What are the terpenes in weed and CBD cannabis?
Terpenes are aromatic compounds produced by a range of plants, cannabis among them. Interest in the potential therapeutic benefits of terpenes has grown considerably of late, since these components could influence not only the aroma but also the effect of cannabis. In this article we'll walk you through the fascinating world of the terpenes in weed and CBD cannabis.
Cannabis sativa and its wide variety of compounds
One of the defining features of the Cannabis sativa plant is its extraordinary ability to produce diverse compounds. There are a great many of them, and they are generally classified into primary and secondary metabolites.
Primary metabolites are those absolutely essential to the growth and reproduction of the plant, such as fibres, which provide structure and support, or sugars, which feed the cells.
But plants also have an abundance of compounds whose function is not always known. That large group of phytochemicals is called secondary metabolites, and it is where terpenes belong. Secondary metabolites are compounds produced by plants that are not directly involved in the growth, development or reproduction of the organism.
What is the function of terpenes in cannabis?
Terpenes can give the organism an advantage by increasing the plant's chances of survival or its fecundity [1, 2]. For example, the secondary metabolites that plants produce serve as a defence against herbivory or against disease [5, 6].
These secondary metabolites are not unique to plants; a great many organisms produce them, including bacteria, plants, animals and fungi [3, 4], but they are fairly specific to the organism that produces them.
You may be interested in: Effects of terpenes in cannabis
What other components does cannabis produce?
The Cannabis sativa plant, as I was saying, produces many secondary metabolites. Some of them are cannabinoids, such as CBD and THC, the ones that interact with our endocannabinoid system.
Cannabinoids are compounds that are fairly specific to the cannabis plant [7]. There are other plants that also produce cannabinoids, and that also interact with our endocannabinoid system [8, 9], but these are not related to the cannabinoids produced by *C. sativa *[7].
The Cannabis sativa plant produces a wide variety of compounds, among them cannabinoids, terpenes and flavonoids. These compounds can influence the effect that cannabis produces.
Terpenes in chemistry: structure and isoprene
Terpenes are a large and diverse group of organic compounds (carbon-based ones) derived from a five-carbon molecule called isoprene. They are produced by living organisms, and more than 30,000 terpene compounds have been described.
Their function in plants may be, for example, to attract pollinating animals or seed dispersers, to inhibit the growth of competing plants, or to deter herbivory, among other functions [13-15].
Types of terpenes: monoterpenes, sesquiterpenes and diterpenes
Terpenes are classified according to the number of carbons they contain: those with ten carbons are called monoterpenes, those with fifteen carbons are sesquiterpenes, and those with twenty, diterpenes [16].
These three terpenes common in cannabis that I mentioned above: limonene and beta-myrcene are monoterpenes with ten carbons, and beta-caryophyllene is a sesquiterpene with fifteen carbons.
What other plants produce the same terpenes as cannabis
It may surprise you to learn that the three most common terpenes produced by Cannabis sativa are also produced by other plants: the mango fruit produces beta-myrcene, in black pepper we find beta-caryophyllene, and lemons are rich in limonene. The same goes for alpha and beta pinene, produced by pine trees, the linalool in lavender, and the alpha humulene in hops.
Plants such as mango, lavender or pine trees produce the same terpenes as cannabis.
How many terpenes cannabis produces, and why they vary by strain
What is interesting about the *Cannabis sativa *plant is that it produces all these compounds and more. The different cannabis strains differ in the number, the abundance and the rate at which they produce these terpenes [12].
It is possible that terpene content also influences the effect of cannabis and the sensations that using it produces in the body.
What is extraordinary about the Cannabis sativa plant is that it is capable of producing a wide variety of terpenes, resulting in different aromas and, possibly, different effects.
Can terpenes be used to classify cannabis strains?
Besides giving the plant the signature smells behind several cannabis strain names (e.g. Lemon Skunk or Super Lemon Haze), these terpenes could also serve to classify the different commercial cannabis strains [12, 17-20].
Terpenes have been found to be useful for grouping the strains or types of cannabis, being a more reliable grouping measure than the names assigned by the industry, such as “sativa” or “indica” [12]. To go deeper into this popular debate, don't miss the post on the differences between sativa and indica.
