generation run 2026-05-03
503 min completedmodel pipeline-v5plan not recordedrun/2459ce8c…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
Reproduce
- inputs
- 28 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
18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | OpenAlex | 2-fluorodeschloroketamine 2-FDCK dissociative | 11 | 5 | Direct 2-FDCK studies selected; peripherally related NPS papers noted |
| 2 | PubMed · absence | 2-fluorodeschloroketamine 2-FDCK fluoroketamine pharmacology | 0 | — | — |
| 3 | PubMed | deschloroketamine pharmacology NMDA dissociative new psychoactive substance | 1 | 1 | Direct mention of 2-fluoro-2-deschloroketamine in class review |
| 4 | ClinicalTrials.gov · absence | 2-fluorodeschloroketamine fluoroketamine 2-FDCK | 0 | — | — |
| 5 | PubChem | 2-Fluorodeschloroketamine | 1 | 1 | Primary chemical identity verification |
| 6 | PubMed · absence | 2-(2-fluorophenyl)-2-(methylamino)cyclohexanone NMDA dissociative | 0 | — | — |
| 7 | OpenAlex | 2-fluorodeschloroketamine ketamine analogue forensic toxicology detection NPS | 17 | 3 | Fatal intoxication case, NPS adverse events systematic context, WBE stability for 2-FDCK |
| 8 | PubMed · absence | 2-fluorodeschloroketamine ketamine reinforcing self-administration rats abuse potential | 0 | — | — |
| 9 | Web | 2-FDCK WHO 46th ECDD scheduling recommendation 2024 psychotropic convention | 9 | 2 | WHO and international scheduling documentation |
| 10 | ECDD Repository | — | 1 | 1 | Authoritative WHO source for pharmacology and scheduling rationale |
| 11 | Web | 2-fluorodeschloroketamine synthesis 1987 first appearance market 2016 2017 | 10 | 2 | Historical timeline of 2-FDCK development and market emergence |
| 12 | Web | 2-fluorodeschloroketamine legal status scheduling UK USA EU 2026 | 10 | 1 | Key legal status data for US, UK, EU, international |
| 13 | ClinicalTrials.gov · absence | 2-fluorodeschloroketamine fluoroketamine 2-FDCK | 0 | — | — |
| 14 | PubMed | ketamine dopamine reuptake inhibitor sigma-1 receptor pharmacology | 3 | 2 | Arylcyclohexylamine pharmacology (NMDA/DAT/sigma-1) for class-level inference; CYP review for metabolism analog |
| 15 | Multiple sources | Synthesis history and market emergence of 2-FDCK | 3 | 3 | Historical timeline compiled from multiple sources for discovery/emergence narrative |
| 16 | Multiple APIs | DOI verification for key 2-FDCK papers | 3 | 1 | DOI verification for api_verified status confirmation |
| 17 | Web | 2-FDCK stereoisomer enantiomer S R chirality potency | 10 | 0 | Stereochemistry gap confirmed |
| 18 | UNODC Substance Database | — | 1 | 1 | Authoritative international scheduling confirmation |
81 claims by section — every cited sentence, checked against its source
safety23 · 18 ok
In the largest clinical series (Tang et al. 2020, n = 20), all patients recovered with supportive management, suggesting that acute 2-FDCK intoxication at typical recreational doses is survivable with appropriate medical caresupported
20 cases of 2F-DCK exposure... All recovered. j.forsciint.2020.110327
Clinical presentations include impaired consciousness, agitation, abnormal behavior, nystagmus, hallucinations, tachycardia, and hypertension.supported
Clinical effects: neurological (impaired consciousness, agitation), cardiovascular (hypertension, tachycardia); 5 patients lost consciousness or had convulsions. j.forsciint.2020.110327
Gicquel et al. (2021) attributed death to respiratory depression in a case involving co-use of 2-FDCK and 3-meo-pcesupported
First fatal case involving 2F-DCK and 3-MeO-PCE... Death attributed primarily to respiratory depression from polydrug use. j.forsciint.2021.110852
Claim in safety — inconclusiveinconclusiveworking →
Tachycardia and hypertension are consistently documented across clinical case presentations and represent the primary acute cardiovascular risk.supported
cardiovascular (hypertension, tachycardia) j.forsciint.2020.110327
