generation run 2026-05-15
62 min completedmodel pipeline-v5plan not recordedrun/0b255672…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
- future_opportunity
Reproduce
- inputs
- 20 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 | PubMed | Lovinger NMDA receptor alcohol inhibition; ethanol GABA-A modulation; GABA cross-tolerance alcohol | 10 | 4 | Class-level pharmacological evidence for NMDA antagonism and GABA-A modulation applicable to 2M2B |
| 2 | WebSearch | amylene hydrate tert-amyl alcohol history sedative 19th century pharmacology | 10 | 4 | Historical context and basic toxicological data |
| 3 | Crossref via verify_doi | DOI verification for key papers | 6 | 1 | Verification of citation accuracy |
| 4 | PubMed · absence | 2-methylbutan-2-ol pharmacology psychoactive | 0 | — | — |
| 5 | HandWiki | tert-amyl alcohol comprehensive data | 1 | 4 | Key physical and toxicological data not in PubMed |
| 6 | PubMed | 2-methyl-2-butanol recreational misuse ethanol substitute | 1 | 1 | Primary clinical reference for 2M2B recreational use |
| 7 | PubMed · absence | tertiary alcohols GABA receptor anesthesia sedation | 0 | — | — |
| 8 | psychiatrist.com | 2M2B pharmacology dosing case | 1 | 3 | Full article detail not available via PubMed abstract |
| 9 | WebSearch | 2M2B 2-methylbutan-2-ol recreational drug pharmacology effects | 10 | 4 | Primary sources for clinical and user-report data |
| 10 | Erowid | 2M2B user experience report | 1 | 3 | User-report data for subjective effects characterization |
| 11 | PubMed | tert-amyl alcohol pharmacology; tert-amyl alcohol intoxication toxicology; 2m2b acute intoxication | 10 | 8 | All directly relevant: cytotoxicity, forensic detection, case reports, biotransformation |
| 12 | PubChem | 2-methylbutan-2-ol | 1 | 1 | Primary chemical identity verification |
| 13 | WebSearch | 2M2B legal status scheduling controlled substance law UK US Germany | 10 | 3 | Legal status data for major jurisdictions |
| 14 | ClinicalTrials.gov · absence | 2-methylbutan-2-ol tert-amyl alcohol | 0 | — | — |
61 claims by section — every cited sentence, checked against its source
safety16 · 11 ok
Two published cases document respiratory failure requiring emergency intubation: a 28-year-old male in deep coma with acute respiratory failure (blood tert-amyl alcohol 83 μg/mL), and a 41-year-old female requiring field intubation and ICU admission.partially supported
A case of 28 year-old male found in deep coma complicated with acute respiratory failure due to recreational intoxication with tert-amyl alcohol. Blood level 83 ug/mL by GC-MS. j.forsciint.2014.07.020
Claim in safety — inconclusiveinconclusiveworking →
In HEK293 cells, 2M2B cytotoxicity (MTT assay) is comparable to ethanol and significantly lower than 3-methyl-1-butanol (an isoamyl alcohol isomer)supported
The MTT test indicated that the toxicity of 2M2B was comparable to that of ethanol, but it was much lower than that observed after 3-methyl-1-butanol. j.tiv.2016.07.009
At higher concentrations, 2M2B induces cell cycle arrest and autophagy in retinoblastoma cells via the PI3K/Akt pathway, with dose-dependent toxicity to normal cells.supported
2M2B leads to HXO-RB44 cell death but is cytotoxic to normal cells at higher concentrations. MBT induced cell cycle arrest, apoptosis and autophagy through the PI3K/Akt pathway. 1414-431x20176889
Rat studies of the structurally related compound TAME (which is metabolized to 2M2B) showed elevated liver toxicity markers and significant CYP enzyme induction (up to 260-fold CYP2B1 induction), suggesting hepatic stress with chronic exposuresupported
Hepatomegaly and CYP2E1 induction (2-fold) and CYP2B1 induction (up to 260-fold) observed in TAME-treated rats. j.etap.2006.07.003
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Cross-tolerance with other GABAergic drugs — including benzodiazepines, barbiturates, neurosteroids, and other alcohols — is supported by extensive class-level evidence from ethanol researchsupported
Tolerance to ethanol results in cross-tolerance to other GABAergic drugs including benzodiazepines, anesthetics, and neurosteroids. s13041-017-0325-8
Withdrawal from 2M2B is expected to produce a syndrome clinically indistinguishable from alcohol or benzodiazepine withdrawal: tremor, anxiety, insomnia, diaphoresis, seizures, and potentially delirium tremenssupported
Describes spectrum of alcohol withdrawal from minor symptoms to delirium tremens. Benzodiazepines are the best-assessed drugs for preventing severe alcohol withdrawal including seizures. pmid:17323538
Withdrawal from 2M2B is expected to produce a syndrome clinically indistinguishable from alcohol or benzodiazepine withdrawal: tremor, anxiety, insomnia, diaphoresis, seizures, and potentially delirium tremenssupported
Spectrum of alcohol withdrawal from insomnia and tremulousness to seizures and delirium tremens. Pharmacologic treatment involves medications cross-tolerant with alcohol. Benzodiazepines are agents of choice. pmid:15053409
Co-administration with opioids, benzodiazepines, barbiturates, ethanol, or GHB produces synergistic respiratory depression through convergent mechanisms: additive GABA-A potentiation and, in the case of ethanol, additive NMDA antagonismsupported
