{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:00:49Z","timestamp":1790092849250,"version":"4.0.1"},"reference-count":102,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000026","name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["K23DA052682"],"award-info":[{"award-number":["K23DA052682"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA060066"],"award-info":[{"award-number":["R01DA060066"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuropsychopharmacol."],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Even during opioid agonist treatment (OAT) for opioid use disorder (OUD), chronic pain remains common and unrelieved, as opioids impair endogenous pain modulation. Cannabidiol (CBD) may represent a non-opioid adjunct, but its effects among persons with co-occurring OUD and chronic pain receiving OAT are unknown. We conducted a randomized, double-blind, placebo-controlled crossover study evaluating acute oral CBD (400, 800, 1200\u2009mg) effects on pain modulation, craving, and cognition among 23 participants (11 female) with co-occurring OUD and chronic pain receiving methadone (mean dose 85.7; SD: 29.7\u2009mg\/day). An opioid withholding model assessed CBD effects during two phases: Pre-OAT (delayed methadone dosing) and Post-OAT (following methadone administration). Primary outcomes included conditioned pain modulation (CPM; descending inhibition) and temporal summation of pain (TSP; ascending facilitation) assessed via quantitative sensory testing. Secondary outcomes included heat pain threshold and tolerance, and exploratory outcomes included cue-induced craving and cognitive performance. Pre-OAT, CBD was associated with a significant linear dose-response for enhanced descending pain inhibition (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.034; d\u2019=0.34 at 800\u2009mg, d\u2019=0.59 at 1200\u2009mg). Post-OAT, CBD 1200\u2009mg was associated with significant reduction of heat pain threshold relative to placebo (d\u2019=-0.63,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.017). CBD showed no significant effects on opioid craving. Cognitive performance was preserved across doses and CBD demonstrated a favorable safety profile. Among persons with co-occurring OUD and chronic pain receiving OAT, CBD demonstrated phase-dependent effects on pain modulation\u2014dose-dependent enhanced descending inhibition Pre-OAT but worsened pain sensitivity Post-OAT at higher doses. These findings highlight OAT timing as a critical consideration for CBD-based pain interventions.\n                  <\/jats:p>","DOI":"10.1038\/s41386-026-02443-w","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:19:35Z","timestamp":1779297575000},"page":"2280-2289","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An opioid-withholding human laboratory paradigm during opioid agonist treatment for opioid use disorder and chronic pain: Phase- and dose-dependent effects of cannabidiol"],"prefix":"10.1038","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8702-5436","authenticated-orcid":false,"given":"Gabriel","family":"P. A. Costa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Sofuoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Compton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-2923","authenticated-orcid":false,"given":"Mohini","family":"Ranganathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Pittman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-8215","authenticated-orcid":false,"given":"Joao P.","family":"De Aquino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"2443_CR1","unstructured":"Substance Abuse Mental Health Services Administration. in National Substance Use and Mental Health Services Survey (N-SUMHSS) (U.S. Department of Health and Human Services, Rockville, MD, 2024)."},{"key":"2443_CR2","unstructured":"National Center for Health Statistics. (Centers for Disease Control and Prevention (CDC), Hyattsville, MD, 2025)."},{"key":"2443_CR3","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1056\/NEJMra1511480","volume":"374","author":"ND Volkow","year":"2016","unstructured":"Volkow ND, Koob GF, McLellan AT. Neurobiologic Advances from the Brain Disease Model of Addiction. N Engl J Med. 2016;374:363\u201371.","journal-title":"N Engl J Med"},{"key":"2443_CR4","doi-asserted-by":"publisher","first-page":"j1550","DOI":"10.1136\/bmj.j1550","volume":"357","author":"L Sordo","year":"2017","unstructured":"Sordo L, Barrio G, Bravo MJ, Indave BI, Degenhardt L, Wiessing L, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550.","journal-title":"BMJ"},{"key":"2443_CR5","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.jpain.2022.08.008","volume":"24","author":"J Delorme","year":"2023","unstructured":"Delorme J, Kerckhove N, Authier N, Pereira B, Bertin C, Chenaf C. Systematic Review and Meta-Analysis of the Prevalence of Chronic Pain Among Patients With Opioid Use Disorder and Receiving Opioid Substitution Therapy. J Pain. 2023;24:192\u2013203.","journal-title":"J