jensen LH · Brain research bulletinpmid:2824007	moderate	consumed	1 section
1983	Lorazepam and oxazepam kinetics in women on low-dose oral contraceptivesAbernethy DR, Greenblatt DJ, Ochs HR, Weyers D, Divoll M, Harmatz JS, Shader RI · Clinical pharmacology and therapeuticspmid:6132698	strong	consumed	1 section
1982	Pharmacokinetic comparison of sublingual lorazepam with intravenous, intramuscular, and oral lorazepamGreenblatt DJ, Divoll M, Harmatz JS, Shader RI · Journal of pharmaceutical sciencespmid:6121043	strong	consumed	1 section
1981	Clinical pharmacokinetics of oxazepam and lorazepamGreenblatt DJ · Clinical pharmacokineticspmid:6111408	strong	consumed	5 sections
1980	Pharmacokinetic study of lorazepam overdosageAllen MD, Greenblatt DJ, LaCasse Y, Shader RI · The American journal of psychiatrypmid:6108079	weak	consumed	3 sections
1979	Lorazepam kinetics in the elderlyGreenblatt DJ, Allen MD, Locniskar A, Harmatz JS, Shader RI · Clinical pharmacology and therapeuticspmid:36252	moderate	consumed	3 sections
1977	Clinical pharmacokinetics of lorazepam. II. Intramuscular injectionGreenblatt DJ, Joyce TH, Comer WH, Knowles JA, Shader RI, Kyriakopoulos AA, MacLaughlin DS, Ruelius HW · Clinical pharmacology and therapeuticspmid:13960	moderate	consumed	1 section

4Docket

one filing per activity — decisions, correspondence, reports

awaiting ruling — 1

dependence · taper2026-07-03

0012026-05-09revisionRevision 1
Initial LLM generation (v5 pipeline, wiki, prose phase)
psx:substance/lorazepam/version/1
0022026-06-04proposal34 value proposals approved together
one review action inferred from a shared reviewer and instant — the graph records one activity per proposal
34 items in this filing
- contraindication · respiratory
- contraindication · other
- contraindication · respiratory
- contraindication · other
- contraindication · age
- contraindication · pregnancy_breastfeeding
- contraindication · psychiatric
- contraindication · age
- contraindication · hepatic
- contraindication · other
- contraindication · other
- dose_tier · threshold
- dose_tier · light
- dose_tier · common
- dose_tier · strong
- dose_tier · heavy
- 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 · oral
- duration · oral · onset
- duration · oral · come_up
- duration · oral · peak
- duration · oral · offset
- duration · oral · total
- duration · oral · aftereffects
psx:substance/lorazepam/proposal/contraindication/73ebb704-a43a-462e-be5a-3b05dc3f832b
0032026-06-04publicationPublication — backfill
psx:substance/lorazepam/pub/0aac5353-3baf-4d3c-b916-7cfe0d7cfd9b
0042026-10-02rulingRuling — psx:substance/lorazepam/proposal/article_section_proposals/3e232eb7-29b9-4359-ab4d-08e719c69148founder
psx:substance/lorazepam/ruling/harm-reduction-headings/3e232eb7-29b9-4359-ab4d-08e719c69148
0052026-10-02rulingRuling — psx:substance/lorazepam/proposal/article_section_proposals/52c42611-f6f3-489c-b36a-1aebb09d601afounder
psx:substance/lorazepam/ruling/harm-reduction-headings/52c42611-f6f3-489c-b36a-1aebb09d601a
0062026-10-02revisionr1.a1
no edit summary recorded
psx:substance/lorazepam/version/2
0072026-10-02publicationPublication — publishagent-psx
psx:substance/lorazepam/pub/0b349203-6936-4370-b5e9-840dcb4756fe

5Issued documents

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

Issued documents
document	content hash	issued	from version	superseded
info_card	aa4553fac7108e5fc8a3d1c2…	2026-10-02 13:09	Revision 2	current
emergency	dcd2ca271fbe095dc7fb6211…	2026-09-04 04:30	Revision 1	current
info_card	1e472eaff3a937fa2c74197d…	2026-09-04 04:30	Revision 1	superseded2026-10-02
notice	5e0b2fa53726c91a2b579816…	2026-09-04 04:30	Revision 1	current

Lorazepam

6Node page

1Provenance card

2Build

generation run 2026-05-09

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