generation run 2026-05-11
79 min completedmodel pipeline-v5plan not recordedrun/a1a98f4c…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
- safety_data_unverified
Reproduce
- inputs
- 30 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
13 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov · absence | 5F-AKB48 synthetic cannabinoid | 0 | — | No trials exist - expected for a Schedule I substance |
| 2 | OpenAlex | 5F-AKB48 APINACA synthetic cannabinoid forensic detection metabolism | 34 | 3 | Forensic detection and toxicity papers with confirmed 5F-AKB48 analytical data |
| 3 | PubMed | 5F-APINACA AKB48 CB1 CB2 binding affinity receptor | 1 | 1 | Key pharmacology paper |
| 4 | OpenAlex | 5F-AKB48 synthetic cannabinoid | 176 | 5 | High citation count pharmacology, toxicology and forensic detection papers |
| 5 | PubMed | 5F-AKB48 synthetic cannabinoid pharmacology | 10 | 7 | All directly relevant to 5F-AKB48 pharmacology, toxicology, or legal status |
| 6 | PubChem | 5F-AKB48 | 1 | 1 | Primary compound identity verification |
| 7 | WHO ECDD Information Repository | — | 1 | 4 | Authoritative pharmacological and safety data from WHO review |
| 8 | PubMed | APINACA UR-144 5F-APINACA impaired driving blood concentration | 1 | 1 | Blood concentration data for forensic and pharmacokinetic context |
| 9 | WebSearch | 5F-AKB48 5F-APINACA legal status UK Psychoactive Substances Act scheduling EU controlled | 10 | 3 | Legal status across jurisdictions |
| 10 | WebSearch | AKB48 APINACA first synthesis Pfizer patent 2009 2010 adamantyl indazole cannabinoid history | 10 | 3 | Discovery history |
| 11 | PubMed | AKB-48 metabolism hepatocytes first characterization synthetic cannabinoid | 1 | 1 | Historical/discovery context and metabolic baseline for parent compound |
| 12 | WebSearch | DEA 5F-APINACA 5F-AKB48 final rule Schedule I permanent scheduling date | 10 | 1 | US regulatory history |
| 13 | PubChem REST API | CID 71711119 SMILES | 1 | 1 | Chemical identity verification |
92 claims by section — every cited sentence, checked against its source
safety29 · 25 ok
The most comprehensive clinical case data originates from the Serbian National Poison Control Centre, where 58 patients presented with acute intoxication from products analytically confirmed to contain 5F-AKB48 and other SCRAssupported
58 patients treated for SC overdose in Serbia 2013-2016. 5F-AKB48 detected in herbal products. aiht-2018-69-3096
All patients recovered within 8 hours with symptomatic and supportive care.supported
All recovered within 8 hours. aiht-2018-69-3096
A 2025 study from the French Poison Control Centers describes 5F-AKB48 as an emerging public health concern in France, documenting the largest dedicated epidemiological case series for this compoundsupported
This study aimed to describe the sociodemographic and clinical characteristics of 5F-AKB48 exposures reported to French Poison Control Centers (PCCs). j.drugpo.2025.104972
Analytically confirmed acute toxicity from 5F-derivative SCRAs, including 5F-AKB48, has been reported in a United Kingdom case series.supported
Case series of acute toxicity with analytically confirmed 5F-derivative SCRAs including 5F-AKB48. pmid:27456262
5F-AKB48 inhibits the hERG potassium channel with an IC50 of 2.16 μM, creating a mechanistically documented risk of QT interval prolongation and potentially fatal cardiac arrhythmiasupported
5F-AKB48 inhibited wild-type hERG current (I_hERG) with an IC50 of 2.16 µM via a noncanonical binding site distinct from S6 aromatic residues. j.bcp.2025.117257
Claim in safety — inconclusiveinconclusiveworking →
Co-application with the antipsychotic olanzapine produces additive hERG inhibition — a critical drug interaction given that antipsychotics may be administered clinically to manage SCRA-induced agitation.supported
Additive inhibition recorded with co-application of olanzapine. j.bcp.2025.117257
At the class level, SCRAs are associated with profound hypotension, bradycardia, ischemic stroke, and embolic events.partially supported
Major complications: cardiovascular events, acute kidney injury, seizures, psychiatric presentations. Most presentations: tachycardia (37-77%), agitation (16-41%). 15563650.2015.1110590
The synthetic cannabinoid class is strongly associated with acute kidney injury (AKI), including rhabdomyolysis-induced acute renal failuresupported
First case of synthetic cannabinoid hyperemesis leading to rhabdomyolysis and acute renal failure. j.ajem.2015.08.051
Multiple organ failure involving hepatic, renal, and cardiovascular systems has been documented with SCRA usesupported