Pain"},{"key":"2443_CR6","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1056\/NEJMra1507771","volume":"374","author":"ND Volkow","year":"2016","unstructured":"Volkow ND, McLellan AT. Opioid Abuse in Chronic Pain-Misconceptions and Mitigation Strategies. N Engl J Med. 2016;374:1253\u201363.","journal-title":"N Engl J Med"},{"key":"2443_CR7","first-page":"59","volume":"9","author":"BB Dennis","year":"2015","unstructured":"Dennis BB, Bawor M, Naji L, Chan CK, Varenbut J, Paul J, et al. Impact of Chronic Pain on Treatment Prognosis for Patients with Opioid Use Disorder: A Systematic Review and Meta-analysis. Subst Abus. 2015;9:59\u201380.","journal-title":"Subst Abus"},{"key":"2443_CR8","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1080\/09540261.2018.1514369","volume":"30","author":"TJ Speed","year":"2018","unstructured":"Speed TJ, Parekh V, Coe W, Antoine D. Comorbid chronic pain and opioid use disorder: literature review and potential treatment innovations. Int Rev Psychiatry. 2018;30:136\u201346.","journal-title":"Int Rev Psychiatry"},{"key":"2443_CR9","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jsat.2017.03.006","volume":"77","author":"YI Hser","year":"2017","unstructured":"Hser YI, Mooney LJ, Saxon AJ, Miotto K, Bell DS, Huang D. Chronic pain among patients with opioid use disorder: Results from electronic health records data. J Subst Abus Treat. 2017;77:26\u201330.","journal-title":"J Subst Abus Treat"},{"key":"2443_CR10","doi-asserted-by":"publisher","first-page":"e146","DOI":"10.1093\/pm\/pnz228","volume":"21","author":"RR MacLean","year":"2020","unstructured":"MacLean RR, Spinola S, Manhapra A, Sofuoglu M. Systematic Review of Pain Severity and Opioid Craving in Chronic Pain and Opioid Use Disorder. Pain Med. 2020;21:e146\u2013e63.","journal-title":"Pain Med"},{"key":"2443_CR11","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.jpain.2020.10.005","volume":"22","author":"MS Ellis","year":"2021","unstructured":"Ellis MS, Kasper Z, Cicero T. Assessment of Chronic Pain Management in the Treatment of Opioid Use Disorder: Gaps in Care and Implications for Treatment Outcomes. J Pain. 2021;22:432\u201339.","journal-title":"J Pain"},{"key":"2443_CR12","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1111\/j.1360-0443.2007.01759.x","volume":"102","author":"MJ Larson","year":"2007","unstructured":"Larson MJ, Paasche-Orlow M, Cheng DM, Lloyd-Travaglini C, Saitz R, Samet JH. Persistent pain is associated with substance use after detoxification: a prospective cohort analysis. Addiction. 2007;102:752\u201360.","journal-title":"Addiction"},{"key":"2443_CR13","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1097\/AJP.0000000000000855","volume":"36","author":"PA Compton","year":"2020","unstructured":"Compton PA, Wasser TE, Cheatle MD. Increased Experimental Pain Sensitivity in Chronic Pain Patients Who Developed Opioid Use Disorder. Clin J Pain. 2020;36:667\u201374.","journal-title":"Clin J Pain"},{"key":"2443_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2022.1014768","volume":"16","author":"JA Higginbotham","year":"2022","unstructured":"Higginbotham JA, Markovic T, Massaly N, Mor\u00f3n JA. Endogenous opioid systems alterations in pain and opioid use disorder. Front Syst Neurosci. 2022;16:1014768.","journal-title":"Front Syst Neurosci"},{"key":"2443_CR15","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1007\/s13181-015-0521-9","volume":"12","author":"EA Salsitz","year":"2016","unstructured":"Salsitz EA. Chronic Pain, Chronic Opioid Addiction: a Complex Nexus. J Med Toxicol. 2016;12:54\u20137.","journal-title":"J Med Toxicol"},{"key":"2443_CR16","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.neuroscience.2016.06.029","volume":"338","author":"LA Roeckel","year":"2016","unstructured":"Roeckel LA, Le Coz GM, Gav\u00e9riaux-Ruff C, Simonin F. Opioid-induced hyperalgesia: Cellular and molecular mechanisms. Neuroscience. 2016;338:160\u201382.","journal-title":"Neuroscience"},{"key":"2443_CR17","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1124\/pr.112.005942","volume":"65","author":"JT Williams","year":"2013","unstructured":"Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, et al. Regulation of \u03bc-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharm Rev. 2013;65:223\u201354.","journal-title":"Pharm Rev"},{"key":"2443_CR18","doi-asserted-by":"publisher","first-page":"145","DOI":"10.36076\/ppj.2011\/14\/145","volume":"14","author":"M Lee","year":"2011","unstructured":"Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14:145\u201361.","journal-title":"Pain Physician"},{"key":"2443_CR19","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.biopsych.2019.05.023","volume":"87","author":"GF Koob","year":"2020","unstructured":"Koob GF. Neurobiology of Opioid Addiction: Opponent Process, Hyperkatifeia, and Negative Reinforcement. Biol Psychiatry. 