{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T12:27:02Z","timestamp":1775910422028,"version":"3.50.1"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Psychopharmacology"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Rationale\/Objectives<\/jats:title>\n                <jats:p>Targeting cannabinoid receptor type 1 (CB1R) has shown promise for treating opioid withdrawal symptoms. This study aimed to investigate the efficacy of a specific CB1R negative allosteric modulator (NAM), Org27569, in reducing both naloxone-precipitated and protracted withdrawal symptoms in oxycodone-dependent mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Mice received escalating doses of oxycodone (9\u201333\u00a0mg\/kg IP) or saline twice daily for 9 days, followed by a final dose of oxycodone (33\u00a0mg\/kg) or saline in the morning of day 9. In one cohort, the impact of Org27569 (3, 10, and 30\u00a0mg\/kg) on naloxone (10\u00a0mg\/kg IP) precipitated withdrawal symptoms was assessed. In another cohort, Org27569 (3\u00a0mg\/kg) effects on the acquisition of conditioned place aversion to naloxone (0.6\u00a0mg\/kg) precipitated opioid withdrawal, on behaviour following a 7\u20139-day abstinence period, and on naloxone (0.6\u00a0mg\/kg) precipitated withdrawal-induced escape behaviour in a novel assay were assessed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Although Org27569 decreased opioid withdrawal-induced jumping at doses of 10 and 30\u00a0mg\/kg, these effects were confounded by reduced locomotion. At all doses tested, Org27569 had a modest inhibitory effect on gastrointestinal motility. At the lower dose of 3\u00a0mg\/kg, which was not confounded by locomotor effects, Org27569 did not impact naloxone-precipitated withdrawal-induced jumping, acquisition of oxycodone withdrawal-induced conditioned place aversion, or naloxone-precipitated withdrawal-induced escape behaviour in a novel assay. A clear protracted opioid withdrawal phenotype was not observed in assays of anxiety-like or social behaviour.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Org27569 effects on negative affective-like symptoms were confounded by locomotor effects and effects on gastrointestinal motility were not opioid withdrawal specific. Further studies are needed in a model that produces a more pronounced protracted withdrawal syndrome.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00213-024-06591-z","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T07:03:00Z","timestamp":1714201380000},"page":"1705-1717","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of CB1 receptor negative allosteric modulator Org27569 on oxycodone withdrawal symptoms in mice"],"prefix":"10.1007","volume":"241","author":[{"given":"Rhianne L.","family":"Scicluna","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas A.","family":"Everett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connie J.","family":"Badolato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca B.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Bowen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"issue":"2","key":"6591_CR1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.neulet.2012.03.047","volume":"515","author":"H Azizi","year":"2012","unstructured":"Azizi H, Ranjbar-Slamloo Y, Semnanian S (2012) Height-dependent difference in the expression of naloxone-induced withdrawal jumping behavior in morphine dependent rats. Neurosci Lett 515(2):174\u2013176","journal-title":"Neurosci Lett"},{"issue":"2","key":"6591_CR2","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1124\/mol.112.080879","volume":"83","author":"GL Baillie","year":"2013","unstructured":"Baillie GL, Horswill JG, Anavi-Goffer S, Reggio PH, Bolognini D, Abood ME, McAllister S, Strange PG, Stephens GJ, Pertwee RG, Ross RA (2013) CB(1) receptor allosteric modulators display both agonist and signaling pathway specificity. Mol