Cannabidiol

6Node page

what any key link opens

psx:substance/cbd/value/contraindication/6c465995-5fd7-4bdb-8193-59b7ae9b6ec7@1

valuereferenced by edges — no row of its own

derived from · upstream

derived_fromcontraindication · metabolicpsx:substance/cbd/proposal/contraindication/e4673b68-1951-43f5-b71c-69b9a3f710d7

feeds · downstream

none recorded

psx:substance/cbd/value/contraindication/6c465995-5fd7-4bdb-8193-59b7ae9b6ec7@1
└─ derived_from  proposal/contraindication/e4673b68-1951-43f5-b71c-69b9a3f710d7  contraindication · metabolic

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

5046 with DOI

29 strong · 21 moderate · 0 weak

Compilations

12026-05-07T00:50:50.093Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

29last ruled 2026-06-04

0 awaiting a ruling

Issued documents

52026-10-19T20:31:04.044Z

notice · info card · emergency

Searches

251 with no results

queries and counts on the build

Claims checked

1885 supported

5 supported · 183 not

Correspondence

0received

consent field ships in Phase 4

Edges

495

derivations recorded for this entity

Complete over 50 sources, 1 compilation, and 29 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/cbd/archive

2Build

one panel per compilation run

generation run 2026-05-07

61 min completedmodel pipeline-v5plan not recordedrun/8333cdf5…

Selection

results seen147

selected by the model54

consumed as sources50

Verification

claims checked188

supported2

partially supported3

not supported1

inconclusive182

record
seen / partial
working

The model's own caveats

contradictory_sources
safety_data_note

Reproduce

inputs: 50 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

25 searches — query, source, results, what was kept and why

25 searches for this run
#	source	query	seen	kept	rationale
1	PubMed	cannabidiol pharmacology receptor binding mechanism of action	12	4	Most relevant to pharmacology/receptor binding. Others were too specific to cancer/delivery.
2	PubMed	cannabidiol pharmacokinetics bioavailability human	10	5	Key PK papers: comparative PK of formulations, EFSA safety update 2026, epilepsy PK review, lymphatic transport pig model
3	OpenAlex	cannabidiol CBD pharmacology mechanism	10	4	Landmark papers on CBD pharmacology, receptor targets, and PK
4	PubChem	cannabidiol	1	1	Confirms chemical identity of CBD
5	PubMed	cannabidiol drug interaction CYP2C19 CYP3A4 clobazam antiepileptic	4	4	Essential drug interaction papers for interactions section
6	PubMed · absence	cannabidiol discovery history isolation Adams mechoulam 1940 1963	0	0	Will use web search for historical context
7	PubMed	cannabidiol tolerance dependence withdrawal abuse potential	5	2	Key tolerance/dependence papers for CBD specifically
8	PubMed	cannabidiol safety toxicity liver adverse effects hepatotoxicity	8	6	Key safety papers for toxicity section
9	OpenAlex	cannabidiol isolation structure Adams Mechoulam history discovery	8	2	Historical context for CBD discovery and phytocannabinoid chemistry
10	OpenAlex	cannabidiol anxiety antipsychotic clinical trial human	8	1	Major systematic review of cannabinoid clinical evidence
11	ClinicalTrials.gov	cannabidiol CBD treatment	12	5	Most clinically relevant trials across different indications
12	OpenAlex	cannabidiol anti-inflammatory neuroprotective antioxidant mechanisms	8	4	Important mechanistic and historical review papers
13	PubMed	cannabidiol 5-HT1A serotonin receptor binding affinity Ki EC50	3	3	Quantitative binding data for 5-HT1A pharmacology
14	PubMed	cannabidiol nausea emesis antiemetic serotonin 5-HT	5	2	Evidence for CBD nausea suppression mechanism via 5-HT1A
15	PubMed	cannabidiol Devinsky Dravet syndrome randomized controlled trial 2017	1	1	Pivotal Phase 3 RCT leading to FDA approval
16	WebSearch	cannabidiol history discovery isolation Roger Adams 1940 Mechoulam 1963 structure	10	1	Historical context for CBD discovery narrative
17	WebSearch	cannabidiol legal status UK EU Canada Australia DEA Schedule V US 2024 2025	10	0	Legal status data for multiple jurisdictions
18	WebSearch	cannabidiol Australia TGA approved legal status CBD scheduling 2024	10	0	Australian regulatory information
19	PubMed	cannabidiol adverse effects diarrhea somnolence appetite clinical Epidiolex trials	6	3	Real-world adverse effect profile from clinical trials
20	PubMed	cannabidiol opioid substance use disorder addiction treatment	5	1	Most current and high-quality evidence for CBD in substance use disorders
21	PubMed	cannabidiol autism spectrum disorder clinical trial children	5	2	Evidence for CBD in ASD - emerging indication
22	PubMed	cannabidiol Zuardi historical review first human trials	1	1	Key historical review from the group that conducted first human CBD studies
23	PubChem	CBD CID 644019 chemical properties	1	1	Chemical identity verification against seed data - no contradictions found
24	PubMed	Devinsky Patel Cross GWPCARE3 cannabidiol Lennox-Gastaut drop seizures NEJM 2018	1	1	Companion trial to 2017 Dravet syndrome paper; led to FDA approval for LGS
25	Multiple	Cross-referencing seed data dose ranges against EFSA safety statement and Epidiolex clinical dosing	3	0	Safety-critical cross-reference flagged in research output

