Secondary Terpenes in Cannabis sativa L.: Synthesis and Synergy

Abstract

Cannabis is a complex biosynthetic plant, with a long history of medicinal use. While cannabinoids have received the majority of the attention for their psychoactive and pharmacological activities, cannabis produces a diverse array of phytochemicals, such as terpenes. These compounds are known to play a role in the aroma and flavor of cannabis but are potent biologically active molecules that exert effects on infectious as well as chronic diseases. Furthermore, terpenes have the potential to play important roles, such as synergistic and/or entourage compounds that modulate the activity of the cannabinoids. This review highlights the diversity and bioactivities of terpenes in cannabis, especially minor or secondary terpenes that are less concentrated in cannabis on a by-mass basis. We also explore the question of the entourage effect in cannabis, which studies to date have supported or refuted the concept of synergy in cannabis, and where synergy experimentation is headed, to better understand the interplay between phytochemicals within Cannabis sativa L.

Keywords: biosynthesis; cannabinoids; cannabis; entourage effect; phytochemistry; synergy; terpenes.

Figure 1

General scheme of terpene synthesis pathway in Cannabis sativa L.

Figure 2

Structures of secondary terpenes present in Cannabis sativa L.

Figure 3

Bioactivities of the nine secondary terpenes covered in this review, along with cannabis’s principal cannabinoids (CBD, cannabidiol; THC, tetrahydrocannabinol; CBG, cannabigerol; CBN, cannabinol; CBC, cannabichromene). Bioactivity circles are color-coded to match the legend in the middle; the presence of a particular shading in the circle is indicative that the terpene or cannabinoid has been reported to possess that bioactivity. The figure demonstrates that not only do terpenes have multiple potential bioactivities, but different compounds possess overlapping activities, suggesting their potential to exert combination effects.