generation run 2026-05-11
62 min completedmodel pipeline-v5plan not recordedrun/66dc29e0…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
Reproduce
- inputs
- 23 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
15 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | tetrahydrocannabutol cannabinoid | 5 | 5 | All directly relevant to THCB pharmacology, chemistry, or toxicology |
| 2 | PubChem | tetrahydrocannabutol / THCB / CID 6453891 | 1 | 1 | Confirmed chemical identity data for THCB |
| 3 | OpenAlex | tetrahydrocannabutol cannabinoid butyl | 10 | 5 | Most cited papers providing context for THCB pharmacology and the homolog series |
| 4 | Crossref / DOI verification | doi:10.1021/acs.jnatprod.9b00876 | 1 | 1 | Primary isolation paper DOI verified |
| 5 | HandWiki | — | 1 | 1 | Confirmed PubChem CID and provided structured chemical data |
| 6 | WebSearch | tetrahydrocannabutol THCB legal status scheduling DEA United Kingdom EU | 10 | 1 | Legal status across major jurisdictions |
| 7 | PubMed | delta-9-THC cannabinoid CYP2C9 CYP3A4 metabolism pharmacokinetics | 8 | 6 | THC CYP metabolism data extrapolatable to THCB by structural analogy |
| 8 | WebSearch | THCB tetrahydrocannabutol Canada Controlled Drugs and Substances Act | 10 | 0 | Canada status unresolved - analog provisions may apply |
| 9 | PubMed | minor cannabinoid neuropathic pain analgesic neuronal hypersensitivity | 1 | 1 | Direct testing of minor cannabinoids including THCB for analgesic effects |
| 10 | OpenAlex | THCB tetrahydrocannabutol cannabinoid pharmacology analgesic | 8 | 2 | Expands cannabinoid homolog series context and provides biosynthesis production alternative |
| 11 | WebSearch | THCB effects user reports duration onset dose Reddit forum experience | 10 | 1 | Only available dose/duration data - flagged as user-report-only |
| 12 | ClinicalTrials.gov · absence | tetrahydrocannabutol THCB minor cannabinoid | 0 | 0 | Confirms no clinical trial development for THCB to date |
| 13 | PubMed | THC pharmacokinetics review bioavailability oral inhalation absorption distribution metabolism | 3 | 3 | THC PK data for by-analogy extrapolation to THCB |
| 14 | WebSearch | Australia THCB Poisons Standard tetrahydrocannabinols homologs | 10 | 1 | Australian legal status determination |
| 15 | GOV.UK / ACMD | — | 1 | 1 | Key finding for UK legal status of THCB |
78 claims by section — every cited sentence, checked against its source
safety20 · 11 ok
Claim in safety — inconclusiveinconclusiveworking →
Psychosis precipitation in vulnerable individuals (personal or family history of psychotic disorders) is a recognized risk of CB1 agonismsupported
Contraindications: psychiatric, cardiovascular, renal, hepatic illness. bcp.13710
Repeated high-dose cannabinoid use produces CB1 receptor downregulation in multiple brain regions, with associated cognitive impairmentpartially supported
Region-specific CB1 receptor downregulation in hypothalamus. Reduces CB1 receptor expression and function in a brain region-specific manner. j.phrs.2015.09.006
Claim in safety — inconclusiveinconclusiveworking →
A validated LC-MS/MS method can identify THCB in blood (LOD 1 ng/mL) and urinesupported
Validated LC-MS-MS method for quantitative analysis of THC homologs including THCB in blood and urine. LOD 1 ng/mL. bkaf023
Claim in safety — inconclusiveinconclusiveworking →
User reports describe THCB-associated anxiety, paranoia, disorientation, and excessive intoxication at higher doses, consistent with the CB1 agonist class profile.supported
Covers chemistry, synthesis, pharmacology, analytical methods, and subjective effects from user reports. s42238-024-00226-y
Repeated high-dose CB1 agonist use produces tolerance via receptor downregulation (reduced CB1 density) and desensitization (uncoupling of CB1 from G-protein signaling)supported