2020;87:44\u201353.","journal-title":"Biol Psychiatry"},{"key":"2443_CR20","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s11916-010-0171-1","volume":"15","author":"DA Tompkins","year":"2011","unstructured":"Tompkins DA, Campbell CM. Opioid-induced hyperalgesia: clinically relevant or extraneous research phenomenon? Curr Pain Headache Rep. 2011;15:129\u201336.","journal-title":"Curr Pain Headache Rep"},{"key":"2443_CR21","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1001\/jamapsychiatry.2024.2176","volume":"81","author":"M Tr\u00f8stheim","year":"2024","unstructured":"Tr\u00f8stheim M, Eikemo M. Hyperalgesia in Patients With a History of Opioid Use Disorder: A Systematic Review and Meta-Analysis. JAMA Psychiatry. 2024;81:1108\u201317.","journal-title":"JAMA Psychiatry"},{"key":"2443_CR22","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S0304-3959(00)00391-2","volume":"90","author":"M Doverty","year":"2001","unstructured":"Doverty M, White JM, Somogyi AA, Bochner F, Ali R, Ling W. Hyperalgesic responses in methadone maintenance patients. Pain. 2001;90:91\u20136.","journal-title":"Pain"},{"key":"2443_CR23","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s40263-024-01069-0","volume":"38","author":"K Lang-Illievich","year":"2024","unstructured":"Lang-Illievich K, Lang J, Rumpold-Seitlinger G, Dorn C, Brenna CTA, Klivinyi C, et al. The Dose-Response Relationship between Opioid Agonist Therapy and Alterations in Pain Pathways in Patients with Opioid Use Disorders: A Cross-Sectional Study. CNS Drugs. 2024;38:281\u201390.","journal-title":"CNS Drugs"},{"key":"2443_CR24","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.jpain.2018.10.004","volume":"20","author":"MO Martel","year":"2019","unstructured":"Martel MO, Petersen K, Cornelius M, Arendt-Nielsen L, Edwards R. Endogenous Pain Modulation Profiles Among Individuals With Chronic Pain: Relation to Opioid Use. J Pain. 2019;20:462\u201371.","journal-title":"J Pain"},{"key":"2443_CR25","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.jpain.2008.10.003","volume":"10","author":"JL Hay","year":"2009","unstructured":"Hay JL, White JM, Bochner F, Somogyi AA, Semple TJ, Rounsefell B. Hyperalgesia in opioid-managed chronic pain and opioid-dependent patients. J Pain. 2009;10:316\u201322.","journal-title":"J Pain"},{"key":"2443_CR26","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1097\/j.pain.0000000000002268","volume":"162","author":"DP Finn","year":"2021","unstructured":"Finn DP, Haroutounian S, Hohmann AG, Krane E, Soliman N, Rice ASC. Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies. Pain. 2021;162:S5\u2013s25.","journal-title":"Pain"},{"key":"2443_CR27","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.2147\/JPR.S258433","volume":"13","author":"U Anand","year":"2020","unstructured":"Anand U, Jones B, Korchev Y, Bloom SR, Pacchetti B, Anand P, et al. CBD Effects on TRPV1 Signaling Pathways in Cultured DRG Neurons. J Pain Res. 2020;13:2269\u201378.","journal-title":"J Pain Res"},{"key":"2443_CR28","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s00213-020-05712-8","volume":"238","author":"SC Britch","year":"2021","unstructured":"Britch SC, Babalonis S, Walsh SL. Cannabidiol: pharmacology and therapeutic targets. Psychopharmacology. 2021;238:9\u201328.","journal-title":"Psychopharmacology"},{"key":"2443_CR29","doi-asserted-by":"publisher","first-page":"3364","DOI":"10.1098\/rstb.2011.0389","volume":"367","author":"AC Campos","year":"2012","unstructured":"Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimar\u00e3es FS. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci. 2012;367:3364\u201378.","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"2443_CR30","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1038\/39807","volume":"389","author":"MJ Caterina","year":"1997","unstructured":"Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389:816\u201324.","journal-title":"Nature"},{"key":"2443_CR31","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/978-3-030-57369-0_7","volume":"1264","author":"V Golub","year":"2021","unstructured":"Golub V, Reddy DS. Cannabidiol Therapy for Refractory Epilepsy and Seizure Disorders. Adv Exp Med Biol. 2021;1264:93\u2013110.","journal-title":"Adv Exp Med Biol"},{"key":"2443_CR32","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1097\/j.pain.0000000000001386","volume":"160","author":"D De Gregorio","year":"2019","unstructured":"De Gregorio D, McLaughlin RJ, Posa L, Ochoa-Sanchez R, Enns J, Lopez-Canul M, et al. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain. 2019;160:136\u201350.","journal-title":"Pain"},{"key":"2443_CR33","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.ejphar.2006.11.006","volume":"556","author":"B Costa","year":"2007","unstructured":"Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharm. 2007;556:75\u201383.","journal-title":"Eur J Pharm"},{"key":"2443_CR34","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/sj.bjp.0705920","volume":"143","author":"B Costa","year":"2004","unstructured":"Costa B, Giagnoni G, Franke C, Trovato AE, Colleoni M. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. Br J Pharm. 2004;143:247\u201350.","journal-title":"Br J Pharm"},{"key":"2443_CR35","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.1097\/j.pain.0000000000001052","volume":"158","author":"HT Philpott","year":"2017","unstructured":"Philpott HT, O\u2019Brien M, McDougall JJ. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain. 2017;158:2442\u201351.","journal-title":"Pain"},{"key":"2443_CR36","doi-asserted-by":"crossref","unstructured":"C\u00e1sedas G, Yarza-Sancho M, L\u00f3pez V. Cannabidiol (CBD): A Systematic review of clinical and preclinical evidence in the treatment of pain. Pharmaceuticals. 2024;17:1438.","DOI":"10.3390\/ph17111438"},{"key":"2443_CR37","doi-asserted-by":"publisher","first-page":"73","DOI":"10.2174\/157015907780866884","volume":"5","author":"JC Ashton","year":"2007","unstructured":"Ashton JC, Glass M. The cannabinoid CB2 receptor as a target for inflammation-dependent neurodegeneration. Curr Neuropharmacol. 2007;5:73\u201380.","journal-title":"Curr Neuropharmacol"},{"key":"2443_CR38","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1038\/s41419-024-07249-6","volume":"15","author":"A Sobue","year":"2024","unstructured":"Sobue A, Komine O, Endo F, Kakimi C, Miyoshi Y, Kawade N, et al. Microglial cannabinoid receptor type II stimulation improves cognitive impairment and neuroinflammation in Alzheimer\u2019s disease mice by controlling astrocyte activation. Cell Death Dis. 2024;15:858.","journal-title":"Cell Death Dis"},{"key":"2443_CR39","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1038\/s41386-019-0333-8","volume":"44","author":"CM Pretzsch","year":"2019","unstructured":"Pretzsch CM, Freyberg J, Voinescu B, Lythgoe D, Horder J, Mendez MA, et al. Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder. Neuropsychopharmacology. 2019;44:1398\u2013405.","journal-title":"Neuropsychopharmacology"},{"key":"2443_CR40","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.phrs.2017.02.022","volume":"119","author":"T Bakas","year":"2017","unstructured":"Bakas T, van Nieuwenhuijzen PS, Devenish SO, McGregor IS, Arnold JC, Chebib M. The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABA(A) receptors. Pharm Res. 2017;119:358\u201370.","journal-title":"Pharm Res"},{"key":"2443_CR41","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1111\/bcpt.13710","volume":"130","author":"J Peng","year":"2022","unstructured":"Peng J, Fan M, An C, Ni F, Huang W, Luo J. A narrative review of molecular mechanism and therapeutic effect of cannabidiol (CBD). Basic Clin Pharm Toxicol. 2022;130:439\u201356.","journal-title":"Basic Clin Pharm Toxicol"},{"key":"2443_CR42","doi-asserted-by":"publisher","first-page":"3637","DOI":"10.1007\/s00213-015-4023-x","volume":"232","author":"LR Gerak","year":"2015","unstructured":"Gerak LR, Zanettini C, Koek W, France CP. Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys. Psychopharmacology. 2015;232:3637\u201347.","journal-title":"Psychopharmacology"},{"key":"2443_CR43","doi-asserted-by":"publisher","first-page":"R5","DOI":"10.1016\/S0014-2999(01)00798-1","volume":"415","author":"A Siegling","year":"2001","unstructured":"Siegling A, Hofmann HA, Denzer D, Mauler F, De Vry J. Cannabinoid CB(1) receptor upregulation in a rat model of chronic neuropathic pain. Eur J Pharm. 2001;415:R5\u20137.","journal-title":"Eur J Pharm"},{"key":"2443_CR44","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s40263-024-01085-0","volume":"38","author":"L Weizman","year":"2024","unstructured":"Weizman L, Sharon H, Dayan L, Espaniol J, Brill S, Nahman-Averbuch H, et al. Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial. CNS Drugs. 2024;38:375\u201385.","journal-title":"CNS Drugs"},{"key":"2443_CR45","doi-asserted-by":"crossref","unstructured":"Oliveira D, Costa GPA, Fontenele R, C\u00f3rdoba-Delgado MA, Funaro MC, Campbell CM, et al. Quantitative sensory testing of pain in persons with opioid use disorder on opioid agonist treatment: a scoping review. Pain Med. 2026;27:243\u201353.","DOI":"10.1093\/pm\/pnaf132"},{"key":"2443_CR46","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.neucli.2020.11.002","volume":"51","author":"S Ramaswamy","year":"2021","unstructured":"Ramaswamy S, Wodehouse T. Conditioned pain modulation-A comprehensive review. Neurophysiol Clin. 2021;51:197\u2013208.","journal-title":"Neurophysiol Clin"},{"key":"2443_CR47","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1002\/(SICI)1097-4598(199702)20:2<198::AID-MUS10>3.0.CO;2-#","volume":"20","author":"D Yarnitsky","year":"1997","unstructured":"Yarnitsky D. Quantitative sensory testing. Muscle Nerve. 1997;20:198\u2013204.","journal-title":"Muscle Nerve"},{"key":"2443_CR48","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.jpain.2007.06.006","volume":"8","author":"R Staud","year":"2007","unstructured":"Staud R, Robinson ME, Price DD. Temporal summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patients. J Pain. 2007;8:893\u2013901.","journal-title":"J Pain"},{"key":"2443_CR49","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1176\/appi.ajp.2019.18101191","volume":"176","author":"YL Hurd","year":"2019","unstructured":"Hurd YL, Spriggs S, Alishayev J, Winkel G, Gurgov K, Kudrich C, et al. Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial. Am J Psychiatry. 