Pharmacol 83(2):322\u2013338","journal-title":"Mol Pharmacol"},{"issue":"1","key":"6591_CR3","first-page":"25","volume":"22","author":"HC Becker","year":"1998","unstructured":"Becker HC (1998) Kindling in alcohol withdrawal. Alcohol Health Res World 22(1):25\u201333","journal-title":"Alcohol Health Res World"},{"issue":"5","key":"6591_CR4","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1111\/adb.12405","volume":"22","author":"JAJ Becker","year":"2017","unstructured":"Becker JAJ, Kieffer BL, Le Merrer J (2017) Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol. Addict Biol 22(5):1205\u20131217","journal-title":"Addict Biol"},{"key":"6591_CR5","doi-asserted-by":"crossref","unstructured":"Bentzley BSPD, Barth KSDO, Back SEPD, Book SWMD (2015). Discontinuation of Buprenorphine maintenance therapy: perspectives and outcomes. J Subst Abuse Treat 52: 48\u201357","DOI":"10.1016\/j.jsat.2014.12.011"},{"issue":"4\u20135","key":"6591_CR6","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.physbeh.2007.11.007","volume":"93","author":"J Bergman","year":"2008","unstructured":"Bergman J, Delatte MS, Paronis CA, Vemuri K, Thakur GA, Makriyannis A (2008) Some effects of CB1 antagonists with inverse agonist and neutral biochemical properties. Physiol Behav 93(4\u20135):666\u2013670","journal-title":"Physiol Behav"},{"issue":"3","key":"6591_CR7","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/BF00426828","volume":"49","author":"HN Bhargava","year":"1976","unstructured":"Bhargava HN (1976) Effect of some cannabinoids on naloxone-precipitated abstinence in morphine-dependent mice. Psychopharmacology 49(3):267\u2013270","journal-title":"Psychopharmacology"},{"issue":"2","key":"6591_CR8","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/S0014-2999(00)00689-0","volume":"406","author":"EA Blokhina","year":"2000","unstructured":"Blokhina EA, Sukhotina IA, Bespalov AY (2000) Pretreatment with morphine potentiates naloxone-conditioned place aversion in mice: effects of NMDA receptor antagonists. Eur J Pharmacol 406(2):227\u2013232","journal-title":"Eur J Pharmacol"},{"key":"6591_CR9","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/j.neubiorev.2021.11.017","volume":"132","author":"MT Bowen","year":"2022","unstructured":"Bowen MT, George O, Muskiewicz DE, Hall FS (2022) Factors contributing to the escalation of alcohol consumption. Neurosci Biobehavioral Reviews 132:730\u2013756","journal-title":"Neurosci Biobehavioral Reviews"},{"issue":"3","key":"6591_CR10","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1111\/ejn.14580","volume":"51","author":"IM Bravo","year":"2020","unstructured":"Bravo IM, Luster BR, Flanigan ME, Perez PJ, Cogan ES, Schmidt KT, McElligott ZA (2020) Divergent behavioral responses in protracted opioid withdrawal in male and female C57BL\/6J mice. Eur J Neurosci 51(3):742\u2013754","journal-title":"Eur J Neurosci"},{"issue":"4","key":"6591_CR11","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1111\/bph.12329","volume":"170","author":"EE Cawston","year":"2013","unstructured":"Cawston EE, Redmond WJ, Breen CM, Grimsey NL, Connor M, Glass M (2013) Real-time characterization of cannabinoid receptor 1 (CB1) allosteric modulators reveals novel mechanism of action. Br J Pharmacol 170(4):893\u2013907","journal-title":"Br J Pharmacol"},{"issue":"6","key":"6591_CR12","doi-asserted-by":"publisher","first-page":"e00069","DOI":"10.1002\/prp2.69","volume":"2","author":"Y Ding","year":"2014","unstructured":"Ding Y, Qiu Y, Jing L, Thorn DA, Zhang Y, Li JX (2014) Behavioral effects of the cannabinoid CB1 receptor allosteric modulator ORG27569 in rats. Pharmacol Res Perspect 2(6):e00069","journal-title":"Pharmacol Res Perspect"},{"key":"6591_CR14","doi-asserted-by":"crossref","unstructured":"Elkin LA, Kay M, Higgins JJ, Wobbrock JO (2021) An Aligned Rank Transform Procedure for Multifactor Contrast Tests. The 34th Annual ACM