Inamassu Carolina Henkes, Sordi Regina, Marchioni Camila
Graduate Program of Pharmacology, Federal University of Santa Catarina, Campus Universitário. Rua Engenheiro Agronômico Andrei Cristian Ferreira, s/n - Trindade, Florianópolis, SC, 88040-900, Brazil.
Department of Pharmacology, Biological Science Center, Federal University of Santa Catarina, Florianópolis, Brazil.
Inflamm Res. 2025 Sep 16;74(1):125. doi: 10.1007/s00011-025-02090-9.
Sepsis is a global health problem that ends millions of lives and costs billions of dollars in treatment and management every year. This disease is responsible for one in every five deaths worldwide, and is the third leading cause of death in hospitals. Despite decades of research, no current specific treatment or cure are available, only supportive and symptomatic care, and few preclinical studies reach human trials. Since the discovery of the endocannabinoid system (ECS), cannabinoids have been researched as a potential treatment for various diseases, including sepsis. Our review aimed to summarize what is known about the endocannabinoid system research in preclinical sepsis.
A scoping search was conducted in the databases Pubmed, Scopus and Web of Science. Articles were selected in case they studied a cannabinoid or the ECS in preclinical sepsis or septic shock, with no time limit. Data regarding animals species, model os sepsis, treatments, cannabinoids utilized and main outcomes were analyzed.
We found that the most commonly used animal species was both Mus musculus and Rattus norvegicus, and the most frequently performed sepsis model was the endotoxemia induced by lipopolysaccharide (LPS). The most studied receptor was cannabinoid receptor type 2 (CB2) and among all cannabinoid types, synthetic cannabinoids were researched in the majority of the studies. We also discuss the evaluated outcomes, as well as their involvement with the endocannabinoid system and underlying molecular mechanisms. We highlight the main promising results and explore the limitations and future challenges in the field.
Cannabinoids are promising therapeutic targets in the treatment of sepsis, as they improved survival, and reduced inflammation and organ injury. However, deleterious adverse effects were reported, with the underlying molecular mechanisms still unknown, and further research is needed to evaluate their benefits and future use in clinical research.
脓毒症是一个全球性的健康问题，每年导致数百万人死亡，在治疗和管理方面花费数十亿美元。这种疾病在全球每五例死亡中就有一例与之相关，是医院中第三大死亡原因。尽管经过了数十年的研究，但目前尚无特效治疗方法，仅能进行支持性和对症治疗，而且很少有临床前研究能进入人体试验阶段。自内源性大麻素系统（ECS）被发现以来，大麻素已被研究作为包括脓毒症在内的各种疾病的潜在治疗方法。我们的综述旨在总结临床前脓毒症中内源性大麻素系统研究的已知情况。
在PubMed、Scopus和Web of Science数据库中进行了范围检索。选取研究临床前脓毒症或脓毒性休克中的大麻素或ECS的文章，无时间限制。分析了有关动物物种、脓毒症模型、治疗方法、使用的大麻素和主要结果的数据。
我们发现最常用的动物物种是小家鼠和褐家鼠，最常采用的脓毒症模型是脂多糖（LPS）诱导的内毒素血症。研究最多的受体是大麻素2型受体（CB2），在所有大麻素类型中，大多数研究都涉及合成大麻素。我们还讨论了评估的结果，以及它们与内源性大麻素系统的关系和潜在的分子机制。我们强调了主要的有前景的结果，并探讨了该领域的局限性和未来挑战。
大麻素在脓毒症治疗中是有前景的治疗靶点，因为它们能提高生存率，减轻炎症和器官损伤。然而，也有有害不良反应的报道，其潜在分子机制仍不清楚，需要进一步研究来评估它们的益处以及在临床研究中的未来应用。
