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Psychedex
Sources
29
1 strong · 20 moderate · 8 weak

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

Claims checked
93
58verified12partial23inconclusive

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
144/144 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold1 mg1 mglow
Low1–3 mg1–3 mglow
Common3–5 mg3–5 mglow
Strong5–8 mg5–8 mglow
Heavy8+ mg8+ mglow
Editorial

Carried forward from existing DB / community consensus (PsychonautWiki). No published controlled human dosing study exists for 5F-PB-22 at any ROA. Dose ranges are identical for oral and smoked in seed data, which is pharmacologically implausible — smoked bioavailability is typically higher with faster onset. Oral bioavailability is entirely unstudied. Flagged for editorial review as safety-critical unverified data.

Reasoning

Carried forward from existing DB / community consensus (PsychonautWiki). No published controlled human dosing study exists for 5F-PB-22 at any ROA. Dose ranges are identical for oral and smoked in seed data, which is pharmacologically implausible — smoked bioavailability is typically higher with faster onset. Oral bioavailability is entirely unstudied. Flagged for editorial review as safety-critical unverified data.

Evidence basis: community_consensus_large

smokedtrace

FieldPublishedAI ProposedConfidence
Threshold1 mg1 mglow
Low1–3 mg1–3 mglow
Common3–5 mg3–5 mglow
Strong5–8 mg5–8 mglow
Heavy8+ mg8+ mglow
Editorial

Carried forward from existing DB / community consensus (PsychonautWiki). No published controlled human dosing study exists. Identical ranges to oral route in seed data — pharmacologically implausible given typically higher smoked bioavailability and faster onset. Rapid CES1 ester hydrolysis may limit effective duration especially orally, but smoked route bypasses first-pass metabolism. Flagged for editorial review as safety-critical unverified data.

Reasoning

Carried forward from existing DB / community consensus (PsychonautWiki). No published controlled human dosing study exists. Identical ranges to oral route in seed data — pharmacologically implausible given typically higher smoked bioavailability and faster onset. Rapid CES1 ester hydrolysis may limit effective duration especially orally, but smoked route bypasses first-pass metabolism. Flagged for editorial review as safety-critical unverified data.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Totaltrace2–3 hours2–3 hourslow
Editorial

Carried forward from existing DB / community consensus. No published pharmacokinetic study confirms oral duration. Rapid CES1 ester hydrolysis (Thomsen 2015) is consistent with a relatively short total duration despite high receptor affinity.

Reasoning

Carried forward from existing DB / community consensus. No published pharmacokinetic study confirms oral duration. Rapid CES1 ester hydrolysis (Thomsen 2015) is consistent with a relatively short total duration despite high receptor affinity.

Evidence basis: community_consensus_large

smoked

FieldPublishedAI ProposedConfidence
Onsettrace0.1–0.5 minutes0.1–0.5 minuteslow
Editorial

Community report (PsychonautWiki) states onset ~10 seconds via smoked route. Pulmonary absorption provides near-immediate onset consistent with other smoked synthetic cannabinoids. Not verified in published literature.

Reasoning

Community report (PsychonautWiki) states onset ~10 seconds via smoked route. Pulmonary absorption provides near-immediate onset consistent with other smoked synthetic cannabinoids. Not verified in published literature.

Evidence basis: community_consensus_large

Peaktrace20–40 minutes20–40 minuteslow
Editorial

Community report (PsychonautWiki) states peak ~30 minutes. Widened range (20–40 min) to reflect uncertainty. Not verified in published literature.

Reasoning

Community report (PsychonautWiki) states peak ~30 minutes. Widened range (20–40 min) to reflect uncertainty. Not verified in published literature.

Evidence basis: community_consensus_large

Totaltrace60–120 minutes60–120 minuteslow
Editorial

Community report (PsychonautWiki) states total ~90 minutes. Widened range (60–120 min) to reflect uncertainty. Consistent with rapid CES1 ester hydrolysis limiting parent compound duration. Not verified in published literature.

Reasoning

Community report (PsychonautWiki) states total ~90 minutes. Widened range (60–120 min) to reflect uncertainty. Consistent with rapid CES1 ester hydrolysis limiting parent compound duration. Not verified in published literature.

Evidence basis: community_consensus_large

After effectstrace10–30 minutes10–30 minuteslow
Editorial

Community report (PsychonautWiki) states aftereffects ~15 minutes. Widened range (10–30 min) to reflect uncertainty. Active metabolites (hydroxypentyl compounds retaining CB1/CB2 efficacy per Gamage 2019) may contribute to residual effects. Not verified in published literature.

Reasoning

Community report (PsychonautWiki) states aftereffects ~15 minutes. Widened range (10–30 min) to reflect uncertainty. Active metabolites (hydroxypentyl compounds retaining CB1/CB2 efficacy per Gamage 2019) may contribute to residual effects. Not verified in published literature.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutehighhighmedium
Chronicmoderatemoderatemedium
Organs Affectedcardiovascular, neurological, renal, hepaticcardiovascular, neurological, renal, hepaticmedium
Editorial

Work-notes specify acute=high, chronic=moderate, confidence=medium. Multiple independent fatality case series (Behonick 2014, Angerer 2017, Langford & Bolton 2018) plus Tait et al. 2015 systematic review of ~4,000 SC cases documenting tachycardia, MI, AKI, seizures, MOF. All fatalities involved polydrug context. Postmortem redistribution confounds concentration interpretation. Hepatic organ involvement inferred from CES1 metabolism pathway (Thomsen 2015).

Reasoning

Work-notes specify acute=high, chronic=moderate, confidence=medium. Multiple independent fatality case series (Behonick 2014, Angerer 2017, Langford & Bolton 2018) plus Tait et al. 2015 systematic review of ~4,000 SC cases documenting tachycardia, MI, AKI, seizures, MOF. All fatalities involved polydrug context. Postmortem redistribution confounds concentration interpretation. Hepatic organ involvement inferred from CES1 metabolism pathway (Thomsen 2015).

Evidence basis: published_case_series

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalmoderatemoderatemedium
Psychologicalmoderatemoderatemedium
Compulsive Redosingmoderatemoderatemedium
Dose Escalationmoderatemoderatemedium
Editorial

Work-notes specify physical=moderate, psychological=moderate, compulsive redosing=moderate, dose escalation=moderate, confidence=medium. Dependence data is class-level (Gunderson 2012, Cooper 2016), not 5F-PB-22-specific. Reinforcement mechanism confirmed by De Luca et al. 2016 microdialysis data showing CB1-dependent NAc shell dopamine release.

Reasoning

Work-notes specify physical=moderate, psychological=moderate, compulsive redosing=moderate, dose escalation=moderate, confidence=medium. Dependence data is class-level (Gunderson 2012, Cooper 2016), not 5F-PB-22-specific. Reinforcement mechanism confirmed by De Luca et al. 2016 microdialysis data showing CB1-dependent NAc shell dopamine release.

Evidence basis: community_consensus_large

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitymoderatemoderatelow
Symptomsanxiety, nausea, insomnia, irritabilityanxiety, nausea, insomnia, irritabilitylow
FatalNoNolow
Medical SupervisionNot requiredNot requiredlow
Editorial

Work-notes specify withdrawal exists with mild-to-moderate severity. Symptoms (anxiety, nausea, insomnia, irritability) from class-level data (Cooper 2016). Onset and duration not characterized for 5F-PB-22 specifically. Treatment includes benzodiazepines for symptom relief and quetiapine in some cases.

Reasoning

Work-notes specify withdrawal exists with mild-to-moderate severity. Symptoms (anxiety, nausea, insomnia, irritability) from class-level data (Cooper 2016). Onset and duration not characterized for 5F-PB-22 specifically. Treatment includes benzodiazepines for symptom relief and quetiapine in some cases.

Evidence basis: community_consensus_large

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Buildupmoderatemoderatelow
Half-life5 days5 dayslow
Full Reset10.5 days10.5 dayslow
Cross-tolerancescannabinoidscannabinoidslow
Editorial

Work-notes specify buildup=moderate, half-life=5 days, full reset=1.5 weeks, cross-tolerances=cannabinoids, confidence=low. All values are class-level inferences from synthetic cannabinoid pharmacology. No 5F-PB-22-specific tolerance data exist. Reference class: synthetic cannabinoid receptor agonists (JWH-018 and related compounds).

Reasoning

Work-notes specify buildup=moderate, half-life=5 days, full reset=1.5 weeks, cross-tolerances=cannabinoids, confidence=low. All values are class-level inferences from synthetic cannabinoid pharmacology. No 5F-PB-22-specific tolerance data exist. Reference class: synthetic cannabinoid receptor agonists (JWH-018 and related compounds).

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
cardiovascular Cardiovascular diseasetraceabsoluteabsolutemedium
Editorial

Work-notes list cardiovascular disease as absolute contraindication. Class-level systematic review (Tait et al.) documents tachycardia in 37–77% of SC presentations and MI/arrhythmia as severe adverse events. No 5F-PB-22-specific clinical data, but full CB1 agonist pharmacology strongly supports this contraindication.

Reasoning

Work-notes list cardiovascular disease as absolute contraindication. Class-level systematic review (Tait et al.) documents tachycardia in 37–77% of SC presentations and MI/arrhythmia as severe adverse events. No 5F-PB-22-specific clinical data, but full CB1 agonist pharmacology strongly supports this contraindication.

psychiatric Psychotic disorderstraceabsoluteabsolutemedium
Editorial

Work-notes list psychotic disorders as absolute contraindication. Van Amsterdam et al. 2015 establishes that full CB1 agonism without CBD elevates psychosis risk. Class extrapolation from synthetic cannabinoid systematic review.

Reasoning

Work-notes list psychotic disorders as absolute contraindication. Van Amsterdam et al. 2015 establishes that full CB1 agonism without CBD elevates psychosis risk. Class extrapolation from synthetic cannabinoid systematic review.

other Concurrent ethanol usetraceabsoluteabsolutehigh
Editorial

Work-notes list ethanol co-use as absolute contraindication with high confidence — the only entry with substance-specific evidence. Documented fatalities (Langford & Bolton 2018; Angerer et al. 2017) and confirmed transesterification pathway (Apirakkan 2019, 2021).

Reasoning

Work-notes list ethanol co-use as absolute contraindication with high confidence — the only entry with substance-specific evidence. Documented fatalities (Langford & Bolton 2018; Angerer et al. 2017) and confirmed transesterification pathway (Apirakkan 2019, 2021).

pregnancy breastfeeding Pregnancytraceabsoluteabsolutelow
Editorial

Work-notes list pregnancy as absolute contraindication. Based on Alexandre et al. 2020 in vitro data showing CB1-mediated neurodevelopmental effects. Low confidence reflects in vitro evidence only.

Reasoning

Work-notes list pregnancy as absolute contraindication. Based on Alexandre et al. 2020 in vitro data showing CB1-mediated neurodevelopmental effects. Low confidence reflects in vitro evidence only.

hepatic Hepatic impairmenttracerelativerelativelow
Editorial

Work-notes list hepatic impairment as relative contraindication with low confidence (structural inference). CES1 hepatic metabolism confirmed by Thomsen et al. 2015. No clinical data on hepatically impaired patients.

Reasoning

Work-notes list hepatic impairment as relative contraindication with low confidence (structural inference). CES1 hepatic metabolism confirmed by Thomsen et al. 2015. No clinical data on hepatically impaired patients.

renal Renal impairmenttracerelativerelativelow
Editorial

Work-notes list renal impairment as relative contraindication with low confidence (class extrapolation). AKI is documented in the Tait et al. 2015 systematic review of ~4,000 SC cases.

Reasoning

Work-notes list renal impairment as relative contraindication with low confidence (class extrapolation). AKI is documented in the Tait et al. 2015 systematic review of ~4,000 SC cases.

neurological Seizure disorderstracerelativerelativelow
Editorial

Work-notes list seizure disorders as relative contraindication with low confidence (class extrapolation). Seizures documented in Tait et al. 2015 systematic review.

Reasoning

Work-notes list seizure disorders as relative contraindication with low confidence (class extrapolation). Seizures documented in Tait et al. 2015 systematic review.

Timeline Phases

smoked

FieldPublishedAI ProposedConfidence
Onsettrace5–60 sec(i=0.30)5–60 sec(i=0.30)low
Editorial

Work-notes specify smoked timeline: onset (seconds, 0.3), peak (~30 min, 1.0), resolution (~45–60 min post-peak, 0.4), afterglow (~15 min, 0.15). All duration data from community reports (PsychonautWiki), not verified in published literature. Driving advisory verbatim from work-notes.

Reasoning

Work-notes specify smoked timeline: onset (seconds, 0.3), peak (~30 min, 1.0), resolution (~45–60 min post-peak, 0.4), afterglow (~15 min, 0.15). All duration data from community reports (PsychonautWiki), not verified in published literature. Driving advisory verbatim from work-notes.

