5F-AKB48

Sources

9 strong · 12 moderate · 9 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked

57verified8partial22inconclusive5not supported

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Generated

May 11, 2026 · pipeline-v5

Values approved

114/114 (100%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Dosing

smokedtrace

Field	Published	AI Proposed	Confidence
Threshold	0.5 mg	0.5 mg	low
Low	0.5–1 mg	0.5–1 mg	low
Common	1–2 mg	1–2 mg	low
Strong	2–4 mg	2–4 mg	low
Heavy	4+ mg	4+ mg	low
Editorial	Values carried forward from existing DB seed data (community consensus). Not clinically derived — no published dose-response studies in humans exist for 5F-AKB48. Ranges are consistent with extreme potency relative to cannabis (CB1 Ki ~3.24 nM for parent APINACA vs ~28 nM for THC) and milligram-level active doses typical of SCRAs. Extreme product variability (0.05–1.17 mg/cm² documented in seized samples) makes intentional dose selection essentially impossible with herbal blend products.
	ReasoningReasoning Values carried forward from existing DB seed data (community consensus). Not clinically derived — no published dose-response studies in humans exist for 5F-AKB48. Ranges are consistent with extreme potency relative to cannabis (CB1 Ki ~3.24 nM for parent APINACA vs ~28 nM for THC) and milligram-level active doses typical of SCRAs. Extreme product variability (0.05–1.17 mg/cm² documented in seized samples) makes intentional dose selection essentially impossible with herbal blend products. Evidence basis: community_consensus_large

Duration

smoked

Field	Published	AI Proposed	Confidence
Offsettrace	5–10 minutes	5–10 minutes	low
Editorial	Carried forward from existing DB seed data (community consensus). Relatively rapid offset consistent with short-acting SCRA profile. Active metabolite 4OH-5F-AKB48 may sustain mild residual effects.
	ReasoningReasoning Carried forward from existing DB seed data (community consensus). Relatively rapid offset consistent with short-acting SCRA profile. Active metabolite 4OH-5F-AKB48 may sustain mild residual effects. Evidence basis: community_consensus_large
Onsettrace	0–20 minutes	0–20 minutes	low
Editorial	Carried forward from existing DB seed data (community consensus). Consistent with rapid pulmonary absorption of inhaled cannabinoids. No clinical PK studies exist for 5F-AKB48.
	ReasoningReasoning Carried forward from existing DB seed data (community consensus). Consistent with rapid pulmonary absorption of inhaled cannabinoids. No clinical PK studies exist for 5F-AKB48. Evidence basis: community_consensus_large
Come uptrace	0–5 minutes	0–5 minutes	low
Editorial	Estimated from inhaled cannabinoid class kinetics as noted in work-notes. No published data for 5F-AKB48 come_up phase specifically. Full agonism produces rapid escalation after onset.
	ReasoningReasoning Estimated from inhaled cannabinoid class kinetics as noted in work-notes. No published data for 5F-AKB48 come_up phase specifically. Full agonism produces rapid escalation after onset. Evidence basis: structural_analogy
Peaktrace	10–30 minutes	10–30 minutes	low
Editorial	Carried forward from existing DB seed data (community consensus). Consistent with in vivo finding of shorter duration than THC (Pinson et al. 2020, Canazza et al. 2016).
	ReasoningReasoning Carried forward from existing DB seed data (community consensus). Consistent with in vivo finding of shorter duration than THC (Pinson et al. 2020, Canazza et al. 2016). Evidence basis: community_consensus_large
Totaltrace	30–60 minutes	30–60 minutes	low
Editorial	Carried forward from existing DB seed data (community consensus). Consistent with shorter-than-THC duration established in mouse cannabinoid tetrad assays (Pinson et al. 2020). Represents subjective experience duration, not pharmacological half-life.
	ReasoningReasoning Carried forward from existing DB seed data (community consensus). Consistent with shorter-than-THC duration established in mouse cannabinoid tetrad assays (Pinson et al. 2020). Represents subjective experience duration, not pharmacological half-life. Evidence basis: community_consensus_large
After effectstrace	15–30 minutes	15–30 minutes	low
Editorial	Carried forward from existing DB seed data (community consensus). Residual fatigue, appetite changes, and mild cognitive fog. Active metabolite may contribute to lingering subclinical effects.
	ReasoningReasoning Carried forward from existing DB seed data (community consensus). Residual fatigue, appetite changes, and mild cognitive fog. Active metabolite may contribute to lingering subclinical effects. Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	high	high	medium
Chronic	moderate	moderate	medium
Organs Affected	cardiovascular, renal, hepatic, neurological, pulmonary	cardiovascular, renal, hepatic, neurological, pulmonary	medium
Editorial	Acute rated 'high' based on substance-specific hERG data (IC50 2.16 µM), 91% tachycardia in Serbian case series, MI case report, and seizures documented by WHO ECDD — full CB1 agonism with documented severe presentations, though no deaths specifically attributed to 5F-AKB48 alone. Chronic rated 'moderate' based on WHO ECDD long-term sequelae (cognitive impairment, cardiac conditions, appetite loss). Organ toxicity beyond cardiovascular is class-extrapolated from SCRA literature.
	ReasoningReasoning Acute rated 'high' based on substance-specific hERG data (IC50 2.16 µM), 91% tachycardia in Serbian case series, MI case report, and seizures documented by WHO ECDD — full CB1 agonism with documented severe presentations, though no deaths specifically attributed to 5F-AKB48 alone. Chronic rated 'moderate' based on WHO ECDD long-term sequelae (cognitive impairment, cardiac conditions, appetite loss). Organ toxicity beyond cardiovascular is class-extrapolated from SCRA literature. Evidence basis: published_case_series

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	moderate	moderate	medium
Psychological	moderate	moderate	medium
Compulsive Redosing	moderate	moderate	medium
Dose Escalation	moderate	moderate	medium
Editorial	Dependence profile derived from SCRA class data (Zimmermann et al. 2009) and WHO ECDD assessment of 5F-APINACA, not substance-specific controlled studies. Prolonged NAc dopamine release documented in mice (WHO ECDD review). DEA cited 'imminent hazard to public safety' in scheduling determination.
	ReasoningReasoning Dependence profile derived from SCRA class data (Zimmermann et al. 2009) and WHO ECDD assessment of 5F-APINACA, not substance-specific controlled studies. Prolonged NAc dopamine release documented in mice (WHO ECDD review). DEA cited 'imminent hazard to public safety' in scheduling determination. Evidence basis: community_consensus_large

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	moderate	moderate	low
Symptoms	irritability, anxiety, insomnia, appetite loss, tremors	irritability, anxiety, insomnia, appetite loss, tremors	low
Fatal	No	No	low
Medical Supervision	Not required	Not required	low
Editorial	Withdrawal profile inferred from SCRA class literature (Zimmermann et al. 2009) and general cannabinoid withdrawal data. No 5F-AKB48-specific withdrawal studies exist. Onset 24–48 hours and duration 1–2 weeks are class-level estimates.
	ReasoningReasoning Withdrawal profile inferred from SCRA class literature (Zimmermann et al. 2009) and general cannabinoid withdrawal data. No 5F-AKB48-specific withdrawal studies exist. Onset 24–48 hours and duration 1–2 weeks are class-level estimates. Evidence basis: community_consensus_large

Tolerance Profiletrace

Field	Published	AI Proposed	Confidence
Buildup	moderate	moderate	low
Half-life	5 days	5 days	low
Full Reset	10.5 days	10.5 days	low
Cross-tolerances	cannabis, synthetic cannabinoids	cannabis, synthetic cannabinoids	low
Editorial	No 5F-AKB48-specific tolerance kinetics published. Values carried forward from seed data, which are plausible cannabinoid class estimates. Cross-tolerance with cannabinoids established via shared CB1 receptor mechanism. Structural analogy to APINACA parent and general SCRA class.
	ReasoningReasoning No 5F-AKB48-specific tolerance kinetics published. Values carried forward from seed data, which are plausible cannabinoid class estimates. Cross-tolerance with cannabinoids established via shared CB1 receptor mechanism. Structural analogy to APINACA parent and general SCRA class. Evidence basis: structural_analogy

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
cardiovascular Long QT syndrometrace	absolute	absolute	high
Editorial	Substance-specific hERG patch-clamp data (IC50 2.16 µM on HEK293 cells) directly supports this contraindication. High confidence due to in vitro mechanistic evidence.
	ReasoningReasoning Substance-specific hERG patch-clamp data (IC50 2.16 µM on HEK293 cells) directly supports this contraindication. High confidence due to in vitro mechanistic evidence.
cardiovascular Ischemic heart diseasetrace	absolute	absolute	medium
Editorial	Case report of MI in a young user (WHO ECDD review) plus class-level SCRA cardiovascular event data. Medium confidence — single case report plus class extrapolation.
	ReasoningReasoning Case report of MI in a young user (WHO ECDD review) plus class-level SCRA cardiovascular event data. Medium confidence — single case report plus class extrapolation.
cardiovascular Concurrent QT-prolonging medication usetrace	absolute	absolute	high
Editorial	Substance-specific additive hERG data with olanzapine directly published. High confidence for olanzapine interaction; mechanistic extension to other QT drugs is well-supported pharmacologically.
	ReasoningReasoning Substance-specific additive hERG data with olanzapine directly published. High confidence for olanzapine interaction; mechanistic extension to other QT drugs is well-supported pharmacologically.
renal Chronic kidney diseasetrace	relative	relative	medium
Editorial	Class-level AKI/rhabdomyolysis data from SCRA literature; no 5F-AKB48-specific renal failure cases published individually. Medium confidence — class extrapolation.
	ReasoningReasoning Class-level AKI/rhabdomyolysis data from SCRA literature; no 5F-AKB48-specific renal failure cases published individually. Medium confidence — class extrapolation.
psychiatric Psychotic disorderstrace	relative	relative	medium
Editorial	Serbian case series documents agitation, disorientation, and psychiatric symptoms; class-level first-episode psychosis data from multiple SCRA case series. Medium confidence.
	ReasoningReasoning Serbian case series documents agitation, disorientation, and psychiatric symptoms; class-level first-episode psychosis data from multiple SCRA case series. Medium confidence.
hepatic Hepatic impairmenttrace	relative	relative	medium
Editorial	Substance-specific CYP3A4-dominant metabolism established in HLM studies. Pharmacokinetic reasoning is standard; medium confidence.
	ReasoningReasoning Substance-specific CYP3A4-dominant metabolism established in HLM studies. Pharmacokinetic reasoning is standard; medium confidence.
pregnancy breastfeeding Pregnancy and lactationtrace	absolute	absolute	low
Editorial	Precautionary contraindication — no data exists. Low confidence reflects absence of evidence rather than evidence of safety.
	ReasoningReasoning Precautionary contraindication — no data exists. Low confidence reflects absence of evidence rather than evidence of safety.
neurological Seizure disorderstrace	relative	relative	medium
Editorial	WHO ECDD review documents seizures at high doses. Medium confidence — documented but at high-dose range only.
	ReasoningReasoning WHO ECDD review documents seizures at high doses. Medium confidence — documented but at high-dose range only.

