generation run 2026-05-08
64 min completedmodel pipeline-v5plan not recordedrun/9ac4029a…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- taper_unassessed
- safety_data_unverified
Reproduce
- inputs
- 26 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
14 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | OpenAlex | bromazolam novel benzodiazepine | 10 | 5 | Landmark reviews provide class-level context; specific bromazolam papers provide direct evidence |
| 2 | PubMed | bromazolam toxicology overdose death postmortem | 2 | 1 | Jefferson County case series directly relevant to bromazolam concentrations in fatal overdose |
| 3 | ClinicalTrials.gov · absence | bromazolam | 0 | 0 | No clinical trials exist - bromazolam has no approved medical use or investigational status |
| 4 | PubChem | bromazolam | 1 | 1 | Primary chemical identity verification |
| 5 | PubMed | bromazolam benzodiazepine pharmacology | 13 | 8 | All directly relevant to bromazolam pharmacology, toxicology, clinical presentation |
| 6 | PubMed | Hester von Voigtlander aryl triazolo benzodiazepine pharmacological activity 1979 | 1 | 1 | Original synthesis paper documenting first preparation in 1970s |
| 7 | WHO ECDD | bromazolam WHO ECDD 45th meeting 2022 critical review | 1 | 1 | Authoritative WHO regulatory review; contains binding affinity data from Clayton 2015, synthesis history, dosing, metabolism, legal status |
| 8 | PubMed | Clayton Poe Rallapalli pharmacophore alpha 5 GABA benzodiazepine receptor model | 1 | 1 | Primary source for GABA-A binding affinity data for bromazolam |
| 9 | WebSearch | bromazolam legal status scheduling DEA US UK EU Canada Australia 2023 2024 2025 | 10 | 4 | Primary legal status documentation for key jurisdictions |
| 10 | PubMed | McDermott phenibut bromazolam use disorder withdrawal hospitalization | 1 | 1 | Primary published case report of bromazolam dependence/withdrawal |
| 11 | WHO ECDD 46th Meeting | bromazolam WHO ECDD 46th meeting 2023 updated critical review | 1 | 1 | Updated WHO regulatory review with new in vitro binding data, animal pharmacology, and expanded epidemiology |
| 12 | PubMed | McDermott phenibut bromazolam withdrawal case report | 1 | 1 | Primary source for dependence case evidence |
| 13 | WHO ECDD 45th and 46th Meeting Reports | Extract all bromazolam pharmacology, dosing, metabolism, legal status data | 2 | 3 | Primary authoritative source for all bromazolam-specific data |
| 14 | WebSearch | bromazolam UK Psychoactive Substances Act scheduling status 2024 2025 | 10 | 2 | Legal status verification for key jurisdictions |
81 claims by section — every cited sentence, checked against its source
safety33 · 26 ok
Claim in safety — inconclusiveinconclusiveworking →
A cluster of three patients in Chicago who consumed counterfeit alprazolam tablets containing bromazolam presented with seizures, hyperthermia, and myocardial injury — an atypical and severe presentation that exceeds standard benzodiazepine class toxicitysupported
Three young adults in Chicago consumed counterfeit alprazolam containing bromazolam and experienced seizures, hyperthermia, and myocardial injury. mmwr.mm725253a5
In the largest postmortem case series (96 cases, England and Wales), multiple co-intoxicants were present in the vast majority of casessupported
96 coronial cases with bromazolam quantitation. 48% also had another designer BZD. Cocaine, gabapentinoids, and diazepam most common co-detections. j.forsciint.2023.111891
However, synergistic CNS and respiratory-depression from benzodiazepine–opioid co-exposure is the dominant mechanism in most fatal cases.supported
Documents synergistic respiratory depression from simultaneous BZD and opioid exposure. acem.70104
Postmortem blood concentrations across published case series range from less than 1 ng/mL to 3,220 ng/mL, with mean values of 11.4–401 ng/mL depending on the study setting and case selectionsupported