Reduces CB1 receptor expression and function in a brain region-specific manner. j.phrs.2015.09.006
In mice, tolerance to THC's hypothermic effects develops within days of repeated administration; tolerance to locomotor suppression develops more slowlypartially supported
Tolerance to hypothermic effects of THC develops after repeated administration. [Title: 'induces tolerance to hypothermia but not locomotor suppression in mice'] j.phrs.2015.09.006
Cross-tolerance between THC and other CB1 agonists is well-established — THC-tolerant individuals would be expected to show cross-tolerance to THCB.supported
THC history causes cross-tolerance to synthetic cannabinoids. j.phrs.2015.09.006
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
No approved pharmacotherapies exist for cannabis use disorder; behavioral interventions are first-linesupported
No approved pharmacotherapies. Reviews behavioral and pharmacological interventions. 14651858.cd008940.pub4
Δ9-THC and its analogs competitively inhibit CYP2C9, CYP3A4, and CYP2B6partially supported
THC inhibits CYP2C9 (diclofenac AUC x6.6 oral) > CYP3A > CYP1A2 at clinical doses. dmd.121.000734
Δ9-THC and its analogs competitively inhibit CYP2C9, CYP3A4, and CYP2B6supported
THC inhibits CYP1A2, 2B6, 2C9, 2D6. dmd.121.000442
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Concurrent anticoagulant therapy (relative): Predicted CYP2C9 inhibition could potentiate warfarin and other coumarin anticoagulants.supported
THC inhibits CYP1A2, 2B6, 2C9, 2D6. Basic static modeling suggests potential interactions with drugs metabolized by CYP2B6, 2C9, 2D6. dmd.121.000442
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — not_supportednot supportedworking →
pharmacology19 · 9 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
Competitive radioligand binding assays yielded Ki = 15 nM at CB1 and Ki = 51 nM at CB2supported
CB1 Ki=15 nM, CB2 Ki=51 nM. acs.jnatprod.9b00876
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The partial agonist designation derives from in vivo functional data: in the standard cannabinoid tetrad test in mice (hypolocomotion, catalepsy, antinociception, hypothermia), Δ9-THCB produced cannabimimetic effects but with less full-agonist efficacy than reference compoundssupported
Tetrad test showed partial CB1 agonism. acs.jnatprod.9b00876
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Anand and colleagues included THCB among ten minor cannabinoids tested in an in vitro model of neuronal hypersensitivity relevant to neuropathic pain, suggesting peripheral analgesic modulation beyond the CB1/CB2 axis.supported
Ten minor cannabinoids tested for analgesic effects in neuronal hypersensitivity model (neuropathic pain). Results from in vitro assay. jpr.s547613
Phytocannabinoids with structural similarity to THC can interact with TRPV1, TRPV2, GPR55, GPR18, GABA-A receptors, and voltage-gated sodium channelssupported
Review of CB1, CB2, GPR55, GPR18, TRPV1/2, GABAAR, VGSC as targets for phytocannabinoids. ph13080174
A non-cannabinoid-receptor activity of note: Liu and colleagues screened a library of minor cannabinoids against SARS-CoV-2 main protease (Mpro) and found THCB to be the most potent inhibitor in the library (IC₅₀ = 3.62 µM), outperforming cannabigerolic acid (IC₅₀ = 14.40 µM)supported
Tetrahydrocannabutol was the most active Mpro inhibitor (IC50=3.62 μM). molecules27186127
By analogy with Δ9-THC: inhaled bioavailability is approximately 25–30%, with Tmax around 10 minutes and rapid onset of psychoactive effectssupported
THC bioavailability ~30% inhaled, 4-12% oral. Peak plasma ~152 ng/mL at ~10 min post-inhalation. pmid:16237477
Claim in pharmacology — inconclusiveinconclusiveworking →