Chronic ketamine abuse is well-established to cause severe lower urinary tract symptoms, including ketamine cystitis — characterized by contracted bladder capacity, suprapubic pain, frequency, urgency, and hematuria — and in severe cases, irreversible bladder contracture and bilateral hydronephrosissupported
Clinical spectrum in young recreational ketamine abusers in Hong Kong with severe lower urinary tract symptoms but no bacterial infection. Documents ketamine cystitis as a new syndrome. j.1464-410x.2008.07920.x
Chronic ketamine abuse is well-established to cause severe lower urinary tract symptoms, including ketamine cystitis — characterized by contracted bladder capacity, suprapubic pain, frequency, urgency, and hematuria — and in severe cases, irreversible bladder contracture and bilateral hydronephrosissupported
Case report of severe bilateral hydronephrosis and bladder wall thickening in a young male ketamine abuser. westjem.2014.4.20571
Mechanistic work has implicated urothelial barrier disruption via downregulation of cell junction proteinssupported
patients with urinary tract symptoms had lower Nectin-4 levels, suggesting compromised urothelium barrier function. Chronic ketamine use produces bladder toxicity via urothelial barrier disruption. j.etap.2021.103714
Claim in safety — not_supportednot supportedworking →
Seized 2-FDCK samples have shown purity variability (67–96%) with trace deschloroketamine contamination (0.4–0.6%). 2-FDCK has also been identified as an adulterant in purported 3-mmc samples in a French drug-checking study.partially supported
2-FDCK detected as adulterant in samples supplied as methoxphenidine (MXP). s12954-023-00836-4
Acute psychological adverse effects documented in clinical presentations include agitation, abnormal behavior, hallucinations, and dissociative confusionsupported
neurological (impaired consciousness, agitation) j.forsciint.2020.110327
One case of self-mutilation during 2-FDCK intoxication has been documented.supported
Title: '2-Fluorodeschloroketamine consumption: About two deaths and a case of self-mutilation' bkae021
Cross-tolerance with other NMDA antagonists — including Ketamine, Deschloroketamine, and methoxetamine — is expected by shared mechanism and supported by drug discrimination data demonstrating full generalization between 2-FDCK and ketamine.supported
Drug discrimination: 2-FDCK dose-dependently substituted for ketamine with comparable ED50. adb.13171
Claim in safety — inconclusiveinconclusiveworking →
Li et al. (2022) demonstrated CPP, locomotor sensitization, self-administration, and drug discrimination all at doses comparable to ketaminesupported
2-FDCK induced CPP at minimum 3 mg/kg (mice), comparable to ketamine. Acute 30 mg/kg enhanced locomotor activity; repeated doses induced locomotor sensitization. Self-administration at 0.5 mg/kg/infusion (same as ketamine). Drug discrimination: 2-FDCK dose-dependently substituted for ketamine with comparable ED50. adb.13171
Du et al. (2022) showed similar reinforcing efficacy via behavioral economics demand curves, with drug-seeking reinstatement by both conditioned cues and drug priming, accompanied by bdnf and p-CREB downregulation in nucleus-accumbens and Akt/mTOR/GSK-3β upregulation.supported
Demand curve elasticity (α) and essential value similar between 2F-DCK and ketamine groups. Both showed cue- and drug-primed reinstatement. BDNF and p-CREB downregulated in nucleus accumbens. Akt/mTOR/GSK-3β signaling upregulated in reinstated rats. fnmol.2022.972798
By analogy to ketamine, withdrawal is expected to be primarily psychological — anxiety, irritability, sleep disturbance, cravings — without a prominent somatic withdrawal syndrome or seizure risk.supported
Withdrawal symptoms: sleep disorders and anxiety (no somatic withdrawal). pmid:20214100
The documented fatality reported by Gicquel et al. (2021) involved co-use with 3-MeO-PCE and was attributed to respiratory depressionsupported
First fatal case involving 2F-DCK and 3-MeO-PCE. Death attributed primarily to respiratory depression from polydrug use. j.forsciint.2021.110852
