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Introduction to Terpenes

One of the first things that come to mind when thinking of different plants is their smell. The compounds responsible for the characteristic plant aromas are oily chemicals called terpenes. The origin of the word dates to 1866 when the German chemist August Kekulé shortened the word “turpentine” {call-out, text: chemical derived from the resin of some pine trees}.1 Apart from terpenes, plants also contain terpenoids. The difference between the two is small: terpenes are hydrocarbons and terpenoids are oxygen-containing terpenes.2 In this text we will refer to both as terpenes. Like all plants, cannabis also comprises numerous terpenes. The varying ratio of different terpenes between cultivars is responsible for their distinct aromas. According to Upton and colleagues:
“The [cannabis] aromas as described in modern advertising include: peculiar, narcotic, strong, sweet to sour, fruity to pungent, agreeable, aromatic, fresh and sweet, euphoric, spicy citrusy, musty, skunky, acrid, juniper, floral, sour, diesel, vanilla, complex, blueberry, pineapple, perfumed, piney, sandalwood, mango, skunky-cheese, and more.”3

Why plants produce terpenes

There are thousands of terpenes in nature, and scientists have suggested several possible reasons why plants produce them: [1] One of the purposes of terpenes may be plant protection. They have shown to deter microbes and some herbivores. [2] Next, they help with the plant’s reproduction by attracting some insects, thus aiding the pollination. These arguments are more likely to be the case with cannabis as well, since terpenes are mostly concentrated in the flowers, the plant’s reproductive organs. [3] Some scientists found that another possible role of terpenes may be inter-plant communication.4, 5 [4] Lastly, some terpenes may be included in photosynthesis, while others can influence the plant’s color.6

Terpenes in cannabis products

In cannabis plants, terpenes are synthesized in trichome glands, the hair-like structures that make the cannabis flowers look frosty. Trichome glands are also responsible for producing cannabinoids (e.g. CBDA and THCA). There are several types of trichomes that cover the cannabis plant, but the ones that synthesize terpenes and cannabinoids for the most part are called capitate-stalked trichomes.7 They are densely concentrated on the flowers, which is why they smell the strongest out of all plant parts. frosty cannabis flower

Photo by Esteban Lopez on Unsplash

In addition to more than 115 phytocannabinoids, cannabis trichomes also produce 120 terpenes.8 However, only a few are present in relatively large amounts. The most common terpenes in cannabis include α-pinene, β-pinene, linalool, limonene, β-myrcene, β-caryophyllene and caryophyllene oxide.9 As there is no way to mechanically separate terpenes from cannabinoids, they are an integral part of the dried raw flower used for smoking or vaping. However, other cannabis products can contain a larger variety of cannabinoid and terpene amounts. For example, cannabis extraction methods based on solvents, like hydrocarbons and ethanol, can yield different ratios of terpenes and cannabinoids, and even lose some terpenes in the process due to their volatility. Hydrocarbon extraction will yield relatively more terpenes, whereas ethanol typically yields more cannabinoids. Some products, such as isolates, contain only cannabinoids and no terpenes. It is also common for companies to add terpenes isolated from other plants to their products, even up to levels or ratios that are not found in the cannabis plant itself, in order to better control the terpene content.