GABAergic inhibitory transmission is involved in the acute and chronic effects of ethanol on the brain and behavior. Tolerance to ethanol results in cross-tolerance to other GABAergic drugs including benzodiazepines, anesthetics, and neurosteroids. s13041-017-0325-8
Claim in safety — inconclusiveinconclusiveworking →
Published case reports note that 2M2B users are frequently polysubstance-dependent individuals who combine the compound with other depressants, making these interactions clinically relevant rather than theoretical.supported
Popularity of TAA growing in Europe among alcohol/drug addicted people. Main reasons: self-healing of addiction, low price, and difficulty of detection in screening tests. j.forsciint.2014.07.020
Claim in safety — inconclusiveinconclusiveworking →
CYP2E1 inhibitors — including disulfiram and certain industrial solvents — may impair the cytochrome P450-dependent clearance of 2M2B, prolonging and intensifying intoxicationsupported
CYP2E1 induction (2-fold) and CYP2B1 induction (up to 260-fold) observed in TAME-treated rats. j.etap.2006.07.003
Respiratory insufficiency or compromised airway — 2M2B causes dose-dependent respiratory depression. Published cases document respiratory failure requiring intubation. Pre-existing respiratory compromise reduces the margin to fatal respiratory arrest.supported
A case of 28 year-old male found in deep coma complicated with acute respiratory failure due to recreational intoxication with tert-amyl alcohol. j.forsciint.2014.07.020
pharmacology10 · 8 ok
Chronic intermittent exposure in rodent models produces persistent subunit composition changes lasting months.supported
Chronic exposure leads to persistent changes in GABA-A receptor subunit composition lasting at least 120 days in rats. s13041-017-0325-8
Alcohols inhibit NMDA-activated ion current in hippocampal neurons in a concentration-dependent manner, and the potency for NMDA inhibition correlates linearly with intoxicating potency across a series of aliphatic alcoholssupported
Inhibition increased in a concentration-dependent manner (5-50 mM). The potency for inhibition of NMDA-activated current by several alcohols is linearly related to their intoxicating potency. pmid:2467382
The inhibition is non-competitive and voltage-independent; ethanol neither acts as a channel pore blocker nor competes with glutamate or glycine at their binding sitessupported
Ethanol inhibited NMDA-activated current in a voltage-independent manner. Ethanol decreased the maximal response to NMDA and glycine without affecting their EC50 values. Results consistent with ethanol inhibiting NMDA receptor function by a non-competitive mechanism. pmid:9401766
NMDA receptor selectivity over other ionotropic glutamate receptor subtypes (AMPA, kainate) is established for the alcohol class.supported
Ethanol is less effective in inhibiting ion current produced by non-NMDA glutamate receptors. pmid:1701093
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
CYP2E1 and CYP2B1 are the principal isoforms responsible for oxidationsupported
CYP2E1 induction (2-fold) and CYP2B1 induction (up to 260-fold) observed in TAME-treated rats. j.etap.2006.07.003
The major metabolites — 2-methyl-2,3-butanediol (free and glucuronide-conjugated), 2-hydroxy-2-methylbutyric acid, and 3-hydroxy-3-methylbutyric acid — are non-toxic relative to acetaldehyde, which accounts for the reduced hangover reported by users.supported
Major urinary metabolites: glucuronidated 2-methyl-2,3-butanediol, 2-hydroxy-2-methylbutyric acid, 3-hydroxy-3-methylbutyric acid. These reactions are mediated by cytochrome P450-dependent oxidations. tx990078x
Urinary metabolite elimination half-lives range from 6 to 40 hours in humans, substantially slower than in rats (under 6 hours)supported
Metabolite excretion in humans was slower than rats; elimination half-lives between 6 and 40 h in humans for TAA metabolites. pmid:10828258
Urinary metabolite elimination half-lives range from 6 to 40 hours in humans, substantially slower than in rats (under 6 hours)supported
Human metabolite elimination half-lives between 6 and 40 h. pmid:11504147
pharmacokinetic-detail9 · 6 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
The principal CYP isoforms implicated are CYP2E1 and CYP2B1, based on rat induction studies of the structurally related compound TAME, which produced 2-fold CYP2E1 induction and up to 260-fold CYP2B1 inductionsupported
CYP2E1 induction (2-fold) and CYP2B1 induction (up to 260-fold) observed in TAME-treated rats. j.etap.2006.07.003
The primary metabolites identified in human urine following TAME exposure are:partially supported
Biotransformation of tert-amyl alcohol studied in rats after gavage. Major urinary metabolites: glucuronidated 2-methyl-2,3-butanediol, 2-hydroxy-2-methylbutyric acid, 3-hydroxy-3-methylbutyric acid. tx990078x
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Urinary metabolite elimination half-lives in humans range from 6 to 40 hours — markedly slower than the under-6-hour half-lives observed in ratssupported
Metabolite excretion in humans was slower than rats; elimination half-lives between 6 and 40 h in humans for TAA metabolites. pmid:10828258
Urinary metabolite elimination half-lives in humans range from 6 to 40 hours — markedly slower than the under-6-hour half-lives observed in ratssupported
Human metabolite elimination half-lives between 6 and 40 h. pmid:11504147
