{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:20:58Z","timestamp":1792099258828,"version":"4.4.0"},"reference-count":96,"publisher":"Canadian Science Publishing","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/deed.en_GB"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:p>The growing epidemic of opioid misuse presents numerous challenges for healthcare practitioners and patients alike as friction exists between ease of use and efficacy, and potential for overuse and addiction. With over 82\u2009000 deaths related to opioid overdose in North America in 2020, it is imperative to gain a better understanding of the underlying mechanisms behind the addiction process, as well as the current methods being used in the arsenal against this disease. The current best pharmacological approaches for mediating opioid use disorder are methadone, buprenorphine, naltrexone, and naloxone, which act on opioid receptors to produce diverse effects based upon the patients\u2019 needs. The variety of effects that these drugs produce, which include removing opioid withdrawal, reversing overdose effects, and blocking opioid properties, makes this arsenal of therapeutics a global necessity in addressing the opioid use epidemic. Accordingly, this narrative review provides a summary of the available data regarding the physiological processes by which opioid addiction takes place and discusses the current and future potential of interventional methods used to mitigate opioid use disorder. The mechanisms of action and subsequent functional outcomes must be understood to reduce the number of opioid-related deaths worldwide.<\/jats:p>","DOI":"10.1139\/cjpp-2024-0281","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T16:35:26Z","timestamp":1739291726000},"page":"111-122","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["The addictive process of opioids: current and novel interventions in opioid use disorder"],"prefix":"10.1139","volume":"103","author":[{"given":"James M.","family":"Duerksen","sequence":"first","affiliation":[{"name":"Asper Clinical Research Institute, St. Boniface Hospital","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Ramjiawan","sequence":"additional","affiliation":[{"name":"Asper Clinical Research Institute, St. Boniface Hospital","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4272-5715","authenticated-orcid":false,"given":"Julia","family":"Witt","sequence":"additional","affiliation":[{"name":"University of Manitoba","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Fitzpatrick-Wong","sequence":"additional","affiliation":[{"name":"Asper Clinical Research Institute, St. Boniface Hospital","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8307-2760","authenticated-orcid":false,"given":"Paramjit S.","family":"Tappia","sequence":"additional","affiliation":[{"name":"Asper Clinical Research Institute, St. Boniface Hospital","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3450-0887","authenticated-orcid":false,"given":"Bram","family":"Ramjiawan","sequence":"additional","affiliation":[{"name":"University of Manitoba","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behzad","family":"Mansouri","sequence":"additional","affiliation":[{"name":"Brain, Vision and Concussion Clinic","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8573-6495","authenticated-orcid":false,"given":"Jitender","family":"Sareen","sequence":"additional","affiliation":[{"name":"University of Manitoba","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3863-2990","authenticated-orcid":false,"given":"Erin","family":"Knight","sequence":"additional","affiliation":[{"name":"University of Manitoba","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318238bba6"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.07.021"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.3390\/ph12020095"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1177\/1178632918819440"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1111\/febs.17049"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2004.07.006"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.370"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2021.1969"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b03334"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-022-06125-5"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2014.896913"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126912"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13962"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.07.035"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000000457"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14209"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2022.109389"},{"key":"refg18\/ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.copsyc.2018.07.014"},{"key":"refg19\/ref19","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0028-x"},{"key":"refg20\/ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.05.041"},{"key":"refg21\/ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-023-02720-8"},{"key":"refg22\/ref22","doi-asserted-by":"publisher","DOI":"10.2307\/3343343"},{"key":"refg23\/ref23","first-page":"100437","volume":"19","author":"Fischer B.","year":"2023","journal-title":"Lancet Reg. Health Am"},{"key":"refg24\/ref24","doi-asserted-by":"publisher","DOI":"10.1111\/add.12224"},{"key":"refg25\/ref25","doi-asserted-by":"publisher","DOI":"10.1186\/s12954-023-00906-7"},{"key":"refg26\/ref26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06030-7"},{"key":"refg27\/ref27","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25415"},{"key":"refg28\/ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadr.2023.100133"},{"key":"refg29\/ref29","volume-title":"Essentials of pain medicine and regional anesthesia. 