Multicenter descriptive case series of 6 patients with synthetic cannabinoid intoxication resulting in multiple organ failure. phar.2241
Driving impairment is an established concern; 5F-APINACA has been detected in blood samples from DUID cases.supported
In DUID cases: 5F-APINACA 0.24-6.5 μg/L whole blood. j.forsciint.2014.11.012
Acute psychosis, delusions, paranoia, anxiety, and confusion are commonly reported at higher doses of 5F-AKB48 and related SCRAspartially supported
Clinical signs: tachycardia (91%), mydriasis (53%), somnolence/nausea/vomiting/agitation (28%), dizziness (17%), disorientation (16%). aiht-2018-69-3096
Acute psychosis, delusions, paranoia, anxiety, and confusion are commonly reported at higher doses of 5F-AKB48 and related SCRAssupported
Major complications: cardiovascular events, acute kidney injury, seizures, psychiatric presentations. 15563650.2015.1110590
Acute psychosis, delusions, paranoia, anxiety, and confusion are commonly reported at higher doses of 5F-AKB48 and related SCRAssupported
Most common toxicities: tachycardia, agitation, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, chest pain. maj.0000000000000466
Claim in safety — inconclusiveinconclusiveworking →
Users escalating dose in pursuit of stronger euphoric effects cross this threshold unpredictably, particularly given the extreme variability in SCRA concentrations within herbal products (documented at 0.05–1.17 mg/cm² across samples; 0.47–2.38 mg/cm² variability within a single seized paper).partially supported
SCRA concentrations 0.05-1.17 mg/cm2. Market evolution documented. dta.2767
Claim in safety — not_supportednot supportedworking →
Synthetic cannabinoids can substitute for cannabis in users experiencing cannabis withdrawal syndrome, indicating overlapping but not identical dependence mechanismssupported
SC use effectively alleviated cannabis withdrawal. j.1521-0391.2012.00240.x
Claim in safety — inconclusiveinconclusiveworking →
Both the WHO ECDD and the US DEA have recognized a high potential for abuse as a basis for scheduling, with the DEA citing 5F-APINACA as posing an "imminent hazard to public safety".supported
DEA notice of intent to temporarily schedule 5F-APINACA (5F-AKB48) as Schedule I under the Controlled Substances Act, citing imminent hazard to public safety. pmid:28068047
Both the WHO ECDD and the US DEA have recognized a high potential for abuse as a basis for scheduling, with the DEA citing 5F-APINACA as posing an "imminent hazard to public safety".supported
DEA notice of intent to temporarily schedule 5F-APINACA (5F-AKB48) as Schedule I under the Controlled Substances Act, citing imminent hazard to public safety. pmid:28068047
The most significant documented interaction involves hERG potassium channel inhibition. 5F-AKB48 (IC50 = 2.16 μM) produces additive hERG blockade when combined with olanzapinesupported
5F-AKB48 inhibited wild-type hERG current (I_hERG) with an IC50 of 2.16 µM via a noncanonical binding site. Additive inhibition recorded with co-application of olanzapine. j.bcp.2025.117257
Since CYP3A4 is the dominant metabolic enzyme for 5F-AKB48, pharmacokinetic interactions with CYP3A4 modulators are predicted:supported
CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans. metabo12080773
In mouse models, pre-treatment with the CB1 antagonist rimonabant attenuates the effects of 5F-AKB48supported
5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC; attenuated by rimonabant. j.pbb.2020.172949
Cardiac conditions: Pre-existing cardiac conduction abnormalities, long QT syndrome (congenital or acquired), or concurrent use of QT-prolonging medications represent absolute contraindications given the documented hERG channel inhibition (IC50 = 2.16 μM)supported
5F-AKB48 inhibited wild-type hERG current (I_hERG) with an IC50 of 2.16 µM via a noncanonical binding site distinct from S6 aromatic residues. j.bcp.2025.117257
Renal impairment: The SCRA class association with acute kidney injury and rhabdomyolysis makes pre-existing renal disease a relative contraindication; reduced clearance could additionally prolong exposure.supported
First case of synthetic cannabinoid hyperemesis leading to rhabdomyolysis and acute renal failure. j.ajem.2015.08.051
Renal impairment: The SCRA class association with acute kidney injury and rhabdomyolysis makes pre-existing renal disease a relative contraindication; reduced clearance could additionally prolong exposure.supported
Multicenter descriptive case series of 6 patients with synthetic cannabinoid intoxication resulting in multiple organ failure. phar.2241