Symposium on User Interface Software and Technology. Virtual Event, USA, Association for Computing Machinery: 754\u2013768","DOI":"10.1145\/3472749.3474784"},{"key":"6591_CR15","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.ejphar.2016.07.006","volume":"789","author":"RM Enga","year":"2016","unstructured":"Enga RM, Jackson A, Damaj MI, Beardsley PM (2016) Oxycodone physical dependence and its oral self-administration in C57BL\/6J mice. Eur J Pharmacol 789:75\u201380","journal-title":"Eur J Pharmacol"},{"issue":"3","key":"6591_CR16","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1097\/ADM.0000000000000474","volume":"13","author":"M Fishman","year":"2019","unstructured":"Fishman M, Tirado C, Alam D, Gullo K, Clinch T, Gorodetzky CW (2019) Safety and Efficacy of Lofexidine for medically managed opioid withdrawal: a Randomized Controlled Clinical Trial. J Addict Med 13(3):169\u2013176","journal-title":"J Addict Med"},{"issue":"2","key":"6591_CR17","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1176\/appi.ps.201300235","volume":"65","author":"CA Fullerton","year":"2014","unstructured":"Fullerton CA, Kim M, Thomas CP, Lyman DR, Montejano LB, Dougherty RH, Daniels AS, Ghose SS, Delphin-Rittmon ME (2014) Medication-assisted treatment with methadone: assessing the evidence. Psychiatr Serv 65(2):146\u2013157","journal-title":"Psychiatr Serv"},{"key":"6591_CR18","unstructured":"Gamage FT (2013) Differential effects of endocannabinoid catabolic inhibitors on opioid withdrawal in mice. PhD Dissertation"},{"issue":"2","key":"6591_CR19","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1097\/FBP.0000000000000027","volume":"25","author":"FT Gamage","year":"2014","unstructured":"Gamage FT, Ignatowska-Jankowska MB, Wiley LJ, Abdelrahman RM, Trembleau AL, Greig AI, Thakur GG, Tichkule HR, Poklis HJ, Ross HR, Pertwee HR, Lichtman HA (2014) In-vivo pharmacological evaluation of the CB1-receptor allosteric modulator Org-27569. Behav Pharmacol 25(2):182\u2013185","journal-title":"Behav Pharmacol"},{"key":"6591_CR20","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.drugalcdep.2014.11.015","volume":"146","author":"TF Gamage","year":"2015","unstructured":"Gamage TF, Ignatowska-Jankowska BM, Muldoon PP, Cravatt BF, Damaj MI, Lichtman AH (2015) Differential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice. Drug Alcohol Depend 146:7\u201316","journal-title":"Drug Alcohol Depend"},{"issue":"2","key":"6591_CR21","doi-asserted-by":"publisher","first-page":"e237","DOI":"10.1016\/j.ddtec.2012.08.004","volume":"10","author":"Z-G Gao","year":"2013","unstructured":"Gao Z-G, Jacobson KA (2013) Allosteric modulation and functional selectivity of G protein-coupled receptors. Drug Discovery Today Technol 10(2):e237\u2013e243","journal-title":"Drug Discovery Today Technol"},{"issue":"2","key":"6591_CR22","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s00213-011-2478-y","volume":"220","author":"JA Garcia-Carmona","year":"2012","unstructured":"Garcia-Carmona JA, Almela P, Baroja-Mazo A, Milanes MV, Laorden ML (2012) Restricted role of CRF1 receptor for the activity of brainstem catecholaminergic neurons in the negative state of morphine withdrawal. Psychopharmacology 220(2):379\u2013393","journal-title":"Psychopharmacology"},{"issue":"2","key":"6591_CR23","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1345\/aph.1M347","volume":"44","author":"EC Gish","year":"2010","unstructured":"Gish EC, Miller JL, Honey BL, Johnson PN (2010) Lofexidine, an {alpha}2-receptor agonist for opioid detoxification. Ann Pharmacother 44(2):343\u2013351","journal-title":"Ann Pharmacother"},{"issue":"3","key":"6591_CR24","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.neuint.2012.06.011","volume":"61","author":"I Gomez-Milanes","year":"2012","unstructured":"Gomez-Milanes I, Almela P, Garcia-Carmona JA, Garcia-Gutierrez MS, Aracil-Fernandez A, Manzanares J, Milanes