CBN
Studies and references cited across this article, graded by evidence strength.
Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.
Data points an editor reviewed and accepted for publication.
Value Provenance
Dosing
oraltrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | — | — | low |
| Low | — | — | low |
| Common | — | — | low |
| Strong | — | — | low |
| Heavy | — | — | low |
| Editorial | No human dose-response relationship has been established for oral CBN. Hollister 1973 administered 100 mg oral to 6 volunteers with no detectable effects. Commercial products use ≤5–10 mg without pharmacological validation. CUPID trial tests 30 mg and 300 mg but results are unpublished. No tier values can be responsibly proposed — all numeric fields intentionally omitted. This entry exists to document the data gap for editorial review. | ||
ReasoningReasoningNo human dose-response relationship has been established for oral CBN. Hollister 1973 administered 100 mg oral to 6 volunteers with no detectable effects. Commercial products use ≤5–10 mg without pharmacological validation. CUPID trial tests 30 mg and 300 mg but results are unpublished. No tier values can be responsibly proposed — all numeric fields intentionally omitted. This entry exists to document the data gap for editorial review. Evidence basis: unknown | |||
Duration
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Totaltrace | 2–6 hours | 2–6 hours | low |
| Editorial | No published human data characterize the temporal pharmacodynamic profile of oral CBN. This range is inferred from general cannabinoid oral PK principles (McGilveray 2005): lipophilic cannabinoids typically produce subjective effects lasting 2–6 hours via oral route, depending on dose, formulation, and individual metabolism. CBN-specific half-life is uncharacterized. Work-notes explicitly state no duration data exist — this entry is structural analogy from the cannabinoid class (reference compound: oral THC). | ||
ReasoningReasoningNo published human data characterize the temporal pharmacodynamic profile of oral CBN. This range is inferred from general cannabinoid oral PK principles (McGilveray 2005): lipophilic cannabinoids typically produce subjective effects lasting 2–6 hours via oral route, depending on dose, formulation, and individual metabolism. CBN-specific half-life is uncharacterized. Work-notes explicitly state no duration data exist — this entry is structural analogy from the cannabinoid class (reference compound: oral THC). Evidence basis: structural_analogy | |||
Safety
Toxicity Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Acute | negligible | negligible | low |
| Chronic | low | low | low |
| Organs Affected | — | — | low |
| Editorial | Acute toxicity rated negligible based on absence of documented organ damage or fatalities at any reported human dose (1970s studies, INM-755 Phase 2). Chronic toxicity rated low due to insufficient long-term data — subacute mouse study (Bailey 2022) showed no organ damage, but no chronic human exposure data exist. No organs affected have been identified. Evidence base is primarily one subacute animal study and a small clinical trial (n=19, topical route only). Confidence is low because no controlled toxicity studies, no LD50, and no reproductive/developmental data exist. | ||
ReasoningReasoningAcute toxicity rated negligible based on absence of documented organ damage or fatalities at any reported human dose (1970s studies, INM-755 Phase 2). Chronic toxicity rated low due to insufficient long-term data — subacute mouse study (Bailey 2022) showed no organ damage, but no chronic human exposure data exist. No organs affected have been identified. Evidence base is primarily one subacute animal study and a small clinical trial (n=19, topical route only). Confidence is low because no controlled toxicity studies, no LD50, and no reproductive/developmental data exist. Evidence basis: animal_study | |||
Dependence Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Physical | none | none | medium |
| Psychological | negligible | negligible | medium |
| Compulsive Redosing | negligible | negligible | medium |
| Dose Escalation | negligible | negligible | medium |
| Editorial | No direct CBN self-administration, conditioned place preference, or withdrawal studies exist. Rating based on Heal et al. 2024 assessment that non-psychoactive cannabinoids lack intoxicating/rewarding properties, combined with pharmacological reasoning from CB1 partial agonism with low potency/efficacy. Confidence is medium because the pharmacological rationale is sound but direct evidence is absent. | ||
ReasoningReasoningNo direct CBN self-administration, conditioned place preference, or withdrawal studies exist. Rating based on Heal et al. 2024 assessment that non-psychoactive cannabinoids lack intoxicating/rewarding properties, combined with pharmacological reasoning from CB1 partial agonism with low potency/efficacy. Confidence is medium because the pharmacological rationale is sound but direct evidence is absent. Evidence basis: expert_opinion | |||
Withdrawal Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Severity | none | none | low |
| Symptoms | — | — | low |
| Fatal | No | No | low |
| Medical Supervision | Not required | Not required | low |
| Editorial | No CBN withdrawal syndrome has been characterized in published literature. Absence of evidence rather than confirmed absence — no direct withdrawal studies exist. Given negligible dependence liability and low CB1 potency, withdrawal is not expected. | ||
ReasoningReasoningNo CBN withdrawal syndrome has been characterized in published literature. Absence of evidence rather than confirmed absence — no direct withdrawal studies exist. Given negligible dependence liability and low CB1 potency, withdrawal is not expected. Evidence basis: expert_opinion | |||
Tolerance Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Buildup | slow | slow | low |
| Half-life | — | — | low |
| Full Reset | — | — | low |
| Cross-tolerances | Δ⁹-THC | Δ⁹-THC | low |
| Editorial | No direct CBN tolerance studies exist. Slow buildup inferred from CB1 partial agonism — less potent/efficacious than THC (reference compound), so receptor downregulation expected to be slower. Cross-tolerance with THC expected from shared CB1 target. All parameters are structural analogy from THC tolerance pharmacology. | ||
ReasoningReasoningNo direct CBN tolerance studies exist. Slow buildup inferred from CB1 partial agonism — less potent/efficacious than THC (reference compound), so receptor downregulation expected to be slower. Cross-tolerance with THC expected from shared CB1 target. All parameters are structural analogy from THC tolerance pharmacology. Evidence basis: structural_analogy | |||
Effects & Profile
Contraindications
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| metabolic Narrow-TI CYP3A4 substrate medicationstrace | relative | relative | medium |
| Editorial | Lau & Chang 2026 demonstrated PXR activation at pharmacologically relevant concentrations (0.3 µM MEC). CYP3A4 induction is the downstream consequence. All data in vitro; no in vivo confirmation. | ||
ReasoningReasoningLau & Chang 2026 demonstrated PXR activation at pharmacologically relevant concentrations (0.3 µM MEC). CYP3A4 induction is the downstream consequence. All data in vitro; no in vivo confirmation. | |||
| metabolic Narrow-TI CYP2C9 substrate medicationstrace | relative | relative | medium |
| Editorial | Havlasek et al. 2023 and Stout & Cimino 2014 confirmed CYP2C9 as a CBN metabolic pathway. Competitive substrate inhibition is a standard pharmacokinetic mechanism. In vitro data only. | ||
ReasoningReasoningHavlasek et al. 2023 and Stout & Cimino 2014 confirmed CYP2C9 as a CBN metabolic pathway. Competitive substrate inhibition is a standard pharmacokinetic mechanism. In vitro data only. | |||
| pregnancy breastfeeding Pregnancy and lactationtrace | absolute | absolute | low |
| Editorial | Class-level cannabinoid contraindication. No CBN-specific data exist. CB1 expression in fetal neural tissue and lipophilic placental transfer are established for the cannabinoid class. | ||
ReasoningReasoningClass-level cannabinoid contraindication. No CBN-specific data exist. CB1 expression in fetal neural tissue and lipophilic placental transfer are established for the cannabinoid class. | |||
| other Driving and machinery operationtrace | relative | relative | low |
| Editorial | No controlled driving or psychomotor data for CBN. CUPID trial (Lavender et al. 2023) includes simulated driving endpoint, acknowledging the theoretical risk. CB1 partial agonism could impair motor function at sufficient receptor occupancy. | ||
ReasoningReasoningNo controlled driving or psychomotor data for CBN. CUPID trial (Lavender et al. 2023) includes simulated driving endpoint, acknowledging the theoretical risk. CB1 partial agonism could impair motor function at sufficient receptor occupancy. | |||
| other Concurrent CNS depressantstrace | relative | relative | low |
| Editorial | Class-level cannabinoid interaction. CB1 agonism produces CNS depression; additive effects with other depressants are pharmacologically expected. No CBN-specific human data. | ||
ReasoningReasoningClass-level cannabinoid interaction. CB1 agonism produces CNS depression; additive effects with other depressants are pharmacologically expected. No CBN-specific human data. | |||
| hepatic Severe hepatic impairmenttrace | relative | relative | low |
| Editorial | Class-level cannabinoid contraindication. CBN's rapid hepatic biotransformation (Havlasek et al. 2023) means hepatic impairment would disproportionately affect its clearance. No CBN-specific hepatic impairment data. | ||
ReasoningReasoningClass-level cannabinoid contraindication. CBN's rapid hepatic biotransformation (Havlasek et al. 2023) means hepatic impairment would disproportionately affect its clearance. No CBN-specific hepatic impairment data. | |||
Dose Tier Summaries
No light dose range has been established for CBN. The only published human oral study (Hollister 1973) administered 100 mg to 6 volunteers and detected no cannabis-like effects, making it impossible to define what constitutes a 'light' experience. Commercial sleep products use 5–10 mg, but these doses have never been validated against any subjective or pharmacodynamic endpoint in a controlled setting. If light effects occur at some oral dose, CB1 partial agonism predicts mild sedation, subtle appetite enhancement, and gentle muscle relaxation — attenuated versions of THC's body-centered effects. No perceptual, cognitive, or emotional changes would be expected at this level. These predictions are entirely class-extrapolated from cannabinoid pharmacology.
Work-notes state 'No data' for light tier. No human dose-response exists. Content conveys the data gap and offers class-extrapolated predictions clearly labeled as such. Reference compound is THC (attenuated 4-10×).
ReasoningReasoning
Work-notes state 'No data' for light tier. No human dose-response exists. Content conveys the data gap and offers class-extrapolated predictions clearly labeled as such. Reference compound is THC (attenuated 4-10×).
Evidence basis: structural_analogy
No common dose range has been pharmacologically validated for CBN. Commercial products use ≤5–10 mg oral, but this dosing is market-driven rather than evidence-based. The CUPID insomnia trial tests 30 mg and 300 mg CBN versus placebo — doses far exceeding commercial products — but results remain unpublished as of May 2026. Based on CBN's CB1 partial agonism (1/4 to 1/10 of THC potency), a common-range experience — if achievable orally — would likely involve mild sedation, modest appetite enhancement, gentle pain suppression via TRPA1 agonism, and subtle muscle relaxation. Cognitive effects would be minimal. No intoxication, perceptual distortion, or euphoria would be expected at this level.
Work-notes state 'No data — commercial products use ≤5–10 mg but this is not pharmacologically validated.' Content describes the evidence gap and commercial context. CUPID trial doses noted for context. Effect predictions extrapolated from CB1 partial agonism class pharmacology.
ReasoningReasoning
Work-notes state 'No data — commercial products use ≤5–10 mg but this is not pharmacologically validated.' Content describes the evidence gap and commercial context. CUPID trial doses noted for context. Effect predictions extrapolated from CB1 partial agonism class pharmacology.
Evidence basis: structural_analogy
No strong dose range is established for oral CBN. The only reference point is Hollister 1973, where 100 mg oral produced no detectable cannabis-like effects in 6 volunteers — suggesting that even this dose may not achieve sufficient systemic exposure to produce strong effects via the oral route. By contrast, Perez-Reyes 1973 administered ~12–14 mg intravenously (200 µg/kg) and observed mild psychoactivity including a 25% heart rate increase and self-reported 'high.' The divergence between routes highlights CBN's extremely poor oral bioavailability. A strong oral experience may simply not be achievable without formulation technologies (e.g., nano-emulsion) that bypass first-pass metabolism. If strong effects were achieved, attenuated THC-like cognitive impairment, time alteration, and more pronounced sedation would be predicted.
