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psx:substance/cocoa/claim/75b1473c-13b3-4fa1-8027-6042b37a0f8f

claim2026-07-17workinginconclusive

derived from · upstream

feeds · downstream

Closure of psx:substance/cocoa/claim/75b1473c-13b3-4fa1-8027-6042b37a0f8f: 93 upstream, 106 downstream.

psx:substance/cocoa/claim/75b1473c-13b3-4fa1-8027-6042b37a0f8f
├─ used  src/pmid:11326548  Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement.
  ├─ informed_by  claim/186e0b7a-a035-4991-9e82-c2b926a1de66  Claim in safety — inconclusive  working
  ├─ informed_by  claim/61e4096e-f921-4bea-bdb0-eb8fd017c11b  Claim in safety — inconclusive  working
  ├─ informed_by  claim/8eefa2d3-1976-4e9f-9660-4b1762e98589  Claim in safety — inconclusive  working
  ├─ informed_by  claim/b828486a-81b6-4538-a99a-9c0650912f3a  Claim in safety — inconclusive  working
  ├─ informed_by  claim/c5427e71-c82a-4a2a-ab20-742aa3214061  Claim in safety — inconclusive  working
  ├─ informed_by  claim/b89df34d-2bf6-4c29-b8ec-78e20d3cc853  Claim in safety — inconclusive  working
  ├─ informed_by  claim/66429b7c-a55c-4f5a-9980-b15494a96dca  Claim in safety — inconclusive  working
  ├─ informed_by  claim/a4c56e2c-2403-4802-aa23-018985b42d36  Claim in safety — inconclusive  working
  ├─ informed_by  claim/6621e35e-046d-4400-aa86-0b9cffe50ddf  Claim in safety — inconclusive  working
  ├─ informed_by  claim/534f3d14-c17d-470c-bf89-a41f9cd63b7f  Claim in safety — inconclusive  working
  ├─ informed_by  claim/007b99e0-4ac3-44af-a643-f32da70a59be  Claim in safety — inconclusive  working
  ├─ informed_by  claim/2dadf628-cf95-42ed-a707-e802fb86d4eb  Claim in safety — inconclusive  working
  ├─ informed_by  claim/6b9e2509-3298-487f-b7e2-39a048a1440c  Claim in safety — inconclusive  working
  ├─ informed_by  claim/a12f8303-6e9f-4eff-b2c8-2c90bee3fca6  Claim in safety — inconclusive  working
  ├─ informed_by  claim/2944aa61-db19-47e2-b8ec-c7b6f6476774  Claim in safety — inconclusive  working
  ├─ informed_by  claim/511dec4c-b022-4632-9c5a-deb700dba532  Claim in safety — inconclusive  working
  ├─ informed_by  claim/e21e0b61-b286-4c79-9f5d-0af228db8bb4  Claim in safety — inconclusive  working
  ├─ informed_by  claim/552a3b50-357c-4baf-901f-26a36895804e  Claim in safety — inconclusive  working
  ├─ informed_by  claim/097bed54-4fc9-48ca-8834-b2ba72a6388d  Claim in safety — inconclusive  working
  ├─ informed_by  claim/7a88a3dd-57c3-4caa-9168-ff60f35c6e7c  Claim in safety — inconclusive  working
  ├─ informed_by  claim/a6de28f7-4136-47eb-b747-d5580c497f9b  Claim in safety — inconclusive  working
  ├─ informed_by  claim/2009b8f2-6a94-4334-934d-cd360fe773ff  Claim in safety — inconclusive  working
  ├─ informed_by  claim/77926478-5612-4872-b70c-9a3392d7a47e  Claim in safety — inconclusive  working
  ├─ informed_by  claim/d974bf96-ee00-4b08-99e5-2921d5427c80  Claim in safety — inconclusive  working
  ├─ informed_by  claim/3cc8f74a-cc34-48a6-be32-290b48157612  Claim in safety — inconclusive  working
  ├─ informed_by  claim/3162c503-4d5b-44c2-b843-7287f2a1ce4f  Claim in safety — inconclusive  working
  ├─ informed_by  claim/c6d198cc-1cd6-42c7-9a55-097045ccefd3  Claim in safety — inconclusive  working
  ├─ informed_by  claim/79a155d0-2111-4fdb-b9c8-b3cd599cc2d7  Claim in safety — supported
  ├─ informed_by  claim/50ae4ed7-7046-43c9-876d-68025be248fe  Claim in safety — inconclusive  working
  ├─ informed_by  claim/0e7f1604-bc4b-4887-8188-f1d7a3545378  Claim in safety — inconclusive  working
  ├─ informed_by  claim/16c9f17a-2118-40c2-9df2-81d3957bd38e  Claim in safety — inconclusive  working
  ├─ informed_by  claim/bc2afb1f-e20b-4b28-8acc-716ce4cd70e8  Claim in safety — inconclusive  working
  ├─ informed_by  claim/c7d23630-30e2-42bb-9f67-8f98f4393116  Claim in safety — inconclusive  working
  ├─ informed_by  claim/53ab0fab-a249-4ead-9b3a-2f6ee48c9766  Claim in safety — inconclusive  working
  ├─ informed_by  claim/eb30c38b-a381-4476-91f2-ff3159ffa0ce  Claim in safety — inconclusive  working
  ├─ informed_by  claim/425d843a-8e7d-4889-9a61-38c5e3aa3a7f  Claim in safety — inconclusive  working
  ├─ informed_by  claim/b78fd402-86a5-4c90-8a82-9740917129aa  Claim in safety — inconclusive  working
  ├─ informed_by  claim/01f354e0-5f5c-44fc-82f0-dbcdfd4d8855  Claim in safety — inconclusive  working
  ├─ informed_by  claim/143b273c-6d9e-4b81-a631-d6c8b5c25ea4  Claim in safety — supported
  ├─ informed_by  claim/f3b2743b-6981-498d-b3ae-0501c40863f7  Claim in safety — inconclusive  working