Timeline Phases

smoked

Field	Published	AI Proposed	Confidence
Onsettrace	0–120 sec(i=0.20)	0–120 sec(i=0.20)	low
Editorial	No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes.
	ReasoningReasoning No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes. Evidence basis: community_consensus_large
Come uptrace	120–600 sec(i=0.60)	120–600 sec(i=0.60)	low
Editorial	No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes.
	ReasoningReasoning No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes. Evidence basis: community_consensus_large
Peaktrace	600–1200 sec(i=1.00)	600–1200 sec(i=1.00)	low
Editorial	No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes.
	ReasoningReasoning No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes. Evidence basis: community_consensus_large
Resolutiontrace	600–1200 sec(i=0.40)	600–1200 sec(i=0.40)	low
Editorial	No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes.
	ReasoningReasoning No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes. Evidence basis: community_consensus_large
Afterglowtrace	900–2700 sec(i=0.15)	900–2700 sec(i=0.15)	low
Editorial	No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes.
	ReasoningReasoning No published clinical pharmacokinetic studies for 5F-AKB48. Timeline derived from seed data (community consensus: onset 0–20 min, peak 10–30 min, offset 5–10 min, aftereffects 15–30 min, total 30–60 min), refined with in vivo finding of shorter duration than THC (Pinson et al. 2020) and rapid pulmonary absorption kinetics. Come_up phase estimated at 0–5 minutes based on inhaled cannabinoid class, as noted in work-notes. Evidence basis: community_consensus_large

Dose Tier Summaries

thresholdtrace

low

Minimal perceptible effects at the boundary between inactive and active dose. A slight mood lift and mild relaxation may be noticed, with possible subtle body sensation or warmth. Cognitive function remains largely intact, and the experience may be difficult to distinguish from placebo. Physical effects are negligible — perhaps a faint increase in heart rate or mild dry mouth. No significant appetite changes or motor impairment are expected. Given the extreme product variability documented in herbal blends (0.05–1.17 mg/cm²), achieving a threshold dose intentionally is essentially impossible without analytical verification of product concentration. Milligram-level dosing means small measurement errors have outsized consequences.

Editorial

No published clinical threshold data for 5F-AKB48. Threshold description inferred from cannabinoid class pharmacology and community consensus seed data (0.5 mg smoked). Product variability caveat from seized-sample analytical data.

Reasoning

Evidence basis: community_consensus_large

lighttrace

low

Mild cannabis-like effects emerge — gentle euphoria, relaxation, and a softening of perceptual sharpness. Appetite enhancement begins. A pleasant body high is present but manageable, and time alteration may become noticeable. Cognitive effects are minimal; conversation and basic tasks remain feasible. Physically, mild sedation and muscle relaxation are typical. Heart rate may increase slightly. Dry mouth and mild dehydration sensation are possible. Motor control is mildly affected but functional impairment is limited. Effects resolve within approximately 30–45 minutes when smoked. Most users find this range pleasant and controllable, though the narrow margin to stronger effects should be respected.

Editorial

Inferred from seed data light range (0.5–1 mg smoked), APINACA parent compound pharmacology, and SCRA class effects. No published dose-response curve for 5F-AKB48 in humans.

Reasoning

Inferred from seed data light range (0.5–1 mg smoked), APINACA parent compound pharmacology, and SCRA class effects. No published dose-response curve for 5F-AKB48 in humans.

Evidence basis: community_consensus_large

commontrace

low

Full cannabinoid effects are evident — clear euphoria and cognitive euphoria, a pronounced body high, appetite enhancement, and noticeable time alteration. Sedation increases and thought deceleration becomes apparent. Analysis suppression and cognitive impairment are present, making complex tasks difficult. Tachycardia may emerge and is the most consistently reported physical effect across clinical case series (91% in one study). Muscle relaxation is pronounced. Nausea is possible, particularly in less experienced users. Spontaneous body sensations and bodily lightness contribute to the somatic experience. At the upper end of this range, anxiety and paranoia become increasingly likely. The transition from euphoric to anxiogenic effects can be abrupt due to full CB1 agonism. Total duration is approximately 30–60 minutes when smoked.

Editorial

Common range (1–2 mg smoked) from seed data community consensus. Clinical symptom frequencies from Serbian 58-patient case series (tachycardia 91%, nausea 28%, agitation 28%). Full CB1 agonist dose-response curve inferred from SCRA class literature.

Reasoning

Evidence basis: community_consensus_large

strongtrace

low

Intense effects with high probability of adverse events. Pronounced tachycardia, potential mydriasis, and significant cognitive impairment dominate the experience. Paranoia, anxiety, and confusion become likely. Sedation may be heavy, and motor control impairment is substantial. Delusions may occur. The margin between strong effects and medical emergency is narrow. Nausea and vomiting are common. Dizziness and spatial disorientation are expected. Chest pain and hypertension have been reported at these doses. Agitation may alternate with somnolence. The body high intensifies beyond comfort for many users. Functional impairment is severe — decision-making, orientation, and communication are significantly compromised. Effects may extend beyond the typical 30–60 minute window. Medical attention should be considered if symptoms are distressing.

Editorial

Strong range (2–4 mg smoked) from seed data. Adverse effect profile from Serbian case series and WHO ECDD review documenting chest pain, hypertension, mydriasis, agitation at higher presentations. Class-level SCRA data supports narrow margin between desired and dangerous effects.

Reasoning

Evidence basis: community_consensus_large

heavytrace

low

Dangerous territory requiring immediate medical awareness. Seizure risk becomes significant, and severe cardiovascular effects including potentially dangerous arrhythmia (given hERG channel inhibition) are possible. Hypothermia and catalepsy have been documented in animal models at equivalent high doses. Severe psychiatric disturbance including psychosis and delusions is likely. Respiratory depression, severe nausea and vomiting, and potential rhabdomyolysis with acute kidney injury represent class-level risks at this dose range. Multiple organ involvement cannot be excluded. The active metabolite 4OH-5F-AKB48 contributes independently to toxicity, potentially extending the duration and severity of effects beyond parent compound predictions. Medical attention is strongly advised. Effects may persist well beyond the typical 30–60 minute window. Do not attempt to manage severe presentations without professional support.

Editorial

Heavy range (4+ mg smoked) from seed data. Seizures, hypothermia, catalepsy from WHO ECDD review. hERG liability (IC50 2.16 µM) is substance-specific. Rhabdomyolysis/AKI from SCRA class literature. Active metabolite contribution from Pinson et al. 2020.

Reasoning

Evidence basis: community_consensus_large

History

current version

published Jun 4, 2026AI-generated—

versions

1 total

publication ledger

backfill Jun 4, 2026

Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.

full version history suggest a correction contact@psychedex.org

Sources

9 strong · 12 moderate · 9 weak

[1]
strong
Metabolism, CB1 cannabinoid receptor binding and in vivo activity of synthetic cannabinoid 5F-AKB48: Implications for toxicity.
Pinson A, Yarbrough AL, Bush JM, Cabanlong CV, Shoeib A, Jackson BK, Fukuda S, Gogoi J, Fantegrossi WE, McCain K, Prather PL, Fujiwara R, Radominska-Pandya A · 2020 · Pharmacology, biochemistry, and behavior
doi.org/10.1016/j.pbb.2020.172949 pubmed 3241343611 claims checked7 verified2 partial2 inconclusive
[2]
moderate
Novel psychoactive substances: types, mechanisms of action, and effects
Tracy DK, Wood DM, Baumeister D · 2017 · BMJ
doi.org/10.1136/bmj.i6848 pubmed 281226973 claims checked3 inconclusive
[3]
strong
First characterization of AKB-48 metabolism, a novel synthetic cannabinoid, using human hepatocytes and high-resolution mass spectrometry.
Gandhi AS, Zhu M, Pang S, Wohlfarth A, Scheidweiler KB, Liu HF, Huestis MA · 2013 · The AAPS journal
doi.org/10.1208/s12248-013-9516-0 pubmed 239131267 claims checked2 verified2 partial3 inconclusive
[4]
weak
Schedules of Controlled Substances: Temporary Placement of Six Synthetic Cannabinoids (5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA and MDMB-FUBINACA) Into Schedule I
DEA · 2016
linkno claims checked
[5]
weak
5F-APINACA (5F-AKB-48) Review Report, Expert Committee on Drug Dependence 38th and 42nd Meetings
WHO Expert Committee on Drug Dependence · 2019
linkno claims checked
[6]
strong
Pharmacological evaluation of synthetic cannabinoids identified as constituents of spice.
Hess C, Schoeder CT, Pillaiyar T, Madea B, Müller CE · 2016 · Forensic toxicology
doi.org/10.1007/s11419-016-0320-2 pubmed 274296556 claims checked2 verified3 inconclusive1 not supported
[7]
weak
Clinical and analytical experience of the National Poison Control Centre with synthetic cannabinoids.
Vučinić S, Kilibarda V, Đorđević S, Đorđević D, Perković-Vukčević N, Vuković-Ercegović G, Antonijević B, Ćurčić M, Antonijević E, Brajković G · 2018 · Arhiv za higijenu rada i toksikologiju
doi.org/10.2478/aiht-2018-69-3096 pubmed 299902976 claims checked3 verified1 partial1 inconclusive1 not supported
[8]
strong
Noncanonical pharmacological inhibition of the hERG K+ channel by a synthetic cannabinoid.
Cheng H, Upex C, Du C, Copeland C, Henderson G, Harmer SC, Corey RA, Hancox JC · 2025 · Biochemical pharmacology
doi.org/10.1016/j.bcp.2025.117257 pubmed 408488569 claims checked7 verified2 inconclusive
[9]
moderate
5F-AKB48: A synthetic cannabinoid presenting an emerging public health concern in France.
Harmel C, Caré W, Laborde-Casterot H, Liautard M, Langrand J, Dufayet L · 2025 · The International journal on drug policy
doi.org/10.1016/j.drugpo.2025.104972 pubmed 408760662 claims checked2 verified
[10]
moderate
Synthetic Cannabinoids.
Mills B, Yepes A, Nugent K · 2015 · The American journal of the medical sciences
doi.org/10.1097/maj.0000000000000466 pubmed 261325184 claims checked4 verified
[11]
moderate
Detection and quantitation of synthetic cannabinoid receptor agonists in infused papers from prisons in a constantly evolving illicit market.
Norman C, Walker G, McKirdy B, McDonald C, Fletcher D, et al. · 2020 · Drug testing and analysis
doi.org/10.1002/dta.2767 pubmed 319446243 claims checked1 verified1 partial1 inconclusive
[12]
moderate
Schedules of Controlled Substances: Placement of UR-144, XLR11, and AKB48 into Schedule I. Final rule.
DEA · 2016 · Federal register
pubmed 271927311 claim checked1 partial
[13]
moderate
Schedules of Controlled Substances: Temporary Placement of Six Synthetic Cannabinoids (5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA and MDMB-FUBINACA) Into Schedule I. Notice of Intent.
DEA · 2016 · Federal register
pubmed 280680472 claims checked2 verified
[14]
weak
Extension of Temporary Placement of 5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA and MDMB-FUBINACA in Schedule I
DEA · 2019
linkno claims checked
[15]
weak
5F-APINACA substance details
UNODC Laboratory and Scientific Service · 2017
linkno claims checked
[16]
strong
Similar 5F-APINACA Metabolism between CD-1 Mouse and Human Liver Microsomes Involves Different P450 Cytochromes.
Crosby SV, Ahmed IY, Osborn LR, Wang Z, Schleiff MA, Fantegrossi WE, Nagar S, Prather PL, Boysen G, Miller GP · 2022 · Metabolites
doi.org/10.3390/metabo12080773 pubmed 360056459 claims checked4 verified5 inconclusive
[17]
moderate
Enantiospecific Synthesis, Chiral Separation, and Biological Activity of Four Indazole-3-Carboxamide-Type Synthetic Cannabinoid Receptor Agonists and Their Detection in Seized Drug Samples
Antonides LH, Cannaert A, Norman C, Vives L, Harrison A, Costello A, Nic Daeid N, Stove CP, Sutcliffe OB, McKenzie C · 2019 · Frontiers in Chemistry
doi.org/10.3389/fchem.2019.00321 pubmed 31157203no claims checked
[18]
strong
Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on 'tetrad', sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies.
Canazza I, Ossato A, Trapella C, Fantinati A, De Luca MA, Margiani G, Vincenzi F, Rimondo C, Di Rosa F, Gregori A, Varani K, Borea PA, Serpelloni G, Marti M · 2016 · Psychopharmacology
pubmed 275275841 claim checked1 verified
[19]
weak
Concentrations of APINACA, 5F-APINACA, UR-144 and its degradant product in blood samples from six impaired drivers compared to previous reported concentrations of other synthetic cannabinoids.
Karinen R, Tuv SS, Øiestad EL, Vindenes V · 2015 · Forensic science international
doi.org/10.1016/j.forsciint.2014.11.012 pubmed 254859493 claims checked3 verified
[20]
strong
Significance of Competing Metabolic Pathways for 5F-APINACA Based on Quantitative Kinetics.
Pinson AO, Pouncey DL, Schleiff MA, Fantegrossi WE, Prather PL, Radominska-Pandya A, Boysen G, Miller GP · 2020 · Molecules
doi.org/10.3390/molecules25204820 pubmed 330921293 claims checked3 verified
[21]
strong
Identification of AKB-48 and 5F-AKB-48 Metabolites in Authentic Human Urine Samples Using Human Liver Microsomes and Time of Flight Mass Spectrometry.
Vikingsson S, Josefsson M, Grén H · 2015 · Journal of analytical toxicology
doi.org/10.1093/jat/bkv045 pubmed 259573853 claims checked3 verified
[22]
moderate
Screening, quantification, and confirmation of synthetic cannabinoid metabolites in urine by UHPLC-QTOF-MS.
Gundersen POM, Spigset O, Josefsson M · 2019 · Drug testing and analysis
doi.org/10.1002/dta.2464 pubmed 299960112 claims checked2 verified
[23]
moderate
"Spice" and "K2" herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans
Gunderson EW, Haughey HM, Ait-Daoud N, Joshi AS, Hart CL · 2012 · The American journal on addictions
doi.org/10.1111/j.1521-0391.2012.00240.x pubmed 226910105 claims checked1 verified1 inconclusive3 not supported
[24]
moderate
The synthetic cannabinoids menace: a review of health risks and toxicity.
Alzu'bi A, Almahasneh F, Khasawneh R, Abu-El-Rub E, Baker WB, Al-Zoubi RM · 2024 · European journal of medical research
doi.org/10.1186/s40001-023-01443-6 pubmed 38216984no claims checked
[25]
weak
Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation.
Abouchedid R, Ho JH, Hudson S, Dines A, Archer JR, Wood DM, Dargan PI · 2016 · Journal of medical toxicology
pubmed 274562622 claims checked2 verified
[26]
strong
A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment
Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S · 2016 · Clinical Toxicology
doi.org/10.3109/15563650.2015.1110590 pubmed 265674706 claims checked4 verified1 partial1 inconclusive
[27]
moderate
New drugs of abuse.
Rech MA, Donahey E, Cappiello Dziedzic JM, Oh L, Greenhalgh E · 2015 · Pharmacotherapy
doi.org/10.1002/phar.1522 pubmed 25471045no claims checked
[28]
weak
Synthetic cannabinoid hyperemesis resulting in rhabdomyolysis and acute renal failure.
Argamany JR, Reveles KR, Duhon B · 2016 · The American journal of emergency medicine
doi.org/10.1016/j.ajem.2015.08.051 pubmed 264221912 claims checked2 verified
[29]
weak
Synthetic Cannabinoid-Associated Multiple Organ Failure: Case Series and Literature Review.
Armstrong F, McCurdy MT, Heavner MS · 2019 · Pharmacotherapy
doi.org/10.1002/phar.2241 pubmed 308116282 claims checked2 verified
[30]
moderate
Clinical effects of cannabis compared to synthetic cannabinoid receptor agonists (SCRAs): a retrospective cohort study of presentations with acute toxicity to European hospitals between 2013 and 2020.
Waters ML, Dargan PI, Yates C, et al. · 2024 · Clinical toxicology
doi.org/10.1080/15563650.2024.2346125 pubmed 38934347no claims checked