Effects of terpenes on the body

Some manufacturers advertise their cannabis products as providing certain benefits specifically due to their terpene content. These claims are generally unfounded, or even illegal if they include medical effects, as there is no (sufficient) scientific evidence to support them. The truth is that scientists have yet to research to what extent terpenes exert effects, either by themselves, or in combination with cannabinoids. Outcomes on cannabinoid-terpene combination effects that would be stronger than the sum of the individual effects (which is another claim that is commonly made) are generally inconclusive, or do not find any extra-proportional effects. For example, a recent study in cells by researcher Finlay and colleagues found that none of the five major cannabinoid terpenes (myrcene, α- and β- pinene, β-caryophyllene, and limonene) directly interact with the human endocannabinoid receptors, CB1 and CB2,10 while another study from 2019 that looked at α-Pinene, β-pinene, β-caryophyllene, linalool, limonene, and β-myrcene also showed that these terpenes do not modulate the functional activity of Δ9-THC at human CB1 and CB2 receptors.9 A study by Gallily and colleagues found that three essential oils rich in terpenoids can alleviate acute inflammation, while purified CBD alone is more effective in chronic (long-lasting) inflammation compared to the terpenoid-rich oils.11 Many effect suggestions and claims are based on animal studies in which dosages that are too high for humans are administrated via a route one would never choose, for example, via an injection. Studies like these are interesting, but are not applicable to what would happen if one inhaled or swallowed only a small amount of terpenes. Could terpenes in their naturally occurring amounts in cannabis plants exert psychoactive and physiological effects in humans? It is possible, but there is little to no proof, and outcomes of the more abundant animal studies are not directly translatable to the human situation. We know that some animal studies showed that limonene was anxiolytic, myrcene gave sedative, analgesic, and muscle relaxant effects, pinene improved gastrointestinal tract motility, while linalool produced anxiolytic, sedative, and anticonvulsant effects.9 Silexan, a product containing the terpenes linalool and linalyl acetate extracted from lavender oil, has been observed to decrease anxiety when taken in high dosages via an oral capsule (note that linalyl acetate is not found in cannabis).12 Researcher John McPartland summarized results from various studies on the most prominent cannabis terpenes and their effects as found in tissue and in animals, see more in Table 1. Note that tissue and animal studies do not necessarily translate to human situations, and the effects should not be considered valuable for any type of (self) medication. The dosages used in these studies are, moreover, not representative of the terpene quantities typically seen in cannabis (products). Terpenes certainly affect our bodies, but studies have yet to uncover how exactly and what it could mean to our health and general functioning. There are ongoing studies (for example, see the study by Johns Hopkins University) which should tell us more in the coming time about the interaction between THC, CBD, and single terpenes, about which we will keep you updated. Table 1. The summary of characteristics of the most common terpenes in cannabis plants.13
Terpene Concentration Properties
β-myrcene 0.47% Analgesic; Antiinflammatory; Antibiotic; Antimutagenic
β-caryophyllene 0.05% Antiinflammatory; Cytoprotective (gastric mucosa); Antimalarial
d-limonene 0.14% Immune potentiator; Antidepressant; Antimutagenic
linalool 0.002% Sedative; Antidepressant; Anxiolytic; Immune potentiator
pulegone 0.001% AChE inhibitor; Sedative; Antipyretic
1,8-cineole (eucalyptol) >0.001% AChE inhibitor; Increases cerebral blood flow; Stimulant; Antibiotic; Antiviral; Antiinflammatory; Antinociceptive
α-pinene 0.04% Antiinflammatory; Bronchodilator; Stimulant; Antibiotic; Antineoplastic; AChE inhibitor
α-terpineol 0.02% Sedative; Antibiotic; AChE inhibitor; Antioxidant; Antimalarial
terpineol-4-ol 0.0004% AChE inhibitor; Antibiotic
p-cymene 0.0004% Antibiotic; Anticandidal; AChE inhibitor
borneol 0.008% Antibiotic
∆-3-carene 0.004% Antiinflammatory
References:
  1. Dev, Sukh (1989). Terpenoids. Natural Products of Woody Plants (691-807). Springer, Berlin, Heidelberg.
  2. Krill, C.; Rochfort, S.; Spangenberg, G. (2020). A High-Throughput Method for the Comprehensive Analysis of Terpenes and Terpenoids in Medicinal Cannabis Biomass. Metabolites, 10(7), 276.
  3. Upton, Roy; Craker, Lyle; ElSohly, Mahmoud; Romm, Aviva; Russo, Ethan; Sexton, Michelle (2014). Cannabis Inflorescence Standards of identify, analysis and quality control (65). American Herbal Pharmacopoeia.
  4. Dudareva, Natalia; Pichersky, Eran; Gershenzon, Jonathan (2004). Biochemistry of plant volatiles (1893-902).
  5. Reinhard, Judith; Srinivasan, Mandyam V.; Zhang, Shaowu (2004). Olfaction: scent-triggered navigation in honeybees. Nature, 427(6973), 411.
  6. Mccreath, Simone Badal; Delgoda, Rupika (2017). Pharmacognosy: Fundamentals, Applications and Strategies. Academic Press.
  7. Pertwee, Roger G. (2014). Handbook of Cannabis. Handbooks in Psychopharmacology, 44(8), 085201.
  8. Aizpurua-Olaizola, Oier; Soydaner, Umut; Ozturk, Ekin; Schibano, Daniele; Simsir, Yilmaz; Navarro, Patricia; Etxebarria, Nestor; Usobiaga, Aresatz (2016). Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis sativa Plants from Different Chemotypes. Journal of natural products, 79(2), 324--331.
  9. Santiago, Marina; Sachdev, Shivani; Arnold, Jonathon C.; McGregor, Iain S.; Connor, Mark (2019). Absence of entourage: Terpenoids commonly found in Cannabis sativa do not modulate the functional activity of Δ9-THC at human CB1and CB2 receptors. bioRxiv
  10. Finlay, David B. (2020). Terpenoids from cannabis do not mediate an entourage effect by acting at cannabinoid receptors. Frontiers in pharmacology, 11, 359.
  11. Gallily, Ruth; Yekhtin, Zhannah; Hanuš, Lumír Ondřej (2018). The anti-inflammatory properties of terpenoids from cannabis. Cannabis and cannabinoid research, 3(1), 282-290.
  12. Müller, Walter E.; Sillani, Giacomo; Schuwald, Anita; Friedland, Kristina (2021). Pharmacological basis of the anxiolytic and antidepressant properties of Silexan®, an essential oil from the flowers of lavender. Neurochemistry International, 143
  13. McPartland, John M.; Russo, Ethan B. (2001). Cannabis and cannabis extracts: greater than the sum of their parts?. Journal of Cannabis Therapeutics, 1(3-4), 103-132.