  ├─ informed_by  claim/10805ec5-01a2-4b23-a770-e979de672bda  Claim in safety — inconclusive  working
  ├─ informed_by  claim/041f1060-c82d-4ad5-95c4-2915ae62b25c  Claim in safety — inconclusive  working
    ├─ used  src/doi:10.1111/1750-3841.70979  Chromatographic Profiling of Artisanal Chocolates: Volatile Composition and Methylxanthines as Markers of Cocoa Content.
    ├─ used  src/pmid:12124611  Cacao usage by the earliest Maya civilization.
    ├─ used  src/doi:10.1002/alz.12767  Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial (COSMOS-Mind).
    ├─ used  src/doi:10.3390/ijms231810510  Theobromine Targets Adenosine Receptors to Control Hippocampal Neuronal Function and Damage
    ├─ used  src/doi:10.1016/j.vph.2015.05.011  The cardiovascular benefits of dark chocolate.
    ├─ used  src/doi:10.3389/fphar.2015.00030  The relevance of theobromine for the beneficial effects of cocoa consumption.
    ├─ used  src/doi:10.1021/acs.jafc.9b08295  Perspective on Cadmium and Lead in Cocoa and Chocolate.
    ├─ used  src/doi:10.1094/phyto-05-20-0178-rvw  The History of Cacao and Its Diseases in the Americas.
    ├─ used  src/url:30f9ffb844cf77a0  Theobroma cacao (L.) — First described by Linnaeus, Species Plantarum, 1753; European Introduction timeline
    ├─ used  src/url:3785f4fea644a5a3  Theobroma cacao — Plants of the World Online
    ├─ used  src/doi:10.1093/ajcn/nqac055  Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: COSMOS randomized clinical trial.
    ├─ used  src/pmid:12939635  Cacao domestication II: progenitor germplasm of the Trinitario cacao cultivar.
    ├─ used  src/doi:10.3390/foods12132583  Profile of Bioactive Components of Cocoa (Theobroma cacao L.) By-Products from Ecuador.
    ├─ used  src/pmid:18068204  Caffeine and related purine alkaloids: biosynthesis, catabolism, function and genetic engineering.
    ├─ used  src/pmid:10552788  HPLC method for the quantification of procyanidins in cocoa and chocolate samples.
    ├─ used  src/pmid:8751435  Brain cannabinoids in chocolate.
    ├─ used  src/pmid:10876983  Cannabinoid mimics in chocolate utilized as an argument in court.
    ├─ used  src/pmid:11363932  Marijuana and chocolate.
    ├─ used  src/doi:10.1007/s10068-017-0196-x  Effect of the solid state fermentation of cocoa shell on the secondary metabolites, antioxidant activity, and fatty acids.
    ├─ used  src/doi:10.1016/j.foodres.2018.08.028  Identification and quantification of free and bound phenolic compounds in high-molecular weight melanoidin fractions derived from two different types of cocoa beans.
    ├─ used  src/doi:10.1111/j.1753-4887.2008.00114.x  Clinical benefit and preservation of flavonols in dark chocolate manufacturing.
    ├─ used  src/doi:10.1016/j.freeradbiomed.2023.01.003  Flavan-3-ol-methylxanthine interactions: Modulation of flavan-3-ol bioavailability in volunteers with a functional colon and an ileostomy
    ├─ used  src/doi:10.1016/j.vph.2015.02.010  Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregation
    ├─ used  src/doi:10.3390/nu11112800  Sub-Chronic Consumption of Dark Chocolate Enhances Cognitive Function and Releases Nerve Growth Factors: A Parallel-Group Randomized Trial
    ├─ used  src/doi:10.1002/14651858.cd008893.pub3  Effect of cocoa on blood pressure.
    ├─ used  src/doi:10.1007/s11064-018-2492-0  Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease
    ├─ used  src/doi:10.3390/molecules21080974  Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks.
    ├─ used  src/pmid:15548587  Theobromine inhibits sensory nerve activation and cough
    ├─ used  src/doi:10.1039/d5fo05193b  Simulated gastrointestinal digestion of cocoa powder (INFOGEST): methylxanthine bioaccessibility and antioxidant properties.
    ├─ used  src/doi:10.1016/j.mam.2022.101146  Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis.
    ├─ used  src/doi:10.1080/01480545.2019.1635615  Pre-clinical and cellular toxicity evaluation of 7-methylxanthine.
    ├─ used  src/pmid:3744189  Evaluation of the teratogenic potential of cocoa powder and theobromine in New Zealand White rabbits
    ├─ used  src/pmid:41030422  Severe hypernatremia in a dog following activated charcoal treatment for chocolate ingestion.
    ├─ used  src/doi:10.1016/j.scitotenv.2020.137645  Cocoa-laden cadmium threatens human health and cacao economy: A critical view.
    ├─ used  src/doi:10.1016/j.fct.2025.115799  Dark chocolate, heavy metals, and neurodevelopment in children.
