{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T03:21:23Z","timestamp":1794626483111,"version":"4.9.1"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009437","name":"Tel Aviv Sourasky Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009437","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cannabis Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tetrahydrocannabinol (THC) has shown efficacy in alleviating chronic pain, particularly in disorders characterized by central sensitization. Offset analgesia (OA) and conditioned pain modulation (CPM) are key biomarkers used to evaluate central pain modulation. This study aimed to compare the effects of THC on OA and CPM in fibromyalgia syndrome (FMS), a prototypical condition of central sensitization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a randomized, double-blind, placebo-controlled crossover design, 23 FMS patients participated in two experimental sessions. Each session included the McGill Pain Questionnaire, visual analogue scale (VAS) assessments, and evaluations of OA and CPM, conducted both before and after sublingual administration of either THC (0.2\u00a0mg\/kg) or placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      THC significantly reduced spontaneous pain ratings on the McGill scale compared to both baseline and placebo (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.01 and\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.02, respectively). THC also significantly enhanced OA relative to baseline and placebo (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.04 and\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.008), while no effect was observed on CPM (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.27). Notably, baseline OA magnitude significantly predicted THC-induced pain relief (R\u00b2 = 0.404,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.003), whereas CPM did not show a significant association (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.121).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is the first study to evaluate THC\u2019s distinct effects on central pain modulation using both OA and CPM. THC selectively enhanced OA without influencing CPM, highlighting differential neural mechanisms underlying these paradigms. Furthermore, OA predicted treatment response, suggesting its potential as a biomarker for personalized cannabinoid-based therapies in FMS and other central sensitization disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      The study was prospectively registered on ClinicalTrials.gov (ID: NCT05644054) at 1.1.2023. Further details can be found at:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT05644054?locStr=Israel%26;country=Israel%26;cond=fibromyalgi215a%20%26;intr=THC%26;aggFilters=status:not%20rec%26;rank=1\" ext-link-type=\"uri\">https:\/\/clinicaltrials.gov\/study\/NCT05644054?locStr=Israel&amp;country=Israel&amp;cond=fibromyalgi215a%20&amp;intr=THC&amp;aggFilters=status:not%20rec&amp;rank=1<\/jats:ext-link>\n                      <jats:bold>\n                        <jats:italic>.<\/jats:italic>\n                      <\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42238-025-00348-x","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T10:23:51Z","timestamp":1762424631000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The impact of tetrahydrocannabinol on central pain modulation in chronic pain: a randomized clinical comparative study of offset analgesia and conditioned pain modulation in fibromyalgia"],"prefix":"10.1186","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4356-1211","authenticated-orcid":false,"given":"Yara","family":"Agbaria","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raz","family":"Preger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Aloush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob N.","family":"Ablin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haggai","family":"Sharon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giris","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"348_CR1","doi-asserted-by":"publisher","DOI":"10.1177\/17448069221074991","volume":"18","author":"BJ Alter","year":"2022","unstructured":"Alter BJ, Santosa H, Nguyen QH, Huppert TJ, Wasan AD. Offset analgesia is associated with opposing modulation of medial versus dorsolateral prefrontal cortex activations: a functional near-infrared spectroscopy study. Mol Pain. 2022;18:17448069221074991.","journal-title":"Mol Pain"},{"issue":"1","key":"348_CR2","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1093\/rheumatology\/kei183","volume":"45","author":"DR Blake","year":"2006","unstructured":"Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology. 2006;45(1):50\u20132.","journal-title":"Rheumatology"},{"issue":"12","key":"348_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare11121794","volume":"11","author":"K Bu\u0142dy\u015b","year":"2023","unstructured":"Bu\u0142dy\u015b K, G\u00f3rnicki T, Ka\u0142ka D, Szuster E, Biernikiewicz M, Markuszewski L, et al. What do we know about nociplastic pain? Healthcare. 2023;11(12):1794.","journal-title":"Healthcare"},{"issue":"1","key":"348_CR4","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.semarthrit.2014.01.001","volume":"44","author":"B Cagnie","year":"2014","unstructured":"Cagnie B, Coppieters I, Denecker S, Six J, Danneels L, Meeus M. Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI. Semin Arthritis Rheum. 2014;44(1):68\u201375.","journal-title":"Semin Arthritis Rheum"},{"key":"348_CR5","unstructured":"Chakrabarty S, Zoorob R. Fibromyalgia. Afp. 2007;76(2):247\u201354."},{"issue":"10","key":"348_CR6","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1093\/pm\/pnaa303","volume":"21","author":"C Chaves","year":"2020","unstructured":"Chaves C, Bittencourt PCT, Pelegrini A. Ingestion of a THC-rich cannabis oil in people with fibromyalgia: a randomized, double-blind, placebo-controlled clinical trial. Pain Med. 2020;21(10):2212\u20138.","journal-title":"Pain Med"},{"issue":"1","key":"348_CR7","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1097\/PSY.0b013e3182408f04","volume":"74","author":"I Cifre","year":"2012","unstructured":"Cifre I, Sitges C, Fraiman D, Mu\u00f1oz M\u00c1, Balenzuela P, Gonz\u00e1lez-Rold\u00e1n A, et al. Disrupted functional connectivity of the pain network in fibromyalgia. Psychosom Med. 2012;74(1):55\u201362.","journal-title":"Psychosom Med"},{"issue":"5","key":"348_CR8","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1037\/pha0000465","volume":"30","author":"MJ De Vita","year":"2022","unstructured":"De Vita MJ, Maisto SA, Gilmour CE, McGuire L, Tarvin E, Moskal D. The effects of Cannabidiol and analgesic expectancies on experimental pain reactivity in healthy adults: a balanced placebo design trial. Exp Clin Psychopharmacol. 2022;30(5):536\u201346.","journal-title":"Exp Clin Psychopharmacol"},{"issue":"3","key":"348_CR9","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/j.neuroimage.2009.04.032","volume":"47","author":"SWG Derbyshire","year":"2009","unstructured":"Derbyshire SWG, Osborn J. Offset analgesia is mediated by activation in the region of the periaqueductal grey and rostral ventromedial medulla. Neuroimage. 2009;47(3):1002\u20136.","journal-title":"Neuroimage"},{"issue":"18","key":"348_CR10","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1007\/s40265-021-01602-1","volume":"81","author":"MA Fitzcharles","year":"2021","unstructured":"Fitzcharles MA, Petzke F, T\u00f6lle TR, H\u00e4user W. Cannabis-based medicines and medical cannabis in the treatment of nociplastic pain. Drugs. 