2019;176:911\u201322.","journal-title":"Am J Psychiatry"},{"key":"2443_CR50","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1089\/imr.2022.0070","volume":"1","author":"J Suzuki","year":"2022","unstructured":"Suzuki J, Martin B, Prostko S, Chai PR, Weiss RD. Cannabidiol Effect on Cue-Induced Craving for Individuals with Opioid Use Disorder Treated with Buprenorphine: A Small Proof-of-Concept Open-Label Study. Integr Med Rep. 2022;1:157\u201363.","journal-title":"Integr Med Rep"},{"key":"2443_CR51","doi-asserted-by":"publisher","first-page":"e2455165","DOI":"10.1001\/jamanetworkopen.2024.55165","volume":"8","author":"J Ye","year":"2025","unstructured":"Ye J, Mehta S, Peterson H, Ibrahim A, Saeed G, Linsky S, et al. Neural Variability and Cognitive Control in Individuals With Opioid Use Disorder. JAMA Netw Open. 2025;8:e2455165.","journal-title":"JAMA Netw Open"},{"key":"2443_CR52","doi-asserted-by":"crossref","unstructured":"Patel M, Hasoon J, Diez Tafur R, Lo Bianco G, Abd-Elsayed A. The Impact of Chronic Pain on Cognitive Function. Brain Sci. 2025;15:559.","DOI":"10.3390\/brainsci15060559"},{"key":"2443_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2023.115335","volume":"326","author":"G Bhatia","year":"2023","unstructured":"Bhatia G, Ganesh R, Kulkarni A. Cognitive impairment in opioid use disorders: Is there a case for use of nootropics? Psychiatry Res. 2023;326:115335.","journal-title":"Psychiatry Res"},{"key":"2443_CR54","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1017\/S1355617725101057","volume":"31","author":"TR Bell","year":"2025","unstructured":"Bell TR, Elman JA, Gustavson DE, Lyons MJ, Fennema-Notestine C, Williams ME, et al. History of chronic pain and opioid use is associated with cognitive decline and mild cognitive impairment. J Int Neuropsychol Soc. 2025;31:307\u201317.","journal-title":"J Int Neuropsychol Soc"},{"key":"2443_CR55","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1007\/s12035-019-01831-2","volume":"57","author":"E Kozela","year":"2020","unstructured":"Kozela E, Krawczyk M, Kos T, Juknat A, Vogel Z, Popik P. Cannabidiol Improves Cognitive Impairment and Reverses Cortical Transcriptional Changes Induced by Ketamine, in Schizophrenia-Like Model in Rats. Mol Neurobiol. 2020;57:1733\u201347.","journal-title":"Mol Neurobiol"},{"key":"2443_CR56","doi-asserted-by":"publisher","first-page":"e0296586","DOI":"10.1371\/journal.pone.0296586","volume":"20","author":"MN Goodland","year":"2025","unstructured":"Goodland MN, Banerjee S, Niehoff ML, Young BJ, Macarthur H, Butler AA, et al. Cannabidiol improves learning and memory deficits and alleviates anxiety in 12-month-old SAMP8 mice. PLoS ONE. 2025;20:e0296586.","journal-title":"PLoS ONE"},{"key":"2443_CR57","doi-asserted-by":"crossref","unstructured":"Toledano RS, Akirav I. Cannabidiol prevents cognitive and social deficits in a male rat model of Alzheimer\u2019s disease through CB1 activation and inflammation modulation. Neuropsychopharmacology. 2025;50:1916\u201327.","DOI":"10.1038\/s41386-025-02213-0"},{"key":"2443_CR58","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.jpsychires.2021.09.007","volume":"143","author":"J Hotz","year":"2021","unstructured":"Hotz J, Fehlmann B, Papassotiropoulos A, de Quervain DJ, Schicktanz NS. Cannabidiol enhances verbal episodic memory in healthy young participants: A randomized clinical trial. J Psychiatr Res. 2021;143:327\u201333.","journal-title":"J Psychiatr Res"},{"key":"2443_CR59","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1089\/can.2017.0043","volume":"3","author":"N Solowij","year":"2018","unstructured":"Solowij N, Broyd SJ, Beale C, Prick JA, Greenwood LM, van Hell H, et al. Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial. Cannabis Cannabinoid Res. 2018;3:21\u201334.","journal-title":"Cannabis Cannabinoid Res"},{"key":"2443_CR60","doi-asserted-by":"publisher","first-page":"l4378","DOI":"10.1136\/bmj.l4378","volume":"366","author":"K Dwan","year":"2019","unstructured":"Dwan K, Li T, Altman DG, Elbourne D. CONSORT 2010 statement: extension to randomised crossover trials. Bmj. 2019;366:l4378.","journal-title":"Bmj"},{"key":"2443_CR61","doi-asserted-by":"publisher","first-page":"e081124","DOI":"10.1136\/bmj-2024-081124","volume":"389","author":"S Hopewell","year":"2025","unstructured":"Hopewell S, Chan A-W, Collins GS, Hr\u00f3bjartsson A, Moher D, Schulz KF, et al. CONSORT 2025 explanation and elaboration: updated guideline for reporting randomised trials. BMJ. 2025;389:e081124.","journal-title":"BMJ"},{"key":"2443_CR62","doi-asserted-by":"crossref","unstructured":"American Psychiatric A. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. American Psychiatric Association Publishing; 2013.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"2443_CR63","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s11419-024-00686-0","volume":"42","author":"I Papoutsis","year":"2024","unstructured":"Papoutsis I, Hatzidouka V, Ntoupa SP, Angelis A, Dona A, Sakelliadis E, et al. Determination of \u0394(9)-tetrahydrocannabinol, 11-nor-carboxy-\u0394(9)-tetrahydrocannabinol and cannabidiol in human plasma and urine after a commercial cannabidiol oil product intake. Forensic Toxicol. 