188 claims by section — every cited sentence, checked against its source

safety70 · 3 ok

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In iPSC-derived hepatocytes, the transcriptomic point-of-departure is 0.106 µM, with impairment of CYP activity, mitochondrial membrane potential, and lipid accumulation at 0.1–3 µM.partially supported
Transcriptomic analysis of hemp cannabinoids in human iPSC-derived hepatocytes. CBG has lowest transcriptional activity among cannabinoids tested (CBN > CBD > CBC > CBG). All cannabinoids impaired liver metabolism and caused oxidative stress. Hemp extract adverse effects largely driven by CBD. j.tox.2024.153885
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Additive cardiovascular effects with sympathomimetic agents represent a theoretical concernsupported
Cardiac toxicity via additive hypertension and tachycardia with sympathomimetics. bcp.13710
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Non-psychoactive cannabinoids do not produce intoxicating, cognitive, or rewarding properties in humanssupported
Non-psychoactive cannabinoids do not produce intoxicating, cognitive or rewarding properties in humans. Delta-9-THC has moderate reinforcing effects with a 2-6 day withdrawal syndrome. fpsyt.2024.1322434
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pharmacology46 · 1 ok

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CBD subsequently desensitizes TRPV1 to capsaicin challenge, and additionally activates and desensitizes TRPV2, TRPA1, and TRPM8partially supported
CBD, CBG, CBGV and THCV stimulated and desensitized human TRPV1. CBC, CBD and CBN were potent rat TRPA1 agonists. j.1476-5381.2010.01166.x
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clinical-evidence20 · 0 ok

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comparative-pharmacology6 · 1 ok

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THC is a cb1-receptor partial-agonist producing euphoria, perceptual distortion, and cognitive impairment; CBD is a CB1 negative allosteric modulator producing none of these effectspartially supported
Delta9-THC is a CB1 and CB2 receptor partial agonist. Responses strongly influenced by receptor expression level, signalling efficiency, and ongoing endocannabinoid release. sj.bjp.0707442
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pharmacokinetic-detail6 · 0 ok

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chemistry4 · 0 ok

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receptor-pharmacology4 · 0 ok

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3Sources

50 consumed · sorted by year · feeds = sections resting on it

Sources 1 to 30
year	source	tier	status	feeds
2026	Cannabinoid-based interventions for behavioral outcomes in children and adolescents with autism spectrum disorder: A systematic reviewVasconcelos QDJS, de Freitas RF, Freitas MC, et al. · Progress in Neuro-Psychopharmacology and Biological Psychiatrydoi:10.1016/j.pnpbp.2026.111697	strong	consumed	cited only
2026	Comparative Pharmacokinetics and Safety of Cannabidiol in a Powder Formulation, CBtru, vs an Oil-Based Formulation, Epidyolex, Under Fasted and Fed Conditions in Healthy ParticipantsBendik I, Beck M, Manderra A, et al. · CNS Drugsdoi:10.1007/s40263-026-01280-1	strong	consumed	1 section
2026	Functional selectivity of cannabinoids at CB1 receptors: Comprehensive analysis of G proteins, beta-arrestin and cAMP signalling dynamics in HEK293T cellsAlAli N, Wheaton BJ, Jacobsson SOP · European Journal of Pharmacologydoi:10.1016/j.ejphar.2026.178735	moderate	consumed	1 section
2026	In silico insights on the binding site and function of cannabinoids and cannabinoid acids on human 5-HT1A receptorYap BK, Palmer S, Piccariello T · Journal of Molecular Graphics and Modellingdoi:10.1016/j.jmgm.2025.109186	moderate	consumed	1 section
2026	Species differences in pregnane X receptor activation by delta-9-tetrahydrocannabinol, cannabidiol, and cannabinolLau AJ, Chang TKH · Biochemical and Biophysical Research Communicationsdoi:10.1016/j.bbrc.2026.153250	moderate	consumed	2 sections
2026	The efficacy and safety of cannabinoids for the treatment of mental disorders and substance use disorders: a systematic review and meta-analysisWilson J, Dobson O, Langcake A, et al. · The Lancet Psychiatrydoi:10.1016/s2215-0366(26)00015-5	strong	consumed	cited only
2026	Update of the statement on safety of cannabidiol as a novel foodTurck D, Bohn T, Camara M, et al. · EFSA journaldoi:10.2903/j.efsa.2026.9862	strong	consumed	5 sections
2025	Epilepsy, neuroinflammation and cannabidiol What do we know thus far?Pesantez Rios G, Perucca E, Striano P, et al. · Frontiers in Pharmacologydoi:10.3389/fphar.2025.1749260	strong	consumed	1 section
2025	Medical Marijuana and Treatment Personalization: The Role of Genetics and Epigenetics in Response to THC and CBDKalak M, Brylak-Blaszkow A, Blaszkow L, Kalak T · Genesdoi:10.3390/genes16121487	strong	consumed	3 sections
2025	Pharmacological and Pharmacokinetic Profile of Cannabidiol in Human Epilepsy: A Review of Metabolism, Therapeutic Drug Monitoring, and Interactions with Antiseizure MedicationsNa JH, Lee YM · Biomoleculesdoi:10.3390/biom15121668	strong	consumed	1 section
2025	Short-term repeated oral intake of low dose cannabidiol: effects on liver enzyme activity and creatinine concentration during intense exerciseIsenmann E, Lachenmeier DW, Flenker U, et al. · Archives of Toxicologydoi:10.1007/s00204-024-03904-1	strong	consumed	1 section
2024	A critical assessment of the abuse, dependence and associated safety risks of naturally occurring and synthetic cannabinoidsHeal DJ, Gosden J, Smith SL · Frontiers in Psychiatrydoi:10.3389/fpsyt.2024.1322434	strong	consumed	1 section
2024	CBD in the Treatment of EpilepsyBorowicz-Reutt K, Czernia J, Krawczyk M · Moleculesdoi:10.3390/molecules29091981	strong	consumed	1 section
2024	Comparison on the mechanism and potency of hepatotoxicity among hemp extract and its four major constituent cannabinoidsGao X, Campasino K, Yourick MR, et al. · Toxicologydoi:10.1016/j.tox.2024.153885	moderate	consumed	1 section
