Women with fibromyalgia have elevated endocannabinoid levels linked to pain and poor fitness | Research

The takeaway

Women with fibromyalgia had significantly higher plasma anandamide levels than healthy controls, and these elevated levels correlated with greater pain intensity and lower physical fitness.

Fibromyalgia researchers, pain scientists, and clinicians interested in exercise as a treatment mechanism.

What the researchers found

Significantly higher anandamide (AEA) concentrations were found in fibromyalgia patients compared to controls. AEA correlated positively with pain intensity and inversely with physical fitness. Physical fitness was inversely correlated with pain and psychological distress. PAG-thalamus brain connectivity was related to physical activity but not to circulating endocannabinoids.

Why it matters

Finding elevated anandamide in fibromyalgia patients supports the hypothesis that the endocannabinoid system is dysregulated in this condition, though in a more complex way than simple deficiency. Physical fitness appears to be a key modifiable factor.

The numbers in context

31 women with fibromyalgia, 29 healthy controls. AEA significantly elevated in FM. AEA positively correlated with pain intensity, inversely with physical fitness. PAG-thalamus connectivity associated with physical activity but not circulating endocannabinoids.

How the study worked

Exploratory study comparing plasma endocannabinoid and N-acylethanolamine concentrations in 31 women with fibromyalgia and 29 healthy controls. fMRI measured brain connectivity. Physical fitness and pain/psychological questionnaires were included.

What this study cannot tell us

Small sample size (31 FM, 29 HC). Cross-sectional design cannot determine if elevated AEA causes or results from pain/deconditioning. Women only. Plasma levels may not reflect brain endocannabinoid activity.

How to read the evidence

Novel multimodal approach combining blood biomarkers, brain imaging, and fitness testing, but small sample limits conclusions.

When this study was published

2025 publication.

The bigger picture

Previous theories proposed endocannabinoid deficiency in fibromyalgia, but elevated AEA could represent a compensatory response to chronic pain rather than a deficiency. The connection to physical fitness suggests exercise may be a pathway to normalizing ECS function.

Questions still open

Does exercise reduce endocannabinoid levels in fibromyalgia patients?
Are elevated AEA levels in fibromyalgia a compensatory response or part of the pathology?

Common questions

Why would endocannabinoid levels be elevated rather than deficient in fibromyalgia?

Elevated anandamide may represent the body's attempt to compensate for chronic pain by increasing pain-modulating signals. Alternatively, it could reflect impaired endocannabinoid receptor function where more signal is needed to achieve the same effect.

Does exercise help fibromyalgia through the endocannabinoid system?

The inverse relationship between fitness and AEA suggests it might. Physical fitness was also linked to brain connectivity changes in pain-processing regions, suggesting exercise may normalize both peripheral and central pain mechanisms.

Read the original research

Investigation of endocannabinoids in plasma and their correlation with physical fitness and resting state functional connectivity of the periaqueductal grey in women with fibromyalgia: An exploratory secondary study.

Scandinavian journal of pain, 25(1)

View on PubMed ↗Publisher’s paper ↗

Citation

Ghafouri, Bijar; Stensson, Niclas; Simon, Rozalyn; Mayo, Leah M; Lund, Eva; Forsgren, Mikael F; Leinhard, Olof Dahlqvist; Lundberg, Peter; van Ettinger-Veenstra, Helene. (2025). Investigation of endocannabinoids in plasma and their correlation with physical fitness and resting state functional connectivity of the periaqueductal grey in women with fibromyalgia: An exploratory secondary study.. Scandinavian journal of pain, 25(1). https://doi.org/10.1515/sjpain-2025-0023