{"id":"45544665-d344-55d4-b06c-f710ae3587a7","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-withdraw-flow","predicate":"changes","statement":"At 24 hours after placebo substitution, withdrawal increased middle- and anterior-cerebral arterial flow velocities.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"e2fb60d5-7c9c-5e94-8bae-e94c946677fe","mechanism_event_label":"Stopping after repeated use produced a measurable response.","subject":{"id":"819b234b-c649-5a6c-852b-eb1fe634f6fb","slug":"caffeine-withdrawal-state","display_name":"Acute withdrawal after repeated caffeine exposure","entity_type_key":"cellular_process"},"object":{"id":"c36bfa8d-77d0-535b-9f76-ba0422464856","slug":"cerebral-blood-flow-velocity","display_name":"Cerebral arterial blood-flow velocity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e2fb60d5-7c9c-5e94-8bae-e94c946677fe","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-withdraw-flow-event","event_type":"observed_relationship","label":"Stopping after repeated use produced a measurable response.","description":"At 24 hours after placebo substitution, withdrawal increased middle- and anterior-cerebral arterial flow velocities.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"819b234b-c649-5a6c-852b-eb1fe634f6fb","slug":"caffeine-withdrawal-state","display_name":"Acute withdrawal after repeated caffeine exposure","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c36bfa8d-77d0-535b-9f76-ba0422464856","slug":"cerebral-blood-flow-velocity","display_name":"Cerebral arterial blood-flow velocity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"16 regular users; double-blind within-subject study; at least 14 days on 400 mg/day or placebo, with acute challenges.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Withdrawal is adaptation to repeated exposure, not an essential-nutrient deficiency. Blood-flow velocity is not absolute cerebral perfusion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Caffeine collection; salts, coffee, species and coexposure contexts retain their identities.","comparator":null,"unit":null,"notes":"","entity":{"slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Stopping after repeated use produced a measurable response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Caffeine withdrawal, acute effects, tolerance, and absence of net beneficial effects of chronic administration: cerebral blood flow velocity, quantitative EEG, and subjective effects. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19241060/ · DOI 10.1007/s00213-009-1489-4","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5cc1efa1-a9ea-5089-b855-e3b5420f55b8","evidence_kind":"source_excerpt","locator":"Lines 108-114","start_line":108,"end_line":114,"excerpt":"## caf-withdraw-flow\nStopping after repeated use produced a measurable response.\nAt 24 hours after placebo substitution, withdrawal increased middle- and anterior-cerebral arterial flow velocities.\nModel: 16 regular users; double-blind within-subject study; at least 14 days on 400 mg/day or placebo, with acute challenges.\nLimitations: Withdrawal is adaptation to repeated exposure, not an essential-nutrient deficiency. Blood-flow velocity is not absolute cerebral perfusion.\nEvidence access: Primary abstract\nCaffeine withdrawal, acute effects, tolerance, and absence of net beneficial effects of chronic administration: cerebral blood flow velocity, quantitative EEG, and subjective effects. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19241060/ · DOI 10.1007/s00213-009-1489-4","model_system":"16 regular users; double-blind within-subject study; at least 14 days on 400 mg/day or placebo, with acute challenges.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access stated with the claim.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"40a654db-878c-5471-bc6c-88f4f52599c0","stable_key":"import-ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6","title":"Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. 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