The specific goals of this research were to develop an optimized niosomal patch formulation for improved transdermal delivery of ZOL and to explore possible novel mechanisms for the antimigraine action of ZOL via alternative pathways, including those affecting the altered migraine chronification genes (RAMP-1, and NPTX-2), or microRNAs, and modulation of the endocannabinoid; CB-1/MAPK pathway. This evidence concerns the gene RAMP1 and migraine disorder.