Evidence basis: community_consensus_large

Peaktrace1200–2700 sec(i=1.00)1200–2700 sec(i=1.00)low
Editorial

Work-notes specify smoked timeline: onset (seconds, 0.3), peak (~30 min, 1.0), resolution (~45–60 min post-peak, 0.4), afterglow (~15 min, 0.15). All duration data from community reports (PsychonautWiki), not verified in published literature. Driving advisory verbatim from work-notes.

Reasoning

Work-notes specify smoked timeline: onset (seconds, 0.3), peak (~30 min, 1.0), resolution (~45–60 min post-peak, 0.4), afterglow (~15 min, 0.15). All duration data from community reports (PsychonautWiki), not verified in published literature. Driving advisory verbatim from work-notes.

Evidence basis: community_consensus_large

Resolutiontrace2700–3600 sec(i=0.40)2700–3600 sec(i=0.40)low
Editorial

Work-notes specify smoked timeline: onset (seconds, 0.3), peak (~30 min, 1.0), resolution (~45–60 min post-peak, 0.4), afterglow (~15 min, 0.15). All duration data from community reports (PsychonautWiki), not verified in published literature. Driving advisory verbatim from work-notes.

Reasoning

Work-notes specify smoked timeline: onset (seconds, 0.3), peak (~30 min, 1.0), resolution (~45–60 min post-peak, 0.4), afterglow (~15 min, 0.15). All duration data from community reports (PsychonautWiki), not verified in published literature. Driving advisory verbatim from work-notes.

Evidence basis: community_consensus_large

Afterglowtrace600–1800 sec(i=0.15)600–1800 sec(i=0.15)low
Editorial

Work-notes specify smoked timeline: onset (seconds, 0.3), peak (~30 min, 1.0), resolution (~45–60 min post-peak, 0.4), afterglow (~15 min, 0.15). All duration data from community reports (PsychonautWiki), not verified in published literature. Driving advisory verbatim from work-notes.

Reasoning

Work-notes specify smoked timeline: onset (seconds, 0.3), peak (~30 min, 1.0), resolution (~45–60 min post-peak, 0.4), afterglow (~15 min, 0.15). All duration data from community reports (PsychonautWiki), not verified in published literature. Driving advisory verbatim from work-notes.

Evidence basis: community_consensus_large

oral

FieldPublishedAI ProposedConfidence
Onsettrace900–2700 sec(i=0.20)900–2700 sec(i=0.20)low
Editorial

Work-notes specify oral timeline with only three phases (onset/peak/resolution) due to insufficient data to subdivide further. Total duration 2–3 hours from existing DB / community consensus. Onset timing, peak timing, and phase boundaries are unknown — durations estimated from total window and pharmacological reasoning (CES1 ester hydrolysis). Driving advisory verbatim from work-notes.

Reasoning

Work-notes specify oral timeline with only three phases (onset/peak/resolution) due to insufficient data to subdivide further. Total duration 2–3 hours from existing DB / community consensus. Onset timing, peak timing, and phase boundaries are unknown — durations estimated from total window and pharmacological reasoning (CES1 ester hydrolysis). Driving advisory verbatim from work-notes.

Evidence basis: community_consensus_large

Peaktrace2700–5400 sec(i=1.00)2700–5400 sec(i=1.00)low
Editorial

Work-notes specify oral timeline with only three phases (onset/peak/resolution) due to insufficient data to subdivide further. Total duration 2–3 hours from existing DB / community consensus. Onset timing, peak timing, and phase boundaries are unknown — durations estimated from total window and pharmacological reasoning (CES1 ester hydrolysis). Driving advisory verbatim from work-notes.

Reasoning

Work-notes specify oral timeline with only three phases (onset/peak/resolution) due to insufficient data to subdivide further. Total duration 2–3 hours from existing DB / community consensus. Onset timing, peak timing, and phase boundaries are unknown — durations estimated from total window and pharmacological reasoning (CES1 ester hydrolysis). Driving advisory verbatim from work-notes.

Evidence basis: community_consensus_large

Resolutiontrace1800–3600 sec(i=0.40)1800–3600 sec(i=0.40)low
Editorial

Work-notes specify oral timeline with only three phases (onset/peak/resolution) due to insufficient data to subdivide further. Total duration 2–3 hours from existing DB / community consensus. Onset timing, peak timing, and phase boundaries are unknown — durations estimated from total window and pharmacological reasoning (CES1 ester hydrolysis). Driving advisory verbatim from work-notes.

Reasoning

Work-notes specify oral timeline with only three phases (onset/peak/resolution) due to insufficient data to subdivide further. Total duration 2–3 hours from existing DB / community consensus. Onset timing, peak timing, and phase boundaries are unknown — durations estimated from total window and pharmacological reasoning (CES1 ester hydrolysis). Driving advisory verbatim from work-notes.

Evidence basis: community_consensus_large

Dose Tier Summaries

thresholdtrace
low

Minimal perceptible effects — a slight shift in mood or body awareness emerges at approximately 1 mg. Users may notice faint relaxation, a mild warmth, or subtle changes in sensory texture without clear intoxication. Physical effects are minimal: slight dry mouth or a marginal increase in heart rate may be detectable. Appetite changes are unlikely at this level. The margin between threshold and adverse effects is narrow. As a full CB1 agonist with no intrinsic safety ceiling, even threshold doses engage a receptor system capable of escalating to full activation with small dose increases. Herbal blend products contain unknown and variable concentrations — accurate dosing requires pure compound and a milligram-precision scale.

Editorial

Work-notes specify threshold at ~1 mg. No controlled human dosing study exists; values derived from community consensus (PsychonautWiki). Dose ranges identical for oral and smoked in seed data, which is pharmacologically implausible — flagged for editorial review.

Reasoning

Work-notes specify threshold at ~1 mg. No controlled human dosing study exists; values derived from community consensus (PsychonautWiki). Dose ranges identical for oral and smoked in seed data, which is pharmacologically implausible — flagged for editorial review.

Evidence basis: community_consensus_large

lighttrace
low

Mild euphoria and relaxation become clearly perceptible. Slight color enhancement and music enhancement may emerge. Cognitive tempo begins to slow — thought deceleration is noticeable but manageable. Mood elevation is gentle, with emotional enhancement adding warmth to social or introspective settings. Physically, motor control impairment begins to appear. Bodily heaviness may set in, and appetite enhancement often emerges. Heart rate may increase modestly. Sedation is mild but present. Effects remain manageable for most users, but individual sensitivity varies enormously with this compound class. The steep dose-response curve of full CB1 agonists means small increases beyond this range produce disproportionately stronger effects.

Editorial

Work-notes specify light range at 1–3 mg. Effect descriptions inferred from JWH-018 user-report data and synthetic cannabinoid class pharmacology. No controlled subjective study exists for 5F-PB-22.

Reasoning

Work-notes specify light range at 1–3 mg. Effect descriptions inferred from JWH-018 user-report data and synthetic cannabinoid class pharmacology. No controlled subjective study exists for 5F-PB-22.

Evidence basis: community_consensus_large

commontrace
low

Clear cannabis-like intoxication with full CB1 agonist intensity. Euphoria is pronounced, accompanied by sedation and cognitive slowing. Thought deceleration and analysis suppression become obvious. Immersion enhancement may deepen engagement with media or music. Perceptual shifts include color enhancement, music enhancement, and mild vestibular distortion. Physically, motor control impairment is noticeable — coordination and reaction time are reduced. Bodily heaviness is prominent. Appetite enhancement is reliable. Heart rate elevation (abnormal heartbeat) may become perceptible. Spontaneous body sensations and dehydration sensation are common. Anxiety and paranoia are possible, especially in naive users, unfamiliar settings, or at the upper end of this range. The compressed margin between desired effects and toxicity makes careful dosing essential.

Editorial

Work-notes specify common range at 3–5 mg. Effect profile drawn from work-notes effects list at common dose. All effect descriptions are class-inferred from JWH-018 and synthetic cannabinoid pharmacology; no controlled 5F-PB-22 subjective study exists.

Reasoning

Work-notes specify common range at 3–5 mg. Effect profile drawn from work-notes effects list at common dose. All effect descriptions are class-inferred from JWH-018 and synthetic cannabinoid pharmacology; no controlled 5F-PB-22 subjective study exists.

Evidence basis: community_consensus_large

strongtrace
low

Intense sedation dominates, with pronounced cognitive impairment and strong perceptual distortion. Thought deceleration and analysis suppression are heavy. Delusions may emerge. Conceptual thinking and thought connectivity may produce unusual ideation that feels significant but lacks coherence. Anxiety and paranoia become more likely and may be difficult to manage. Physically, motor control is significantly impaired — standing and walking may be difficult. Bodily heaviness is pronounced. Risk of tachycardia and cardiovascular stress increases substantially. Pain suppression is noticeable. Vasoconstriction may contribute to peripheral discomfort. This range approaches the adverse event threshold. The overlap between strong-dose blood concentrations and those found in published fatalities underscores the absence of a pharmacological safety buffer inherent to full CB1 agonism.

Editorial

Work-notes specify strong range at 5–8 mg. Adverse event threshold language from work-notes. Fatality blood concentration overlap documented in article prose (Behonick et al. 2014; Kakehashi et al. 2020).

Reasoning

Work-notes specify strong range at 5–8 mg. Adverse event threshold language from work-notes. Fatality blood concentration overlap documented in article prose (Behonick et al. 2014; Kakehashi et al. 2020).

Evidence basis: community_consensus_large

heavytrace
low

High risk of serious adverse events. Severe tachycardia, psychosis, loss of consciousness, and seizures are possible at class level. Full CB1 agonism provides no pharmacological ceiling on receptor activation — there is no intrinsic limit preventing escalation to life-threatening toxicity. Physically, cardiovascular stress may be severe. Nausea, vomiting, and loss of motor control are likely. Respiratory depression is a concern, particularly with co-administered CNS depressants. Published fatalities have occurred at postmortem blood concentrations (0.37–1.5 ng/mL) that overlap with impairment-level concentrations. Polydrug combinations at this dose level are potentially lethal. Concurrent ethanol use is documented as fatal. Herbal blend products with unknown concentrations make accidental heavy dosing a persistent risk — milligram-precision weighing of pure compound is the only way to control dose at this level.

Editorial

Work-notes specify heavy at 8+ mg. Fatality data and polydrug lethality from article prose and research output (Behonick et al. 2014; Langford & Bolton 2018; Angerer et al. 2017). All characterizations are class-inferred; no controlled study at heavy doses.

Reasoning

Work-notes specify heavy at 8+ mg. Fatality data and polydrug lethality from article prose and research output (Behonick et al. 2014; Langford & Bolton 2018; Angerer et al. 2017). All characterizations are class-inferred; no controlled study at heavy doses.

Evidence basis: community_consensus_large

02

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 correctioncontact@psychedex.org
03