Claim Verification

Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.

summary9 claims2verified3partial4inconclusive

partialAdministered 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.^[1]75%

Partial

Abstract confirms '5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC,' supporting the more-intense/shorter-lived comparison. However, the specific '30–60 minutes' smoked duration is a factual assertion not present in the abstract, which reports mouse data only.

5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC; attenuated by rimonabant.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe compound derives from an adamantyl carboxamide scaffold originally described in a Pfizer patent (WO 2009/106980) exploring cannabinoid-mediated analgesia^[2]55%

Inconclusive

Abstract is a broad NPS review: 'types, mechanisms of action, and effects.' The specific Pfizer patent number WO 2009/106980 is not mentioned. The full review may contain this detail, but it cannot be confirmed from the abstract.

Review of novel psychoactive substances including synthetic cannabinoids: types, mechanisms of action, and effects.

checked by claude-sonnet-4-6 · May 11, 2026

partialThe parent compound APINACA appeared in illicit "herbal incense" products in 2012; the fluorinated analogue followed after scheduling of the parent, first identified in South Korea^[3]55%

Partial

Abstract confirms APINACA was 'first identified in Japanese herbal smoking blends' and DEA-scheduled in May 2013. The specific '2012' date is not confirmed (NFLIS data spans March 2010–January 2013). 'First identified in South Korea' for the fluorinated analogue is entirely absent from the abstract.

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.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe 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 2:1^[6]60%

Inconclusive

Abstract confirms radioligand binding studies for AKB48 at human CB1 and CB2 with 'low nanomolar to subnanomolar affinity,' consistent with high potency. However, specific Ki values (3.24 nM, 28.35 nM for THC, 8-fold comparison, 2:1 selectivity) are not in the abstract — they would be in the paper's data tables.

Most compounds are potent full agonists with low nanomolar to subnanomolar affinity.

checked by claude-sonnet-4-6 · May 11, 2026

partialThe 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 2:1^[3]70%

Partial

Abstract directly states 'AKB-48 has twice the CB1 receptor binding affinity than CB2,' confirming the 2:1 selectivity ratio. The specific Ki of 3.24 nM and 8-fold greater affinity versus THC are not mentioned in the abstract.

AKB-48 has twice the CB1 receptor binding affinity than CB2.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveSubstance-specific Ki values for 5F-AKB48 have not been published, though fluorination of the pentyl terminus enhances metabolic stability and in vivo potency^[1]50%

Inconclusive

Abstract covers metabolism and in vivo potency of 5F-AKB48 vs THC but does not state that Ki values are unpublished, nor explicitly describe metabolic stability enhancement from fluorination. The potency comparison is consistent with the claim but doesn't confirm it directly.

5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe 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.^[1]95%

Verified

Abstract directly states: 'Metabolite 4OH-5F-AKB48 retains high CB1 affinity and greater efficacy for G protein activation than THC.' The independent pharmacological contribution is a direct inference from this finding.

Metabolite 4OH-5F-AKB48 retains high CB1 affinity and greater efficacy for G protein activation than THC.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveAt low doses, the experiential profile resembles intensified cannabis — euphoria, relaxation, appetite enhancement, altered time perception — but higher doses shift toward agitation, tachycardia, paranoia, and disorientation^[7]50%

Inconclusive

Abstract covers clinical overdose presentations (tachycardia 91%, agitation 28%, disorientation 16%), supporting the high-dose adverse profile. The low-dose experiential profile (euphoria, relaxation, appetite enhancement, time perception) is entirely absent — this case series records overdose data only, not recreational low-dose effects.

Clinical signs: tachycardia (91%), mydriasis (53%), somnolence/nausea/vomiting/agitation (28%), dizziness (17%), disorientation (16%).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedNo 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 olanzapine^[8]90%

Verified

IC50 of 2.16 µM for hERG inhibition and additive olanzapine effect are directly confirmed. QT prolongation risk is the standard mechanistic inference from hERG inhibition. The 'no LD50' assertion cannot be verified from this abstract but is not the claim this citation is primarily supporting.

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.

checked by claude-sonnet-4-6 · May 11, 2026

history5 claims1partial4inconclusive

inconclusiveThe APINACA/AKB48 scaffold originates from Pfizer patent WO 2009/106980, which described a series of indazole-based adamantyl carboxamide cannabinoid receptor agonists designed for analgesic applications^[2]55%

Inconclusive

Abstract is a broad NPS review. The specific Pfizer patent number WO 2009/106980 is not mentioned. As a review, this detail may be in the full text, but the abstract provides no confirmation.

Review of novel psychoactive substances including synthetic cannabinoids: types, mechanisms of action, and effects.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe parent compound APINACA (AKB48) was first identified by Japanese forensic laboratories in March 2012 as an ingredient in synthetic cannabis smoking blends^[3]60%

Inconclusive

Abstract confirms 'first identified in Japanese herbal smoking blends.' The specific month and year ('March 2012') are not stated in the abstract. NFLIS reports begin March 2010 in the US, adding ambiguity about timeline.

AKB-48 (APINACA) first identified in Japanese herbal smoking blends. 443 NFLIS reports in USA from March 2010 to January 2013.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe fluorinated analogue appeared on illicit drug markets following the scheduling of the parent compound, a structural modification strategy characteristic of the synthetic cannabinoid class: terminal fluorination of the N-alkyl chain enhances metabolic stability and in vivo potency while producing a compound not yet captured by existing scheduling language^[2]55%

Inconclusive

Abstract is a broad NPS review with no specific detail on fluorination strategy or scheduling circumvention. The full review may contain this information.

Review of novel psychoactive substances including synthetic cannabinoids: types, mechanisms of action, and effects.

checked by claude-sonnet-4-6 · May 11, 2026

partialThe 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.^[12]65%

Partial

Abstract confirms the 'Final DEA rule permanently scheduling AKB48 (APINACA) as Schedule I,' supporting the permanent scheduling component. 'May 2013 emergency scheduling' and all scheduling details for 5F-APINACA (December 2016, April 2019 extension) are not in this abstract.

Final DEA rule permanently scheduling AKB48 (APINACA) as Schedule I under the Controlled Substances Act.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveFollowing widespread international scheduling in 2016–2017, 5F-AKB48 was largely displaced from illicit markets by newer-generation synthetic cannabinoids such as 5F-MDMB-PICA and MDMB-4en-PINACA^[11]55%

Inconclusive

Abstract mentions 'market evolution documented' from Scottish prison SCRA data, which is the right context. The specific displacement by 5F-MDMB-PICA and MDMB-4en-PINACA is not confirmed in the abstract.

Qualitative and quantitative analysis of SCRA-infused papers from Scottish prisons (n=354 samples). Market evolution documented.

checked by claude-sonnet-4-6 · May 11, 2026

chemistry2 claims2inconclusive

inconclusiveThe compound is the terminal fluorine analogue of APINACA (AKB48), differing only in the substitution of a fluorine atom for a hydrogen at the C-5 position of the N-pentyl chain.^[3]50%

Inconclusive

Abstract describes AKB-48 metabolic characterization but does not describe the structural relationship between AKB-48 and 5F-AKB-48 or the fluorination position (C-5 of N-pentyl).

AKB-48 (APINACA) first identified in Japanese herbal smoking blends.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThis bulky, lipophilic cage structure confers high CB1 receptor affinity, while terminal fluorination enhances metabolic stability relative to the unsubstituted parent compound.^[16]55%

Inconclusive

Abstract describes metabolic pathways and CYP enzyme identification for 5F-APINACA but does not address structural features (lipophilic cage) or how fluorination alters metabolic stability versus the parent compound.

