# Non-Cannabinoid Metabolites of _Cannabis sativa_ L. with Therapeutic Potential
## 2 Non-Cannabinoid Compounds
### Tepenes and Their Derivatives, Tepenoids  
The word \"terpene\" was devised in 1866 by [PERSON], a German organic chemist. Tepenes are hydrocarbons and are made up of isoprene units (5-carbon building blocks) [14], while terpenoids are an oxidized and denatured form of terpen that differ in that they contain an additional functional group with oxygen [14]. They are not the same, despite being used synonymously. This oxidation occurs during the drying and curing processes when the plant is exposed to open air. Tepenes are typically classified by the number of isoprene units in the molecule. Isoterpene is the only hemiterpenes. Hemiterpenes and hemiterpenoids such as phenol and isovaleric acid only have a single isoprene  
Figure 1: Synthesis of cannabinoids and non-cannabinoids produced by _Cannabis sativa_ L. [2]. unit. Monoterpenes and monoterpenoids such as pinene (most common terpene produced across plant species), limonene, myrcene, geraniol, and terpineol have two isoprene units. Sesquiterpenes and sesquiterpenoids such as humulene and farnesol have three isoprene units. Triterpenes, such as squalene--the precursors to all steroids [14]--have six isoprene units. Sesquiterpenes and tetraterpenes have seven and eight isoprene units, respectively. Polyterpenes and norisoprenoids have multiple isoprene units in their molecule. Figure 2 below shows the structures of some terpen. Figure 1 above shows the biosynthetic pathway of terpen and terpenoids, which are synthesized from an isoprenoid precursor Isopentenyl pyrophosphate (IPP). This is achieved via the plastidial deoxyxylulose phosphate/methyl-erythitol phosphate (DOXP/MEP) pathway (monoterpenoids), and the cytoplasmic mevalonate (MVA) pathway (sesquiterpenoids, triterpenoids, and sterols) [2]. Along with cannabinoids, terpen are considered a main physiological marker of secondary metabolites [15; 16]. Terpenes are a large and diverse class of aromatic compounds responsible for the unique flavors and scents of many herbs and plants and phenotypic variation across plant species. Over 20,000 terpen exist across plant species [17], and over 150 alone in the cannabis plant [18]. This makes terpen the largest classification of phytochemicals ([PERSON], [PERSON], [PERSON], 2016). Their primary role in plants vary but, in some plants, may attract pollinators, and in others, deter herbivores and inhibit microbial growth. The most common terpen in cannabis include limonene, \(\alpha\)-pinene, \(\beta\)-pinene, humulene, \(\beta\)-caryophyllene, linalool and myrcene [2]. Other common terpen in cannabis include bisabolol, borneol, camphene, geraniol, ocinene, terpineol, and valencene. These fall into the monoterpenoids and sesquiterpenoids categories. Refer to Table 2 below for examples of mono- and sesquiterpenoids profiled in a 2020 study by [PERSON] and colleagues that profiled secondary metabolites in cannabis inflorescences, leaves, stem bars, and roots for medicinal purposes [2]. Figure 2: The chemical structures of some terpenoids produced by _Cannabis sativa_ L. (**a**.) \(\alpha\)-pinene; (**b**.) Borneol; (**c**.) Humulene; (**d**.) \(\beta\)-caryophyllene; (**e**.) Linalool; (**f**.) \(\alpha\)-Myrcene; (**g**.) D-linonene. Terpenes provide aromatherapeutic benefits to humans including stress, anxiety, and depression relief, decongestion, and a general pharmacologically synergistic effect in combination with cannabinoids and flavonoids. As a result, terpen are frequently used in cosmeceuticals, perfumes and beverage flavoring. Terpenes and terpenoids are highly concentrated in the essential oils extracted from the cannabis plant, and are also responsible for the therapeutic benefits that essential oils provide. A study by [PERSON] et al., 2016 explored the biological properties of some terpenes making up said essential oils extracted from the cannabis plant (Table 3) by distillation and characterized by gas chromatography-mass spectrometry (GC-MS). Table 3 also shows the biological properties of other common terpenes found in cannabis.