{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:11:34Z","timestamp":1790687494612,"version":"4.1.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Key Research and Development Program of Guangzhou Science and Technology Bureau","award":["202206080012, 202201011827"],"award-info":[{"award-number":["202206080012, 202201011827"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82104951"],"award-info":[{"award-number":["82104951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010883","name":"Administration of Traditional Chinese Medicine of Guangdong Province","doi-asserted-by":"crossref","award":["20221081"],"award-info":[{"award-number":["20221081"]}],"id":[{"id":"10.13039\/501100010883","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M744100"],"award-info":[{"award-number":["2023M744100"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Provincial Enterprise Joint Fund","award":["2022A1515220120"],"award-info":[{"award-number":["2022A1515220120"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Psychopharmacology"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1007\/s00213-025-06781-3","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T12:33:01Z","timestamp":1743769981000},"page":"2021-2033","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Decoding the genetic links between substance use disorder and cancer vulnerability"],"prefix":"10.1007","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6433-5485","authenticated-orcid":false,"given":"Xin","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Kan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"6781_CR1","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s10654-023-00969-7","volume":"38","author":"AMF Turner","year":"2023","unstructured":"A MF, Turner MC, Warnakulasuriya S, Richardson DB, Hosseini B, Kamangar F, Pourshams A, Sewram V, Cronin-Fenton D, Etemadi A, Glass DC, Rahimi-Movaghar A, Sheikh M, Malekzadeh R, Schubauer-Berigan MK (2023) The carcinogenicity of opium consumption: a systematic review and meta-analysis. Eur J Epidemiol 38: 373-389.","journal-title":"Eur J Epidemiol"},{"key":"6781_CR2","doi-asserted-by":"publisher","first-page":"102229","DOI":"10.1016\/j.eclinm.2023.102229","volume":"64","author":"K Alcala","year":"2023","unstructured":"Alcala K, Poustchi H, Viallon V, Islami F, Pourshams A, Sadjadi A, Nemati S, Khoshnia M, Gharavi A, Roshandel G, Hashemian M, Dawsey SM, Abnet CC, Brennan P, Boffetta P, Zendehdel K, Kamangar F, Malekzadeh R, Sheikh M (2023) Incident cancers attributable to using opium and smoking cigarettes in the Golestan cohort study. EClinicalMedicine 64:102229","journal-title":"EClinicalMedicine"},{"key":"6781_CR3","doi-asserted-by":"publisher","first-page":"e0244285","DOI":"10.1371\/journal.pone.0244285","volume":"16","author":"U Barlass","year":"2021","unstructured":"Barlass U, Deshmukh A, Beck T, Bishehsari F (2021) Opioid use as a potential risk factor for pancreatic cancer in the united States: an analysis of state and National level databases. PLoS ONE 16:e0244285","journal-title":"PLoS ONE"},{"key":"6781_CR4","doi-asserted-by":"crossref","unstructured":"Birney E (2022) Mendelian Randomization. Cold Spring Harb Perspect Med 12","DOI":"10.1101\/cshperspect.a041302"},{"key":"6781_CR5","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","volume":"40","author":"J Bowden","year":"2016","unstructured":"Bowden J, Davey Smith G, Haycock PC, Burgess S (2016) Consistent Estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol 40:304\u2013314","journal-title":"Genet