2nd ed.","author":"Holtsman M.","year":"2005"},{"key":"refg30\/ref30","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2017.22"},{"key":"refg31\/ref31","doi-asserted-by":"publisher","DOI":"10.1111\/ijpp.12049"},{"key":"refg32\/ref32","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000005017"},{"key":"refg33\/ref33","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-052120-091058"},{"key":"refg34\/ref34","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3954"},{"key":"refg35\/ref35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2009.02724.x"},{"key":"refg36\/ref36","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/zxz105"},{"key":"refg37\/ref37","doi-asserted-by":"publisher","DOI":"10.1111\/ajad.12862"},{"key":"refg38\/ref38","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-021-00941-8"},{"key":"refg39\/ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjao.2023.100141"},{"key":"refg40\/ref40","doi-asserted-by":"publisher","DOI":"10.1007\/s40800-014-0002-0"},{"key":"refg41\/ref41","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00200-8"},{"key":"refg42\/ref42","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32812-X"},{"key":"refg43\/ref43","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.48118"},{"key":"refg44\/ref44","doi-asserted-by":"publisher","DOI":"10.3390\/ijms10030954"},{"key":"refg45\/ref45","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-8716(02)00011-X"},{"key":"refg46\/ref46","doi-asserted-by":"publisher","DOI":"10.1213\/01.ane.0000287652.42309.5c"},{"key":"refg47\/ref47","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2017.07.002"},{"key":"refg48\/ref48","first-page":"CD002207","volume":"2014","author":"Mattick R.P.","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"refg49\/ref49","volume-title":"The opioid epidemic: a geography in two phases, USDA Economic Research Service","author":"McGranahan D.A.","year":"2021"},{"key":"refg50\/ref50","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-019-00660-0"},{"key":"refg51\/ref51","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2024.1334850"},{"key":"refg52\/ref52","volume":"23","author":"Mogull S.A.","year":"2008","journal-title":"Am. Med. Writers Assoc. J"},{"key":"refg53\/ref53","volume-title":"America's addiction to opioids: heroin and prescription drug abuse","author":"National Institute on Drug Abuse (NIDA)","year":"2014"},{"key":"refg55\/ref55","first-page":"2016","volume-title":"In CADTH issues in emerging health technologies","author":"Ndegwa S.","year":"2016"},{"key":"refg56\/ref56","first-page":"CD011117","volume":"9","author":"Nielsen S.","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"refg57\/ref57","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2012.03870.x"},{"key":"refg58\/ref58","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp068113"},{"key":"refg59\/ref59","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810635"},{"key":"refg60\/ref60","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03101.x"},{"key":"refg61\/ref61","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.2.201"},{"key":"refg62\/ref62","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-8716(99)00071-X"},{"key":"refg63\/ref63","doi-asserted-by":"publisher","DOI":"10.1192\/j.eurpsy.2021.2219"},{"key":"refg64\/ref64","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.06.001"},{"key":"refg65\/ref65","doi-asserted-by":"publisher","DOI":"10.1080\/15563650.2020.1758325"},{"key":"refg66\/ref66","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.087254"},{"key":"refg67\/ref67","doi-asserted-by":"publisher","DOI":"10.1007\/s10879-020-09487-z"},{"key":"refg68\/ref68","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2004.00743.x"},{"key":"refg69\/ref69","doi-asserted-by":"publisher","DOI":"10.1080\/15412550802093108"},{"key":"refg70\/ref70","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94331"},{"key":"refg71\/ref71","doi-asserted-by":"publisher","DOI":"10.1037\/adb0000277"},{"key":"refg72\/ref72","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1604339"},{"key":"refg73\/ref73","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2019.06.006"},{"key":"refg74\/ref74","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00166"},{"key":"refg75\/ref75","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1049-18.2018"},{"key":"refg76\/ref76","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010617-052534"},{"key":"refg77\/ref77","doi-asserted-by":"publisher","DOI":"10.1111\/add.15601"},{"key":"refg78\/ref78","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j1550"},{"key":"refg79\/ref79","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2022.109507"},{"key":"refg80\/ref80","doi-asserted-by":"publisher","DOI":"10.1097\/PR9.0000000000000650"},{"key":"refg81\/ref81","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-062613-093100"},{"key":"refg82\/ref82","doi-asserted-by":"publisher","DOI":"10.3310\/hta23030"},{"key":"refg83\/ref83","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2016.16050548"},{"key":"refg84\/ref84","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107730"},{"key":"refg85\/ref85","doi-asserted-by":"publisher","DOI":"10.1111\/papr.13440"},{"key":"refg86\/ref86","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-020-00722-8"},{"key":"refg87\/ref87","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-019-0385-9"},{"key":"refg88\/ref88","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.0c00064"},{"key":"refg89\/ref89","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2020.108348"},{"key":"refg90\/ref90","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03283.x"},{"key":"refg91\/ref91","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20846"},{"key":"refg92\/ref92","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0661-4"},{"key":"refg93\/ref93","doi-asserted-by":"publisher","DOI":"10.1177\/0963689718811060"},{"key":"refg94\/ref94","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174294"},{"key":"refg95\/ref95","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113710"},{"key":"refg96\/ref96","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-018-9946-5"},{"key":"refg97\/ref97","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1753-2000-2-26","volume":"2","author":"Zito J.M.","year":"2008","journal-title":"Child Adolesc. Psychiatry Ment. Health"}],"container-title":["Canadian Journal of Physiology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdnsciencepub.com\/doi\/full-xml\/10.1139\/cjpp-2024-0281","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdnsciencepub.com\/doi\/pdf\/10.1139\/cjpp-2024-0281","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T11:57:25Z","timestamp":1751457445000},"score":1,"resource":{"primary":{"URL":"https:\/\/cdnsciencepub.com\/doi\/10.1139\/cjpp-2024-0281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":96,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,1]]}},"alternative-id":["10.1139\/cjpp-2024-0281"],"URL":"https:\/\/doi.org\/10.1139\/cjpp-2024-0281","relation":{},"ISSN":["0008-4212","1205-7541"],"issn-type":[{"value":"0008-4212","type":"print"},{"value":"1205-7541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]},"assertion":[{"value":"2025-02-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}