2021;81(18):2103\u201316.","journal-title":"Drugs"},{"issue":"4","key":"348_CR11","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s12160-016-9775-y","volume":"50","author":"CR France","year":"2016","unstructured":"France CR, Burns JW, Gupta RK, Buvanendran A, Chont M, Schuster E, et al. Expectancy effects on conditioned pain modulation are not influenced by Naloxone or morphine. Ann Behav Med. 2016;50(4):497\u2013505.","journal-title":"Ann Behav Med"},{"issue":"5","key":"348_CR12","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1002\/art.10225","volume":"46","author":"RH Gracely","year":"2002","unstructured":"Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002;46(5):1333\u201343.","journal-title":"Arthritis Rheum"},{"issue":"3","key":"348_CR13","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.pain.2006.02.003","volume":"122","author":"M Granot","year":"2006","unstructured":"Granot M, Granovsky Y, Sprecher E, Nir RR, Yarnitsky D. Contact heat-evoked temporal summation: tonic versus repetitive-phasic stimulation. Pain. 2006;122(3):295\u2013305.","journal-title":"Pain"},{"issue":"1","key":"348_CR14","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.pain.2007.06.029","volume":"136","author":"M Granot","year":"2008","unstructured":"Granot M, Weissman-Fogel I, Crispel Y, Pud D, Granovsky Y, Sprecher E, et al. Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: do conditioning stimulus painfulness, gender and personality variables matter? Pain. 2008;136(1):142\u20139.","journal-title":"Pain"},{"key":"348_CR15","doi-asserted-by":"publisher","unstructured":"H\u00e4user W, Fitzcharles MA, Radbruch L, Petzke F. Cannabinoids in pain management and palliative medicine. Dtsch Arztebl Int. 2017(38). https:\/\/doi.org\/10.3238\/arztebl.2017.0627.","DOI":"10.3238\/arztebl.2017.0627"},{"issue":"4","key":"348_CR16","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s00221-013-3580-7","volume":"228","author":"L Honigman","year":"2013","unstructured":"Honigman L, Yarnitsky D, Sprecher E, Weissman-Fogel I. Psychophysical testing of spatial and temporal dimensions of endogenous analgesia: conditioned pain modulation and offset analgesia. Exp Brain Res. 2013;228(4):493\u2013501.","journal-title":"Exp Brain Res"},{"key":"348_CR17","doi-asserted-by":"crossref","unstructured":"Huynh V, L\u00fctolf R, Rosner J, Luechinger R, Curt A, Kollias S, et al. Intrinsic brain connectivity alterations despite intact pain inhibition in subjects with neuropathic pain after spinal cord injury: a pilot study. Sci Rep. 2023;13(1):11943.","DOI":"10.1038\/s41598-023-37783-w"},{"key":"348_CR18","doi-asserted-by":"crossref","unstructured":"Ioachim G, Warren HJM, Powers JM, Staud R, Pukall CF, Stroman PW. Altered pain in the brainstem and spinal cord of fibromyalgia patients during the anticipation and experience of experimental pain. Front Neurol. 2022;13. Available from:\u00a0https:\/\/www.frontiersin.org\/journals\/neurology\/articles\/10.3389\/fneur.2022.862976\/full. Cited 2025 Mar 12.","DOI":"10.3389\/fneur.2022.862976"},{"issue":"4","key":"348_CR19","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1185\/030079908X280635","volume":"24","author":"W John Redmond","year":"2008","unstructured":"John Redmond W, Goffaux P, Potvin S, Marchand S. Analgesic and antihyperalgesic effects of Nabilone on experimental heat pain. Curr Med Res Opin. 2008;24(4):1017\u201324.","journal-title":"Curr Med Res Opin"},{"issue":"1","key":"348_CR20","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.pain.2004.12.032","volume":"114","author":"N Julien","year":"2005","unstructured":"Julien N, Goffaux P, Arsenault P, Marchand S. Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain. 2005;114(1):295\u2013302.","journal-title":"Pain"},{"issue":"10","key":"348_CR21","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1097\/j.pain.0000000000000989","volume":"158","author":"H Kobinata","year":"2017","unstructured":"Kobinata H, Ikeda E, Zhang S, Li T, Makita K, Kurata J. Disrupted offset analgesia distinguishes patients with chronic pain from healthy controls. Pain. 2017;158(10):1951\u20139.","journal-title":"Pain"},{"issue":"1","key":"348_CR22","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1515\/sjpain-2021-0137","volume":"22","author":"DB Larsen","year":"2022","unstructured":"Larsen DB, Uth XJ, Arendt-Nielsen L, Petersen KK. Modulation of offset analgesia in patients with chronic pain and healthy subjects \u2013 a systematic review and meta-analysis. Scand J Pain. 2022;22(1):14\u201325.","journal-title":"Scand J Pain"},{"issue":"9","key":"348_CR23","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.jpain.2009.06.012","volume":"10","author":"A Latremoliere","year":"2009","unstructured":"Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10(9):895\u2013926.","journal-title":"J Pain"},{"issue":"4","key":"348_CR24","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1007\/s11682-022-00652-7","volume":"16","author":"T Li","year":"2022","unstructured":"Li T, Zhang S, Ikeda E, Kobinata H. Functional connectivity modulations during offset analgesia in chronic pain patients: an fMRI study. Brain Imaging Behav. 