CBD and THC:CBD exacerbate TLR4-induced TNF-α expression in PBMCs from HC subjects and pwMS. Treatment of PBMCs from (a) HCs, and (b) pwMS with LPS (100 ng/mL; 24 h) increased TNF-α protein expression. Pre-treatment with CBD (10 μM) alone, and in combination (1:1) with THC (10 μM) (45 min pre-treatment), significantly exacerbated LPS-induced TNF-α expression in PBMCs from (a) HCs (Kruskal–Wallis statistic = 106.9), and (b) pwMS (Kruskal–Wallis statistic = 101.7). Effect of LPS, THC (10 μM) and CBD (10 μM) treatment on TNF-α mRNA expression in PBMCs from (c) HCs (Kruskal–Wallis statistic = 14.6), and (d) pwMS (Kruskal–Wallis statistic = 17.9). (e) Summary of the stimulatory effect of THC (10 μM), CBD (10 μM), and THC:CBD (10 μM:10 μM) on TLR4-induced TNF-α protein expression in PBMCs from HCs and pwMS (expressed as % increase from LPS treatment). Treatment of PBMCs from pwMS with THC:CBD (10 μM:10 μM) in the presence of LPS, significantly increased TNF-α protein expression when compared to PBMCs treated with LPS + THC (10 μM) (Kruskal–Wallis statistic = 14.0). Statistical significance was determined by Kruskal–Wallis tests, with Dunn’s multiple comparison post-hoc test to compare means of preselected pairs of groups. Data are presented as median cytokine expression, minimum and maximum values and IQR. Symbols indicate individual data points in PBMCs from 22 HCs and 19 pwMS for protein analysis, and 18 HCs and 10 pwMS for mRNA analysis. * p < 0.05, ** p < 0.01 vs. vehicle control group. +
p < 0.05 compared to cells treated with LPS. ##
p < 0.01 vs. PBMCs treated with LPS in the presence of THC:CBD in a 1:1 combination.