    ├─ used  src/pmid:3772801  Human coffee drinking: reinforcing and physical dependence producing effects of caffeine.
    ├─ used  src/doi:10.1007/s10654-014-9944-x  Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis.
    ├─ derived_from  gen/a758634f-1ba3-4a6e-8292-c39b48de3a96  Generation — pipeline-v5
    ├─ generated_by  pub/67ed14d7-b116-41bc-a1b8-75fb27bd0f1c  Publication — backfill
      ├─ used  search/100c2553-f938-4020-b497-635bc4a063f9  Searched PubMed for "Theobroma cacao alkaloids theobromine caffeine phytochemistry"
      ├─ used  search/0aa73ad9-3a3e-4943-93c5-ffa27893444e  Searched PubMed for "cocoa theobromine pharmacology mechanism receptor"
      ├─ used  search/41fd3df8-5d26-4912-be3c-d010dacb45b6  Searched PubChem for "theobromine, caffeine, phenethylamine, anandamide"
      ├─ used  search/2f848edf-ab1c-403b-bdbf-29c2889ab8c6  Searched PubMed for "cocoa flavanols polyphenols health effects cardiovascular"
      ├─ used  search/e0585a69-36b3-4b9a-9fe7-125ef93df42f  Searched OpenAlex for "Theobroma cacao cocoa phytochemistry constituents methylxanthines flavonoids"
      ├─ used  search/26a0707b-39c9-42a0-bab8-3cf121c8d918  Searched PubMed for "chocolate phenylethylamine tyramine biogenic amine content analysis"
      ├─ used  search/7eb9b992-0c1b-4f91-895e-73ac691d0eb2  Searched OpenAlex for "Theobroma cacao history ethnobotany Maya Aztec Mesoamerica chocolate"
      ├─ used  search/18fb2b7d-687b-49ba-996f-6547c5cd0187  Searched POWO (Plants of the World Online) for "Theobroma cacao taxonomy"
      ├─ used  search/080616c8-46b3-4830-8360-a4f7f3185661  Searched WebSearch for "Theobroma cacao POWO accepted taxonomy family Malvaceae native range synonyms"
      ├─ used  search/0e31f800-d689-46a8-a1b9-200ff8aefb97  Searched PubMed for "cocoa chocolate heavy metal cadmium lead contamination safety"
      └─ used  search/4b88d7e3-15c0-4b85-ba2d-0c40911ca53b  Searched ClinicalTrials.gov for "cocoa flavanols cognitive function randomized"
├─ informed_by  section/safety.full@2
  ├─ used  version/2  Revision 2
  ├─ used  claim/072deedc-78c5-41d5-979d-bdef1310feaf  Claim in safety — inconclusive  working
  ├─ used  claim/d270f214-08fd-455c-8fba-f364013d89ba  Claim in safety — inconclusive  working
  ├─ used  claim/0766b63c-a4e9-4eb9-87b0-2f446d612c65  Claim in safety — inconclusive  working
  ├─ used  claim/a04de868-6877-431c-acc7-3a0c93a6aad5  Claim in safety — inconclusive  working
  ├─ used  claim/99e6cf3b-0c2e-4c62-904b-05499a740655  Claim in safety — inconclusive  working
  ├─ used  claim/40c1f867-acc7-4295-aeb4-494af1c7a343  Claim in safety — inconclusive  working
  ├─ used  claim/51b221f7-e7eb-478b-a0be-a890f105453a  Claim in safety — inconclusive  working
    ├─ derived_from  issue/notice@fb6e5e61c982  Issued notice
    ├─ derived_from  issue/info_card@7cc1504b4e1f  Issued info_card
    ├─ derived_from  issue/emergency@777b5863d801  Issued emergency
    ├─ derived_from  issue/info_card@0d2fd79fa411  Issued info_card
      ├─ used  claim/26d3741a-47a7-44e1-ba22-8eb0ddbb4545  Claim in preparations — inconclusive  working
      ├─ used  claim/a8b90ee4-ca59-45b7-984d-9cd5c1d2246b  Claim in preparations — inconclusive  working
      ├─ used  claim/56c7c97d-b467-475a-befc-efad8b5a2358  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/8ac2fa50-afd6-4d00-8736-b4886255a57d  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/df2afecf-9856-4e26-9f91-57bd5f7c4541  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/198b86ed-52ca-4de6-a6cd-668f1b54d89f  Claim in summary — inconclusive  working
      ├─ used  claim/dcb9ceb8-91ef-442b-8c4c-ffb819965e9a  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/bc394def-c265-4556-834a-57db4cd0a50e  Claim in summary — inconclusive  working
      ├─ used  claim/64b4554d-4496-4df3-8ef7-ddfda99a5d46  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/cf2a6928-66e3-4685-a5a7-31163b72876a  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/6534cbe0-c83e-4935-91bc-e2fd29bf3ddd  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/22f07560-5734-4b34-9c06-ad3c7cdd7183  Claim in preparations — inconclusive  working
      ├─ used  claim/b7a60f4b-292a-4346-9898-6e7c9c012966  Claim in preparations — inconclusive  working
      ├─ used  claim/bc324185-262f-4e95-8455-f0ee1d32a1af  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/14a89f13-fdce-4ff2-935e-f7bacd0f8d69  Claim in summary — inconclusive  working