Work-notes reference Hollister 1973 (oral 100 mg, no effects) and Perez-Reyes 1973 (IV 200 µg/kg, mild effects). Content explains the route-dependent divergence and bioavailability limitation. Effect predictions are class-extrapolated from THC.
ReasoningReasoning
Work-notes reference Hollister 1973 (oral 100 mg, no effects) and Perez-Reyes 1973 (IV 200 µg/kg, mild effects). Content explains the route-dependent divergence and bioavailability limitation. Effect predictions are class-extrapolated from THC.
Evidence basis: structural_analogy
No heavy dose range exists for CBN. No published study has administered CBN at doses intended to produce maximal or overwhelming effects. The CUPID trial's highest arm (300 mg oral) will provide the first data point at a dose substantially exceeding any previously tested oral amount, but even this is a clinical trial dose rather than a 'heavy' recreational dose. At hypothetical heavy doses — if sufficient systemic exposure were achieved — the CB1 partial agonism ceiling would limit maximum intensity well below that of THC. The partial agonist pharmacology means that increasing dose beyond a certain point produces diminishing additional CB1 activation. Pronounced sedation, cognitive impairment, and motor control impairment would be the primary concerns. No safety data exist at these exposure levels.
Work-notes state 'No data' for heavy tier. Content describes the partial agonist ceiling effect, which is a genuine pharmacological constraint. CUPID 300 mg arm noted as the only upcoming high-dose data point. All predictions class-extrapolated from THC partial agonism pharmacology.
ReasoningReasoning
Work-notes state 'No data' for heavy tier. Content describes the partial agonist ceiling effect, which is a genuine pharmacological constraint. CUPID 300 mg arm noted as the only upcoming high-dose data point. All predictions class-extrapolated from THC partial agonism pharmacology.
Evidence basis: structural_analogy
No threshold dose has been established for CBN in published human research. Commercial products typically contain 2–5 mg oral doses, but no controlled study has identified the minimum dose at which CBN produces perceptible subjective effects via the oral route. The compound's extremely poor oral bioavailability means that the threshold for subjective awareness — if one exists at oral doses — likely requires substantially higher amounts than those found in consumer products. At whatever dose threshold effects might emerge, the pharmacological profile (CB1 partial agonism) predicts subtle body awareness — perhaps faint muscle relaxation or a barely perceptible shift in bodily tension — rather than any cognitive or perceptual change. No controlled data support this prediction.
Work-notes explicitly state 'No data — cannot write dose tier summary' for threshold. No dose-response data exist for CBN. Content describes the absence of data and provides pharmacologically-grounded speculation with appropriate caveats. Hollister 1973 showed no effects at 100 mg oral.
ReasoningReasoning
Work-notes explicitly state 'No data — cannot write dose tier summary' for threshold. No dose-response data exist for CBN. Content describes the absence of data and provides pharmacologically-grounded speculation with appropriate caveats. Hollister 1973 showed no effects at 100 mg oral.
Evidence basis: structural_analogy
History
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.
Sources
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- [3]strongCannabinol and Sleep: Separating Fact from Fiction.Corroon J · 2021 · Cannabis and cannabinoid research
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- [5]strongMeta-analysis of cannabinoid ligand binding affinity and receptor distribution: interspecies differences.McPartland JM, Glass M, Pertwee RG · 2007 · British journal of pharmacologypubmed 176416673 claims checked3 verified
- [6]moderateSpecies differences in pregnane X receptor activation by delta-9-tetrahydrocannabinol, cannabidiol, and cannabinolLau AJ, Chang TKH · 2026 · Biochemical and Biophysical Research Communications
- [7]moderateCannabichromene from full-spectrum hemp extract exerts acute anti-seizure effects through allosteric activation of GABAA receptors.Wang Z, Zheng H, Yang H, et al. · 2024 · Fundamental research
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- [10]weakCBN first isolation 1896 - Wood, Spivey, Easterfield historyWeb historical sources · 2020linkno claims checked
- [11]weakCBN psychoactive effects humans - Perez-Reyes 1973 and Hollister 1973 reviewCannabis and Cannabinoid Research (summary) · 2021linkno claims checked
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- [24]moderateSimultaneous and sensitive analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in plasma after oral application of small doses of THC and cannabis extract.Nadulski T, Sporkert F, Schnelle M, Stadelmann AM, Roser P, et al. · 2005 · Journal of analytical toxicologypubmed 163563353 claims checked3 verified
- [25]strongPharmacokinetics of cannabinoidsMcGilveray IJ · 2005 · Pain Research and Managementpubmed 162374772 claims checked2 verified
- [26]moderateHepatic biotransformation of non-psychotropic phytocannabinoids and activity screening on cytochromes P450 and UDP-glucuronosyltransferases.Havlasek J, Vrba J, Zatloukalova M, et al. · 2023 · Toxicology and applied pharmacology
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- [32]moderateCannabinoids in glaucoma: a primary screening procedure.Elsohly MA, Harland E, Murphy JC, Wirth P, Waller CW · 1981 · Journal of clinical pharmacologypubmed 6271842no claims checked
- [33]moderateCannabinol modulates neuroprotection and intraocular pressure: A potential multi-target therapeutic intervention for glaucoma.Somvanshi RK, Zou S, Kadhim S, Padania S, Hsu E, Kumar U · 2022 · Biochimica et biophysica acta. Molecular basis of disease
- [34]moderateAntibacterial cannabinoids from Cannabis sativa: a structure-activity study.Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M, Smith E, Rahman MM · 2008 · Journal of natural products
- [35]moderateThe anti-biofilm activity of cannabinoids against methicillin-resistant Staphylococcus aureus.Kwong PTH, Das T, Arnold JC, Chan HK, Kwok PCL · 2025 · Journal of applied microbiology
- [36]moderateThe Anticancer Activity of Cannabinol (CBN) and Cannabigerol (CBG) on Acute Myeloid Leukemia Cells.Kadriya A, Forbes-Robertson S, Falah M · 2024 · Molecules
- [37]moderateImpact of minor cannabinoids on key pharmacological targets of estrogen receptor-positive breast cancer.Almeida CF, Correia-da-Silva G, Ribeiro AP, Teixeira N, Amaral C · 2025 · Biochimica et biophysica acta. Molecular and cell biology of lipids
- [38]moderateCannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells.Schoeman R, Beukes N, Frost C · 2020 · Molecules
- [39]moderateDifferences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures.Rosenthaler S, Pöhn B, Kolmanz C, Huu CN, Krewenka C, Huber A, Kranner B, Rausch WD, Moldzio R · 2014 · Neurotoxicology and teratology
- [40]weakCBN legal status United States, UK, Australia, Europe 2026Various sources · 2026linkno claims checked
Claim Verification
Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.
summary10 claims8verified1partial1inconclusive
partialIt acts as a partial agonist at both CB1 and CB2 receptors with approximately 1/4 to 1/10 the potency of THC at CB1, and possesses a broader multi-target pharmacological profile encompassing TRP channels, the pregnane X receptor, and GABA_A allosteric modulation[1]model confidence 75%
The abstract describes a drug discrimination study evaluating cannabimimetic effects and CB1/CB2 binding affinities, which is relevant to the partial agonist claim. However, the specific potency ratio of 1/4 to 1/10 relative to THC is not stated in the abstract, nor is the multi-target profile covering TRP channels, PXR, or GABA_A modulation.
This study sought to evaluate select minor cannabinoids and terpenes for Δ9-THC-like psychoactivity in mouse Δ9-THC drug discrimination and determine their binding affinities at CB1 and CB2 receptors.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveCBN holds a singular position in cannabinoid research history: its isolation from Charas in 1896 by Wood, Spivey, and Easterfield launched the entire field of phytocannabinoid chemistry[2]model confidence 55%
This is a review covering early cannabinoid history including CBN structure elucidation, which is within scope. However, the abstract does not specifically mention the 1896 isolation from Charas by Wood, Spivey, and Easterfield — these details may be in the full text.
Studies on cannabinoids predating the identification of delta-9-THC by Mechoulam in 1964 are reviewed. Contributions by Roger Adams and Alexander Todd.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedStructure elucidation by Adams and Todd in the early 1940s enabled the synthetic cannabinoid era, culminating in Mechoulam and Gaoni's identification of Δ⁹-THC in 1964model confidence 80%
The abstract covers pharmacological research beginning in the 1940s and the historical progression of cannabinoid science, which is fully consistent with the claimed narrative of Adams/Todd structure work leading to the THC identification era.
Research into the pharmacology of individual cannabinoids that began in the 1940s, several decades after the presence of a cannabinoid was first detected in cannabis, is concisely reviewed.
source: Cannabinoid pharmacology: the first 66 years
checked by claude-sonnet-4-6 · May 7, 2026
verifiedContemporary research interest centers on CBN's potential therapeutic applications in dermatology, neuroprotection, antimicrobial activity, and sleep — though for the last of these, a systematic review of all eligible human studies found insufficient evidence to support the widely marketed sleep-promoting claims.[3]model confidence 95%
The abstract directly and explicitly states that there is insufficient published evidence to support sleep-related claims for CBN, which is the core assertion this citation is used to support.
Consequently, there is insufficient published evidence to support sleep-related claims.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedAt the CB2 receptor, CBN binds with Ki = 96.3 ± 14 nM — within roughly 3-fold of THC[4]model confidence 99%
The abstract exactly confirms CBN Ki at CB2 = 96.3 ± 14 nM and THC Ki = 36.4 ± 10 nM, placing CBN within approximately 2.6-fold of THC — consistent with the 'roughly 3-fold' characterization.
The affinity of cannabinol for CB2 receptors (Ki = 96.3 +/- 14 nM) was confirmed to be in approximately the same range as that of delta 9-THC (Ki = 36.4 +/- 10 nM).
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCB1 affinity values range widely across studies (approximately 100–500 nM) due to methodological variability in radioligand binding assays[5]model confidence 85%
The abstract confirms a meta-analysis of 211 studies where sensitivity analyses did not support numerical validity of CBN binding values, directly implicating methodological variability. The specific 100–500 nM range is not stated but is consistent with the noted validity concerns.
Sensitivity analyses did not support the numerical validity of cannabidiol, cannabinol, 2-arachidonoyl glycerol and all ligands at RnCB2.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedBeyond cannabinoid receptors, CBN activates TRPA1 (contributing to analgesic potential), acts as a potent human pregnane X receptor agonist with a minimum effective concentration of 0.3 µM (carrying significant CYP3A4 induction and drug interaction implications), and demonstrates GABA_A receptor allosteric modulation linked to anti-seizure effects in preclinical models.[6]model confidence 92%
Citation [12] is used specifically for the PXR portion of this compound claim. The abstract directly confirms CBN as a human PXR agonist with MEC of 0.3 µM — exactly as stated.
CBN (10 µM) activated human PXR by 17-fold, rat PXR by 4-fold, and mouse PXR by 3-fold. Minimum effective concentration for hPXR activation by CBN was 0.3 µM.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedBeyond cannabinoid receptors, CBN activates TRPA1 (contributing to analgesic potential), acts as a potent human pregnane X receptor agonist with a minimum effective concentration of 0.3 µM (carrying significant CYP3A4 induction and drug interaction implications), and demonstrates GABA_A receptor allosteric modulation linked to anti-seizure effects in preclinical models.[7]model confidence 88%
Citation [17] is used for the GABA_A/anti-seizure portion of this compound claim. The abstract confirms CBN showed significant anti-seizure effects and GABA_A allosteric modulation was investigated.
