Cannabis Terpenes and Terpenoids Explained
Did you ever wonder why certain strains of cannabis have such unusual, yet characteristic scents and savors?
Tastes and aromas as distinctly different as diesel fuel, citrus, skunk, cookies, cheese and wild berries often accompany cannabis.
Did you ever wonder what makes all of the different strains of cannabis smell and taste the way they do? Can the flavour of your favourite cannabis varietal make a difference on how it affects you?
Historically, everyone thought that it must be the amounts and ratios of the cannabinoids that gives each varietal their individual profiles. But they would be mistaken — the answer is far more complex and interesting.
Some of you might remember in the early days when there was only a tiny cottage cannabis industry around the world. To take advantage of a large inventory of ‘variety’ already made available through nature’s machinations, smugglers were at their peak bringing in such exotics as Panama Red, Acapulco Gold, Purple Laotian, Purple Afghani, the flowery patchouli scented Jamaican or the dank dark taste of Columbian weed. Then the Thai sticks arrived; and people couldn’t believe that cannabis could taste like fresh orange juice while it delivered knock down punches to many first-time users.
Then there were the concentrates: the original concentrates, before laboratory science came up with dozens of new items like shatter or wax. The original concentrate of cannabis is, of course, hashish. You may also recall, if you are old enough, the heady aroma of Black Afghani hash or the honeyed scents of Blond Lebanese, Red Lebanese and others. When mixed with opium they took on a sweeter, perfume-like fragrance layered over the hashy elements. Even the perfume Opium made a smash hit based on the sticky resin’s intoxicating bouquet.
TERPENES CREATE UNIQUENESS
Well, what do you suppose gave all these materials their individual signatures? The very pedigree that people really like about certain strains, which compels them to come back for more, has as much to do with the terpene profile as it does the THC and CBD content. As far as the distinctive taste and smell of individual cannabis preparations go, it’s the terpenes that provide much of that uniqueness.
TERPENES ARE ASTONISHINGLY POTENT
In addition to the unique flavour signature, the bewildering variations in the psychic effects of cannabis is now thought to be due, at least in part, to the terpene content as well.
In other words, two unique strains of cannabis that have the exact same THC and CBD content, can have dazzling effects that are completely different, because of differing amounts of dozens, no hundreds, of terpenes. As the mysteries of the cannabinoids are slowly revealed to us, the terpenes within cannabis are finally being recognized as well.
It’s these tiny fragrant molecules that may well turn out to be as, or more, important than the cannabinoids. That’s because they are biologically active on many organ systems explaining many medical applications; and many of these compounds are powerful psychostimulants and depressants, just like some of the cannabinoids.
In other words, there is a class of natural chemicals secreted by cannabis plants that are extremely important in providing its end effects. It’s these effects that breeders often seek out and it’s the terpenes that make this possible. And there are many, many other plants from the botanical world such as the pine tree that also contain differing amounts of unique terpenes. Even some insects secrete them. So, what exactly are these substances and why are they made by plants and some animals?
The short answer it that the terpenes help to protect the plant from natural predation and infestation as it grows, matures and flowers.
Phytocannabinoids and terpenoids are synthesized in cannabis, in secretory cells inside glandular trichomes (Figure 1) that are most highly concentrated in unfertilized female flowers prior to senescence.
First let’s obtain a good working definition of terpenes, terpenoids and anything else related to these novel materials.
Terpenes…are a large and diverse class of organic compounds, produced by a variety of plants, particularly conifers, though also…some insects…emit terpenes…They may protect the plants that produce them by deterring herbivores and by attracting predators and parasites of herbivores. Many terpenes are aromatic [meaning in chemical terms containing an ‘aromatic’ benzene ring] hydrocarbons and thus may have had a protective function. The difference between terpenes and terpenoids is that terpenes are hydrocarbons, whereas terpenoids contain additional functional groups [such as a methyl group, CH3 for example].