2022;16(4):1794\u2013802.","journal-title":"Brain Imaging Behav"},{"issue":"1","key":"348_CR25","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1002\/ejp.1110","volume":"22","author":"D Ligato","year":"2018","unstructured":"Ligato D, Petersen KK, M\u00f8rch CD, Arendt-Nielsen L. Offset analgesia: the role of peripheral and central mechanisms. Eur J Pain. 2018;22(1):142\u20139.","journal-title":"Eur J Pain"},{"issue":"6","key":"348_CR26","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.pain.2012.02.035","volume":"153","author":"KT Martucci","year":"2012","unstructured":"Martucci KT, Eisenach JC, Tong C, Coghill RC. Opioid-independent mechanisms supporting offset analgesia and temporal sharpening of nociceptive information. Pain. 2012;153(6):1232\u201343.","journal-title":"Pain"},{"issue":"8","key":"348_CR27","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.7326\/M21-4520","volume":"175","author":"MS McDonagh","year":"2022","unstructured":"McDonagh MS, Morasco BJ, Wagner J, Ahmed AY, Fu R, Kansagara D, et al. Cannabis-based products for chronic pain: a systematic review. Ann Intern Med. 2022;175(8):1143\u201353.","journal-title":"Ann Intern Med"},{"key":"348_CR28","doi-asserted-by":"crossref","unstructured":"Melzack R. The McGill pain questionnaire: major properties and scoring methods: Pain. 1975;1(3):277\u201399.","DOI":"10.1016\/0304-3959(75)90044-5"},{"key":"348_CR29","doi-asserted-by":"crossref","unstructured":"M G, I WF, Y C, D P, Y G, E S, et al. Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: do conditioning stimulus painfulness, gender and personality variables matter? Pain. 2008;136(1\u20132). Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/17720319\/. Cited 2024 Oct 13.","DOI":"10.1016\/j.pain.2007.06.029"},{"issue":"1","key":"348_CR30","doi-asserted-by":"publisher","first-page":"e25","DOI":"10.1097\/j.pain.0000000000002716","volume":"164","author":"H Nahman-Averbuch","year":"2023","unstructured":"Nahman-Averbuch H, Timmers I. Neural mechanisms underlying the conditioned pain modulation response: a narrative review of neuroimaging studies. Pain. 2023;164(1):e25-46.","journal-title":"Pain"},{"issue":"12","key":"348_CR31","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1016\/j.pain.2014.07.008","volume":"155","author":"H Nahman-Averbuch","year":"2014","unstructured":"Nahman-Averbuch H, Martucci KT, Granovsky Y, Weissman-Fogel I, Yarnitsky D, Coghill RC. Distinct brain mechanisms support spatial vs temporal filtering of nociceptive information. Pain. 2014;155(12):2491\u2013501.","journal-title":"Pain"},{"issue":"1","key":"348_CR32","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1093\/bja\/aeu056","volume":"113","author":"M Niesters","year":"2014","unstructured":"Niesters M, Proto PL, Aarts L, Sarton EY, Drewes AM, Dahan A. Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy. Br J Anaesth. 2014;113(1):148\u201356.","journal-title":"Br J Anaesth"},{"issue":"5","key":"348_CR33","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.ejpain.2010.10.001","volume":"15","author":"R Nirl","year":"2011","unstructured":"Nirl R, Granovskyl Y, Yarnitskyl D, Sprecherl E, Granotl M. A psychophysical study of endogenous analgesia: the role of the conditioning pain in the induction and magnitude of conditioned pain modulation. Eur J Pain. 2011;15(5):491\u20137.","journal-title":"Eur J Pain"},{"issue":"5","key":"348_CR34","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1111\/bcp.13183","volume":"83","author":"P Okkerse","year":"2017","unstructured":"Okkerse P, Van Amerongen G, De Kam ML, Stevens J, Butt RP, Gurrell R, et al. The use of a battery of pain models to detect analgesic properties of compounds: a two-part four\u2010way crossover study. Brit J Clin Pharma. 