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Cardiovascular disease and hypertension are contraindicated due to the documented acute sympathomimetic effects (tachycardia, hypertension) observed across clinical case presentations.supported
cardiovascular (hypertension, tachycardia) j.forsciint.2020.110327
Pre-existing urological conditions are relatively contraindicated given the documented bladder toxicity of the structurally related ketamine.supported
Documents ketamine cystitis as a new syndrome. j.1464-410x.2008.07920.x
Respiratory compromise is contraindicated, as fatal outcomes in polydrug contexts involved respiratory depression.supported
Death attributed primarily to respiratory depression from polydrug use. j.forsciint.2021.110852
pharmacology17 · 11 ok
By analogy to ketamine, N-demethylation to nor-2F-DCK is predicted to involve cyp3a4, CYP2B6, and CYP2C9 as the primary metabolizing enzymessupported
N-demethylation by CYP3A4, CYP2B6, CYP2C9 to norketamine. j.neuropharm.2021.108936
Claim in pharmacology — inconclusiveinconclusiveworking →
Drug discrimination testing provides the most direct pharmacological evidence: 2-FDCK dose-dependently substituted for ketamine in trained rats with a comparable ED₅₀, consistent with shared nmda-receptor-mediated interoceptive effects.supported
Drug discrimination: 2-FDCK dose-dependently substituted for ketamine with comparable ED50. adb.13171
Arylcyclohexylamine class compounds, including ketamine and methoxetamine, inhibit dopamine reuptake via the dopamine-transporter (DAT), a shared class property contributing to their stimulant and reinforcing qualities.supported
Methoxetamine pharmacodynamics review. Acts as NMDA receptor antagonist, dopamine reuptake inhibitor... j.mehy.2012.07.002
Claim in pharmacology — inconclusiveinconclusiveworking →
Ketamine binds sigma-1-receptor and sigma-2 receptors at micromolar affinitiessupported
Ketamine bound to sigma-1 and sigma-2 receptors with µM affinities. j.euroneuro.2011.08.002
Davidsen et al. (2020) performed in vitro–in vivo extrapolation (IVIVE) comparing hepatic clearance across ketamine analogues, establishing the ranking: ketamine > norketamine ≈ 2-FDCK > methoxetamine > deschloroketaminepartially supported
DCK IVIVE hepatic clearance was disregarded due to low drug elimination under experimental conditions. j.jpba.2019.113049
The unbound fraction (f_u) across the ketamine analogue series ranged from 0.54 to 0.84; the specific value for 2-FDCK falls within this range but was not individually reported.partially supported
DCK had lowest protein binding (fu 0.54-0.84) j.jpba.2019.113049
Shao et al. (2021) predicted a renal clearance excretion factor of 3.7 for 2-FDCK using a quantitative structure–pharmacokinetic relationship (QSPKR) model.supported
Renal excretion factor 3.7 predicted by QSPKR model. dta.3098
Ketamine has oral bioavailability of approximately 17–29% due to extensive CYP-mediated first-pass effectsupported
Oral bioavailability 17-29% due to first-pass. j.neuropharm.2021.108936
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
This inference is supported by the prominence of nor-2F-DCK as the primary detected metabolite across all published human studies.supported
Nor-2F-DCK (208.1137 m/z) and hydrogenated metabolite (224.1443 m/z) proposed as reliable HRMS library targets. dta.3162
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Luo et al. (2023) characterized the full set of oxidative metabolites via LC-IT-TOF-MS in human urine, identifying 17 compounds across 4 oxidative groups and characterizing stereoselectivity of carbonyl reductionsupported
LC-IT-TOF-MS analysis of 2-FDCK metabolites in human urine. 17 oxidative metabolites identified in 4 groups. Enantiomers of dihydro-2-FDCK characterized. Stereoselectivity of hydrogenation enzymes clarified. bkad021
