Characterised by chronic widespread musculoskeletal pain, generalised hyperalgesia, and psychological distress, fibromyalgia (FM) is a significant unmet clinical need. The endogenous cannabinoid system plays an important role in modulating both pain and the stress response. Here, we appraise the evidence, from preclinical and clinical studies, for a role of the endocannabinoid system in FM and the therapeutic potential of targeting the endocannabinoid system. While many animal models have been used to study FM, the reserpine-induced myalgia model has emerged as perhaps the most translatable to the clinical phenotype. Inhibition of fatty acid amide hydrolase (FAAH) has shown promise in preclinical studies, ameliorating pain- and anxiety-related behaviour .

Clinically, there is evidence for alterations in the endocannabinoid system in patients with FM, including single nucleotide polymorphisms and increased levels of circulating endocannabinoids and related N-acylethanolamines. Single entity cannabinoids, cannabis, and cannabis-based medicines in patients with FM show promise therapeutically but limitations in methodology and lack of longitudinal studies to assess efficacy and tolerability preclude the current recommendation for their use in patients with FM. Gaps in the literature that warrant further investigation are discussed, particularly the need for further development of animal models with high validity for the multifaceted nature of FM, balanced studies to eliminate sex-bias in preclinical research, and ultimately, better translation between preclinical and clinical research.

纤维肌痛 (FM) 以慢性广泛性肌肉骨骼疼痛、全身性痛觉过敏和心理困扰为特征，是一项未得到满足的重大临床需求。内源性大麻素系统在调节疼痛和应激反应方面起着重要作用。在这里，我们评估来自临床前和临床研究的证据，证明内源性大麻素系统在 FM 中的作用以及靶向内源性大麻素系统的治疗潜力。虽然许多动物模型已被用于研究 FM，但利血平诱导的肌痛模型可能已成为最可转化为临床表型的模型。抑制脂肪酸酰胺水解酶 (FAAH) 在临床前研究中显示出前景，可改善与疼痛和焦虑相关的行为。

临床上，有证据表明 FM 患者的内源性大麻素系统发生了改变，包括单核苷酸多态性以及循环内源性大麻素和相关N水平升高-酰基乙醇胺。单一实体大麻素、大麻和基于大麻的药物在 FM 患者中显示出治疗前景，但方法学的局限性以及缺乏评估疗效和耐受性的纵向研究排除了目前对 FM 患者使用它们的建议。讨论了需要进一步调查的文献空白，特别是需要进一步开发对 FM 的多方面性质具有高有效性的动物模型，平衡研究以消除临床前研究中的性别偏见，并最终在临床前和临床之间更好地转化研究。