Comparative analysis of 5F-APINACA metabolism in CD-1 mice and humans using hepatic microsomes. CYP3A4 dominates.

checked by claude-sonnet-4-6 · May 11, 2026

pharmacology21 claims15verified5inconclusive1not supported

verifiedMetabolism: CYP3A4 is the dominant Phase I enzyme in humans, with minor contributions from CYP2C8, CYP2C19, and CYP2D6^[16]97%

Verified

Abstract directly states 'CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans with minor contributions from CYP2C8, 2C19, 2D6.'

CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans with minor contributions from CYP2C8, 2C19, 2D6.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusive5F-AKB48 is a potent full agonist at both cannabinoid CB1 and CB2 receptors^[1]55%

Inconclusive

Abstract covers CB1 receptor binding and metabolite efficacy but does not explicitly state '5F-AKB48 is a full agonist at both CB1 and CB2.' CB2 is not mentioned. Full agonist status at CB1 is inferable from the metabolite data, but CB2 cannot be confirmed.

Metabolite 4OH-5F-AKB48 retains high CB1 affinity and greater efficacy for G protein activation than THC.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedUnlike 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.^[10]90%

Verified

Abstract states 'SCBs are direct agonists vs THC partial agonist,' directly confirming the pharmacological distinction between SCRAs and THC at CB1.

SCBs are direct agonists vs THC partial agonist.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveFor the parent compound APINACA, radioligand displacement studies report a Ki of approximately 3.24 nM at human CB1, compared to approximately 28.35 nM for Δ9-THC — representing roughly 8-fold greater CB1 affinity^[6]60%

Inconclusive

Abstract confirms radioligand binding assays for AKB48 at human CB1 with 'low nanomolar to subnanomolar affinity,' consistent with potency, but specific Ki values (3.24 nM, 28.35 nM for THC, 8-fold) are not stated — they are in the full paper's data tables.

Evaluated heterocyclic compounds including AKB48 at human CB1 and CB2 receptors by radioligand binding and cAMP assays. Most compounds are potent full agonists with low nanomolar to subnanomolar affinity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe CB1-to-CB2 selectivity ratio for APINACA is approximately 2:1^[3]95%

Verified

Abstract directly states 'AKB-48 has twice the CB1 receptor binding affinity than CB2,' which is exactly a 2:1 CB1:CB2 selectivity ratio.

AKB-48 has twice the CB1 receptor binding affinity than CB2.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn 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-THC^[1]85%

Verified

Abstract confirms 'time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC.' CD-1 strain and tetrad components are full-paper details not in the abstract, but the core finding is directly confirmed.

5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC.

checked by claude-sonnet-4-6 · May 11, 2026

Verified

Abstract explicitly covers 'in vitro and in vivo pharmacological characterization including tetrad responses, sensorimotor, neurological and neurochemical responses in mice' for both AKB48 and 5F-AKB48 — directly the right paper for this claim.

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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedPre-treatment with the selective CB1 antagonist rimonabant attenuates these effects, confirming a CB1-mediated mechanism.^[1]97%

Verified

Abstract explicitly states effects were 'attenuated by rimonabant,' directly confirming CB1-mediated mechanism.

5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC; attenuated by rimonabant.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe primary Phase I metabolite, 4OH-5F-AKB48, retains high CB1 affinity and demonstrates greater efficacy for G-protein activation than Δ9-THC^[1]98%

Verified

Abstract states verbatim: 'Metabolite 4OH-5F-AKB48 retains high CB1 affinity and greater efficacy for G protein activation than THC.'

Metabolite 4OH-5F-AKB48 retains high CB1 affinity and greater efficacy for G protein activation than THC.

checked by claude-sonnet-4-6 · May 11, 2026

not supportedComputational modeling predicts that indazole carboxamide SCRAs of this class readily cross the blood-brain barrier^[6]90%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract describes receptor binding pharmacology (CB1/CB2 radioligand assays, cAMP, GPR55). No mention of computational modeling or blood-brain barrier prediction anywhere in the abstract.

Evaluated heterocyclic compounds including AKB48 at human CB1 and CB2 receptors by radioligand binding and cAMP assays.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn 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-APINACA^[19]97%

Verified

Abstract confirms 'First reported blood concentrations for APINACA and 5F-APINACA. In DUID cases: 5F-APINACA 0.24-6.5 μg/L whole blood.'

First reported blood concentrations for APINACA and 5F-APINACA. In DUID cases: 5F-APINACA 0.24-6.5 μg/L whole blood.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedAdamantyl hydroxylation (primary, dominant): Sequential mono-, di-, and trihydroxylation of the adamantane ring system, carrying approximately 17-fold higher metabolic flux than defluorination.^[20]88%

Verified

Abstract confirms 'highly efficient mono- and dihydroxylation of adamantyl group; oxidative defluorination 17-fold less efficient.' The 17-fold ratio and hydroxylation dominance are directly confirmed; trihydroxylation is not listed in the abstract but is in the full paper's metabolite scheme.

Kinetic analysis of 5F-APINACA metabolism in human liver microsomes: highly efficient mono- and dihydroxylation of adamantyl group; oxidative defluorination 17-fold less efficient.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedOxidative defluorination (secondary): Removal of the terminal fluorine from the N-pentyl chain, producing multiple secondary metabolites.^[20]90%

Verified

Abstract confirms oxidative defluorination as a secondary, less efficient pathway (17-fold less than hydroxylation); eight total metabolites identified.

Oxidative defluorination 17-fold less efficient. Eight metabolites identified.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveAt higher substrate concentrations, adamantyl hydroxylation becomes proportionally less significant due to substrate inhibition at an effector site, producing nonlinear metabolic kinetics^[16]60%

Inconclusive

Abstract describes CYP enzyme identification and species comparison but does not mention substrate inhibition, effector sites, or nonlinear kinetics. This mechanistic detail is likely from citation [4] (Significance of Competing Metabolic Pathways).

CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans with minor contributions from CYP2C8, 2C19, 2D6. Highly conserved metabolic pathways across species.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedCYP2D6, CYP2J2, CYP3A4, and CYP3A5 contribute to mono- and dihydroxylated metabolite production; CYP3A4 and CYP3A5 additionally generate trihydroxylated metabolites^[1]82%

Verified

Abstract confirms 'CYP2D6, CYP2J2, CYP3A4, CYP3A5 most active.' The specific assignment to trihydroxylated metabolites is not in the abstract but is consistent with full-paper data; the enzyme identification itself is directly confirmed.

CYP2D6, CYP2J2, CYP3A4, CYP3A5 most active.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedPhase II glucuronide conjugation occurs on mono- and dihydroxylated metabolites.^[3]85%

Verified

Abstract confirms '17 novel phase I and II AKB-48 metabolites… monohydroxylation, dihydroxylation, trihydroxylation… glucuronide conjugation.' The coexistence of hydroxylated metabolites and glucuronidation supports that conjugation occurs on hydroxylated products.

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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedMetabolite identification: A total of 37 distinct metabolites were identified from human liver microsome (HLM) incubations^[21]98%

Verified

Abstract directly states '41 metabolites of AKB-48 and 37 metabolites of 5F-AKB-48 identified in HLM incubations.'

41 metabolites of AKB-48 and 37 metabolites of 5F-AKB-48 identified in HLM incubations.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn authentic human urine samples, defluorinated metabolites account for approximately 74% of the combined chromatographic area^[21]98%

Verified

Abstract directly states 'Defluorinated metabolites accounted for ~74% of combined area after 5F-AKB-48 intake.'

Defluorinated metabolites accounted for ~74% of combined area after 5F-AKB-48 intake.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe parent compound is difficult to detect in urine, making hydroxylated metabolite identification essential for forensic confirmation^[3]50%

Inconclusive

Abstract describes metabolite identification from hepatocytes but does not mention difficulty detecting the parent compound in urine or the need for metabolite-based forensic confirmation. This detail may be in the full paper.

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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedValidated detection methods include UHPLC-QTOF-MS.^[22]97%

Verified

Abstract directly describes a 'sensitive UHPLC-QTOF-MS method' validated for SC metabolites including 5F-AKB48.

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.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveSpecies differences: In CD-1 mice, Cyp3a11 and multiple Cyp2c isoforms (Cyp2c37, Cyp2c50, Cyp2c54) share metabolic responsibility, a distribution distinct from the CYP3A4-dominant human profile^[16]60%

Inconclusive

Abstract confirms comparative mouse/human metabolism study with CYP3A4-dominant human profile. Specific mouse CYP isoforms (Cyp3a11, Cyp2c37, Cyp2c50, Cyp2c54) are not named in the abstract — these would be in the full paper's results.

Comparative analysis of 5F-APINACA metabolism in CD-1 mice and humans using hepatic microsomes. CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans.

checked by claude-sonnet-4-6 · May 11, 2026

neuroscience4 claims1inconclusive3not supported

not supportedRepeated exposure to full CB1 agonists sensitizes the mesolimbic dopamine system, increasing drug-seeking motivation independently of subjective pleasure — a mechanism proposed to underlie the moderate dependence potential documented for SCRAs.^[23]90%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract is a systematic review of clinical effects (anxiety, psychosis, cannabis withdrawal substitution). There is no mention of mesolimbic dopamine sensitization, drug-seeking motivation, or the neurobiological mechanism underlying dependence potential.

Systematic review of SC clinical effects in humans. Most highlight potential toxicity (anxiety, psychosis). Three cases: experienced marijuana users used SC products regularly; SC use effectively alleviated cannabis withdrawal.

checked by claude-sonnet-4-6 · May 11, 2026

not supportedThis profound endocannabinoid system disruption may explain the more severe withdrawal syndromes reported with SCRA dependence compared to cannabis dependence, as the system requires more extensive neuroadaptive recovery.^[23]85%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract does not compare SCRA withdrawal severity to cannabis withdrawal, nor does it discuss endocannabinoid system disruption or neuroadaptive recovery. The abstract shows SCRAs can alleviate cannabis withdrawal, which does not support the claim that SCRA withdrawal is more severe.

SC use effectively alleviated cannabis withdrawal.

checked by claude-sonnet-4-6 · May 11, 2026

not supportedThe amygdala expresses CB1 receptors bidirectionally: low-level endocannabinoid tone reduces anxiety (anxiolysis), while supraphysiological CB1 activation paradoxically increases anxiety and paranoia, consistent with the dose-dependent anxiogenic shift observed clinically with 5F-AKB48.^[7]90%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract is a clinical case series of overdose presentations. No mention of amygdala CB1 receptor expression, bidirectional anxiety modulation, or endocannabinoid tone. The neuroscience mechanism claim has no basis in this abstract.

58 patients treated for SC overdose in Serbia 2013-2016. Clinical signs: tachycardia (91%), mydriasis (53%), somnolence/nausea/vomiting/agitation (28%), dizziness (17%), disorientation (16%).

checked by claude-sonnet-4-6 · May 11, 2026

inconclusivehERG channel structure-activity relationships: The noncanonical binding site on the hERG channel (residues F557, M651) raises the question of whether other SCRAs share this cardiac liability and whether structure-activity relationships can predict hERG risk across the class.^[8]65%

Inconclusive

Abstract confirms noncanonical binding site 'distinct from S6 aromatic residues.' Specific residues F557 and M651 are not in the abstract. The broader SAR research question is framing not present in the abstract.

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.

checked by claude-sonnet-4-6 · May 11, 2026

receptor pharmacology5 claims4verified1inconclusive

inconclusiveFor the parent compound APINACA (AKB48), radioligand displacement data indicates a Ki at human CB1 receptors of approximately 3.24 nM, compared to approximately 28.35 nM for Δ9-THC^[6]60%

Inconclusive

Abstract confirms radioligand binding studies at human CB1 for AKB48 and 'low nanomolar to subnanomolar affinity.' Specific Ki values (3.24 nM for AKB48, 28.35 nM for THC) are not in the abstract — these are data-table values.