Psychiatric vulnerability: Pre-existing psychotic disorders, history of first-episode psychosis, or family history of psychotic illness represent relative contraindications, given the documented capacity of SCRAs to precipitate acute psychosis and paranoid states.supported
Major complications: cardiovascular events, acute kidney injury, seizures, psychiatric presentations. 15563650.2015.1110590
Hepatic impairment: CYP3A4-dependent metabolism means significant hepatic dysfunction could impair clearance, elevating plasma concentrations and prolonging pharmacological effects.supported
CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans. metabo12080773
pharmacology21 · 15 ok
Metabolism: CYP3A4 is the dominant Phase I enzyme in humans, with minor contributions from CYP2C8, CYP2C19, and CYP2D6supported
CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans with minor contributions from CYP2C8, 2C19, 2D6. metabo12080773
Claim in pharmacology — inconclusiveinconclusiveworking →
Unlike Δ9-THC, which acts as a partial agonist at CB1, 5F-AKB48 achieves full receptor activation — a pharmacological distinction that accounts for its greater maximum efficacy and narrower safety margin.supported
SCBs are direct agonists vs THC partial agonist. maj.0000000000000466
Claim in pharmacology — inconclusiveinconclusiveworking →
The CB1-to-CB2 selectivity ratio for APINACA is approximately 2:1supported
AKB-48 has twice the CB1 receptor binding affinity than CB2. s12248-013-9516-0
In vivo, 5F-AKB48 produces dose-dependent cannabimimetic effects in CD-1 mice — hypothermia, antinociception, catalepsy, and hypolocomotion (the cannabinoid tetrad) — that are more potent but shorter in duration than those of Δ9-THCsupported
5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC. j.pbb.2020.172949
In vivo, 5F-AKB48 produces dose-dependent cannabimimetic effects in CD-1 mice — hypothermia, antinociception, catalepsy, and hypolocomotion (the cannabinoid tetrad) — that are more potent but shorter in duration than those of Δ9-THCsupported
AKB48 and 5F-AKB48: novel synthetic cannabinoids with indazole core. In vitro and in vivo pharmacological characterization including tetrad responses, sensorimotor, neurological and neurochemical responses in mice. pmid:27527584
Pre-treatment with the selective CB1 antagonist rimonabant attenuates these effects, confirming a CB1-mediated mechanism.supported
5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC; attenuated by rimonabant. j.pbb.2020.172949
The primary Phase I metabolite, 4OH-5F-AKB48, retains high CB1 affinity and demonstrates greater efficacy for G-protein activation than Δ9-THCsupported
Metabolite 4OH-5F-AKB48 retains high CB1 affinity and greater efficacy for G protein activation than THC. j.pbb.2020.172949
Claim in pharmacology — not_supportednot supportedworking →
In driving-under-the-influence-of-drugs (DUID) cases, whole blood concentrations of 0.24–6.5 μg/L have been reported — the first published blood concentrations for 5F-APINACAsupported
First reported blood concentrations for APINACA and 5F-APINACA. In DUID cases: 5F-APINACA 0.24-6.5 μg/L whole blood. j.forsciint.2014.11.012
Adamantyl hydroxylation (primary, dominant): Sequential mono-, di-, and trihydroxylation of the adamantane ring system, carrying approximately 17-fold higher metabolic flux than defluorination.supported
Kinetic analysis of 5F-APINACA metabolism in human liver microsomes: highly efficient mono- and dihydroxylation of adamantyl group; oxidative defluorination 17-fold less efficient. molecules25204820
Oxidative defluorination (secondary): Removal of the terminal fluorine from the N-pentyl chain, producing multiple secondary metabolites.supported
Oxidative defluorination 17-fold less efficient. Eight metabolites identified. molecules25204820
Claim in pharmacology — inconclusiveinconclusiveworking →
CYP2D6, CYP2J2, CYP3A4, and CYP3A5 contribute to mono- and dihydroxylated metabolite production; CYP3A4 and CYP3A5 additionally generate trihydroxylated metabolitessupported
CYP2D6, CYP2J2, CYP3A4, CYP3A5 most active. j.pbb.2020.172949
Phase II glucuronide conjugation occurs on mono- and dihydroxylated metabolites.supported
17 novel phase I and II AKB-48 metabolites identified from hepatocytes: monohydroxylation, dihydroxylation, trihydroxylation on adamantane ring or N-pentyl side chain; glucuronide conjugation. s12248-013-9516-0
Metabolite identification: A total of 37 distinct metabolites were identified from human liver microsome (HLM) incubationssupported
41 metabolites of AKB-48 and 37 metabolites of 5F-AKB-48 identified in HLM incubations. bkv045
In authentic human urine samples, defluorinated metabolites account for approximately 74% of the combined chromatographic areasupported