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      ├─ used  claim/2d6d355d-b38c-4578-92c6-51e42812fdb2  Claim in neuroscience — inconclusive  working
      ├─ used  claim/ef22d918-885b-4ad1-a95f-b843749fb242  Claim in neuroscience — inconclusive  working
      ├─ used  claim/de87d88a-3792-4ac7-a0c6-ca54fc3406f8  Claim in summary — partially_supported
      ├─ used  claim/2266d3ea-d288-4c60-9a65-b02c563d1672  Claim in neuroscience — supported
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      ├─ used  claim/0d5c365d-cb03-4220-a107-16828bc254c5  Claim in neuroscience — inconclusive  working
      ├─ used  claim/1ddb7863-c973-43c7-9d86-0a21d5c12348  Claim in summary — inconclusive  working
      ├─ used  claim/10787feb-51a1-45d1-bfbc-830a54dae472  Claim in neuroscience — inconclusive  working
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      ├─ used  claim/63025510-2dcd-406b-b27c-1338e4309b7e  Claim in neuroscience — inconclusive  working
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      ├─ used  claim/85e1705e-23a5-4121-a760-6e96152b946e  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/744f56f5-f290-40e5-a329-b364265eaf17  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/2dcf0716-5ee2-4812-9360-ce9032e14c7f  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/8156765f-3ec5-4d73-bf2c-c1bfb51b930c  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/76fb92e1-3945-4d47-9f40-8b341379e7ac  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/23d80e91-4b8d-438e-9e2f-afc36b37b850  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/3245e83d-35a5-4e06-986f-63208fc48b92  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/a2a62592-a415-46a3-b433-82cd3b34edb9  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/d779a80e-047c-4a55-8365-2a1b508f9a22  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/f9c0ef63-ad60-4662-9768-65a48be60e02  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/0fcd8252-a3b3-46ba-ba0c-424c4fd26f05  Claim in preparations — inconclusive  working
      ├─ used  claim/4de54379-904a-4cff-91bb-ea29ad122af0  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/0fb7bfbc-8809-4aa6-a646-0c700b8b490e  Claim in preparations — inconclusive  working
      ├─ used  claim/a1b00ac4-e37b-41c7-aeb6-25a6a2253673  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/355a3827-2b82-439c-9ba9-c2875833ffbe  Claim in preparations — inconclusive  working
      ├─ used  claim/70a44946-0815-46ae-ae55-80a1f6873f5a  Claim in preparations — inconclusive  working
      ├─ used  claim/f8bf579b-57ab-41f7-a70d-c88a5e0513cf  Claim in alkaloid-profile — inconclusive  working
      ├─ used  claim/ea719af2-871f-4cfc-af00-8a5ccdaa9606  Claim in preparations — inconclusive  working
      ├─ used  claim/668edcd1-3498-47f6-a20e-f2ca33a81c7d  Claim in preparations — inconclusive  working
      ├─ used  claim/8c0142ab-5c39-4253-b602-1061cfc01912  Claim in preparations — inconclusive  working
      ├─ used  claim/10526f10-a900-4c94-aac2-f1e700876478  Claim in preparations — inconclusive  working
      ├─ used  claim/83ba54a6-de9f-449d-a9fb-66aebcf38ea5  Claim in preparations — inconclusive  working
      ├─ used  claim/d8f9c7ce-16f5-4064-a0c3-ec552bcf1557  Claim in preparations — inconclusive  working
      ├─ used  claim/f721cf4a-8129-4e4e-9c90-e1a78a9a0a27  Claim in neuroscience — inconclusive  working
      ├─ used  claim/1a2c4fa2-0243-4608-b00e-52373d75e851  Claim in neuroscience — inconclusive  working
      ├─ used  claim/7ce6a39c-6913-4a9e-bf4b-3409d38f193d  Claim in neuroscience — inconclusive  working
      ├─ used  claim/90e6b67c-6d7d-4804-a0ba-994838c2e0b1  Claim in neuroscience — inconclusive  working
      ├─ used  claim/ff0beef4-706d-4893-b492-bf328c17bbec  Claim in neuroscience — inconclusive  working
      ├─ used  claim/6f625f1c-d22a-47fc-9dbb-d718a11b8f64  Claim in neuroscience — supported
      ├─ used  claim/b1e5d21d-e51a-4636-8b71-948e1286c935  Claim in neuroscience — inconclusive  working
      ├─ used  claim/f8385d49-5098-4ade-9845-8cb311ccc83b  Claim in neuroscience — inconclusive  working
      ├─ used  claim/dd885cb9-46ed-4342-a7af-c9fd77a5a2a7  Claim in neuroscience — inconclusive  working
      ├─ used  claim/e5f7ea1a-42f4-4408-9b74-c6efdbceabc3  Claim in neuroscience — inconclusive  working
      ├─ used  claim/b19cc131-a8c8-4afd-9285-dddb23b4b9f0  Claim in neuroscience — inconclusive  working
      └─ used  claim/656640eb-162a-4ac8-89de-6eeda517bd91  Claim in neuroscience — inconclusive  working
… closure truncated at 200 nodes