Gicquel et al. (2022) used molecular networking across HLM and HepaRG cell models, identifying 13 in vitro metabolites and 7 additional metabolites in post-mortem samples, and proposed nor-2F-DCK (208.1137 m/z) and dihydro-2F-DCK (224.1443 m/z) as primary HRMS library targets for forensic detection.supported
13 metabolites of 2F-DCK produced in vitro (HLMs and HepaRG cells). 7 additional metabolites in post-mortem samples (bile, urine). Nor-2F-DCK (208.1137 m/z) and hydrogenated metabolite (224.1443 m/z) proposed as reliable HRMS library targets. dta.3162
summary8 · 4 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Drug discrimination studies confirm that 2-FDCK dose-dependently substitutes for ketamine in trained rodents with a comparable ED₅₀, consistent with a shared nmda-receptor-mediated mechanismsupported
Drug discrimination: 2-FDCK dose-dependently substituted for ketamine with comparable ED50. adb.13171
Claim in summary — inconclusiveinconclusiveworking →
Fatal outcomes have occurred exclusively in polydrug contextssupported
Death attributed primarily to respiratory depression from polydrug use. j.forsciint.2021.110852
Preclinical self-administration and conditioned place preference studies demonstrate abuse-liability comparable to ketamine, and clinical dependence with chronic daily use has been documented. tolerance develops with repeated use and cross-tolerance with other NMDA antagonists is expected, though the specific rate of tolerance acquisition and reset in humans has not been pharmacologically characterizedsupported
2-FDCK induced CPP at minimum 3 mg/kg (mice), comparable to ketamine. Self-administration at 0.5 mg/kg/infusion (same as ketamine). adb.13171
Preclinical self-administration and conditioned place preference studies demonstrate abuse-liability comparable to ketamine, and clinical dependence with chronic daily use has been documented. tolerance develops with repeated use and cross-tolerance with other NMDA antagonists is expected, though the specific rate of tolerance acquisition and reset in humans has not been pharmacologically characterizedsupported
Demand curve elasticity (α) and essential value similar between 2F-DCK and ketamine groups. fnmol.2022.972798
Claim in summary — inconclusiveinconclusiveworking →
pharmacokinetic-detail7 · 2 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Gicquel et al. (2022) proposed nor-2F-DCK (exact mass 208.1137) and dihydro-2F-DCK (exact mass 224.1443) as the primary forensic detection targets for HRMS libraries.supported
Nor-2F-DCK (208.1137 m/z) and hydrogenated metabolite (224.1443 m/z) proposed as reliable HRMS library targets. dta.3162
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Confirmatory analysis requires LC-MS/MS or LC-HRMS.supported
Nor-2F-DCK (208.1137 m/z) and hydrogenated metabolite (224.1443 m/z) proposed as reliable HRMS library targets. dta.3162
chemistry6 · 1 ok
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Luo et al. (2023) characterized the two enantiomers of dihydro-2-FDCK (the hydrogenated metabolite), demonstrating stereoselectivity of the carbonyl reductase enzymes involved in metabolism.supported
Enantiomers of dihydro-2-FDCK characterized. Stereoselectivity of hydrogenation enzymes clarified. bkad021
Claim in chemistry — not_supportednot supportedworking →
clinical-evidence6 · 6 ok
Li et al. (2022) demonstrated that 2-FDCK produced conditioned place preference (CPP) at 3 mg/kg in mice (comparable to ketamine at the same dose), locomotor sensitization with repeated 30 mg/kg dosing, intravenous self-administration at 0.5 mg/kg/infusion, and dose-dependent substitution for ketamine in drug discrimination.supported
2-FDCK induced CPP at minimum 3 mg/kg (mice), comparable to ketamine. Acute 30 mg/kg enhanced locomotor activity; repeated doses induced locomotor sensitization. Self-administration at 0.5 mg/kg/infusion (same as ketamine). Drug discrimination: 2-FDCK dose-dependently substituted for ketamine with comparable ED50. adb.13171