The thin line between terpenes and cannabinoids
Although terpenes are far more volatile than cannabinoids [21], I think the difference between cannabinoids and terpenes is rather blurred. I may well be wrong, and chemists are welcome to correct me, but I believe a major difference between terpenes and cannabinoids lies in the tools used to measure them.
How are the cannabinoids and terpenes in cannabis determined?
Cannabinoids and terpenes can be measured by chromatography, a technique in which a mixture of compounds is separated. But terpenes, given their volatility, can only be measured using gas chromatography (GC), where the compounds can be evaporated without decomposing, that is, without breaking apart [22].
By contrast, for cannabinoids to be measured by GC, they have to be heated, and therefore this chromatography only gives the result for cannabinoids in their neutral form and not the acidic one.
Cannabinoids, unlike terpenes, can also be measured using high-performance liquid chromatography (HPLC), where both the acidic and the neutral form are measured [22-24].
What similarities are there between terpenes and cannabinoids?
Cannabinoids and terpenes have a great deal in common. Both compounds share a biochemical pathway; that is, there is a point in the metabolic route that leads to the production of both cannabinoids and terpenes, since both use the same precursor compounds [10, 25, 26]. In addition, some terpenes can also interact with our endocannabinoid system [27, 28].
Cannabinoids and terpenes share the same biochemical pathway upstream; that is, at some point the precursor compounds are the same.
Finally, some propose that cannabinoid and terpene genes act as a network [29] (what in biology we call pleiotropy and epistasis) to generate this complex phenotype of secondary metabolites. All of this opens the door to a fascinating world in which cannabis terpenes take on a far more prominent role and cannabinoids cease to be the main actors in the therapeutic effects of cannabis.
Possible therapeutic uses of terpenes
Many of these terpenes have potential therapeutic applications, among them anti-inflammatory, anticancer, antiseptic, astringent and digestive properties among others [15]. For example, humulene appears to have anti-inflammatory and analgesic properties [30, 31]. Linalool seems to have anti-inflammatory and antimicrobial properties too [32], but also antidepressant ones [33], and it is one of the terpenes most used in yoga classes. When we clean our homes we use products containing alpha and beta pinene for their antimicrobial properties [34].
Terpenes are produced by many plants besides cannabis, and these are not related to one another
Finally, something that has always amazed me about the terpenes produced by the Cannabis sativa plant is that it shares these components with many other plants, both close and distant. For example, hops — an essential ingredient in beer and the closest living species to C. sativa, with which it shares a common ancestor that lived roughly 25 million years ago — also produces alpha humulene [35].
But with pines, which also produce alpha and beta pinene, it shares an ancestor that lived some 250 million years ago! In other words, pines and the *C. sativa *plant are very distantly related and still produce the same compounds. And again, something interesting about this Cannabis sativa plant is that it produces all these compounds, and more!
What is still to be researched about cannabis terpenes
One terpene puzzle I would like to see solved is the reason why the Cannabis sativa plant produces all these compounds — that is, the ecological function that terpenes serve. Some suggest the plant produces them to defend itself against ultraviolet radiation, others to fight off herbivory [36, 37], for example.
And something I have heard here and there, without any scientific confirmation, is that when the plant is grown outdoors it produces a greater quantity and diversity of compounds, terpenes included. This would be explained by the instability of outdoor growing, exposed to changes in temperature, sun exposure, hail, disease and insects, among other hazards the plant would have to defend itself against.
It seems logical that those plants would produce more terpenes as a defence against the elements than plants grown indoors, under standardised conditions of light, nutrients, temperature and so on.
These are some of the questions that can be answered through experiments. I hope you have enjoyed this short review of cannabis terpenes.
Frequently asked questions about terpenes
What are terpenes and what are they for?
Terpenes are aromatic compounds produced by a great many plants, cannabis among them, and they are responsible for their smell. In the plant they are not there as perfume: they help defend it against herbivores and disease, attract pollinating animals and the animals that disperse seeds, and inhibit the growth of competing plants. In cannabis, they could also influence the effect it produces, and not just the aroma.