Defluorinated metabolites accounted for ~74% of combined area after 5F-AKB-48 intake. bkv045
Claim in pharmacology — inconclusiveinconclusiveworking →
Validated detection methods include UHPLC-QTOF-MS.supported
Developed sensitive UHPLC-QTOF-MS method for 18 synthetic cannabinoid metabolites including 5F-AKB48. Validated method confirmed hydroxylated metabolite of 5F-AKB48 in ~2.3% of 1000 urine samples. dta.2464
Claim in pharmacology — inconclusiveinconclusiveworking →
summary9 · 5 ok
Administered primarily by inhalation, its effects are more intense but shorter-lived than those of Δ9-THC, with a total smoked duration of approximately 30–60 minutes.partially supported
5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC; attenuated by rimonabant. j.pbb.2020.172949
Claim in summary — inconclusiveinconclusiveworking →
The parent compound APINACA appeared in illicit "herbal incense" products in 2012; the fluorinated analogue followed after scheduling of the parent, first identified in South Koreapartially supported
AKB-48 (APINACA) first identified in Japanese herbal smoking blends. 443 NFLIS reports in USA from March 2010 to January 2013. DEA listed AKB-48 as Schedule I in May 2013. s12248-013-9516-0
Claim in summary — inconclusiveinconclusiveworking →
The parent compound APINACA binds CB1 with a Ki of approximately 3.24 nM — roughly 8-fold greater affinity than Δ9-THC — with a CB1-to-CB2 selectivity ratio of approximately 2:1partially supported
AKB-48 has twice the CB1 receptor binding affinity than CB2. s12248-013-9516-0
Claim in summary — inconclusiveinconclusiveworking →
The primary Phase I metabolite 4OH-5F-AKB48 retains CB1 affinity with greater G-protein efficacy than THC, contributing independently to the pharmacological and toxicological profile.supported
Metabolite 4OH-5F-AKB48 retains high CB1 affinity and greater efficacy for G protein activation than THC. j.pbb.2020.172949
Claim in summary — inconclusiveinconclusiveworking →
No LD50 data exist for any species. 5F-AKB48 inhibits hERG potassium channels (IC50 = 2.16 μM), creating mechanistically documented risk of QT prolongation and potentially fatal arrhythmia that is additive with the antipsychotic olanzapinesupported
5F-AKB48 inhibited wild-type hERG current (I_hERG) with an IC50 of 2.16 µM via a noncanonical binding site distinct from S6 aromatic residues. Additive inhibition recorded with co-application of olanzapine. j.bcp.2025.117257
clinical-evidence6 · 6 ok
Analytically confirmed acute toxicity from 5F-derivative SCRAs, including 5F-AKB48, has been reported in a United Kingdom case series.supported
Case series of acute toxicity with analytically confirmed 5F-derivative SCRAs including 5F-AKB48. Characterizes harms with confirmed analytical identification. pmid:27456262
The most comprehensive published case series originates from the Serbian National Poison Control Centre, where 58 patients presented with acute intoxication from products analytically confirmed to contain 5F-AKB48 and other SCRAssupported
58 patients treated for SC overdose in Serbia 2013-2016. 5F-AKB48 detected in herbal products. aiht-2018-69-3096
The first dedicated epidemiological study of 5F-AKB48 was published by Harmel et al. in 2025, describing the compound as an emerging public health concern in France with documentation of sociodemographic and clinical characteristics through the French Poison Control Center networksupported
This study aimed to describe the sociodemographic and clinical characteristics of 5F-AKB48 exposures reported to French Poison Control Centers (PCCs). j.drugpo.2025.104972
Pinson et al. (2020) extended these findings by characterizing the active metabolite 4OH-5F-AKB48, establishing that metabolites independently contribute to pharmacological activity and demonstrating CB1-mediated mechanism via rimonabant attenuation.supported
Metabolite 4OH-5F-AKB48 retains high CB1 affinity and greater efficacy for G protein activation than THC. 5F-AKB48 produces… effects in mice… attenuated by rimonabant. j.pbb.2020.172949
Clinical management is symptomatic and supportive: most acute presentations resolve within 8 hours with intravenous fluids and monitoringsupported
Typically resolve within 8 hours with supportive care. 15563650.2015.1110590
Benzodiazepines are first-line for agitation and tachycardia; antipsychotics (haloperidol, quetiapine) may be used for severe agitation or psychosis, though caution is warranted given the documented additive hERG inhibition with olanzapinesupported
Additive inhibition recorded with co-application of olanzapine. j.bcp.2025.117257
