Challenges and opportunities for therapeutic use of medical cannabis

Research has advanced and pre and post-harvest management strategies for Cannabis sativa have been proposed, aiming to improve cannabis production and efficiently attain industrial scale cannabinoid production. In general, studies have focused on genetic modification and cultivation methods designed to increase the content of the substance of interest (in general, cannabidiol; CBD) and obtain varieties with high productivity and resistance to pests. For the cannabis industry, propagating vigorous and uniform plants remains a challenge, as it is a dioecious crop and therefore depends on cross-fertilization for seed production. In this context, this review, through searches in international databases, examined aspects of the C. sativa plant associated with its genotypic plasticity and chemical variability, as well as strategies and perspectives for achieving success in industrial scale production of phytocannabinoids. The methods and techniques that have been used include micropropagation to generate exclusively female individuals; development of semi-dwarf cannabis cultivars, which have a high leaf density and low Delta(9)-Tetrahidrocanabinol (THC) levels; and alterations in the spectrum of LED lights to stimulate photoreceptors and maximize the yield and quality of cannabis, with reduced operational costs. Polyploidization has been used to develop new strains of cannabis with significant increases in CBD concentration in the terpene profile and in the buds of tetraploid clones, without increased THC content. Genetically modified microorganisms have been developed for large-scale production of both natural (phytocannabinoids) and non-natural cannabinoids. Parameters such as plant variety and density, light intensity, and fertilization affect biomass and cannabinoid yields. Considering the complexity of the endocannabinoid system and the specificities of the diseases that medicinal cannabis could be used to treat, obtaining a pharmaceutical product that meets this demand remains a great challenge.