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

3824 with DOI

9 strong · 25 moderate · 4 weak

Compilations

12026-05-13T08:52:52.271Z

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

Decisions

20last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:31:13.284Z

notice · info card · emergency

Searches

200 with no results

queries and counts on the build

Claims checked

1436 supported

6 supported · 137 not

Correspondence

0received

consent field ships in Phase 4

Edges

375

derivations recorded for this entity

Complete over 38 sources, 1 compilation, and 20 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/cocoa/archive

2Build

one panel per compilation run

generation run 2026-05-13

56 min completedmodel pipeline-v5plan not recordedrun/73845b2f…

research

citationsRegistryrecordresearchOutputworking

draft

articleDraftworking

audit

articleAuditedworking

verify

verificationResultworking

simplify

articleSimplifiedworking

publish

runMetarecordrunSummaryrecord

Selection

results seen108
selected by the model46
consumed as sources38

Verification

claims checked143
supported4
partially supported2
not supported0
inconclusive137
  • record
  • seen / partial
  • working

The model's own caveats

  • sparse_evidence
  • taper_not_applicable

Reproduce

inputs
38 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
20 searches — query, source, results, what was kept and why
20 searches for this run
#sourcequeryseenkeptrationale
1PubMedcocoa theobromine pharmacology mechanism receptor64Core mechanistic pharmacology papers for theobromine and caffeine in cocoa
2PubMedTheobroma cacao alkaloids theobromine caffeine phytochemistry11Key review on caffeine/theobromine biosynthesis in Theobroma and related plants
3PubMedcocoa flavanols polyphenols health effects cardiovascular103High-quality RCTs and systematic reviews on cocoa health effects
4PubChemtheobromine, caffeine, phenethylamine, anandamide44Core active constituents of cocoa confirmed
5OpenAlexTheobroma cacao cocoa phytochemistry constituents methylxanthines flavonoids104High-citation papers covering cocoa phytochemistry and health effects
6WebSearchTheobroma cacao POWO accepted taxonomy family Malvaceae native range synonyms102Confirms botanical taxonomy
7PubMedcocoa chocolate heavy metal cadmium lead contamination safety84Safety-critical contaminant data: cadmium in cocoa major documented concern
8POWO (Plants of the World Online)Theobroma cacao taxonomy11Authoritative taxonomy source
9PubMedchocolate phenylethylamine tyramine biogenic amine content analysis11Confirms phenylethylamine/tyramine presence in chocolate via fermentation
10PubMedTheobroma cacao genetics cultivar criollo forastero trinitario genotype11Key paper on cultivar genetics and domestication history
11PubMedcocoa cacao Maya evidence residue history11Foundational archaeological evidence of earliest Maya cacao use, Nature publication
12ClinicalTrials.govcocoa flavanols cognitive function randomized64Active clinical research base on cocoa cognitive/neurological effects
13OpenAlexTheobroma cacao history ethnobotany Maya Aztec Mesoamerica chocolate103Key ethnobotanical and archaeological literature on cacao origin and indigenous use
14WebSearchTheobroma cacao Linnaeus 1753 history European introduction colonial Mexico102Historical context for ethnobotany section
15PubMedtheobromine cough antitussive effect clinical trial11Pharmacological effect of theobromine beyond CNS/cardiovascular — antitussive clinical RCT
16Multiple PubMed + OpenAlex sourcesTheobromine/caffeine quantitative data in cocoa53Quantitative alkaloid data for alkaloid profile section
17PubMeddi Tomaso Beltramo Piomelli chocolate brain cannabinoid13Key papers on endocannabinoid-mimic hypothesis for chocolate — relevant to psychoactive effects discussion
18OpenAlexcocoa blood pressure meta-analysis systematic review81Highest quality evidence on cocoa cardiovascular effects — Cochrane review
19PubMedcaffeine pregnancy birth outcomes systematic review41Safety: pregnancy contraindication data for caffeine in cocoa
20OpenAlextheobromine pharmacology cardiovascular respiratory stimulant mechanism102Foundational pharmacology reviews on theobromine mechanism
143 claims by section — every cited sentence, checked against its source
safety50 · 2 ok