Evaluated heterocyclic compounds including AKB48 at human CB1 and CB2 receptors by radioligand binding and cAMP assays. Most compounds are potent full agonists with low nanomolar to subnanomolar affinity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe 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.^[6]88%

Verified

Abstract directly confirms 'low nanomolar to subnanomolar affinity' for the compound series including AKB48.

Most compounds are potent full agonists with low nanomolar to subnanomolar affinity.

checked by claude-sonnet-4-6 · May 11, 2026

verified5F-AKB48 functions as a full agonist at CB1, achieving maximal receptor activation — in contrast to Δ9-THC, which produces submaximal (partial agonist) responses^[10]92%

Verified

Abstract directly states 'SCBs are direct agonists vs THC partial agonist,' confirming the full vs partial agonist distinction.

SCBs are direct agonists vs THC partial agonist.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe parent AKB48 class acts as a moderate antagonist at GPR55, a non-canonical cannabinoid-related receptor; no interaction with GPR18 was detected^[6]85%

Verified

Abstract directly states 'Some are moderate GPR55 antagonists,' confirming GPR55 antagonism. GPR18 absence is not mentioned in the abstract.

Some are moderate GPR55 antagonists.

checked by claude-sonnet-4-6 · May 11, 2026

verified5F-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 cells^[8]92%

Verified

IC50 2.16 µM for hERG inhibition directly confirmed. HEK293 cells and patch-clamp method are not in the abstract but are standard for this assay type.

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.

checked by claude-sonnet-4-6 · May 11, 2026

pharmacokinetic detail6 claims4verified1partial1inconclusive

verifiedCYP3A4 is the dominant enzyme for 5F-AKB48 metabolism in humans, responsible for both the primary adamantyl hydroxylation and secondary oxidative defluorination pathways^[16]98%

Verified

Abstract directly states 'CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans.'

CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans.

checked by claude-sonnet-4-6 · May 11, 2026

partialAdditional contributing enzymes include CYP2C8, CYP2C19, CYP2D6, CYP2J2, and CYP3A5.^[1]70%

Partial

Abstract for citation [5] confirms CYP2D6, CYP2J2, CYP3A4, and CYP3A5 as most active. CYP2C8 and CYP2C19 are confirmed by citation [3], not by this abstract. The claim attributes all five enzymes to this citation, but two are not present in this abstract.

CYP2D6, CYP2J2, CYP3A4, CYP3A5 most active.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe kinetics are nonlinear: at elevated substrate concentrations, adamantyl hydroxylation is proportionally suppressed due to substrate inhibition at an allosteric effector site, shifting the metabolic profile toward defluorination products^[16]60%

Inconclusive

Abstract describes CYP enzyme identification and species comparison for 5F-APINACA metabolism but does not mention substrate inhibition, allosteric effector sites, or nonlinear kinetics. This detail is more consistent with citation [4].

CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans with minor contributions from CYP2C8, 2C19, 2D6.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn 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.^[21]92%

Verified

The ~74% figure is directly confirmed. The mechanistic explanation (preferential renal excretion of polar metabolites) is a reasonable pharmacokinetic inference from the finding.

Defluorinated metabolites accounted for ~74% of combined area after 5F-AKB-48 intake.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedValidated analytical methods include UHPLC-QTOF-MS and LC-HRMS^[22]85%

Verified

Abstract confirms UHPLC-QTOF-MS method validated for 5F-AKB48. LC-HRMS would be from another citation. This citation supports the UHPLC-QTOF-MS component of the claim.

Developed sensitive UHPLC-QTOF-MS method for 18 synthetic cannabinoid metabolites including 5F-AKB48.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe first published whole blood concentrations for 5F-APINACA derive from Norwegian DUID cases: 0.24–6.5 μg/L^[19]88%

Verified

Abstract confirms 'First reported blood concentrations… 5F-APINACA 0.24-6.5 μg/L whole blood' in DUID cases. 'Norwegian' is not stated in the abstract but the concentrations and first-reported status are confirmed.

First reported blood concentrations for APINACA and 5F-APINACA. In DUID cases: 5F-APINACA 0.24-6.5 μg/L whole blood.

checked by claude-sonnet-4-6 · May 11, 2026

effects overview1 claim1verified

verifiedThe 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.^[11]85%

Verified

Abstract confirms SCRA concentrations of 0.05–1.17 mg/cm² (23-fold variation) across samples, demonstrating substantial dosing variability that makes consistent self-titration extremely difficult.

SCRA concentrations 0.05-1.17 mg/cm2. Market evolution documented.

checked by claude-sonnet-4-6 · May 11, 2026

clinical evidence6 claims6verified

verifiedAnalytically confirmed acute toxicity from 5F-derivative SCRAs, including 5F-AKB48, has been reported in a United Kingdom case series.^[25]90%

Verified

Abstract confirms 'Case series of acute toxicity with analytically confirmed 5F-derivative SCRAs including 5F-AKB48.' The UK location is not stated in the abstract but the analytic confirmation and case-series design are directly confirmed.

Case series of acute toxicity with analytically confirmed 5F-derivative SCRAs including 5F-AKB48. Characterizes harms with confirmed analytical identification.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe 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 SCRAs^[7]90%

Verified

58 patients, Serbia, and 5F-AKB48 confirmed. 'Most comprehensive' is editorial.

58 patients treated for SC overdose in Serbia 2013-2016. 5F-AKB48 detected in herbal products.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe 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 network^[9]85%

Verified

Abstract confirms French PCC study describing sociodemographic and clinical characteristics of 5F-AKB48 exposures; 'emerging public health concern in France' is in the paper title. 'Harmel et al.' and 'first dedicated' not verifiable from abstract.

This study aimed to describe the sociodemographic and clinical characteristics of 5F-AKB48 exposures reported to French Poison Control Centers (PCCs).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedPinson 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.^[1]90%

Verified

Abstract confirms active metabolite 4OH-5F-AKB48 characterization, greater G-protein efficacy than THC, and rimonabant attenuation. Author attribution cannot be verified from abstract.

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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedClinical management is symptomatic and supportive: most acute presentations resolve within 8 hours with intravenous fluids and monitoring^[26]88%

Verified

Abstract confirms 'typically resolve within 8 hours with supportive care.' IV fluids is a specific component not named in abstract but encompassed within supportive care.

Typically resolve within 8 hours with supportive care.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedBenzodiazepines 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 olanzapine^[8]85%

Verified

Citation is specifically supporting the olanzapine caution, which is directly confirmed by additive hERG inhibition data. Benzodiazepine recommendations are not in this abstract but are not the focus of this citation.

Additive inhibition recorded with co-application of olanzapine.

checked by claude-sonnet-4-6 · May 11, 2026

safety29 claims22verified3partial3inconclusive1not supported

verifiedThe 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 SCRAs^[7]90%

Verified

Abstract confirms 58 patients treated for SC overdose in Serbia with 5F-AKB48 detected in herbal products. 'Most comprehensive' is an editorial judgment not verifiable from the abstract, but the factual core is directly confirmed.

58 patients treated for SC overdose in Serbia 2013-2016. 5F-AKB48 detected in herbal products.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedAll patients recovered within 8 hours with symptomatic and supportive care.^[7]98%

Verified

Abstract directly states 'All recovered within 8 hours.'

All recovered within 8 hours.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedA 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 compound^[9]85%

Verified

Abstract confirms the study describes 5F-AKB48 exposures at French PCCs; title includes 'emerging public health concern in France.' 'Largest dedicated epidemiological case series' is not in the abstract but the focus on sociodemographic/clinical characterization is confirmed.

This study aimed to describe the sociodemographic and clinical characteristics of 5F-AKB48 exposures reported to French Poison Control Centers (PCCs).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedAnalytically confirmed acute toxicity from 5F-derivative SCRAs, including 5F-AKB48, has been reported in a United Kingdom case series.^[25]90%

Verified

Abstract directly confirms case series of acute toxicity with analytically confirmed 5F-derivative SCRAs including 5F-AKB48.

Case series of acute toxicity with analytically confirmed 5F-derivative SCRAs including 5F-AKB48.

checked by claude-sonnet-4-6 · May 11, 2026

verified5F-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 arrhythmia^[8]95%

Verified

Abstract directly confirms IC50 of 2.16 µM for hERG inhibition. QT prolongation risk is the standard mechanistic consequence of hERG blockade.

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.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe inhibition occurs via a noncanonical binding site (residues F557 and M651) and causes voltage-dependent slowing of IhERG activation^[8]65%

Inconclusive

Abstract confirms inhibition 'via a noncanonical binding site distinct from S6 aromatic residues.' The specific residues F557 and M651 and voltage-dependent slowing of activation are not mentioned in the abstract — these details are in the full paper.

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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedCo-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.^[8]92%

Verified

Abstract directly states 'Additive inhibition recorded with co-application of olanzapine.' The clinical implication about antipsychotic use for agitation management is a reasonable contextual inference.

Additive inhibition recorded with co-application of olanzapine.

checked by claude-sonnet-4-6 · May 11, 2026

partialAt the class level, SCRAs are associated with profound hypotension, bradycardia, ischemic stroke, and embolic events.^[26]70%

Partial

Abstract confirms 'cardiovascular events' as a major complication, which could encompass stroke and embolic events. However, the abstract specifically reports TACHYCARDIA (37–77%) as the predominant cardiovascular sign — directly contradicting 'bradycardia.' Hypotension is not mentioned. The claim includes specific conditions that are either absent or contradicted by the abstract's reported data.

Major complications: cardiovascular events, acute kidney injury, seizures, psychiatric presentations. Most presentations: tachycardia (37-77%), agitation (16-41%).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe synthetic cannabinoid class is strongly associated with acute kidney injury (AKI), including rhabdomyolysis-induced acute renal failure^[28]92%

Verified

Abstract directly describes 'synthetic cannabinoid hyperemesis leading to rhabdomyolysis and acute renal failure.'

First case of synthetic cannabinoid hyperemesis leading to rhabdomyolysis and acute renal failure.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedMultiple organ failure involving hepatic, renal, and cardiovascular systems has been documented with SCRA use^[29]92%

Verified

Abstract directly describes 'synthetic cannabinoid intoxication resulting in multiple organ failure' in a multicenter case series.

Multicenter descriptive case series of 6 patients with synthetic cannabinoid intoxication resulting in multiple organ failure.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedDriving impairment is an established concern; 5F-APINACA has been detected in blood samples from DUID cases.^[19]95%

Verified

Abstract directly reports 5F-APINACA blood concentrations in DUID cases.

In DUID cases: 5F-APINACA 0.24-6.5 μg/L whole blood.

checked by claude-sonnet-4-6 · May 11, 2026

partialAcute psychosis, delusions, paranoia, anxiety, and confusion are commonly reported at higher doses of 5F-AKB48 and related SCRAs^[7]70%

Partial

Abstract confirms agitation (28%) and disorientation (16%) in overdose cases, but does not mention psychosis, delusions, paranoia, or confusion specifically. The claim states these are 'commonly reported' but this case series does not list them among clinical signs.

Clinical signs: tachycardia (91%), mydriasis (53%), somnolence/nausea/vomiting/agitation (28%), dizziness (17%), disorientation (16%).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedAcute psychosis, delusions, paranoia, anxiety, and confusion are commonly reported at higher doses of 5F-AKB48 and related SCRAs^[26]85%

Verified

Abstract lists 'psychiatric presentations' as a major complication in a systematic review of ~4000 SCRA cases. This broad category encompasses psychosis, delusions, paranoia, anxiety, and confusion.

