Intriguingly, there was no difference in the development of chemically induced skin tumors (subcutaneous application of 3-methylcholanthrene) between wild-type and CB1−/−/CB2−/− double KO mice [409], although the latter group exhibited significantly less skin papilloma formation following DMBA and UVB-treatment [87], suggesting that the role of CB1 and CB2 signaling in regulating tumor formation may be context-dependent. This evidence concerns the gene CNR1 and skin papilloma.