2024	Consensus panel recommendations for the optimization of EPIDIOLEX treatment for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complexWechsler RT, Burdette DE, Gidal BE, et al. · Epilepsia Opendoi:10.1002/epi4.12956	moderate	consumed	1 section
2024	Effect of cannabidiol and hemp extract on viability and function of hepatocytes derived from human induced pluripotent stem cellsCampasino K, Yourick MR, Zhao Y, et al. · Toxicology in Vitrodoi:10.1016/j.tiv.2024.105933	moderate	consumed	1 section
2023	Cannabidiol reveals a disruptive strategy for 21st century epilepsy drug discoveryDel Pozo A, Barker-Haliski M · Experimental Neurologydoi:10.1016/j.expneurol.2022.114288	moderate	consumed	3 sections
2023	Establishment of a point of departure for CBD hepatotoxicity employing human HepaRG spheroidsLi J, Zagorski JW, Kaminski NE · Toxicologydoi:10.1016/j.tox.2023.153469	moderate	consumed	1 section
2023	The therapeutic potential of purified cannabidiolO'Sullivan SE, Jensen SS, Nikolajsen GN, et al. · Journal of Cannabis Researchdoi:10.1186/s42238-023-00186-9	strong	consumed	2 sections
2022	Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical TrialCrippa JAS, Pacheco JC, Zuardi AW, et al. · Cannabis and Cannabinoid Researchdoi:10.1089/can.2021.0093	strong	consumed	2 sections
2022	Cannabidiol Interferes with Establishment of delta9-Tetrahydrocannabinol-Induced Nausea Through a 5-HT1A MechanismDeVuono MV, La Caprara O, Petrie GN, et al. · Cannabis and Cannabinoid Researchdoi:10.1089/can.2020.0083	moderate	consumed	1 section
2022	Time to onset of cannabidiol treatment effect and resolution of adverse events in tuberous sclerosis complex: Post hoc analysis of GWPCARE6Wu JY, Cock HR, Devinsky O, et al. · Epilepsiadoi:10.1111/epi.17199	strong	consumed	cited only
2021	Add-on cannabidiol in patients with Dravet syndrome: Results of a long-term open-label extension trial (GWPCARE5)Scheffer IE, Halford JJ, Miller I, et al. · Epilepsiadoi:10.1111/epi.17036	moderate	consumed	2 sections
2021	Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young PeopleAnderson LL, Doohan PT, Oldfield L, et al. · Journal of Clinical Psychopharmacologydoi:10.1097/jcp.0000000000001427	moderate	consumed	cited only
2021	Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: Results of a long-term open-label extension trialPatel AD, Mazurkiewicz-Beldzinska M, Chin RF, et al. · Epilepsiadoi:10.1111/epi.17000	moderate	consumed	1 section
2021	Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut SyndromeIannone LF, Arena G, Battaglia D, et al. · Frontiers in Neurologydoi:10.3389/fneur.2021.673135	moderate	consumed	2 sections
2020	Cannabidiol Acts at 5-HT1A Receptors in the Human Brain: Relevance for Treating Temporal Lobe EpilepsyMartinez-Aguirre C, Carmona-Cruz F, Velasco AL, et al. · Frontiers in Behavioral Neurosciencedoi:10.3389/fnbeh.2020.611278	moderate	consumed	4 sections
2020	Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugsPatsalos PN, Szaflarski JP, Gidal B, et al. · Epilepsiadoi:10.1111/epi.16674	strong	consumed	1 section
2020	Evaluation of repeated or acute treatment with cannabidiol (CBD), cannabidiolic acid (CBDA) or CBDA methyl ester (HU-580) on nausea and/or vomiting in rats and shrewsRock EM, Sullivan MT, Collins SA, et al. · Psychopharmacologydoi:10.1007/s00213-020-05559-z	moderate	consumed	cited only
2019	Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactionsAnderson LL, Absalom NL, Abelev SV, et al. · Epilepsiadoi:10.1111/epi.16355	moderate	consumed	1 section

