Effect of Cannabidiol and Δ9-tetrahydrocannabinol on Anti-Inflammatory Lipid Mediator Synthesis in Humans

<b>Background:</b> Eicosanoids-lipid mediators derived from polyunsaturated fatty acids such as arachidonic acid-have a notable role in inflammatory signaling. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) have been shown in preclinical studies to modulate inflammatory pathways the modulating the enzymes that generate eicosanoids, namely lipoxygenase (LOX), cyclooxygenase (COX), and cytochrome P450 (CYP450). <b>Methods:</b> This present study aimed to investigate how CBD and THC effect plasma levels of eicosanoids generated through LOX, COX, and cytochrome P450 (CYP450) pathways. Using plasma sample data from multiple clinical studies, we tested the hypothesis that high-CBD cannabis use would increase eicosanoid levels compared with high-THC cannabis. <b>Results:</b> Following cannabis use, high-CBD cannabis led to a rise in plasma eicosanoids, particularly lipoxins, while high-THC cannabis did not. <b>Conclusions:</b> CBD promoted anti-inflammatory eicosanoid production <i>via</i> the 15-LOX pathway, therefore supporting the potential role of CBD as a therapeutic candidate for inflammatory diseases.