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The role of the endocannabinoid system and medicinal cannabis in fibromyalgia syndrome
Thesis   Open access

The role of the endocannabinoid system and medicinal cannabis in fibromyalgia syndrome

Inna Kurlyandchik
Southern Cross University
Doctor of Philosophy (PhD), Southern Cross University
2025
DOI:
https://doi.org/10.25918/thesis.583
Appears in  Recent Southern Cross PhD Theses
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Abstract

Fibromyalgia Medicinal cannabis Endocannabinoid system N-acylethanolamines
This thesis investigated the role of the endocannabinoid system (ECS) and medicinal cannabis in fibromyalgia syndrome (FMS) through three interconnected studies. The research program integrated systematic evidence synthesis, clinical intervention, and biomarker analysis to address critical knowledge gaps in FMS pathophysiology and treatment. First, a systematic review and meta-analysis of eight studies examined plasma and interstitial endocannabinoid and N-acylethanolamine profiles in FMS and chronic widespread pain (CWP). The analysis revealed significantly elevated plasma oleoylethanolamide (OEA) and stearoylethanolamide (SEA) in FMS patients compared to controls (p=0.005 and p<0.0001, respectively), and increased plasma palmitoylethanolamide (PEA) and interstitial SEA in CWP (p=0.05 and p=0.001, respectively). However, no consistent differences were observed in canonical endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Second, a randomised, double-blind, placebo-controlled feasibility trial evaluated a 1:1 THC:CBD (10 mg/mL each) cannabis oil in 24 adults with FMS. Following 4-week titration and 12-week stable dosing, the intervention demonstrated high feasibility (100% adherence and 92% retention) and safety, with predominantly mild adverse events. Medium to large effect sizes favoured treatment for pain reduction (η²p=0.180), sleep quality improvement (η²p=0.184), and decreased fibromyalgia impact (η²p=0.132). Clinically meaningful pain reduction (≥30%) was achieved by 70% of the cannabis group at both post‑titration (Week 1) and Week 12, compared with 20% and 40% in the placebo group, respectively. At Week 12, 40% of the cannabis group achieved the substantial fibromyalgia impact reduction versus 10% in the placebo group. Third, longitudinal plasma analysis during 16-week cannabis treatment examined N-acylethanolamine dynamics. Despite clinical improvements, no significant changes were observed in plasma PEA, OEA, or SEA over 16 weeks (all p>0.05), with minimal effect sizes (η²p≤0.03). This dissociation between peripheral markers and clinical response suggests therapeutic effects likely occur through central mechanisms rather than peripheral biomarker normalisation. The integrated findings advance our understanding of endocannabinoid dysregulation in FMS and provide foundational evidence supporting medicinal cannabis as a feasible intervention, while highlighting the need for larger trials and mechanistic studies focusing on central rather than peripheral markers. This research informs clinical practice by validating a pragmatic titration protocol and identifying key safety considerations, while also establishing research priorities for definitive efficacy trials and central mechanism investigation.

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