Oral bioavailability is considerably lower (4–12%) and highly variable, with Tmax of 1–6 hours; the extended oral duration reflects first-pass hepatic metabolism generating an active 11-hydroxy metabolitesupported
THC bioavailability ~30% inhaled, 4-12% oral. 11-OH-THC active metabolite. pmid:16237477
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Δ9-THC is primarily metabolized by CYP2C9 (both intestinal and hepatic) to 11-hydroxy-THC (active metabolite), then to 11-nor-9-carboxy-THC (inactive)partially supported
THC primarily metabolized by CYP2C9 in intestine (fm=0.89), CYP3A in fetal liver. 11-OH-THC metabolized by CYP3A and UGT2B7. dmd.122.000868
Claim in pharmacology — not_supportednot supportedworking →
CYP3A contributes, particularly in fetal liversupported
CYP3A in fetal liver. dmd.122.000868
Claim in pharmacology — inconclusiveinconclusiveworking →
summary9 · 6 ok
THCB binds the human CB1 receptor with high affinity (Ki = 15 nM) and functions as a partial CB1 agonistsupported
CB1 Ki=15 nM, CB2 Ki=51 nM. Tetrad test showed partial CB1 agonism. acs.jnatprod.9b00876
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
The discovery was part of a systematic effort that also identified Δ9-THCP (C7 chain) and Δ9-THCH (C6 chain), mapping the full phytocannabinoid alkyl homolog series from C3 to C7supported
Identifies CBDH and Δ9-THCH (hexyl analogs) in Cannabis sativa FM2. THCB explicitly referenced as part of the expanding homolog series (butyl, pentyl, hexyl, heptyl). s41598-020-79042-2
Since approximately 2021, THCB products — including both Δ8 and Δ9 isomers — have appeared on recreational markets.partially supported
Identified Δ8-THCB and Δ9-THCB in internet-sold oil products in Japan from 2022-2023. yakushi.24-00029
Claim in summary — inconclusiveinconclusiveworking →
In mice, THCB produces a partial cannabinoid tetrad response (hypolocomotion, catalepsy, antinociception, hypothermia) and demonstrates analgesic and anti-inflammatory activity in the formalin modelsupported
Formalin test in vivo. Tetrad test showed partial CB1 agonism. acs.jnatprod.9b00876
Dependence and withdrawal have not been studied; by class analogy with Δ9-THC, CB1 receptor downregulation with repeated use and a mild-to-moderate cannabis-type withdrawal syndrome are expectedsupported
Region-specific CB1 receptor downregulation in hypothalamus. j.phrs.2015.09.006
Products on the unregulated market may contain Δ8-THCB (semi-synthetic) and the synthesis byproduct Δ11-THCB, whose safety profiles are entirely unknownsupported
Identified Δ8-THCB and Δ9-THCB in internet-sold oil products in Japan from 2022-2023. Δ11-THCB identified as synthesis byproduct. yakushi.24-00029
history7 · 4 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Concurrently, Citti and colleagues isolated cannabidibutol (CBDB), the CBD butyl analogsupported
Isolation and characterization of CBDB (cannabidibutol), the CBD butyl analog, from hemp extract. j.jpba.2019.06.049
In 2020, the group further identified Δ9-THCH and cannabidihexol (CBDH), the hexyl (C6) series memberssupported
Identifies CBDH and Δ9-THCH (hexyl analogs) in Cannabis sativa FM2. s41598-020-79042-2
Forensic analyses in Japan (2022–2023) confirmed the presence of both isomers in commercial oil productssupported
Identified Δ8-THCB and Δ9-THCB in internet-sold oil products in Japan from 2022-2023. yakushi.24-00029
Forensic analysis has also identified Δ11-THCB as a minor byproduct of Δ8-THCB synthesissupported
Δ11-THCB identified as synthesis byproduct. yakushi.24-00029
Claim in history — inconclusiveinconclusiveworking →
pharmacokinetic-detail6 · 4 ok
All values sourced from THC pharmacokinetic reviews.supported
THC bioavailability ~30% inhaled, 4-12% oral. Peak plasma ~152 ng/mL at ~10 min post-inhalation. pmid:16237477
All values sourced from THC pharmacokinetic reviews.supported