Epidemiol"},{"key":"6781_CR6","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1093\/aje\/kwu283","volume":"181","author":"S Burgess","year":"2015","unstructured":"Burgess S, Thompson SG (2015) Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol 181:251\u2013260","journal-title":"Am J Epidemiol"},{"key":"6781_CR7","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","volume":"32","author":"S Burgess","year":"2017","unstructured":"Burgess S, Thompson SG (2017) Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol 32:377\u2013389","journal-title":"Eur J Epidemiol"},{"key":"6781_CR8","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1002\/hep.32183","volume":"75","author":"L Chen","year":"2022","unstructured":"Chen L, Yang H, Li H, He C, Yang L, Lv G (2022a) Insights into modifiable risk factors of cholelithiasis: A Mendelian randomization study. Hepatology 75:785\u2013796","journal-title":"Hepatology"},{"key":"6781_CR9","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/s12967-022-03407-6","volume":"20","author":"X Chen","year":"2022","unstructured":"Chen X, Hong X, Gao W, Luo S, Cai J, Liu G, Huang Y (2022b) Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study. J Transl Med 20:216","journal-title":"J Transl Med"},{"key":"6781_CR10","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/s41416-022-02053-5","volume":"128","author":"MC Conroy","year":"2023","unstructured":"Conroy MC, Lacey B, Be\u0161evi\u0107 J, Omiyale W, Feng Q, Effingham M, Sellers J, Sheard S, Pancholi M, Gregory G, Busby J, Collins R, Allen NE (2023) UK biobank: a globally important resource for cancer research. Br J Cancer 128:519\u2013527","journal-title":"Br J Cancer"},{"key":"6781_CR11","doi-asserted-by":"publisher","first-page":"1211506","DOI":"10.3389\/fphar.2023.1211506","volume":"14","author":"I Creanga-Murariu","year":"2023","unstructured":"Creanga-Murariu I, Filipiuc LE, Cuciureanu M, Tamba BI, Alexa-Stratulat T (2023) Should oncologists trust cannabinoids? Front Pharmacol 14:1211506","journal-title":"Front Pharmacol"},{"key":"6781_CR12","unstructured":"Cunha ARD, Compton K, Xu R, Mishra R, Drangsholt MT, Antunes JLF, Kerr AR, Acheson AR, Lu D, Wallace LE, Kocarnik JM, Fu W, Dean FE, Pennini A, Henrikson HJ, Alam T,Ababneh E, Abd-Elsalam S, Abdoun M, Abidi H, Abubaker Ali H, Abu-Gharbieh E, Adane TD, Addo IY, Ahmad A, Ahmad S, Ahmed Rashid T, Akonde M, Al Hamad H, Alahdab F, Alimohamadi Y, Alipour V, Al-Maweri SA, Alsharif U, Ansari-Moghaddam A, Anwar SL, Anyasodor AE,Arabloo J, Aravkin AY, Aruleba RT, Asaad M, Ashraf T, Athari SS, Attia S, Azadnajafabad S, Azangou-Khyavy M, Badar M, Baghcheghi N, Banach M, Bardhan M, Barqawi HJ, Bashir NZ, Bashiri A, Benzian H, Bernabe E, Bhagat DS, Bhojaraja VS, Bj\u00f8rge T, Bouaoud S,Braithwaite D, Briko NI, Calina D, Carreras G, Chakraborty PA, Chattu VK, Chaurasia A, Chen MX, Cho WCS, Chu DT, Chukwu IS, Chung E, Cruz-Martins N, Dadras O, Dai X,Dandona L, Dandona R, Daneshpajouhnejad P, Darvishi Cheshmeh Soltani R, Darwesh AM,Debela SA, Derbew Molla M, Dessalegn FN, Dianati-Nasab M, Digesa LE, Dixit SG, Dixit A, Djalalinia S, El Sayed I, El Tantawi M, Enyew DB, Erku DA, Ezzeddini R, Fagbamigbe AF, Falzone L, Fetensa G, Fukumoto T, Gaewkhiew P, Gallus S, Gebrehiwot M, Ghashghaee A, Gill PS, Golechha M, Goleij P, Gomez RS, Gorini G, Guimaraes ALS, Gupta B, Gupta S, Gupta VB, Gupta VK, Haj-Mirzaian A, Halboub ES, Halwani R, Hanif A, Hariyani N,Harorani M, Hasani H, Hassan AM, Hassanipour S, Hassen MB, Hay SI, Hayat K, Herrera-Serna BY, Holla R, Horita N, Hosseinzadeh M, Hussain