Understanding Fibromyalgia & the Endocannabinoid System (ECS)
Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain, fatigue, cognitive disturbances (“fibro-fog”), and heightened pain sensitivity. Despite affecting approximately 2-4% of the population, its causes remain elusive (Burke et al, 2022, Garcia-Dominguez, 2025).
The ECS, comprising endocannabinoids like anandamide (AEA) and 2-arachidonoylglycerol (2-AG), their receptors CB1 & CB2, and metabolic enzymes (FAAH & MAGL), regulates pain perception, mood, inflammation, and immune function (Garcia-Dominguez, 2025).
How the ECS Relates to Fibromyalgia
Garcia-Dominguez emphasizes that ECS dysfunction might contribute to the core symptoms of fibromyalgia, especially hyperalgesia, and chronic pain, suggesting a link between ECS hypofunction and persistent symptomatology.
Evidence from Preclinical & Clinical Research
1. Elevated ECS Biomarkers:
Research shows fibromyalgia patients may exhibit altered ECS activity, including:
Elevated circulating endocannabinoids and related N-acylethanolamines (Burke et al, 2022)
Genetic polymorphisms in ECS components, hinting at dysregulation (Garcia-Dominguez, 2025)
2. Enzyme Inhibition Trials
Preclinical studies using FAAH inhibitors, which block the enzyme that breaks down AEA, yield reduced pain and anxiety in fibromyalgia models (e.g., reserpine-induced myalgia) (Burke et al, 2022).
3. Cannabinoid Therapies
Clinical trials of cannabis-based products (THC, CBD, or combos) show symptomatic relief in some patients, especially concerning pain and sleep disturbances, but methodological flaws and lack of long-term data limit definitive recommendations (Strand, et al, 2023).
The Clinical Endocannabinoid Deficiency (CECD) Hypothesis
The CECD model suggests that certain individuals, especially those with fibromyalgia, may have insufficient ECS tone. Without enough endocannabinoid activity, symptoms like chronic pain, migraine, and irritable bowel syndrome can persist.
A prominent discussion from 2004 by Dr. Russo articulates that:
“Fibromyalgia is now conceived as a central sensitization state… cannabinoids have similarly demonstrated the ability to block spinal, peripheral, and gastrointestinal mechanisms that promote pain…”
Patient communities echo this sentiment, with testimonials like:
“Medical cannabis has been a game changer for me… better than anything else out on the market.”
Gaps, Challenges & Future Directions
According to Garcia-Dominguez (2025), future research must address:
- Improved animal models that closely capture fibromyalgia’s multifaceted nature (pain, fatigue, mood).
- Balanced design in both sexes (many studies favor male-only models).
- Better ECS-targeting therapies, focusing on specificity, safety, and minimal side effects.
- Longitudinal clinical trials that establish optimal dosing, formulations, and long-term tolerability.
Takeaways
–ECS dysfunction likely plays a key role in fibromyalgia’s pathophysiology.
–ECS-targeted interventions (like FAAH inhibitors and cannabinoids) show therapeutic promise but need robust clinical validation.
–The CECD hypothesis offers a compelling framework, supported by molecular insights and living patient experiences.
-The field urgently needs rigorous, inclusive, long-term clinical trials to confirm efficacy, safety, and best-use protocols.
Final Thoughts
Understanding and targeting the ECS holds the promise of transforming fibromyalgia care. While early results are encouraging, the journey toward safe, effective ECS-based therapies remains in early stages, driven by research innovation and the lived experiences of patients seeking relief.
References
Bourke, S. L., Schlag, A. K., O’Sullivan, S. E., Nutt, D. J., & Finn, D. P. (2022). Cannabinoids and the endocannabinoid system in fibromyalgia: A review of preclinical and clinical research. Pharmacology & Therapeutics, 240, 108216. https://doi.org/10.1016/j.pharmthera.2022.108216
García-Domínguez, M. (2025a). A comprehensive analysis of fibromyalgia and the role of the endogenous opioid system. Biomedicines, 13(1), 165. https://doi.org/10.3390/biomedicines13010165
García-Domínguez, M. (2025b). Role of the endocannabinoid system in fibromyalgia. Current Issues in Molecular Biology, 47(4), 230. https://doi.org/10.3390/cimb47040230
Rousseau, J. (2004). Lettres. In classiques des sciences sociales. https://doi.org/10.1522/cla.roj.let
Strand, N. H., Maloney, J., Kraus, M., Wie, C., Turkiewicz, M., Gomez, D. A., Adeleye, O., & Harbell, M. W. (2023). Cannabis for the Treatment of Fibromyalgia: A Systematic review. Biomedicines, 11(6), 1621. https://doi.org/10.3390/biomedicines11061621
Love Hawkins graduated from Cohort 1 of the CannyNurse® Certificate Program in 2021 and joined Ariana as the Assistant Instructor for the CannyNurse® Certificate Program in August of 2022 with Cohort 4. Love was so committed to her study of cannabis nursing that she completed both the CannyNurse® certificate program and the Pacific College of Health Sciences Medical Cannabis Certificate at the same time. It is an honor to have her on the CannyNurse® faculty!