First meta-analysis finds altered endocannabinoid levels in fibromyalgia patients | Research

The takeaway

The first meta-analysis of endocannabinoid levels in fibromyalgia found increased levels of certain lipid mediators in patients compared to controls, supporting the theory of endocannabinoid system involvement in chronic widespread pain.

Fibromyalgia researchers, pain medicine specialists, and patients interested in the biological basis of their condition.

First meta-analysis of endocannabinoid levels in fibromyalgia

What the researchers found

Plasma levels of oleoylethanolamide and stearoylethanolamide were significantly increased in fibromyalgia patients compared to controls. Interstitial levels of palmitoylethanolamide and stearoylethanolamide were also altered. No significant differences were found in anandamide or 2-AG, the classical endocannabinoids.

Why it matters

If endocannabinoid system dysfunction underlies fibromyalgia, it could explain why some patients report benefit from cannabis and provide targets for more specific treatments.

The numbers in context

8 studies reviewed, 7 meta-analyzed. Increased plasma OEA (p=0.005) and SEA in fibromyalgia. Altered interstitial PEA (p=0.05) and SEA (p=0.001). No significant differences in classical endocannabinoids (anandamide, 2-AG).

How the study worked

First systematic review and meta-analysis of endocannabinoid and N-acylethanolamine levels in chronic widespread pain and fibromyalgia. Eight studies included for qualitative review, seven for meta-analysis. Compared plasma and interstitial levels between patients and healthy controls.

What this study cannot tell us

Small number of studies (7-8). Most studies did not account for variables that influence endocannabinoid function (cannabis use, medications, physical activity, sleep, diet). Heterogeneous measurement methods.

How to read the evidence

First systematic review and meta-analysis in this area, but limited by small number of included studies and heterogeneous methods.

When this study was published

Published in 2022.

The bigger picture

The finding that non-classical endocannabinoid-like molecules (N-acylethanolamines) are altered while classical endocannabinoids are not suggests a more nuanced role for the broader endocannabinoidome in fibromyalgia than previously appreciated.

Questions still open

Could N-acylethanolamine levels serve as fibromyalgia biomarkers? Would therapies targeting specific endocannabinoid-like molecules be more effective than broad-spectrum cannabis?

Common questions

Is the endocannabinoid system involved in fibromyalgia?

This first meta-analysis found that certain endocannabinoid-like molecules are significantly altered in fibromyalgia patients compared to controls, supporting the theory of endocannabinoid system involvement.

Does cannabis help fibromyalgia because of endocannabinoid problems?

The finding that endocannabinoid-related molecules are altered in fibromyalgia provides a biological rationale for why some patients report cannabis benefit, but the classical endocannabinoids (anandamide, 2-AG) were not significantly different.

Read the original research

Plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis.

Pain reports, 7(6), e1045

View on PubMed ↗Publisher’s paper ↗

Citation

Kurlyandchik, Inna; Lauche, Romy; Tiralongo, Evelin; Warne, Leon N; Schloss, Janet. (2022). Plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis.. Pain reports, 7(6), e1045. https://doi.org/10.1097/PR9.0000000000001045