Sources

1 strong · 20 moderate · 8 weak
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    moderate
    Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.
    De Luca MA, Castelli MP, Loi B, Porcu A, Martorelli M, Miliano C, Kellett K, Davidson C, Stair JL, Schifano F, Di Chiara G · 2016 · Neuropharmacology
    doi.org/10.1016/j.neuropharm.2015.11.017pubmed 2668639114 claims checked6 verified1 partial7 inconclusive
  2. [2]
    moderate
    Metabolism of synthetic cannabinoids PB-22 and its 5-fluoro analog, 5F-PB-22, by human hepatocyte incubation and high-resolution mass spectrometry.
    Wohlfarth A, Gandhi AS, Pang S, Zhu M, Scheidweiler KB, Huestis MA · 2014 · Analytical and Bioanalytical Chemistry
    doi.org/10.1007/s00216-014-7668-0pubmed 245189035 claims checked1 verified1 partial3 inconclusive
  3. [3]
    moderate
    Schedules of Controlled Substances: Placement of PB-22, 5F-PB-22, AB-FUBINACA and ADB-PINACA into Schedule I. Final rule.
    DEA (Drug Enforcement Administration) · 2016 · Federal Register
    pubmed 276328032 claims checked2 partial
  4. [4]
    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.xpubmed 226910102 claims checked2 verified
  5. [5]
    weak
    Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5F-PB-22.
    Behonick G, Shanks KG, Firchau DJ, Mathur G, Lynch CF, Nashelsky M, Jaskierny DJ, Meroueh C · 2014 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bku048pubmed 248763645 claims checked2 verified3 partial
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    moderate
    Effects of lipophilicity and functional groups of synthetic cannabinoids on their blood concentrations and urinary excretion.
    Kakehashi H, Shima N, Ishikawa A, Nitta A, Asai R, Wada M, Nakano S, Matsuta S, Sasaki K, Kamata H, Kamata T, Nishioka H, Miki A, Katagi M · 2020 · Forensic Science International
    doi.org/10.1016/j.forsciint.2019.110106pubmed 319026617 claims checked6 verified1 partial
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    moderate
    Large-scale evaluation of ion mobility spectrometry for the rapid detection of synthetic cannabinoid receptor agonists in infused papers in prisons.
    Norman C, McKirdy B, Walker G, Dugard P, NicDaéid N, McKenzie C · 2021 · Drug Testing and Analysis
    doi.org/10.1002/dta.2945pubmed 33058556no claims checked
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    moderate
    Synthetic cannabimimetic agents metabolized by carboxylesterases.
    Thomsen R, Nielsen LM, Holm NB, Rasmussen HB, Linnet K · 2015 · Drug Testing and Analysis
    doi.org/10.1002/dta.1731pubmed 253465275 claims checked2 verified1 partial2 inconclusive
  9. [9]
    moderate
    Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135.
    Banister SD, Stuart J, Kevin RC, Edington A, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Hibbs DE, Glass M, Connor M, McGregor IS, Kassiou M · 2015 · ACS Chemical Neuroscience
    doi.org/10.1021/acschemneuro.5b00107pubmed 259214077 claims checked1 verified1 partial5 inconclusive
  10. [10]
    weak
    Schedules of Controlled Substances: Temporary Placement of Four Synthetic Cannabinoids Into Schedule I
    DEA (Drug Enforcement Administration) · 2014 · Federal Register
    linkno claims checked
  11. [11]
    weak
    Substance Details 5F-PB-22 - UNODC
    UNODC · 2018
    linkno claims checked
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    moderate
    Analytical differentiation of quinolinyl- and isoquinolinyl-substituted 1-(5-fluoropentyl)-1H-indole-3-carboxylates: 5F-PB-22 and its ten isomers.
    Kohyama E, Chikumoto T, Tada H, Kitaichi K, Ito T · 2017 · Forensic Toxicology
    doi.org/10.1007/s11419-016-0334-9pubmed 281274082 claims checked2 verified
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    moderate
    Comprehensive Protocol for the Identification and Characterization of New Psychoactive Substances in the Service of Law Enforcement Agencies.
    Bulska E, Bachlińśki R, Cyrański MK, Michalska-Kacymirow M, Kośnik W, Małecki P, Grela K, Dobrowolski MA · 2020 · Frontiers in Chemistry
    doi.org/10.3389/fchem.2020.00693pubmed 331024271 claim checked1 verified
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    moderate
    Synthetic cannabinoid receptor agonists and their human metabolites in sewage water: Stability assessment and identification of transformation products.
    Hehet P, Köke N, Zahn D, Frömel T, Rößler T, Knepper TP, Pütz M · 2021 · Drug Testing and Analysis
    doi.org/10.1002/dta.3129pubmed 34272823no claims checked
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    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/s40001-023-01443-6pubmed 382169841 claim checked1 verified
  16. [16]
    moderate
    Sensitive quantification of 5F-PB-22 and its three metabolites 5F-PB-22 3-carboxyindole, B-22 N-5-hydroxypentyl and PB-22 N-pentanoic acid in authentic urine specimens obtained from four individuals by liquid chromatography-tandem mass spectrometry.
    Minakata K, Hasegawa K, Yamagishi I, Nozawa H, Kikura-Hanajiri R, Suzuki M, Kitamoto T, Suzuki O, Watanabe K · 2017 · Forensic Toxicology
    doi.org/10.1007/s11419-017-0395-46 claims checked5 verified1 inconclusive
  17. [17]
    moderate
    Metabolic Profile of Synthetic Cannabinoids 5F-PB-22, PB-22, XLR-11 and UR-144 by Cunninghamella elegans.
    Watanabe S, Kuzhiumparambil U, Nguyen MA, Cameron J, Fu S · 2017 · The AAPS Journal
    doi.org/10.1208/s12248-017-0078-4pubmed 284556762 claims checked1 verified1 inconclusive
  18. [18]
    weak
    Evidence of enzyme-mediated transesterification of synthetic cannabinoids with ethanol: potential toxicological impact.
    Apirakkan O, Gavrilović I, Floresta G, Pierre C, Cannaert A · 2019 · Forensic Toxicology
    doi.org/10.1007/s11419-019-00491-03 claims checked1 verified2 partial
  19. [19]
    weak
    The First Reported Case of a Synthetic Cannabinoid Ethyl Ester Detected in a Postmortem Blood Toxicological Analysis.
    Apirakkan O, Hudson S, Couchman L, Cowan D, Morley S, Abbate V · 2021 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bkaa030pubmed 323691633 claims checked3 verified
  20. [20]
    moderate
    Synthetic Cannabinoid Hydroxypentyl Metabolites Retain Efficacy at Human Cannabinoid Receptors.
    Gamage TF, Farquhar CE, McKinnie RJ, Kevin RC, McGregor IS, Trudell ML, Wiley JL, Thomas BF · 2019 · Journal of Pharmacology and Experimental Therapeutics
    doi.org/10.1124/jpet.118.254425pubmed 305522952 claims checked2 verified
  21. [21]
    moderate
    The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects
    van Amsterdam J, Brunt T, van den Brink W · 2015 · Journal of psychopharmacology
    doi.org/10.1177/0269881114565142pubmed 255863983 claims checked3 verified
  22. [22]
    moderate
    The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations.
    Alexandre J, Malheiro R, Dias da Silva D, Carmo H, Carvalho F, Silva JP · 2020 · International Journal of Molecular Sciences
    doi.org/10.3390/ijms21176277pubmed 328726174 claims checked4 verified
  23. [23]
    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.2464pubmed 299960111 claim checked1 verified
  24. [24]
    weak
    Three fatalities associated with the synthetic cannabinoids 5F-ADB, 5F-PB-22, and AB-CHMINACA.
    Angerer V, Jacobi S, Franz F, Auwärter V, Pietsch J · 2017 · Forensic Science International
    doi.org/10.1016/j.forsciint.2017.10.042pubmed 291330105 claims checked3 verified2 inconclusive
  25. [25]
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    Synthetic cannabinoids: Variety is definitely not the spice of life.
    Langford AM, Bolton JR · 2018 · Journal of Forensic and Legal Medicine
    doi.org/10.1016/j.jflm.2018.07.012pubmed 301307004 claims checked4 verified
  26. [26]
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    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/10.3109/15563650.2015.1110590pubmed 265674705 claims checked5 verified
  27. [27]
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    Synthetic Cannabinoid-Associated Multiple Organ Failure: Case Series and Literature Review.
    Armstrong F, McCurdy MT, Heavner MS · 2019 · Pharmacotherapy
    doi.org/10.1002/phar.2241pubmed 308116281 claim checked1 inconclusive
  28. [28]
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    Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal
    Cooper ZD · 2016 · Current Psychiatry Reports
    doi.org/10.1007/s11920-016-0694-1pubmed 270749342 claims checked1 verified1 inconclusive
  29. [29]
    moderate
    Differentiation and identification of 5F-PB-22 and its isomers.
    Tang ASY, Loh SWX, Koh HB, Tan S, Yap ATW, Zhang SH · 2017 · Forensic Science International
    doi.org/10.1016/j.forsciint.2017.08.009pubmed 288469131 claim checked1 verified
04

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.

summary11 claims3verified5partial3inconclusive
verifiedIt functions as a high-potency full agonist at the cannabinoid CB1 receptor (Ki = 0.13 nM), approximately 26-fold more potent than JWH-018 at the same target[1]model confidence 99%
Verified

Abstract directly confirms Ki=0.13 nM for 5F-PB-22 and states it is 26 times lower than JWH-018 (3.38 nM).

BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM)

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

partialDuration of action is approximately 90 minutes via inhalation and 2-3 hours orally, consistent with rapid ester hydrolysis by carboxylesterase 1.[8]model confidence 80%
Partial

Abstract confirms CES1 mediates ester hydrolysis, supporting the mechanism. Specific duration values (90 min inhalation, 2-3 hrs oral) are not present in the abstract.

CES1 identified as the major human hepatic and pulmonary enzyme responsible for ester hydrolysis of PB-22, 5F-PB-22, and BB-22.

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

partial5F-PB-22 emerged on recreational drug markets in 2012-2013 as a component of herbal Spice blends, representing the first synthetic cannabinoid class to combine an ester bond linkage with a quinoline substructure[2]model confidence 82%
Partial

Abstract confirms PB-22 and 5F-PB-22 are the first marketed SCs with ester bond + quinoline, supporting structural novelty. The 2012-2013 emergence date is not in the abstract.

PB-22 and 5F-PB-22 are the first marketed synthetic cannabinoids with an ester bond linkage and a quinoline substructure.

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

partialThe compound was permanently placed in United States Schedule I in 2016 and United Nations Schedule II in 2018[3]model confidence 85%
Partial

Abstract confirms permanent US Schedule I placement via DEA final rule. The United Nations Schedule II 2018 placement is not mentioned.

Final rule permanently placing quinolin-8-yl 1-(5-fluoropentyl)-1H-indole-3-carboxylate (5F-PB-22) into Schedule I of the Controlled Substances Act.

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

inconclusiveFull CB1 agonism is confirmed by complete blockade with the antagonist/inverse agonist AM251 and absence of activity in CB1-knockout mice[1]model confidence 75%
Inconclusive

Abstract confirms potent CB1 full agonist activity by Emax data but does not mention AM251 blockade experiments or CB1-knockout mouse studies. These data may be in the full paper.

potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018

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

partialFunctional potency is high at both CB1 (EC50 = 2.8-3.7 nM, Emax = 203%) and CB2 (EC50 = 11 nM)[1]model confidence 85%
Partial

Abstract confirms CB1 EC50=3.7 nM and Emax=203% for 5F-PB-22. CB2 data (EC50=11 nM) is not reported in this abstract.

potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018

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

inconclusiveFunctional potency is high at both CB1 (EC50 = 2.8-3.7 nM, Emax = 203%) and CB2 (EC50 = 11 nM)[9]model confidence 65%
Inconclusive

Abstract covers CB1 (range 2.8-1959 nM) and CB2 (range 6.5-206 nM) for multiple compounds. Specific values for 5F-PB-22 individually cannot be confirmed from aggregate ranges.

All compounds demonstrated agonist activity at CB1 (EC50 = 2.8-1959 nM) and CB2 (EC50 = 6.5-206 nM) receptors

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

inconclusiveThe compound stimulates mesolimbic dopamine release in the nucleus accumbens shell via a CB1-dependent mechanism - a pharmacological signature of abuse liability.[1]model confidence 70%
Inconclusive

Title and SCOPE reference NAc shell dopamine stimulant properties, but the abstract text only covers receptor binding data (Ki, EC50, Emax). The dopamine release findings are absent from the abstract excerpt.

Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids

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

partialMultiple fatalities have been attributed to 5F-PB-22, with postmortem blood concentrations (0.37-1.5 ng/mL) overlapping those observed in impaired but surviving individuals (0.10-5.0 ng/mL)[5]model confidence 82%
Partial

Abstract confirms postmortem blood concentrations of 1.1-1.5 ng/mL, supporting the upper portion of the range. The 0.37 ng/mL lower bound comes from a separate German fatalities report and is not present here.

Quantitative detection in four postmortem cases (July-October 2013). Blood concentrations 1.1-1.5 ng/mL.

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

verifiedMultiple fatalities have been attributed to 5F-PB-22, with postmortem blood concentrations (0.37-1.5 ng/mL) overlapping those observed in impaired but surviving individuals (0.10-5.0 ng/mL)[6]model confidence 92%
Verified

Abstract confirms blood concentrations 0.10-5.0 ng/mL in DUI (impaired but surviving) specimens, directly supporting the impaired driver range.

Blood concentrations 0.10-5.0 ng/mL in DUI specimens.

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

verifiedDependence liability is moderate at the class level, with cross-tolerance to other cannabinoids[4]model confidence 88%
Verified

Abstract confirms SC users meeting cannabis dependence criteria and that SC use alleviated cannabis withdrawal, establishing cross-dependence and implying cross-tolerance.

Case series of SC users meeting cannabis dependence criteria; SC use alleviated cannabis withdrawal; potential for dependence documented.

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

history3 claims1verified2partial
verifiedWohlfarth et al. identified PB-22 and 5F-PB-22 as the first marketed substances with an ester bond linkage among synthetic cannabinoids - a structurally novel class that expanded the chemical diversity of available synthetic cannabinoid receptor agonists.[2]model confidence 99%
Verified

Abstract directly states PB-22 and 5F-PB-22 are the first marketed synthetic cannabinoids with an ester bond linkage and a quinoline substructure.

PB-22 and 5F-PB-22 are the first marketed synthetic cannabinoids with an ester bond linkage and a quinoline substructure.