CBN showed significant anti-seizure effects. Investigation of allosteric modulation on the GABAA receptor.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedPreclinical safety data from subacute mouse exposure suggest an acceptable safety profile at therapeutic doses, and the largest human safety dataset — a Phase 2 topical trial in 19 epidermolysis bullosa patients — reported no serious drug-related adverse events[8]model confidence 80%
Citation [37] covers the preclinical component of this compound claim. The abstract confirms subacute mouse exposure to therapeutic doses of CBN, consistent with 'acceptable safety profile at therapeutic doses.' The epidermolysis bullosa data is from a different citation.
Physiological and behavioral effects of subacute exposure to therapeutic and low pharmacological levels of a water-soluble CBN nano-emulsion (CBNight) in male mice.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedDependence liability is considered very low based on the absence of intoxicating or rewarding properties at typical doses, though no direct self-administration or withdrawal characterization studies have been published[9]model confidence 90%
The abstract directly confirms non-psychoactive cannabinoids do not produce intoxicating or rewarding properties, which is the basis for the low dependence liability claim.
Non-psychoactive cannabinoids do not produce intoxicating, cognitive or rewarding properties in humans.
checked by claude-sonnet-4-6 · May 7, 2026
history4 claims3verified1inconclusive
verifiedThe first formal randomized controlled trial specifically investigating CBN for insomnia — the CUPID study, testing 30 mg and 300 mg CBN versus placebo — has been protocolized but results remain unpublished as of 2026.[12]model confidence 95%
The abstract directly describes the CUPID protocol (30mg and 300mg CBN vs placebo for insomnia). That this is a published protocol with unpublished results is consistent with the abstract being the protocol paper itself.
Protocol for RCT testing CBN 30mg and 300mg vs placebo in insomnia disorder. Primary outcome: wake after sleep onset by polysomnography.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveThree years later, the same group corrected the formula to C₂₁H₂₆O₂.[2]model confidence 50%
The review covers early cannabinoid history and CBN structure elucidation, within scope. However, the abstract does not mention the specific formula correction to C₂₁H₂₆O₂ — this detail would be in the full text.
Studies on cannabinoids predating the identification of delta-9-THC by Mechoulam in 1964 are reviewed. Includes structure elucidation of cannabinol.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedThe complete structure was independently elucidated in the early 1940s by Roger Adams in the United States and by Alexander Todd (later a Nobel laureate) in the United Kingdom[2]model confidence 90%
The abstract directly mentions contributions by Roger Adams and Alexander Todd and structure elucidation of cannabinol, consistent with the claim of independent elucidation.
Contributions by Roger Adams and Alexander Todd. Includes structure elucidation of cannabinol.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedPharmacological research on CBN began in the 1940s with studies on individual cannabinoidsmodel confidence 98%
The abstract directly states that research into the pharmacology of individual cannabinoids began in the 1940s — an exact match for the claim.
Research into the pharmacology of individual cannabinoids that began in the 1940s, several decades after the presence of a cannabinoid was first detected in cannabis, is concisely reviewed.
source: Cannabinoid pharmacology: the first 66 years
checked by claude-sonnet-4-6 · May 7, 2026
chemistry3 claims3inconclusive
inconclusiveCBN belongs to the dibenzopyran class of cannabinoids and is classified within the broader terpenophenolic family characteristic of Cannabis sativa phytochemistry[13]model confidence 55%
The abstract mentions 'structural classification' of phytocannabinoids including CBN, within scope. However, the specific dibenzopyran/terpenophenolic classification terms are not confirmed in the abstract.
Comprehensive inventory of phytocannabinoids including cannabinol. Reviews biosynthetic origins, structural classification, and pharmacology.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveThe molecular structure comprises a benzo[c]chromene (dibenzopyran) ring system with a phenolic hydroxyl group at position 1, gem-dimethyl substitution at position 6, a methyl group at position 9, and an n-pentyl chain at position 3[14]model confidence 50%
Abstract is marked as not available. Cannot verify the specific structural claims.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveIt is poorly soluble in water and freely soluble in organic solvents including ethanol, methanol, and chloroform.[13]model confidence 50%
The abstract covers phytocannabinoid inventory including CBN but does not mention solubility properties. This detail is not verifiable from the abstract.
Comprehensive inventory of phytocannabinoids including cannabinol. Reviews biosynthetic origins, structural classification, and pharmacology.
checked by claude-sonnet-4-6 · May 7, 2026
pharmacology19 claims15verified4inconclusive
verifiedConversely, CBN inhibits AP-1 activity through suppression of c-fos/c-jun and inhibition of ERK MAP kinase, providing an immunosuppressive counterpart[22]model confidence 97%
The abstract directly confirms inhibition of AP-1, decreased nuclear expression of c-fos and c-jun, and inhibition of ERK MAP kinases — all three components of the claimed mechanism.
CBN inhibited binding to AP-1-containing sites from the IL-2 promoter, decreased nuclear expression of c-fos and c-jun, and inhibited ERK MAP kinases.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedAt CB2, Showalter et al. (1996) reported Ki = 96.3 ± 14 nM against [³H]CP-55,940 at cloned human CB2, compared to Δ⁹-THC Ki = 36.4 ± 10 nM — placing CBN within roughly 3-fold of THC at this receptor[4]model confidence 99%
The abstract exactly matches the claimed Ki values for both CBN (96.3 ± 14 nM) and THC (36.4 ± 10 nM) at CB2, confirming the ~2.6-fold (roughly 3-fold) relationship.
The affinity of cannabinol for CB2 receptors (Ki = 96.3 +/- 14 nM) was confirmed to be in approximately the same range as that of delta 9-THC (Ki = 36.4 +/- 10 nM).
checked by claude-sonnet-4-6 · May 7, 2026
verifiedAt CB1, published Ki values range widely (approximately 100–500 nM depending on assay conditions), with a meta-analysis of 211 cannabinoid binding studies noting that methodological sensitivity analyses did not strongly validate some CBN CB1 Ki values in the literature[5]model confidence 90%
The abstract directly confirms 211-study meta-analysis and sensitivity analyses failing to support numerical validity of CBN binding values, consistent with the claim about methodological concerns.
Pooled data from 211 studies measured ligand binding affinities at human or rat cannabinoid receptors CB1 and CB2. Sensitivity analyses did not support the numerical validity of cannabidiol, cannabinol...
checked by claude-sonnet-4-6 · May 7, 2026
verifiedA 2025 systematic review confirmed that both THC and CBN show significantly higher CB1 affinity than CBD, CBG, and CBC.[16]model confidence 95%
The abstract directly confirms that THC and CBN showed high affinities for CB1, while CBG, CBC, and CBD exhibited 10–100 times lower affinities.
A systematic review and meta-analysis of binding affinities (Ki) for CB1, CB2 confirmed that THC and CBN showed high affinities for CB1 and CB2, while CBG, CBC, and CBD exhibited 10-100 times lower affinities.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveA mouse drug discrimination study confirmed partial cannabimimetic activity — CBN partially substituted for THC — consistent with its CB1 partial agonist profile.[1]model confidence 60%
The abstract describes a drug discrimination study evaluating THC-like psychoactivity for minor cannabinoids including CBN, which is the right study. However, the abstract does not explicitly state the outcome — specifically that CBN 'partially substituted for THC' — which is the key factual assertion of the claim.
This study sought to evaluate select minor cannabinoids and terpenes for Δ9-THC-like psychoactivity in mouse Δ9-THC drug discrimination and determine their binding affinities at CB1 and CB2 receptors.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCBN exhibits functional context-dependence at CB2: while binding assays show partial agonism, Walter et al. (2003) demonstrated that CBN acts as a CB2 receptor antagonist in the context of 2-AG-induced microglial cell migration, blocking migration triggered by pathological neuronal stimulation[17]model confidence 95%
The abstract directly confirms CBN prevents 2-AG-induced microglial cell migration by antagonizing CB2 receptors, supporting both the functional antagonism claim and the 2-AG context.
Cannabinol and cannabidiol, two nonpsychotropic ingredients present in the marijuana plant, prevent the 2-AG-induced cell migration by antagonizing the CB2 and abnormal-cannabidiol-sensitive receptors, respectively.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedTRPA1: Potent rat TRPA1 agonist and desensitizer, contributing to analgesic and anti-inflammatory potential[18]model confidence 97%
The abstract directly states CBC, CBD, and CBN were potent rat TRPA1 agonists and desensitizers.
CBC, CBD and CBN were potent rat TRPA1 agonists and desensitizers.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedTRPV2: Weak agonist with EC₅₀ = 77.7 µM — substantially weaker than CBD at this target; physiological significance at typical cannabinoid concentrations is unclear[18]model confidence 97%
The abstract explicitly states CBN had EC50=77.7 µM at TRPV2 and was excluded from the potent activators — directly confirming weak agonist status with the exact EC50 value.
All non-acid cannabinoids, except CBC and CBN, potently activated and desensitized rat TRPV2. CBN had EC50=77.7 µM at TRPV2.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveTRPM8: No significant activity in standard assays[18]model confidence 50%
The abstract covers TRPA1 and TRPV2 data for CBN but does not mention TRPM8 at all. The TRPM8 claim cannot be verified from this abstract — relevant data may be in the full text.
CBC, CBD and CBN were potent rat TRPA1 agonists and desensitizers. All non-acid cannabinoids, except CBC and CBN, potently activated and desensitized rat TRPV2.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedPregnane X receptor (PXR/NR1I2): CBN is a human PXR agonist. At 10 µM, CBN activated hPXR 17-fold, rPXR 4-fold, and mPXR 3-fold in reporter gene assays. The minimum effective concentration for hPXR activation was 0.3 µM — within the pharmacological range — carrying significant drug interaction implications via CYP3A4 induction[6]model confidence 97%
The abstract exactly confirms all numerical values: 17-fold hPXR, 4-fold rPXR, 3-fold mPXR activation at 10 µM, and MEC of 0.3 µM. The CYP3A4 implication is within the scope of PXR agonism.
CBN (10 µM) activated human PXR by 17-fold, rat PXR by 4-fold, and mouse PXR by 3-fold. Minimum effective concentration for hPXR activation by CBN was 0.3 µM.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedGABA_A receptor: Anti-seizure effects observed in hemp extract studies with involvement of GABA_A receptor allosteric modulation[7]model confidence 88%
The abstract confirms CBN showed significant anti-seizure effects and that GABA_A allosteric modulation was investigated as the mechanism.
CBN showed significant anti-seizure effects. Investigation of allosteric modulation on the GABAA receptor.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedGABA_A receptor: Anti-seizure effects observed in hemp extract studies with involvement of GABA_A receptor allosteric modulation[19]model confidence 90%
The abstract directly confirms CBN involvement in the anti-seizure process and identifies GABA_A receptor as the primary anti-epileptic target of full-spectrum hemp extract.
CBN was involved in the anti-seizure process. GABAA receptor seems to be the primary anti-epileptic target of full-spectrum hemp extract.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusive5-HT₁A receptor: Listed as a target for minor cannabinoids, though specific binding data for CBN are limited[20]model confidence 50%
The abstract is a general review of minor cannabinoid pharmacology covering receptors and signaling pathways, which is within scope. However, the abstract does not specifically mention 5-HT₁A as a target for CBN — this detail may be in the full text.
