Circulating endocannabinoidome signatures of disease activity in amyotrophic lateral sclerosis

Background and purpose Preclinical studies of amyotrophic lateral sclerosis (ALS) have shown altered endocannabinoid (eCB) signalling that may contribute to the disease. Results from human studies are sparse and inconclusive. The aim of this study was to determine the association between serum levels of eCBs or their congeners, the so‐called endocannabinoidome, and disease status and activity in ALS patients. Methods Serum concentrations of 2‐arachidonoylglycerol and N‐arachidonoylethanolamine (AEA), and AEA congeners palmitoylethanolamide (PEA), oleoylethanolamide (OEA), eicosapentaenoylethanolamide (EPEA), 2‐docosahexaenoylglycerol (2‐DHG) and docosahexaenoylethanolamide (DHEA) were measured in samples from 65 ALS patients, 32 healthy controls (HCs) and 16 neurological disease controls (NALS). A subset of 46 ALS patients underwent a longitudinal study. Disease activity and progression were correlated with eCB and congener levels. Results Most circulating mediators were higher in ALS than HCs (all p