Terpenoids and terpenes are aromatic compounds that are found in thousands of plant species, and are responsible for the various flavours and fragrances of cannabis. We have known about their presence in cannabis for decades, but it is only recently that awareness of their potential therapeutic properties has begun to expand.
What are terpenes & terpenoids?
Terpenes are a large class of naturally-occurring organic compounds; they are also known as isoprenes, as their structure is based on repeating isoprene (C5H8) units. Terpenes are major constituents of plant resin and essential oils extracted from such plants.
Terpenes are basic hydrocarbons, whereas terpenoids contain extra functional groups that could be comprised of a range of chemical elements. However, it is common for the term ‘terpene’ to also include terpenoids in many existing writings. Terpenoids, also known as isoprenoids, are the largest group of organic compounds found thus far, comprising at least 20,000 distinct molecules.
The isoprene rule
Limonene, which is comprised of two linked isoprene units, can be expressed as (C5H8)2, which equates to C10H16. Several other terpenes also have this structure, but the two isoprene units are arranged differently; collectively, they are known as monoterpenes (the mono- prefix refers to the number of complete terpene units; i.e. one terpene unit equals two isoprene units).
Terpenoids with three linked isoprene units are known as sesquiterpenes (sesqui-meaning 1.5), and those with four are diterpenes, and so on. The formula (C5H8)n, where n is the number of linked isoprene units, is known as the isoprene rule, and is one of nature’s most common building blocks.
The cannabis plant produces cannabinoids through a convoluted series of chemical reactions that is thought to involve terpenes as ‘building blocks’. Cannabinoids are known as terpenophenolic compounds, as they are comprised of terpene blocks attached to phenol (C6H6O) groups; as terpenes are precursors to cannabinoids, abundance of terpenes is usually a sign of high cannabinoid levels.
Which of these compounds are present in cannabis?
It is thought that cannabis contains over 120 terpenes, although many of these are found in trace amounts and may have negligible, if any, effect.
The primary terpenes and terpenoids that have been identified in cannabis are limonene, myrcene, pinene, linalool, eucalyptol, ?-terpinene, ß-caryophyllene, caryophyllene oxide, nerolidol and phytol.
These compounds, unlike cannabinoids, are not unique to cannabis (although there are now indications that other plant species do contain some phytocannabinoids) and many are in fact very familiar to us.
Limonene is the monoterpene primarily responsible for the fragrance of citrus fruits—specifically, the D-isomer. D-limonene smells strongly orange-fragranced in its isolated form, and is in widespread use as a flavour additive in food production and an aroma compound in perfumery. It is also in use as an alternative medicine, due to its observed ability to reduce heartburn and gastric acid reflux.
As well as this, it is used as a natural, renewable solvent in cleaning products, due to its ability to dissolve oils and other lipids; it is even capable of stripping paint and is considered an effective substitute for turpentine. It must be handled with care by humans, as in high concentrations it can act as an irritant.
D-limonene is now also added to cannabis extracts as a flavour enhancer, as many of the existing terpenes are lost in processing.
Myrcene is another monoterpene, and is the most abundant terpene found in cannabis, making up over 60% of the essential oil of some strains. It is also found in bay leaves, wild thyme, hops, ylang-ylang, lemongrass and verbena.
Myrcene is responsible for the ‘green hop aroma’ found in dry-hopped beers (beers that have hops added post-fermentation, at low temperatures, to enhance their ‘hoppy’ flavour); the aroma itself is described as resinous, herbaceous, and slightly metallic—and very pungent at high concentrations.
Another plant that contains significant myrcene is Myrcia sphaerocarpa (Myrcia is the genus for which myrcene is named), a small shrub with astringent leaves and roots which is native to Brazil and has long been in use there as a treatment for dysentery, diarrhoea, diabetes and hypertension.
Myrcene has been demonstrated to produce analgesic effects in laboratory testing on rats; myrcene and limonene, along with the terpenoid citral (found in many citrus fruits, lemon myrtle, lemongrass and lemon verbena) have also been found to exert sedative and motor relaxant effects in mice.