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

partialIn the United States, 5F-PB-22 was detected forensically in postmortem cases during July-October 2013, found alongside AKB-48 in the herbal product marketed as Psyclone[5]model confidence 80%
Partial

Abstract confirms forensic detection in postmortem cases during July-October 2013. The Psyclone brand name and AKB-48 co-detection details are not mentioned in the abstract.

Quantitative detection in four postmortem cases (July-October 2013).

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

partialThis temporary order was extended in February 2016 and made permanent in September 2016 via DEA final rule[3]model confidence 80%
Partial

Abstract confirms a DEA final rule permanently placing 5F-PB-22 into Schedule I, supporting the permanent placement aspect. The February 2016 extension date is not mentioned.

Final rule permanently placing quinolin-8-yl 1-(5-fluoropentyl)-1H-indole-3-carboxylate (5F-PB-22) into Schedule I of the Controlled Substances Act.

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

chemistry5 claims4verified1partial
verifiedThis architecture places 5F-PB-22 among Class 2 synthetic cannabinoids in the toxicokinetic classification of Kakehashi et al.[6]model confidence 99%
Verified

Abstract directly states 5F-PB-22 has logP 5.80-6.74 (Class 2 SC).

5F-PB-22 has logP 5.80-6.74 (Class 2 SC).

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

verifiedThis bond is susceptible to hydrolysis by carboxylesterases, a property that governs the compound's metabolic fate.[8]model confidence 97%
Verified

Abstract confirms CES1-mediated ester hydrolysis as the major metabolic route for 5F-PB-22.

CES1 identified as the major human hepatic and pulmonary enzyme responsible for ester hydrolysis of PB-22, 5F-PB-22, and BB-22.

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

verifiedTen positional isomers of 5F-PB-22 exist, incorporating quinolinyl and isoquinolinyl substitution variants, not all of which are scheduled under current legislation.[12]model confidence 93%
Verified

Abstract confirms 10 positional isomers and quinolinyl/isoquinolinyl variants. SCOPE notes regulatory loophole discussion.

Analytical differentiation of 5F-PB-22 from 10 positional isomers using GC-EI-MS and LC-MS/MS.

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

verifiedCrystal structure has been determined by single-crystal and powder X-ray diffraction[13]model confidence 99%
Verified

Abstract directly states crystal structure determined by single-crystal and powder X-ray diffraction.

crystal structure determined by single-crystal and powder X-ray diffraction.

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

partialThe compound exhibits high lipophilicity, with measured logP values of 5.80-6.74 and a computed XLogP of 5.0[6]model confidence 82%
Partial

Abstract confirms measured logP 5.80-6.74. The computed XLogP=5.0 is not present in this abstract and cannot be verified here.

5F-PB-22 has logP 5.80-6.74 (Class 2 SC).

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

pharmacology23 claims13verified1partial9inconclusive
verifiedParent compound is detectable in urine only at trace levels (5.1-470 pg/mL) using sensitive LC-MS/MS methods.[16]model confidence 98%
Verified

Abstract directly confirms urinary 5F-PB-22 concentrations of 5.1-470 pg/mL detectable by LC-MS/MS.

Urinary 5F-PB-22: 5.1-470 pg/mL

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

inconclusiveGlucuronide conjugates[2]model confidence 60%
Inconclusive

The abstract for this hepatocyte study does not mention glucuronide conjugates. The abstract only notes that metabolites were identified for urine screening.

No human metabolism data available at time of publication, making urine documentation of intake difficult.

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

verifiedAt CB1, the compound displays a binding affinity of Ki = 0.13 nM in native rat cerebral cortex membrane preparations (competition with [3H]CP55940)[1]model confidence 90%
Verified

Abstract confirms Ki=0.13 nM for 5F-PB-22. Title specifies native CB1 receptor affinity, confirming native receptor preparations. Specific radioligand not in abstract but native condition confirmed.

5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM)

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

verifiedFunctional potency, measured by GTPgammaS accumulation, yields an EC50 of 3.7 nM with an Emax of 203% relative to basal - confirming full agonist status with supramaximal efficacy[1]model confidence 92%
Verified

Abstract directly confirms EC50=3.7 nM and Emax=203% for 5F-PB-22 confirming full agonist status with supramaximal efficacy. GTPgammaS method not stated in abstract but values are confirmed.

potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018

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

inconclusiveIn human CB1 receptor-expressing cells (FLIPR membrane potential assay), functional EC50 is 2.8 nM.[9]model confidence 65%
Inconclusive

Abstract covers FLIPR assay for multiple compounds with CB1 range 2.8-1959 nM. The 2.8 nM specific value for 5F-PB-22 cannot be confirmed from the aggregate range reported.

All compounds demonstrated agonist activity at CB1 (EC50 = 2.8-1959 nM)

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

inconclusiveCB1 dependence of pharmacological effects is established by two convergent lines of evidence: the CB1 antagonist/inverse agonist AM251 (0.1 uM) abolished agonist-stimulated G-protein activation, and no receptor-mediated activity was observed in CB1-knockout mice.[1]model confidence 72%
Inconclusive

Abstract confirms potent CB1 agonist activity but does not describe AM251 blockade or CB1-knockout mouse experiments. These data would be in the full paper.

potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018

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

inconclusiveAt CB2, 5F-PB-22 acts as a full agonist with EC50 = 11 nM (FLIPR, human CB2), yielding an approximate CB1:CB2 selectivity ratio of 4:1.[9]model confidence 65%
Inconclusive

Abstract covers CB2 activity (range 6.5-206 nM) via FLIPR. The specific CB2 EC50=11 nM for 5F-PB-22 and the 4:1 selectivity ratio are not extractable from the aggregate range.

All compounds demonstrated agonist activity at CB2 (EC50 = 6.5-206 nM) receptors

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

verifiedAs a potent full CB1 agonist, 5F-PB-22 may also engage non-cannabinoid targets shared across the synthetic cannabinoid class, including orphan receptors GPR55 and GPR18, peroxisome proliferator-activated receptors (PPARs), and TRPV1 channels[15]model confidence 95%
Verified

Review abstract explicitly lists GPR55, GPR18, PPARs, and TRPV1 as targets activated by synthetic cannabinoids, directly supporting the claim.

Review of SC health risks: activation of CB1R, CB2R, GPR55, GPR18, PPARs, TRPV1.

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

inconclusiveThis dopamine stimulation was completely abolished by pretreatment with AM251 (1.0 mg/kg i.p.), confirming a CB1-mediated mechanism.[1]model confidence 72%
Inconclusive

Paper title references NAc shell dopamine stimulant properties, and SCOPE confirms CB1-mediated mechanism. However, abstract text only covers receptor binding data, not the AM251 in vivo blockade experiment.

Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids

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

verifiedThe compound's high lipophilicity (logP 5.80-6.74) predicts extensive tissue distribution, high protein binding, and efficient CNS penetration[6]model confidence 88%
Verified

Abstract confirms logP 5.80-6.74. The pharmacokinetic inferences are standard consequences of high lipophilicity and represent reasonable scientific inference from the confirmed values.

5F-PB-22 has logP 5.80-6.74 (Class 2 SC).

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

verifiedBlood concentrations in impaired drivers range from 0.10 to 5.0 ng/mL[6]model confidence 99%
Verified

Abstract directly confirms Blood concentrations 0.10-5.0 ng/mL in DUI specimens.

Blood concentrations 0.10-5.0 ng/mL in DUI specimens.

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

verifiedThe primary metabolic pathway is ester hydrolysis catalyzed by carboxylesterase 1 (CES1), the major human hepatic and pulmonary enzyme for this reaction, as determined in human liver microsomes and recombinant enzyme preparations[8]model confidence 93%
Verified

Abstract directly confirms CES1 as major human hepatic and pulmonary enzyme for ester hydrolysis of 5F-PB-22. Methodological detail (recombinant enzymes) not in abstract but core claim confirmed.

CES1 identified as the major human hepatic and pulmonary enzyme responsible for ester hydrolysis of PB-22, 5F-PB-22, and BB-22.

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

inconclusiveSix principal metabolite classes have been identified in human hepatocyte incubations and authentic urine specimens:[2]model confidence 60%
Inconclusive

Abstract describes the first human hepatocyte metabolism study but does not enumerate metabolite classes. The specific count of six cannot be verified from the abstract.

No human metabolism data available at time of publication, making urine documentation of intake difficult.

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

inconclusiveSix principal metabolite classes have been identified in human hepatocyte incubations and authentic urine specimens:[16]model confidence 62%
Inconclusive

Abstract quantifies three specific metabolites in authentic urine but does not enumerate six principal metabolite classes.

Quantification of 5F-PB-22 and three metabolites in authentic urine from 4 individuals.

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

inconclusiveSix principal metabolite classes have been identified in human hepatocyte incubations and authentic urine specimens:[17]model confidence 62%
Inconclusive

Abstract describes four metabolic reaction types (dihydroxylation, oxidative defluorination, ester hydrolysis, glucosidation) but does not enumerate six principal metabolite classes.

5F-PB-22 metabolized by dihydroxylation, oxidative defluorination, ester hydrolysis, and glucosidation via C. elegans fungal model.

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

verified5F-PB-22 3-carboxyindole - the major urinary marker resulting from ester hydrolysis (urinary concentrations 8.25-880 ng/mL)[16]model confidence 98%
Verified

Abstract directly confirms 5F-PB-22 3-carboxyindole concentrations of 8.25-880 ng/mL, the highest of all reported metabolites, confirming it as the major urinary marker.

5F-PB-22 3-carboxyindole: 8.25-880 ng/mL

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

verifiedPB-22 N-5-hydroxypentyl - hydroxylation of the alkyl chain[16]model confidence 90%
Verified

Abstract confirms B-22 N-5-hydroxypentyl as a quantified metabolite. The hydroxypentyl name directly implies alkyl chain hydroxylation.

B-22 N-5-hydroxypentyl

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

verifiedPB-22 N-pentanoic acid - omega-oxidation product (urinary concentrations 12.0-2090 pg/mL)[16]model confidence 98%
Verified

Abstract directly confirms PB-22 N-pentanoic acid concentrations of 12.0-2090 pg/mL in authentic urine.

PB-22 N-pentanoic acid: 12.0-2090 pg/mL

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

inconclusiveDihydroxylation products[2]model confidence 60%
Inconclusive

The abstract for this hepatocyte metabolism paper does not mention dihydroxylation products specifically. The abstract notes metabolites were identified but does not enumerate them.

No human metabolism data available at time of publication, making urine documentation of intake difficult.

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

verifiedOxidative defluorination products (including the corresponding carboxylic acid)[17]model confidence 93%
Verified

Abstract explicitly lists oxidative defluorination as one of the metabolic pathways identified for 5F-PB-22.

5F-PB-22 metabolized by dihydroxylation, oxidative defluorination, ester hydrolysis, and glucosidation via C. elegans fungal model.

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

partialThis has been demonstrated in human liver microsomes in vitro and confirmed in postmortem blood at 0.4 ug/L[18]model confidence 82%
Partial

Abstract confirms in vitro demonstration in human liver microsomes via CES-mediated transesterification. The postmortem blood detection at 0.4 ug/L is from citation [6] and absent from this abstract.

In vitro metabolism of PB-22, NPB-22, 5F-PB-22, and 5F-NPB-22 with ethanol using human liver microsomes. CES enzyme mediates transesterification to produce SC ethyl esters with reduced CB receptor activity.

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

verifiedThis has been demonstrated in human liver microsomes in vitro and confirmed in postmortem blood at 0.4 ug/L[19]model confidence 95%
Verified

Abstract confirms the postmortem blood detection of the 5F-PB-22 ethyl ester transesterification product at 0.4 ug/L, directly supporting the confirmed in postmortem blood part of the claim.

5F-PB22 and ethanol co-consumption producing 5F-PB22 ethyl ester transesterification product detected in postmortem blood at 0.4 ug/L.

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

verifiedHydroxypentyl metabolites of structurally related synthetic cannabinoids retain full efficacy at human CB1 and CB2, albeit with reduced affinity and potency[20]model confidence 97%
Verified

Abstract directly confirms Hydroxypentyl metabolites of synthetic cannabinoids retain full efficacy at hCB1 and hCB2 with reduced affinity.

Hydroxypentyl metabolites of synthetic cannabinoids retain full efficacy at hCB1 and hCB2 with reduced affinity.

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

receptor pharmacology3 claims1verified2inconclusive
inconclusiveThe CB1:CB2 selectivity ratio is approximately 4:1 based on FLIPR functional data.[9]model confidence 65%
Inconclusive

Abstract covers FLIPR assay data for CB1 and CB2 but only reports aggregate ranges across all compounds, not 5F-PB-22-specific values needed to confirm the 4:1 ratio.