S, Ilesanmi OS, Ilic IM, Ilic MD, Isola G, Jaiswal A, Jani CT, Javaheri T, Jayarajah U, Jayaram S, Joseph N, Kadashetti V,Kandaswamy E, Karanth SD, Karaye IM, Kauppila JH, Kaur H, Keykhaei M, Khader YS, Khajuria H, Khanali J, Khatib MN, Khayat Kashani HR, Khazeei Tabari MA, Kim MS, Kompani F,Koohestani HR, Kumar GA, Kurmi OP, La Vecchia C, Lal DK, Landires I, Lasrado S, Ledda C, Lee YH, Libra M, Lim SS, Listl S, Lopukhov PD, Mafi AR, Mahumud RA, Malik AA, Mathur MR, Maulud SQ, Meena JK, Mehrabi Nasab E, Mestrovic T, Mirfakhraie R, Misganaw A,Misra S, Mithra P, Mohammad Y, Mohammadi M, Mohammadi E, Mokdad AH, Moni MA, Moraga P, Morrison SD, Mozaffari HR, Mubarik S, Murray CJL, Nair TS, Narasimha Swamy S, Narayana AI, Nassereldine H, Natto ZS, Nayak BP, Negru SM, Nggada HA, Nouraei H, Nu\u00f1ez-Samudio V, Oancea B, Olagunju AT, Omar Bali A, Padron-Monedero A, Padubidri JR, Pandey A,Pardhan S, Patel J, Pezzani R, Piracha ZZ, Rabiee N, Radhakrishnan V, Radhakrishnan RA, Rahmani AM, Rahmanian V, Rao CR, Rao SJ, Rath GK, Rawaf DL, Rawaf S, Rawassizadeh R, Razeghinia MS, Rezaei N, Rezaei N, Rezaei N, Rezapour A, Riad A, Roberts TJ, Romero-Rodr\u00edguez E, Roshandel G, S M, S NC, Saddik B, Saeb MR, Saeed U, Safaei M, Sahebazzamani M,Sahebkar A, Salek Farrokhi A, Samy AM, Santric-Milicevic MM, Sathian B, Satpathy M,\u0160ekerija M, Senthilkumaran S, Seylani A, Shafaat O, Shahsavari HR, Shamsoddin E, Sharew MM, Sharifi-Rad J, Shetty JK, Shivakumar KM, Shobeiri P, Shorofi SA, Shrestha S, Siddappa Malleshappa SK, Singh P, Singh JA, Singh G, Sinha DN, Solomon Y, Suleman M, Suliankatchi Abdulkader R, Taheri Abkenar Y, Talaat IM, Tan KK, Tbakhi A, Thiyagarajan A, Tiyuri A, Tovani-Palone MR, Unnikrishnan B, Vo B, Volovat SR, Wang C, Westerman R, Wickramasinghe ND, Xiao H, Yu C, Yuce D, Yunusa I, Zadnik V, Zare I, Zhang ZJ, Zoladl M, Force LM,Hugo FN (2023) The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019. JAMA Oncol"},{"key":"6781_CR13","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/fcp.12581","volume":"35","author":"S Dai","year":"2021","unstructured":"Dai S, Zhang X, Zhang P, Zheng X, Pang Q (2021) Fentanyl inhibits acute myeloid leukemia differentiated cells and committed progenitors via opioid receptor-independent suppression of Ras and STAT5 pathways. Fundam Clin Pharmacol 35:174\u2013183","journal-title":"Fundam Clin Pharmacol"},{"key":"6781_CR14","doi-asserted-by":"publisher","first-page":"6059","DOI":"10.1158\/0008-5472.CAN-08-1227","volume":"68","author":"C Friesen","year":"2008","unstructured":"Friesen C, Roscher M, Alt A, Miltner E (2008) Methadone, commonly used as maintenance medication for outpatient treatment of opioid dependence, kills leukemia cells and overcomes chemoresistance. Cancer Res 68:6059\u20136064","journal-title":"Cancer Res"},{"key":"6781_CR15","doi-asserted-by":"publisher","first-page":"e1916318","DOI":"10.1001\/jamanetworkopen.2019.16318","volume":"2","author":"M Ghasemiesfe","year":"2019","unstructured":"Ghasemiesfe M, Barrow B, Leonard S, Keyhani S, Korenstein D (2019) Association between marijuana use and risk of cancer: A systematic review and Meta-analysis. JAMA Netw Open 2:e1916318","journal-title":"JAMA Netw Open"},{"key":"6781_CR16","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s12904-019-0494-6","volume":"18","author":"P Good","year":"2019","unstructured":"Good P, Haywood A, Gogna G, Martin J, Yates P, Greer R, Hardy J (2019) Oral medicinal cannabinoids to relieve symptom burden in the palliative care of patients with advanced cancer: a double-blind, placebo