CBD Reduces IL-1β Expression in LPS-Stimulated BMMs Independent of Classical Cannabinoid Receptors. (A) Bone marrow macrophages isolated from CB1KO mice treated with CBD and stimulated with LPS displayed a significant decrease in IL-1β expression when compared to macrophages treated with DMSO and stimulated with LPS (n=3, 2-Way ANOVA with Bonferroni’s multiple comparisons test, F (1.000, 2.000) = 149.8; Post hoc: Vehicle + LPS vs CBD + LPS: p=0.0143). (B) Bone marrow macrophages isolated from CB2KO mice treated with CBD and stimulated with LPS displayed a significant decrease in IL-1β expression when compared to macrophages treated with DMSO and stimulated with LPS (n=4. 2-Way ANOVA with Bonferroni’s multiple comparisons test, F (1.000, 3.000) = 14.03; Post hoc: Vehicle + LPS vs CBD + LPS: p=0.016). (C) Bone marrow macrophages isolated from CNRO mice treated with CBD and stimulated with LPS displayed a significant decrease in IL-1β expression when compared to macrophages treated with DMSO and stimulated with LPS (n=4. 2-Way ANOVA with Bonferroni’s multiple comparisons test, F (1.000, 3.000) = 3.284; Post hoc: Vehicle + LPS vs CBD + LPS: p=0.22). (D) WT LPS stimulated BMMs treated with CBD display decreased expression of IL-1β independent of TRPV1 antagonism with A784168 (25nM) (n=4). (E) WT LPS stimulated BMDMs treated with PPARγ antagonist T007 (25μM) display decreased expression of IL-1β in a manner that is indistinguishable from CBD treatment. (n=3. 2-Way ANOVA with Bonferroni’s multiple comparisons test, F (3, 6) = 17.25; Post Hoc: Vehicle + LPS vs T007 + LPS p=0.0046, Vehicle + LPS vs CBD + LPS: p=0.0046). (F) WT LPS Stimulated BMDMs treated with PPARγ antagonist secrete no detectable levels of IL-1β (n=3. 2-Way ANOVA with Bonferroni’s multiple comparisons test, F (3, 6) = 7.356; Post hoc: Vehicle + LPS p=0.036). (G) CBD significantly inhibits endocytosis activity in peritoneal macrophages while T007 has no effect (n=5. 2-Way ANOVA with Bonferroni’s multiple comparisons test, F (1.000, 4.000) = 2.042; Post hoc Vehicle vs CBD p=0.0889; T007 vs CBD + T007 p=0.002)