They are the major components of [pine] resin, and of turpentine produced from resin. The name “terpene” is derived from the word “turpentine”. In addition to their roles as end-products in many organisms, terpenes are major biosynthetic building blocks within nearly every living creature. Steroids, for example, are derivatives of the triterpene squalene.
When terpenes are modified chemically, such as by oxidation or rearrangement of the carbon skeleton, the resulting compounds are generally referred to as terpenoids. Some authors will use the term terpene to include all terpenoids. Terpenoids are also known as isoprenoids.
Terpenes are also major constituents of Cannabis sativa plants, which at least 120 [compounds have been identified]…In addition to being responsible for the plant’s aroma, they can act synergistically with cannabinoids. In fact, there are several promising applications based on the combined use of cannabinoids and terpenes, such as new acne therapies utilizing CBD with the monoterpenes limonene, linalool, and pinene; new antiseptic agents with CBG and pinene; treatment of social anxiety disorder using CBD with limonene and linalool; and treatment of sleeping disorders by adding caryophyllene, linalool, and myrcene to 1:1 CBD/THC extracts.
Scientists have discovered that many of the terpenes found in cannabis are of the monoterpene class:
Monoterpenes consist of two isoprene units…monoterpenoids include geraniol, terpineol (present in lilacs), limonene (present in citrus fruits), myrcene (present in hops), linalool (present in lavender) or pinene (present in pine trees). Iridoids derive from monoterpenes.
Substances such as pinene are present in many varietals of cannabis that have been on the market recently. It’s what gives it a fresh pine-like scent, as if walking in a redwood forest.
Limonene is one that’s responsible for the citrusy scent of many modern varietals as well as the old, legendary yet difficult to find, Thai stick.
CANNABIS TERPENES/TERPENOIDS MISSING LINK IN THE ‘ENTOURAGE EFFECT’?
Terpenoids are the main components of essential oils (EO), and they form the largest group of plant chemicals, with up to 20,000 identified so far. It is the terpenoids that give cannabis its characteristic aroma. As of 2011 over 200 terpenoids have been identified in cannabis, but little is known of their pharmacologic properties. Typically the yield is very low at about 1% but the trichomes themselves can contain up to 10% of trichome content.
Monoterpenes usually predominate (limonene, myrcene, pinene) while drying and storage will slightly decrease the quantity. Furthermore, as the product ages, the monoterpene content converts to a higher percentage of of sesquiterpenoids (especially caryophyllene), as often occurs in extracts (such as wax or shatter).
Based on decades of research we now know that:
…the black market cannabis in the UK (Potter et al., 2008), Continental Europe (King et al., 2005) and the USA (Mehmedic et al., 2010) has become almost exclusively a high-THC preparation to the almost total exclusion of other phytocannabinoids. If – as many consumers and experts maintain (Clarke, 2010) – there are biochemical, pharmacological and phenomenological distinctions between available cannabis ‘strains’, such phenomena are most likely related to relative terpenoid contents and ratios.
From the above, we see that the real difference between one AAA cannabis varietal and another, equally as good but completely different in taste, effect and aroma, is actually due to the shuffling of terpenoid ratios during breeding, growing and processing. This may also help to explain the powerful medicinal properties of some strains as they blend with various cannabinoids forming the ‘entourage effect’.
TERPENES ARE ANTIDOTES
In figure 2, we see four representatives of some of the terpenoids commonly found in cannabis that appear to attenuate ‘overdose’ and acute intoxication anxiety.
These prescribed treatments hail from the 10th century literature (Persia) up to the 19th century (Christianson 1851). From the top left moving clockwise we have (A) Lemon (Citrus limon). (B) Calamus plant roots (Acorus calamus). (C) Pine nuts (Pinus spp.). (D) Black pepper (Piper nigrum). It’s the terpenes within these plants that harbour anxiolytic and sedative properties useful in treating acute anxiety or psychosis from cannabis intoxication.
