*Review* **Secondary Terpenes in** *Cannabis sativa* **L.: Synthesis and Synergy**

**Francisco T. Chacon 1, Wesley M. Raup-Konsavage 2, Kent E. Vrana 2 and Joshua J. Kellogg 1,3,\***


**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:** cannabis; phytochemistry; cannabinoids; terpenes; synergy; entourage effect; biosynthesis

**Citation:** Chacon, F.T.;

Raup-Konsavage, W.M.; Vrana, K.E.; Kellogg, J.J. Secondary Terpenes in *Cannabis sativa* L.: Synthesis and Synergy. *Biomedicines* **2022**, *10*, 3142. https://doi.org/10.3390/ biomedicines10123142

Academic Editor: Giovanni Pallio

Received: 31 October 2022 Accepted: 2 December 2022 Published: 6 December 2022

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