The Immunomodulating Effects of Delta-9 Tetrahydrocannabinol (THC) and Cannabidiol (CBD) in the Context of Inflammation and Infection in Vitro

Abstract

The therapeutic potential of cannabinoid-based medicines has led many U.S. states and countries to authorize their clinical use. Delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), the biologically active compounds of cannabis, possess a wide range of immune regulatory properties. Macrophages are specialized immune cells that express endocannabinoid receptors which can affect inflammatory phenotypes and phagocytosis. Increasing prevalence, and legalization of cannabis, has led to regulatory findings of various aspects of physiological, behavioral, and metabolic function; however, the effects on immunological regulation in the setting of infection is less well understood. The purpose of the current study was to test the immunoregulatory effects of various THC and CBD doses in the context of infection. Secondary, THC and CBD temporal and tissue-specific cytotoxic effects were evaluated at 2 or 6 h. Macrophages were pre-treated with THC or CBD (0, 2, 5, 10, 15, 25 µg/mL) and challenged with LPS (2 h) or live Escherichia coli (E. coli) (6 h). Extracellular bacteria were eliminated, macrophage cells lysed, and intracellular bacteria quantified. Unlike CBD, THC-induced phagocytosis was significantly decreased in a dose-dependent manner. CBD-induced phagocytosis was inversely increased at 25 µg/mL. In macrophages, THC increased cytotoxicity and CBD decreased cytotoxicity at doses 15 µg/mL and greater. These findings demonstrate the multifaceted interplay between THC and CBD that affect the immunological interaction between host and microbes. Taken together, it is necessary to understand the immunoregulatory underpinnings of Phyto cannabinoids to maximize therapeutic potential and reduce opportunistic infections.