Koltai, H. - Agricultural Research Organization, Volcani Center, Rishon LeZion, Israel 
Friedman, D. - Hebrew University of Jerusalem, Israel 
Namdar, D. - Agricultural Research Organization, Volcani Center, Rishon LeZion, Israel

Marijuana, Cannabis sativa, is one of the most effective medicinal plants in use for millennia by various civilizations, finding its way in and out of official pharmacopoeia origins. It contains more than 600 different phytochemicals, present in different ratios and compositions in multiple diverse strains grown around the world. C. sativa is known to have many beneficial effects on the human body, relieving the symptoms of different ailments in ways not always connected to the well-studied psychoactive effects. The many cannabis-derived compounds found in the different strains of the plant and the multiplicity of beneficial effects on different physiological conditions suggest a complex relationship between composition and activity. It is this complex relationship, as well as other challenges, that creates a significant and critical barrier to medical cannabis use. Some of these challenges, discussed below, include: (I) determination of the differences in activity between C. sativa whole extracts and single phytocannabinoids, initially described as an "entourage" effect; (II) determination of pharmacodynamics and biological metabolite activity of cannabis-derived compounds; and (III) optimal use of cannabis-based products for the correct indication while managing the challenges posed by the regulatory landscape to cannabis product development. Overcoming these challenges will promote the development of cannabis medicalization through new and improved cannabis-based treatments for different medical conditions.