Cannabis Phytomolecule 'Entourage': From Domestication to Medical Use

Cannabis has been used as a medicine for millennia. Crude extracts of cannabis inflorescence contain numerous phytomolecules, including phytocannabinoids, terpenes, and flavonoids. Combinations of phytomolecules have been recently established as superior to the use of single molecules in medical treatment owing to the 'entourage effect'. Two types of entourage effects are defined: 'intraentourage', resulting from interactions among phytocannabinoids or terpenes, and 'inter-entourage', attributed to interactions between phytocannabinoids and terpenes. It is suggested that the phytomolecule assemblages found in cannabis chemovars today derive from selective breeding during ancient cultivation. We propose that the current cannabis chemotaxonomy should be redefined according to chemical content and medicinal activity. In parallel, combinations of phytomolecules that exhibit entourage activity should be explored further for future drug development.