All compounds demonstrated agonist activity at CB1 (EC50 = 2.8-1959 nM) and CB2 (EC50 = 6.5-206 nM) receptors

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

verifiedA discrepancy exists between the peer-reviewed Ki value (0.13 nM; native rat CB1, [3H]CP55940 competition) and a value reported in non-peer-reviewed web sources (0.055 nM)[1]model confidence 92%
Verified

Abstract confirms Ki=0.13 nM from native CB1 receptor binding, establishing the peer-reviewed reference value.

5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM)

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

inconclusiveBoth lines of evidence were reported by De Luca et al.[1]model confidence 68%
Inconclusive

The abstract does not describe CB1-knockout mouse experiments or AM251 antagonism data. These specific convergent lines of evidence are not verifiable from the abstract text.

Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids

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

neuroscience5 claims3verified2inconclusive
inconclusiveThe compound's demonstrated capacity to stimulate mesolimbic dopamine release selectively in the nucleus accumbens shell - but not the core or medial prefrontal cortex - implicates the ventral tegmental area (VTA) to NAc shell pathway[1]model confidence 65%
Inconclusive

Title references NAc shell dopamine stimulant properties. Abstract text does not contain regional specificity data (shell vs core vs mPFC). Full paper required.

Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids

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

verifiedIn NG108-15 neuroblastoma/glioma cells, 5F-PB-22 at biologically relevant concentrations (<=1 uM) approximately doubled neuronal differentiation and neurite outgrowth via a CB1R-dependent mechanism (blocked by the CB1 antagonist SR141716)[22]model confidence 93%
Verified

Abstract confirms ~2-fold enhancement of differentiation and neurite length in NG108-15 cells via CB1R activation blocked by SR141718 at <=1 uM. SR141718 is the same compound as SR141716 (rimonabant).

Both 5F-PB22 and THJ-2201 enhanced differentiation ratios and neurite length ~2-fold in NG108-15 cells via CB1R activation (blocked by SR141718).

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

verifiedThe compound also increased mitochondrial membrane potential (assessed by TMRE fluorescence accumulation)[22]model confidence 98%
Verified

Abstract directly confirms SCs increased mitochondrial TMRE accumulation at <=1 uM.

SCs increased mitochondrial TMRE accumulation at <=1 uM.

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

verifiedThe absence of CBD - which modulates ECS tone through negative allosteric modulation of CB1 and agonism at 5-HT1A - removes an additional regulatory mechanism present in cannabis.[21]model confidence 85%
Verified

Abstract confirms the absence of CBD contributes to higher psychosis-inducing potential, supporting that CBD's absence removes a regulatory mechanism.

higher psychosis-inducing potential than cannabis due to full agonism and absence of CBD.

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

inconclusiveThe CB1-dependent nature of 5F-PB-22's dopamine release suggests that its reinforcing properties operate through incentive motivation - the compulsive wanting that drives repeated use - rather than direct hedonic amplification.[1]model confidence 60%
Inconclusive

Abstract does not describe dopamine release findings or the incentive motivation interpretation. This mechanistic interpretation and its supporting data are not in the abstract text.

Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids

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

pharmacokinetic detail7 claims5verified2inconclusive
inconclusiveCYP450 isoform involvement in oxidative metabolism is uncharacterized; CES1-mediated ester hydrolysis is the only confirmed metabolic pathway.[8]model confidence 65%
Inconclusive

Abstract confirms CES1 mediation of ester hydrolysis. The claim that CYP450 is uncharacterized and CES1 is the only confirmed pathway requires negative evidence not verifiable from this abstract.

CES1 identified as the major human hepatic and pulmonary enzyme responsible for ester hydrolysis of PB-22, 5F-PB-22, and BB-22.

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

inconclusiveCES1 catalyzes the rate-limiting ester hydrolysis step, yielding the 3-carboxyindole metabolite as the predominant urinary species[8]model confidence 65%
Inconclusive

Abstract confirms CES1 catalyzes ester hydrolysis but does not describe the 3-carboxyindole metabolite or identify it as the predominant urinary species.

CES1 identified as the major human hepatic and pulmonary enzyme responsible for ester hydrolysis of PB-22, 5F-PB-22, and BB-22.

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

verifiedCES1 catalyzes the rate-limiting ester hydrolysis step, yielding the 3-carboxyindole metabolite as the predominant urinary species[16]model confidence 90%
Verified

Abstract confirms 5F-PB-22 3-carboxyindole has the highest urinary concentrations (8.25-880 ng/mL) compared to other metabolites, confirming it as the predominant urinary species.

5F-PB-22 3-carboxyindole: 8.25-880 ng/mL; PB-22 N-pentanoic acid: 12.0-2090 pg/mL

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

verifiedSecondary oxidative pathways - hydroxylation, omega-oxidation, oxidative defluorination - produce metabolites that retain pharmacological activity at CB1 and CB2, potentially extending the effective pharmacological duration beyond that of the parent compound.[20]model confidence 92%
Verified

Abstract directly confirms hydroxypentyl metabolites retain full efficacy at hCB1 and hCB2 and that phase I metabolites contribute to in vivo pharmacology and toxicology.

Hydroxypentyl metabolites of synthetic cannabinoids retain full efficacy at hCB1 and hCB2 with reduced affinity. Phase I metabolites contribute to in vivo pharmacology and toxicology.

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

verifiedThe logP-dependent urinary excretion model places 5F-PB-22 above the threshold (logP > 5) at which parent compound is no longer reliably detectable in urine[6]model confidence 95%
Verified

Abstract confirms logP 5.80-6.74 places 5F-PB-22 above the detectable/non-detectable logP boundary of 4-5, and that 5F-PB-22 is not detectable in urine.

Not detectable in urine due to high lipophilicity (logP boundary between detectable/non-detectable in urine is logP 4-5).

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

verifiedMetabolite-based assays targeting 5F-PB-22 3-carboxyindole are required for urinary confirmation.[23]model confidence 93%
Verified

Abstract confirms a validated UHPLC-QTOF-MS method including 5F-PB-22 3-carboxyindole for urinary confirmation.

Validated UHPLC-QTOF-MS method for 18 SC metabolites in urine (including 5F-PB-22 3-carboxyindole).

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

verifiedCES1-mediated transesterification converts the parent compound to 5F-PB-22 ethyl ester in the presence of ethanol[18]model confidence 97%
Verified

Abstract directly confirms CES enzyme-mediated transesterification of 5F-PB-22 with ethanol to produce SC ethyl esters.

CES enzyme mediates transesterification to produce SC ethyl esters with reduced CB receptor activity.

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

clinical evidence3 claims3verified
verifiedPublished case series document acute intoxication and fatality, but no systematic study of dose-response relationships, subjective pharmacology, or therapeutic efficacy has been conducted[5]model confidence 90%
Verified

Abstract documents four postmortem fatality cases, confirming the existence of published case series on fatality. The nature of the available evidence is consistent with absence of systematic studies.

Quantitative detection in four postmortem cases (July-October 2013). Blood concentrations 1.1-1.5 ng/mL.

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

verifiedPublished case series document acute intoxication and fatality, but no systematic study of dose-response relationships, subjective pharmacology, or therapeutic efficacy has been conducted[24]model confidence 90%
Verified

Abstract documents three fatality cases involving 5F-PB-22, confirming published fatality case reports exist.

Three death cases in Germany with 5F-PB-22 blood concentration of 0.37 ng/mL.

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

verifiedPublished case series document acute intoxication and fatality, but no systematic study of dose-response relationships, subjective pharmacology, or therapeutic efficacy has been conducted[25]model confidence 90%
Verified

Abstract documents a fatality involving 5F-PB-22 and 5F-AKB-48 with high-level alcohol, confirming published fatality case reports exist.

Fatality following ingestion of 5F-PB-22 and 5F-AKB-48.

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

safety26 claims20verified2partial4inconclusive
verifiedThree decedents experienced abrupt sudden death; one had a rapidly deteriorating hospital course.[5]model confidence 97%
Verified

Abstract directly confirms Three decedents experienced abrupt sudden death.

Three decedents experienced abrupt sudden death.

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

inconclusiveThe reporting authors emphasize that tolerance from frequent use must be considered when interpreting blood concentrations.[24]model confidence 65%
Inconclusive

Abstract does not mention tolerance or any authorial caution regarding interpretation of blood concentrations in the context of frequent use.

Male decedents aged 25-41 with known drug use history.

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

verifiedCause of death was certified as combined alcohol and synthetic cannabinoid toxicity.[25]model confidence 99%
Verified

Abstract directly confirms Cause of death: combined alcohol and synthetic cannabinoids.

Cause of death: combined alcohol and synthetic cannabinoids.

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

verifiedBlood concentrations in impaired but surviving drivers (0.10-5.0 ng/mL) overlap substantially with those found in fatal cases (0.37-1.5 ng/mL)[6]model confidence 92%
Verified

Abstract confirms blood concentrations of 0.10-5.0 ng/mL in DUI specimens, supporting the impaired driver range in the claim.

Blood concentrations 0.10-5.0 ng/mL in DUI specimens.

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

partialBlood concentrations in impaired but surviving drivers (0.10-5.0 ng/mL) overlap substantially with those found in fatal cases (0.37-1.5 ng/mL)[5]model confidence 82%
Partial

Abstract confirms fatal case blood concentrations of 1.1-1.5 ng/mL, supporting the upper portion of the cited fatal range. The 0.37 ng/mL lower bound comes from a separate German report not confirmed here.

Blood concentrations 1.1-1.5 ng/mL.

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

verifiedA systematic review of approximately 4,000 synthetic cannabinoid presentations reports the following class-level adverse event profile:[26]model confidence 98%
Verified

Abstract confirms a systematic review of ~4000 SC cases with detailed adverse event data including tachycardia, agitation, nausea, psychosis, MI, AKI, and seizures.

Systematic review of ~4000 SC cases including ~26 deaths. Major complications: cardiovascular events (MI, stroke), AKI, generalized tonic-clonic seizures, psychosis, hyperemesis.

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

inconclusiveRare/critical: Multiple organ failure, intracranial hemorrhage, hemorrhagic coagulopathy (associated with brodifacoum-contaminated products).[27]model confidence 65%
Inconclusive

Abstract confirms multiple organ failure in SC intoxication cases. Intracranial hemorrhage and hemorrhagic coagulopathy associated with brodifacoum contamination are not mentioned.

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

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

verifiedCB1R-mediated enhancement of neuronal differentiation at biologically relevant concentrations (<=1 uM) in vitro raises concern for prenatal and early developmental exposure[22]model confidence 95%
Verified

Abstract confirms CB1R-mediated ~2-fold enhancement of differentiation at <=1 uM, supporting the developmental concern claim.

Both 5F-PB22 and THJ-2201 enhanced differentiation ratios and neurite length ~2-fold in NG108-15 cells via CB1R activation (blocked by SR141718). SCs increased mitochondrial TMRE accumulation at <=1 uM.

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

verifiedFull CB1 agonism without co-present CBD substantially increases psychosis-inducing risk compared to cannabis[21]model confidence 97%
Verified

Abstract directly confirms higher psychosis-inducing potential than cannabis due to full agonism and absence of CBD.

SCRAs are full CB1 agonists more potent than THC; higher psychosis-inducing potential than cannabis due to full agonism and absence of CBD.

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

verifiedClass-level data identify first-episode psychosis, paranoia, and acute agitation as recognized psychiatric complications of synthetic cannabinoid use[26]model confidence 92%
Verified

Abstract confirms psychosis and agitation (16-41%) as major complications from the systematic review. Paranoia is a component of psychosis presentation.

Major complications: cardiovascular events (MI, stroke), AKI, generalized tonic-clonic seizures, psychosis, hyperemesis. Most common: tachycardia 37-77%, agitation 16-41%

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

verifiedRegular synthetic cannabinoid users meeting cannabis dependence criteria have been described, and synthetic cannabinoid use has been reported to alleviate cannabis withdrawal symptoms, confirming cross-dependence[4]model confidence 97%
Verified

Abstract directly confirms SC users meeting cannabis dependence criteria and SC use alleviating cannabis withdrawal.

Case series of SC users meeting cannabis dependence criteria; SC use alleviated cannabis withdrawal; potential for dependence documented.

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

inconclusiveWithdrawal symptoms include anxiety, nausea, insomnia, and irritability, though characterization remains incomplete[28]model confidence 65%
Inconclusive

Abstract describes withdrawal from daily SC use and notes that systematic characterization is needed, but does not list specific symptoms such as anxiety, nausea, insomnia, or irritability.

Review of SC pharmacology, adverse effects of acute intoxication and withdrawal from daily use. Systematic characterization needed.

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

verifiedTreatment approaches include benzodiazepines for symptom relief, with quetiapine (an atypical antipsychotic) showing utility in some cases.[28]model confidence 97%
Verified

Abstract directly confirms Withdrawal symptom relief reported with benzodiazepines and quetiapine.

