Endocannabinoids and related lipids in serum from patients with amyotrophic lateral sclerosis

Muscle Nerve. 2021 Jan;63(1):120-126. doi: 10.1002/mus.27096. Epub 2020 Nov 3.


Background: The goals of this study were to determine whether serum concentrations of endocannabinoids (eCB) and related lipids predict disease status in patients with amyotrophic lateral sclerosis (ALS) relative to healthy controls, and whether concentrations correlate with disease duration and severity.

Methods: Serum concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA), and related lipids palmitoylethanolamine (PEA), oleoylethanolamine (OEA), and 2-oleoylglycerol (2-OG), were measured in samples from 47 patients with ALS and 19 healthy adults. Hierarchical binary logistic and linear regression analyses assessed whether lipid concentrations predicted disease status (ALS or healthy control), duration, or severity.

Results: Binary logistic regression revealed that, after controlling for age and gender, 2-AG, 2-OG and AEA concentrations were unique predictors of the presence of ALS, demonstrating odds ratios of 0.86 (P = .039), 1.03 (P = .023), and 42.17 (P = .026), respectively. When all five lipids and covariates (age, sex, race, ethnicity, body mass index, presence of a feeding tube) were included, the resulting model had an overall classification accuracy of 92.9%. Hierarchical linear regression analyses indicated that in patients with ALS, AEA and OEA inversely correlated with disease duration (P = .030 and .031 respectively), while PEA demonstrated a positive relationship with disease duration (P = .013). None of the lipids examined predicted disease severity.

Conclusions: These findings support previous studies indicating significant alterations in concentrations of circulating lipids in patients with ALS. They suggest that arachidonic and oleic acid containing small lipids may serve as biomarkers for identifying the presence and duration of this disease.

Keywords: ALSFRS-R; amyotrophic lateral sclerosis; biomarker; diagnostic criteria; motor neuron disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amyotrophic Lateral Sclerosis / diagnosis*
  • Arachidonic Acids / blood
  • Biomarkers / blood
  • Endocannabinoids / blood*
  • Female
  • Glycerides / blood
  • Humans
  • Lipids / blood*
  • Male
  • Middle Aged
  • Polyunsaturated Alkamides / blood
  • Severity of Illness Index


  • Arachidonic Acids
  • Biomarkers
  • Endocannabinoids
  • Glycerides
  • Lipids
  • Polyunsaturated Alkamides
  • 2-oleoylglycerol
  • anandamide