The peripheral endocannabinoid system and its association with biomarkers of inflammation in untreated patients with multiple sclerosis

Eur J Neurol. 2023 Oct;30(10):3212-3220. doi: 10.1111/ene.15930. Epub 2023 Jul 7.


Background and purpose: The endocannabinoid system (ECS) has been found altered in patients with multiple sclerosis (MS). However, whether the ECS alteration is present in the early stage of MS remains unknown. First, we aimed to compare the ECS profile between newly diagnosed MS patients and healthy controls (HCs). Next, we explored the association of the ECS, biomarkers of inflammation, and clinical parameters in newly diagnosed MS patients.

Methods: Whole blood gene expression of ECS components and levels of endocannabinoids in plasma were measured by real-time quantitative polymerase chain reaction and ultra-high-pressure liquid chromatography-mass spectrometry, respectively, in 66 untreated MS patients and 46 HCs.

Results: No differences were found in the gene expression or plasma levels of the selected ECS components between newly diagnosed MS patients and HCs. Interferon-γ, encoded by the gene IFNG, correlated positively (ρ = 0.60) with the expression of G protein-coupled receptor 55 (GPR55), and interleukin1β (IL1B) correlated negatively (ρ = -0.50) with cannabinoid receptor 2 (CNR2) in HCs.

Conclusions: We found no alteration in the peripheral ECS between untreated patients with MS and HC. Furthermore, our results indicate that the ECS has a minor overall involvement in the early stage of MS on inflammatory markers and clinical parameters when compared with HCs.

Keywords: 2-AG; AEA; anandamide; biomarker; endocannabinoid; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Endocannabinoids* / genetics
  • Endocannabinoids* / metabolism
  • Endocannabinoids* / therapeutic use
  • Humans
  • Inflammation
  • Mass Spectrometry
  • Multiple Sclerosis* / drug therapy


  • Endocannabinoids
  • Biomarkers