Review of cannabinoid PK/PD. THC and CBD hepatically metabolized. bcp.13710
Δ9-THC undergoes primary oxidative metabolism via CYP2C9 at C-11, generating the pharmacologically active 11-hydroxy-THC, which is subsequently oxidized to the inactive 11-nor-9-carboxy-THC (THC-COOH)supported
THC primarily metabolized by CYP2C9 in intestine (fm=0.89). 11-OH-THC metabolized by CYP3A and UGT2B7. dmd.122.000868
Claim in pharmacokinetic-detail — not_supportednot supportedworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Clinically relevant oral interactions would be expected for narrow-therapeutic-index CYP2C9 substrates (warfarin, diclofenac, phenytoin) and CYP3A4 substrates (midazolam, tacrolimus, cyclosporine)partially supported
THC inhibits CYP1A2, 2B6, 2C9, 2D6. Basic static modeling suggests potential interactions with drugs metabolized by CYP2B6, 2C9, 2D6. dmd.121.000442
receptor-pharmacology5 · 3 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Intrinsic efficacy (Emax relative to a full agonist reference) has not been quantified in a cell-based functional assay; the partial agonist designation rests on the incomplete tetrad response in vivo rather than on direct measurement of receptor-level signaling efficacy.supported
Formalin test in vivo. Tetrad test showed partial CB1 agonism. acs.jnatprod.9b00876
The butyl side chain occupies the same hydrophobic channel as THC's pentyl chain, with the one-carbon reduction producing minimal steric penalty — consistent with SAR data from Huffman et al. demonstrating that C3 through C10 alkyl chains all support high CB1 affinity in the Δ8-THC dimethylalkyl series.partially supported
SAR study of dimethylalkyl-Δ8-THC series with C2-C12 side chains. Optimal CB1 affinity and in vivo potency with C4-C10 chains. pmid:12628666
Phytocannabinoids with similar dibenzopyran scaffolds interact with TRPV1 (vanilloid receptor), TRPV2, GPR55, GPR18, GABA-A receptors, and voltage-gated sodium channelssupported
Review of CB1, CB2, GPR55, GPR18, TRPV1/2, GABAAR, VGSC as targets for phytocannabinoids. ph13080174
chemistry4 · 1 ok
Structure-activity relationship studies on Δ8-THC dimethylalkyl analogs established that alkyl side chains ranging from C3 to C10 all support high CB1 affinity, with optimal affinity in the C4–C8 rangepartially supported
SAR study of dimethylalkyl-Δ8-THC series with C2-C12 side chains. Optimal CB1 affinity and in vivo potency with C4-C10 chains. pmid:12628666
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
comparative-pharmacology4 · 2 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Ki values for THCV and THCB from Linciano et al.; THC and THCP values from Citti et al.supported
Isolation of Δ9-THCP (C7 chain) from Cannabis sativa FM2. CB1 Ki=1.2 nM. s41598-019-56785-1
The critical pharmacological distinction is functional efficacy: THCB produces a partial tetrad response while THC produces a complete responsesupported
Tetrad test showed partial CB1 agonism. acs.jnatprod.9b00876
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
clinical-evidence2 · 2 ok
The totality of published in vivo evidence consists of two assay paradigms performed in mice by Linciano and colleagues:supported
Formalin test in vivo. Tetrad test showed partial CB1 agonism. acs.jnatprod.9b00876
In a separate study, Anand and colleagues tested THCB in an in vitro model of neuronal hypersensitivity relevant to neuropathic pain; detailed quantitative results are not available from the abstract.supported
Ten minor cannabinoids tested for analgesic effects in neuronal hypersensitivity model (neuropathic pain). Results from in vitro assay. jpr.s547613
effects-overview1 · 0 ok
Claim in effects-overview — inconclusiveinconclusiveworking →
neuroscience1 · 0 ok
Claim in neuroscience — inconclusiveinconclusiveworking →