Maquilon MV, Laorden ML (2012) Accumbal dopamine, noradrenaline and serotonin activity after naloxone-conditioned place aversion in morphine-dependent mice. Neurochem Int 61(3):433\u2013440","journal-title":"Neurochem Int"},{"key":"6591_CR25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.drugalcdep.2017.02.020","volume":"176","author":"CW Gorodetzky","year":"2017","unstructured":"Gorodetzky CW, Walsh SL, Martin PR, Saxon AJ, Gullo KL, Biswas K (2017) A phase III, randomized, multi-center, double blind, placebo controlled study of safety and efficacy of lofexidine for relief of symptoms in individuals undergoing inpatient opioid withdrawal. Drug Alcohol Depend 176:79\u201388","journal-title":"Drug Alcohol Depend"},{"key":"6591_CR26","doi-asserted-by":"publisher","first-page":"106474","DOI":"10.1016\/j.phrs.2022.106474","volume":"185","author":"V Iyer","year":"2022","unstructured":"Iyer V, Rangel-Barajas C, Woodward TJ, Kulkarni A, Cantwell L, Crystal JD, Mackie K, Rebec GV, Thakur GA, Hohmann AG (2022) Negative allosteric modulation of CB(1) cannabinoid receptor signaling suppresses opioid-mediated reward. Pharmacol Res 185:106474","journal-title":"Pharmacol Res"},{"key":"6591_CR27","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.drugalcdep.2014.08.004","volume":"143","author":"L Jing","year":"2014","unstructured":"Jing L, Qiu Y, Zhang Y, Li JX (2014) Effects of the cannabinoid CB1 receptor allosteric modulator ORG 27569 on reinstatement of cocaine- and methamphetamine-seeking behavior in rats. Drug Alcohol Depend 143:251\u2013256","journal-title":"Drug Alcohol Depend"},{"key":"6591_CR28","doi-asserted-by":"crossref","unstructured":"Koob GF (2019) Neurobiology of Opioid Addiction. Opponent Process, Hyperkatifeia, and Negative Reinforcement. Biol Psychiatry","DOI":"10.1016\/j.biopsych.2019.05.023"},{"key":"6591_CR29","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1146\/annurev.psych.59.103006.093548","volume":"59","author":"GF Koob","year":"2008","unstructured":"Koob GF, Le Moal M (2008) Addiction and the brain antireward system. Annu Rev Psychol 59:29\u201353","journal-title":"Annu Rev Psychol"},{"issue":"5","key":"6591_CR30","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1089\/can.2021.0089","volume":"7","author":"C Kudrich","year":"2022","unstructured":"Kudrich C, Hurd YL, Salsitz E, Wang AL (2022) Adjunctive Management of Opioid Withdrawal with the Nonopioid Medication Cannabidiol. Cannabis Cannabinoid Res 7(5):569\u2013581","journal-title":"Cannabis Cannabinoid Res"},{"issue":"8","key":"6591_CR31","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1001\/jama.2012.9289","volume":"308","author":"BM Kuehn","year":"2012","unstructured":"Kuehn BM (2012) Methadone overdose deaths rise with increased prescribing for pain. JAMA 308(8):749\u2013750","journal-title":"JAMA"},{"key":"6591_CR32","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3389\/fnbeh.2020.00145","volume":"14","author":"M La-Vu","year":"2020","unstructured":"La-Vu M, Tobias BC, Schuette PJ, Adhikari A (2020) To Approach or avoid: an introductory overview of the study of anxiety using rodent assays. Front Behav Neurosci 14:145","journal-title":"Front Behav Neurosci"},{"issue":"20","key":"6591_CR33","doi-asserted-by":"publisher","first-page":"4790","DOI":"10.1111\/bph.13250","volume":"172","author":"RB Laprairie","year":"2015","unstructured":"Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM (2015) Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol 172(20):4790\u20134805","journal-title":"Br J Pharmacol"},{"issue":"5400","key":"6591_CR34","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1126\/science.283.5400.401","volume":"283","author":"C Ledent","year":"1999","unstructured":"Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, Beslot F, B\u00f6hme GA, Imperato A, Pedrazzini T, Roques BP, Vassart G, Fratta W, Parmentier M (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283(5400):401\u2013404","journal-title":"Science"},{"issue":"3","key":"6591_CR35","first-page":"1007","volume":"298","author":"AH Lichtman","year":"2001","unstructured":"Lichtman AH, Sheikh SM, Loh HH, Martin BR (2001) Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice. J Pharmacol Exp Ther 298(3):1007\u20131014","journal-title":"J Pharmacol Exp Ther"},{"issue":"7","key":"6591_CR36","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1046\/j.1460-9568.2002.01957.x","volume":"15","author":"M Maccarrone","year":"2002","unstructured":"Maccarrone M, Valverde O, Barbaccia ML, Casta\u00f1\u00e9 A, Maldonado R, Ledent C, Parmentier M, Finazzi-Agr\u00f2 A (2002) Age-related changes of anandamide metabolism in CB1 cannabinoid receptor knockout mice: correlation with behaviour. Eur J Neurosci 15(7):1178\u20131186","journal-title":"Eur J Neurosci"},{"key":"6591_CR37","doi-asserted-by":"publisher","first-page":"105508","DOI":"10.1016\/j.phrs.2021.105508","volume":"166","author":"LJ Martin","year":"2021","unstructured":"Martin LJ, Banister SD, Bowen MT (2021) Understanding the complex pharmacology of cannabidiol: mounting evidence suggests a common binding site with cholesterol. Pharmacol Res 166:105508","journal-title":"Pharmacol Res"},{"issue":"8","key":"6591_CR38","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1038\/sj.bjp.0703990","volume":"132","author":"M Mas-Nieto","year":"2001","unstructured":"Mas-Nieto M, Pommier B, Tzavara ET, Caneparo A, Da Nascimento S, Le Fur G, Roques BP, Noble F (2001) Reduction of opioid dependence by the CB(1) antagonist SR141716A in mice: evaluation of the interest in pharmacotherapy of opioid addiction. Br J Pharmacol 132(8):1809","journal-title":"Br J Pharmacol"},{"issue":"9","key":"6591_CR39","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1038\/s41593-018-0209-y","volume":"21","author":"A Mathis","year":"2018","unstructured":"Mathis A, Mamidanna P, Cury KM, Abe T, Murthy VN, Mathis MW, Bethge M (2018) DeepLabCut: markerless pose estimation of user-defined body parts with deep learning. Nat Neurosci 21(9):1281\u20131289","journal-title":"Nat Neurosci"},{"issue":"1","key":"6591_CR40","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.beem.2008.09.003","volume":"23","author":"FA Moreira","year":"2009","unstructured":"Moreira FA, Grieb M, Lutz B (2009) Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: focus on anxiety and depression. Best Pract Res Clin Endocrinol Metab 23(1):133\u2013144","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"15","key":"6591_CR41","doi-asserted-by":"publisher","first-page":"5357","DOI":"10.1523\/JNEUROSCI.5017-09.2010","volume":"30","author":"K Mozhui","year":"2010","unstructured":"Mozhui K, Karlsson RM, Kash TL, Ihne J, Norcross M, Patel S, Farrell MR, Hill EE, Graybeal C, Martin KP, Camp M, Fitzgerald PJ, Ciobanu DC, Sprengel R, Mishina M, Wellman CL, Winder DG, Williams RW, Holmes A (2010) Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability. J Neurosci 30(15):5357\u20135367","journal-title":"J Neurosci"},{"key":"6591_CR42","doi-asserted-by":"publisher","first-page":"172840","DOI":"10.1016\/j.pbb.2019.172840","volume":"190","author":"M Mustafa","year":"2020","unstructured":"Mustafa M, Donvito G, Moncayo L, Swafford A, Poklis J, Grauer R, Olszewska T, Ignatowska-Jankowska B, Kendall DA, Lu D, Lichtman AH (2020) In vivo evaluation of the CB(1) allosteric modulator LDK1258 reveals CB(1)-receptor independent behavioral effects. Pharmacol Biochem Behav 190:172840","journal-title":"Pharmacol Biochem Behav"},{"issue":"2","key":"6591_CR43","doi-asserted-by":"publisher","first-page":"e13150","DOI":"10.1111\/adb.13150","volume":"27","author":"F Navarrete","year":"2022","unstructured":"Navarrete F, Gasparyan A, Manzanares J (2022) CBD-mediated regulation of heroin withdrawal-induced behavioural and molecular changes in mice. Addict Biol 