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
2M2B is not detected by standard immunoassay urine drug screens or breath alcohol analyzers used in emergency, occupational, and forensic settingssupported
Main reasons: self-healing of addiction, low price, and difficulty of detection in screening tests. j.forsciint.2014.07.020
The glucuronide metabolite of tert-amyl alcohol may produce false-positive results on immunological ethyl glucuronide (EtG) screening, creating forensic interpretive complications.supported
False-positive immunological EtG screenings by excretion of different alcohol glucuronides. j.forsciint.2017.10.021
history6 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
The first published case report of acute 2M2B intoxication appeared in 2014, documenting a 28-year-old male found in deep coma with acute respiratory failure and a blood tert-amyl alcohol concentration of 83 μg/mLsupported
A case of 28 year-old male found in deep coma complicated with acute respiratory failure due to recreational intoxication with tert-amyl alcohol. Blood level 83 ug/mL by GC-MS. j.forsciint.2014.07.020
neuroscience6 · 2 ok
These adaptations produce a state of latent neural hyperexcitability that becomes manifest upon abrupt cessation — the neurobiological basis of withdrawal seizures, anxiety, tremor, and delirium tremens in the GABAergic withdrawal syndrome.supported
Describes spectrum of alcohol withdrawal from minor symptoms to delirium tremens. Benzodiazepines are the best-assessed drugs for preventing severe alcohol withdrawal including seizures. pmid:17323538
These adaptations produce a state of latent neural hyperexcitability that becomes manifest upon abrupt cessation — the neurobiological basis of withdrawal seizures, anxiety, tremor, and delirium tremens in the GABAergic withdrawal syndrome.supported
Spectrum of alcohol withdrawal from insomnia and tremulousness to seizures and delirium tremens. pmid:15053409
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
summary5 · 3 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
As a tertiary alcohol, 2M2B potentiates GABA-A receptor-mediated chloride conductance and inhibits NMDA receptor-activated currents — the same dual mechanism responsible for ethanol intoxication, but at substantially lower absolute dosessupported
The potency for inhibition of NMDA-activated current by several alcohols is linearly related to their intoxicating potency. pmid:2467382
Unlike ethanol, 2M2B cannot be oxidized by alcohol dehydrogenase, eliminating acetaldehyde production and the associated hangover syndrome; metabolism proceeds instead through cytochrome P450 oxidation.supported
These reactions are mediated by cytochrome P450-dependent oxidations. tx990078x
Respiratory depression is the primary life-threatening acute toxicity, with published cases requiring emergency intubationsupported
A case of 28 year-old male found in deep coma complicated with acute respiratory failure due to recreational intoxication with tert-amyl alcohol. j.forsciint.2014.07.020
clinical-evidence4 · 2 ok
This represents the earliest published case report of acute 2M2B intoxication and documented the growing European abuse trend in the context of addiction self-medication and toxicological detection evasion.supported
Popularity of TAA growing in Europe among alcohol/drug addicted people. Main reasons: self-healing of addiction, low price, and difficulty of detection in screening tests. j.forsciint.2014.07.020
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
The uniformly negative standard toxicology screen underscores the need for GC-MS confirmation when 2M2B ingestion is suspected.supported
Blood level 83 ug/mL by GC-MS... difficulty of detection in screening tests. j.forsciint.2014.07.020
receptor-pharmacology4 · 2 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Alcohols selectively inhibit NMDA-activated currents while sparing kainate- and quisqualate-activated currents in hippocampal neurons, with potency correlating to intoxicating dose across the alcohol seriessupported
Intoxicating concentrations of ethanol inhibit NMDA-activated ion current... Ethanol is less effective in inhibiting ion current produced by non-NMDA glutamate receptors. pmid:1701093
The mechanism is non-competitive, voltage-independent, and does not involve pore blockade or competition at glutamate or glycine binding sites.supported
Ethanol inhibited NMDA-activated current in a voltage-independent manner. Ethanol decreased the maximal response to NMDA and glycine without affecting their EC50 values. Results consistent with ethanol inhibiting NMDA receptor function by a non-competitive mechanism. pmid:9401766
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
comparative-pharmacology1 · 1 ok
The absence of acetaldehyde production — a direct consequence of the tertiary alcohol structure blocking ADH-mediated oxidation — accounts for both the reported lack of hangover and the absence of disulfiram-type aversive reactions.supported
Biotransformation of tert-amyl alcohol studied in rats after gavage. Major urinary metabolites: glucuronidated 2-methyl-2,3-butanediol, 2-hydroxy-2-methylbutyric acid, 3-hydroxy-3-methylbutyric acid. These reactions are mediated by cytochrome P450-dependent oxidations. tx990078x