Sepsis is a severe disease with high mortality and a major public health challenge. Despite being studied for decades, its treatment remains limited to symptom management and clinical support. In this context, cannabinoids have been investigated in sepsis as prognostic markers and potential treatments. A scoping review of clinical studies on cannabinoids in sepsis was conducted. We sought to answer the question: “What is known about the involvement and therapeutic potential of cannabinoids in sepsis?”, following PRISMA guidelines. The MeSH terms used were “sepsis”/“septic shock” AND “cannabinoids” and similar terms (“endocannabinoids”, “phytocannabinoids”, “synthetic cannabinoids”). The databases PubMed, Scopus, and Web of Science were searched, and clinical studies in Portuguese/English/Spanish related to sepsis/septic shock and cannabinoids/endocannabinoid system (ECS) were included; non-clinical studies were excluded. There was no restriction on publication period. Of 1080 articles, only 9 involved clinical studies (5 in vitro, 4 in vivo), published between 2001 and 2023. In in vitro studies, LPS (lipopolysaccharide) insult was used in immune, cardiac, umbilical cord, brain, liver, lung, and coronary artery cell lines. The in vivo studies analyzed 129 septic patients with respiratory tract infection (44), genitourinary infection (41), unknown focus (25), severe acute pancreatitis (3), wound infection (1), or not mentioned. One study did not report the number of patients and two did not mention the type of infection. Cannabinoids were tested only in in vitro studies, including 12 synthetic cannabinoids (4 studies), the phytocannabinoid CBD (2), and 5 endocannabinoids (1). The main findings were that lower concentrations of AEA, 2-AG, expression of FAAH and CB2 were associated with worse prognosis (longer hospital stay, lung injury, and mechanical ventilation). Additionally, cannabinoids reduced autophagy, inflammation, and damage in cell lines, and the ECS was shown to influence and modulate immune and inflammatory responses. However, studies are at an early stage, limited in tests and sample sizes, and consensus is difficult due to methodological variability. Cannabinoids are promising in the management of sepsis, but there remains a major knowledge gap and few studies. The mechanisms of action are not yet fully elucidated, and most studies have been conducted in animals.
Inamassu et al. (Sun,) studied this question.