Dr. Ethan Russo provides a whimsical account of treating cannabis-induced psychotropy. The quote hails from Pliny, Rome’s most quoted historian:
The gelotophyllis [‘leaves of laughter’ = cannabis] grows in Bactria and along the Borysthenes. If this be taken in myrrh and wine all kinds of phantoms beset the mind, causing laughter which persists until the kernels of pine-nuts are taken with pepper and honey in palm wine.
It can be plainly seen from the above quote that myrrh with wine seems to enhance the potency of cannabis followed by the recommendations he gives to attenuate your laughing spree, induced by ‘leaves of laughter’, should it become uncontrollable.
Investigators, such as Dr. Russo and others, are accumulating compelling science that supports these ancient remedies. Also note that paranoia and anxiety have been “soulmates” with cannabis since humans first started using this plant centuries ago.
TERPENE BIOCHEMISTRY AND MEDICINAL APPLICATIONS
So it appears, based on the latest observations, that one of the main differences between for example, Girl Scout Cookie versus Hindu Kush, are their immensely different terpene syllabi. Let’s examine these chemicals in a bit more detail.
The European Pharmacopoeia, Sixth Edition (2007), lists 28 EOs (Pauli and Schilcher, 2010). Terpenoids are pharmacologically versatile: they are lipophilic, interact with cell membranes, neuronal and muscle ion channels, neurotransmitter receptors, G-protein coupled (odorant) receptors, second messenger systems and enzymes (Bowles, 2003; Buchbauer, 2010).
What this tells us is that these interesting substances have enormously broad biochemical effects, influencing some of the most critical enzyme systems we have, while affecting neurotransmitter levels and other fundamental processes. These effects are exactly what pharmaceutical drugs are designed to do.
What may be one of the most important and fascinating aspects of these novel compounds is that they are pharmacologically active in extremely minute quantities. They can produce profound psychic and or physical effects even when rubbed on the skin, or simply inhaled. This of course, forms the basis for aroma therapy, something ‘evidence-basers’ frown on. But we have plenty of evidence of their biologically active characteristics. Here’s one example of hundreds:
Mice exposed to terpenoid odours inhaled from ambient air for 1 h demonstrated profound effects on activity levels, suggesting a direct pharmacological effect on the brain, even at extremely low serum concentrations.
Terpenoids are bioavailable in high percentages because of their ‘lipophilic’ (fat loving) chemical properties which allows them to effortlessly cross biological membranes and enter the blood stream; and from there to influence activities of the brain, heart or other organs. It’s as if they were specifically designed for human consumption; and to treat medical disorders, because there is no more effective way, other than through IV or IM injection, to introduce a drug than through inhalation.
Breathing in D-limonene, for example, was found to be bioavailable with 70% pulmonary uptake. This material, common to the lemon and orange, is also found in peppermint and juniper. It is the second most widely distributed terpenoid in all of nature. Studies using citrus oils in mice and humans showed profound anxiolytic and antidepressant effects. The antidepressant effect was so prevailing that in one case study 9 of 12 patients were allowed to discontinued their prescription antidepressant. It was also found to boost important immune cell populations in humans.
It may be useful in the treatment breast cancer, esophageal reflux, as a topical antifungal and as a powerful antioxidant; it is also astonishingly safe and non-toxic.
β-Myrcene is another common cannabis monoterpenoid which produces an earthy aroma suggestive of musk but also shares the aroma of cloves, herbal and citrus; while it may be found in mango, thyme, citrus, lemongrass and bay. It has dozens of medicinal as well as psychic effects. It’s an anti-inflammatory, anti-cancer, analgesic (in mice) and muscle relaxant (in mice). It is part of a sleep formula popular in Germany which uses hops in addition to other materials in their preparation. The addition of myrcene appears to be a powerful sedative:
Together, these data would support the hypothesis that myrcene is a prominent sedative terpenoid in cannabis, and combined with THC, may produce the ‘couch-lock’ phenomenon of certain chemotypes that is alternatively decried or appreciated by recreational cannabis consumers.
α-Pinene is another cannabis monoterpene which also appears in conifers, and the most widely encountered terpenoid in nature; it is anti-inflammatory; an antibacterial effective against MRSA; and a bronchodilator. It’s sharp, sweet pine scent profile can be found in pine needles, conifers, and sage.