Pinene is another monoterpene, which occurs naturally as two isomers (molecules with the same chemical formula but different structures). These isomers are known as a-pinene and ß-pinene; they are usually sourced from turpentine (produced by dry distillation of coniferous wood) and make up 58-65% and around 30% of its total volume, respectively.
As well as in cannabis, both a- and ß-pinene are found in pines and other conifers, as well as in Salvia (sage), Artemisia (sagebrush), and Eucalyptus. A-pinene is also found in olive, rosemary, sassafras and bergamot; it is the most widespread naturally-occurring terpene. B-pinene is also found in hops and cumin.
A-pinene is known for its inhibitory effect on root growth in many plant species, thought to occur through the production of reactive oxygen species that cause oxidative stress within the root system; it is believed that many plant species exude it from their leaves as a natural herbicide, preventing other plants from competing against them for resources. In small doses, it also acts as a bronchodilator in humans, and exhibits anti-inflammatory, antibacterial and antibiotic properties.
Linalool is a monoterpenoid with the chemical formula C10H18O; it is found in hundreds of plant species
including mint, laurel, cinnamon, birch, and some citrus. Linalool is a chiral molecule, meaning that it has two enantiomers, or two isomers that are non-superimposable mirror images.
The ‘left’ enantiomer is known as S-linalool, is found in coriander, palmarosa grass and sweet orange, and has a sweet, floral scent; the ‘right’ enantiomer is known as R-linalool, is found in lavender, basil and bay laurel, and has a woody, astringent aroma.
Linalool’s main medicinal function is as an anxiolytic—an anxiety-reducing drug. Lavender has been in use as a calmative for thousands of years, and recent tests on rats have borne out its sedative and motor relaxant effects.
Other terpenes & terpenoids in cannabis
Eucalyptol, a monoterpenoid, is abundant in nature. As well as in cannabis, it is found in eucalyptus, tea tree, bay leaves, basil and sage; it is well-known for its antiseptic, antibacterial and anti-inflammatory properties.
G-terpinene, a monoterpene found in various citrus fruits and herbs such as oregano and marjoram, is known to have antioxidant properties; phytol, a diterpenoid, is used by insects as a deterrent to predators, and is also used in various household products such as detergents and soaps.
B-caryophyllene, a sesquiterpene found in cloves, rosemary and hops, exhibits anti-inflammatory effects and has been demonstrated to act as a selective agonist of the CB2-receptor (no other terpenes or terpenoids have been found to affect the CB receptors). Caryophyllene oxide is the substance in cannabis that is identifiable by drug-sniffing dogs.
Nerolidol, present in neroli, ginger and jasmine, is a sesquiterpenoid with a fresh, woody scent; it is currently being investigated both as a facilitator for transdermal delivery of drugs (due to its ability to penetrate the skin) and as an inhibitor of Leishmania protozoa.
Differences between types of cannabis
Of course, terpene and terpenoids concentration will vary between strains, between related individuals, and even between two clones of the same individual, if subject to different environmental conditions while growing.
However, researchers have noted that plants of the wide-leafed Afghani Cannabis indica type are more likely to contain high ratios of guaiol, isomers of eudesmol, and other unidentified compounds; plants of the narrow-leafed C. indica type that is indigenous to the valleys of the Himalayas are higher in trans–ß-farnesene.
Guaiol is a sesquiterpenoid found in cypress and Guaiacum (a genus of five slow-growing shrubs and trees native to the tropical Americas); guaiacum itself has been in use as a treatment for coughs, arthritis and syphilis for centuries. Eudesmol, another sesquiterpenoid, is used as a fixative in perfumery, while trans–ß-farnesene acts as a natural insecticide in many plant species, including potatoes.
The health benefits of these compounds are not fully understood, but they may contribute to the differences in medicinal properties found between the different subtypes of cannabis. As our understanding grows, so too will knowledge of how best to develop and utilise new medical strains.