Holborn et al. (2025) documented 2-FDCK use for self-medication of depression and anxiety in an online survey (n = 274), indicating awareness of its ketamine-like antidepressant properties among some user communitiessupported
Online survey (n=274, mean age 29.8, 71% male) on NPS self-medication of depression and anxiety. NPS used included 2-FDCK. psychoactives4030028
Tang et al. (2020) reported on 20 patients presenting to emergency departments in Hong Kong between January and July 2019 with confirmed 2-FDCK exposuresupported
20 cases of 2F-DCK exposure. j.forsciint.2020.110327
Domanski et al. (2022) described a case of 2-FDCK intoxication in the United States — a self-described psychonaut with multi-class drug exposure who presented with dissociation and recovered with supportive caresupported
2-Fluorodeschloroketamine (2-FDCK) is a ketamine derivative... We report the case of a patient with a history of polysubstance use presenting after insufflation of 2-FDCK... A 28-year-old man presented to the Emergency Department in a dissociated state. He recovered well with supportive care. 02791072.2021.2006373
Death was attributed to respiratory depression in a polydrug context.supported
Death attributed primarily to respiratory depression from polydrug use. j.forsciint.2021.110852
Riess et al. (2024) reported three forensic cases: one self-mutilation and two deathssupported
Title: '2-Fluorodeschloroketamine consumption: About two deaths and a case of self-mutilation' bkae021
history6 · 3 ok
Luo et al. (2022) later identified 1-[(2'-fluorophenyl)(methylimino)methyl]cyclopentan-1-ol (2-fluorodeschlorohydroxylimine) as the suspected clandestine synthesis precursor, analogous to the hydroxylimine intermediate used in illicit ketamine production.supported
2-fluorodeschlorohydroxylimine identified as suspected chemical precursor of 2-FDCK. dta.3229
Claim in history — inconclusiveinconclusiveworking →
Wastewater-based epidemiology first detected 2-FDCK in Guangzhou, China, in 2018, confirming recreational consumption at a population levelsupported
First WBE detection of 2F-DCK in Chinese wastewater... Detected in Guangzhou (2018). dta.3098
The first clinical case series — 20 patients presenting to emergency departments in Hong Kong between January and July 2019 — was reported by Tang et al. (2020)supported
20 cases of 2F-DCK exposure; DCK co-detected in 50% of cases. All recovered. j.forsciint.2020.110327
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
comparative-pharmacology4 · 2 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
In the IVIVE clearance ranking, DCK had the lowest hepatic clearance of the series — consistent with its reported longer duration of action relative to both ketamine and 2-FDCKsupported
DCK IVIVE hepatic clearance was disregarded due to low drug elimination under experimental conditions. j.jpba.2019.113049
DCK is also a confirmed metabolite of 2-FDCK, complicating forensic differentiation between the two compounds.supported
DCK identified as metabolite. bkad030
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
receptor-pharmacology3 · 1 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Li et al. (2022) trained rats to discriminate ketamine from saline and found that 2-FDCK produced dose-dependent full substitution with a comparable ED₅₀, indicating that the two compounds generate overlapping interoceptive stimulus profiles — a hallmark of shared receptor mechanism.supported
Drug discrimination: 2-FDCK dose-dependently substituted for ketamine with comparable ED50. adb.13171
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
neuroscience1 · 1 ok
Du et al. (2022) provide the only direct neuromolecular data for 2-FDCK, reporting downregulation of BDNF and phosphorylated CREB (p-CREB) in the nucleus-accumbens of rats following 2-FDCK self-administration and extinction, with upregulation of the Akt/mTOR/GSK-3β signaling pathway in rats that reinstated drug-seeking behaviorsupported
BDNF and p-CREB downregulated in nucleus accumbens. Akt/mTOR/GSK-3β signaling upregulated in reinstated rats. fnmol.2022.972798