A promising role for cannabis consumers is its ability to enhance memory by inhibiting a special enzyme in the brain’s hippocampus responsible for short-term memory. This feature could counteract short-term memory deficits induced by THC intoxication. CBD has also been shown to counteract the reduction in short-term memory from cannabis use. A possible future application might include α-Pinene and CBD in an oral preparation or vaporized to help offset the loss of short-term memory. It may even help those with Alzheimer’s Disease where often times the first signs are a faltering memory.
D-Linalool is another cannabis monoterpenoid common to lavender (Lavandula angustifolia), whose psychotropic anxiolytic activity has been reviewed in detail (Russo, 2001). Its other scent profile includes floral, citrus and spice; it can also be found in laurel, birch, rosewood, and citrus. Other amazing properties are: it alleviates pain and heals skin burns without scarring; anesthetic effects are equivalent to procaine and menthol; it is a powerful anticonvulsant which may have applications in treating seizure disorders. Consider the synergistic effects of a medication consisting of the potent anti-seizure compound CBD and D-Linalool in the treatment of refractory seizure disorders. The widespread GABA-ergic (Valium-like) effects are summarized below:
These effects were summarized (Nunes et al., 2010, p. 303): “Overall, it seems reasonable to argue that the modulation of glutamate and GABA neurotransmitter systems are likely to be the critical mechanism responsible for the sedative, anxiolytic and anticonvulsant properties of linalool and EOs [essential oils] containing linalool in significant proportions”.
β-Caryophyllene is the most common sesquiterpenoid encountered in cannabis. Scientists speculate that its evolutionary function may be due to its ability to attract insect predatory green lacewings as a protective mechanism. This chemical is also found commonly in black pepper. It is frequently the predominant terpenoid overall in cannabis extracts, particularly if they have been processed under heat for decarboxylation.
It has the characteristic scents of pepper, wood and spice; it can be found in pepper, cloves, hops, basil and oregano. It has been found to be equipotent to several classes of non-steroidal antiinflammatory drugs (NSAIDs) like etodolac which is similar to Motrin. It may be useful in treating gastric ulcers, and malaria.
Note that GI irritation is a side effect of NSAIDs but not from β-Caryophyllene, a valuable clinical observation that may result in a class of drugs that treat pain without producing stomach ulcers like Advil or Motrin often do.
It’s most novel quality is that it is a selective, full CB2 agonist (stimulant), the first proven phytocannabinoid beyond the cannabis genus (Gertsch et al., 2008). Its non-psychoactive CB2 agonism may have numerous medical applications in the future.
Honorable mention goes to some other cannabis terpenoids:
Humulene is the terpenoid found in hops and coriander. It produces a woody, earthy scent profile. It is anti-inflammatory, antibacterial and has applications in treating pain, while suppressing the appetite.
Nerolidol, a sesquiterpene with sedative properties (Binet et al., 1972), present as a low-level component in orange and other citrus peels.
Caryophyllene oxide is a sesquiterpenoid oxide common to lemon balm, and to eucalyptus. Caryophyllene oxide has the distinction of being the component responsible for cannabis identification by drug-sniffing dogs (Stahl and Kunde, 1973).
Phytol is a diterpene present in cannabis extracts. Phytol increased GABA expression; thus, the presence of phytol could account for the alleged relaxing effect of wild lettuce (Lactuca sativa), or green tea (Camellia sinensis), despite the latter’s caffeine content. GABA is a prominent neurotransmitter in the CNS. It is an inhibitory neurotransmitter. Think of the effects of Valium for example; it acts on the GABA system by stimulating it, thus increasing ‘inhibition’. That’s why it’s good for treating seizures and anxiety. Same with phytol.
As you can see, there are endless combinations and ratios that modern cannabis producers are just starting to appreciate. The future of gourmet, boutique cannabis lies here. The medical applications are beyond measurement.
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