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

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.

Ghafouri, Bijar et al.·Scandinavian journal of pain·2025·Preliminary EvidenceCross-Sectional
RTHC-06532Cross SectionalPreliminary Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Cross-Sectional
Evidence
Preliminary Evidence
Sample
N=31

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

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

Trust & Context

Key Stat:
anandamide levels significantly higher in fibromyalgia patients, correlating with pain intensity and inversely with physical fitness
Evidence Grade:
Novel multimodal approach combining blood biomarkers, brain imaging, and fitness testing, but small sample limits conclusions.
Study Age:
2025 publication.
Original Title:
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.
Published In:
Scandinavian journal of pain, 25(1) (2025)
Database ID:
RTHC-06532

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

A snapshot of a population at one point in time.

What do these levels mean? →

Frequently Asked 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 More on RethinkTHC

Cite This Study

RTHC-06532·https://rethinkthc.com/research/RTHC-06532

APA

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

MLA

Ghafouri, Bijar, et al. "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, 2025. https://doi.org/10.1515/sjpain-2025-0023

RethinkTHC

RethinkTHC Research Database. "Investigation of endocannabinoids in plasma and their correl..." RTHC-06532. Retrieved from https://rethinkthc.com/research/ghafouri-2025-investigation-of-endocannabinoids-in

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.