Cannabidiol and Contributions of Major Hemp Phytocompounds to the “Entourage Effect”; Possible Mechanisms

Abstract

Abstract Cannabidiol (CBD) is the primary cannabinoid in “fibre-type” cannabis chemovars (hemp) and the subject of intensive research. In addition to cannabinoids, Cannabis sativa species produce several hundreds of other phytocompounds such as terpenes and phenolic compounds that can produce a wide variety of effects and are claimed to modify the action of CBD, in extracts and other derivatives (“entourage effect”). Different hemp varieties demonstrate a large genetic variability of the profile of phytocompounds which is further modified by agroclimatic factors and processes after harvest such as extraction. Overall, the pharmacological effects of hemp extracts, particularly when grown in outdoor culture, are likely to vary due to the variable profile of their phytocompounds. Consequently, a generalization of the medicinal properties of different extracts is therefore not possible. This review summarizes the complex interaction of CBD with its main targets, possible modulatory effects by other phyto- and endocannabinoids and the possible impact of concomitant phytosubstances in hemp extracts such as terpenes and flavonoids. For a better understanding of the “entourage effect” and to enable a systematic investigation of differences between chemovars and derivatives, future clinical studies need to ensure proper characterisation of phytocompounds content beyond the concentration of CBD and THC.