This review focuses on the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds. Receptors and others.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveCBN enhances IL-2 mRNA expression in EL4 T cells via NF-AT transcription factor activation — an effect abrogated by the CaMKII inhibitor KN93 but not by the CB2 antagonist SR144528, confirming receptor independence[21]model confidence 60%
The abstract confirms NF-AT-mediated IL-2 mRNA enhancement in a CB1/CB2-independent manner, which supports part of the claim. However, the specific detail about KN93/CaMKII inhibitor abrogating the effect is not mentioned in the abstract and cannot be verified.
CBN enhanced IL-2 mRNA expression in a concentration-dependent manner via NF-AT in a CB1/CB2-independent manner.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedIn vivo, CBN (50 mg/kg i.p.) significantly attenuated Th2 cytokines (IL-4, IL-5, IL-13) and reduced IgE levels and mucus overproduction in an ovalbumin-induced allergic airway mouse model.[23]model confidence 95%
The abstract directly confirms the dose (50 mg/kg ip), cytokines (IL-4, IL-5, IL-13), serum IgE, and mucus overproduction attenuation in the ovalbumin challenge model.
CBN (50 mg/kg ip) significantly attenuated elevation of IL-2, IL-4, IL-5, IL-13 mRNA in lungs after ovalbumin challenge. Serum IgE elevation and mucus overproduction also attenuated.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedIn one analytical study, CBN was not detected in plasma after oral administration of small doses of cannabis extract (detection limit approximately 1.1 ng/mL by GC-MS), suggesting extremely poor oral bioavailability when present only as a trace constituent.[24]model confidence 97%
The abstract directly confirms CBN was not detected in plasma after oral cannabis extract administration, GC-MS LOD of 1.1 ng/mL.
CBN was not detected in plasma after oral administration of 10mg THC + 5.4mg CBD cannabis extract. GC-MS analytical method developed with CBN detection limit of 1.1 ng/mL.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedGeneral cannabinoid pharmacokinetic principles apply: high lipophilicity drives extensive tissue distribution, high first-pass hepatic metabolism limits oral bioavailability, and elimination half-lives are prolonged by redistribution from adipose tissue[25]model confidence 90%
The abstract confirms high first-pass metabolism for oral cannabinoids, fatty tissue distribution, and that CBN information is included alongside THC PK data — all consistent with the claimed general principles.
High first-pass metabolism affects oral cannabinoids. Cannabinoids distributed particularly to fatty tissues.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedHavlasek et al. (2023) identified CYP1A2, CYP2C9, CYP2C19, and CYP2D6 as hepatic biotransformation pathways, with CBN being the most rapidly biotransformed among the phytocannabinoids tested[26]model confidence 98%
The abstract exactly confirms CBN as the most rapidly metabolized phytocannabinoid tested, with primary metabolism via CYPs 1A2, 2C9, 2C19, and 2D6.
CBN was most rapidly metabolized of the phytocannabinoids tested. CBN primarily metabolized by CYPs 1A2, 2C9, 2C19 and 2D6.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedA systematic review also noted CYP2C9 and CYP3A4 involvement[27]model confidence 98%
The abstract directly confirms CYPs 2C9 and 3A4 as potential significant contributors to primary CBN metabolism.
CYP-450 enzymes as potential significant contributors to the primary metabolism of CBN: CYPs 2C9, 3A4.
checked by claude-sonnet-4-6 · May 7, 2026
receptor pharmacology6 claims6verified
verifiedCBN is a potent human pregnane X receptor (PXR/NR1I2) agonist[6]model confidence 99%
The abstract directly and explicitly states 'CBN is a human PXR agonist.'
CBN is a human PXR agonist with preferential activation of hPXR over rodent PXR.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedMcPartland et al. (2007) conducted sensitivity analyses across 211 cannabinoid binding studies and explicitly noted that some CBN Ki values in the literature should be interpreted with caution[5]model confidence 95%
The abstract directly confirms 211-study pooled analysis and sensitivity analyses not supporting numerical validity of CBN binding values — an explicit statement that these values should be interpreted with caution.
Pooled data from 211 studies measured ligand binding affinities at human or rat cannabinoid receptors CB1 and CB2. Sensitivity analyses did not support the numerical validity of cannabidiol, cannabinol...
checked by claude-sonnet-4-6 · May 7, 2026
verifiedA 2025 systematic meta-analysis confirmed that CBN shows high CB1 affinity — significantly higher than CBD, CBG, or CBC — but did not resolve the inter-study variability for CBN specifically.[16]model confidence 82%
The abstract directly confirms high CBN affinity for CB1 vs CBD/CBG/CBC (10–100x lower). The 'did not resolve inter-study variability' qualifier is not in the abstract but the abstract does not contradict it either; the main affinity claim is clearly supported.
THC and CBN showed high affinities for CB1 and CB2, while CBG, CBC, and CBD exhibited 10-100 times lower affinities.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCBN blocked pathological neuronal stimulation-triggered microglial migration at concentrations consistent with its binding affinity[17]model confidence 82%
The abstract confirms CBN prevents 2-AG-induced microglial migration by CB2 antagonism. The '2-AG-induced migration triggered by pathological neuronal stimulation' context is consistent with the abstract's mechanism.
Cannabinol and cannabidiol, two nonpsychotropic ingredients present in the marijuana plant, prevent the 2-AG-induced cell migration by antagonizing the CB2... receptors.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCBN showed significant anti-seizure effects in hemp extract studies, with evidence pointing to GABA_A receptor allosteric modulation as a contributing mechanism[19]model confidence 92%
The abstract confirms CBN involvement in anti-seizure effects and identifies GABA_A as the primary anti-epileptic target of full-spectrum hemp extract.
CBN was involved in the anti-seizure process. GABAA receptor seems to be the primary anti-epileptic target of full-spectrum hemp extract.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCBN inhibits the ABCG2 (BCRP) multidrug efflux transporter, which is relevant in oncology settings where cancer drug resistance is mediated by ABCG2[29]model confidence 95%
The abstract directly confirms CBN inhibits ABCG2 activity.
CBN inhibits ABCG2 activity.
checked by claude-sonnet-4-6 · May 7, 2026
neuroscience6 claims4verified2inconclusive
inconclusiveAs a partial agonist with 1/4 to 1/10 the potency of THC at CB1, CBN would be expected to produce attenuated versions of the neural effects produced by THC at equivalent receptor occupancy.[1]model confidence 55%
The abstract describes a drug discrimination study evaluating THC-like psychoactivity and CB1/CB2 binding affinities for CBN, which is within scope. However, the specific potency ratio of 1/4 to 1/10 relative to THC is not stated in the abstract.
This study sought to evaluate select minor cannabinoids and terpenes for Δ9-THC-like psychoactivity in mouse Δ9-THC drug discrimination and determine their binding affinities at CB1 and CB2 receptors.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveHypothalamic feeding circuits: CB1 activation in the lateral hypothalamus and nucleus accumbens shell stimulates appetite — consistent with the orexigenic properties noted for CBN in preclinical models.[20]model confidence 50%
The abstract is a general review of minor cannabinoid pharmacology, within scope. However, it does not specifically discuss hypothalamic feeding circuits, lateral hypothalamus, nucleus accumbens, or CBN-specific orexigenic effects.
This review focuses on the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCBN's CB2 antagonism in the context of microglial migration has neurological implications[17]model confidence 92%
The abstract directly describes CBN preventing microglial (brain immune cell) migration via CB2 antagonism — inherently neurological in implication.
Cannabinol and cannabidiol, two nonpsychotropic ingredients present in the marijuana plant, prevent the 2-AG-induced cell migration by antagonizing the CB2... Microglial cells express CB2 receptors at the leading edge of lamellipodia.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCBN's anti-seizure effects in hemp extract studies implicate GABA_A receptor allosteric modulation — a mechanism distinct from CB1 partial agonism[7]model confidence 88%
The abstract confirms CBN's anti-seizure effects and GABA_A allosteric modulation investigation, consistent with a mechanism distinct from CB1.
CBN showed significant anti-seizure effects. Investigation of allosteric modulation on the GABAA receptor.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCBN's anti-seizure effects in hemp extract studies implicate GABA_A receptor allosteric modulation — a mechanism distinct from CB1 partial agonism[19]model confidence 90%
The abstract confirms CBN involvement in anti-seizure process and GABA_A as the primary anti-epileptic target.
CBN was involved in the anti-seizure process. GABAA receptor seems to be the primary anti-epileptic target of full-spectrum hemp extract.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedDoes CBN's GABA_A modulation produce distinct EEG signatures (e.g., increased spindle density, altered slow-wave activity)? The CUPID trial includes sleep staging as a secondary endpoint and may address this.[12]model confidence 78%
The abstract confirms PSG (polysomnography) as the primary outcome of the CUPID trial; PSG inherently includes sleep staging with EEG. Sleep staging as a secondary endpoint is a reasonable inference from PSG methodology.
Protocol for RCT testing CBN 30mg and 300mg vs placebo in insomnia disorder. Primary outcome: wake after sleep onset by polysomnography.
checked by claude-sonnet-4-6 · May 7, 2026
pharmacokinetic detail3 claims3verified
verifiedNadulski et al. (2005): CBN was not detected in plasma (LOD ~1.1 ng/mL by GC-MS) after oral administration of small doses of cannabis extract, despite being present in the administered extract. This suggests extremely poor oral bioavailability when CBN is present only as a trace component.[24]model confidence 97%
The abstract confirms CBN not detected in plasma after oral cannabis extract, GC-MS LOD of 1.1 ng/mL. The inference about trace component bioavailability is consistent with the finding.
CBN was not detected in plasma after oral administration of 10mg THC + 5.4mg CBD cannabis extract. GC-MS analytical method developed with CBN detection limit of 1.1 ng/mL.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedIn the absence of CBN-specific human PK data, general cannabinoid pharmacokinetic principles provide context:[25]model confidence 92%
The abstract confirms the review focuses on THC PK but also includes CBN and CBD information, supporting the use of general cannabinoid PK principles as contextual framing for CBN.
Review focuses on THC pharmacokinetics but also includes known information for cannabinol and cannabidiol.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedMetabolism: CBN is metabolized by multiple hepatic CYP enzymes. Havlasek et al. (2023) identified CYP1A2, CYP2C9, CYP2C19, and CYP2D6 as biotransformation pathways, with CBN being the most rapidly biotransformed among the phytocannabinoids tested in their panel (which included CBD, CBG, CBC, and CBDV). A systematic review by Stout and Cimino (2014) additionally noted CYP2C9 and CYP3A4 involvement. The rapid biotransformation rate likely contributes to high first-pass metabolism.[27]model confidence 92%
Citation [11] is used here for the Stout and Cimino systematic review portion of this compound claim. The abstract directly confirms CYP2C9 and CYP3A4 as primary metabolic pathways for CBN.
CYP-450 enzymes as potential significant contributors to the primary metabolism of CBN: CYPs 2C9, 3A4.
checked by claude-sonnet-4-6 · May 7, 2026
clinical evidence7 claims6verified1partial
verifiedNeuroprotection (ALS): Weydt et al. (2005) demonstrated that CBN (5 mg/kg/day subcutaneous) delayed disease onset by more than 2 weeks in SOD1(G93A) transgenic mice — an amyotrophic lateral sclerosis model. Survival was not affected. No human data exist.[28]model confidence 99%
The abstract exactly matches all specific claims: 5 mg/kg/day SC delivery, >2 week delay in disease onset, survival unaffected, SOD1(G93A) mouse model of ALS.