Mean postmortem blood concentration 64.6 ± 79.4 µg/L (range <1–425 µg/L). j.forsciint.2023.111891
Postmortem blood concentrations across published case series range from less than 1 ng/mL to 3,220 ng/mL, with mean values of 11.4–401 ng/mL depending on the study setting and case selectionsupported
Mean concentration 11.4 ± 53.7 ng/mL (median 1.6 ng/mL), range 0.5–319.3 ng/mL. bkad005
Postmortem blood concentrations across published case series range from less than 1 ng/mL to 3,220 ng/mL, with mean values of 11.4–401 ng/mL depending on the study setting and case selectionsupported
Bromazolam concentrations 21–3220 ng/mL (mean 401 ng/mL). bkae067
Postmortem blood concentrations across published case series range from less than 1 ng/mL to 3,220 ng/mL, with mean values of 11.4–401 ng/mL depending on the study setting and case selectionsupported
range 5.9-352 ng/mL, mean 59.1, median 28.5 ng/mL. 1556-4029.70003
In England and Wales, cocaine, gabapentinoids, and diazepam were the most common co-detections, with 48% of cases having at least one other designer benzodiazepine present.supported
48% also had another designer BZD. Cocaine, gabapentinoids, and diazepam most common co-detections. j.forsciint.2023.111891
Bromazolam is frequently sold in counterfeit alprazolam and diazepam tablets or found as an unintended adulterant in opioid and stimulant suppliessupported
Three young adults in Chicago consumed counterfeit alprazolam containing bromazolam. mmwr.mm725253a5
Bromazolam is frequently sold in counterfeit alprazolam and diazepam tablets or found as an unintended adulterant in opioid and stimulant suppliessupported
Bromazolam prevalence, co-occurring substances, and self-reported use among ED patients with bromazolam exposure presenting for opioid/stimulant non-fatal overdose. j.drugalcdep.2025.112776
Bromazolam is frequently sold in counterfeit alprazolam and diazepam tablets or found as an unintended adulterant in opioid and stimulant suppliessupported
Bromazolam not approved in North America or Europe; emerged as adulterant in US illicit drug supply. 15563650.2025.2490831
Dosing variability in illicit preparations is extreme: analysis of Scottish prison samples found bromazolam content ranging from 0.34 to 2.33 mg per tabletsupported
High variability in tablet content (0.34-2.33 mg per tablet). dta.3560
Standard immunoassay benzodiazepine screens may not detect bromazolam; LC-MS/MS or HRMS confirmation is required.supported
Recommended screening targets: alpha-hydroxy bromazolam glucuronide and bromazolam N-glucuronide in urine. bkaa161
Amnesia: Anterograde amnesia is reported with bromazolam use, consistent with its sub-nanomolar α5 GABA-A receptor affinitysupported
Contains binding affinity (Ki) data for bromazolam at... alpha5 (0.62 nM) subunits. 430248
Claim in safety — inconclusiveinconclusiveworking →
McDermott et al. (2022) reported the first case of bromazolam and phenibut use disorders requiring hospitalization for medically supervised withdrawal. No established benzodiazepine dose equivalency was available.supported
Case report of bromazolam use disorder requiring hospitalized medically supervised withdrawal, in combination with phenibut. pcc.21cr03119
Butler et al. (2025) documented a seizure following abrupt cessation of multiple substances including bromazolam, managed with symptom-based diazepam stabilization.supported
Male in early 20s presenting with seizure after abrupt cessation of bromazolam, flubromazepam, alcohol, kratom, tianeptine, phenibut. Symptom-based diazepam stabilization used. bcr-2025-266077
This gap complicates clinical withdrawal management and is specifically highlighted by both published case reports.supported
No approved long-acting BZD equivalents for bromazolam. Discusses challenge of bromazolam withdrawal management. bcr-2025-266077
This gap complicates clinical withdrawal management and is specifically highlighted by both published case reports.supported
