Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate.
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2022
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Scientific Reports
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Abstract
The endocannabinoid system (ECS), a signalling network with immunomodulatory properties, is
a potential therapeutic target in multiple sclerosis (MS). Dimethyl fumarate (DMF) is an approved
drug for MS whose mechanism of action has not been fully elucidated; the possibility exists that its
therapeutic effects could imply the ECS. With the aim of studying if DMF can modulate the ECS, the
endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA)
and palmitoylethanolamide (PEA) were determined by liquid chromatography-mass spectrometry
in peripheral blood mononuclear cells from 21 healthy donors (HD) and 32 MS patients at baseline
and after 12 and 24 months of DMF treatment. MS patients presented lower levels of 2-AG and PEA
compared to HD. 2-AG increased at 24 months, reaching HD levels. AEA and PEA remained stable at
12 and 24 months. OEA increased at 12 months and returned to initial levels at 24 months. Patients
who achieved no evidence of disease activity (NEDA3) presented the same modulation over time as
EDA3 patients. PEA was modulated differentially between females and males. Our results show that
the ECS is dysregulated in MS patients. The increase in 2-AG and OEA during DMF treatment suggests
a possible role of DMF in ECS modulation.