The role of prolonged cannabinoid exposure and cannabinoid receptor activation in pathogen associated pulmonary inflammation
Fall 2020 Graduate Student Award in Social and Biological Determinants of Health
Evolutionary mismatch is a state of disequilibrium in which a trait or response that evolved in one environment that was once neutral or advantageous becomes maladaptive in another environment. Mismatch is a fundamental part of evolution in changing environments and is becoming increasingly common for all species living in human-altered environments. Cannabis (cannabinoids) is the second most commonly used substance in the United States after tobacco. Evidence suggests that the earliest use of cannabis occurred over 2500 years ago. With the legalization of cannabinoids, there has been a surge in daily use, especially amongst adolescents. This raises extreme concern regarding a potential link between cannabinoids and increased risks for developing lung associated diseases. Cannabinoid (CB) use and activation of cannabinoid receptors have been widely demonstrated to be important modulators of the immune system, often inducing immunosuppression. Immunosuppression can be considered advantageous in cases of inflammatory diseases, neuropathic pain, multiple sclerosis, and glaucoma. However, due to the endocannabinoid’s immunomodulatory nature, in cases of respiratory infection, CB has been shown to prime the lungs to more severe inflammation resulting in increased susceptibility to infection and lung damage, a maladaptive response. It is crucial to explore problems associated with using large amounts of CBs as a consequence of evolutionary mismatch, especially in the adolescent population. It is especially important to understand evolutionary mismatch in relation to cannabinoid use since some young adults have so radically altered their lung environment by CB use. Habitual cannabis use has been shown to impair the lung’s defense against infection. This suggests that prolonged cannabinoid use could be a risk factor for the development of respiratory diseases. Although prolonged cannabinoid use is an emerging problem amongst adolescents, the down-stream effects on respiratory health, evolutionary mismatch, and susceptibility to infection are not well studied. This again presents a pressing need to understand the long-term effects of CB use on lung function and pulmonary inflammation within the adolescent population. This proposal aims to evaluate the effect of CB exposure on the inflammatory response of mice challenged with a microbial pathogen introduced to their environment as a consequence of evolutionary mismatch.