There is evidence for the effectiveness of FAAH inhibitors when used acutely in models of migraine resulting from injection of a nitric oxide donor to activate the trigeminal pain system [100,101] However, controversy exists regarding adverse effects of enzyme inhibition since compensatory inactivation of the ligands by other enzymatic degradations are proposed to occur in studies of FAAH and MAGL inhibitors for pain [102]. This evidence concerns the gene FAAH and migraine disorder.