{"id":"2693ffa2-3702-5990-8d9b-5db42ca9a7a7","stable_key":"3238e4f0-8d45-5c72-8624-6e9a8b20527c:ibu-blocks-anandamide-breakdown","predicate":"inhibits","statement":"The time-dependent reduction in potency of anandamide toward inhibition of cannabinoid agonist binding in rat cerebellar membranes was blocked by ibuprofen but not by acetylsalicylic acid, sulindac, acetaminophen or to any significant extent by ketoprofen and naproxen, a direct assay of anandamide amidase gave a half-maximal inhibitory concentration for ibuprofen of approximately 400 micromolar, and that potency was of the same order as required for inhibition of cyclooxygenase-2 in cell-free systems and as the peak plasma concentrations following a two times 200 milligram dose regimen, so following therapeutic doses the metabolism of anandamide may be affected.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ce8927e7-b4bd-50c6-8940-2caf6a493ea8","mechanism_event_label":"Ibuprofen, and not the other painkillers tested, slows the destruction of the body’s own cannabis-like signal.","subject":{"id":"b429f269-1d01-59f4-881a-868de0849d0d","slug":"ibuprofen","display_name":"Ibuprofen","entity_type_key":"drug"},"object":{"id":"43a4c49a-aaaf-5d72-b9e6-ded3b4c61a12","slug":"anandamide-metabolism","display_name":"Metabolism of anandamide by amidohydrolase","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ce8927e7-b4bd-50c6-8940-2caf6a493ea8","stable_key":"3238e4f0-8d45-5c72-8624-6e9a8b20527c:ibu-blocks-anandamide-breakdown-event","event_type":"biochemical_relationship","label":"Ibuprofen, and not the other painkillers tested, slows the destruction of the body’s own cannabis-like signal.","description":"The time-dependent reduction in potency of anandamide toward inhibition of cannabinoid agonist binding in rat cerebellar membranes was blocked by ibuprofen but not by acetylsalicylic acid, sulindac, acetaminophen or to any significant extent by ketoprofen and naproxen, a direct assay of anandamide amidase gave a half-maximal inhibitory concentration for ibuprofen of approximately 400 micromolar, and that potency was of the same order as required for inhibition of cyclooxygenase-2 in cell-free systems and as the peak plasma concentrations following a two times 200 milligram dose regimen, so following therapeutic doses the metabolism of anandamide may be affected.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"daf9c6ee-5fd9-529c-8dfb-f26606ae40e3","slug":"anandamide","display_name":"Anandamide / arachidonylethanolamide","entity_type_key":"small_molecule"},"role":"protected_metabolite","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a4a100bc-130e-5006-bad6-58103aa6da55","slug":"faah","display_name":"Fatty acid amide hydrolase / FAAH","entity_type_key":"protein"},"role":"inhibited_enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8ac405bf-3ea0-539a-8e5e-abf503dc7081","slug":"aspirin","display_name":"Aspirin / acetylsalicylic acid","entity_type_key":"drug"},"role":"inactive_comparator","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"105efa29-5f66-5005-bea2-8082ae7bd180","slug":"naproxen","display_name":"Naproxen","entity_type_key":"drug"},"role":"inactive_comparator","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"63689550-e39a-5d47-bd1f-f2335920e644","slug":"cannabinoid-receptor-binding","display_name":"Binding of a cannabinoid agonist ligand to cannabinoid receptors","entity_type_key":"cellular_process"},"role":"assay_readout","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"f2517df9-ade7-5381-a952-a1df7ff28f1f","slug":"cerebellar-membrane","display_name":"Rat cerebellar membrane preparation","entity_type_key":"cell_type"},"role":"preparation","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"b429f269-1d01-59f4-881a-868de0849d0d","slug":"ibuprofen","display_name":"Ibuprofen","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""},{"entity":{"id":"43a4c49a-aaaf-5d72-b9e6-ded3b4c61a12","slug":"anandamide-metabolism","display_name":"Metabolism of anandamide by amidohydrolase","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":7,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ibuprofen-research/9060042.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543\", \"start_char\": 0, \"end_char\": 1394, \"text_sha256\": \"2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat cerebellar membrane preparations assayed by time-dependent loss of anandamide potency and by direct amidase assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Ibuprofen compared against acetylsalicylic acid, sulindac, acetaminophen, ketoprofen and naproxen","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The comparator set is what distinguishes this from a class effect: five other drugs failed. The concentration required is high, and the authors relate it to peak plasma levels rather than measuring them.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ibuprofen","display_name":"Ibuprofen","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Rat","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ibuprofen, and not the other painkillers tested, slows the destruction of the body’s own cannabis-like signal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ibu-p9060042] Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide. (1997). https://pubmed.ncbi.nlm.nih.gov/9060042/ DOI: 10.1111/j.1600-0773.1997.tb00291.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cerebellar membranes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"04beead7-ab86-5550-a7e8-a5e2ae0cbb99","evidence_kind":"source_excerpt","locator":"Lines 448-459","start_line":448,"end_line":459,"excerpt":"### ibu-blocks-anandamide-breakdown\nThe time-dependent reduction in potency of anandamide toward inhibition of cannabinoid agonist binding in rat cerebellar membranes was blocked by ibuprofen but not by acetylsalicylic acid, sulindac, acetaminophen or to any significant extent by ketoprofen and naproxen, a direct assay of anandamide amidase gave a half-maximal inhibitory concentration for ibuprofen of approximately 400 micromolar, and that potency was of the same order as required for inhibition of cyclooxygenase-2 in cell-free systems and as the peak plasma concentrations following a two times 200 milligram dose regimen, so following therapeutic doses the metabolism of anandamide may be affected.\nCondition category: normal\nnutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers.\nplain_language: Ibuprofen, and not the other painkillers tested, slows the destruction of the body’s own cannabis-like signal.\norganism: Rat\ntissue_or_cell_type: Cerebellar membranes\nexperimental_model: Rat cerebellar membrane preparations assayed by time-dependent loss of anandamide potency and by direct amidase assay\nlimitations: The comparator set is what distinguishes this from a class effect: five other drugs failed. The concentration required is high, and the authors relate it to peak plasma levels rather than measuring them.\nexposure: Ibuprofen compared against acetylsalicylic acid, sulindac, acetaminophen, ketoprofen and naproxen\nevidence_span: {\"source_cache\": \"artifacts/ibuprofen-research/9060042.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543\", \"start_char\": 0, \"end_char\": 1394, \"text_sha256\": \"2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543\"}\n[ibu-p9060042] Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide. (1997). https://pubmed.ncbi.nlm.nih.gov/9060042/ DOI: 10.1111/j.1600-0773.1997.tb00291.x","model_system":"Rat cerebellar membrane preparations assayed by time-dependent loss of anandamide potency and by direct amidase assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ibu-p9060042] Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide. (1997). https://pubmed.ncbi.nlm.nih.gov/9060042/ DOI: 10.1111/j.1600-0773.1997.tb00291.x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"31c4939d-f520-55c0-973b-224743caf245","stable_key":"import-3238e4f0-8d45-5c72-8624-6e9a8b20527c","title":"Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"cc2b388178f97f5906b66ecbe441fc5c86d51fd645947c5260fb0b4bdb4bcd21","revision_id":"0b4e5c65-05d3-5430-a4cd-8d6a03647dcb","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}