By: Due Diligence Horticulture

January 22, 2025

Cannabis produces a complex array of volatile organic compounds (VOCs) that contribute to its distinct aroma. These compounds include terpenes, volatile sulfur compounds (VSCs), and various non-terpenoid volatile compounds. This review provides an overview of the synthesis, distribution, and sensory  perceptions of these major contributors to cannabis odor, beginning with the fundamental role of isoprene as the building block for terpenes.

Synthesis of Terpenes: Isoprene as the Building Block

Terpenes are a large and diverse class of organic compounds found in all living organisms. Five-carbon  isoprene (CH) units serves as the fundamental building block for all terpenes, which are constructed by the sequential addition of these units. The general formula for terpenes is (C5H8)n, where “n” represents the  number of isoprene units. The immense diversity of terpenes arises from the various ways bonds form and twist between isoprene units. 

Terpenes are synthesized through two primary pathways in plants: 1) Methylerythritol Phosphate (MEP)  Pathway and 2) Mevalonic Acid (MVA) Pathway. Isopentenyl diphosphate (IPP) and dimethylallyl  diphosphate (DMAPP) serve as key intermediates in both pathways, leading to the formation of geranyl  diphosphate (GPP) and farnesyl diphosphate (FPP), which are precursors for monoterpenes and  sesquiterpenes, respectively. GPP is also a precursor to cannabigerol acid (CBGA), making the  cannabinoid and terpene synthesis pathways intimately linked (Figure 1).

decorative graphic showing Terpene synthesis
Figure 1: Terpene synthesis begins with pyruvate and glyceraldehyde-3-phosphate (G3P) and acetyl CoA, derived from primary metabolism, to form isopentyl pyrophosphate (IPP), a five-carbon phosphorylated form of isoprene. From Chacone et al. (2022).

Monoterpenes and Sesquiterpenes

Monoterpenes are synthesized via the MEP pathway, where two isoprene units combine to form GPP. Key monoterpenes in cannabis include limonene, myrcene, and pinene. Limonene offers citrus-like notes and  is known for its fresh, uplifting aroma[1]. Myrcene imparts a musky, earthy smell and is one of the most  abundant terpenes in cannabis[2]. Pinene, found in many plant species, has a distinctive pine-like aroma[3].  Monoterpene synthesis dominates the early growth stages and becomes most concentrated during the  flowering phase[4]

Sesquiterpenes are synthesized via the MVA pathway, where three isoprene units combine to form FPP. Important sesquiterpenes in cannabis include β-caryophyllene and humulene. β-Caryophyllene is  responsible for a peppery aroma and interacts with the CBreceptor, exhibiting anti-inflammatory  properties[5]. Humulene contributes to woody and earthy aromas and is also found in hops[6]. Sesquiterpene  synthesis typically occurs later in the plant’s development compared to monoterpenes, peaking during the  flowering stage and influencing the plant’s spicy or woody scent[7]

The biosynthesis of terpenes is controlled by a family of enzymes known as terpene synthases (TPS),  which catalyze the cyclization and modification of GPP and FPP to produce the diverse array of terpenes  found in cannabis[8]. Recent studies have demonstrated that genetic variation in TPS genes is associated  with the chemical diversity observed in cannabis[9]. Vergara et al. (2021) found that this genetic variation  influences terpene profiles, affecting strain classification and consumer perception.

Volatile Sulfur Compounds (VSCs)

Volatile sulfur compounds have gained attention for their significant role in the “skunky” aroma often  associated with cannabis[10](Figure 2). These compounds are synthesized through metabolic pathways  involving sulfur-containing precursors. Key VSCs include 3-methyl-2-butene-1-thiol, a highly pungent compound also found in garlic and hops[11], and prenylated thiols that intensify during the curing process[12]

Volatile sulfur compounds (VSCs) identified in Cannabis
Figure 2: Volatile sulfur compounds (VSCs) identified in Cannabis. VSCs impart a skunky odor and are structurally similar to compounds produced by garlic. From Oswald et al. (2021).

VSCs are produced primarily in the later stages of cannabis flowering and peak during curing[13]. Advancements in analytical techniques have enhanced the detection and quantification of these  compounds, improving our understanding of their role in cannabis aroma[12]. Comprehensive two dimensional gas chromatography has been particularly instrumental in identifying new families of  prenylated VSCs, offering deeper insights into their contributions to the overall scent profile[10].

Sensory Perception of Cannabis Volatiles

The complex interplay among volatile compounds produced by cannabis drives the perception of the user. Monoterpenes such as limonene and pinene provide fresh, citrusy, or pine-like aromas. These lighter  molecules contribute bright and uplifting notes to the fragrance profile. In contrast, sesquiterpenes like β caryophyllene introduce deeper, more robust aromas, offering spicy, woody, or peppery notes that add  complexity and warmth to the sensory experience[7]. Figure 3 summarizes aroma descriptors reported by a  sensory panel[13].

graphic depicting aroma descriptors for a variety of cannabis strains reported by a sensory panel
Figure 3: Aroma descriptors for a variety of cannabis strains reported by a sensory panel. There were clear differences in sweet and savory descriptors among cultivars. From Oswald et al. (2023).

VSCs, particularly 3-methyl-2-butene-1-thiol, are associated with skunky, pungent odors[10]. Even in  vanishingly low concentrations, these compounds can dominate the scent profile, contributing to the overall  pungency. Non-terpene compounds like alcohols, aldehydes, and esters add earthy or floral nuances[13].  The balance and concentration of these compounds within each chemovar contribute to the unique aromas  and flavors of different cannabis strains[14]. Sensory evaluation studies have demonstrated strong  correlations between chemical profiles and human perception, providing valuable insights for breeders and  producers. By understanding how these compounds interact to shape aroma and flavor, the industry can  develop cannabis products with desired aromatic profiles, enhancing the overall consumer experience[15].

Conclusion

The aroma of cannabis is shaped by a wide range of volatile compounds. Monoterpenes and  sesquiterpenes, derived from isoprene building blocks, dominate the terpenoid profile, while volatile sulfur  compounds and non-terpenoid volatiles add complexity to the scent. Genetic variation in terpene synthase  genes plays a crucial role in terpene diversity, influencing strain classification and consumer perception.

 

References

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  3. Tholl, D. (2015). Biosynthesis and Biological Functions of Terpenoids in Plants. Advances in Biochemical  Engineering/Biotechnology, 148, 63–106. 
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  8. Booth, J. K., Page, J. E., & Bohlmann, J. (2017). Terpene synthases from Cannabis sativa. PLoS ONE,  12(3), e0173911. 
  9. Vergara, D., et al. (2021). Cannabis labelling is associated with genetic variation in terpene synthase  genes. Nature Plants, 7(11), 1330–1334. 
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  13. Oswald, I. W. H., et al. (2023). Minor, Nonterpenoid Volatile Compounds Drive the Aroma Differences of  Exotic Cannabis. ACS Omega, 8(36), 39203–39216. 
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