Case report of bromazolam use disorder requiring hospitalized medically supervised withdrawal, in combination with phenibut. pcc.21cr03119
Synergistic CNS and respiratory-depression from benzodiazepine–opioid co-exposure is the dominant mechanism in most bromazolam-associated fatalities. Fentanyl is co-detected in 75–88% of postmortem bromazolam-positive casespartially supported
Documents synergistic respiratory depression from simultaneous BZD and opioid exposure. acem.70104
Claim in safety — inconclusiveinconclusiveworking →
Alcohol: Additive-to-synergistic CNS and respiratory depression by class, without bromazolam-specific human data.supported
Review of 31 designer BZDs. Covers toxicology, public health risks, adverse events 2008–2021. ph14060560
Gabapentinoids were frequently co-detected in UK coronial cases involving bromazolam.supported
Cocaine, gabapentinoids, and diazepam most common co-detections. j.forsciint.2023.111891
CYP3A4 inhibitors (azole antifungals, macrolide antibiotics, ritonavir, grapefruit juice): Expected to increase bromazolam plasma concentrations and prolong duration of effect, as CYP3A4 is the dominant Phase I metabolic pathway.supported
CYP3A4 involved in all phase I metabolism. bkaa161
CYP3A4 inducers (rifampin, carbamazepine, St. John's wort): Expected to decrease bromazolam plasma concentrations, potentially precipitating withdrawal in dependent users.supported
CYP3A4 involved in all phase I metabolism. bkaa161
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Absolute contraindications: * Concurrent opioid use without medical supervision: Synergistic respiratory depression is the primary mechanism in bromazolam-associated fatalities * Severe respiratory insufficiency: GABA-A-mediated respiratory depression compounds pre-existing ventilatory impairment * Known hypersensitivity to benzodiazepines: Cross-reactivity expected across the classsupported
Documents synergistic respiratory depression from simultaneous BZD and opioid exposure. acem.70104
Relative contraindications: * Hepatic impairment: CYP3A4-dependent metabolism predicts impaired clearance and prolonged exposure * History of substance use disorder: Full benzodiazepine agonist activity and documented reinforcing properties indicate high abuse liability * Concurrent use of CYP3A4 inhibitors: Predicted elevation of plasma concentrations * Pregnancy: Benzodiazepine-class teratogenicity risk; no bromazolam-specific reproductive toxicity data exist * Myasthenia gravis: GABA-A-mediated muscle relaxation may worsen neuromuscular junction impairment * Acute narrow-angle glaucoma: Standard benzodiazepine class contraindication * Elderly patients: Increased sensitivity to CNS depressants, fall risk, and likely reduced metabolic clearance — no geriatric-specific data for bromazolamsupported
CYP3A4 involved in all phase I metabolism; UGT1A4 and UGT2B10 catalyze N-glucuronidation. bkaa161
Relative contraindications: * Hepatic impairment: CYP3A4-dependent metabolism predicts impaired clearance and prolonged exposure * History of substance use disorder: Full benzodiazepine agonist activity and documented reinforcing properties indicate high abuse liability * Concurrent use of CYP3A4 inhibitors: Predicted elevation of plasma concentrations * Pregnancy: Benzodiazepine-class teratogenicity risk; no bromazolam-specific reproductive toxicity data exist * Myasthenia gravis: GABA-A-mediated muscle relaxation may worsen neuromuscular junction impairment * Acute narrow-angle glaucoma: Standard benzodiazepine class contraindication * Elderly patients: Increased sensitivity to CNS depressants, fall risk, and likely reduced metabolic clearance — no geriatric-specific data for bromazolamsupported
CYP3A4 involved in all phase I metabolism; UGT1A4 and UGT2B10 catalyze N-glucuronidation. bkaa161
clinical-evidence8 · 7 ok
Plasma bromazolam concentrations were 6 µg/L and 29 µg/L respectively.supported
Bromazolam plasma concentrations determined at 6 and 29 µg/L. bkaa161