controlled, randomised clinical trial of efficacy and safety of Cannabidiol (CBD). BMC Palliat Care 18:110","journal-title":"BMC Palliat Care"},{"key":"6781_CR17","doi-asserted-by":"publisher","first-page":"e329","DOI":"10.1016\/S1470-2045(23)00352-2","volume":"24","author":"E Gourd","year":"2023","unstructured":"Gourd E (2023) Growing liver cancer death rates in the UK call for healthier lifestyle choices. Lancet Oncol 24:e329","journal-title":"Lancet Oncol"},{"key":"6781_CR18","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1111\/1471-0528.15199","volume":"125","author":"E Hariton","year":"2018","unstructured":"Hariton E, Locascio JJ (2018) Randomised controlled trials - the gold standard for effectiveness research: study design: randomised controlled trials. BJOG 125:1716","journal-title":"BJOG"},{"key":"6781_CR19","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1158\/0008-5472.CAN-03-3720","volume":"64","author":"S Hart","year":"2004","unstructured":"Hart S, Fischer OM, Ullrich A (2004) Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE\/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res 64:1943\u20131950","journal-title":"Cancer Res"},{"key":"6781_CR20","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nrcardio.2017.78","volume":"14","author":"MV Holmes","year":"2017","unstructured":"Holmes MV, Ala-Korpela M, Smith GD (2017) Mendelian randomization in cardiometabolic disease: challenges in evaluating causality. Nat Rev Cardiol 14:577\u2013590","journal-title":"Nat Rev Cardiol"},{"key":"6781_CR21","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, Oprescu AM, Salsitz E (2019) 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 176:911\u2013922","journal-title":"Am J Psychiatry"},{"key":"6781_CR22","doi-asserted-by":"crossref","unstructured":"Irrera N, Bitto A, Sant\u2019Antonio E, Lauro R, Musolino C, Allegra A (2021) Pros and cons of the cannabinoid system in cancer: focus on hematological malignancies. Molecules 26","DOI":"10.3390\/molecules26133866"},{"key":"6781_CR23","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.jtho.2017.12.013","volume":"13","author":"J Jett","year":"2018","unstructured":"Jett J, Stone E, Warren G, Cummings KM (2018) Cannabis use, lung cancer, and related issues. J Thorac Oncol 13:480\u2013487","journal-title":"J Thorac Oncol"},{"key":"6781_CR25","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.jpainsymman.2009.06.008","volume":"39","author":"JR Johnson","year":"2010","unstructured":"Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT (2010) Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage 39:167\u2013179","journal-title":"J Pain Symptom Manage"},{"key":"6781_CR24","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1016\/S2215-0366(20)30339-4","volume":"7","author":"EC Johnson","year":"2020","unstructured":"Johnson EC, Demontis D, Thorgeirsson TE, Walters RK, Polimanti R, Hatoum AS, Sanchez-Roige S, Paul SE, Wendt FR, Clarke TK, Lai D, Reginsson GW, Zhou H, He J, Baranger DAA, Gudbjartsson DF, Wedow R, Adkins DE, Adkins AE, Alexander J, Bacanu SA, Bigdeli TB, Boden J, Brown SA, Bucholz KK, Bybjerg-Grauholm J, Corley RP, Degenhardt L, Dick DM, Domingue BW, Fox L, Goate AM, Gordon SD, Hack LM, Hancock DB, Hartz SM, Hickie IB, Hougaard DM, Krauter K, Lind PA, McClintick JN, McQueen MB, Meyers JL, Montgomery GW, Mors O, Mortensen PB, Nordentoft M, Pearson JF, Peterson RE, Reynolds MD, Rice JP, Runarsdottir V, Saccone NL, Sherva R, Silberg JL, Tarter RE, Tyrfingsson T, Wall TL, Webb BT, Werge T, Wetherill L, Wright MJ, Zellers S, Adams