  • Claim in safety — inconclusiveinconclusiveworking →

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  • At 125-200 mg/kg/day, fetal weight decreases and skeletal malformations were observed, while dietary exposure at 63 mg/kg/day or less showed no fetotoxicity or teratogenicity.supported

    Developmental variations at 125-200 mg/kg. No teratogenicity at dietary levels. Highest test doses 38x human maximum consumption. pmid:3744189

  • Claim in safety — inconclusiveinconclusiveworking →

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  • A meta-analysis of 60 studies found that each 100 mg increment in daily caffeine intake was associated with a 14% increase in spontaneous abortion risk, a 19% increase in stillbirth risk, and a 10% increase in small-for-gestational-age birth risksupported

    Meta-analysis of 60 publications: per 100mg caffeine increment associated with 14% increased spontaneous abortion risk, 19% stillbirth, 7% low birth weight, 10% SGA. s10654-014-9944-x

  • Claim in safety — inconclusiveinconclusiveworking →

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alkaloid-profile26 · 0 ok

  • Claim in alkaloid-profile — inconclusiveinconclusiveworking →

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neuroscience20 · 3 ok

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  • At physiologically relevant concentrations (30 uM), theobromine facilitates synaptic transmission via A1R blockade and impairs long-term potentiation via A2AR blockade in hippocampal neuronssupported

    Theobromine (30 uM) facilitated synaptic transmission while decreasing LTP magnitude. A1R antagonist eliminated theobromine-dependent facilitation; A2AR antagonist abrogated LTP impairment. ijms231810510

  • This dual action also confers neuroprotection against amyloid-beta1-42-induced neuronal loss in vitro. Caffeine shares these receptor targets but is present in cocoa at approximately one-tenth the concentration of theobrominepartially supported

    Theobromine prevented LTP deficits and neuronal loss in Abeta1-42 exposed hippocampal preparations. ijms231810510

  • Claim in neuroscience — inconclusiveinconclusiveworking →

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  • The proposed mechanism is peripheral inhibition of capsaicin-induced sensory nerve depolarization of the vagus nerve, a pathway distinct from adenosine receptor antagonism.supported

    Theobromine directly inhibits capsaicin-induced sensory nerve depolarization of guinea-pig and human vagus nerve suggestive of an inhibitory effect on afferent nerve activation. Actions of theobromine appear to be peripherally mediated. pmid:15548587

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preparations20 · 0 ok

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summary13 · 1 ok

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  • Theobromine exerts its primary central and peripheral effects through antagonism of adenosine A1 and A2A receptors and inhibition of phosphodiesterases, increasing intracellular cAMPpartially supported

    A1R antagonist eliminated theobromine-dependent facilitation; A2AR antagonist abrogated LTP impairment. ijms231810510