pharmacokinetic-detail6 · 5 ok
CYP3A4 is the dominant enzyme for 5F-AKB48 metabolism in humans, responsible for both the primary adamantyl hydroxylation and secondary oxidative defluorination pathwayssupported
CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans. metabo12080773
Additional contributing enzymes include CYP2C8, CYP2C19, CYP2D6, CYP2J2, and CYP3A5.partially supported
CYP2D6, CYP2J2, CYP3A4, CYP3A5 most active. j.pbb.2020.172949
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
In authentic urinary case samples, defluorinated metabolites constitute approximately 74% of the combined chromatographic peak area, despite defluorination being the less efficient pathway — reflecting preferential renal excretion of these more polar metabolites.supported
Defluorinated metabolites accounted for ~74% of combined area after 5F-AKB-48 intake. bkv045
Validated analytical methods include UHPLC-QTOF-MS and LC-HRMSsupported
Developed sensitive UHPLC-QTOF-MS method for 18 synthetic cannabinoid metabolites including 5F-AKB48. dta.2464
The first published whole blood concentrations for 5F-APINACA derive from Norwegian DUID cases: 0.24–6.5 μg/Lsupported
First reported blood concentrations for APINACA and 5F-APINACA. In DUID cases: 5F-APINACA 0.24-6.5 μg/L whole blood. j.forsciint.2014.11.012
history5 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
The United States DEA placed the parent compound AKB48 into Schedule I via emergency scheduling in May 2013, with permanent scheduling finalized in 2016. 5F-APINACA was temporarily placed in Schedule I in December 2016, with the temporary order extended in April 2019.partially supported
Final DEA rule permanently scheduling AKB48 (APINACA) as Schedule I under the Controlled Substances Act. pmid:27192731
Claim in history — inconclusiveinconclusiveworking →
receptor-pharmacology5 · 4 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The broader APINACA compound series exhibits low nanomolar to subnanomolar CB1 affinities, though specific Ki and EC50 data for the fluorinated 5F-AKB48 were not extractable from accessible literature.supported
Most compounds are potent full agonists with low nanomolar to subnanomolar affinity. s11419-016-0320-2
5F-AKB48 functions as a full agonist at CB1, achieving maximal receptor activation — in contrast to Δ9-THC, which produces submaximal (partial agonist) responsessupported
SCBs are direct agonists vs THC partial agonist. maj.0000000000000466
The parent AKB48 class acts as a moderate antagonist at GPR55, a non-canonical cannabinoid-related receptor; no interaction with GPR18 was detectedsupported
Some are moderate GPR55 antagonists. s11419-016-0320-2
5F-AKB48 inhibits the human ether-a-go-go-related gene (hERG) potassium channel with an IC50 of 2.16 μM in whole-cell patch-clamp experiments on HEK293 cellssupported
5F-AKB48 inhibited wild-type hERG current (I_hERG) with an IC50 of 2.16 µM via a noncanonical binding site distinct from S6 aromatic residues. j.bcp.2025.117257
comparative-pharmacology4 · 3 ok
THC functions as a partial agonist, producing submaximal receptor activation with an inherent ceiling on efficacy. 5F-AKB48 achieves full receptor activation, translating to greater maximum pharmacological and toxicological effects.supported
SCBs are direct agonists vs THC partial agonist. maj.0000000000000466
Clinically, SCRA presentations to emergency departments are significantly more severe than cannabis exposures, with higher rates of tachycardia, agitation, psychosis, organ failure, and requirement for intensive care.supported
Major complications: cardiovascular events, acute kidney injury, seizures, psychiatric presentations. Most presentations: tachycardia (37-77%), agitation (16-41%), nausea (13-94%). Typically resolve within 8 hours with supportive care. 15563650.2015.1110590
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
The fluorine substitution also alters the metabolic pathway balance, influencing the relative contribution of adamantyl hydroxylation versus defluorination products.supported
Kinetic analysis: highly efficient mono- and dihydroxylation of adamantyl group; oxidative defluorination 17-fold less efficient. Describes competing and intersecting metabolic pathways. molecules25204820
neuroscience4 · 0 ok
chemistry2 · 0 ok
effects-overview1 · 1 ok
The primary route-dependent consideration is dosing precision: SCRA concentrations in infused herbal products vary by orders of magnitude between and within samples, making consistent self-titration essentially impossible.supported
SCRA concentrations 0.05-1.17 mg/cm2. Market evolution documented. dta.2767