REVIEW article
Front. Neurol.
Sec. Multiple Sclerosis and Neuroimmunology
Enhancing the Endocannabinoid System to treat residual disease in Relapse-Free Multiple Sclerosis
P Annovazzi 1
Marinella Clerico 2
Eleonora Cocco 3
Antonella Conte 4
GIROLAMA ALESSANDRA MARFIA 5
Marco Salvetti 4
Valentina Tomassini 6
R Totaro 7
Diego Centonze 4
1. Ospedale Sant'Antonio Abate di Gallarate, Gallarate, Italy
2. Universita degli Studi di Torino Scuola di Medicina, Turin, Italy
3. Azienda Ospedaliero-Universitaria di Cagliari Dipartimento delle Medicine Specialistiche, Cagliari, Italy
4. Neuroscience, Unit of Neurology, IRCCS Neuromed, Pozzilli (IS), Italy, 00133
5. Universita degli Studi di Roma Tor Vergata, Rome, Italy
6. Universita degli Studi Gabriele d'Annunzio Chieti Pescara, Chieti, Italy
7. Universita degli Studi dell'Aquila, L'Aquila, Italy
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Abstract
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).
Summary
Keywords
Algorithms of treatment, lifestyle interventions, Nabiximols, smouldering disease, Spasticity-plus-Syndrome
Received
15 November 2025
Accepted
27 January 2026
Copyright
© 2026 Annovazzi, Clerico, Cocco, Conte, ALESSANDRA MARFIA, Salvetti, Tomassini, Totaro and Centonze. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Diego Centonze
Disclaimer
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