MJ, Bierut LJ, Boardman JD, Copeland WE, Farrer LA, Foroud TM, Gillespie NA, Grucza RA, Harris KM, Heath AC, Hesselbrock V, Hewitt JK, Hopfer CJ, Horwood J, Iacono WG, Johnson EO, Kendler KS, Kennedy MA, Kranzler HR, Madden PAF, Maes HH, Maher BS, Martin NG, McGue M, McIntosh AM, Medland SE, Nelson EC, Porjesz B, Riley BP, Stallings MC, Vanyukov MM, Vrieze S, Davis LK, Bogdan R, Gelernter J, Edenberg HJ, Stefansson K, B\u00f8rglum AD, Agrawal A (2020) A large-scale genome-wide association study meta-analysis of cannabis use disorder. Lancet Psychiatry 7:1032\u20131045","journal-title":"Lancet Psychiatry"},{"key":"6781_CR26","doi-asserted-by":"crossref","unstructured":"Kann AE, Jepsen P, Madsen LG, West J, Askgaard G (2023) Cause-specific mortality in patients with alcohol-related liver disease in Denmark: a population-based study. Lancet Gastroenterol Hepatol","DOI":"10.1016\/S0168-8278(23)00682-7"},{"key":"6781_CR27","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1213\/ANE.0000000000001293","volume":"123","author":"JY Kim","year":"2016","unstructured":"Kim JY, Ahn HJ, Kim JK, Kim J, Lee SH, Chae HB (2016) Morphine suppresses lung cancer cell proliferation through the interaction with opioid growth factor receptor: an in vitro and human lung tissue study. Anesth Analg 123:1429\u20131436","journal-title":"Anesth Analg"},{"key":"6781_CR28","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1189\/jlb.0303101","volume":"74","author":"TW Klein","year":"2003","unstructured":"Klein TW, Newton C, Larsen K, Lu L, Perkins I, Nong L, Friedman H (2003) The cannabinoid system and immune modulation. J Leukoc Biol 74:486\u2013496","journal-title":"J Leukoc Biol"},{"key":"6781_CR29","doi-asserted-by":"crossref","unstructured":"Kurki MI, Karjalainen J, Palta P, Sipil\u00e4 TP, Kristiansson K, Donner KM, Reeve MP, Laivuori H, Aavikko M, Kaunisto MA, Loukola A, Lahtela E, Mattsson H, Laiho P, Della Briotta Parolo P, Lehisto AA, Kanai M, Mars N, R\u00e4m\u00f6 J, Kiiskinen T, Heyne HO, Veerapen K, R\u00fceger S, Lemmel\u00e4 S, Zhou W, Ruotsalainen S, P\u00e4rn K, Hiekkalinna T, Koskelainen S, Paajanen T, Llorens V, Gracia-Tabuenca J, Siirtola H, Reis K, Elnahas AG, Sun B, Foley CN, Aalto-Set\u00e4l\u00e4 K, Alasoo K, Arvas M, Auro K, Biswas S, Bizaki-Vallaskangas A, Carpen O, Chen CY, Dada OA, Ding Z, Ehm MG, Eklund K, F\u00e4rkkil\u00e4 M, Finucane H, Ganna A, Ghazal A, Graham RR, Green EM, Hakanen A, Hautalahti M, Hedman \u00c5K, Hiltunen M, Hinttala R, Hovatta I, Hu X, Huertas-Vazquez A, Huilaja L, Hunkapiller J, Jacob H, Jensen JN, Joensuu H, John S, Julkunen V, Jung M, Junttila J, Kaarniranta K, K\u00e4h\u00f6nen M, Kajanne R, Kallio L, K\u00e4lvi\u00e4inen R, Kaprio J, Kerimov N, Kettunen J, Kilpel\u00e4inen E, Kilpi T, Klinger K, Kosma VM, Kuopio T, Kurra V, Laisk T, Laukkanen J, Lawless N, Liu A, Longerich S, M\u00e4gi R, M\u00e4kel\u00e4 J, M\u00e4kitie A, Malarstig A, Mannermaa A, Maranville J, Matakidou A, Meretoja T, Mozaffari SV, Niemi MEK, Niemi M, Niiranen T, CJ OD, Obeidat ME, Okafo G, Ollila HM, Palom\u00e4ki A, Palotie T, Partanen J, Paul DS, Pelkonen M, Pendergrass RK, Petrovski S, Pitk\u00e4ranta A, Platt A, Pulford D, Punkka E, Pussinen P, Raghavan N, Rahimov F, Rajpal D, Renaud NA, Riley-Gillis B, Rodosthenous R, Saarentaus E, Salminen A, Salminen E, Salomaa V, Schleutker J, Serpi R, Shen HY, Siegel R, Silander K, Siltanen S, Soini S, Soininen H, Sul JH, Tachmazidou I, Tasanen K, Tienari P, Toppila-Salmi S, Tukiainen T, Tuomi T, Turunen JA, Ulirsch JC, Vaura F, Virolainen P, Waring J, Waterworth