27(2):e13150","journal-title":"Addict Biol"},{"issue":"15","key":"6591_CR44","doi-asserted-by":"publisher","first-page":"3397","DOI":"10.1097\/00001756-199810260-00012","volume":"9","author":"M Navarro","year":"1998","unstructured":"Navarro M, Chowen J, Carrera MRA, del Arco I, Villan\u00faa MA, Martin Y, Roberts AJ, Koob GF, de Fonseca FR (1998) CB1 cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats. NeuroReport 9(15):3397\u20133402","journal-title":"NeuroReport"},{"key":"6591_CR45","doi-asserted-by":"publisher","first-page":"173106","DOI":"10.1016\/j.pbb.2021.173106","volume":"201","author":"J Navarro-Zaragoza","year":"2021","unstructured":"Navarro-Zaragoza J, Mart\u00ednez-Laorden E, Teruel-Fern\u00e1ndez FJ, G\u00f3mez-Murcia V, C\u00e1novas A, Milan\u00e9s MV, Laorden ML, Almela P (2021) Naloxone-induced conditioned place aversion score and extinction period are higher in C57BL\/6J morphine-dependent mice than in Swiss: role of HPA axis. Pharmacol Biochem Behav 201:173106","journal-title":"Pharmacol Biochem Behav"},{"key":"6591_CR46","unstructured":"NIDA (2023) Drug overdose death rats. N. National Institute on Drug Abuse"},{"issue":"3","key":"6591_CR47","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1007\/s00213-005-0022-7","volume":"181","author":"MC Olmstead","year":"2005","unstructured":"Olmstead MC, Burns LH (2005) Ultra-low-dose naltrexone suppresses rewarding effects of opiates and aversive effects of opiate withdrawal in rats. Psychopharmacology 181(3):576\u2013581","journal-title":"Psychopharmacology"},{"issue":"6","key":"6591_CR48","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1136\/gut.48.6.859","volume":"48","author":"RG Pertwee","year":"2001","unstructured":"Pertwee RG (2001) Cannabinoids and the gastrointestinal tract. Gut 48(6):859\u2013867","journal-title":"Gut"},{"issue":"5","key":"6591_CR49","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1124\/mol.105.016162","volume":"68","author":"MR Price","year":"2005","unstructured":"Price MR, Baillie GL, Thomas A, Stevenson LA, Easson M, Goodwin R, McLean A, McIntosh L, Goodwin G, Walker G, Westwood P, Marrs J, Thomson F, Cowley P, Christopoulos A, Pertwee RG, Ross RA (2005) Allosteric modulation of the cannabinoid CB1 receptor. Mol Pharmacol 68(5):1484\u20131495","journal-title":"Mol Pharmacol"},{"issue":"4","key":"6591_CR50","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41386-018-0292-5","volume":"44","author":"K Rasmussen","year":"2019","unstructured":"Rasmussen K, White DA, Acri JB (2019) NIDA\u2019s medication development priorities in response to the Opioid Crisis: ten most wanted. Neuropsychopharmacology 44(4):657\u2013659","journal-title":"Neuropsychopharmacology"},{"issue":"22","key":"6591_CR51","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1016\/S0024-3205(00)00547-6","volume":"66","author":"T Rubino","year":"2000","unstructured":"Rubino T, Massi P, Vigan\u00f2 D, Fuzio D, Parolaro D (2000) Long-term treatment with SR141716A, the CB1 receptor antagonist, influences morphine withdrawal syndrome. Life Sci (1973) 66(22):2213\u20132219","journal-title":"Life Sci (1973)"},{"issue":"23\u201324","key":"6591_CR52","doi-asserted-by":"publisher","first-page":"3991","DOI":"10.1007\/s00213-016-4425-4","volume":"233","author":"V Sanchez","year":"2016","unstructured":"Sanchez V, Carpenter MD, Yohn NL, Blendy JA (2016) Long-lasting effects of adolescent oxycodone exposure on reward-related behavior and gene expression in mice. Psychopharmacology 233(23\u201324):3991\u20134002","journal-title":"Psychopharmacology"},{"key":"6591_CR53","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.neuroscience.2013.04.034","volume":"248","author":"JL Scavone","year":"2013","unstructured":"Scavone JL, Sterling RC, Van Bockstaele EJ (2013) Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal. Neuroscience 