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A June 2022 research study conducted in Croatia and entitled "Endocannabinoids, Anandamide and 2-Arachidonoylglycerol, as Prognostic Markers of Sepsis Outcome and Complications" that was published in the journal Cannabis and Cannabinoid Research explored the potential benefits and underlying dynamics of the endocannabinoids anandamide and 2-AG in sepsis patients.
Understanding Sepsis
According to the Mayo Clinic, sepsis (also known as blood poisoning) is a "potentially life-threatening condition that occurs when the body's response to an infection damages its own tissues." Sepsis occurs when the infection-fighting processes "turn on the body" and cause "organs to function poorly and abnormally."
Sepsis may progress to septic shock, which is a dramatic drop in blood pressure that "can lead to severe organ problems and death." Traditional treatments include antibiotics and intravenous fluids.
Sepsis Statistics
Statistics published by the U.S. Centers for Disease Control and Prevention report that, in a typical year, about 1.7 million adults in the U.S. will develop sepsis. Of these, 350,000 will die during their hospitalization or will be discharged to hospice. One in three people who die in a hospital "had sepsis during that hospitalization." The organization notes that sepsis, "or the infection causing sepsis, starts before a patient goes to the hospital in nearly 87 percent of cases."
Nearly half of the 49 million cases in 2017 were children, "with an estimated 20 million cases and 2.9 million global deaths in children under five years of age."
According to the World Health Organization, sepsis is a "syndromic response to infection." It is estimated that, in 2017, there were 49 million cases of sepsis and 11 million sepsis-related deaths worldwide (accounting for 20 percent of all global deaths). Nearly half of the 49 million cases in 2017 were children, "with an estimated 20 million cases and 2.9 million global deaths in children under five years of age."
Most Sepsis Cases in Low-income Countries
The organization reported that "significant regional disparities in sepsis incidence and mortality exist" and that "approximately 85 percent of sepsis cases and sepsis-related deaths worldwide occurred in low- and middle-income countries."
The study noted that sepsis is a "complex, heterogeneous syndrome that causes multiple organ dysfunction due to a dysregulated host response to infection. Despite a better understanding of its pathophysiology and improved management, sepsis remains a major clinical challenge due to its fearsome complications."
The Study
The study's authors reported that a major challenge in the goal to improve treatment of sepsis patients is "early prediction of sepsis complications." Because so little is known about the role of the endocannabinoid system (ECS) in sepsis, the goal of this scientific investigation was to "assess the prognostic role of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as early predictors of mortality" and the overall treatment of sepsis.
106 Sepsis Patients in Cohort
The research design was that of a human trial involving 106 sepsis patients, all of whom were a minimum of 18 years of age and "admitted with suspected sepsis to the Emergency Unit of the Department of Infectious Disease and the Department of Emergency Medicine and then hospitalized at the Department of Infectious Diseases or the Intensive Care Unit." The study was conducted at University Hospital Osijek in Croatia over a 15-month period from February 2018 to April 2019.
This was the first peer-reviewed research to "report the prognostic role of endocannabinoids, AEA and 2-AG, as independent risk factors for outcomes...in sepsis."
Exclusion criteria included patients younger than 18, those lacking a confirmed sepsis diagnosis, and those who had recently undergone surgery. The endocannabinoid levels of the patients were measured in an effort to better understand "sepsis outcomes and complications."
The scientists reported that theirs was the first peer-reviewed research study to "report the prognostic role of endocannabinoids, AEA and 2-AG, as independent risk factors for outcomes...in sepsis."
Results
The scientists reported that their data contribute to the "growing evidence of an endocannabinoid role in sepsis and acute respiratory distress syndrome (ARDS) caused by inflammation." One of the greatest benefits provided by endocannabinoids such as AEA and 2-AG appears to be anti-inflammatory mechanisms and that anandamide increased "the action of anti-inflammatory immune cells."
The study reported that its results were consistent with "previous studies showing that lower baseline AEA and 2-AG concentrations are associated with greater inflammation and organ dysfunction" in cases of sepsis. "We also found a strong correlation between the two endocannabinoids, indicating that they tend to increase together during sepsis."
Anti-inflammatory Role of 2-AG & AEA
The study reported that the ECS "tends to be activated early, at the beginning of the hyperinflammatory phase of sepsis." It noted that, in cases of sepsis involving more severe damage and respiratory system function impairment, concentrations of both AEA and 2-AG were lower. They theorized that this "might indicate an anti-inflammatory role of endocannabinoids."
The study reported that the ECS "tends to be activated early, at the beginning of the hyperinflammatory phase of sepsis."
The study found that the most "prevalent underlying causes of sepsis were pneumonia and urinary tract infection" and that these causal agents together represented 79 percent of the sepsis research participant group (cohort) studied. Of 106, only seven patients featured sepsis "of undefined origin."
Conclusions
The study's authors concluded that their results "support the involvement of AEA and 2-AG in sepsis." They reported that "baseline AEA and 2-AG concentrations predict" various aspects of sepsis, including severity and aspects like hospital length of stay. "The ability to early identify patients at higher risk for sepsis complications may encourage timely intervention and result in better clinical outcomes," reported the scientists.
Endocannabinoids such as 2-AG and anandamide "might be important anti-inflammatory [agents] and [provide a] protective factor in ARDS, but further research of this potential role in humans is needed" summarized the research.
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