2024;42:191\u2013201.","journal-title":"Forensic Toxicol"},{"key":"2443_CR64","unstructured":"NarcoCheck. THC urine test (marijuana). https:\/\/www.narcocheck.com\/en\/urine-drug-tests\/thc-test-marijuana.html."},{"key":"2443_CR65","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1097\/j.pain.0000000000000775","volume":"158","author":"RB Fillingim","year":"2017","unstructured":"Fillingim RB. Individual differences in pain: understanding the mosaic that makes pain personal. Pain. 2017;158:S11\u2013s18.","journal-title":"Pain"},{"key":"2443_CR66","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1007\/s40263-018-0578-5","volume":"32","author":"L Taylor","year":"2018","unstructured":"Taylor L, Gidal B, Blakey G, Tayo B, Morrison G. A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects. CNS Drugs. 2018;32:1053\u201367.","journal-title":"CNS Drugs"},{"key":"2443_CR67","doi-asserted-by":"publisher","first-page":"2977","DOI":"10.1111\/bcp.16027","volume":"90","author":"RR MacLean","year":"2024","unstructured":"MacLean RR, Spinola S, Pittman B, Meyerovich J, Szollosy SK, Wolkowicz NR, et al. The relationship of pain intensity and opioid craving with delayed methadone dose: A preliminary study of individuals with opioid use disorder. Br J Clin Pharm. 2024;90:2977\u201384.","journal-title":"Br J Clin Pharm"},{"key":"2443_CR68","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.pain.2006.01.041","volume":"123","author":"R Rolke","year":"2006","unstructured":"Rolke R, Baron R, Maier C, T\u00f6lle TR, Treede DR, Beyer A, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123:231\u201343.","journal-title":"Pain"},{"key":"2443_CR69","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1097\/ACO.0b013e32833c348b","volume":"23","author":"D Yarnitsky","year":"2010","unstructured":"Yarnitsky D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol. 2010;23:611\u20135.","journal-title":"Curr Opin Anaesthesiol"},{"key":"2443_CR70","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1097\/SPC.0000000000000055","volume":"8","author":"MH Ossipov","year":"2014","unstructured":"Ossipov MH, Morimura K, Porreca F. Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care. 2014;8:143\u201351.","journal-title":"Curr Opin Support Palliat Care"},{"key":"2443_CR71","doi-asserted-by":"publisher","first-page":"3779","DOI":"10.1172\/JCI43766","volume":"120","author":"MH Ossipov","year":"2010","unstructured":"Ossipov MH, Dussor GO, Porreca F. Central modulation of pain. J Clin Invest. 2010;120:3779\u201387.","journal-title":"J Clin Invest"},{"key":"2443_CR72","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1097\/j.pain.0000000000002719","volume":"164","author":"L Sirucek","year":"2023","unstructured":"Sirucek L, Ganley RP, Zeilhofer HU, Schweinhardt P. Diffuse noxious inhibitory controls and conditioned pain modulation: a shared neurobiology within the descending pain inhibitory system? Pain. 2023;164:463\u201368.","journal-title":"Pain"},{"key":"2443_CR73","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1053\/eujp.1999.0154","volume":"4","author":"PK Eide","year":"2000","unstructured":"Eide PK. Wind-up and the NMDA receptor complex from a clinical perspective. Eur J Pain. 2000;4:5\u201315.","journal-title":"Eur J Pain"},{"key":"2443_CR74","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.ejpain.2005.02.003","volume":"10","author":"R Rolke","year":"2006","unstructured":"Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, et al. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain. 2006;10:77\u201388.","journal-title":"Eur J Pain"},{"key":"2443_CR75","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2025.112753","volume":"274","author":"AC May","year":"2025","unstructured":"May AC, McNaughton-Long BA, Davis CB, Pleiman AJ, Buchfink C, Kuplicki R, et al. Reliability and clinical utility of heroin craving questionnaire factors in treatment-enrolled individuals with opioid use disorder. Drug Alcohol Depend. 2025;274:112753.","journal-title":"Drug Alcohol Depend"},{"key":"2443_CR76","unstructured":"Conners CK. Conners\u2019 continuous performance test. Multi-Health Systems North Tonawanda NY; 2000."},{"key":"2443_CR77","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1080\/13854049108403297","volume":"5","author":"J Brandt","year":"1991","unstructured":"Brandt J. The Hopkins Verbal Learning Test: Development of a new memory test with six equivalent forms. Clin Neuropsychol. 1991;5:125\u201342.","journal-title":"Clin Neuropsychol"},{"key":"2443_CR78","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3109\/00952998709001515","volume":"13","author":"L Handelsman","year":"1987","unstructured":"Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abus. 1987;13:293\u2013308.","journal-title":"Am J Drug Alcohol Abus"},{"key":"2443_CR79","doi-asserted-by":"publisher","first-page":"863","DOI":"10.3389\/fpsyg.2013.00863","volume":"4","author":"D Lakens","year":"2013","unstructured":"Lakens D. Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol. 2013;4:863.","journal-title":"Front Psychol"},{"key":"2443_CR80","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0376-8716(03)00190-X","volume":"72","author":"TB Mitchell","year":"2003","unstructured":"Mitchell TB, White JM, Somogyi AA, Bochner F. Comparative pharmacodynamics and pharmacokinetics of methadone and slow-release oral morphine for maintenance treatment of opioid dependence. Drug Alcohol Depend. 2003;72:85\u201394.","journal-title":"Drug Alcohol Depend"},{"key":"2443_CR81","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1111\/j.1365-2125.2005.02464.x","volume":"60","author":"J Hanna","year":"2005","unstructured":"Hanna J, Foster DJ, Salter A, Somogyi AA, White JM, Bochner F. Within- and between- subject variability in methadone pharmacokinetics and pharmacodynamics in methadone maintenance subjects. Br J Clin Pharm. 2005;60:404\u201313.","journal-title":"Br J Clin Pharm"},{"key":"2443_CR82","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-02891-6","volume":"19","author":"AH Sadaka","year":"2021","unstructured":"Sadaka AH, Ozuna AG, Ortiz RJ, Kulkarni P, Johnson CT, Bradshaw HB, et al. Cannabidiol has a unique effect on global brain activity: a pharmacological, functional MRI study in awake mice. J Transl Med. 2021;19:220.","journal-title":"J Transl Med"},{"key":"2443_CR83","doi-asserted-by":"publisher","first-page":"2620","DOI":"10.1111\/j.1476-5381.2011.01621.x","volume":"165","author":"EM Rock","year":"2012","unstructured":"Rock EM, Bolognini D, Limebeer CL, Cascio MG, Anavi-Goffer S, Fletcher PJ, et al. Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. Br J Pharm. 2012;165:2620\u201334.","journal-title":"Br J Pharm"},{"key":"2443_CR84","doi-asserted-by":"publisher","first-page":"239","DOI":"10.2174\/157015906778019527","volume":"4","author":"J Manzanares","year":"2006","unstructured":"Manzanares J, Julian M, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006;4:239\u201357.","journal-title":"Curr Neuropharmacol"},{"key":"2443_CR85","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/sj.bjp.0704327","volume":"134","author":"Tiziana Bisogno","year":"2001","unstructured":"Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharm. 2001;134:845\u201352.","journal-title":"Br J Pharm"},{"key":"2443_CR86","doi-asserted-by":"crossref","unstructured":"Coates S, Bardhi K, Lazarus P. Cannabinoid-Induced Inhibition of Morphine Glucuronidation and the Potential for In Vivo Drug-Drug Interactions. Pharmaceutics. 2024;16:418.","DOI":"10.3390\/pharmaceutics16030418"},{"key":"2443_CR87","doi-asserted-by":"crossref","unstructured":"Qian L, Beers JL, Jackson KD, Zhou Z. CBD and THC in Special Populations: Pharmacokinetics and Drug-Drug Interactions. Pharmaceutics. 2024;16:484.","DOI":"10.3390\/pharmaceutics16040484"},{"key":"2443_CR88","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3902740","volume":"2020","author":"M V\u00e1zquez","year":"2020","unstructured":"V\u00e1zquez M, Guevara N, Maldonado C, Guido PC, Schaiquevich P. Potential Pharmacokinetic Drug-Drug Interactions between Cannabinoids and Drugs Used for Chronic Pain. Biomed Res Int. 2020;2020:3902740.","journal-title":"Biomed Res Int"},{"key":"2443_CR89","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.ejphar.2015.10.049","volume":"769","author":"S Mercadante","year":"2015","unstructured":"Mercadante S. Opioid metabolism and clinical aspects. Eur J Pharm. 2015;769:71\u20138.","journal-title":"Eur J Pharm"},{"key":"2443_CR90","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1046\/j.1365-2125.1999.00921.x","volume":"47","author":"DJ Foster","year":"1999","unstructured":"Foster DJ, Somogyi AA, Bochner F. Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4. Br J Clin Pharm. 1999;47:403\u201312.","journal-title":"Br J Clin Pharm"},{"key":"2443_CR91","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2022.114076","volume":"435","author":"CHA Jesus","year":"2022","unstructured":"Jesus CHA, Ferreira MV, Gasparin AT, Rosa ES, Genaro K, Crippa JAS, et al. Cannabidiol enhances the antinociceptive effects of morphine and attenuates opioid-induced tolerance in the chronic constriction injury model. Behav Brain Res. 2022;435:114076.","journal-title":"Behav Brain Res"},{"key":"2443_CR92","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1111\/bcp.14973","volume":"88","author":"CA Arout","year":"2022","unstructured":"Arout CA, Haney M, Herrmann ES, Bedi G, Cooper ZD. A placebo-controlled investigation of the analgesic effects, abuse liability, safety and tolerability of a range of oral cannabidiol doses in healthy humans. Br J Clin Pharm. 