Withdrawal symptom relief reported with benzodiazepines and quetiapine.

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

inconclusiveAngerer et al. explicitly caution that synthetic cannabinoid blood concentrations cannot be judged as toxic or lethal without accounting for tolerance from frequent use.[24]model confidence 65%
Inconclusive

Abstract mentions known drug use history in decedents but does not explicitly state an authorial caution about tolerance and blood concentration interpretation.

Male decedents aged 25-41 with known drug use history.

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

verifiedPharmacokinetic: CES enzymes catalyze transesterification of 5F-PB-22 with ethanol, producing 5F-PB-22 ethyl ester - a novel bioactive metabolite detected in postmortem blood at 0.4 ug/L. In vitro data confirm this CES-mediated reaction.[19]model confidence 95%
Verified

Abstract directly confirms the 5F-PB-22 ethyl ester transesterification product detected in postmortem blood at 0.4 ug/L.

5F-PB22 and ethanol co-consumption producing 5F-PB22 ethyl ester transesterification product detected in postmortem blood at 0.4 ug/L.

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

partialPharmacokinetic: CES enzymes catalyze transesterification of 5F-PB-22 with ethanol, producing 5F-PB-22 ethyl ester - a novel bioactive metabolite detected in postmortem blood at 0.4 ug/L. In vitro data confirm this CES-mediated reaction.[18]model confidence 82%
Partial

Abstract confirms in vitro CES-mediated transesterification in human liver microsomes. The postmortem blood detection at 0.4 ug/L is from citation [6] and is not in this abstract.

CES enzyme mediates transesterification to produce SC ethyl esters with reduced CB receptor activity.

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

verifiedFatality data: The UK fatality involved blood alcohol of 311 mg/100 mL; the German fatality involved ethanol co-detection.[25]model confidence 97%
Verified

Abstract confirms the UK fatality involved 311 mg/100 mL alcohol alongside 5F-PB-22 and 5F-AKB-48.

Post-mortem blood samples detected both SCs plus 311 mg/100mL alcohol.

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

verifiedFatality data: The UK fatality involved blood alcohol of 311 mg/100 mL; the German fatality involved ethanol co-detection.[24]model confidence 95%
Verified

Abstract confirms relevant ethanol co-consumption in one German fatality case involving 5F-PB-22.

Relevant ethanol co-consumption in one case.

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

verifiedNo published data are specific to 5F-PB-22, but the polypharmacy risk is underscored by fatality case series in which multiple CNS-active substances were co-detected.[24]model confidence 88%
Verified

Abstract confirms fatalities involving 5F-PB-22 where ethanol and known drug use history was co-detected, supporting polypharmacy risk in fatality cases.

Male decedents aged 25-41 with known drug use history. Relevant ethanol co-consumption in one case.

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

verifiedCardiovascular disease (absolute): Full CB1 agonism produces tachycardia and may precipitate myocardial infarction or arrhythmia. Fatalities with cardiac involvement have been reported for synthetic cannabinoids as a class.[26]model confidence 95%
Verified

Abstract confirms tachycardia (37-77%) and MI as major complications from the systematic review of SC cases.

Major complications: cardiovascular events (MI, stroke), AKI, generalized tonic-clonic seizures, psychosis, hyperemesis. Most common: tachycardia 37-77%

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

verifiedPsychotic disorders or family history of psychosis (absolute): Full CB1 agonism without CBD substantially elevates psychosis risk.[21]model confidence 97%
Verified

Abstract directly confirms higher psychosis-inducing potential due to full agonism and absence of CBD.

SCRAs are full CB1 agonists more potent than THC; higher psychosis-inducing potential than cannabis due to full agonism and absence of CBD.

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

verifiedConcurrent ethanol use (absolute): Documented fatalities and a unique pharmacokinetic interaction (transesterification) establish this as a high-risk combination.[19]model confidence 95%
Verified

Abstract documents both a fatality context and the novel transesterification product when 5F-PB-22 and ethanol are co-consumed.

5F-PB22 and ethanol co-consumption producing 5F-PB22 ethyl ester transesterification product detected in postmortem blood at 0.4 ug/L.

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

verifiedConcurrent ethanol use (absolute): Documented fatalities and a unique pharmacokinetic interaction (transesterification) establish this as a high-risk combination.[25]model confidence 95%
Verified

Abstract documents a fatality with combined 5F-PB-22 and high-level ethanol, confirming the high-risk combination.

Cause of death: combined alcohol and synthetic cannabinoids.

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

verifiedPregnancy (absolute): In vitro evidence of CB1-mediated enhancement of neuronal differentiation at biologically relevant concentrations raises developmental concern.[22]model confidence 95%
Verified

Abstract confirms CB1R-mediated ~2-fold enhancement of neuronal differentiation at <=1 uM in NG108-15 cells, supporting the developmental concern.

Both 5F-PB22 and THJ-2201 enhanced differentiation ratios and neurite length ~2-fold in NG108-15 cells via CB1R activation (blocked by SR141718).

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

verifiedRenal impairment (relative): Acute kidney injury is reported in class-level synthetic cannabinoid data.[26]model confidence 98%
Verified

Abstract explicitly lists AKI as a major complication in the systematic review of ~4000 SC cases.

Major complications: cardiovascular events (MI, stroke), AKI, generalized tonic-clonic seizures, psychosis, hyperemesis.

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

verifiedSeizure disorders (relative): Generalized tonic-clonic seizures are reported in synthetic cannabinoid presentations.[26]model confidence 98%
Verified

Abstract explicitly lists generalized tonic-clonic seizures as a major complication in the systematic review.

Major complications: cardiovascular events (MI, stroke), AKI, generalized tonic-clonic seizures, psychosis, hyperemesis.

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

comparative pharmacology5 claims3verified1partial1inconclusive
inconclusiveIn vivo potency, ranked by magnitude and duration of hypothermia in rats (0.3-10 mg/kg), yields a different ordering: PB-22 > 5F-PB-22 = JWH-018 > AM-2201 > APICA = STS-135 = XLR-11 > UR-144[9]model confidence 65%
Inconclusive

Abstract confirms all SCs induced dose-dependent hypothermia in rats but the specific potency ordering claimed is not stated in the abstract.

All SCs dose-dependently induced hypothermia and reduced heart rate in rats.

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

partialFluorine substitution improves CB1 potency approximately 1.8-fold and CB2 potency approximately 3.4-fold, while shifting the selectivity profile toward CB2[9]model confidence 75%
Partial

Abstract confirms fluorinated analogues show increased CB1 potency (~2-5 times) which does not match the specific 1.8-fold claimed. CB2 3.4-fold improvement is not verifiable from the abstract.

fluorinated analogues generally showing increased CB1 receptor potency (~2-5 times)

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

verifiedThis pattern - enhanced potency and reduced CB1 selectivity with terminal fluorination - is consistent across multiple synthetic cannabinoid series (JWH-018 to AM-2201; UR-144 to XLR-11; APICA to STS-135).[9]model confidence 90%
Verified

Abstract covers exactly these compound pairs and confirms fluorinated analogues show increased potency across the series.

Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135.

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

verifiedUnder identical assay conditions (native rat CB1, [3H]CP55940 competition), 5F-PB-22 (Ki = 0.13 nM) is approximately 26-fold more potent than JWH-018 (Ki = 3.38 nM).[1]model confidence 99%
Verified

Abstract directly confirms 5F-PB-22 Ki=0.13 nM is 26 times lower than JWH-018 (3.38 nM) under native CB1 conditions.

5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM)

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

verifiedTHC functions as a partial agonist at CB1, with self-limiting activation even at receptor saturation. 5F-PB-22 is a full agonist (Emax = 203% of basal), with no intrinsic ceiling on receptor activation[1]model confidence 88%
Verified

Abstract confirms 5F-PB-22 Emax=203% confirming supramaximal full agonist status. The primary data for 5F-PB-22 is directly confirmed.

efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018

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

legal status2 claims2verified
verifiedNot all isomers are explicitly scheduled under current legislation, and analytical differentiation requires LC-MS/MS with collision-induced dissociation spectrum analysis.[12]model confidence 92%
Verified

Abstract confirms 10 positional isomers and that LC-MS/MS with collision-induced dissociation enables differentiation. SCOPE notes regulatory loophole discussion.

Analytical differentiation of 5F-PB-22 from 10 positional isomers using GC-EI-MS and LC-MS/MS. LC separation achieved for all isomers; collision-induced dissociation enables mass spectrometric differentiation.

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

verifiedNot all isomers are explicitly scheduled under current legislation, and analytical differentiation requires LC-MS/MS with collision-induced dissociation spectrum analysis.[29]model confidence 88%
Verified

Abstract confirms fluoropentyl positional isomers of 5F-PB-22 can be separated and identified, supporting forensic/analytical challenge and regulatory concerns.

Fluoropentyl positional isomers of 5F-PB-22 separated and identified using GC-MS, GC-IR, and 1H/13C NMR.

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

05

Coverage & Gaps

effect links
114 links · 114 approved · 0 audited0/114 with evidence basis
interactions
4 approved pairs0/4 graded
06

Research Trail

substance-article pipeline-v5 May 11, 2026

StepSourceQueryResults
1database lookupPubChem5F-PB-221 result, 1 selected
selection rationale

Primary chemical identity data; confirms formula/MW absent from seed data

2literature searchPubMed5F-PB-22 synthetic cannabinoid15 results, 6 selected
selection rationale

Selected for pharmacology, toxicology, forensic identification, and metabolism relevance

3clinical trial searchClinicalTrials.gov5F-PB-22 synthetic cannabinoid0 results
selection rationale

No relevant trials found - expected for an unscheduled research chemical

4literature searchPubMed5F-PB-22 pharmacology receptor binding cannabinoid CB12 results, 2 selected
selection rationale

Primary receptor binding and functional activity data for 5F-PB-22

5literature searchPubMedquinolin-8-yl indole carboxylate synthetic cannabinoid forensic case report2 results, 2 selected
selection rationale

Fatality data and novel metabolite in forensic context

6literature searchOpenAlex5F-PB-22 synthetic cannabinoid pharmacology receptor10 results, 3 selected
selection rationale

High-citation papers providing pharmacology, toxicology, and epidemiology context

7literature searchOpenAlex5F-PB-22 PB-22 QUPIC metabolism biotransformation10 results, 3 selected
selection rationale

Metabolism and pharmacology data directly relevant to 5F-PB-22

8literature searchPubMedPB-22 5F-PB-22 carboxylesterase ester hydrolysis human liver microsome1 result, 1 selected
selection rationale

Direct metabolic pathway data for 5F-PB-22 - CES1 identified as primary metabolizing enzyme

9legal status searchWeb (Google Search)5F-PB-22 legal status scheduling DEA Schedule I UK Misuse of Drugs Act10 results, 3 selected
selection rationale

Legal scheduling history for US, UK, China - key jurisdictions

10document retrievalPubMedPMID 24518903 - Wohlfarth 2014 5F-PB-22 metabolism1 result, 1 selected
selection rationale

Primary metabolism data for 5F-PB-22

11document retrievalPubMedPMID 28455676 - Watanabe 2017 fungal model metabolism1 result, 1 selected
selection rationale

Detailed metabolic pathway data for 5F-PB-22

12document retrievalPubMedPMID 27632803 - DEA final rule Schedule I placement 20161 result, 1 selected
selection rationale

Definitive US legal status documentation

13web searchWeb (Google Search)5F-PB-22 5F-QUPIC controlled substance Japan Canada Australia UK legal status10 results, 2 selected
selection rationale

Legal status data for major jurisdictions

14document retrievalPubMedPMID 25586398, 41423817, 30552295, 27074934, 30811628 - toxicology and dependence papers5 results, 5 selected
selection rationale

Toxicology, dependence, withdrawal, and severe outcomes - needed for safety section

15web searchWeb (Google Search)5F-PB-22 metabolism hepatocyte metabolites urine 3-carboxyindole Wohlfarth 201410 results, 2 selected
selection rationale

Key metabolism data for urinary detection and metabolite identification

16legal status searchWeb (Google Search)UK Psychoactive Substances Act 2016 synthetic cannabinoids 5F-PB-2210 results, 2 selected
selection rationale

UK legal history for 5F-PB-22

17cross referenceCrossref DOI verificationDOI 10.1007/s11419-017-0395-41 result, 1 selected
selection rationale

Confirming this key metabolism paper

18database lookupPubChem REST APICID 72710774 properties JSON1 result, 1 selected
selection rationale

Physical property data for lipophilicity assessment

19web searchWeb (Google Search)Banister 2015 5F-PB-22 CB1 CB2 EC50 FLIPR ACS Chemical Neuroscience10 results, 1 selected
selection rationale

Specific receptor potency values for CB1 and CB2

Research document (raw, unedited pipeline output)
# Research Output: 5F-PB-22

**PSX ID:** PSX-0083  
**Slug:** 5f-pb-22  
**Research Date:** 2026-05-11  
**Provenance ID:** 566e053f-db34-4d5b-89b3-fc7d42284661

---

## Chemical Identity

5F-PB-22 (also known as 5F-QUPIC and quinolin-8-yl 1-(5-fluoropentyl)indole-3-carboxylate) is the terminally fluorinated analog of PB-22 (QUPIC). It is notable for being among the first synthetic cannabinoids with both an ester bond linkage and a quinoline substructure — a novel structural class when it appeared on the market in 2013 [Ref 13].

