Cannabinoids in preclinical research of sepsis: a scoping review

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.