248:637\u2013654","journal-title":"Neuroscience"},{"issue":"4","key":"6591_CR54","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1056\/NEJMra1604339","volume":"375","author":"MA Schuckit","year":"2016","unstructured":"Schuckit MA (2016) Treatment of Opioid-Use disorders. N Engl J Med 375(4):357\u2013368","journal-title":"N Engl J Med"},{"key":"6591_CR55","unstructured":"Scicluna RL, Wilson BB, Thelaus SH, Arnold JC, McGregor IS, Bowen MT (2022) Cannabidiol reduced the severity of gastrointestinal symptoms of opioid withdrawal in male and female mice. Cannabis Cannabinoid Res"},{"issue":"5","key":"6591_CR56","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.neuropharm.2012.06.046","volume":"63","author":"KA Seely","year":"2012","unstructured":"Seely KA, Brents LK, Franks LN, Rajasekaran M, Zimmerman SM, Fantegrossi WE, Prather PL (2012) AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: implications for opioid\/cannabinoid interaction studies. Neuropharmacology 63(5):905\u2013915","journal-title":"Neuropharmacology"},{"issue":"12","key":"6591_CR57","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1038\/s41589-019-0387-2","volume":"15","author":"Z Shao","year":"2019","unstructured":"Shao Z, Yan W, Chapman K, Ramesh K, Ferrell AJ, Yin J, Wang X, Xu Q, Rosenbaum DM (2019) Structure of an allosteric modulator bound to the CB1 cannabinoid receptor. Nat Chem Biol 15(12):1199\u20131205","journal-title":"Nat Chem Biol"},{"issue":"1","key":"6591_CR58","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/sj.npp.1300782","volume":"31","author":"JR Shoblock","year":"2006","unstructured":"Shoblock JR, Maidment NT (2006) Constitutively active micro opioid receptors mediate the enhanced conditioned aversive effect of naloxone in morphine-dependent mice. Neuropsychopharmacology 31(1):171\u2013177","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"6591_CR59","first-page":"256","volume":"126","author":"T Trang","year":"2006","unstructured":"Trang T, Ma W, Chabot J-G, Quirion R, Jhamandas K (2006) Spinal modulation of calcitonin gene-related peptide by endocannabinoids in the development of opioid physical dependence. Pain (Amsterdam) 126(1):256\u2013271","journal-title":"Pain (Amsterdam)"},{"issue":"4","key":"6591_CR60","doi-asserted-by":"publisher","first-page":"e265","DOI":"10.1097\/ADM.0000000000000922","volume":"16","author":"NB Varshneya","year":"2022","unstructured":"Varshneya NB, Thakrar AP, Hobelmann JG, Dunn KE, Huhn AS (2022) Evidence of buprenorphine-precipitated withdrawal in persons who use Fentanyl. J Addict Med 16(4):e265\u2013e268","journal-title":"J Addict Med"},{"issue":"6","key":"6591_CR61","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1097\/AJP.0b013e318169d03b","volume":"24","author":"M Von Korff","year":"2008","unstructured":"Von Korff M, Saunders K, Thomas Ray G, Boudreau D, Campbell C, Merrill J, Sullivan MD, Rutter CM, Silverberg MJ, Banta-Green C, Weisner C (2008) De facto long-term opioid therapy for noncancer pain. Clin J Pain 24(6):521\u2013527","journal-title":"Clin J Pain"},{"issue":"4","key":"6591_CR62","doi-asserted-by":"publisher","first-page":"701","DOI":"10.33549\/physiolres.933106","volume":"65","author":"F Wang","year":"2016","unstructured":"Wang F, Jing X, Yang J, Wang H, Xiang R, Han W, Liu X, Wu C (2016) The role of the insular cortex in naloxone-induced conditioned place aversion in morphine-dependent mice. Physiol Res 65(4):701\u2013709","journal-title":"Physiol Res"},{"issue":"1","key":"6591_CR63","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.biopsych.2019.07.027","volume":"87","author":"L Welsch","year":"2020","unstructured":"Welsch L, Bailly J, Darcq E, Kieffer BL (2020) The negative affect of protracted opioid abstinence: Progress and perspectives from Rodent models. Biol Psychiatry 87(1):54\u201363","journal-title":"Biol Psychiatry"},{"issue":"2","key":"6591_CR64","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1080\/02791072.2003.10400007","volume":"35","author":"DR