**Confirmed chemical identity from PubChem (CID 72710774) [Ref N/A — database lookup]:**

| Property | Value | Source |
|---|---|---|
| PubChem CID | 72710774 | PubChem [api_verified] |
| IUPAC name | quinolin-8-yl 1-(5-fluoropentyl)indole-3-carboxylate | PubChem |
| Molecular formula | C₂₃H₂₁FN₂O₂ | PubChem |
| Molecular weight | 376.4 g/mol | PubChem |
| InChIKey | MBOCMBFDYVSGLJ-UHFFFAOYSA-N | PubChem / UNODC [Ref 30] |
| CAS number | 1411742-41-7 | UNODC [Ref 30] |
| XLogP | 5.0 | PubChem REST API |
| Measured logP | 5.80–6.74 | Kakehashi et al. 2020 [Ref 12] |

**Note on SMILES:** The canonical SMILES was not successfully retrieved via the PubChem REST API due to page rendering limitations. The structure is fully characterized as a quinoline ester of an indole-3-carboxylic acid bearing a 5-fluoropentyl chain at the nitrogen. Generation agent should source SMILES from PubChem CID 72710774 directly.

**Seed data gaps resolved:**
- The seed data was missing molecular formula, molecular weight, InChIKey, and PubChem CID. All confirmed above.
- The brief's seed SMILES field was blank — remains blank pending direct PubChem query.

**Physical properties:**
- Crystal structure determined by single-crystal and powder X-ray diffraction (Bulska et al. 2020 [Ref 10]).
- High lipophilicity (logP 5.80–6.74) classifies 5F-PB-22 alongside Class 2 synthetic cannabinoids (quinolinyl ester indoles) in the Kakehashi et al. toxicokinetic framework [Ref 12]. This lipophilicity explains the absence of detectable parent compound in urine and the blood distribution pattern.

---

## Pharmacology

### Primary Target: Cannabinoid CB1 Receptor

5F-PB-22 is a potent, high-efficacy full agonist at cannabinoid receptor type 1 (CB1). The following binding and functional data are from two primary research papers using different assay methods:

**Binding affinity:**
- Ki = 0.13 nM at native rat CB1 (cerebral cortex membrane binding, [³H]CP55940 competition) — De Luca et al. 2016 [Ref 1]
- For comparison: JWH-018 Ki = 3.38 nM under identical conditions; 5F-PB-22 is approximately 26-fold more potent [Ref 1]

**Functional potency (CB1 agonist):**
- EC50 = 3.7 nM (GTPγS assay, native rat CB1, relative efficacy 203% vs. basal) — De Luca et al. 2016 [Ref 1]
- EC50 = 2.8 nM (FLIPR membrane potential assay, human CB1) — Banister et al. 2015 [Ref 2]
- Emax = 203% relative to basal [Ref 1] — confirms full agonist status

**Comparison to parent compound PB-22:**
- PB-22 (non-fluorinated precursor): CB1 EC50 = 5.1 nM, CB2 EC50 = 37 nM (FLIPR, human)
- 5F-PB-22: CB1 EC50 = 2.8 nM, CB2 EC50 = 11 nM (FLIPR, human)
- Fluorine substitution confers ~1.8x improved CB1 potency and ~3.4x improved CB2 potency [Ref 2]

**Intrinsic activity:** The CB1 antagonist/inverse agonist AM251 (0.1 μM) abolished or drastically reduced agonist activity; no G-protein activation was observed in CB1-knockout mice, confirming full CB1-mediated activity [Ref 1].

### Secondary Target: Cannabinoid CB2 Receptor

- EC50 = 11 nM at human CB2 (FLIPR assay) — Banister et al. 2015 [Ref 2]
- 5F-PB-22 acts as a full agonist at both CB1 and CB2, showing a CB1:CB2 selectivity ratio of approximately 4:1 (Banister 2015 [Ref 2])

### Non-Cannabinoid Targets

As a potent full cannabinoid agonist, 5F-PB-22 may also engage non-cannabinoid targets shared by other potent synthetic cannabinoids, including orphan receptors GPR55 and GPR18, peroxisome proliferator-activated receptors (PPARs), and TRPV1. These targets are broadly expressed in the brain and heart and may contribute to adverse pharmacological effects beyond CB1/CB2 mediation (Alzu'bi et al. 2024 [Ref 29]). No published studies have directly characterized 5F-PB-22 activity at these non-cannabinoid targets.

### Dopaminergic Effects

In rodent microdialysis experiments, 5F-PB-22 (0.01 mg/kg i.v.) significantly increased dialysate dopamine in the nucleus accumbens (NAc) shell — but not the core or medial prefrontal cortex — a pattern consistent with the mesolimbic dopamine stimulant profile shared by drugs of abuse. This effect was completely abolished by the CB1 antagonist AM251 (1.0 mg/kg i.p.), confirming CB1 dependence (De Luca et al. 2016 [Ref 1]). This finding has direct implications for abuse liability.

### In Vivo Pharmacodynamics (Animal)

- In rats: 5F-PB-22 dose-dependently induced hypothermia and reduced heart rate at doses 0.3–10 mg/kg (Banister et al. 2015 [Ref 2]).
- In vivo potency ranking from magnitude and duration of hypothermia: PB-22 > **5F-PB-22 = JWH-018** > AM-2201 > APICA = STS-135 = XLR-11 > UR-144 [Ref 2]

### Neurodevelopmental Pharmacology

In vitro, 5F-PB-22 enhanced neuronal differentiation and neurite outgrowth approximately two-fold in NG108-15 neuroblastoma/glioma cells at biologically relevant concentrations (≤1 μM). This effect was CB1R-mediated (blocked by SR141718) and required repeated exposure to match a single dose of THJ-2201. The compound also increased mitochondrial membrane potential (TMRE accumulation) at these concentrations (Alexandre et al. 2020 [Ref 7]). These findings raise concerns about developmental exposure.

### Pharmacokinetics

No human pharmacokinetic study has been published for 5F-PB-22. The following is inferred from forensic and in vitro data:

**Lipophilicity and distribution:**
- logP 5.80–6.74 (calculated, Kakehashi et al. [Ref 12]); XLogP = 5.0 (PubChem)
- High lipophilicity predicts extensive tissue distribution, protein binding, and CNS penetration
- Due to logP > 5, parent compound is NOT detectable in urine by routine analysis — the boundary for urinary detectability lies between logP 4–5 [Ref 12]
- Blood concentrations in impaired drivers: 0.10–5.0 ng/mL (Kakehashi et al. 2020 [Ref 12])

**Metabolism:**
The primary metabolic pathway for 5F-PB-22 is ester hydrolysis catalyzed by carboxylesterase 1 (CES1) — the major human hepatic and pulmonary enzyme responsible for this reaction, as determined in human liver microsomes and recombinant enzyme studies (Thomsen et al. 2015 [Ref 8]).

Key metabolites identified in human hepatocyte incubations and authentic human urine specimens (Wohlfarth et al. 2014 [Ref 13]; Minakata et al. 2017 [Ref 27]; Watanabe et al. 2017 [Ref 14]):

1. **5F-PB-22 3-carboxyindole** — major urinary marker; indole ring hydrolysis product; urinary levels 8.25–880 ng/mL [Ref 27]
2. **PB-22 N-5-hydroxypentyl** — hydroxylation metabolite [Ref 27]
3. **PB-22 N-pentanoic acid** — omega-oxidation product; urinary levels 12.0–2090 pg/mL [Ref 27]
4. **Dihydroxylation products**
5. **Oxidative defluorination products** (including carboxylic acid)
6. **Glucosidation conjugates**

Parent compound in urine: 5.1–470 pg/mL (Minakata et al. 2017 [Ref 27])

**Ethanol interaction — transesterification:**
In the presence of ethanol, 5F-PB-22 undergoes CES-enzyme-mediated transesterification to form 5F-PB-22 ethyl ester. This has been demonstrated in vitro (human liver microsomes) and confirmed in a postmortem blood specimen (0.4 μg/L). The ethyl ester has reduced CB receptor activity compared to the parent compound. This novel metabolite serves as a marker of concurrent 5F-PB-22 and ethanol consumption (Apirakkan et al. 2019, 2021 [Refs 6, 29]).

**Metabolite activity:**
Hydroxypentyl metabolites of structurally related synthetic cannabinoids retain full efficacy (though reduced affinity and potency) at hCB1 and hCB2 (Gamage et al. 2019 [Ref 19]), suggesting that metabolites of 5F-PB-22 may contribute to its in vivo pharmacological duration and toxicity profile.

**No published data on:** bioavailability, Tmax, plasma half-life, or CYP450 enzyme involvement in hydroxylation reactions for 5F-PB-22 specifically.

---

## History

### Discovery and First Market Appearance

PB-22 (the non-fluorinated parent compound) was first identified in Japanese herbal blend seizures in 2013, as an ingredient in products distributed via the internet between July 2012 and January 2013. 5F-PB-22 is the terminally fluorinated analog, first appearing in commercially sold "Spice" herbal blends. Wohlfarth et al. (2014) identified PB-22 and 5F-PB-22 as "the first marketed substances with an ester bond linkage" in synthetic cannabinoids — a structurally novel class at the time [Ref 13].

In the United States, 5F-PB-22 was detected forensically in postmortem cases during July–October 2013 (Behonick et al. 2014 [Ref 3]). The compound was found in the herbal product "Psyclone" alongside AKB-48. Its designer drug status and structural novelty (quinoline ester) allowed it to circumvent then-existing analog act provisions.

No named academic researcher is credited with its deliberate synthesis or patent filing, consistent with its origin as a clandestine designer drug.

### Regulatory Timeline

| Date | Jurisdiction | Action |
|---|---|---|
| Jan 10, 2014 | United States | Temporary Schedule I placement (DEA) [Ref 3, Ref 20] |
| Oct 2015 | China | Controlled substance |
| May 26, 2016 | United Kingdom | Covered under Psychoactive Substances Act 2016 (blanket ban) |
| Feb 2016 | United States | Extension of temporary Schedule I order [Ref 15] |
| Sep 2016 | United States | Permanent Schedule I (DEA final rule) [Ref 15] |
| Dec 2016 | United Kingdom | Class B under Misuse of Drugs Act 1971 amendment |
| 2018 | United Nations | Schedule II, 1971 Convention on Psychotropic Substances [Ref 30] |

Additional jurisdictions: Canada (controlled under CDSA, quinolinyl indole-carboxylate structural class); Australia (prohibited import). Japan scheduling date not confirmed from available sources.

---

## Subjective Effects

No controlled human dosing study has been published for 5F-PB-22. Subjective effect data is derived entirely from:
1. User reports aggregated by harm reduction platforms (community consensus, source: PsychonautWiki, label accordingly)
2. Case reports of intoxication and overdose (adverse effects only)
3. Class-level data from the Tait et al. 2015 systematic review of ~4,000 synthetic cannabinoid cases [Ref 16]

**From class-level clinical data (Tait et al. 2015 [Ref 16]):**
Most synthetic cannabinoid presentations (predominantly non-specific generation) involved: tachycardia (~37–77% of presentations), agitation (~16–41%), nausea (~13–94%). The majority were not serious, resolving with symptomatic care within 8 hours.

**Reported duration (community consensus — not controlled study data):**
- Smoked route: Onset ~10 seconds; Peak ~30 minutes; Total duration ~90 minutes; After-effects ~15 minutes [web_retrieved, PsychonautWiki]
- Oral route: Total duration 2–3 hours [seed data — source not independently confirmed in published literature]

**Effect profile:** The compound's high CB1 potency and full agonist efficacy relative to THC would predict stronger versions of cannabis-like effects (euphoria, sedation, distorted perception, altered cognition) with a compressed therapeutic window — consistent with the potency data showing 26x greater CB1 affinity than JWH-018 [Ref 1].

**Important note for the generation agent:** No controlled subjective effects study exists for 5F-PB-22. All effect profile claims in the article must be attributed to class-level cannabinoid pharmacology, user reports, or case descriptions — not direct clinical observation.

