{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:24:30Z","timestamp":1792016670053,"version":"4.4.0"},"reference-count":139,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100003965","name":"Migraine Research Foundation","doi-asserted-by":"publisher","award":["2019 Migraine Research Foundation Impact Award"],"award-info":[{"award-number":["2019 Migraine Research Foundation Impact Award"]}],"id":[{"id":"10.13039\/100003965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Migraine is a complex and highly disabling neurological disease whose treatment remains challenging in many patients, even after the recent advent of the first specific\u2010preventive drugs, namely monoclonal antibodies that target calcitonin gene\u2010related peptide. For this reason, headache researchers are actively searching for new therapeutic targets. Cannabis has been proposed for migraine treatment, but controlled clinical studies are lacking. A major advance in cannabinoid research has been the discovery of the endocannabinoid system (ECS), which consists of receptors CB1 and CB2; their endogenous ligands, such as N\u2010arachidonoylethanolamine; and the enzymes that catalyze endocannabinoid biosynthesis or degradation. Preclinical and clinical findings suggest a possible role for endocannabinoids and related lipids, such as palmitoylethanolamide (PEA), in migraine\u2010related pain treatment. In animal models of migraine\u2010related pain, endocannabinoid tone modulation via inhibition of endocannabinoid\u2010catabolizing enzymes has been a particular focus of research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To conduct a narrative review of available data on the possible effects of cannabis, endocannabinoids, and other lipids in migraine\u2010related pain, relevant key words were used to search the PubMed\/MEDLINE database for basic and clinical studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Endocannabinoids and PEA seem to reduce trigeminal nociception by interacting with many pathways associated with migraine, suggesting a potential synergistic or similar effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Modulation of the metabolic pathways of the ECS may be a basis for new migraine treatments. The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area. Multiple molecules related to the ECS or to allosteric modulation of CB1 receptors have emerged as potential therapeutic targets in migraine\u2010related pain. The complexity of the ECS calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14267","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T11:13:57Z","timestamp":1645182837000},"page":"227-240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The endocannabinoid system and related lipids as potential targets for the treatment of migraine\u2010related pain"],"prefix":"10.1111","volume":"62","author":[{"given":"Rosaria","family":"Greco","sequence":"first","affiliation":[{"name":"Headache Science &amp; Neurorehabilitation Center IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Demartini","sequence":"additional","affiliation":[{"name":"Headache Science &amp; Neurorehabilitation Center IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Zanaboni","sequence":"additional","affiliation":[{"name":"Headache Science &amp; Neurorehabilitation Center IRCCS Mondino Foundation  Pavia Italy"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Francavilla","sequence":"additional","affiliation":[{"name":"Headache Science &amp; Neurorehabilitation Center IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"De Icco","sequence":"additional","affiliation":[{"name":"Headache Science &amp; Neurorehabilitation Center IRCCS Mondino Foundation  Pavia Italy"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Headache Science &amp; Neurorehabilitation Center IRCCS Mondino Foundation  Pavia Italy"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tassorelli","sequence":"additional","affiliation":[{"name":"Headache Science &amp; Neurorehabilitation Center IRCCS Mondino Foundation  Pavia Italy"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00034.2015"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13083"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14090"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2020.04.027"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102416678382"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-0621-8"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-019-1038-4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000119"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2009.04.019"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.11.029"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/can.2015.29003.ebr"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0720-6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.10.054"},{"key":"e_1_2_9_15_1","first-page":"243","article-title":"Cannabinoids block release of serotonin from platelets induced by plasma from migraine patients","volume":"5","author":"Volfe Z","year":"1985","journal-title":"Int J Clin Pharmacol Res"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707448"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419865252"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1673"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10194-012-0490-1"},{"key":"e_1_2_9_20_1","first-page":"123","article-title":"Therapeutic use of cannabinoids\u2014dose finding, effects, and pilot data of effects in chronic migraine and cluster headache. 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