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Abnormalities in the cerebrospinal fluid levels of endocannabinoids in Multiple Sclerosis
  1. Massimiliano Di Filippo
  1. Clinica Neurologica, Universita' di Perugia, Perugia, and IRCCS Fondazione S Lucia, Rome, Italy
    1. Luigi Alberto Pini (pinila{at}
    1. Istituto di Tossicologia e Farmacologia Clinica, Universita' di Modena e Reggio Emilia, Italy
      1. Gian Piero Pelliccioli (gianpiero.pelliccioli{at}
      1. Servizio di Neuroradiologia, Azienda Ospedaliera di Perugia, Perugia, Italy
        1. Paolo Calabresi (calabre{at}
        1. Clinica Neurologica, Universita' di Perugia, Perugia, and IRCCS Fondazione S Lucia, Rome, Italy
          1. Paola Sarchielli ({at}
          1. Clinica Neurologica, Universita' di Perugia, Perugia, Italy


            Objective: Endocannabinoids (eCBs) play a pivotal role in the modulation of neuroinflammation and experimental findings suggest that they may be directly involved in the pathogenesis of multiple sclerosis (MS). The objective of our study was to measure eCBs levels in the cerebrospinal fluid (CSF) of MS patients.

            Patients and methods: Arachidonoyl-ethanolamide (anandamide, AEA), palmitylethanolamide (PEA), 2-arachidonoyl-glycerol (2-AG) and oleoylethanolamide (OEA) levels were measured in the CSF of 50 MS patients and 20 control subjects by isotope dilution gas-chromatography/mass-spectrometry. Patients included thirty-five MS patients in the relapsing-remitting (RR) form of the disease, 20 in a stable clinical phase and 15 during a relapse, and 15 MS patients in the secondary progressive form (SP).

            Results: Significantly reduced levels of all the tested eCBs were found in the CSF of MS patients compared to control subjects, with lower values detected in the SP MS group. Higher levels of AEA and PEA, although below those of controls, were found in the CSF of RR MS patients during a relapse. Higher levels of AEA 2-AG and OEA were found in patients with MRI gadolinium-enhancing (Gd+) lesions.

            Discussion: The present findings suggest the presence of an impaired eCB system in MS. Increased CSF levels of AEA during relapses or in RR patients with Gd+ lesions suggest its potential role in limiting the ongoing inflammatory process with potential neuroprotective implications. These findings provide further support for the development of drugs targeting eCBs as potential pharmacological strategy to reduce the symptoms and slow disease progression in MS.

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