{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:44:06Z","timestamp":1777517046714,"version":"3.51.4"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>The recent introduction of High-Efficacy Therapies (HETs) in clinical practice has drastically reduced the frequency of acute inflammatory episodes and relapses, in patients with Multiple Sclerosis (MS), gradually shifting the interest of clinicians toward preventing disease progression and treating symptoms associated with the residual disease. This article summarizes the output of a recent meeting (June 2025, in Rome) among an Italian group of neurologists, who discussed about published evidence supporting the involvement of the endocannabinoid system (ECS) in MS spasticity and its associated symptoms. Sharing their clinical experiences about the silent progression of the disease, in patients with Relapse-Free Multiple Sclerosis (RFMS), treated with HETs, authors propose a new algorithm to treat residual disease in RFMS, by enhancing ECS with both cannabinoid agents and lifestyle interventions (diet and physical activity).<\/jats:p>","DOI":"10.3389\/fneur.2026.1747131","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:22:28Z","timestamp":1772626948000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing the endocannabinoid system to treat residual disease in relapse-free multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Pietro","family":"Annovazzi","sequence":"first","affiliation":[{"name":"Neuroimmunology Unit, ASST Valle Olona, Gallarate Hospital","place":["Gallarate, VA, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marinella","family":"Clerico","sequence":"additional","affiliation":[{"name":"Clinical and Biological Sciences Department, University of Torino","place":["Torino, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Cocco","sequence":"additional","affiliation":[{"name":"Medical Sciences and Public Health Department, University of Cagliari","place":["Cagliari, Italy"]},{"name":"Multiple Sclerosis Center, Cagliari ASL","place":["Cagliari, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Conte","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University","place":["Rome, Italy"]},{"name":"Unit of Neurology, IRCCS Neuromed","place":["Pozzilli, IS, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girolama Alessandra","family":"Marfia","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, Tor Vergata University","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Salvetti","sequence":"additional","affiliation":[{"name":"Unit of Neurology, IRCCS Neuromed","place":["Pozzilli, IS, Italy"]},{"name":"Department of Neurosciences, Mental Health and Sensory Organs, Sapienza University","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Tomassini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Imaging and Clinical Sciences, University G. D\u2019Annunzio","place":["Chieti-Pescara, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocco","family":"Totaro","sequence":"additional","affiliation":[{"name":"Demyelinating Disease Center Department of Neurology, San Salvatore Hospital","place":["L\u2019Aquila, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Centonze","sequence":"additional","affiliation":[{"name":"Unit of Neurology, IRCCS Neuromed","place":["Pozzilli, IS, Italy"]},{"name":"Department of Systems Medicine, Tor Vergata University","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"958665","DOI":"10.3389\/fneur.2022.958665","article-title":"Clinical insights on the spasticity-plus syndrome in multiple sclerosis","volume":"13","author":"Alami Marrouni","year":"2022","journal-title":"Front 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