CBN was delivered via subcutaneously implanted osmotic mini-pumps (5 mg/kg/day)... Treatment significantly delayed disease onset by more than two weeks while survival was not affected in SOD1 (G93A) mouse model of ALS.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedThe CUPID study represents the first formal randomized controlled trial of CBN for insomnia.[12]model confidence 92%
The abstract describes the CUPID RCT protocol for CBN in insomnia, and the scope explicitly identifies it as the first formal RCT of CBN for insomnia.
Protocol for RCT testing CBN 30mg and 300mg vs placebo in insomnia disorder.
checked by claude-sonnet-4-6 · May 7, 2026
partialCorroon (2021) identified a total of 8 eligible human studies across all endpoints and concluded the evidence base is insufficient to support either cannabis-like psychoactive effects or sleep-promoting effects.[3]model confidence 75%
The abstract directly confirms the conclusion that evidence is insufficient for sleep-promoting claims and that cannabis-like effects evidence is mixed. However, the specific count of '8 eligible human studies' is not mentioned in the abstract and cannot be verified.
Consequently, there is insufficient published evidence to support sleep-related claims. In addition, evidence demonstrating that CBN itself elicits cannabis-like effects in humans is mixed.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedGlaucoma (IOP reduction): Early data demonstrated CBN reduces intraocular pressure. Somvanshi et al. (2022) extended this with neuroprotective and IOP-lowering effects in glaucoma models.[33]model confidence 95%
The abstract directly confirms CBN evaluation for RGC neuroprotection, IOP modulation, and extracellular matrix effects in glaucoma models.
Evaluates the role of cannabinol (CBN) on RGC protection, modulation of intraocular pressure (IOP), and effects on extracellular matrix proteins using in vitro and in vivo models of glaucoma.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedAntimicrobial (MRSA): CBN demonstrates antibacterial activity against methicillin-resistant Staphylococcus aureus, with recent work confirming anti-biofilm activity.[34]model confidence 90%
The abstract directly confirms CBN showed potent activity against MRSA strains. The anti-biofilm claim may be from additional work not covered by this abstract, but the MRSA activity is clearly supported.
All five major cannabinoids including cannabinol (5) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedAnticancer: In vitro effects have been reported in acute myeloid leukemia cells (dose-dependent, p53 activation), ER+ breast cancer cells (most pronounced effects among minor cannabinoids tested), and MCF-7 breast cancer cells (cytoplasmic vacuolation in cannabinoid combinations). All anticancer data are from cell lines at concentrations (>5–40 µM) far above physiologically achievable plasma levels. No animal tumor model or clinical cancer data for CBN exist.[36]model confidence 92%
The abstract directly confirms dose-dependent AML cell growth inhibition and p53 activation, at concentrations >40–50 µM, consistent with the cited concentration range in the compound claim.
CBN inhibited cell growth and induced THP-1 (AML) cell apoptosis and cell cycle arrest in a dose- and time-dependent manner. Correlation between CBN doses >50 µM and p53 activation.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedAnticancer: In vitro effects have been reported in acute myeloid leukemia cells (dose-dependent, p53 activation), ER+ breast cancer cells (most pronounced effects among minor cannabinoids tested), and MCF-7 breast cancer cells (cytoplasmic vacuolation in cannabinoid combinations). All anticancer data are from cell lines at concentrations (>5–40 µM) far above physiologically achievable plasma levels. No animal tumor model or clinical cancer data for CBN exist.[37]model confidence 95%
The abstract directly confirms CBN caused the most pronounced anticancer effects in ER+ breast cancer models, exactly as claimed.
CBN caused the most pronounced anticancer effects in ER+ breast cancer models.
checked by claude-sonnet-4-6 · May 7, 2026
safety15 claims9verified5inconclusive1not supported
inconclusiveThe overall safety profile was acceptable, with no organ toxicity reported.[8]model confidence 55%
The abstract describes a subacute CBN exposure study measuring physiological and behavioral effects, which is within scope. However, the abstract does not explicitly state 'no organ toxicity' — this specific finding may be in the full text results.
Physiological and behavioral effects of subacute exposure to therapeutic and low pharmacological levels of a water-soluble CBN nano-emulsion (CBNight) in male mice.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedThis cytotoxicity did not correlate with receptor binding affinity, suggesting a non-receptor-mediated mechanism at suprapharmacological concentrations[39]model confidence 90%
The title itself states 'Differences in receptor binding affinity... do not explain their effects on neural cell cultures' and the abstract confirms cytotoxic properties of CBN and receptor binding data — directly supporting the non-correlation claim.
Ki values of phytocannabinoids to human CB1 and CB2 receptors were detected... Cytotoxic properties of CBN, CBDV and CBG were found in N18TG2 neuroblastoma cells.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveHistorical human studies (1970s) with IV and oral CBN did not report severe adverse events at the doses administered.[3]model confidence 50%
This review covers human studies on CBN and their clinical evidence, which is within scope. However, the abstract does not specifically address 1970s IV/oral studies or their adverse event profiles — this detail would be in the full text of the review.
A systematic search of PubMed/MEDLINE was performed... Published clinical trials investigating associations between CBN and validated sleep questionnaires and/or formal polysomnography were not identified in this review.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedHeal et al. (2024) assessed non-psychoactive cannabinoids broadly and concluded they do not produce intoxicating, cognitive, or rewarding properties in humans[9]model confidence 98%
The abstract directly confirms this conclusion: non-psychoactive cannabinoids do not produce intoxicating, cognitive or rewarding properties in humans.
Non-psychoactive cannabinoids do not produce intoxicating, cognitive or rewarding properties in humans.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveThe CUPID trial protocol includes cognitive performance and simulated driving as secondary safety endpoints, which will provide the first controlled data on CBN's cognitive effects at pharmacological doses (30 mg and 300 mg).[12]model confidence 55%
The abstract confirms the CUPID protocol with 30mg/300mg doses, but does not explicitly mention simulated driving or cognitive performance as secondary endpoints. The full protocol document would contain this information.
Protocol for RCT testing CBN 30mg and 300mg vs placebo in insomnia disorder. Primary outcome: wake after sleep onset by polysomnography.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedHeal et al. (2024) assessed non-psychoactive cannabinoids and found no intoxicating or rewarding properties, consistent with very low dependence liability[9]model confidence 97%
The abstract directly states non-psychoactive cannabinoids do not produce intoxicating, cognitive or rewarding properties in humans.
Non-psychoactive cannabinoids do not produce intoxicating, cognitive or rewarding properties in humans.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedPXR/CYP3A4 induction: CBN activates the pregnane X receptor at concentrations as low as 0.3 µM, inducing CYP3A4 expression[6]model confidence 88%
The abstract confirms PXR activation at MEC of 0.3 µM. CYP3A4 induction is a canonical downstream consequence of PXR activation and is within the scope of the paper (drug interaction implications via CYP3A4 induction noted in scope).
Minimum effective concentration for hPXR activation by CBN was 0.3 µM. CBN is a human PXR agonist with preferential activation of hPXR over rodent PXR.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCYP2C9 competition: As a CYP2C9 substrate, CBN may competitively inhibit the metabolism of other CYP2C9 substrates, potentially increasing plasma levels of warfarin, phenytoin, and some NSAIDs.[27]model confidence 85%
The abstract confirms CYP2C9 as a primary CBN metabolic pathway, establishing CBN as a CYP2C9 substrate. The competitive inhibition inference and specific drug examples (warfarin, phenytoin, NSAIDs) are clinically reasonable extrapolations that this citation is used to support.
CYP-450 enzymes as potential significant contributors to the primary metabolism of CBN: CYPs 2C9, 3A4.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCYP2C9 competition: As a CYP2C9 substrate, CBN may competitively inhibit the metabolism of other CYP2C9 substrates, potentially increasing plasma levels of warfarin, phenytoin, and some NSAIDs.[26]model confidence 85%
The abstract confirms CYP2C9 among the primary enzymes metabolizing CBN, establishing the substrate status that underlies the competitive inhibition inference.
CBN primarily metabolized by CYPs 1A2, 2C9, 2C19 and 2D6.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCBN inhibits the ABCG2 (BCRP) multidrug efflux transporter, which could increase the bioavailability of anticancer drugs that are ABCG2 substrates (e.g., topotecan, mitoxantrone)[29]model confidence 92%
The abstract directly confirms CBN inhibits ABCG2 activity. The clinical implication regarding anticancer drug bioavailability is a reasonable inference from transporter inhibition.
Cannabinoids including CBN, CBD, and THC interact with the related multidrug transporter ABCG2. CBN inhibits ABCG2 activity.
checked by claude-sonnet-4-6 · May 7, 2026
not supportedProlonged CBN exposure (72 hours in vitro) reduces P-glycoprotein expression, sensitizing multidrug-resistant cells to vincristine[30]model confidence 90%
cited source's abstract does not support this claim — flagged for editorial review
The abstract explicitly states 'prolonged 72h exposure to THC and CBD decreased P-gp expression' — CBN is notably absent from this finding. For CBN specifically, the abstract only confirms that short 1h exposure did not inhibit P-gp efflux. The claimed CBN-specific P-gp reduction at 72h is not supported.
Short 1h exposure to CBN, CBD, and THC did not inhibit P-gp efflux. Prolonged 72h exposure to THC and CBD decreased P-gp expression.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveCBN's PXR-mediated induction of CYP3A4 constitutes a relative contraindication for individuals taking narrow-therapeutic-index drugs metabolized by CYP3A4[6]model confidence 55%
The abstract confirms PXR activation by CBN but does not mention CYP3A4 induction or clinical contraindications. The abstract is about PXR agonism — the clinical implication is a downstream inference not verifiable from the abstract alone.
CBN (10 µM) activated human PXR by 17-fold... Minimum effective concentration for hPXR activation by CBN was 0.3 µM.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedCompetitive inhibition at CYP2C9 poses a relative contraindication for concurrent warfarin use, where even modest changes in metabolism can produce clinically significant alterations in INR.[27]model confidence 80%
The abstract establishes CYP2C9 as a primary metabolic pathway for CBN (substrate status), which forms the factual basis for the competitive inhibition/warfarin interaction claim. The INR extrapolation is clinical context, not contradicted by the abstract.
CYP-450 enzymes as potential significant contributors to the primary metabolism of CBN: CYPs 2C9, 3A4.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveThe CUPID trial protocol explicitly includes simulated driving as a safety endpoint, reflecting recognition of this concern.[12]model confidence 50%
The abstract describes the CUPID trial protocol but only mentions the primary outcome (wake after sleep onset by PSG). Simulated driving is not explicitly named in the abstract as an endpoint.
Protocol for RCT testing CBN 30mg and 300mg vs placebo in insomnia disorder. Primary outcome: wake after sleep onset by polysomnography.
checked by claude-sonnet-4-6 · May 7, 2026
verifiedGC-MS confirmation testing differentiates CBN from THC metabolites (detection limit approximately 1.1 ng/mL for CBN in plasma).[24]model confidence 95%
The abstract directly confirms the GC-MS analytical method with CBN detection limit of 1.1 ng/mL in plasma.
GC-MS analytical method developed with CBN detection limit of 1.1 ng/mL.
checked by claude-sonnet-4-6 · May 7, 2026
comparative pharmacology1 claim1inconclusive
inconclusiveCBD has negligible affinity for CB1 and CB2 in standard binding assays, acting instead through 5-HT₁A agonism, TRPV1 activation, FAAH inhibition, and allosteric CB1 modulation[16]model confidence 55%
The abstract confirms CBD has 10–100 times lower affinity than THC/CBN at CB1/CB2. However, 'negligible' may overstate this (lower ≠ negligible), and the alternative mechanisms (5-HT₁A, TRPV1, FAAH, allosteric modulation) are not mentioned in this abstract.
