{"id":"W4409119267","doi":"10.1007/s40263-025-01172-w","title":"Opioid Analgesics: Rise and Fall of Ligand Biased Signaling and Future Perspectives in the Quest for the Holy Grail","year":2025,"lang":"en","type":"review","venue":"CNS Drugs","topic":"Neuropeptides and Animal Physiology","field":"Neuroscience","cited_by":6,"is_retracted":false,"has_abstract":false,"ca_institutions":"McGill University; Université de Sherbrooke","funders":"Canadian Institutes of Health Research; Université de Caen Normandie","keywords":"Holy Grail; Medicine; Opioid; Addiction; Chronic pain; Analgesic; Intensive care medicine; Methadone; Heroin; Buprenorphine; Morphine; Pharmacology; Neuropathic pain; Anesthesia; Drug; Psychiatry; Receptor; Internal medicine","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0008115484,0.0007472311,0.001192576,0.001148498,0.0003042223,0.001673943,0.001016781,0.001514812,0.003929914],"category_scores_gemma":[0.000856371,0.0002434062,0.000324837,0.001357251,0.001230332,0.00276941,0.0008442686,0.003129006,0.001944542],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0007863786,"about_ca_system_score_gemma":0.001223384,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0007751568,"about_ca_topic_score_gemma":0.002322687,"domain_scores_codex":[0.9998249,0.00003422154,0.00001932361,0.0000335348,0.00006412171,0.00002391116],"domain_scores_gemma":[0.9995969,0.000211468,0.00003829725,0.00001317106,0.00009532326,0.00004494039],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"design_other","study_design_gemma":"not_applicable","study_design_scores_codex":[0.0001852783,0.00007063539,0.000171506,0.00847379,0.00005947041,0.0002317694,0.00008911728,0.0004140931,0.002773128,0.02813428,0.05285269,0.9065442],"study_design_scores_gemma":[0.00001742905,0.00008272057,0.0003917531,0.001582336,0.0000319786,0.0005423301,0.00007862096,0.000118527,0.0002644964,0.007897093,0.9889752,0.0000174443],"study_design_candidate":"not_applicable","study_design_consensus":null,"genre_codex":"review","genre_gemma":"review","genre_scores_codex":[0.00008800854,0.9976538,0.0001569916,0.0007840491,0.0004375847,0.00000179423,0.00001474351,0.000006529043,0.0008566259],"genre_scores_gemma":[0.0007309117,0.9971524,0.0002039451,0.000667462,0.0004835835,0.000004768925,0.00001902478,0.000001981987,0.0007358288],"genre_candidate":"review","genre_consensus":"review","teacher_disagreement_score":0.003929914,"threshold_uncertainty_score":0.01314688,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.04980184346512773,"score_gpt":0.3254815639558009,"score_spread":0.2756797204906731,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}