The authors noted that high-dose bromazolam may produce severe toxicity inconsistent with the benzodiazepine classsupported
Three young adults in Chicago consumed counterfeit alprazolam containing bromazolam and experienced seizures, hyperthermia, and myocardial injury. mmwr.mm725253a5
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Dunlop et al. (2025) published the ASSIST (A Surveillance Study of Illicit Substance Toxicity) study clinically characterizing analytically confirmed bromazolam use in Scotland, where bromazolam has become the predominant novel benzodiazepine in "street valium".supported
Bromazolam predominant in 'street valium'. Study describes analytically confirmed bromazolam use features. 15563650.2025.2524078
Falise et al. (2025) documented bromazolam co-exposure patterns in US emergency department patients presenting for suspected opioid and/or stimulant-related non-fatal overdose, establishing bromazolam as a significant adulterant in the illicit drug supply.supported
Bromazolam prevalence, co-occurring substances, and self-reported use among ED patients with bromazolam exposure presenting for opioid/stimulant non-fatal overdose. US-based surveillance study. j.drugalcdep.2025.112776
Cembellin-Kao et al. (2025) documented occult bromazolam exposure in patients presenting with opioid or stimulant overdose — cases in which neither the patient nor treating clinicians were aware of benzodiazepine involvement.supported
Documents occult (unknown) exposure in patients presenting for other drug overdoses. 15563650.2025.2490831
The report documents that no established benzodiazepine dose equivalency for bromazolam was available to guide clinical management.supported
Case report of bromazolam use disorder requiring hospitalized medically supervised withdrawal, in combination with phenibut. pcc.21cr03119
Farah et al. (2026) reported a case series of 32 patients presenting with bromazolam-positive urines at a US emergency department.supported
Case series of 32 patients presenting with bromazolam-positive urines. 15563650.2025.2583250
pharmacokinetic-detail8 · 5 ok
CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John's wort) are expected to decrease bromazolam plasma concentrations, potentially precipitating withdrawal in dependent userssupported
CYP3A4 involved in all phase I metabolism. bkaa161
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
In clinical cases, plasma concentrations of 6–29 µg/L were measured — concentrations that fall below the sensitivity threshold of many routine clinical assays.supported
Bromazolam plasma concentrations determined at 6 and 29 µg/L. Recommended screening targets: alpha-hydroxy bromazolam glucuronide and bromazolam N-glucuronide in urine. bkaa161
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
The α-hydroxy bromazolam glucuronide and the bromazolam N-glucuronide are the most abundant urinary metabolites, making them the preferred targets for urine-based drug screening.supported
Recommended screening targets: alpha-hydroxy bromazolam glucuronide and bromazolam N-glucuronide in urine. bkaa161
CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, grapefruit juice) are expected to increase bromazolam plasma concentrations and prolong duration of effect — an interaction pattern well-established for alprazolam and other CYP3A4-substrate benzodiazepinessupported
CYP3A4 involved in all phase I metabolism. bkaa161
Liquid chromatography–tandem mass spectrometry (LC-MS/MS) or high-resolution mass spectrometry (HRMS) is required for analytical confirmationsupported
Bromazolam plasma concentrations determined at 6 and 29 µg/L. Recommended screening targets: alpha-hydroxy bromazolam glucuronide and bromazolam N-glucuronide in urine. bkaa161
comparative-pharmacology7 · 6 ok
Bromazolam Ki values; alprazolam and diazepam Ki values are approximate published ranges from multiple sourcessupported