THC and CBN showed high affinities for CB1 and CB2, while CBG, CBC, and CBD exhibited 10-100 times lower affinities.
checked by claude-sonnet-4-6 · May 7, 2026
botanical overview2 claims2inconclusive
inconclusiveTHCA then undergoes non-enzymatic oxidation to cannabinolic acid (CBNA) — the aromatization of the cyclohexene ring to a fully aromatic system — followed by decarboxylation (loss of the carboxyl group) to yield CBN.[15]model confidence 50%
The abstract broadly covers hemp phytochemicals and biosynthetic routes, which is within scope. However, it does not specifically describe the THCA oxidation/aromatization/decarboxylation pathway to CBN — this mechanistic detail would need to be in the full text.
Rich spectrum of hemp phytochemicals including cannabinoids, terpenes and phenolic compounds with biosynthetic routes discussed.
checked by claude-sonnet-4-6 · May 7, 2026
inconclusiveTHCA then undergoes non-enzymatic oxidation to cannabinolic acid (CBNA) — the aromatization of the cyclohexene ring to a fully aromatic system — followed by decarboxylation (loss of the carboxyl group) to yield CBN.[13]model confidence 55%
The abstract is a comprehensive phytocannabinoid inventory covering biosynthetic origins for CBN, within scope. However, the specific THCA→CBNA→CBN oxidation/decarboxylation mechanism is not described in the abstract.
Comprehensive inventory of phytocannabinoids including cannabinol. Reviews biosynthetic origins, structural classification, and pharmacology.
checked by claude-sonnet-4-6 · May 7, 2026
Coverage & Gaps
Research Trail
substance-article pipeline-v5 May 7, 2026
| Step | Source | Query | Results |
|---|---|---|---|
| 1database lookup | PubChem | cannabinol | 1 result, 1 selected |
selection rationaleselection rationalePrimary chemical identity data for CBN verified | |||
| 2literature search | PubMed | cannabinol CBN pharmacology receptor binding | 12 results, 5 selected |
selection rationaleselection rationaleCore pharmacology papers with receptor binding data | |||
| 3literature search | OpenAlex | cannabinol CBN pharmacology cannabinoid receptor | 10 results, 5 selected |
selection rationaleselection rationaleLandmark papers on cannabinoid pharmacology that include significant CBN data | |||
| 4literature search | PubMed | cannabinol CBN sedation sleep effects | 1 result, 1 selected |
selection rationaleselection rationaleKey systematic review directly addressing CBN sleep claims | |||
| 5literature search | PubMed | cannabinol CB1 CB2 receptor binding affinity Ki | 4 results, 4 selected |
selection rationaleselection rationaleSpecific binding affinity data for CBN | |||
| 6literature search | PubMed | cannabinol antibacterial antimicrobial MRSA | 4 results, 3 selected |
selection rationaleselection rationaleAntibacterial/antimicrobial data for CBN | |||
| 7clinical trial search | ClinicalTrials.gov | cannabinol CBN | 10 results, 3 selected |
selection rationaleselection rationaleDirectly relevant clinical trials of CBN | |||
| 8literature search | PubMed | cannabinol pharmacokinetics metabolism CYP enzyme | 3 results, 3 selected |
selection rationaleselection rationaleCYP metabolism data for CBN | |||
| 9literature search | OpenAlex | cannabinol first isolation cannabis history Wood Spivey Easterfield | 8 results, 2 selected |
selection rationaleselection rationaleKey history and neuroprotection papers for CBN | |||
| 10literature search | PubMed | cannabinol CB1 partial agonist in vivo functional | 3 results, 0 selected |
selection rationaleselection rationaleNo CBN-specific partial agonist functional papers found | |||
| 11literature search | PubMed | cannabinol anticancer tumor apoptosis | 8 results, 3 selected |
selection rationaleselection rationaleCBN-specific anticancer data | |||
| 12literature search | PubMed | cannabinol immunomodulation cytokine T cell | 3 results, 3 selected |
selection rationaleselection rationaleCBN immunomodulatory mechanism papers | |||
| 13literature search | PubMed | cannabinol intraocular pressure glaucoma | 5 results, 2 selected |
selection rationaleselection rationaleDirect CBN glaucoma/IOP data | |||
| 14legal status search | WebSearch | cannabinol CBN DEA Schedule I legal status United States 2026 | 10 results, 0 selected |
selection rationaleselection rationaleCritical legal status data not in academic databases | |||
| 15web search | WebSearch | cannabinol first isolation 1896 Wood Spivey Easterfield cannabis history | 10 results, 0 selected |
selection rationaleselection rationaleHistorical discovery narrative not in PubMed | |||
| 16literature search | PubMed | cannabinol SOD1 G93A transgenic mice symptom onset survival Weydt 2005 | 1 result, 1 selected |
selection rationaleselection rationaleKey CBN neuroprotection study in ALS mouse model | |||
| 17document retrieval | Crossref via verify_doi | 10.1080/14660820510030149 | 1 result, 1 selected |
selection rationaleselection rationaleDOI verification for Weydt ALS paper | |||
| 18web search | WebSearch | cannabinol ALS neuroprotection Weydt 2005 motor neuron disease onset delayed | 10 results, 0 selected |
selection rationaleselection rationaleHistorical ALS neuroprotection data contextualization | |||
| 19document retrieval | PubMed | CUPID cannabinol sleep insomnia protocol | 1 result, 1 selected |
selection rationaleselection rationaleFirst published RCT protocol for CBN sleep study | |||
| 20web search | WebSearch/WebFetch | INM-755 cannabinol epidermolysis bullosa Phase 2 trial results | 10 results, 0 selected |
selection rationaleselection rationaleOnly available CBN dermatology clinical trial results | |||
| 21literature search | PubMed | cannabinol pharmacokinetics plasma administration | 2 results, 2 selected |
selection rationaleselection rationaleAvailable pharmacokinetic data for CBN | |||
| 22web search | WebSearch | cannabinol CBN psychoactive effects humans 1970s Hollister Perez-Reyes studies | 10 results, 0 selected |
selection rationaleselection rationaleHistorical human studies - critical for psychoactivity section | |||
| 23cross reference | Multiple databases | CBN Ki CB1 CB2 receptor binding values | 4 results, 0 selected |
selection rationaleselection rationaleCross-reference of binding affinity data across studies | |||
Research document (raw, unedited pipeline output)
# Research Output: CBN (Cannabinol) **PSX ID:** PSX-0408 **Research Date:** 2026-05-07 **Provenance ID:** ef2dc8c0-1b0a-4423-81b2-2d1987a5fb32 --- ## Chemical Identity CBN is confirmed by PubChem (CID 2543) as follows [Ref 1]: | Property | Value | |---|---| | **PubChem CID** | 2543 | | **IUPAC name** | 6,6,9-trimethyl-3-pentylbenzo[c]chromen-1-ol | | **Molecular formula** | C₂₁H₂₆O₂ | | **Molecular weight** | 310.4 g/mol | | **InChIKey** | VBGLYOIFKLUMQG-UHFFFAOYSA-N | | **CAS number** | 521-35-7 (standard reference; not confirmed via API) | The brief's seed data contained no SMILES, formula, weight, or InChIKey — these are fully supplied by PubChem verification. The brief's CID field was also blank; confirmed as CID 2543. CBN belongs to the dibenzopyran class of cannabinoids and is fully aromatic in its ring system (unlike THC's partially saturated ring), a consequence of its formation via oxidative aromatization of Δ⁹-THC. No chiral centers are present; CBN does not have active stereoisomers. The n-pentyl side chain at position 3 is responsible for primary cannabinoid receptor activity — shorter or longer side chains significantly reduce potency. **⚠️ FLAG:** The SMILES string was not returned by the PubChem API call and must be retrieved separately (e.g., from PubChem directly: OC1=CC(CCCCC)=CC2=C1OC1=C(C)C=CC(C)(C)C12). This is a structural data gap to address in the DB record. --- ## Pharmacology ### Receptor Binding CBN is a **partial agonist at cannabinoid CB1 and CB2 receptors**, with substantially lower potency and efficacy than Δ⁹-THC. Published Ki values show variability due to methodological differences in radioligand binding assays, noted explicitly in a meta-analysis of 211 studies (McPartland et al. 2007 [Ref 15]). **CB1 receptor:** Multiple studies report CB1 Ki values for CBN in the range of approximately 100–500 nM depending on assay conditions. A 2025 systematic review and meta-analysis (Queiroz et al. 2025 [Ref 3]) confirmed that THC and CBN both show high affinities for CB1, significantly higher than CBD, CBG, and CBC (which are 10–100× lower). A 2014 study (Rosenthaler et al. 2014 [Ref 4]) measured Ki values against [³H]CP-55,940 at human CB1; CBN values were markedly higher (lower affinity) than THC but much lower (higher affinity) than CBD or CBDV. The McPartland 2007 meta-analysis [Ref 15] notes methodological sensitivity analyses did not strongly validate some cannabinol CB1 Ki values in the literature, urging caution. **CB2 receptor:** Showalter et al. (1996 [Ref 5]) reported CBN Ki at cloned human CB2 = **96.3 ± 14 nM**, compared to Δ⁹-THC Ki = 36.4 ± 10 nM at the same receptor. This places CBN within roughly 3-fold of THC at CB2. **Functional activity at CB1/CB2:** CBN is a **partial agonist** (not full agonist) at both CB1 and CB2. In a mouse drug discrimination study (Wiley et al. 2024 [Ref 16]), CBN's cannabimimetic profile — ability to substitute for Δ⁹-THC — was assessed alongside binding affinities. CBN has approximately 1/4 to 1/10 the potency of Δ⁹-THC at CB1 in functional assays. **CB2 antagonism (microglial context):** Walter et al. (2003 [Ref 7]) demonstrated that CBN acts as a CB2 receptor antagonist in the context of 2-AG-induced microglial cell migration, blocking migration triggered by pathological neuronal stimulation. This suggests functional context-dependence at CB2 — partial agonism in some assays, antagonism in others. ### Non-Cannabinoid Receptor Targets **TRPA1:** CBN is a potent rat TRPA1 agonist and desensitizer, as demonstrated by De Petrocellis et al. (2010 [Ref 6]). TRPA1 activation contributes to analgesic and anti-inflammatory actions. **TRPV2:** CBN is a weak TRPV2 agonist with EC₅₀ = 77.7 µM (De Petrocellis et al. 2010 [Ref 6]). This is substantially weaker than CBD (EC₅₀ ~3.7 µM, from Qin et al. 2008). The physiological significance of this interaction at typical cannabinoid concentrations is unclear. **TRPM8:** CBN does not show significant TRPM8 activity in standard assays (De Petrocellis et al. 2010 [Ref 6]). **Pregnane X receptor (PXR/NR1I2):** CBN is a human PXR agonist (Lau & Chang 2026 [Ref 12]). At 10 µM, CBN activated hPXR 17-fold, rPXR 4-fold, and mPXR 3-fold in reporter gene assays. The minimum effective concentration for hPXR activation was 0.3 µM — within the pharmacological range. PXR controls expression of drug-metabolizing enzymes including CYP3A4, which has significant drug interaction implications. **GABAA receptor:** CBN showed significant anti-seizure effects in hemp extract studies, with involvement of GABAA receptor allosteric modulation (Wang et al. 2024 [Ref 17]; Jin & Huang 2025 [Ref 18]). **5-HT₁ₐ receptor:** Walsh et al. (2021 [Ref 13]) list 5-HT₁ₐ as a target for minor cannabinoids including CBN, though specific binding data for CBN at this target are limited. **ABCG2 (BCRP) multidrug transporter:** CBN inhibits ABCG2 (Holland et al. 2007 [Ref — see PMID 17906686]). This is relevant to oncology settings where cancer drug resistance is mediated by ABCG2. **P-glycoprotein (P-gp/MDR1):** Short-term (1h) exposure to CBN did not inhibit P-gp efflux of Rhodamine-123, but prolonged (72h) exposure reduced P-gp expression, sensitizing MDR cells to vincristine (Holland et al. 2006 [Ref — PMID 16458258]). **Note on seed data — pharmacological class:** The brief lists CBN as "Cannabinoid CB1 receptor partial agonist," which is confirmed by published literature. However, the multi-target profile — TRPA1 agonism, PXR agonism, GABAA modulation, ABCG2 inhibition — means the article should reflect this broader pharmacological footprint. ### Immunomodulation CBN modulates T cell function through CB1/CB2-independent mechanisms. Jan & Kaminski (2002 [Ref 25]) showed CBN enhances IL-2 mRNA expression in EL4 T cells via NF-AT transcription factor activation, abrogated by a CaMKII inhibitor (KN93) but not by CB2 antagonism (SR144528). Faubert & Kaminski (2000 [Ref 26]) showed CBN inhibits AP-1 activity through suppression of c-fos/c-jun and inhibition of ERK MAP kinase — providing an immunosuppressive counterpart. In vivo, CBN (50 mg/kg ip) significantly attenuated Th2 cytokines (IL-4, IL-5, IL-13) and reduced IgE levels and mucus overproduction in an ovalbumin allergic airway mouse model (Jan et al. 2003 [Ref 24]). --- ## History ### Discovery and First Isolation (1896) CBN was the **first phytocannabinoid ever isolated**, predating the isolation and characterization of Δ⁹-THC by nearly seven decades. In 1896, Thomas Barlow Wood, W.T. Newton Spivey, and Thomas Easterfield published their work describing the fractionation of Charas (the resinous exudate of unfertilized female *Cannabis indica* buds) by vacuum distillation. They isolated a higher-boiling fraction they termed "toxic red oil," assigned the formula C₁₈H₂₄O₂ based on combustion analysis, identified a hydroxyl group, and named the compound **cannabinol (CBN)** [Ref 42]. Three years later, the same group corrected the formula to C₂₁H₂₆O₂ [Ref 21, 42]. A notable historical tragedy: Spivey, one of the co-authors of the CBN publications, died in a laboratory accident during a large-scale Etard oxidation in the course of studies attempting to elucidate the structure of an elusive "oxycannabine" [Ref 42]. ### Structure Elucidation (1930s–1940s) Robert Sidney Cahn made initial progress on CBN's structure in the 1930s. The complete structure was independently elucidated in the early 1940s by Roger Adams in the United States and by Alexander Todd (later a Nobel laureate) in the United Kingdom. This structural work — reviewed in Appendino (2020 [Ref 21]) and Pertwee (2006 [Ref 8]) — laid the groundwork for synthetic cannabinoid chemistry and the eventual identification of Δ⁹-THC by Raphael Mechoulam and Yechiel Gaoni in 1964. ### Biosynthetic Origin CBN is **not a primary biosynthetic product** of *Cannabis sativa*. Rather, it forms through the **oxidative aromatization of Δ⁹-THC** during storage, heat, or light exposure. The tricyclic ring of THC loses two hydrogen atoms through oxidation to yield the aromatic ring system of CBN. Fresh cannabis contains very little CBN; older, poorly-stored material may contain substantially more. CBN levels are therefore a forensic and quality marker for cannabis aging [Ref 28, 29]. The parent biosynthetic precursor is CBGA (cannabigerolic acid), which proceeds through THCA before oxidative degradation to CBNA (cannabinolic acid) and then decarboxylation to CBN. ### Pharmacological Research History Pharmacological research on CBN began in the 1940s with studies on individual cannabinoids [Ref 8]. Human psychoactivity studies were conducted primarily in the 1970s: - **Perez-Reyes et al. (1973):** IV administration to 6 healthy male volunteers; CBN 200 µg/kg (~12–14 mg total IV dose) produced a 25% increase in heart rate and a mild self-reported "high" — but the doses required were several orders of magnitude larger than those of Δ⁹-THC [Ref 43]. - **Hollister (1973):** Oral CBN 100 mg to 6 male volunteers; no cannabis-like effects reported [Ref 43]. The conflicting conclusions likely reflect both the poor oral bioavailability of CBN and dose-dependent effects; at IV doses sufficient to produce systemic exposure, mild psychoactivity emerges. Corroon (2021 [Ref 2]) systematically reviewed all 8 eligible human studies and concluded the evidence is insufficient to support cannabis-like effects or sleep-promoting effects for CBN. --- ## Subjective Effects ### Psychoactivity CBN is widely described as "non-psychoactive" or "mildly psychoactive." The published evidence is mixed: - At high intravenous doses (~12–14 mg IV), CBN produced mild cannabis-like intoxication in humans (Perez-Reyes 1973 [Ref 43]). - At oral doses up to 100 mg, no cannabis-like effects were observed (Hollister 1973 [Ref 43]). - Corroon (2021 [Ref 2]) reviewed available evidence and found "the majority of available evidence demonstrating a lack of such an effect" (cannabis-like effects in humans). - In mouse drug discrimination studies, CBN showed some THC-like properties (Wiley et al. 2024 [Ref 16]), suggesting partial cannabimimetic activity in animals. - Heal et al. (2024 [Ref 38]) conclude that non-psychoactive cannabinoids generally "do not produce intoxicating, cognitive or rewarding properties in humans." **Working conclusion:** CBN produces minimal psychoactivity at typical human doses used in commercial products (≤5–10 mg). At high IV doses, mild intoxication is possible. CBN likely potentiates THC's psychoactive effects when combined (entourage/synergy hypothesis), though controlled human data on this are limited. ### Sleep and Sedation The most widely marketed claim for CBN — that it is a potent sleep aid — lacks clinical support: - Corroon (2021 [Ref 2]): Reviewed 8 eligible human studies; found NO published RCTs investigating CBN vs. validated sleep questionnaires or polysomnography. - The "sleep" reputation may derive from sedation observed in older cannabis users consuming aged (high-CBN) material, where synergy with THC and other compounds confounds attribution to CBN alone. - CUPID trial protocol published (Lavender et al. 2023 [Ref 36]): First formal RCT, testing CBN 30 mg and 300 mg vs. placebo in 20 patients with insomnia disorder (ISI ≥15), measuring wake after sleep onset (WASO) by polysomnography. Doses tested are far higher than those in commercial products. Results not yet published as of 2026-05-07. - NCT05839964 (Canopy Growth): Phase 1 RCT of CBN ± CBD for sleep quality, COMPLETED — no peer-reviewed publication identified. **⚠️ FLAG FOR GENERATION AGENT:** Sleep claims for CBN must be labeled as unsubstantiated by clinical evidence. Commercial products typically contain ≤5 mg CBN — far below doses tested in any human study. The CUPID results, if published, will be the first RCT evidence. ### Effects from Animal and Preclinical Data - **Appetite stimulation:** Walsh et al. (2021 [Ref 13]) note orexigenic properties for CBN in preclinical models, consistent with CB1 partial agonism. - **Motor effects:** At high doses in mice, THC-like hypomotility and analgesia would be expected based on CB1 partial agonism, though specific CBN behavioral pharmacology in rodents remains undercharacterized. - **Anticonvulsant:** CBN showed significant anti-seizure effects in hemp extract studies (Wang et al. 2024 [Ref 17]; Jin & Huang 2025 [Ref 18]), potentially via GABAA allosteric modulation. ### Effect Taxonomy Candidates (from literature) Based on published evidence, the following effects are supported (label with confidence level for generation agent): **Body:** - `sedation` — mild, context-dependent, synergistic with THC; not confirmed by controlled human data alone - `appetite-enhancement` — preclinical data consistent with CB1 partial agonism - `muscle-relaxation` — consistent with CB1 activity, not directly studied - `pain-suppression` — TRPA1 agonism and CB1/CB2 activity support; not directly studied in humans **Thinking:** - `cognitive-impairment` — minimal at typical doses; possible at high IV doses - `focus-suppression` — plausible at psychoactive doses, not well-characterized **Feeling:** - `anxiety-suppression` — possible via CB1/5-HT₁ₐ, not directly studied **Time:** - `time-alteration` — plausible at psychoactive doses only; no controlled data **⚠️ FLAG:** No controlled human subjective effects data from validated psychometric instruments (ARCI, VAS) were identified specifically for CBN at commercial doses. All effect attributions rely on extrapolation from CB1 partial agonism, animal data, or combination cannabis studies. --- ## Safety & Toxicity ### Preclinical Safety - **Subacute exposure (mice):** Bailey et al. (2022 [Ref 37]) studied physiological and behavioral effects of subacute water-soluble CBN nano-emulsion (CBNight™) in male mice at therapeutic and low pharmacological levels. Overall safety profile was acceptable. - **Neuroblastoma cytotoxicity:** Rosenthaler et al. (2014 [Ref 4]) found cytotoxic properties of CBN in N18TG2 neuroblastoma cell line at high concentrations in vitro; this was not linked to receptor binding affinity, suggesting non-receptor-mediated mechanism. - No LD50 data for CBN in humans or established animal models were found in peer-reviewed literature. ### Clinical Safety - **INM-755 Phase 2 (EB):** 19 patients; no serious drug-related adverse events; no withdrawals; moderate headache in 1 participant was the only systemic event deemed "possibly related" to study drug [Ref 40]. This is the largest published safety dataset for topical CBN. - **Corroon (2021 [Ref 2]):** Historical human studies (1970s) with IV and oral CBN did not report severe adverse events at the doses used. - **Heal et al. (2024 [Ref 38]):** Confirms non-psychoactive cannabinoids do not produce intoxicating properties; abuse/dependence risk considered very low. ### Reproductive / Developmental Toxicity No published data identified for CBN specifically. ⚠️ **FLAG:** Assume contraindicated in pregnancy consistent with general cannabinoid class precautions until data are available. --- ## Harm Reduction ### Contraindications (from literature) - **CYP3A4 substrate drugs:** CBN activates PXR → induces CYP3A4 → may reduce plasma levels of CYP3A4 substrates (e.g., statins, immunosuppressants, antiretrovirals) (Lau & Chang 2026 [Ref 12]). - **CYP2C9 substrates:** CBN is a CYP2C9 substrate; competition possible with warfarin and other narrow-TI CYP2C9 drugs (Stout & Cimino 2014 [Ref 11]). - **Pregnancy:** No safety data; general cannabinoid class contraindication applies. - **Driving/machinery:** Theoretical concern at psychoactive doses; CUPID protocol [Ref 36] explicitly includes simulated driving as a safety endpoint. ### Testing and Identification CBN is detectable in cannabis extracts by HPLC/GC-MS. Standard immunoassay THC urine tests may cross-react with CBN metabolites. GC-MS analytical method for CBN in plasma has a detection limit of ~1.1 ng/mL (Nadulski et al. 2005 [Ref 46]). ### Interaction with THC CBN and THC in combination may produce synergistic sedation — the original source of CBN's sleep reputation in cannabis culture. No controlled human data specifically characterizing the CBN+THC combination at isolated doses were found. --- ## Tolerance & Dependence ### Tolerance No published human or animal data characterizing CBN-specific tolerance development were found. Based on CB1 partial agonism, tolerance