A recent study published in Progress in Neuropsychopharmacology & Biological Psychiatry suggests that cannabidiol (commonly known as CBD) may have a significant effect in reducing fever. The researchers found that CBD effectively lowered fever in mice by altering certain biological pathways related to the body’s stress and inflammation response. This discovery adds new insight into CBD’s possible health benefits, specifically for conditions involving inflammation and fever.
CBD, a non-psychoactive component derived from cannabis plants, has been increasingly used to address various health issues. While previous research has shown that CBD can help with anxiety, depression, and pain, the researchers aimed to understand whether it could also lower fevers and reduce inflammation. Fevers, particularly those caused by chronic inflammatory diseases, can be challenging to treat with standard fever medications, which often have side effects. The team hypothesized that CBD could help by influencing the body’s inflammatory pathways, providing a natural alternative for fever management.
“My interest in this topic stems from the compelling interplay between systemic inflammation and thermoregulation, particularly in the context of fever as a hallmark of systemic infection. Fever, while protective in moderation, can lead to severe complications when excessive,” said study author Luiz Guilherme S. Branco, a full professor at the School of Dentistry of Ribeirao Preto at the University of São Paulo.
“Cannabidiol (CBD), with its broad anti-inflammatory and antioxidant properties, presents an exciting therapeutic potential that is not yet fully understood in the context of fever. By focusing on CBD’s role in modulating inflammatory mediators like cytokines and prostaglandin E2, this research offers the opportunity to deepen our understanding of its mechanisms and explore safer alternatives to traditional antipyretics. This aligns with my broader interests in physiological regulation and therapeutic innovation.”
“The study of CBD in regulating inflammation and fever extends beyond the realm of physiology, touching upon psychological well-being,” Branco continued. “Chronic inflammation is increasingly recognized as a contributor to mental health challenges, including anxiety and depression. By understanding how CBD modulates systemic inflammatory responses and their associated physiological stressors, researchers open new avenues for exploring the mind-body connection and potential therapeutic approaches for both physical and psychological health.”
The research team used male mice aged 12 to 14 weeks, all housed in consistent conditions. Before testing, they administered a fever-inducing substance known as lipopolysaccharide (LPS), which triggers an inflammatory response. This step allowed the researchers to replicate the conditions of a fever associated with infection or inflammation. To measure the impact of CBD on this response, some mice were given a CBD injection while others received a saline solution. The researchers recorded the mice’s body temperature every five minutes for over five hours, carefully noting any differences between the CBD-treated and untreated groups.
Along with monitoring temperature, the researchers collected blood samples and tissue samples from the spleen and a specific brain region linked to body temperature regulation, called the anteroventral preoptic area. This sampling allowed them to measure various chemicals in the blood and tissue that contribute to fever and inflammation, including tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and prostaglandin E2. The anti-inflammatory marker interleukin-10 was also measured to gauge any shift toward reduced inflammation.
The researchers found that CBD reduced fever in those exposed to the fever-inducing LPS. Mice treated with CBD showed lower levels of several key inflammatory markers that contribute to fever. The levels of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and prostaglandin E2 were notably lower in CBD-treated mice than in the untreated group. Additionally, CBD raised the levels of interleukin-10, which helps the body fight inflammation, suggesting that CBD has a balancing effect on the immune system’s response to fever.
“One surprising aspect of our findings was the comprehensive way in which CBD modulates the inflammatory response,” Branco told PsyPost. “Not only did CBD reduce the fever caused by LPS-induced inflammation, but it also had a broader anti-inflammatory effect by decreasing pro-inflammatory cytokines and prostaglandin E2 (PGE2) levels while increasing levels of the anti-inflammatory cytokine IL-10. Our research suggests that CBD, a compound derived from cannabis, may help reduce fever caused by inflammation without the psychoactive effects typically associated with cannabis use.”