Wesson","year":"2003","unstructured":"Wesson DR, Ling W (2003) The clinical opiate Withdrawal Scale (COWS). J Psychoact Drugs 35(2):253\u2013259","journal-title":"J Psychoact Drugs"},{"key":"6591_CR67","doi-asserted-by":"publisher","first-page":"187","DOI":"10.3389\/fphar.2016.00187","volume":"7","author":"KL Wills","year":"2016","unstructured":"Wills KL, Parker LA (2016) Effect of pharmacological modulation of the Endocannabinoid System on Opiate Withdrawal: a review of the Preclinical Animal Literature. Front Pharmacol 7:187","journal-title":"Front Pharmacol"},{"issue":"22","key":"6591_CR65","doi-asserted-by":"publisher","first-page":"4291","DOI":"10.1007\/s00213-014-3575-5","volume":"231","author":"K Wills","year":"2014","unstructured":"Wills K, Vemuri K, Kalmar A, Lee A, Limebeer C, Makriyannis A, Parker L (2014) CB 1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats. Psychopharmacology 231(22):4291\u20134300","journal-title":"Psychopharmacology"},{"issue":"4","key":"6591_CR66","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1037\/bne0000201","volume":"131","author":"KL Wills","year":"2017","unstructured":"Wills KL, DeVuono MV, Limebeer CL, Vemuri K, Makriyannis A, Parker LA (2017) CB1 receptor antagonism in the bed nucleus of the stria terminalis interferes with affective opioid withdrawal in rats. Behav Neurosci 131(4):304\u2013311","journal-title":"Behav Neurosci"},{"key":"6591_CR68","doi-asserted-by":"crossref","unstructured":"Wobbrock J, Findlater L, Gergle D, Higgins J (2011) The aligned rank transform for nonparametric factorial analyses using only anova procedures. Conference on Human Factors in Computing Systems, ACM","DOI":"10.1145\/1978942.1978963"},{"issue":"8","key":"6591_CR69","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/s41589-022-01038-y","volume":"18","author":"X Yang","year":"2022","unstructured":"Yang X, Wang X, Xu Z, Wu C, Zhou Y, Wang Y, Lin G, Li K, Wu M, Xia A, Liu J, Cheng L, Zou J, Yan W, Shao Z, Yang S (2022) Molecular mechanism of allosteric modulation for the cannabinoid receptor CB1. Nat Chem Biol 18(8):831\u2013840","journal-title":"Nat Chem Biol"}],"updated-by":[{"DOI":"10.1007\/s00213-024-06605-w","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000}}],"container-title":["Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-024-06591-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00213-024-06591-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-024-06591-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T10:05:47Z","timestamp":1721815547000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00213-024-06591-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,27]]},"references-count":68,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["6591"],"URL":"https:\/\/doi.org\/10.1007\/s00213-024-06591-z","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s00213-024-06605-w","asserted-by":"object"}]},"ISSN":["0033-3158","1432-2072"],"issn-type":[{"value":"0033-3158","type":"print"},{"value":"1432-2072","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,27]]},"assertion":[{"value":"6 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s00213-024-06605-w","URL":"https:\/\/doi.org\/10.1007\/s00213-024-06605-w","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"In addition to his academic role, Associate Professor Michael Bowen is co-founder and Chief Scientific Officer of Kinoxis Therapeutics Pty Ltd, an Australian-based company developing novel small molecule treatments for brain disorders, including the treatment of opioid withdrawal and Associate Professor Michael Bowen receives research funding from Kinoxis Therapeutics. This industry work does not involve the research presented in this manuscript. Rhianne Scicluna, Nicholas Everett, Connie Badolato and Bianca Wilson do not have any conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}