D, Yang R, Nelis M, Reigo A, Metspalu A, Milani L, Esko T, Fox C, Havulinna AS, Perola M, Ripatti S, Jalanko A, Laitinen T, M\u00e4kel\u00e4 TP, Plenge R, McCarthy M, Runz H, Daly MJ, Palotie A (2023) FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 613: 508\u2013518","DOI":"10.1038\/s41586-022-05473-8"},{"key":"6781_CR30","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1002\/sim.3034","volume":"27","author":"DA Lawlor","year":"2008","unstructured":"Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G (2008) Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 27:1133\u20131163","journal-title":"Stat Med"},{"key":"6781_CR31","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1097\/ALN.0b013e31824b9512","volume":"116","author":"FE Lennon","year":"2012","unstructured":"Lennon FE, Moss J, Singleton PA (2012) The \u00b5-opioid receptor in cancer progression: is there a direct effect? Anesthesiology 116:940\u2013945","journal-title":"Anesthesiology"},{"key":"6781_CR32","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.neubiorev.2021.01.019","volume":"124","author":"S Lopez-Leon","year":"2021","unstructured":"Lopez-Leon S, Gonz\u00e1lez-Giraldo Y, Wegman-Ostrosky T, Forero DA (2021) Molecular genetics of substance use disorders: an umbrella review. Neurosci Biobehavioral Reviews 124:358\u2013369","journal-title":"Neurosci Biobehavioral Reviews"},{"key":"6781_CR33","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1213\/ANE.0b013e31820568af","volume":"112","author":"B Mathew","year":"2011","unstructured":"Mathew B, Lennon FE, Siegler J, Mirzapoiazova T, Mambetsariev N, Sammani S, Gerhold LM, LaRiviere PJ, Chen CT, Garcia JG, Salgia R, Moss J, Singleton PA (2011) The novel role of the mu opioid receptor in lung cancer progression: a laboratory investigation. Anesth Analg 112:558\u2013567","journal-title":"Anesth Analg"},{"key":"6781_CR34","doi-asserted-by":"publisher","first-page":"105729","DOI":"10.1016\/j.phrs.2021.105729","volume":"170","author":"G Morris","year":"2021","unstructured":"Morris G, Walder K, Kloiber S, Amminger P, Berk M, Bortolasci CC, Maes M, Puri BK, Carvalho AF (2021) The endocannabinoidome in neuropsychiatry: opportunities and potential risks. Pharmacol Res 170:105729","journal-title":"Pharmacol Res"},{"key":"6781_CR35","doi-asserted-by":"crossref","unstructured":"Muhammad I, Ibrahim MA, Kumarihamy M, Lambert JA, Zhang J, Mohammad MH, Khan SI, Pasco DS, Balachandran P (2023) Cannabinoid and opioid receptor affinity and modulation of Cancer-Related signaling pathways of Machaeriols and Machaeridiols from Machaerium Pers. Molecules. (Basel, Switzerland) 28","DOI":"10.3390\/molecules28104162"},{"key":"6781_CR36","doi-asserted-by":"publisher","first-page":"e664","DOI":"10.1016\/S2468-2667(23)00158-5","volume":"8","author":"RL Murray","year":"2023","unstructured":"Murray RL, O\u2019Dowd E (2023) Smoking cessation and lung cancer: never too late to quit. Lancet Public Health 8:e664\u2013e665","journal-title":"Lancet Public Health"},{"key":"6781_CR37","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1200\/JCO.22.02198","volume":"41","author":"JA Paice","year":"2023","unstructured":"Paice JA, Bohlke K, Barton D, Craig DS, El-Jawahri A, Hershman DL, Kong LR, Kurita GP, LeBlanc TW, Mercadante S, Novick KLM, Sedhom R, Seigel C, Stimmel J, Bruera E (2023) Use of opioids for adults with pain from cancer or cancer treatment: ASCO guideline. J Clin Oncol 41:914\u2013930","journal-title":"J Clin Oncol"},{"key":"6781_CR38","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1111\/add.14234","volume":"113","author":"A