What are terpenes in chemistry?
In chemistry, terpenes are a group of organic compounds derived from isoprene, a five-carbon molecule that acts as a building block. They are classified by how many carbons they contain: those with ten are monoterpenes, those with fifteen sesquiterpenes and those with twenty diterpenes. More than 30,000 terpene compounds have been described, and they are not exclusive to plants: bacteria, fungi and animals produce them too.
What is the difference between terpenes and terpenoids?
A terpene is a pure hydrocarbon, made up only of carbon and hydrogen. A terpenoid is a terpene that has undergone a chemical modification, usually the addition of oxygen or a rearrangement of its skeleton. In practice, and especially in the cannabis sector, the two terms are often used as synonyms: many of the compounds listed as “terpenes” on a label or in a lab report are, strictly speaking, terpenoids.
What is the structure of a terpene?
All terpenes are built from the same unit: isoprene, a molecule with five carbon atoms. These units join together in chains and then fold, close into rings or branch, and that is where the huge variety of existing structures comes from. That is why they are classified by counting carbons in multiples of five: limonene and beta-myrcene have ten, beta-caryophyllene fifteen.
How many terpenes does cannabis produce?
More than a hundred different terpenes have been described in Cannabis sativa, although only a few reach significant amounts in any one plant. The most common are beta-myrcene, limonene and beta-caryophyllene. What sets one strain apart from another is not so much which terpenes they produce, but in what proportion and at what rate they produce them.
References
1. Demain, A.L. and A. Fang, The natural functions of secondary metabolites. History of modern biotechnology I, 2000: p. 1-39.
2. Vining, L.C., Functions of secondary metabolites. Annual review of microbiology, 1990. 44(1): p. 395-427.
3. Wink, M., Plant breeding: importance of plant secondary metabolites for protection against pathogens and herbivores. Theoretical and applied genetics, 1988. 75(2): p. 225-233.
4. Bennett, R.N. and R.M. Wallsgrove, Secondary metabolites in plant defence mechanisms. New phytologist, 1994. 127(4): p. 617-633.
5. Hadacek, F., Secondary metabolites as plant traits: current assessment and future perspectives. Critical Reviews in Plant Sciences, 2002. 21(4): p. 273-322.
6. Forbey, J.S., et al., Exploitation of secondary metabolites by animals: A response to homeostatic challenges. Integrative and comparative biology, 2009. 49(3): p. 314-328.
7. van Velzen, R. and M.E. Schranz, Origin and evolution of the cannabinoid oxidocyclase gene family. bioRxiv, 2020.
8. Bauer, R., K. Woelkart, and O.M. Salo-Ahen,* CB receptor ligands from plants*. Current Topics in Medicinal Chemistry, 2008. 8(3): p. 173-186.
9. Gertsch, J., R.G. Pertwee, and V. Di Marzo, *Phytocannabinoids beyond the Cannabis plant–do they exist? *British journal of pharmacology, 2010. 160(3): p. 523-529.
10. Booth, J.K. and J. Bohlmann, Terpenes in Cannabis sativa–From plant genome to humans. Plant Science, 2019. 284: p. 67-72.
11. Gershenzon, J. and N. Dudareva, The function of terpene natural products in the natural world. Nature chemical biology, 2007. 3(7): p. 408-414.
12. Smith, C.J., et al., The Phytochemical Diversity of Commercial Cannabis in the United States. bioRxiv, 2021.
13. Aizpurua-Olaizola, O., et al., Evolution of the cannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes. Journal of natural products, 2016. 79(2): p. 324-331.
14. Chen, F., et al., The family of terpene synthases in plants: a mid‐size family of genes for specialized metabolism that is highly diversified throughout the kingdom. The Plant Journal, 2011. 66(1): p. 212-229.
15. Cox-Georgian, D., et al., Therapeutic and medicinal uses of terpenes, in Medicinal Plants. 2019, Springer. p. 333-359.