---

## Safety & Toxicity

### Fatal Cases

Multiple fatalities associated with 5F-PB-22 have been published:

1. **Four US postmortem cases (2013)** — Behonick et al. 2014 [Ref 3]: Blood concentrations 1.1–1.5 ng/mL in three postmortem specimens and one antemortem serum. Three decedents experienced abrupt sudden death; one had a rapidly deteriorating hospital course.

2. **German fatality (one of three in series)** — Angerer et al. 2017 [Ref 4]: Male, 25–41 years old, history of drug use. Femoral blood 5F-PB-22 = 0.37 ng/mL; ethanol co-detected. Authors note these concentrations are in the lower range for postmortem cases, and that tolerance from frequent use must be considered when interpreting concentrations.

3. **UK fatality** — Langford & Bolton 2018 [Ref 5]: 5F-PB-22 + 5F-AKB-48 detected with blood alcohol 311 mg/100 mL. Cause of death certified as combined alcohol and synthetic cannabinoid toxicity.

**Blood concentration observations:**
- Impaired driver specimens: 0.10–5.0 ng/mL (Kakehashi et al. 2020 [Ref 12])
- Postmortem blood: 0.37–1.5 ng/mL across published cases [Refs 3, 4]
- The overlap between "impaired" and "fatal" concentrations illustrates the narrow therapeutic/toxic margin; postmortem redistribution and tolerance are significant confounders

### Lethal Dose

No published LD50 data exists for 5F-PB-22 in any species. The exact lethal human dose is unknown. Fatalities have been documented at blood concentrations as low as 0.37 ng/mL in polydrug contexts. ⚠️ FLAG: This is safety-critical data that cannot be confirmed from published sources.

### Class-Level Adverse Effects

From the systematic review by Tait et al. (2016 [Ref 16]), across ~4,000 synthetic cannabinoid cases (mixed compounds):

- **Common (most presentations):** Tachycardia, agitation, nausea — typically resolving with supportive care (<8 hours inpatient)
- **Severe (less common):** Myocardial infarction, ischemic stroke, thromboembolism, acute kidney injury (AKI), generalized tonic-clonic seizures, first-episode psychosis, paranoia, self-harm/suicidal ideation, hyperemesis, rhabdomyolysis
- **Rare/critical:** Multiple organ failure (Armstrong et al. 2019 [Ref 24]), intracranial hemorrhage, hemorrhagic coagulopathy (brodifacoum-contaminated products)

The van Amsterdam et al. (2015) review specifically highlights that full CB1 agonism (as in 5F-PB-22) combined with the absence of CBD (which has antipsychotic properties in cannabis) substantially increases the psychosis-inducing risk compared to natural cannabis [Ref 17].

### Neurodevelopmental Risk

CB1R-mediated enhancement of neuronal differentiation observed in vitro at ≤1 μM concentrations suggests potential risk for prenatal exposure (Alexandre et al. 2020 [Ref 7]). This finding is from in vitro cell culture; no human or animal developmental toxicity studies have been published for 5F-PB-22.

### Analytical Detection Notes

5F-PB-22 presence in complex matrices:
- **Urine:** Parent compound typically absent (high logP); best detected via 3-carboxyindole metabolite (Minakata 2017 [Ref 27]); validated UHPLC-QTOF-MS method exists (Gundersen 2019 [Ref 14-related])
- **Blood:** Detectable at ng/mL levels by LC-MS/MS
- **Hair:** LOD 0.065–0.125 ng/mg (Musile et al. 2023 [Ref 33])
- **Oral fluid:** No validated method specifically for 5F-PB-22 found in literature
- **Colorimetric:** Detected by Ehrlich reagent (indole-specific reaction, validated) (Durmus et al. 2018 [Ref 30-related])
- **Infused paper:** Detectable by ATR-FTIR (Coombs et al. 2023 [Ref 32]); ion mobility spectrometry (Norman et al. 2021 [Ref 22])

---

## Harm Reduction

### Drug Testing and Identification

- Reagent testing: 5F-PB-22 is detectable by Ehrlich reagent (indole-specific) but cannot distinguish it from other indole-containing substances
- More specific identification requires analytical chemistry (GC-MS, LC-MS/MS): ATR-FTIR validated for infused paper (non-destructive); mass spectrometric techniques required for isomer differentiation [Refs 25, 26, 32]
- 5F-PB-22 has 10 known positional isomers (quinolinyl/isoquinolinyl); not all are legally controlled; forensic differentiation requires LC-MS/MS with CID spectrum analysis [Refs 25, 26]

### Key Risks to Communicate

1. **Potency is extreme:** 5F-PB-22 is approximately 26x more potent than JWH-018 at CB1, with no dose ceiling from partial agonism — full agonists offer no intrinsic safety mechanism against overdose from excess dosing [Ref 1]
2. **Alcohol combination is documented lethal:** Multiple published fatalities involve co-use of 5F-PB-22 and alcohol. Beyond additive CNS depression, ethanol causes a novel metabolic interaction (transesterification) that can produce additional bioactive metabolites [Refs 5, 6]
3. **Urine tests will not detect it:** Due to high lipophilicity, standard urine drug screens are negative for the parent compound — harm reduction communication should note this
4. **Dose measurement is critical:** Given mg-range dosing (1–8+ mg community consensus) and extreme potency, accurate weighing equipment (0.001 g precision scale) is essential
5. **Prison/mail-infused paper context:** 5F-PB-22 was one of the most prevalent SCRAs in UK prison mail seizures in the period leading up to the PSA 2016 [Ref 22, web sources]

### Acute Intoxication Management (Class-Level)

Per Tait et al. 2016 [Ref 16]:
- IV fluids for tachycardia/dehydration
- Benzodiazepines for agitation and seizures
- Anti-emetics for nausea/hyperemesis
- Most cases resolve without intensive care within 8 hours
- Severe presentations (AKI, myocardial ischemia, psychosis) require appropriate specialist management

---

## Tolerance & Dependence

### Tolerance

No published study has directly measured tolerance development for 5F-PB-22. The seed data tolerance parameters (5-day half-life, 1.5-week full reset, cross-tolerance with cannabinoids) are class-level inferences based on cannabinoid pharmacology. They are reasonable for a potent CB1 agonist but are not confirmed by 5F-PB-22-specific research.

**⚠️ FLAG (safety-critical):** Tolerance half-life and reset timelines are not verified against a published source for 5F-PB-22 specifically.

### Dependence

Physical and psychological dependence have been documented for synthetic cannabinoids as a class. Key findings:
- Regular users meeting cannabis dependence criteria have reported SC use [Ref 28 — Gunderson 2012]
- SC use has been reported to alleviate cannabis withdrawal symptoms (cross-dependence) [Ref 28]
- Withdrawal characterization is incomplete; case reports describe anxiety, nausea, insomnia, irritability [Ref 23 — Cooper 2016]
- Treatment: benzodiazepines for symptom relief; quetiapine (atypical antipsychotic) has also shown utility in some cases [Ref 23]

The Angerer et al. fatality report explicitly cautions that blood SC concentrations cannot be judged as toxic or lethal without considering tolerance from frequent use [Ref 4].

---

## Interactions

### Alcohol (Ethanol)

Multiple lines of evidence establish that alcohol co-use with 5F-PB-22 is particularly dangerous:

1. **Pharmacodynamic:** Both CNS depressants; additive respiratory/cardiovascular depression
2. **Pharmacokinetic:** CES enzymes mediate transesterification of 5F-PB-22 with ethanol to produce 5F-PB-22 ethyl ester — a novel bioactive metabolite detected in postmortem blood at 0.4 μg/L (Apirakkan et al. 2021 [Ref 6])
3. **Fatal case data:** UK fatality (blood alcohol 311 mg/100mL) [Ref 5]; German fatality with ethanol co-detection [Ref 4]

Severity classification: **Severe** (documented fatalities; mechanism plausible)

### Other CNS Depressants

Expected additive/synergistic CNS depression with opioids, benzodiazepines, barbiturates, and other sedative-hypnotics based on class pharmacology. No published data specific to 5F-PB-22. In the Angerer 2017 German fatality, case 3 involved non-toxic concentrations of trimipramine and olanzapine alongside 5F-ADB [Ref 4] — alerting to polypharmacy risk.

### Cocaine, DMT, LSD, Mescaline

No published interaction data. Seed data lists all as "unknown" — this assessment is confirmed. No update possible from the evidence base.

**⚠️ FLAG:** All four listed interactions (cocaine, DMT, LSD, mescaline) lack published data and remain unresolvable from published sources. Generation agent should retain "unknown" severity.

---

## Legal Status

| Jurisdiction | Status | Notes |
|---|---|---|
| United States | Schedule I (permanent) | DEA final rule, September 2016 [Ref 15]; temp placement Jan 10, 2014 [Ref 20] |
| United Kingdom | Class B (MDA 1971) | December 2016 MDA amendment; also covered by PSA 2016 from May 26, 2016 |
| China | Controlled | October 2015 |
| United Nations | Schedule II (1971 Convention) | 2018 [Ref 30] |
| Canada | Controlled | Under CDSA; quinolinyl indolecarboxylate structural class |
| Australia | Prohibited import | Criminal Code Regulations |
| Japan | Scheduling date not confirmed | PB-22 (parent) found in Japanese herbal blends 2012–2013 |
| European Union | Varies by member state | No EU-wide specific control as of data gathered; covered under blanket NPS legislation in many states |

---

## Clinical Trials

No clinical trials are registered for 5F-PB-22 on ClinicalTrials.gov. No therapeutic applications have been investigated. Expected: none, given Schedule I/Class B designation and adverse safety profile.

---

## Community Feedback Analysis

No community feedback submitted in Part A2 of the brief. No feedback items to analyze.

---

## Gaps & Flags

### Safety-Critical Flags (require editorial review before publication)

1. **⚠️ Dose ranges not verified in published literature.** The seed data dose ranges (Threshold 1 mg, Light 1–3 mg, Common 3–5 mg, Strong 5–8 mg, Heavy 8+ mg for both oral and smoked) appear to originate from community consensus (PsychonautWiki). No published controlled human dosing study exists for 5F-PB-22. These ranges should be labeled as community-derived in the article.

2. **⚠️ Duration data (2–3h oral; 90 min smoked) not verified in published literature.** The smoked duration data (90 min, from PsychonautWiki retrieval) and oral duration (2–3h from seed) are community-based. No controlled pharmacokinetic study confirms these timelines.

3. **⚠️ LD50/lethal dose unknown.** No published LD50 exists for any species. Fatalities have occurred at blood concentrations overlapping with impairment-level concentrations (0.37–1.5 ng/mL). Lethal dose cannot be stated.

4. **⚠️ Tolerance/dependence parameters (5-day half-life, 1.5-week reset) not verified against a published source** for 5F-PB-22 specifically. Based on class inference only.

5. **⚠️ Drug interactions with cocaine, DMT, LSD, and mescaline** have no published data. All remain "unknown."

### Data Gaps (non-safety-critical)

6. **SMILES string** was not retrieved via PubChem API due to JavaScript rendering requirements. Generation agent should directly query PubChem CID 72710774 for canonical SMILES before publishing chemical structure data.

7. **No human pharmacokinetics study** — Tmax, bioavailability, plasma half-life, protein binding are unknown. CYP450 enzyme involvement in oxidative metabolism is not characterized (CES1 is the primary enzyme for ester hydrolysis; oxidative pathways may involve CYP3A4 based on structural analogy, but not published).

8. **Japan scheduling date** — PB-22 was identified in Japanese herbal blends in 2012–2013; Japan likely controlled it, but specific date and regulatory action not confirmed in available sources.

9. **No subjective effects controlled study** — all effect descriptions must be inferred from cannabinoid class pharmacology and case report presentations, not direct clinical observation.

10. **CB2 in vivo relevance** — 5F-PB-22 acts at CB2 (EC50 = 11 nM), but no immune or peripheral pharmacology studies specific to 5F-PB-22 exist.

11. **No published data on the Spice/K2 product formulations** containing 5F-PB-22 (concentrations in herbal products unknown; batch-to-batch variability not characterized).

12. **Oral bioavailability** — the compound has been primarily studied via smoked/inhaled route in case reports and impaired driving contexts. Oral pharmacokinetics are entirely unstudied. The dose equivalence between oral and smoked routes is not established.

### Contradictions Between Seed Data and Published Sources

- **CB1 Ki value discrepancy:** One web source cited Ki = 0.055 nM; the peer-reviewed De Luca et al. 2016 [Ref 1] reports Ki = 0.13 nM (native rat CB1). Different assay systems (recombinant vs. native, different radioligands) explain this variation. Use De Luca 2016 [Ref 1] as the canonical primary reference.
- **No other direct contradictions** between seed data and published sources detected.

---

*Research completed: 2026-05-11. 33 citations in registry. No community feedback to analyze.*