Abstract: Provided is a Cannabis plant with reduced delta-9-tetrahydrocannabinol (THC) content, or reduced cannabidiol (CBD) content, or reduced THC and CBD content. According to a core aspect of the invention, the Cannabis plant comprises at least one targeted genome modification effective in decreasing expression of. at least one Cannabis gene encoding a cannabinoid biosynthesis enzyme selected from the group consisting of Cannabis tetrahydrocannabinolic acid synthase (CsTHCAS), Cannabis cannabidiolic acid synthase (CsCBDAS), Cannabis aromatic prenyltransferase (CsPT), Cannabis olivetol synthase (CsOLS), Cannabis acyl-activating enzyme 1 (CsAAE1) and any combination thereof. Further disclose are methods for production of the Cannabis plants and use thereof.