A Cannabis sativa-derived formulation for transmucosal and transdermal delivery is disclosed comprising Cannabis sativa-derived compounds nanoencapsulated in phospholipid-based vesicles. A method of encapsulating cannabis-derived compounds in nanosized phospholipid vesicles is also disclosed. Cannabis sativa-derived extracts have enhanced bioavailability when encapsulated in nanosized phospholipid vesicles prior to administration to a subject as compared to non-encapsulated cannabinoids. Also disclosed herein are methods of transmucosal and transdermal administration of the formulation having phospholipid vesicles with nanoencapsulated Cannabis sativa-derived substances.