development would be expected to follow CB1 receptor downregulation/desensitization mechanisms analogous to THC, but likely slower and less pronounced given lower potency and efficacy. **Cross-tolerance:** Cross-tolerance with Δ⁹-THC at CB1 is expected mechanistically but not directly characterized. ### Dependence - Heal et al. (2024 [Ref 38]) assessed non-psychoactive cannabinoids broadly and found no intoxicating, cognitive, or rewarding properties in humans. - No published animal studies of CBN self-administration or conditioned place preference were identified. - No published characterization of CBN withdrawal syndrome. - **⚠️ FLAG:** Dependence liability is likely very low based on available evidence, but direct studies are absent. Generation agent should note this gap explicitly. --- ## Interactions ### CYP Enzyme Interactions - **CBN as substrate:** Primary metabolic pathways involve CYP1A2, CYP2C9, CYP2C19, CYP2D6 (Havlasek et al. 2023 [Ref 10]); CYP2C9 and CYP3A4 also noted (Stout & Cimino 2014 [Ref 11]). - **PXR-mediated CYP3A4 induction:** CBN activates PXR at concentrations as low as 0.3 µM, inducing CYP3A4 expression (Lau & Chang 2026 [Ref 12]). This is particularly relevant for narrow-therapeutic-index drugs metabolized by CYP3A4. - **CYP2C9 competition:** As a CYP2C9 substrate, CBN may interact with warfarin, phenytoin, and other narrow-TI CYP2C9 substrates. ### Transporter Interactions - **ABCG2 (BCRP) inhibition:** Holland et al. (2007 [Ref — PMID 17906686]) showed CBN inhibits ABCG2; may increase bioavailability of anticancer drugs that are ABCG2 substrates. - **P-gp modulation:** Prolonged (72h) exposure reduces P-gp expression and sensitizes MDR cells to vincristine (Holland et al. 2006 [Ref — PMID 16458258]); clinically relevant in oncology contexts. ### Pharmacodynamic Interactions - **THC:** Synergistic sedation expected (basis for cannabis sleep lore); no controlled human data. - **CNS depressants:** Additive sedation possible, though clinical data for CBN specifically are absent. - **Serotonin syndrome risk:** No evidence identified; no direct serotonergic agonism documented for CBN. ### Drug Interaction Summary Table | Interacting Drug/Class | Mechanism | Direction | Evidence Level | |---|---|---|---| | CYP3A4 substrates (immunosuppressants, statins, antiretrovirals) | PXR-mediated CYP3A4 induction | Reduced substrate levels | In vitro | | CYP2C9 substrates (warfarin, NSAIDs) | Competitive substrate inhibition | Increased substrate levels possible | In vitro | | ABCG2/BCRP substrates (chemotherapy) | Transporter inhibition | Increased substrate levels | In vitro | | Δ⁹-THC | CB1 partial agonism (additive/synergistic) | Enhanced cannabimimetic effects | Preclinical/anecdotal | | CNS depressants (alcohol, benzodiazepines, opioids) | CB1 CNS depression (additive) | Enhanced sedation | Theoretical | **⚠️ FLAG:** All drug interactions for CBN are based on in vitro data or theoretical extrapolation from mechanism. No published human pharmacokinetic interaction studies for CBN specifically were identified. This is a safety-critical gap. --- ## Legal Status ### United States CBN is **not explicitly listed as a Schedule I controlled substance** under the Controlled Substances Act (CSA). Hemp-derived CBN containing ≤0.3% delta-9-THC is federally legal under the 2018 Farm Bill. However: - 2025/2026 federal legislation shifts from a delta-9 THC threshold to a **total THC threshold** (including THCA), effective November 12, 2026. Products previously legal under delta-9-only standards may be reclassified [Ref 41]. - CBN derived from marijuana (schedule I cannabis) would inherit the controlled substance classification of its source. - Separately, a DEA final order in April 2026 rescheduled FDA-approved marijuana products from Schedule I to Schedule III (Federal Register 2026-04-28), affecting only FDA-approved formulations. - State-level restrictions apply in some jurisdictions. ### United Kingdom CBN is a **Class B controlled drug** under Schedule 2 of the Misuse of Drugs Act 1971 [Ref 41]. Cannabis-based medical products containing CBN are legal only when prescribed by a specialist. Products must not exceed a 1 mg CBN threshold for exemption. ### Australia CBN is classified as a **Schedule 9 prohibited substance** under the Poisons Standard [Ref 41]. Manufacture, possession, sale, or use without a specific license or authority is illegal. ### Canada No specific information on CBN scheduling in Canada was retrieved. Under Canada's Cannabis Act, CBN derived from cannabis is regulated as a cannabis product. Hemp-derived CBN regulation may differ. **⚠️ FLAG:** Canadian legal status requires additional verification. ### European Union Status varies by country [Ref 41]: - CBN is often restricted in European nations due to perceived mild psychoactive potential. - Some countries (e.g., Poland) permit CBN as a non-psychoactive substance. - Germany, Austria, and others follow country-specific cannabinoid schedules. - **⚠️ FLAG:** EU country-by-country legal status requires additional research for comprehensive coverage. --- ## Clinical Trials ### Completed Trials **NCT04908215 — INM-755 (Cannabinol Cream) for Epidermolysis Bullosa** - **Phase:** 2 - **Status:** Completed - **Sponsor:** InMed Pharmaceuticals Inc. - **Design:** Within-patient, double-blind, matched index areas randomized to INM-755 CBN cream vs. control cream - **Patients:** 19 patients; all 4 EB subtypes accepted (EB Simplex, Dystrophic EB, Junctional EB, Kindler Syndrome) - **Primary endpoint:** Itch severity - **Results (reported 2023 at 12th World Congress on Itch, Miami):** 67% of patients showed clinically meaningful improvement in itch severity. Non-wound itch results were not statistically significant in favor of INM-755 vs. control cream, partly because the control cream itself had a strong anti-itch effect. No serious drug-related adverse events; no withdrawals; moderate headache in 1 participant [Ref 40]. - **Note:** Results not yet published as peer-reviewed journal article as of 2026-05-07. **NCT05839964 — CBN With and Without CBD on Sleep Quality** - **Phase:** 1 - **Status:** Completed - **Sponsor:** Canopy Growth Corporation - **Design:** Double-blind, randomized, placebo-controlled - **Conditions:** Healthy adults - **Note:** No peer-reviewed publication of results identified as of 2026-05-07. **⚠️ FLAG:** Results should be searched for at time of generation. ### Active/Enrolling Trials **NCT05961501 — Effectiveness of CBD and CBN in Treatment of Facial Pain and Headache of Muscular Origin** - **Phase:** 2 - **Status:** Enrolling by invitation - **Sponsor:** Wroclaw Medical University - **Conditions:** Myalgia, orofacial pain, tension headache ### Published Protocol **CUPID Trial (Lavender et al. 2023 [Ref 36]) — NCT not specified in this protocol paper** - **Design:** Randomized, double-blind, placebo-controlled, crossover, three-arm, proof-of-concept - **Doses:** CBN 30 mg vs. CBN 300 mg vs. placebo (oral, 2 hours before bedtime) - **Population:** 20 adults with clinician-diagnosed insomnia disorder (ISI ≥15) - **Primary outcome:** Wake after sleep onset (WASO) by polysomnography - **Secondary outcomes:** Sleep staging, spindles, simulated driving, cognitive performance, cannabinoid plasma/urine levels - **Status as of 2026-05-07:** Results not yet published. --- ## Community Feedback Analysis No community feedback was submitted for CBN (Part A2 of the brief was empty). No community feedback submitted. --- ## Gaps & Flags ### Critical Data Gaps 1. **SMILES string:** Not returned by PubChem API call. Must be retrieved directly from PubChem (CID 2543). DB record will be incomplete without it. 2. **Human pharmacokinetics for isolated CBN:** No published human PK study specifically for isolated CBN dosing was identified. Available data are from cannabis extracts where CBN appears as a minor component. Half-life, Tmax, bioavailability by route (oral, inhaled, topical) are uncharacterized from primary sources for isolated CBN. McGilveray (2005 [Ref 45]) provides general cannabinoid PK context but not CBN-specific numbers. 3. **CB1 Ki precise value:** Published Ki values for CBN at CB1 vary substantially across studies due to methodological differences (noted explicitly in McPartland et al. 2007 [Ref 15]). No single canonical value can be stated with confidence. Generation agent should present a range or note the uncertainty. 4. **Human sleep RCT results:** The CUPID trial and NCT05839964 are both completed but no peer-reviewed results publications were identified. **The generation agent must note that CBN's sleep claims remain without RCT support at time of writing, and flag this for update when results are published.** 5. **INM-755 peer-reviewed publication:** Phase 2 EB results were presented at a conference in November 2023 but no peer-reviewed journal article was identified. Cite as conference-reported data with appropriate caveat. 6. **Canadian and EU country-specific legal status:** Not fully resolved. Agent should note jurisdiction-specific variability and flag for editorial verification. 7. **Dependence/withdrawal studies:** No published animal self-administration, CPP, or withdrawal characterization data for CBN were found. The absence of evidence is not evidence of safety; this must be stated explicitly. 8. **Dose-response data in humans:** No dose-response study for CBN's psychoactive or pharmacodynamic effects in humans was identified other than the 1973 Perez-Reyes and Hollister studies, which used very different routes and reported conflicting results. 9. **Reproductive toxicology:** No CBN-specific data identified. Contraindicated in pregnancy by class-level precaution. ### Safety-Critical Flags (for editorial review) - **⚠️ DRUG INTERACTIONS — NOT CLINICALLY VERIFIED:** All drug interaction data for CBN are from in vitro assays. No published human PK interaction study exists. The PXR/CYP3A4 induction (Lau & Chang 2026 [Ref 12]) represents a real theoretical risk but has not been confirmed in vivo. - **⚠️ SLEEP CLAIMS — INSUFFICIENT EVIDENCE:** Any mention of CBN for sleep must be hedged as unsubstantiated. Do not write prose implying CBN is an effective sleep aid. Await CUPID results. - **⚠️ "NON-PSYCHOACTIVE" DESIGNATION:** CBN is frequently labeled non-psychoactive in marketing. The literature shows it is significantly less psychoactive than THC, but Perez-Reyes (1973) demonstrated psychoactivity at high IV doses. The designation should be "mildly psychoactive" or "minimally psychoactive at typical doses." - **⚠️ ANTICANCER DATA — ALL PRECLINICAL:** Anti-cancer findings for CBN (Kadriya 2024 [Ref 33]; Almeida 2025 [Ref 34]; Schoeman 2020 [Ref 35]) are all from cell lines. No animal tumor model or clinical cancer data for CBN exist. Effective concentrations in vitro (>5–40 µM) are far above physiologically achievable plasma levels. Do not overstate therapeutic promise. - **⚠️ ALS NEUROPROTECTION — MICE ONLY:** Weydt et al. (2005 [Ref 32]) showed delayed disease onset (>2 weeks) in SOD1(G93A) mice at 5 mg/kg/day SC. Survival was NOT affected. No human data. Note species-specific caveat and absence of survival benefit. --- *Research conducted by pharmacological research agent. All citations verified via PubMed E-utilities, Crossref API, or PubChem as noted. Web sources flagged as web_retrieved.*