16. Davis, E.M. and R. Croteau, Cyclization enzymes in the biosynthesis of monoterpenes, sesquiterpenes, and diterpenes. Biosynthesis, 2000: p. 53-95.
17. Henry, P., et al., Predicting chemovar cluster and variety verification in vegetative cannabis accessions using targeted single nucleotide polymorphisms. PeerJ Preprints, 2018. 6: p. e27442v1.
18. Orser, C., et al., Terpenoid Chemoprofiles Distinguish Drug-type Cannabis sativa L. Cultivars in Nevada. Natural Products Chemistry and Research, 2017. 6(1).
19. Reimann-Philipp, U., et al., Cannabis Chemovar Nomenclature Misrepresents Chemical and Genetic Diversity; Survey of Variations in Chemical Profiles and Genetic Markers in Nevada Medical Cannabis Samples. Cannabis and Cannabinoid Research, 2019.
20. Watts, S., et al., Cannabis labelling is associated with genetic variation in terpene synthase genes. Nature plants, 2021. 7(10): p. 1330-1334.
21. Bueno, J., et al., The preservation and augmentation of volatile terpenes in cannabis inflorescence. Journal of cannabis research, 2020. 2(1): p. 1-11.
22. Jiang, Z., C. Kempinski, and J. Chappell, Extraction and analysis of terpenes / terpenoids. Current protocols in plant biology, 2016. 1(2): p. 345-358.
23. Micalizzi, G., et al., Cannabis Sativa L.: A comprehensive review on the analytical methodologies for cannabinoids and terpenes characterization. Journal of Chromatography A, 2021. 1637: p. 461864.
24. Jin, D., et al., Classification of Cannabis cultivars marketed in Canada for medical purposes by quantification of cannabinoids and terpenes using HPLC-DAD and GC-MS. J. Anal. Bioanal. Tech, 2017. 8(01): p. 2.
25. Booth, J.K., J.E. Page, and J. Bohlmann, Terpene synthases from Cannabis sativa. Plos one, 2017. 12(3): p. e0173911.
26. Booth, J.K., et al., Terpene synthases and terpene variation in Cannabis sativa. Plant physiology, 2020. 184(1): p. 130-147.
27. Ferber, S.G., et al., The “entourage effect”: terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Current neuropharmacology, 2020. 18(2): p. 87-96.
28. LaVigne, J., R. Hecksel, and J.M. Streicher, In Defense of the “Entourage Effect”: Terpenes Found in Cannabis sativa Activate the Cannabinoid Receptor 1 In Vivo. The FASEB Journal, 2020. 34(S1): p. 1-1.
29. Zager, J.J., et al., Gene networks underlying cannabinoid and terpenoid accumulation in cannabis. Plant physiology, 2019. 180(4): p. 1877-1897.
30. Rogerio, A.P., et al., Preventive and therapeutic anti‐inflammatory properties of the sesquiterpene alpha humulene in experimental airways allergic inflammation. British Journal of Pharmacology, 2009. 158(4): p. 1074-1087.
31. Chaves, J.S., et al., Pharmacokinetics and tissue distribution of the sesquiterpene alpha humulene in mice. Planta medica, 2008. 74(14): p. 1678-1683.
32. Kamatou, G.P. and A.M. Viljoen, Linalool–A review of a biologically active compound of commercial importance. Natural product communications, 2008. 3(7): p. 1934578X0800300727.
33. dos Santos, É.R., et al., Linalool as a Therapeutic and Medicinal Tool in Depression Treatment: A Review. Current Neuropharmacology, 2022. 20(6): p. 1073-1092.
34. Salehi, B., et al., Therapeutic potential of alpha and beta pinene: A miracle gift of nature. Biomolecules, 2019. 9(11): p. 738.
35. Richter, G., et al., Cannabis sativa: an overview. Nutraceuticals, 2021: p. 603-624.
36. Vergara, D., et al., Genetic and Genomic Tools for Cannabis sativa. Critical Reviews in Plant Sciences, 2016. 35(5-6): p. 364-377.
37. Kovalchuk, I., et al., The Genomics of Cannabis and Its Close Relatives. Annual Review of Plant Biology, 2020. 71.