Peacock","year":"2018","unstructured":"Peacock A, Leung J, Larney S, Colledge S, Hickman M, Rehm J, Giovino GA, West R, Hall W, Griffiths P, Ali R, Gowing L, Marsden J, Ferrari AJ, Grebely J, Farrell M, Degenhardt L (2018) Global statistics on alcohol, tobacco and illicit drug use: 2017 status report. Addiction (Abingdon England) 113:1905\u20131926","journal-title":"Addiction (Abingdon England)"},{"key":"6781_CR39","doi-asserted-by":"publisher","first-page":"13892","DOI":"10.1038\/s41598-021-93411-5","volume":"11","author":"AS Reece","year":"2021","unstructured":"Reece AS, Hulse GK (2021) Epidemiological overview of multidimensional chromosomal and genome toxicity of cannabis exposure in congenital anomalies and cancer development. Sci Rep 11:13892","journal-title":"Sci Rep"},{"key":"6781_CR40","doi-asserted-by":"publisher","first-page":"e364","DOI":"10.1016\/S1470-2045(23)00320-0","volume":"24","author":"J Ritter","year":"2023","unstructured":"Ritter J, Allen S, Cohen PD, Fajardo AF, Marx K, Loggetto P, Auste C, Lewis H, de S\u00e1 Rodrigues KE, Hussain S, Omotola A, Bolous NS, Thirumurthy H, Essue BM, Steliarova-Foucher E, Huang IC, Meheus F, Bhakta N (2023) Financial hardship in families of children or adolescents with cancer: a systematic literature review. Lancet Oncol 24:e364\u2013e375","journal-title":"Lancet Oncol"},{"key":"6781_CR41","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12954-021-00468-6","volume":"18","author":"T Rosic","year":"2021","unstructured":"Rosic T, Kapoor R, Panesar B, Naji L, Chai DB, Sanger N, Marsh DC, Worster A, Thabane L, Samaan Z (2021) The association between cannabis use and outcome in Pharmacological treatment for opioid use disorder. Harm Reduct J 18:24","journal-title":"Harm Reduct J"},{"key":"6781_CR42","doi-asserted-by":"crossref","unstructured":"Sanderson E, Glymour MM, Holmes MV, Kang H, Morrison J, Munaf\u00f2 MR, Palmer T, Schooling CM, Wallace C, Zhao Q, Smith GD (2022) Mendelian randomization. Nat Rev Methods Primers 2","DOI":"10.1038\/s43586-021-00092-5"},{"key":"6781_CR43","first-page":"7","volume":"71","author":"RL Siegel","year":"2021","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin 71:7\u201333","journal-title":"CA Cancer J Clin"},{"key":"6781_CR44","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1001\/jama.2021.18236","volume":"326","author":"VW Skrivankova","year":"2021","unstructured":"Skrivankova VW, Richmond RC, Woolf BAR, Yarmolinsky J, Davies NM, Swanson SA, VanderWeele TJ, Higgins JPT, Timpson NJ, Dimou N, Langenberg C, Golub RM, Loder EW, Gallo V, Tybjaerg-Hansen A, Davey Smith G, Egger M, Richards JB (2021) Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: the STROBE-MR statement. JAMA 326:1614\u20131621","journal-title":"JAMA"},{"key":"6781_CR45","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209\u2013249","journal-title":"CA Cancer J Clin"},{"key":"6781_CR46","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.neo.2020.12.011","volume":"23","author":"S Tripolt","year":"2021","unstructured":"Tripolt S, Neubauer HA, Knab VM, Elmer DP, Aberger F, Moriggl R, Fux DA (2021) Opioids drive breast cancer metastasis through the \u03b4-opioid receptor and oncogenic STAT3. Neoplasia 23:270\u2013279","journal-title":"Neoplasia"},{"key":"6781_CR47","doi-asserted-by":"publisher","first-page":"e574","DOI":"10.1210\/clinem\/dgad089","volume":"108","author":"X Wang","year":"2023","unstructured":"Wang X, Zhao C, Feng H, Li G, He L, Yang L, Liang Y, Tan X, Xu Y, Cui R, Sun Y, Guo S, Zhao G, Zhang J, Ai