Show all 51 sources — 21 more

Sources 31 to 51
year	source	tier	status	feeds
2018	Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled TrialMcGuire P, Robson P, Cubala WJ, et al. · American Journal of Psychiatrydoi:10.1176/appi.ajp.2017.17030325	strong	consumed	1 section
2018	Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut SyndromeDevinsky O, Patel AD, Cross JH, et al. (GWPCARE3) · New England Journal of Medicinedoi:10.1056/nejmoa1714631	strong	consumed	cited only
2018	Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overviewMandolini GM, Lazzaretti M, Pigoni A, et al. · Epidemiology and Psychiatric Sciencesdoi:10.1017/s2045796018000239	strong	consumed	cited only
2018	The pharmacokinetics and the pharmacodynamics of cannabinoidsLucas C, Galettis P, Schneider J · British Journal of Clinical Pharmacologydoi:10.1111/bcp.13710	strong	consumed	1 section
2017	Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet SyndromeDevinsky O, Cross JH, Laux L, et al. · New England Journal of Medicinedoi:10.1056/nejmoa1611618	strong	consumed	cited only
2016	Phytocannabinoids: a unified critical inventoryHanus LO, Meyer S, Munoz E, Taglialatela-Scafati O, Appendino G · Natural Product Reportsdoi:10.1039/c6np00074f	strong	consumed	cited only
2015	Cannabidiol as a Potential Treatment for Anxiety DisordersBlessing EM, Steenkamp MM, Manzanares J, Marmar CR · Neurotherapeuticsdoi:10.1007/s13311-015-0387-1	strong	consumed	cited only
2015	Cannabinoids for Medical Use: A Systematic Review and Meta-analysisWhiting P, Wolff R, Deshpande S, et al. · JAMAdoi:10.1001/jama.2015.6358	strong	consumed	cited only
2012	Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophreniaLeweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW · Translational Psychiatrydoi:10.1038/tp.2012.15	strong	consumed	2 sections
2011	Abuse potential and psychoactive effects of delta-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex)Robson P · Expert Opinion on Drug Safetydoi:10.1517/14740338.2011.575778	moderate	consumed	1 section
2011	Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatumPandolfo P, Silveirinha V, dos Santos-Rodrigues A, et al. · European Journal of Pharmacologydoi:10.1016/j.ejphar.2011.01.013	moderate	consumed	2 sections
2011	Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymesDe Petrocellis L, Ligresti A, Moriello AS, et al. · British Journal of Pharmacologydoi:10.1111/j.1476-5381.2010.01166.x	moderate	consumed	1 section
2008	Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of actionZuardi AW · Revista Brasileira de Psiquiatriapmid:18833429	strong	consumed	1 section
2007	The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarinPertwee RG · British Journal of Pharmacologydoi:10.1038/sj.bjp.0707442	strong	consumed	2 sections
2006	Cannabinoid pharmacology: the first 66 yearsPertwee RG · British Journal of Pharmacologypmid:16402100	strong	consumed	1 section
2005	Agonistic properties of cannabidiol at 5-HT1a receptorsRusso EB, Burnett A, Hall B, Parker KK · Neurochemical Researchpmid:16258853	moderate	consumed	1 section
2005	Pharmacokinetics of cannabinoidsMcGilveray IJ · Pain Research and Managementpmid:16237477	strong	consumed	1 section
2003	Pharmacokinetics and Pharmacodynamics of CannabinoidsGrotenhermen F · Clinical Pharmacokineticsdoi:10.2165/00003088-200342040-00003	strong	consumed	cited only
2001	Medicinal Use of Cannabis: History and Current StatusKalant H · Pain Research and Managementdoi:10.1155/2001/469629	strong	consumed	cited only
2001	Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamideBisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE · British Journal of Pharmacologydoi:10.1038/sj.bjp.0704327	moderate	consumed	5 sections
—	Searched PubMed for "cannabidiol discovery history isolation Adams mechoulam 1940 1963" — no resultsabsence		no results	—

4Docket

one filing per activity — decisions, correspondence, reports

0012026-05-07revisionRevision 1
Initial LLM generation (v5 pipeline, wiki, prose phase)
psx:substance/cbd/version/1
0022026-06-04proposal27 value proposals approved together
one review action inferred from a shared reviewer and instant — the graph records one activity per proposal
27 items in this filing
- contraindication · hepatic
- contraindication · hepatic
- contraindication · metabolic
- contraindication · age
- contraindication · metabolic
- dose_tier · threshold
- dose_tier · light
- dose_tier · common
- dose_tier · strong
- dose_tier · heavy
- timeline · oral · onset
- timeline · oral · come_up
- timeline · oral · peak
- timeline · oral · resolution
- timeline · oral · afterglow
- toxicity
- dependence · full
- withdrawal
- tolerance
- dosage · oral
- duration · oral · onset
- duration · oral · come_up
- duration · oral · peak
- duration · oral · offset
- duration · oral · total
- duration · oral · aftereffects
psx:substance/cbd/proposal/contraindication/18a9b832-7e26-4f56-874a-1fa8c95fe0ad
0032026-06-04publicationPublication — backfill
psx:substance/cbd/pub/8f7608c4-1826-49c9-aa60-8ea4c8890bee

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
document	content hash	issued	from version	superseded
emergency	7386375eac1334714f070b93…	2026-10-19 20:31	Revision 1	current
info_card	58595b79721f6004733effca…	2026-10-19 20:31	Revision 1	current
emergency	207cf682e28a91d88136b9a2…	2026-09-04 04:29	Revision 1	superseded2026-10-19
info_card	27f7a011ee46dc6f4a5bee17…	2026-09-04 04:29	Revision 1	superseded2026-10-19
notice	64878b43a1d2932a5305f55b…	2026-09-04 04:29	Revision 1	current

Cannabidiol

6Node page

derived from · upstream

feeds · downstream

1Provenance card

2Build

generation run 2026-05-07

research→

draft→

audit→

verify→

simplify→

publish

Selection

Verification

The model's own caveats

Reproduce

3Sources

4Docket

5Issued documents

research

draft

audit

verify

simplify