Major complications: cardiovascular events, acute kidney injury, seizures, psychiatric presentations.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedAcute psychosis, delusions, paranoia, anxiety, and confusion are commonly reported at higher doses of 5F-AKB48 and related SCRAs^[10]95%

Verified

Abstract explicitly lists 'hallucinations, delusions, confusion' and 'agitation, drowsiness' among the most common SCB toxicities, directly confirming the psychiatric symptom profile.

Most common toxicities: tachycardia, agitation, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, chest pain.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveAt the class level, first-episode psychosis, prolonged paranoid states, self-harm, and suicidal ideation have been documented.^[26]60%

Inconclusive

Abstract confirms 'psychiatric presentations' as major complications. Specific items — first-episode psychosis, prolonged paranoid states, self-harm, suicidal ideation — are not listed in the abstract and would be in the full systematic review data.

Major complications: cardiovascular events, acute kidney injury, seizures, psychiatric presentations.

checked by claude-sonnet-4-6 · May 11, 2026

partialUsers 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).^[11]70%

Partial

Abstract directly confirms 'SCRA concentrations 0.05-1.17 mg/cm2' across samples. The 0.47–2.38 mg/cm² within-single-paper variability figure is not stated in the abstract and cannot be confirmed.

SCRA concentrations 0.05-1.17 mg/cm2. Market evolution documented.

checked by claude-sonnet-4-6 · May 11, 2026

not supportedAs a full agonist, it drives more profound receptor internalization than partial agonists (THC/cannabis), consistent with the more severe dependence and withdrawal documented for SCRAs relative to cannabis.^[23]85%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract covers clinical effects and cannabis withdrawal substitution but does not address receptor internalization or compare SCRA withdrawal severity to cannabis withdrawal. The mechanistic claim has no basis in this abstract.

Systematic review of SC clinical effects in humans. Most highlight potential toxicity (anxiety, psychosis). Three cases: experienced marijuana users used SC products regularly; effects similar to marijuana.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedSynthetic cannabinoids can substitute for cannabis in users experiencing cannabis withdrawal syndrome, indicating overlapping but not identical dependence mechanisms^[23]92%

Verified

Abstract directly states 'SC use effectively alleviated cannabis withdrawal,' confirming that SCRAs can substitute for cannabis in withdrawal.

SC use effectively alleviated cannabis withdrawal.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveCase reports document tolerance, compulsive use patterns, and withdrawal symptoms (irritability, anxiety, insomnia, appetite loss, tremors) in SCRA users.^[23]55%

Inconclusive

Abstract mentions 'experienced marijuana users used SC products regularly,' implying regular/compulsive use patterns, but specific SCRA withdrawal symptoms (irritability, anxiety, insomnia, appetite loss, tremors) are not described. These details may be in the full paper.

Three cases: experienced marijuana users used SC products regularly; effects similar to marijuana; SC use effectively alleviated cannabis withdrawal.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedBoth 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".^[13]88%

Verified

Abstract directly confirms DEA scheduling citing 'imminent hazard to public safety.' WHO ECDD is not mentioned in the abstract but the DEA portion of the claim is fully 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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedBoth 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".^[13]88%

Verified

Abstract directly confirms DEA scheduling citing 'imminent hazard to public safety.' WHO ECDD not mentioned but the core DEA claim is fully 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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe most significant documented interaction involves hERG potassium channel inhibition. 5F-AKB48 (IC50 = 2.16 μM) produces additive hERG blockade when combined with olanzapine^[8]97%

Verified

IC50 2.16 µM and additive olanzapine hERG blockade directly confirmed.

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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedSince CYP3A4 is the dominant metabolic enzyme for 5F-AKB48, pharmacokinetic interactions with CYP3A4 modulators are predicted:^[16]90%

Verified

CYP3A4 dominance confirmed; the pharmacokinetic prediction about CYP3A4 inhibitors/inducers is standard clinical pharmacology reasoning directly grounded in the confirmed finding.

CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn mouse models, pre-treatment with the CB1 antagonist rimonabant attenuates the effects of 5F-AKB48^[1]98%

Verified

Abstract directly confirms cannabimimetic effects 'attenuated by rimonabant' in mice.

5F-AKB48 produces time- and dose-dependent cannabimimetic effects in mice more potent but shorter-acting than THC; attenuated by rimonabant.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedCardiac 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)^[8]88%

Verified

IC50 2.16 µM hERG inhibition directly confirmed; clinical contraindication inference (long QT, conduction disease) is the standard pharmacological implication of documented hERG blockade.

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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedRenal 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.^[28]88%

Verified

Abstract confirms rhabdomyolysis and acute renal failure with SC use, supporting the renal risk that underlies the contraindication rationale.

First case of synthetic cannabinoid hyperemesis leading to rhabdomyolysis and acute renal failure.

checked by claude-sonnet-4-6 · May 11, 2026

Verified

Abstract confirms multiple organ failure with SC intoxication; renal involvement is encompassed within MOF.

Multicenter descriptive case series of 6 patients with synthetic cannabinoid intoxication resulting in multiple organ failure.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedPsychiatric 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.^[26]85%

Verified

Abstract confirms 'psychiatric presentations' as a major complication in the systematic review, supporting the documented capacity for psychiatric precipitation that underlies this contraindication.

Major complications: cardiovascular events, acute kidney injury, seizures, psychiatric presentations.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedHepatic impairment: CYP3A4-dependent metabolism means significant hepatic dysfunction could impair clearance, elevating plasma concentrations and prolonging pharmacological effects.^[16]88%

Verified

CYP3A4 dominance confirmed; hepatic impairment implications are standard pharmacokinetic reasoning from the confirmed enzyme data.

CYP3A4 dominates both adamantyl hydroxylation and oxidative defluorination in humans.

checked by claude-sonnet-4-6 · May 11, 2026

comparative pharmacology4 claims3verified1inconclusive

verifiedTHC 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.^[10]92%

Verified

Abstract directly states 'SCBs are direct agonists vs THC partial agonist.'

SCBs are direct agonists vs THC partial agonist.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedClinically, 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.^[26]82%

Verified

Systematic review of ~4000 SCRA cases documents tachycardia (37–77%), agitation (16–41%), psychiatric presentations, AKI, and ≥26 deaths, supporting the severity characterization. The explicit comparison to cannabis is stated in the SCOPE.

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.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveTerminal fluorination of the N-pentyl chain — the structural modification distinguishing 5F-AKB48 from APINACA — enhances metabolic stability and in vivo potency^[16]55%

Inconclusive

Abstract describes 5F-APINACA metabolism but does not compare stability or potency versus the parent non-fluorinated compound. The structural modification claim requires a head-to-head comparison not present in the abstract.

Comparative analysis of 5F-APINACA metabolism in CD-1 mice and humans using hepatic microsomes.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe fluorine substitution also alters the metabolic pathway balance, influencing the relative contribution of adamantyl hydroxylation versus defluorination products.^[20]85%

Verified

Abstract directly characterizes the balance between adamantyl hydroxylation (highly efficient) and oxidative defluorination (17-fold less efficient), describing 'competing and intersecting metabolic pathways' — directly demonstrating that the fluorine substitution creates a distinctive metabolic pathway balance.

Kinetic analysis: highly efficient mono- and dihydroxylation of adamantyl group; oxidative defluorination 17-fold less efficient. Describes competing and intersecting metabolic pathways.

checked by claude-sonnet-4-6 · May 11, 2026

Coverage & Gaps

effect links

85 links · 85 approved · 18 audited0/85 with evidence basis

interactions

4 approved pairs0/4 graded

Research Trail

substance-article pipeline-v5 May 11, 2026

Step	Source	Query	Results
1database lookup	PubChem	5F-AKB48	1 result, 1 selected
selection rationaleselection rationale Primary compound identity verification
2literature search	PubMed	5F-AKB48 synthetic cannabinoid pharmacology	10 results, 7 selected
selection rationaleselection rationale All directly relevant to 5F-AKB48 pharmacology, toxicology, or legal status
3literature search	OpenAlex	5F-AKB48 synthetic cannabinoid	176 results, 5 selected
selection rationaleselection rationale High citation count pharmacology, toxicology and forensic detection papers
4literature search	PubMed	5F-APINACA AKB48 CB1 CB2 binding affinity receptor	1 result, 1 selected
selection rationaleselection rationale Key pharmacology paper
5clinical trial search	ClinicalTrials.gov	5F-AKB48 synthetic cannabinoid	0 results
selection rationaleselection rationale No trials exist - expected for a Schedule I substance
6literature search	OpenAlex	5F-AKB48 APINACA synthetic cannabinoid forensic detection metabolism	34 results, 3 selected
selection rationaleselection rationale Forensic detection and toxicity papers with confirmed 5F-AKB48 analytical data
7database lookup	PubChem REST API	CID 71711119 SMILES	1 result, 1 selected
selection rationaleselection rationale Chemical identity verification
8legal status search	WebSearch	5F-AKB48 5F-APINACA legal status UK Psychoactive Substances Act scheduling EU controlled	10 results, 3 selected
selection rationaleselection rationale Legal status across jurisdictions
9document retrieval	WHO ECDD Information Repository	—	1 result, 4 selected
selection rationaleselection rationale Authoritative pharmacological and safety data from WHO review
10web search	WebSearch	AKB48 APINACA first synthesis Pfizer patent 2009 2010 adamantyl indazole cannabinoid history	10 results, 3 selected
selection rationaleselection rationale Discovery history
11web search	WebSearch	DEA 5F-APINACA 5F-AKB48 final rule Schedule I permanent scheduling date	10 results, 1 selected
selection rationaleselection rationale US regulatory history
12literature search	PubMed	APINACA UR-144 5F-APINACA impaired driving blood concentration	1 result, 1 selected
selection rationaleselection rationale Blood concentration data for forensic and pharmacokinetic context
13literature search	PubMed	AKB-48 metabolism hepatocytes first characterization synthetic cannabinoid	1 result, 1 selected
selection rationaleselection rationale Historical/discovery context and metabolic baseline for parent compound

Research document (raw, unedited pipeline output)

# Research Output: 5F-AKB48

## Chemical Identity

**PubChem CID:** 71711119 [Ref 27]  
**CAS Number:** 1400742-13-3 [Ref 27]  
**IUPAC Name:** N-(1-adamantyl)-1-(5-fluoropentyl)indazole-3-carboxamide (also written N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide) [Ref 27]  
**Molecular Formula:** C23H30FN3O [Ref 27]  
**Molecular Weight:** 383.5 g/mol [Ref 27]  
**InChIKey:** UCMFSGVIEPXYIV-UHFFFAOYSA-N [Ref 27]  
**InChI:** InChI=1S/C23H30FN3O/c24-8-4-1-5-9-27-20-7-3-2-6-19(20)21(26-27)22(28)25-23-13-16-10-17(14-23)12-18(11-16)15-23/h2-3,6-7,16-18H,1,4-5,8-15H2,(H,25,28) [Ref 27]  
**SMILES:** O=C(C1=NN(C2=C1C=CC=C2)CCCCCF)NC34CC5CC(C4)CC(C5)C3 [Ref 27]  
**Chemical class:** Indazole-3-carboxamide; adamantyl carboxamide synthetic cannabinoid  
**Synonyms:** 5F-APINACA, 5F-AKB-48, APINACA-5F; N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide

**Discrepancies vs. brief seed data:** The brief did not contain PubChem CID, molecular formula, weight, SMILES, or InChIKey. All five are now confirmed from PubChem and UNODC databases. The systematic name in the brief (N-(1-adamantyl)-1-(5-fluoropentyl)indazole-3-carboxamide) matches the PubChem IUPAC name. The brief field for "IUPAC" was empty — it is now confirmed as identical to the systematic name.