S (2023a) Associations of insomnia with insulin resistance traits: A Cross-sectional and Mendelian randomization study. J Clin Endocrinol Metab 108:e574\u2013e582","journal-title":"J Clin Endocrinol Metab"},{"key":"6781_CR48","doi-asserted-by":"crossref","unstructured":"Wang YX, Mitsunami M, Manson JE, Gaskins AJ, Rich-Edwards JW, Wang L, Zhang C, Chavarro JE (2023b) Association of gestational diabetes with subsequent Long-Term risk of mortality. JAMA Intern Med","DOI":"10.1001\/jamainternmed.2023.4401"},{"key":"6781_CR49","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1111\/jcpe.13782","volume":"50","author":"Z Wang","year":"2023","unstructured":"Wang Z, Li S, Tan D, Abudourexiti W, Yu Z, Zhang T, Ding C, Gong J (2023c) Association between inflammatory bowel disease and periodontitis: A bidirectional two-sample Mendelian randomization study. J Clin Periodontol 50:736\u2013743","journal-title":"J Clin Periodontol"},{"key":"6781_CR50","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1186\/s12967-023-04335-9","volume":"21","author":"Y Xiang","year":"2023","unstructured":"Xiang Y, Zhang C, Wang J, Cheng Y, Wang L, Tong Y, Yan D (2023) Identification of host gene-microbiome associations in colorectal cancer patients using Mendelian randomization. J Transl Med 21:535","journal-title":"J Transl Med"},{"key":"6781_CR51","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1093\/ije\/dyx034","volume":"46","author":"OO Yavorska","year":"2017","unstructured":"Yavorska OO, Burgess S (2017) MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol 46:1734\u20131739","journal-title":"Int J Epidemiol"},{"key":"6781_CR52","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/0024-3205(84)90651-9","volume":"35","author":"IS Zagon","year":"1984","unstructured":"Zagon IS, McLaughlin PJ (1984) Duration of opiate receptor Blockade determines tumorigenic response in mice with neuroblastoma: a role for endogenous opioid systems in cancer. Life Sci 35:409\u2013416","journal-title":"Life Sci"},{"key":"6781_CR53","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1002\/mds.29386","volume":"38","author":"R Zeng","year":"2023","unstructured":"Zeng R, Wang J, Zheng C, Jiang R, Tong S, Wu H, Zhuo Z, Yang Q, Leung FW, Sha W, Chen H (2023) Lack of causal associations of inflammatory bowel disease with Parkinson\u2019s disease and other neurodegenerative disorders. Mov Disord 38:1082\u20131088","journal-title":"Mov Disord"},{"key":"6781_CR54","doi-asserted-by":"crossref","unstructured":"Zhou Q, Zhang Z, Long S, Li W, Wang B, Liang N (2022) Opioids in cancer: the \u03ba\u2013opioid receptor (Review). Molecular medicine reports 25.","DOI":"10.3892\/mmr.2021.12560"}],"container-title":["Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-025-06781-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00213-025-06781-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-025-06781-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T12:14:13Z","timestamp":1757160853000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00213-025-06781-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":54,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["6781"],"URL":"https:\/\/doi.org\/10.1007\/s00213-025-06781-3","relation":{},"ISSN":["0033-3158","1432-2072"],"issn-type":[{"value":"0033-3158","type":"print"},{"value":"1432-2072","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]},"assertion":[{"value":"1 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare that they have no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}