2017;83(5):976\u201390.","journal-title":"Brit J Clin Pharma"},{"issue":"12","key":"348_CR35","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1097\/j.pain.0000000000000321","volume":"156","author":"LCJ Oudejans","year":"2015","unstructured":"Oudejans LCJ, Smit JM, Van Velzen M, Dahan A, Niesters M. The influence of offset analgesia on the onset and offset of pain in patients with fibromyalgia. Pain. 2015;156(12):2521\u20137.","journal-title":"Pain"},{"issue":"11","key":"348_CR36","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(11):3779\u201387.","journal-title":"J Clin Invest"},{"issue":"8","key":"348_CR37","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1097\/j.pain.0000000000000573","volume":"157","author":"S Potvin","year":"2016","unstructured":"Potvin S, Marchand S. Pain facilitation and pain inhibition during conditioned pain modulation in fibromyalgia and in healthy controls. Pain. 2016;157(8):1704\u201310.","journal-title":"Pain"},{"issue":"2","key":"348_CR38","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.berh.2011.02.005","volume":"25","author":"K Phillips","year":"2011","unstructured":"Phillips K, Clauw DJ. Central pain mechanisms in chronic pain states \u2013 maybe it is all in their head. Best Pract Res Clin Rheumatol. 2011;25(2):141\u201354.","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"2","key":"348_CR39","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare11020223","volume":"11","author":"I Ruschak","year":"2023","unstructured":"Ruschak I, Montes\u00f3-Curto P, Rossell\u00f3 L, Aguilar Mart\u00edn C, S\u00e1nchez-Montes\u00f3 L, Toussaint L. Fibromyalgia syndrome pain in men and women: a scoping review. Healthcare. 2023;11(2):223.","journal-title":"Healthcare"},{"issue":"2","key":"348_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12020307","volume":"12","author":"K Safi","year":"2024","unstructured":"Safi K, Sobieraj J, B\u0142aszkiewicz M, \u017by\u0142a J, Salata B, Dzier\u017canowski T. Tetrahydrocannabinol and cannabidiol for pain treatment\u2014an update on the evidence. Biomedicines. 2024;12(2):307.","journal-title":"Biomedicines"},{"issue":"1","key":"348_CR41","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.cnur.2003.11.012","volume":"39","author":"JL Shaver","year":"2004","unstructured":"Shaver JL. Fibromyalgia syndrome in women. Nurs Clin North Am. 2004;39(1):195\u2013204.","journal-title":"Nurs Clin North Am"},{"issue":"2","key":"348_CR42","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.jpain.2007.09.002","volume":"9","author":"RQ Skrabek","year":"2008","unstructured":"Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008;9(2):164\u201373.","journal-title":"J Pain"},{"issue":"1","key":"348_CR43","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0304-3959(00)00432-2","volume":"91","author":"R Staud","year":"2001","unstructured":"Staud R, Vierck CJ, Cannon RL, Mauderli AP, Price DD. Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain. 2001;91(1):165\u201375.","journal-title":"Pain"},{"issue":"6","key":"348_CR44","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1002\/ejp.1007","volume":"21","author":"S Sugimine","year":"2017","unstructured":"Sugimine S, Saito S, Araki T, Yamamoto K, Obata H. Endogenous analgesic effect of pregabalin: a double-blind and randomized controlled trial. Eur J Pain. 2017;21(6):997\u20131006.","journal-title":"Eur J Pain"},{"issue":"5","key":"348_CR45","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1002\/ejp.1740","volume":"25","author":"TM Szikszay","year":"2021","unstructured":"Szikszay TM, Adamczyk WM, Hoegner A, Woermann N, Luedtke K. The effect of acute-experimental pain models on offset analgesia. Eur J Pain. 2021;25(5):1150\u201361.","journal-title":"Eur J Pain"},{"key":"348_CR46","doi-asserted-by":"crossref","unstructured":"Weizman L, Dayan L, Brill S, Nahman-Averbuch H, Hendler T, Jacob G, et al. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology. 