  • Claim in summary — inconclusiveinconclusiveworking →

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history12 · 0 ok

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botanical-overview2 · 0 ok

  • Claim in botanical-overview — inconclusiveinconclusiveworking →

  • Claim in botanical-overview — inconclusiveinconclusiveworking →

3Sources

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

Sources 1 to 30
yearsourcetierstatusfeeds
2026Chromatographic Profiling of Artisanal Chocolates: Volatile Composition and Methylxanthines as Markers of Cocoa Content.Altissimo J et al. · Journal of Food Sciencedoi:10.1111/1750-3841.70979moderateconsumed3 sections
2026Dark chocolate, heavy metals, and neurodevelopment in children.Avasarala J · Food and Chemical Toxicologydoi:10.1016/j.fct.2025.115799moderateconsumed1 section
2026Simulated gastrointestinal digestion of cocoa powder (INFOGEST): methylxanthine bioaccessibility and antioxidant properties.Rivera-Manzorro L et al. · Food & Functiondoi:10.1039/d5fo05193bmoderateconsumed1 section
2025Severe hypernatremia in a dog following activated charcoal treatment for chocolate ingestion.Genareo C, Durkan S · Canadian Veterinary Journalpmid:41030422weakconsumed1 section
2024Theobroma cacao — Plants of the World OnlineRoyal Botanic Gardens Kewurl:3785f4fea644a5a3weakconsumedcited only
2024Theobroma cacao (L.) — First described by Linnaeus, Species Plantarum, 1753; European Introduction timelineVarious (Wikipedia, Kew, Oxford)url:30f9ffb844cf77a0weakconsumedcited only
2023Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial (COSMOS-Mind).Baker LD, Manson JE, Rapp SR, Sesso HD, Gaussoin SA, Shumaker SA, Espeland MA · Alzheimer's & Dementiadoi:10.1002/alz.12767strongconsumed3 sections
2023Flavan-3-ol-methylxanthine interactions: Modulation of flavan-3-ol bioavailability in volunteers with a functional colon and an ileostomyOttaviani JI, Fong RY, Borges G, et al. · Free Radical Biology & Medicinedoi:10.1016/j.freeradbiomed.2023.01.003strongconsumedcited only
2023Profile of Bioactive Components of Cocoa (Theobroma cacao L.) By-Products from Ecuador.Llerena W et al. · Foodsdoi:10.3390/foods12132583moderateconsumed1 section
2023Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis.Di Pede G, Mena P et al. · Molecular Aspects of Medicinedoi:10.1016/j.mam.2022.101146strongconsumed2 sections
2022Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: COSMOS randomized clinical trial.Sesso HD, Manson JE, et al. · American Journal of Clinical Nutritiondoi:10.1093/ajcn/nqac055strongconsumed2 sections
2022Theobromine Targets Adenosine Receptors to Control Hippocampal Neuronal Function and DamageValada P, Alcada-Morais S, Cunha RA, Lopes JP · International Journal of Molecular Sciencesdoi:10.3390/ijms231810510moderateconsumed2 sections
2021Pre-clinical and cellular toxicity evaluation of 7-methylxanthine.Singh H et al. · Drug and Chemical Toxicologydoi:10.1080/01480545.2019.1635615moderateconsumed1 section
2020Cocoa-laden cadmium threatens human health and cacao economy: A critical view.Maddela NR et al. · Science of the Total Environmentdoi:10.1016/j.scitotenv.2020.137645moderateconsumed1 section
2020Perspective on Cadmium and Lead in Cocoa and Chocolate.Abt E, Robin LP · Journal of Agricultural and Food Chemistrydoi:10.1021/acs.jafc.9b08295moderateconsumed2 sections
2020The History of Cacao and Its Diseases in the Americas.Diaz-Valderrama JR, Leiva S, Aime MC · Phytopathologydoi:10.1094/phyto-05-20-0178-rvwmoderateconsumed2 sections
2019Identification and quantification of free and bound phenolic compounds in high-molecular weight melanoidin fractions derived from two different types of cocoa beans.Oracz J, Nebesny E, Zyzelewicz D · Food Research Internationaldoi:10.1016/j.foodres.2018.08.028moderateconsumed2 sections
2019Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative DiseaseCamandola S, Plick N, Mattson MP · Neurochemical Researchdoi:10.1007/s11064-018-2492-0moderateconsumed1 section
2019Sub-Chronic Consumption of Dark Chocolate Enhances Cognitive Function and Releases Nerve Growth Factors: A Parallel-Group Randomized TrialSumiyoshi E, Matsuzaki K, Sugimoto N, Tanabe Y, Hara T, Katakura M, Miyamoto M, Mishima S, Shido O · Nutrientsdoi:10.3390/nu11112800strongconsumedcited only
2017Effect of cocoa on blood pressure.Ried K, Fakler P, Stocks N · Cochrane Database of Systematic Reviewsdoi:10.1002/14651858.cd008893.pub3strongconsumed1 section
2017Effect of the solid state fermentation of cocoa shell on the secondary metabolites, antioxidant activity, and fatty acids.Lessa OA et al. · Food Science and Biotechnologydoi:10.1007/s10068-017-0196-xmoderateconsumedcited only
2016Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks.Monteiro JP, Alves MG, Oliveira PF, Silva BM · Moleculesdoi:10.3390/molecules21080974moderateconsumed1 section
2015Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregationRull G, Mohd-Zain ZN, Shiel J, Lundberg MH, Collier DJ, Johnston A, Warner TD, Corder R · Vascular Pharmacologydoi:10.1016/j.vph.2015.02.010strongconsumed1 section
2015The cardiovascular benefits of dark chocolate.Kerimi A, Williamson G · Vascular Pharmacologydoi:10.1016/j.vph.2015.05.011moderateconsumed3 sections
2015The relevance of theobromine for the beneficial effects of cocoa consumption.Martinez-Pinilla E, Onatibia-Astibia A, Franco R · Frontiers in Pharmacologydoi:10.3389/fphar.2015.00030moderateconsumed3 sections
2014Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis.Greenwood DC, Thatcher NJ, Ye J, Garrard L, et al. · European Journal of Epidemiologydoi:10.1007/s10654-014-9944-xstrongconsumed1 section
2008Caffeine and related purine alkaloids: biosynthesis, catabolism, function and genetic engineering.Ashihara H, Sano H, Crozier A · Phytochemistrypmid:18068204moderateconsumed1 section
2008Clinical benefit and preservation of flavonols in dark chocolate manufacturing.McShea A, Ramiro-Puig E, Munro SB, Casadesus G, Castell M · Nutrition Reviewsdoi:10.1111/j.1753-4887.2008.00114.xmoderateconsumed2 sections
2005Theobromine inhibits sensory nerve activation and coughUsmani OS, Belvisi MG, Patel HJ, Crispino N, Birrell MA, Korbonits M, Korbonits D, Barnes PJ · FASEB Journalpmid:15548587strongconsumed1 section
2003Cacao domestication II: progenitor germplasm of the Trinitario cacao cultivar.Motamayor JC, Risterucci AM, Heath M, Lanaud C · Hereditypmid:12939635moderateconsumedcited only
Show all 38 sources — 8 more
Sources 31 to 38
yearsourcetierstatusfeeds
2002Cacao usage by the earliest Maya civilization.Hurst WJ, Tarka SM, Powis TG, Valdez F, Hester TR · Naturepmid:12124611moderateconsumed2 sections
2000Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement.Griffiths RR, Chausmer AL · Japanese Journal of Psychopharmacologypmid:11326548moderateconsumed1 section
2000Cannabinoid mimics in chocolate utilized as an argument in court.Tytgat J, Van Boven M, Paulie Daenens P · International Journal of Legal Medicinepmid:10876983weakconsumed2 sections
1999HPLC method for the quantification of procyanidins in cocoa and chocolate samples.Adamson GE et al. · Journal of Agricultural and Food Chemistrypmid:10552788moderateconsumed1 section
1996Brain cannabinoids in chocolate.di Tomaso E, Beltramo M, Piomelli D · Naturepmid:8751435moderateconsumed2 sections
1996Marijuana and chocolate.James JS · AIDS Treatment Newspmid:11363932moderateconsumed2 sections
1986Evaluation of the teratogenic potential of cocoa powder and theobromine in New Zealand White rabbitsTarka SM, Applebaum RS, Borzelleca JF · Food and Chemical Toxicologypmid:3744189moderateconsumed1 section
1986Human coffee drinking: reinforcing and physical dependence producing effects of caffeine.Griffiths RR, Bigelow GE, Liebson IA · Journal of Pharmacology and Experimental Therapeuticspmid:3772801moderateconsumed1 section