Contains binding affinity (Ki) data for bromazolam at alpha1 (2.8 nM), alpha2 (0.69 nM), and alpha5 (0.62 nM) subunits. 430248
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Hikin et al., Mérette et al., Green et al., Ballotari et al.supported
96 coronial cases with bromazolam quantitation. j.forsciint.2023.111891
Hikin et al., Mérette et al., Green et al., Ballotari et al.supported
First Canadian bromazolam postmortem report. First detected in BC January 2021. bkad005
Hikin et al., Mérette et al., Green et al., Ballotari et al.supported
10 postmortem cases with bromazolam May 2022–December 2023. bkae067
Hikin et al., Mérette et al., Green et al., Ballotari et al.supported
GC-MS method for designer BZDs in postmortem blood. 20 of 21 positive cases were bromazolam-positive. 1556-4029.70003
In most cases, multiple co-intoxicants were present, and bromazolam has not been confirmed as the sole cause of death in any published case.supported
Bromazolam not associated with death in isolation from toxic concentrations. Cocaine, gabapentinoids, and diazepam most common co-detections. j.forsciint.2023.111891
history7 · 7 ok
In San Francisco, 44 bromazolam-related fatalities were recorded in 2023 alone, with postmortem blood concentrations increasing over the study period — a pattern suggesting rising availability and purity in the local drug supplysupported
44 bromazolam fatalities in 2023. Blood concentrations increased during study period. add.16520
In Australia, bromazolam emerged as a significant contributor to novel benzodiazepine-related fatalities, with changing patterns documented across Victoria and other states.supported
Characteristics, toxicology and autopsy findings of NBZD-related poisoning in Australia 2000-2025. Documents changes in characteristics of cases from 2020 onward. j.drugalcdep.2026.113085
In Australia, bromazolam emerged as a significant contributor to novel benzodiazepine-related fatalities, with changing patterns documented across Victoria and other states.supported
Novel benzodiazepines increased in availability and use since mid-2000s with corresponding rise in associated deaths in Victoria, Australia. dar.14054
Reports from the United States followed in 2019, with subsequent detections in British Columbia, Canada in January 2021 and Jefferson County, Alabama in May 2022.supported
10 postmortem cases with bromazolam May 2022–December 2023. bkae067
Reports from the United States followed in 2019, with subsequent detections in British Columbia, Canada in January 2021 and Jefferson County, Alabama in May 2022.supported
First detected in BC January 2021. bkad005
The compound has been found in counterfeit pharmaceutical tablets (principally imitating alprazolam and diazepam), loose powder, capsules, gummies, and infused paper or cardsupported
High variability in tablet content (0.34-2.33 mg per tablet). Infused paper/cards increased during Covid-19. dta.3560
In Scotland, bromazolam became the predominant novel benzodiazepine detected in "street valium," contributing to a context in which 58% of Scottish drug-related deaths in 2023 involved benzodiazepinessupported
Scotland drug death crisis context: 58% of drug-related deaths involved benzodiazepines in 2023. Bromazolam predominant in 'street valium'. 15563650.2025.2524078
neuroscience6 · 4 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Bromazolam's Ki of 2.8 nM at α1β3γ2 receptors predicts efficient engagement of this pathway at low doses.supported
Contains binding affinity (Ki) data for bromazolam at alpha1 (2.8 nM). 430248
Bromazolam's highest measured affinity is at α2 subtypes (Ki = 0.69 nM), consistent with its reported anxiolytic propertiespartially supported
Contains binding affinity (Ki) data for bromazolam at alpha1 (2.8 nM), alpha2 (0.69 nM), and alpha5 (0.62 nM) subunits. 430248
Bromazolam's sub-nanomolar α5 affinity (Ki = 0.62 nM) predicts memory-impairing effects, consistent with user reports of amnesia — though community reports suggest amnesia may be less prominent with bromazolam than with some other designer benzodiazepines.supported