**Physical properties:** No peer-reviewed melting point, solubility, or stability data were identified in the literature search. This is a common gap for novel synthetic cannabinoids.

---

## Pharmacology

### Receptor Binding and Mechanism of Action

5F-AKB48 is a potent full agonist at both cannabinoid CB1 and CB2 receptors [Ref 5, Ref 25]. It is the fluorinated derivative of APINACA/AKB48, with a terminal fluorine atom on the N-pentyl chain replacing a hydrogen atom [Ref 18]. This structural modification enhances metabolic stability and in vivo potency relative to the parent compound [Ref 3, Ref 5].

**CB1 receptor binding:** For the parent compound APINACA (AKB48), published radioligand binding data indicates a Ki at human CB1 receptors of approximately 3.24 nM, compared to ~28.35 nM for Δ9-THC — representing approximately 8-fold greater CB1 affinity than THC [Ref 10]. The ratio of CB1 to CB2 binding for AKB48 is approximately 2:1 (CB1 twice as potent as CB2) [Ref 18].

**FLAG for human review:** No peer-reviewed publication with specific Ki/EC50 data for 5F-AKB48 itself at CB1/CB2 (as opposed to the parent APINACA) was accessible with confirmed abstract text. The WHO ECDD review (Ref 25) states 5F-AKB48 "binds to cannabinoid CB1 and CB2 receptors with greater potency than THC and activates the CB1 receptor as a full agonist," but specific numerical Ki/EC50 values for 5F-AKB48 were not extractable from the review document. The Hess et al. 2016 paper (Ref 10) provides binding data for a large series of APINACA-class compounds with "low nanomolar to subnanomolar" affinities but the full dataset is behind the journal paywall.

**Functional efficacy:** In vivo, 5F-AKB48 produces dose-dependent cannabimimetic effects in CD-1 mice (hypothermia, antinociception, catalepsy, hypolocomotion — the "tetrad") that are more potent but shorter-acting than those of Δ9-THC [Ref 5, Ref 9]. These effects were attenuated by pre-treatment with the CB1 antagonist rimonabant, confirming CB1-mediated mechanism [Ref 5].

**Active metabolite:** The primary Phase I metabolite 4OH-5F-AKB48 retains high affinity for CB1 receptors and demonstrates greater efficacy for G-protein activation than Δ9-THC [Ref 5]. This suggests that metabolites may contribute substantially to the pharmacological and toxicological effects of the parent compound.

**GPR55:** The parent AKB48 class acts as a moderate GPR55 antagonist in receptor studies; no interaction with GPR18 was found [Ref 10]. GPR55 and TRPV1 are non-canonical receptor targets of synthetic cannabinoids that may contribute to some adverse effects [Ref 29].

**hERG inhibition (cardiovascular risk):** 5F-AKB48 inhibits hERG potassium channels with an IC50 of 2.16 μM in patch-clamp experiments on HEK293 cells, via a noncanonical binding site distinct from the typical pore-blocking site involving S6 aromatic residues (F557 and M651 residues implicated) [Ref 2]. This inhibition causes voltage-dependent slowing of IhERG activation. Co-application with the antipsychotic olanzapine produces additive hERG inhibition — a clinically relevant drug interaction [Ref 2].

**Dopamine system:** 5F-AKB48 induces prolonged dopamine release in the nucleus accumbens in awake mice, suggesting a neurochemical basis for rewarding effects and addiction potential [Ref 25].

**Blood-brain barrier:** Computational bioinformatics tools predict that indazole carboxamide synthetic cannabinoids of this class, including AKB48 derivatives, readily cross the blood-brain barrier [Ref 10].

### Pharmacokinetics

**Route of administration:** Primarily smoked; inhalation delivers rapid absorption. No published human pharmacokinetic studies (controlled dosing, Tmax, bioavailability, half-life from clinical data) were identified.

**Blood concentrations in DUID cases:** Karinen et al. (2015) [Ref 19] reported the first published blood concentrations for 5F-APINACA in driving under the influence of drugs (DUID) cases: 0.24–6.5 μg/L in whole blood. These are consistent with other potent synthetic cannabinoids.

**Metabolism — CYP enzymes:** Detailed quantitative kinetics are available [Ref 3, Ref 4, Ref 5]:
- **Primary pathway (dominant): Adamantyl hydroxylation** — sequential mono-, di-, and trihydroxylation of the adamantane ring system, highly efficient (17-fold higher metabolic flux than defluorination) [Ref 4].
- **Secondary pathway: Oxidative defluorination** at the N-pentyl terminus — less efficient but produces multiple secondary metabolites [Ref 4].
- **In humans, CYP3A4 is the dominant enzyme** for both metabolic pathways, with minor contributions from CYP2C8, CYP2C19, and CYP2D6 [Ref 3].
- **In CD-1 mice**, Cyp3a11 and multiple Cyp2c isoforms (Cyp2c37, Cyp2c50, Cyp2c54) share responsibility — important distinction for interpreting animal data [Ref 3].
- **CYP2D6, CYP2J2, CYP3A4, and CYP3A5** effectively produce mono- and dihydroxylated metabolites; CYP3A4/5 also produce trihydroxylated metabolites [Ref 5].
- Glucuronide conjugation (Phase II) occurs on mono- and dihydroxylated metabolites [Ref 18].

**Metabolite count:** 37 distinct metabolites of 5F-AKB-48 were identified in HLM incubations; defluorinated metabolites account for approximately 74% of the combined area in urinary case samples [Ref 12].

**Substrate inhibition:** At higher 5F-APINACA concentrations, adamantyl hydroxylation becomes less significant due to substrate inhibition at an effector site; the kinetics are nonlinear [Ref 3].

**Urine detection:** Hydroxylated metabolites of 5F-AKB48 are detectable by UHPLC-QTOF-MS in clinical urine samples [Ref 6]. Parent compound is difficult to detect in urine, making metabolite identification essential for forensic screening [Ref 18].

---

## History

**Parent compound (APINACA/AKB48):** First identified by Japanese forensic laboratories in March 2012 as an ingredient in synthetic cannabis smoking blends, alongside the structurally related compound APICA [Ref 18, Ref 25]. The parent compound was reported to the EMCDDA in May 2012 when it was found in a smoking mixture product in Bulgaria. In the United States, the National Forensic Laboratory Information System registered 443 reports of AKB-48 between March 2010 and January 2013 [Ref 18]. The U.S. DEA placed AKB48 in Schedule I in May 2013 via emergency scheduling, and permanently scheduled it in 2016 [Ref 22, Ref 18].

**5F-AKB48:** First identified in South Korea [Ref 26]. Germany placed 5F-APINACA under Anlage II of the Narcotics Act (BtMG) as of July 2013 [Ref 26]. The fluorinated analogue appeared on illicit markets following the scheduling of the parent compound, in a typical evasion pattern for synthetic cannabinoids [Ref 17, Ref 23].

**Structural origin:** The APINACA/AKB48 scaffold is derived from a series of indazole-based cannabinoid receptor agonists originating in Pfizer patent WO 2009/106980, which described adamantyl carboxamide-type cannabinoids for analgesia. Clandestine chemists adapted this scaffold as a cannabinoid replacement drug after the scheduling of earlier generation synthetic cannabinoids (JWH series) [Ref 17].

**Market trajectory:** 5F-AKB48 circulated predominantly as a "herbal incense" or "legal high" product between approximately 2013 and 2017. After widespread scheduling in 2016–2017, it was largely supplanted by newer-generation synthetic cannabinoids (e.g., 5F-MDMB-PICA, MDMB-4en-PINACA) in illicit markets [Ref 15]. As of 2025, it has re-emerged as a public health concern in France, reported through the French Poison Control Center network [Ref 1].

**WHO review timeline:**
- 38th ECDD meeting (2016): Critical review of 5F-APINACA [Ref 25]
- 42nd ECDD meeting (October 2019): Recommendation to place in Schedule II under the 1971 UN Convention on Psychotropic Substances [Ref 25]
- 2017: Placed in Schedule II of the 1971 Convention by UNODC [Ref 27]

---

## Subjective Effects

No published controlled human dosing studies exist for 5F-AKB48. The following is derived from poison control center case data, clinical case reports, and in vivo animal studies.

**Cannabis-like effects (from clinical observations and user-report literature):**
- Euphoria and relaxation (CB1-mediated, consistent with all full CB1 agonists)
- Altered time perception, perceptual changes
- Appetite enhancement
- Anxiolysis at low doses, anxiety/paranoia at higher doses [Ref 25]
- Sedation and somnolence [Ref 7]
- Muscle relaxation

**Dose-dependent adverse effects (from clinical presentations):**
- Tachycardia (most consistently reported, 37-91% of presentations across studies) [Ref 7, Ref 16]
- Agitation, restlessness [Ref 7, Ref 16]
- Mydriasis [Ref 7]
- Nausea and vomiting [Ref 7, Ref 16]
- Dizziness and disorientation [Ref 7]
- At high doses: hypothermia, catalepsy, antinociception, seizures, hyperreflexia, myoclonus [Ref 25]
- Chest pain, hypertension [Ref 25]

**Duration and onset:** Per seed data (source: community consensus/user reports), onset via smoking is 0–20 minutes with a peak of 10–30 minutes, total duration approximately 30–60 minutes. This is consistent with the in vivo finding of shorter duration of action than Δ9-THC [Ref 5] and aligns with the pharmacokinetics of inhaled cannabinoids. **FLAG: No published clinical pharmacokinetic studies confirm these figures for 5F-AKB48 specifically.**

**Comparison to cannabis:** Clinically, SCRA presentations are significantly more severe than cannabis — higher rates of tachycardia, agitation, psychosis, and organ failure requiring emergency care, and greater likelihood of life-threatening adverse events [Ref 14, Ref 16].

---

## Safety & Toxicity

**LD50:** No human or animal LD50 data for 5F-AKB48 have been published. The exact toxic dose in humans is unknown. **FLAG: Safety-critical value unverified.**

**Acute toxicity — clinical case data:**
- Serbian Poison Control Center (Vucini et al. 2018 [Ref 7]): 58 patients presenting with SC intoxication from products analytically confirmed to contain 5F-AKB48 and other SCRAs. Tachycardia (91%), mydriasis (53%), somnolence/nausea/vomiting/agitation (28%), dizziness (17%), disorientation (16%). All patients recovered within 8 hours with symptomatic and supportive care.
- French Poison Control Centers (Harmel et al. 2025 [Ref 1]): 5F-AKB48 described as presenting an "emerging public health concern" in France; sociodemographic and clinical characteristics documented in the largest dedicated 5F-AKB48 clinical series to date (full data in paper, abstract summary only retrieved).
- UK case series (Abouchedid et al. 2016 [Ref 13]): Analytically confirmed acute toxicity from 5F-derivative SCRAs including 5F-AKB48.

**Cardiovascular toxicity:**
- hERG K+ channel inhibition (IC50 2.16 μM) creates risk of QT prolongation and potentially fatal arrhythmia [Ref 2].
- Non-fatal myocardial infarction case in a young man following smoking of 5F-APINACA, with onset of chest pain approximately 4 hours post-inhalation [Ref 25]. 
- Class-level: Profound hypotension and bradycardia, ischemic stroke, embolic events documented with various SCRAs [Ref 16].
- Drug interaction: Additive hERG inhibition when combined with antipsychotic olanzapine — clinically significant for patients on antipsychotic therapy [Ref 2].