4Docket

one filing per activity — decisions, correspondence, reports

  1. 0012026-03-17importImported from Curiosity v1

    imported 2026-03; original sourcing not recoverable

    psx:substance/cocoa/import/curiosity-v1
  2. 0022026-03-17publicationPublication — backfill
    psx:substance/cocoa/pub/8e690ee9-7a71-4302-8601-db8d6c031224
  3. 0032026-03-17revisionRevision 1

    no edit summary recorded

    psx:substance/cocoa/version/1
  4. 0042026-05-13revisionRevision 2

    Initial LLM generation (plant pipeline v1, wiki, prose phase)

    psx:substance/cocoa/version/2
  5. 0052026-06-04proposal15 value proposals approved together

    one review action inferred from a shared reviewer and instant — the graph records one activity per proposal

    15 items in this filing

    • contraindication · age
    • contraindication · other
    • contraindication · hepatic
    • contraindication · psychiatric
    • contraindication · cardiovascular
    • dose_tier · threshold
    • dose_tier · light
    • dose_tier · common
    • dose_tier · strong
    • dose_tier · heavy
    • toxicity
    • dependence · full
    • withdrawal
    • tolerance
    psx:substance/cocoa/proposal/contraindication/1fa6ea56-15bc-488e-9837-7bfe1d012c7d
  6. 0062026-06-04publicationPublication — backfill
    psx:substance/cocoa/pub/67ed14d7-b116-41bc-a1b8-75fb27bd0f1c

5Issued documents

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

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_card0d2fd79fa4115ab6d7c5b8c9…2026-10-19 20:31Revision 2current
emergency777b5863d801327b008f5610…2026-09-04 04:29Revision 2current
info_card7cc1504b4e1fc009fd9b9f12…2026-09-04 04:29Revision 2superseded2026-10-19
noticefb6e5e61c98289464444fa49…2026-09-04 04:29Revision 2current