2022;88:347\u201355.","journal-title":"Br J Clin Pharm"},{"key":"2443_CR93","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1097\/j.pain.0000000000002591","volume":"163","author":"M Dieterle","year":"2022","unstructured":"Dieterle M, Zurbriggen L, Mauermann E, Mercer-Chalmers-Bender K, Frei P, Ruppen W, et al. Pain response to cannabidiol in opioid-induced hyperalgesia, acute nociceptive pain, and allodynia using a model mimicking acute pain in healthy adults in a randomized trial (CANAB II). Pain. 2022;163:1919\u201328.","journal-title":"Pain"},{"key":"2443_CR94","doi-asserted-by":"publisher","first-page":"e175","DOI":"10.1097\/j.pain.0000000000003561","volume":"166","author":"CL Bergeria","year":"2025","unstructured":"Bergeria CL, Mun CJ, Speed TJ, Huhn AS, Wolinsky D, Vandrey R, et al. A within-subject, double-blind, placebo-controlled randomized evaluation of the combined effects of cannabidiol and hydromorphone in a human laboratory pain model. Pain. 2025;166:e175\u2013e84.","journal-title":"Pain"},{"key":"2443_CR95","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1093\/brain\/awm255","volume":"131","author":"G Henriksen","year":"2008","unstructured":"Henriksen G, Willoch F. Imaging of opioid receptors in the central nervous system. Brain. 2008;131:1171\u201396.","journal-title":"Brain"},{"key":"2443_CR96","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/S0893-133X(00)00110-X","volume":"23","author":"J-K Zubieta","year":"2000","unstructured":"Zubieta J-K, Greenwald MK, Lombardi U, Woods JH, Kilbourn MR, Jewett DM, et al. Buprenorphine-Induced Changes in Mu-Opioid Receptor Availability in Male Heroin-Dependent Volunteers: A Preliminary Study. Neuropsychopharmacology. 2000;23:326\u201334.","journal-title":"Neuropsychopharmacology"},{"key":"2443_CR97","doi-asserted-by":"publisher","first-page":"2000","DOI":"10.1038\/sj.npp.1300251","volume":"28","author":"MK Greenwald","year":"2003","unstructured":"Greenwald MK, Johanson CE, Moody DE, Woods JH, Kilbourn MR, Koeppe RA, et al. Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacology. 2003;28:2000\u20139.","journal-title":"Neuropsychopharmacology"},{"key":"2443_CR98","doi-asserted-by":"publisher","first-page":"2872","DOI":"10.1038\/npp.2016.99","volume":"41","author":"KE Courtney","year":"2016","unstructured":"Courtney KE, Ghahremani DG, Ray LA. The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans. Neuropsychopharmacology. 2016;41:2872\u201381.","journal-title":"Neuropsychopharmacology"},{"key":"2443_CR99","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1001\/jamapsychiatry.2016.3084","volume":"74","author":"M Luijten","year":"2017","unstructured":"Luijten M, Schellekens AF, K\u00fchn S, Machielse MW, Sescousse G. Disruption of Reward Processing in Addiction : An Image-Based Meta-analysis of Functional Magnetic Resonance Imaging Studies. JAMA Psychiatry. 2017;74:387\u201398.","journal-title":"JAMA Psychiatry"},{"key":"2443_CR100","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s41386-018-0232-4","volume":"44","author":"H Moningka","year":"2019","unstructured":"Moningka H, Lichenstein S, Worhunsky PD, DeVito EE, Scheinost D, Yip SW. Can neuroimaging help combat the opioid epidemic? A systematic review of clinical and pharmacological challenge fMRI studies with recommendations for future research. Neuropsychopharmacology. 2019;44:259\u201373.","journal-title":"Neuropsychopharmacology"},{"key":"2443_CR101","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/npp.2013.289","volume":"39","author":"VB Gradin","year":"2014","unstructured":"Gradin VB, Baldacchino A, Balfour D, Matthews K, Steele JD. Abnormal Brain Activity During a Reward and Loss Task in Opiate-Dependent Patients Receiving Methadone Maintenance Therapy. Neuropsychopharmacology. 2014;39:885\u201394.","journal-title":"Neuropsychopharmacology"},{"key":"2443_CR102","volume":"23","author":"GPA Costa","year":"2026","unstructured":"Costa GPA, Suh R, Sofuoglu M, De Aquino JP. Exploring the effects of cannabidiol on pain sensitivity using quantitative sensory testing among individuals receiving methadone or buprenorphine for opioid use disorder: an open-label, proof-of-concept study. Addict Behav Rep. 2026;23:100654.","journal-title":"Addict Behav Rep"}],"container-title":["Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02443-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02443-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02443-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:05:44Z","timestamp":1790089544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02443-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":102,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["2443"],"URL":"https:\/\/doi.org\/10.1038\/s41386-026-02443-w","relation":{},"ISSN":["0893-133X","1740-634X"],"issn-type":[{"value":"0893-133X","type":"print"},{"value":"1740-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"assertion":[{"value":"22 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. De Aquino has received medication provisions from Jazz Pharmaceuticals and Ananda Scientific. Additionally, Dr. De Aquino has been a compensated consultant for Boehringer Ingelheim. Remaining authors declare no competing interests. Jazz Pharmaceuticals had no role in study design, data collection, analysis, interpretation, or manuscript preparation.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}