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. The gene discussed is NPTX2; the disease is migraine disorder.