The researchers noted that CBD’s effect on fever could be linked to the hypothalamic-pituitary-adrenal axis, a system that regulates stress and immune response. CBD seemed to influence this system, leading to lower levels of corticosterone, a hormone released in response to stress and inflammation. Lower corticosterone levels were observed in the CBD-treated mice compared to those that did not receive CBD, indicating that CBD may help regulate the body’s stress response, further contributing to its fever-reducing effects.
“Another intriguing observation was that CBD had no impact on body temperature in euthermic (normal) conditions, indicating it specifically targets inflammatory states,” Branco said. “This level of specificity adds to its therapeutic appeal and was an unexpected highlight of our research.”
“CBD’s ability to regulate inflammation and fever underscores its potential as a safer alternative to traditional fever-reducing medications, which can have undesirable side effects or may not be suitable for all individuals.”
The researchers also found that CBD influenced a neural pathway called the inflammatory reflex. This reflex helps control inflammation through the nervous system, and it appeared that CBD had a role in activating this reflex. Specifically, CBD lowered inflammatory responses in the spleen, showing that it has an impact not only on the central brain region responsible for fever but also on other parts of the immune system.
“Medical research spans a wide spectrum, from basic research—focused on understanding fundamental scientific principles in preclinical settings—to clinical research, which evaluates treatments in people to improve health outcomes,” Branco explained. “Our findings are rooted in basic research, specifically on how CBD interacts with the body’s systems, such as the hypothalamic-pituitary-adrenal axis and the inflammatory reflex, to modulate immune responses.”
“This foundational work paves the way for future clinical research to explore CBD’s role in treating fever and inflammatory diseases. By elucidating the mechanisms through which CBD reduces fever and inflammation, our research highlights its potential to become a valuable tool for managing these conditions. This could lead to the development of new therapies that are both safer and more tailored to individual needs.”
While the study provides promising results, it has certain limitations.
“It is important to recognize the distinctions between basic research and clinical trials; therefore, conclusions must be drawn with caution,” Branco noted. “Our study was conducted on animal models, specifically mice, using a controlled model of LPS-induced inflammation. While these models provide valuable insights, the findings may not fully translate to humans due to physiological and metabolic differences.”
“We identified key pathways through which CBD reduces inflammation and fever—such as modulation of cytokines, the HPA axis, and the inflammatory reflex—but these pathways are complex and involve interactions with many other biological processes. Further research is needed to fully elucidate these mechanisms.”
“Despite the promising results, CBD use in humans must account for regulatory, safety, and dosing concerns,” Branco said. “Potential long-term side effects, interactions with other medications, or variations in individual responses to CBD were not addressed in this study. Ultimately, the therapeutic potential of CBD for treating fever or systemic inflammation must be validated in well-designed clinical trials to assess efficacy, safety, and dosing in human populations.”
Branco’s long-term goals for CBD research include uncovering the molecular mechanisms by which CBD reduces inflammation and fever, especially its effects on the hypothalamic-pituitary-adrenal axis, cytokine networks, and prostaglandin E2 synthesis. He aims to expand this research to chronic inflammation models and different populations, including varying sexes and ages, to ensure comprehensive applicability. Future steps involve bridging preclinical and clinical studies with human trials to validate CBD’s safety and effectiveness, developing new CBD-based therapies, and exploring CBD’s potential in treating various fever-related conditions.
“These goals will indeed be very long-term, reflecting the complexity and scope of the work required to fully understand and apply CBD as a therapeutic agent,” Branco explained. “By pursuing these goals, we aim to establish a comprehensive framework for understanding and leveraging CBD’s therapeutic potential, ultimately improving patient care and expanding the scope of safer alternatives in medicine and dentistry.”
The study, “Cannabidiol exerts antipyretic effects by downmodulating inflammatory mediators in LPS-induced fever,” was authored by Emilly S.S. Andres, Patrícia Passaglia, Wanderson S. Santosa, Isis P. Trajano, Renato Nery Soriano, Lucas Miranda Marques, Glauce C. Nascimento, Elaine Del-Bela, and Luiz G.S. Branco.
