WIN55,212 is an agonist of both CB1 and CB2 and ameliorates colitis whether used prophylactically or therapeutically in TNBS and DSS models.76–78 AM841 [CB1 agonist] improves colitis in a cannabinoid receptor-dependent manner, with the effect lost in CB1-/- and CB2-/- mice.79 The same is true for the CB1 agonist, HU210,67 which also has effects on sustaining intestinal barrier function in a TLR4-independent manner.80 Interestingly the effect of non-selective cannabinoid receptor activation may be through central rather than peripheral mechanisms. Here, CNR2 is linked to colitis.