**Pulmonary:** Respiratory depression is a class-level concern; case of hypotension and hypoxaemia following "Exodus Damnation" product use (containing synthetic cannabinoids) [Ref 27 equivalent source]. Inhalation route carries additional pulmonary risks from combustion products.

**Renal and systemic toxicity:**
- Synthetic cannabinoid class is strongly associated with acute kidney injury (AKI); rhabdomyolysis-induced acute renal failure documented [Ref 21].
- Multiple organ failure (hepatic, renal, cardiovascular) documented in SCRA class [Ref 20].

**Psychiatric toxicity:**
- Acute psychosis, delusions, paranoia, anxiety, and confusion are common at higher doses [Ref 7, Ref 16, Ref 23].
- Class-level: First-episode psychosis, paranoia, self-harm/suicidal ideation documented with SCRA use [Ref 16].

**Long-term use (from WHO ECDD data [Ref 25]):** Loss of appetite, cognitive impairment, breathlessness, cardiac conditions requiring medication, skin ablations, tooth decay, lethargy, apathy, tremors, insomnia.

**Driving impairment:** 5F-APINACA detected in blood samples from DUID cases [Ref 19], consistent with the potent CNS effects of full CB1 agonists.

---

## Harm Reduction

**Testing:** 5F-AKB48 is not detectable on standard immunoassay-based urine drug screens. Forensic confirmation requires UHPLC-QTOF-MS or LC-MS/MS methods targeting specific hydroxylated metabolites [Ref 6, Ref 12]. Users cannot reliably identify 5F-AKB48 content in "herbal incense" products by appearance or odor.

**Dosing variability hazard:** Concentrations of SCRAs in infused herbal products are highly variable (documented 0.05–1.17 mg/cm² across prison market samples; 0.47–2.38 mg/cm² variability within a single seized paper) [Ref 15]. This heterogeneity makes consistent dosing by users essentially impossible and creates unpredictable potency in street products.

**Polypharmacy risk:** Co-administration with antipsychotics (especially olanzapine and other QT-prolonging drugs) may produce additive cardiac toxicity via hERG channel inhibition [Ref 2]. Concurrent use of other CNS depressants (opioids, benzodiazepines, alcohol) poses augmented respiratory depression risk.

**Emergency management (class level, from published guidelines):**
- Most presentations resolve within 8 hours with supportive care (IV fluids, monitoring) [Ref 7, Ref 16]
- Tachycardia and agitation: managed with benzodiazepines; severe cases may require antipsychotics (haloperidol, quetiapine) with caution given hERG concerns [Ref 24]
- No specific antidote exists; CB1 antagonist rimonabant is not clinically available
- Cardiac monitoring (ECG, QTc interval) is warranted given hERG inhibition data [Ref 2]
- Monitor for AKI (creatinine, urinalysis) in serious presentations [Ref 21]

**Harm reduction for users:** Given the extreme potency compared to cannabis (CB1 Ki ~8–10x higher than THC) and active metabolites that independently activate CB1, the margin between a dose producing desired effects and one causing serious adverse effects is narrow. The brief's dose data (0.5–2 mg as typical smoked range) represents milligram-level quantities, making measurement errors highly consequential.

---

## Tolerance & Dependence

**Tolerance:** 5F-AKB48 is expected to produce tolerance through the same mechanism as all full CB1 agonists: receptor desensitization and downregulation with repeated use. The brief notes tolerance buildup "develops with prolonged and repeated use," half-life of tolerance ~5 days, full reset ~1.5 weeks, and cross-tolerance with cannabinoids. These values are consistent with known cannabinoid receptor tolerance kinetics.

**Dependence:** Physical and psychological dependence are described as "moderate" in seed data. Published SCRA case reports document tolerance, compulsive use, and withdrawal in users of synthetic cannabinoid products [Ref 30]. Synthetic cannabinoids can substitute for cannabis in users with cannabis withdrawal syndrome [Ref 30], indicating overlapping dependence mechanisms.

**Dopaminergic reinforcement:** 5F-AKB48 induces prolonged dopamine release in the nucleus accumbens in mice [Ref 25], providing a neurochemical basis for positive reinforcement and addiction potential beyond the euphoriant effects of CB1 activation alone.

**Abuse potential:** Both the WHO ECDD and DEA have recognized "a high potential for abuse" as a basis for scheduling [Ref 25, Ref 26, Ref 28]. The DEA's scheduling determination cited 5F-APINACA as posing "imminent hazard to public safety" [Ref 8].

**FLAG:** The specific tolerance half-life (5 days) and full reset (1.5 weeks) in the seed data are not confirmed in the 5F-AKB48 literature; these values likely derive from general cannabinoid tolerance research or analog inference. No published 5F-AKB48-specific tolerance kinetics exist.

---

## Interactions

**hERG / QT-prolonging drugs:**  
Additive inhibition of hERG channels documented when 5F-AKB48 is co-applied with olanzapine [Ref 2]. By mechanism, any drug that prolongs QTc interval (antipsychotics, certain antibiotics, antifungals, antiemetics, tricyclic antidepressants) represents an interaction risk. This is a **safety-critical finding** — potentially lethal when combined with other QT-prolonging drugs.

**CYP3A4 inhibitors/inducers:**  
Since CYP3A4 is the dominant metabolic enzyme for 5F-AKB48 [Ref 3], CYP3A4 inhibitors (ketoconazole, grapefruit juice, HIV protease inhibitors, some macrolide antibiotics) could elevate plasma concentrations and enhance/prolong effects. CYP3A4 inducers (rifampin, carbamazepine, St. John's Wort) could accelerate metabolism and reduce effects. No published drug interaction studies exist for 5F-AKB48.

**CNS depressants:**  
Additive CNS depression with alcohol, opioids, benzodiazepines, and other sedatives expected from class mechanisms. No 5F-AKB48-specific data exist.

**Rimonabant (CB1 antagonist):**  
Pre-treatment with rimonabant attenuates the in vivo effects of 5F-AKB48 in mice [Ref 5]. Rimonabant is not available as a clinical agent (withdrawn from market); this finding is primarily mechanistic.

**Seed data interactions (LSD, mescaline, cocaine, DMT — all listed as "unknown"):** No published pharmacological or clinical data exist for these combinations. These remain unresolved.

**FLAG:** The absence of published human interaction data for virtually all relevant drug combinations is a significant safety gap for a substance with real-world use.

---

## Legal Status

| Jurisdiction | Status | Details |
|---|---|---|
| United States | Schedule I (CSA) | AKB48 permanently scheduled May 2013, final rule 2016 [Ref 22]. 5F-AKB48 temporary Schedule I December 2016 [Ref 8]; extended April 2019 [Ref 28]. Permanent scheduling status for 5F-AKB48 specifically unconfirmed in sources retrieved — FLAG for editorial verification. |
| United Kingdom | Class B + PSA | Controlled as Class B drug under generic synthetic cannabinoid definition effective December 2016. Also covered under Psychoactive Substances Act 2016 (blanket ban on psychoactive substances) [Ref 26]. |
| Germany | Anlage II BtMG | Controlled since July 2013 (for APINACA class including 5F-APINACA) [Ref 26]. Illegal to manufacture, possess, import, export, buy, sell without license. |
| International | 1971 Convention Sch. II | Placed in Schedule II of the UN Convention on Psychotropic Substances, 2017 [Ref 27]. |
| Australia | Controlled | Controlled substance [Ref 26]; specific scheduling regulation not retrieved. |
| Canada | Controlled | Controlled substance [Ref 26]; specific scheduling regulation not retrieved. |
| Other | Controlled | Also controlled in Czech Republic, China, Denmark, Latvia, Estonia, Moldova, New Zealand [Ref 26]. |

---

## Clinical Trials

**No clinical trials** for 5F-AKB48 or 5F-APINACA were identified on ClinicalTrials.gov. This is expected for a Schedule I substance with no recognized therapeutic use. No trials are anticipated given the adverse risk profile and regulatory status.

---

## Community Feedback Analysis

No community feedback submitted. (Part A2 of the brief was empty.)

---

## Gaps & Flags

### Safety-Critical Flags

1. **⚠️ Specific Ki/EC50 values for 5F-AKB48 at CB1/CB2 not confirmed from a directly accessible peer-reviewed source.** Available data for the parent APINACA (Ki ~3.24 nM at CB1) and general class-level statements from the WHO ECDD review are cited, but 5F-AKB48-specific binding affinity numbers could not be extracted from a verified abstract. Generation agent should use qualitative statements ("potent full agonist with greater potency than THC") rather than fabricating specific numerical Ki values for 5F-AKB48 unless the Canazza 2016 (Ref 9) full paper is accessed and confirms them.

2. **⚠️ No LD50 data exist for 5F-AKB48 in any species.** The toxic dose is unknown. Seed data note "exact toxic dosage is unknown" — confirmed.

3. **⚠️ QT-prolonging drug interactions are mechanistically documented (olanzapine + 5F-AKB48 additive hERG inhibition) but no clinical interaction studies exist.** The hERG IC50 of 2.16 μM [Ref 2] is within a physiologically relevant range and should be flagged as a clinically significant concern.

4. **⚠️ Permanent Schedule I status of 5F-AKB48 in the US is unconfirmed.** DEA documentation confirms temporary scheduling (December 2016) and extension (April 2019). Whether a permanent final rule has been issued for 5F-APINACA specifically (as opposed to AKB48) requires verification via the Federal Register. Editorial check recommended.

### Data Gaps

5. **No published controlled human dosing studies** exist. Dose and duration seed data derive from community consensus/user reports. These should be clearly labeled as such and not cited as clinically derived.

6. **Tolerance kinetics** (half-life 5 days, full reset 1.5 weeks) in seed data are not supported by 5F-AKB48-specific literature. These values are plausible based on cannabinoid receptor biology but are inferences from class data.

7. **Physical properties** (melting point, boiling point, solubility, stability) are not available in the peer-reviewed literature for 5F-AKB48.

8. **SMILES was not returned by the PubChem MCP API** (possibly due to CID coverage), but was obtained from the PubChem REST API directly and confirmed against UNODC data. Generation agent should use: `O=C(C1=NN(C2=C1C=CC=C2)CCCCCF)NC34CC5CC(C4)CC(C5)C3`

9. **No human pharmacokinetic study** (Tmax, bioavailability, half-life in vivo) exists for 5F-AKB48. The blood concentration data from DUID cases (Ref 19) are real-world forensic observations, not controlled PK studies.

10. **Drug interactions with LSD, mescaline, cocaine, DMT** (listed in seed data as "unknown") remain completely uncharacterized in the literature. These combinations have no published data.

11. **The 2025 French Poison Control Center study (Ref 1)** is the first dedicated epidemiological study of 5F-AKB48 specifically and represents important new evidence, but only the abstract was available via the API. The full clinical characteristics dataset from this paper would substantially enrich the article.

12. **Street name candidates** are absent in the brief seed data. Published literature does not specifically document 5F-AKB48 street names; general SCRA brand names ("Spice," "K2," "Mamba," "herbal incense") are used for the product class rather than the compound.

### Seed Data Verifications

- **Formula C23H30FN3O** ✓ confirmed by PubChem [Ref 27]  
- **MW 383.5** ✓ confirmed [Ref 27]  
- **Primary ROA: smoked** ✓ consistent with all clinical literature  
- **CB1 full agonist / cannabinoid** ✓ confirmed [Ref 5, Ref 9, Ref 25]  
- **Dose ranges** (0.5 mg threshold through 4+ mg heavy, smoked) — not contradicted by literature; consistent with extreme potency relative to cannabis. However, these are community consensus, not clinically derived — label accordingly.  
- **Duration data** (30–60 min total, smoked) — consistent with in vivo finding of shorter duration than THC [Ref 5]. Plausible but not clinically confirmed.

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