Background/Purpose: Accumulating evidence suggests that medical cannabis therapy might have beneficial therapeutic effects in the fibromyalgia syndrome (FMS) and in difficult-to-treat rheumatoid arthritis (RA) patients. We hypothesized that changes in the concentrations of specific endogenous cannabinoids (‘endocannabinoids’) in rheumatic inflammatory/autoimmune diseases patients, might explain, at least in part, some of the subjective clinical symptoms (such as chronic pain and sleep disturbances) in these patients. Therefore, in the current study, we aimed to evaluate the circulating endocannabinoids levels of patients with RA and FMS vs. sex- and age-matched healthy controls.       

Methods: The circulating level of various endocannabinoids and endocannabinoids-like molecules (a total of 30 molecules) in the plasma of rheumatoid arthritis patients (n=46), fibromyalgia syndrome patients (n=34) and sex and age matched healthy controls (n=40), were evaluated using LC/HRMS method. RA patients were recruited and diagnosed according to the 2010 ACR/EULAR criteria and their disease severity was evaluated using Disease Activity Score in 28 joints (DAS28) score. FMS patients were diagnosed according to the ACR 2010 Fibromyalgia Diagnostic Criteria and their disease severity was evaluated using fibromyalgia impact questionnaire (FIQ) questionnaire.

Results: We found a significant difference in the level of various endocannabinoids in RA as compared to healthy donors (P< 0.01 for AEA, PEA, LEA, O-AEA, N-O-ALANINE) (Figure 1). For FMS patients, the level of various endocannabinoids was significantly changed as compared to sex and aged matched healthy controls (p< 0.01 for AEA, PEA, OEA, N-P-Glycine, N-O-Glycine, N-O-Leucine, 2-AG, 2-LG, 2-AGE, 2-OG, 2-PG and p< 0.04 for LEA, O-AEA). Importantly, we found a significant correlation between the levels of few endocannabinoids with the severity of the disease in both RA (p< 0.01 for AEA, PEA, DHEA, OEA, O-AEA, N-O-Glycine; p< 0.04 for AA, N-L-Glycine) and FMS (p< 0.03 for DHEA).

Conclusion: The observed changes in the level and composition of various endocannabinoids in the blood of rheumatoid inflammatory/autoimmune disease patients might shed a light on the pathophysiology of the disease, its severity, the appearance of unexplained and subjective symptoms and might indicate new therapeutic candidates in the future.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-significant-alteration-in-circulating-endocannabinoid-levels-in-rheumatoid-arthritis-and-fibromyalgia-syndrome-patients-and-its-correlation-with-diseases-severity/