Cannabis sativa; A Drugmaker's DevKit - Crafting Medicines for Complex Maladies

Since 2637BC when Chinese Emperor Shen-Nung first described the medicinal properties of cannabis there has been recognition for the utility of the plant in human health.  We now know that cannabinoids, structurally related compounds unique to the cannabis plant, target endogenous systems in the body that regulate homeostasis. The first plant based cannabinoid medicine, Sativex, is now approved in 23 countries for treatment of spasticity in Multiple Sclerosis. Chronic and complex diseases, particularly those with neurological/immune system involvement, are poorly treated with single focus medicines; the conventional “magic bullet” approach has been largely unsuccessful. Disease causation is multifactorial and therefore a ‘broadside’ approach may be more successful. Plants contain a hierarchy of constituents which interact synergistically and extracts are often more potent than equivalent dose of isolated compounds. Each cannabinoid has their own often complementary pharmacology and through an intensive breeding programme novel plants with novel cannabinoid profiles have been developed. In the genetic model used, the cannabinoid content of each chemical phenotype (chemotype) is controlled by four independent loci and by manipulating these genes the precise cannabinoid composition of a plant can be controlled. This has allowed the generation of a broad pipeline of products under clinical investigation specifically geared towards the following therapeutic indications; diabetes, epilepsy, oncology, schizophrenia and inflammatory bowel disease. The paradigm described in this talk allows developments of medicines with superior risk/benefit profiles compared to synthetically produced compounds, meeting stringent regulatory requirements, whilst still providing an intellectual property framework to encourage industry in this pursuit.