Contains binding affinity (Ki) data for bromazolam at... alpha5 (0.62 nM) subunits. 430248
Claim in neuroscience — inconclusiveinconclusiveworking →
Does high-dose bromazolam produce seizures through an on-target or off-target mechanism? The Chicago cluster (seizures, hyperthermia, myocardial injury) is atypical for benzodiazepine intoxication. Possible explanations include excitotoxic rebound from rapid receptor desensitization at very high doses, undetected co-intoxicants, or bromazolam-specific off-target activity.supported
Three young adults in Chicago consumed counterfeit alprazolam containing bromazolam and experienced seizures, hyperthermia, and myocardial injury. mmwr.mm725253a5
pharmacology5 · 4 ok
Bromazolam demonstrated high affinity at α1β3γ2 (Ki = 2.8 nM), α2β3γ2 (Ki = 0.69 nM), and α5β3γ2 (Ki = 0.62 nM) subtypes, with no detectable binding at α3β3γ2, α4β3γ2, or α6β3γ2 subtypessupported
Contains binding affinity (Ki) data for bromazolam at alpha1 (2.8 nM), alpha2 (0.69 nM), and alpha5 (0.62 nM) subunits in HEK cells expressing recombinant GABA-A/BZD receptor subtypes. 430248
Plasma concentrations: In the only published human analytical data, plasma bromazolam concentrations from two clinical cases were 6 µg/L and 29 µg/L — concentrations sufficiently low to require sensitive LC-MS/MS methods for reliable detection.supported
Bromazolam plasma concentrations determined at 6 and 29 µg/L. Recommended screening targets: alpha-hydroxy bromazolam glucuronide and bromazolam N-glucuronide in urine. bkaa161
Eight metabolites were identified:supported
Eight bromazolam metabolites identified in vitro and in vivo. bkaa161
Phase II N-glucuronidation is catalyzed by UGT1A4 and UGT2B10; multiple UGT isoforms contribute to glucuronidation of hydroxylated metabolites.supported
UGT1A4 and UGT2B10 catalyze N-glucuronidation. bkaa161
Claim in pharmacology — inconclusiveinconclusiveworking →
summary4 · 4 ok
Bromazolam binds with high affinity at GABA-A receptors containing α1 (Ki = 2.8 nM), α2 (Ki = 0.69 nM), and α5 (Ki = 0.62 nM) subunits, with no detectable binding at α3, α4, or α6 subtypessupported
Contains binding affinity (Ki) data for bromazolam at alpha1 (2.8 nM), alpha2 (0.69 nM), and alpha5 (0.62 nM) subunits in HEK cells expressing recombinant GABA-A/BZD receptor subtypes. 430248
One cluster of three patients consuming counterfeit alprazolam tablets presented with seizures, hyperthermia, and myocardial injury — a presentation atypical for the benzodiazepine classsupported
Three young adults in Chicago consumed counterfeit alprazolam containing bromazolam and experienced seizures, hyperthermia, and myocardial injury. mmwr.mm725253a5
Dependence develops with chronic use by class-level inference, but no validated diazepam-equivalent dose for withdrawal management has been establishedsupported
No approved long-acting BZD equivalents for bromazolam. Symptom-based diazepam stabilization used. Discusses challenge of bromazolam withdrawal management. bcr-2025-266077
Dependence develops with chronic use by class-level inference, but no validated diazepam-equivalent dose for withdrawal management has been establishedsupported
Case report of bromazolam use disorder requiring hospitalized medically supervised withdrawal, in combination with phenibut. pcc.21cr03119
receptor-pharmacology2 · 1 ok
Bromazolam's binding profile across GABA-A receptor subtypes has been characterized in a single published study using radioligand displacement in HEK cell membranes expressing recombinant α(x)β3γ2 receptors:supported
Contains binding affinity (Ki) data for bromazolam at alpha1 (2.8 nM), alpha2 (0.69 nM), and alpha5 (0.62 nM) subunits in HEK cells expressing recombinant GABA-A/BZD receptor subtypes. 430248
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
chemistry1 · 0 ok
Claim in chemistry — inconclusiveinconclusiveworking →