2018;91(14). Available from:\u00a0https:\/\/www.neurology.org\/doi\/10.1212\/WNL.0000000000006293. Cited 2024 Oct 22.","DOI":"10.1212\/WNL.0000000000006293"},{"key":"348_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2009\/827290","volume":"2009","author":"J Weber","year":"2009","unstructured":"Weber J, Schley M, Casutt M, Gerber H, Schuepfer G, Rukwied R, et al. Tetrahydrocannabinol (Delta 9-THC) treatment in chronic central neuropathic pain and fibromyalgia patients: results of a multicenter survey. Anesthesiol Res Pract. 2009;2009:1\u20139.","journal-title":"Anesthesiol Res Pract"},{"issue":"5","key":"348_CR48","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\u20139-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(5):375\u201385.","journal-title":"CNS Drugs"},{"issue":"3","key":"348_CR49","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","volume":"152","author":"CJ Woolf","year":"2011","unstructured":"Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3):S2-15.","journal-title":"Pain"},{"issue":"6","key":"348_CR50","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1016\/j.pain.2012.02.021","volume":"153","author":"D Yarnitsky","year":"2012","unstructured":"Yarnitsky D, Granot M, Nahman-Averbuch H, Khamaisi M, Granovsky Y. Conditioned pain modulation predicts Duloxetine efficacy in painful diabetic neuropathy. Pain. 2012;153(6):1193\u20138.","journal-title":"Pain"},{"issue":"1","key":"348_CR51","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.pain.2007.10.033","volume":"138","author":"D Yarnitsky","year":"2008","unstructured":"Yarnitsky D, Crispel Y, Eisenberg E, Granovsky Y, Ben-Nun A, Sprecher E, et al. Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk. Pain. 2008;138(1):22\u20138.","journal-title":"Pain"},{"issue":"6","key":"348_CR52","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1002\/ejp.605","volume":"19","author":"D Yarnitsky","year":"2015","unstructured":"Yarnitsky D, Bouhassira D, Drewes AM, Fillingim RB, Granot M, Hansson P, et al. Recommendations on practice of conditioned pain modulation (CPM) testing. Eur J Pain. 2015;19(6):805\u20136.","journal-title":"Eur J Pain"},{"issue":"4","key":"348_CR53","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1037\/pha0000281","volume":"27","author":"JA Yanes","year":"2019","unstructured":"Yanes JA, McKinnell ZE, Reid MA, Busler JN, Michel JS, Pangelinan MM, et al. Effects of cannabinoid administration for pain: a meta-analysis and meta-regression. Exp Clin Psychopharmacol. 2019;27(4):370\u201382.","journal-title":"Exp Clin Psychopharmacol"},{"key":"348_CR54","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918767512","volume":"14","author":"S Zhang","year":"2018","unstructured":"Zhang S, Li T, Kobinata H, Ikeda E, Ota T, Kurata J. Attenuation of offset analgesia is associated with suppression of descending pain modulatory and reward systems in patients with chronic pain. Mol Pain. 2018;14:1744806918767512.","journal-title":"Mol Pain"}],"container-title":["Journal of Cannabis Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42238-025-00348-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s42238-025-00348-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42238-025-00348-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:31:20Z","timestamp":1781613080000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s42238-025-00348-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["348"],"URL":"https:\/\/doi.org\/10.1186\/s42238-025-00348-x","relation":{},"ISSN":["2522-5782"],"issn-type":[{"value":"2522-5782","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]},"assertion":[{"value":"31 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 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":"The study received approval from the Tel Aviv Sourasky Medical Center Research Ethics Committee (Protocol No. TLV\u2212320\u2212016) and was conducted in accordance with the Declaration of Helsinki. All participants gave written informed consent after receiving a comprehensive explanation of the study\u2019s objectives and procedures (Protocol Version 3.4, approved on March 22, 2022).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}