Cannabinoids prevent DSS-induced colitis and reduce effector cell phenotypes. Female C57BL/6 mice were treated with either: vehicle [10% EtOH in PBS+Tween-80], CBD [10 mg/kg], THC [10 mg/kg], or a combination of THC and CBD [10 mg/kg, both] by oral gavage for 3 days before 2% DSS was added to their drinking water. DSS remained in the drinking water until termination of the study 14 days later. Treatments continued daily. Mice were sacrificed at 14 days post disease induction, and blood as well as organs of interest were harvested and analysed for colitis-relevant parameters. [A] Percent weight change and [B] stool score assessed over the course of disease [n = 5]. [C] Representative colonoscopy images taken on Day 10. [D] Quantification of colitis scores at indicated time points throughout disease course [n = 8 per group, per time point]. [E] Representative image and [F] length of colons at sacrifice [n = 5]. [G‐I] ELISAs from serum at sacrifice quantifying disease relevant biomarkers of colitis severity [n = 10, SAA n = 5, LCN-2, MPO]. [J] PAS stain of proximal colons from representative mice taken at sacrifice. [K] Representative flow cytometry psuedocolour dot plots [gate: Live,CD45+] displaying effector cell types in the cLP. [L] Representative flow cytometry contour plots [gate: Live,CD45+CD3+CD4+] of T-bet+ Th1 or Gata3+ Th2 cells in the cLP. Each symbol represents an individual mouse. Data are presented as mean ± standard error of the mean [SEM]. NS, not significant; *p <0.05; **p <0.01, ***p <0.001, ****p <0.0001 by two-way ANOVA with Tukey’s multiple comparisons test. Data are from one experiment representative of four independent experiments.